High-repeatability and high-precision exposed contaminated animal experiment system and method

Abstract

The invention belongs to the technical field of toxicity testing, and discloses a high-repeatability and high-precision exposure contamination animal experiment system and method, and the exposure contamination animal experiment system comprises an animal exposure contamination experiment unit, an aerosol inlet sleeve, a contamination exposure cabin, an isolation mouse cage, a trumpet-shaped upper guide cylinder and a cylindrical lower guide cylinder of the unit jointly form two contamination exposure channels which are isolated from each other, and contamination exposure mixed gas is independently input into contamination exposure small chambers; animal contamination exposure experiments in a mouth and nose exposure mode or a whole body exposure mode can be completed through one experiment system. Through synchronous improvement of an experimental system structure and an experimental method, mouth-nose or whole-body exposure modes can be flexibly switched, a trace sample high-concentration exposure experiment of a plurality of contamination exposure chambers can be simultaneously carried out, the precision experiment and repeatability of an animal contamination exposure experiment are remarkably improved, and the experimental efficiency is improved. Various limitations of an existing experiment system and method are broken through, and the system and method have wide application prospects.

Description

Technical Field

[0001] The present invention belongs to the field of environmental protection technology, and in particular relates to a highly repeatable and high-precision animal exposure and poisoning experimental system and method. Background Art

[0002] Currently, whole-body exposure and oral and nasal exposure are two common methods of poisoning in animal exposure experiments. However, there are significant differences in their experimental equipment, methods, requirements, and other aspects. Each has its own advantages and disadvantages, and its applicable situations are also different. Whole-body exposure and oral and nasal exposure must each use their own dedicated equipment and methods to complete the corresponding whole-body exposure and oral and nasal exposure experiments and obtain corresponding experimental results. They are two independent experimental methods and systems.

[0003] Among them, the whole-body exposure method (Whole-Body Exposure) and system is to expose the entire body of the animal (including skin, respiratory tract, eyes, etc.) to the test substance (such as gas, aerosol or particulate matter), usually through a closed poisoning chamber. The whole-body exposure method is easy to operate, but there are many interference factors, the inhalation amount is difficult to control, and the data accuracy is relatively low; the whole-body exposure experiment is mainly used to study the impact of environmental pollutants on the overall health of animals. For example, in the assessment of industrial pollution areas or chemical leakage sites, animals may be exposed to multiple harmful substances at the same time through multiple pathways such as breathing and skin contact, and preliminarily explore the toxic effects of a certain poison, especially when there is little understanding of its action pathway and mechanism. Whole-body exposure can observe the comprehensive impact of the poison on various systems of the animal body, providing clues for subsequent research.

[0004] Oral and nasal inhalation exposure (Nose-Only or Head-Only Exposure) and systems expose only the animal's nose and mouth to the test substance, isolating the rest of the body (e.g., via a hood or restraint) to minimize the effects of non-respiratory exposure pathways. The inhalation volume of the oral and nasal inhalation method can be precisely controlled, but the equipment is complex, and the animal's stress response may affect the experimental results. Oral and nasal exposure experiments are suitable for studies focusing on respiratory-related diseases or toxicological mechanisms, such as studying the damage to the respiratory system caused by smog, industrial exhaust, etc. Oral and nasal exposure can more accurately simulate the process of humans inhaling harmful substances through the respiratory tract in similar environments, helping to gain a deeper understanding of the pathophysiological changes and toxic mechanisms of the respiratory tract. This is particularly important in drug development, where the safety and efficacy of drugs administered through the respiratory tract are evaluated, including the development of inhaled anesthetics and antiasthmatics. Oral and nasal exposure allows for precise control of drug dosage, observation of the drug's effects on the respiratory tract and systemic system, and provides a basis for the drug's clinical application.

[0005] Therefore, whole-body exposure and oronasal inhalation studies each have their own advantages and disadvantages, and data accuracy depends on the experimental purpose and the characteristics of the test substance. Oronasal inhalation offers advantages in terms of dose control and specificity, while whole-body exposure offers advantages in terms of operational simplicity and ecological validity. Existing technologies for these two methods are neither interchangeable nor compatible, requiring the experimenter to select one method and system based on a comprehensive consideration of factors such as the experimental purpose, the nature of the test substance, the research objectives, and the animal species.

[0006] Whole-body exposure chambers are commonly used in chemical toxicity assessments, biomedical research, environmental health studies, and other fields, and are therefore highly utilized. Currently, most common whole-body exposure chambers are rectangular or cubic, with a few adopting cylindrical structures. These chambers typically utilize a dynamic circulation principle, mixing the toxicant with air and continuously introducing it into the chamber. Exhaust gases are then treated and discharged. Toxicokinetic simulations are performed, allowing exposed animals to absorb the toxicant through respiration and skin contact, simulating real-world exposure pathways. Quantitative exposure is then performed, using mathematical models to calculate the inhaled dose (e.g., concentration × time × respiratory volume). During the experiment, the aerosol entering from the top needs to fill the entire internal structure and then be discharged from the bottom or side. For example, CN208805406U discloses a toxicity test inhalation poisoning device, which includes a poisoning device, an air intake control device, and an air outlet control device. The poisoning device includes a test chamber and a guide fan and a disturbance fan arranged in the test chamber. The test chamber is provided with an animal placement board for placing the test animals. There is a gap between the animal placement board and the bottom of the test chamber, and several small holes are opened on the animal placement board. The test chamber also has a fixed frame arranged between the guide fan and the disturbance fan, and a mosquito coil and / or electric heater are placed on the fixed frame. Because it is a whole-body exposure animal experimental device, the accuracy of the data obtained is relatively limited. The dose estimate of whole-body exposure is usually based on the concentration in the poisoning chamber, but the actual inhalation amount of the animal is affected by individual differences (such as respiratory volume, activity level) and exposure through non-inhalation routes, resulting in large data variability. In particular, when the research goal is to clarify respiratory toxicity, whole-body exposure may introduce confounding factors due to skin absorption or licking behavior, which will significantly reduce the specificity of the data. The self-controlled continuous test simulation poisoning system disclosed in CN1036267A not only uses four poisoning cabinets that meet international standards, but also adopts a dynamic gas distribution system and an exhaust gas treatment tank. However, it also has shortcomings such as the actual inhalation volume is affected by factors such as animal activity and respiratory rate, and the inhalation dose is difficult to calculate accurately. It cannot replace the oral and nasal inhalation method of poisoning experiments.

[0007] In summary, the above-mentioned whole-body exposure equipment and experimental methods are not compatible with or can replace oral and nasal inhalation exposure equipment and experimental methods due to various technical limitations. They have single functions and the following five limitations: First, the data accuracy and repeatability are low. Even if the whole-body exposure equipment is optimized, the experimental data accuracy can be improved to a certain extent, but it still cannot fully reach the accuracy level of oral and nasal inhalation. Second, the aerosol at the top fills the entire space, resulting in uneven aerosol concentration distribution. The coefficient of variation of the concentration and particle size distribution of aerosol inhaled from exposure areas at different positions is usually greater than 30%. Third, the same volume of aerosol distributed over a larger space will cause a decrease in concentration. Therefore, it is often difficult to achieve highly repeatable exposure experiments with trace test substances, especially for whole-body exposure experiments with very precious test substances. Fourth, it is usually difficult to obtain high-precision experimental data equivalent to oral and nasal exposure under highly repeatable conditions through synchronous control of the whole-body exposure test system and method. Fifth, the experimental cost is high (equipment maintenance, consumables), and a large number of experimental animals need to be handled after each experiment, which is ethically controversial. Summary of the Invention

[0008] In view of the deficiencies of the above-mentioned prior art, the object of the present invention is to provide a highly repeatable and high-precision animal exposure and poisoning experimental system and method. On the one hand, the animal exposure and poisoning experimental system is improved and optimized by setting up two isolated exposure channels so that the whole-body exposure experiment or the oral and nasal exposure experiment can be carried out in a time-sharing manner, thus realizing dual-purpose use of one machine. At the same time, the experimental method is improved, and the experimental animals are reasonably restricted or lured to maintain a better body position. During the experiment, drinking water and feeding rewards are added so that the heads of the experimental animals can be concentrated in the smaller space where the aerosol is concentrated or uniformly distributed in each poisoning exposure chamber. On the one hand, the repeatability of the aerosol concentration particle size inhaled by the experimental animals is improved, the aerosol concentration is increased, and various interference factors can be reduced, thereby greatly improving the accuracy of the oral and nasal exposure inhalation amount and the whole-body exposure experimental data, saving experimental reagents. Using a set of animal exposure and poisoning experimental systems, two types of poisoning exposure experiments can be carried out, and they can be flexibly switched to obtain high-precision and high-repeatability data for both oral and nasal exposure and whole-body exposure experiments, so as to solve the above-mentioned problems in many aspects.

[0009] The present invention provides the following technical solutions to achieve the above-mentioned objectives: A highly repeatable and high-precision animal exposure and poisoning experimental system includes an animal exposure and poisoning experimental unit, wherein the animal exposure and poisoning experimental unit includes: an aerosol air inlet sleeve, a poisoning exposure chamber, an isolation mouse cage, a trumpet-shaped upper guide tube, and a cylindrical lower guide tube; The poison exposure chamber is a closed chamber with a spindle-shaped overall outline and a hollow interior; The aerosol air inlet sleeve is hollow inside, the upper section is a mixing and dilution chamber, and the lower section is arranged in the opening at the top of the poison exposure chamber; The isolation cage is a cylindrical, air-permeable flat cage with an overall annular shape, which is arranged in the middle section of the spindle-shaped exposure chamber. The interior space of the isolation cage is hollow near the center of the circle, forming a through groove, and the rest of the space is divided into multiple centrally symmetrical, independent exposure chambers. The trumpet-shaped upper guide tube is in the shape of a trumpet with an opening downward, and is disposed as a whole in the upper section of the shuttle-shaped poison exposure chamber 8; the upper section of the trumpet wall divides the internal space of the lower section of the aerosol air inlet sleeve into two mutually isolated gas channels: the outer surface of the trumpet wall and the inner surface of the aerosol air inlet sleeve and the poison exposure chamber together form a whole-body poison exposure diffusion zone, and the hollow inside the trumpet wall forms the trumpet inner tube channel; The cylindrical lower guide tube is hollow and is disposed in a through groove in the middle of the isolation cage. The upper portion of the hollow cylindrical inner tube channel is connected to the horn inner tube channel, and the bottom portion is provided with a plurality of exposure chamber branches leading to the front of each poison exposure chamber. When the mixing and dilution chamber is connected with the trumpet inner tube channel, the cylindrical inner tube channel, and the exposure chamber branch pipe, an exposure channel is formed for inputting the exposure mixed gas into the independent exposure chamber, namely, the oral and nasal exposure channel A, which is used to implement oral and nasal exposure animal experiments; When the mixing and dilution chamber is connected to the whole-body poison exposure diffusion zone, an exposure channel is formed for inputting the poison exposure mixed gas into the independent poison exposure chamber, namely the whole-body poison exposure channel B, which is used to implement whole-body poison exposure animal experiments.

[0010] A highly repeatable and highly precise animal exposure and poisoning experiment method is implemented using the highly repeatable and highly precise animal exposure and poisoning experiment system. After the various parts of the highly repeatable and highly precise animal exposure and poisoning experiment system are connected, an aerosol generator and an air compressor respectively input aerosol and clean air into a mixing and dilution chamber and mix them. Two mutually isolated exposure channels, namely, an oral and nasal exposure channel A and a whole-body exposure channel B, are switched by a poisoning channel switching plug. One of the exposure channels independently inputs a poisoning exposure mixed gas into each poisoning exposure chamber, thereby achieving completion of animal poisoning exposure experiments in oral and nasal exposure mode or whole-body exposure mode using a set of experimental systems, and obtaining highly repeatable and highly precise animal exposure and poisoning experiment data.

[0011] The highly repeatable and high-precision animal exposure experiment system and method provided by the present invention have at least the following advantages and effects compared with the existing technology: 1. The present invention first improves and optimizes the animal exposure experiment system. In order to overcome the shortcomings of existing experimental systems and methods such as the single function, two isolated exposure channels are set up to enable the whole-body exposure experiment or the oral and nasal exposure experiment to be carried out in a time-sharing manner, realizing dual-purpose use and flexible switching of one machine; in the smaller internal space of the exposure chamber (the poison exposure chamber), it is convenient to further restrict the body position of the experimental animal so that its head is concentrated in the area with higher exposure gas concentration, so that high-concentration oral and nasal exposure or whole-body exposure of precious or expensive samples can be carried out, thereby improving the accuracy of the exposure experiment and reducing the amount of drugs used.

[0012] 2. The present invention further improves the experimental method, matches the experimental method with the experimental system, and realizes dual use of one machine and flexible switching; through the physical passive restriction of the poison exposure chamber combined with inducement, the experimental animals are actively kept in a better body position, and drinking water and feeding rewards are used to induce the experimental animals to maintain a better body position during the experiment. Passive and active measures are combined to enable the heads of the experimental animals to be concentrated in the poison exposure chamber where aerosols are concentrated or the concentration is uniformly distributed in a smaller space. On the one hand, the repeatability of the particle size of the aerosols inhaled by the experimental animals is improved, and the aerosol concentration is increased. It can also reduce various interference factors, greatly improve the accuracy of the oral and nasal exposure inhalation amount and the whole-body exposure experimental data, save experimental reagents, and achieve high precision and high repeatability compatible with both oral and nasal exposure and whole-body exposure experiments. Using a set of exposure animal experimental systems, two exposure experiments can be carried out and can be flexibly switched.

[0013] 3. Through the simultaneous improvement of structure and experimental methods, the present invention can reduce the coefficient of variation of the concentration and particle size distribution of inhaled aerosols of experimental animals in multiple separate isolation areas at different locations in the current whole-body exposure experiment to less than 10%; multiple independent oral and nasal exposure or whole-body exposure experiments with trace samples with high concentrations can be carried out simultaneously. This design has greatly improved the accuracy and repeatability of animal exposure experiments. The exposure accuracy of the oral and nasal inhalation method can replace conventional oral and nasal exposure equipment, and experimental animals do not need to suffer the huge experimental pressure caused by the oral and nasal restraint of conventional oral and nasal inhalation experiments during the experiment; the system and method applied for by the present invention can replace the conventional oral and nasal inhalation exposure experiment and can meet the experimental accuracy requirements; at the same time, it can greatly improve the data accuracy of whole-body exposure.

[0014] 4. The present invention adopts a shuttle-shaped exposure chamber and two independent exposure passage structures, which can effectively control the speed and direction of the aerosol, reduce air resistance, avoid airflow interference and eddy effects, and ensure that the aerosol is distributed very uniformly within the exposure chamber. It can also meet the needs of long-term, high-precision exposure of experimental animals. That is, as the animals continue to grow and their weight and size gradually increase, the size of the cage isolation area can be changed to isolate and restrict the animal's activity area, preventing the animals from moving over a large range. The animals are placed in the center of the exposure chamber where the aerosol concentration and particle size are more uniform. 5. The exposure passage of the present invention mainly releases exposure gas at the center of the exposure chamber. Combined with the separately provided drinking water and feeding, it not only provides the necessary prerequisites for a single long-term exposure (meeting the survival needs of experimental animals), but also allows experimental animals to spend more time in the center of the exposure chamber where the aerosol concentration and particle size are more uniform, thereby limiting and improving the accuracy and repeatability of animal exposure doses, greatly reducing the exposure experiment's requirements for software and hardware, the number of experimental animals, and consumables, reducing experimental costs, and improving animal welfare.

[0015] 6. The present invention adopts a high-precision mass flow controller in conjunction with a single-chip microcomputer and software, which can achieve fully automatic control of pressure difference and concentration through PID control, with high control accuracy and fast response speed. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is a schematic diagram of the overall structure of the animal exposure experiment system according to an embodiment of the present invention; Figure 2 This is a schematic diagram of the overall three-dimensional structure of the poison exposure chamber in an embodiment of the present invention; Figure 3 This is a schematic diagram of the three-dimensional assembly structure of the poison exposure cabin in an embodiment of the present invention; Figure 4 This is a schematic diagram of the main structure of the poison exposure cabin in an embodiment of the present invention; Figure 5 For the present invention Figure 4 Schematic diagram of the overall cross-sectional structure of the medium AA poison exposure chamber; Figure 6 This is a schematic diagram of the three-dimensional structure of the interior of the poison exposure chamber in an embodiment of the present invention; Figure 7 For the present invention Figure 6 Schematic diagram of the top view structure; Figure 8 For the present invention Figure 6 Schematic diagram of the three-dimensional assembly structure; Figure 9 For the present invention Figure 6 Schematic diagram of the main structure; Figure 10For the present invention Figure 9 Schematic diagram of the overall cross-sectional structure of AA; Figure 11 For the embodiment of the present invention Figure 9 Schematic diagram of the overall cross-sectional structure of the middle BB; Figure 12 This is a schematic diagram of the three-dimensional assembly structure of the poison exposure cabin of the present invention; Figure 13 For the embodiment of the present invention Figure 12 Schematic diagram of the three-dimensional assembly structure of the middle part structure; Figure 14 For the embodiment of the present invention Figure 13 Schematic diagram of the main structure; Figure 15 For the embodiment of the present invention Figure 14 Schematic diagram of the cross-sectional structure of AA; Figure 16 This is a schematic diagram of the three-dimensional appearance structure of the poison channel switching plug A in an embodiment of the present invention; Figure 17 Schematic diagram of the three-dimensional appearance structure of the poison channel switching plug B in an embodiment of the present invention; Figure 18 Schematic diagram of the control flow of the poison exposure experimental method according to an embodiment of the present invention.

[0017] In the picture: 1. Control computer; 2. Single chip microcomputer controller; 3. Air compressor; 4. Generator MFC; 5. Clean air MFC; 6. Aerosol generator; 7. Aerosol air inlet sleeve; 71. Aerosol connecting pipe; 72. Clean air connecting pipe; 73. Insert slot; 74. Mixing and dilution chamber; 8. Contaminated exposure chamber; 81. Upper cover; 811. Sealing ring; 82. Middle cabin coaming; 83. Support plate; 84. Lower cover; 9. Impact sampler; 10. Exhaust gas treatment module; 11. Particle size spectrometer; 12. Exhaust MFC; 13. Sampling MFC; 14. Negative pressure vacuum pump; 15: Differential pressure sensor, 16: Particle concentration sensor, 17: Oxygen concentration sensor; 18: Connecting lines; 19: Connecting pipes; 20. Poison channel switching plug; 20a, infection channel switching plug A; 20a1, plug A base plate; 20a1, plug A through hole; 20b, infection channel switching plug B; 20b1, plug B base plate; 20b2, plug B through hole; 21. Isolation cage; 211. Cage bottom plate; 212. Cage cover plate; 2121. Spliced cover plate; 213. Outer cage panel; 214. Vertical partition; 215. Through groove; 22. Trumpet-shaped upper guide tube; 221. Trumpet tube wall; 222. Columnar conduit; 223. Conduit channel; 224. Trumpet inner tube channel; 225. Hollow horizontal support plate; 23. Cylindrical lower guide tube; 231. Lower guide tube wall; 232. Lower guide tube seat; 233. Fins; 234. Cylindrical inner tube channel; 235. Exposed chamber branch pipe; 236. Exposed chamber diffusion guide groove; 24. Drinking water bottle; 241. Bottle body; 242. Bottle cap; 243. Water supply pipe; 25. Oral and nasal contamination exposure channel A; 26. Whole body poison exposure channel B; 261. Whole body poison exposure diffusion zone; 30. Contamination exposure chamber; 301. Fan-shaped passage; 302. Front and rear limit plates; 303. Top lifting limit plate; 304. Lifting bolts; 305. Feed bin; 35. Aerosol discharge pipeline interface; 36. Waste gas sampling pipeline interface. DETAILED DESCRIPTION

[0018] In order to make the objectives, technical solutions, and advantages of the present invention more clearly understood, the technical solutions of the present invention are further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely for the purpose of explaining the present invention and are not intended to limit the present invention. In addition, the technical features involved in the various embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.

[0019] Example 1 See attached Figures 1-18 The highly repeatable and high-precision animal exposure and poisoning experimental system provided in this embodiment includes an animal exposure and poisoning experimental unit, an operation support unit, and an operation control unit. The specific components and connection relationships of each unit are as follows: Figure 1 As shown, they work together and the control principle is as follows Figure 18 shown.

[0020] The animal exposure and poisoning experimental unit comprises: an aerosol air inlet sleeve 7, a poisoning exposure chamber 8, an isolation cage 21, a trumpet-shaped upper guide tube 22, and a cylindrical lower guide tube 23; The operation support unit includes: an air compressor 3, an aerosol generator 6, an exhaust gas treatment module 10, and a negative pressure vacuum pump 14, which are connected to each other through a connecting pipe 19 and are finally connected to the poison exposure chamber 8 respectively; the first air path of the air compressor 3 passes through the generating MFC 4 (aerosol generating air mass flow controller referred to as generating MFC), the aerosol generator 6 is connected to the aerosol connecting pipe 71 of the aerosol inlet sleeve 7; the second air path passes through the clean air MFC 5 (clean air mass flow controller, referred to as clean air MFC), is connected to the clean air connecting pipe 72 of the aerosol inlet sleeve 7; the exhaust gas treatment module 10 is connected to the lower section of the poison exposure chamber 8 through the aerosol exhaust pipe interface 35, and then connected to the first air path of the negative pressure vacuum pump 14 through the exhaust MFC12 (exhaust air mass flow controller, referred to as exhaust MFC); the second air path of the negative pressure vacuum pump 14 is connected to the impact sampler 9 and the particle size spectrometer 11 at the same time through the sampling MFC13 (sampling air mass flow controller, referred to as sampling MFC), and then connected to the lower section of the poison exposure chamber 8 through the exhaust gas sampling pipe interface 36.

[0021] The operation control unit includes an operation control group and a concentration monitoring group interconnected by a connecting line 18 or a connecting pipe 19; the operation control group is used to control the operation of each part in the exposed animal poisoning experimental unit and the operation support unit, and includes a control computer 1, a single-chip controller 2, a generating MFC 4, a clean air MFC 5, an impactor sampler 9, a particle size spectrometer 11, an exhaust MFC 12, and a sampling MFC 13; the concentration monitoring group is used to feedback data in real time, and automatically adjusts the input concentration after calculation by the operation control group to perform closed-loop control of the exposed animal poisoning experimental unit and the operation support unit, and includes: a differential pressure sensor 15, a particulate matter concentration sensor 16, an oxygen concentration sensor 17, an impactor sampler 9, and a particle size spectrometer 11; The specific connection method is: the control computer 1 is connected to the single-chip controller 2; the single-chip controller 2 is respectively connected to the generating MFC 4, the clean air MFC 5, the aerosol generator 6, the particle size spectrometer 11, the exhaust MFC 12, and the sampling MFC 13, and is also connected to the pressure difference sensor 15, the particle concentration sensor 16, and the oxygen concentration sensor 17; one end of the pressure difference sensor 15, the particle concentration sensor 16, and the oxygen concentration sensor 17 are all connected to the single-chip controller 2, and the other end is connected to the aerosol air inlet sleeve 7, corresponding to the pressure difference, particle concentration and oxygen concentration of the contaminated exposure mixed gas of the aerosol and the clean air in the mixed dilution chamber 74; one end of the impact sampler 9 is connected to the exhaust gas sampling pipeline interface 36, and the other end is connected to the particle size spectrometer 11 and the sampling MFC 13; one end of the particle size spectrometer 11 is connected to the exhaust gas sampling pipeline interface 36, and the other end is connected to the sampling MFC 13; MFC is the abbreviation of mass flow controller.

[0022] The poison exposure chamber 8 is a closed chamber with a spindle-shaped overall outline and a hollow interior, comprising: a hopper-shaped upper cover 81, a cylindrical middle chamber coaming 82, a funnel-shaped lower cover 84, and a support plate 83; The overall outline of the inverted bucket-shaped upper cover 81 is conical, with an opening at the center of its top circle. The conical hollow portion inside is the upper section. The lower section of the aerosol inlet sleeve 7 is embedded in the opening and extends into the interior of the inverted bucket-shaped upper cover 81. A sealing ring 811 is provided in the gap between the aerosol inlet sleeve 7 and the opening. The middle cabin coaming 82 is a vertically arranged cylindrical coaming (made of transparent material), and the cylindrical hollow portion inside the middle cabin coaming 82 is the middle section; The overall outline of the funnel-shaped lower cover 84 is funnel-shaped, and the conical hollow portion inside it is the lower section; The lower end surface of the inverted hopper-shaped upper cover 81 is fastened to the middle cabin coaming 82 and forms a sealing joint surface; the funnel-shaped lower cover 84 and the middle cabin coaming 82 are an integral structure; on the outer horizontal surface of the connection between the funnel-shaped lower cover 84 and the middle cabin coaming 82, an annular support plate 83 extending outward is provided to facilitate the overall movement of the contaminated exposure cabin 8; The three hollow sections of the upper section, the middle section and the lower section are connected to each other to form a closed structure inside the contaminated exposure chamber 8. The isolation cage 21, the trumpet-shaped upper guide tube 22 and the cylindrical lower guide tube 23 are all arranged as a whole in the closed structure.

[0023] The aerosol air inlet sleeve 7 is hollow inside, the upper section is a mixing and dilution chamber 74, and the lower section is arranged in the opening at the top of the poison exposure chamber 8; The aerosol inlet sleeve 7 is a hollow cylinder with a closed upper end and an open lower end. A slot 73 is horizontally provided on the side of the middle part of the hollow cylinder. The upper part of the slot 73 is the upper section (mixing and dilution chamber 74), and the lower part of the slot 73 is the lower section, which is arranged in the opening at the top of the exposure chamber 8. An aerosol connecting pipe 71 for connecting to an aerosol input pipeline is provided at the center position of the upper end surface of the hollow cylinder of the aerosol inlet sleeve 7; On the side of the upper section of the hollow cylinder of the aerosol inlet sleeve 7, a clean air connecting pipe 72 for connecting to the clean air input pipeline is provided; The aerosol connecting pipe 71 and the clean air connecting pipe 72 are joined above the insert slot 73 to form a mixing and dilution chamber 74 .

[0024] The isolation cage 21 is a cylindrical, air-permeable flat cage with an overall annular shape, and is disposed in the middle section of the spindle-shaped exposure chamber 8. The interior space of the isolation cage 21 is hollow near the center, forming a through groove 215, and the remaining portion is divided into a plurality of centrally symmetrical, independent exposure chambers 30. The trumpet-shaped upper guide tube 22 is generally trumpet-shaped with its opening downward, and is disposed entirely in the upper section of the shuttle-shaped poison exposure chamber 8. The upper section of its trumpet wall 221 divides the internal space of the lower section of the aerosol air inlet sleeve 7 into two mutually isolated gas channels: the outer surface of the trumpet wall 221 and the inner surfaces of the aerosol air inlet sleeve 7 and the poison exposure chamber 8 together form a whole-body poison exposure diffusion zone 261, and the hollow space inside the trumpet wall 221 forms the trumpet inner tube channel 224. The cylindrical lower guide tube 23 is hollow and is disposed within the through groove 215 in the middle of the isolation cage 21. The upper portion of the hollow cylindrical inner tube channel 234 is connected to the trumpet inner tube channel 224, and the bottom portion is provided with a plurality of exposure chamber branches 235 leading to the front of each of the contaminated exposure chambers 30. When the mixing and dilution chamber 74 is connected to the trumpet inner tube channel 224, the cylindrical inner tube channel 234, and the exposure chamber branch pipe 235, an exposure channel is formed for inputting the exposure mixed gas into the independent exposure chamber 30, namely, the oral and nasal exposure channel A 25, for conducting oral and nasal exposure animal experiments; When the mixing and dilution chamber 74 is connected to the whole-body poison exposure diffusion zone 261, an exposure channel for inputting the poison exposure mixed gas into the independent poison exposure chamber 30 is formed, namely the whole-body poison exposure channel B 26, which is used to implement whole-body poison exposure animal experiments.

[0025] The trumpet-shaped upper guide tube 22 comprises: a columnar guide tube 222, a trumpet tube wall 221, and a hollow horizontal support frame 225; The upper section of the horn wall 221 is a hollow columnar conduit 222, which is arranged at the center of the circle just above the horn wall 221. A conduit channel 223 is vertically provided inside the columnar conduit 222, which is connected to the inner tube channel 224 inside the horn wall 221. An annular hollow horizontal support plate 225 is also provided on the lower end surface of the horn wall 221; The trumpet-shaped speaker wall 221 is integrally arranged inside the bucket-shaped upper cover 81, and the hollow horizontal support frame 225 is arranged on the outer surface of the bottom of the trumpet-shaped speaker wall 221, extending horizontally outward and deep, surrounding the trumpet-shaped speaker wall 221. The trumpet-shaped upper guide cylinder 22 is integrally arranged directly above the cylindrical lower guide cylinder 23 through its hollow horizontal support plate 225, so that the trumpet inner cylinder channel 224 and the cylindrical inner cylinder channel 234 are aligned with each other and connected to the isolation cage 21; The cylindrical conduit 222 is inserted upward into the interior of the aerosol inlet sleeve 7, dividing the internal space of the lower section of the aerosol inlet sleeve 7 into two isolated gas channels: the outer surface of the cylindrical conduit 222 and the inner surface of the aerosol inlet sleeve 7 and the exposure chamber 8 together form a whole-body exposure diffusion zone 261, which is part of the whole-body exposure channel B26; the hollow conduit channel 223 inside the cylindrical conduit 222 forms the upper section of the trumpet inner tube channel 224, which is connected to the cylindrical inner tube channel 234 and the exposure chamber branch 235 to form the oral and nasal exposure channel A25; After the external aerosol and clean air are mixed in the mixing and dilution chamber 74 at the upper section of the aerosol inlet sleeve 7, they are introduced into one of the two isolated gas channels to carry out the corresponding poison exposure experiment.

[0026] In order to facilitate the switching of exposure channels, the animal exposure experiment unit of this embodiment further includes: a poison exposure channel switching plug 20; The poison exposure channel switching plug 20 is a sheet substrate with a semicircular end, and two switching plugs with through-hole structures are provided at different positions of the sheet substrate: Contamination channel switching insert A 20a: A central through hole 20a2 is provided at the center of the semicircular shape of the sheet substrate 20a1, and the sheet substrate portion around the central through hole 20a2 is closed; Poison channel switching insert B 20b: The center of the semicircular circle of the sheet substrate 20b1 is closed, and plum blossom-shaped through holes 20b2 are provided around the periphery of the semicircular circle center; The poison exposure channel switching plug 20 is pluggable and disposed in the plug slot 73 for switching between the oral and nasal poison exposure channel A 25 and the whole body poison exposure channel B 26: When the poison channel switching plug A 20a is inserted into the plug slot 73, the central through hole 20a2 opens (conducts) the hollow conduit channel 223 inside the columnar conduit 222, so that the oral and nasal poison exposure channel A 25 is connected to the mixing and dilution chamber 74 upward and to each poison exposure chamber 30 downward. At the same time, the whole-body poison exposure diffusion area 261 outside the columnar conduit 222 is closed, that is, the entrance of the whole-body poison exposure channel B 26 is closed, and the poison exposure mixed gas after the aerosol and clean air are mixed in the mixing and dilution chamber 74 is passed through the oral and nasal poison exposure channel A 25 and input into each poison exposure chamber 30 from the opening of the exposure chamber branch pipe 235, and is mainly inhaled by the mouth and nose of the experimental animals to carry out the oral and nasal poison exposure experiment; When the poison channel switching plug B 20b is inserted into the plug slot 73, its plum blossom-shaped through hole 20b2 opens (conducts) the whole-body poison exposure diffusion area 261 outside the columnar catheter 222, so that the whole-body poison exposure channel B 26 is connected to each poison exposure chamber 30. At the same time, the internal catheter channel 223 of the columnar catheter 222 is closed, that is, the entrance of the oral and nasal poison exposure channel A 25 is closed, and the poison exposure mixture gas of aerosol and clean air is input into each poison exposure chamber 30 from the whole-body poison exposure diffusion area 261 inside the poison exposure chamber 8 and outside the horn wall 221 through the whole-body poison exposure channel B 26, and is mainly absorbed by the experimental animals and partially adsorbed by the fur of the experimental animals to carry out the whole-body poison exposure experiment.

[0027] To simplify the overall structure, the isolation cage 21 of this embodiment is a semi-enclosed cage in the shape of an annular flat cylinder, wherein one side facing the center is open, and a cylindrical through groove 215 is formed in the hollow position around the center of the circle, extending vertically therethrough. The cage 21 comprises the following interlocking metal perforated plates: a cage bottom plate 211, a cage cover plate 212, an outer cage enclosure plate 213, and a plurality of vertical partitions 214. The metal perforated plates are provided with a plurality of openings, each having a cylindrical or circular outline, and the cylindrical openings are parallel to each other. The cage bottom plate 211 is a ring-shaped metal perforated plate with a through hole in the center (a through hole is provided at the center of the circle), which is arranged on the boss at the junction of the funnel-shaped lower cover 84 and the middle cabin coaming 82; The cage cover plate 212 is formed by splicing together a plurality of sector-shaped plates 2121. After splicing, the overall shape of the metal perforated plate is annular. Each spliced cover plate 2121 covers the upper part of the sector-shaped channel of the poison exposure chamber 30, sealing the sector-shaped channel of the poison exposure chamber 30 from the top. The outer cage panel 213 is a vertically arranged annular plate connected end to end, and is arranged between the cage bottom plate 211 and the cage cover plate 212; The vertical partitions 214 are vertical plates. Multiple vertical partitions 214 are centrally symmetrical and vertically arranged between the bottom plate 211, the cage cover plate 212, and the outer cage enclosure plate 213. The cylindrical lower guide tube 23 is disposed in the through groove 215, and together they divide the interior space of the isolation cage 21 into multiple independent poison exposure chambers 30. Each independent poison exposure chamber 30 is a fan-shaped channel 301 surrounded by six sides, and the fan-shaped channel 301 is narrow in front and wide in the back, and is used to place experimental animals. When conducting experiments using the whole-body exposure method, the entire (larger) internal space of the fan-shaped channel 301 of each poison exposure chamber 30 is used. When conducting experiments using the mouth and nose exposure method, the front space of the fan-shaped channel 301 is further reduced by the front and rear limit plates 302 and the top lifting limit plate 303, forcing the experimental animals to be confined to the narrow front space of the fan-shaped channel 301.

[0028] Specifically, each independent exposure chamber 30 is further provided with a top lifting limit plate 303 and front and rear limit plates 302 for limiting the position of the experimental animal. The top lifting limit plate 303 is suspended on the cage cover 212 by lifting bolts 304 and moves up and down during use to limit the height movement space of the experimental animal in the fan-shaped channel 301. The front and rear limiting plates 302 are vertically inserted into the middle of the fan-shaped channel 301 of each poison exposure chamber 30 (the inserts provided on the upper and lower sides thereof are inserted into the openings of the perforated plates), dividing the fan-shaped channel 301 of each poison exposure chamber 30 into two parts, front and back. The experimental animal is placed in the front part, restricting the experimental animal to move with its head facing forward, in the narrow space in front of the fan-shaped channel 301 (it can only move forward and backward, and cannot turn around or jump); When conducting an animal's mouth and nose exposure experiment, the top lifting limit plate 303 moves downward and the front and rear limit plates 302 move forward, confining the experimental animal to the front of the fan-shaped channel 301 of the exposure chamber 30, so that the animal always keeps its head forward and cannot jump or turn around, forcing the mouth and nose of the experimental animal to passively approach the outlet of the exposure chamber branch pipe 235; When conducting a whole-body exposure experiment on animals, the top lifting limit plate 303 is moved upward, and the front and rear limit plates 302 are moved backward or directly removed, so as to confine the experimental animals within the entire space of the fan-shaped channel 301, or within a larger area within the fan-shaped channel 301, so that they can move freely within the space, including jumping or turning.

[0029] In order to accelerate the descent rate of the poisonous exposure mixed gas and reduce the high-concentration area during whole-body exposure, a sloped outer surface of the lower guide tube wall 231 is designed. Guide and isolation fins 233 and exposure chamber diffusion guide grooves 236 are provided on this outer surface corresponding to each poisonous exposure chamber 30 to increase the settling rate of the poisonous exposure mixed gas and concentrate the high-concentration exposure area in the area of each poisonous exposure chamber 30 near the center of the isolation cage 21. Specifically: The cylindrical lower guide tube 23 includes a lower guide tube wall 231 and a lower guide tube base 232. A plurality of parallel fins 233 are vertically provided on the outer surface of the lower guide tube wall 231. A cylindrical inner tube channel 234 is vertically provided inside the lower guide tube wall 231, and the lower end of the cylindrical inner tube channel 234 is closed by the lower guide tube base 232. A plurality of exposure chamber branches 235 leading to the contaminated exposure chambers 30 are provided at an angle from the inside to the outside of the cylindrical inner tube channel 234 near the lower guide tube base 232. The inclined cavity formed between the outer surface of the lower guide tube wall 231 and the fins 233 is the exposure chamber diffusion guide groove 236, which communicates with each contaminated exposure chamber 30 from the outside of the lower guide tube wall 231. The upper end surfaces of the lower guide tube wall 231 and the fins 233 are connected to the horn tube wall 221 and the hollow horizontal support frame 225 respectively, and the centers of the lower guide tube wall 231 and the horn tube wall 221 are on a vertical line, and the cylindrical inner tube channel 234 of the cylindrical lower guide tube 23 is connected to the horn inner tube channel 224; When the cylindrical lower guide tube 23 is integrally disposed within the through groove 215 of the isolation cage 21, the upper and lower end surfaces of the lower guide tube wall 231 are flush with the cage bottom plate 211 and the cage cover plate 212, respectively. The lower guide tube wall 231 and the fins 233 seal the opening of each contaminated exposure chamber 30 toward the center of the circle, so that all six sides of each contaminated exposure chamber 30 are closed (air permeability is maintained by the openings of the metal perforated plate).

[0030] To further improve experimental accuracy and repeatability, the cavity (i.e., the exposure chamber diffusion guide groove 236) between the outer side surface of the lower guide tube wall 231 and the fins 233, which is connected to the front end of each exposure chamber 30, and the lower part near the outlet of the exposure chamber branch pipe 235, also serves as a feed bin 305 for storing feed for experimental animals (which is placed in advance before the experiment begins); The hollow horizontal support frame 225 is also provided with a plurality of drinking bottles 24 with downward-facing openings. The drinking bottles include a bottle body 241, a bottle cap 242, and a water supply pipe 243. The water supply pipe 243 extends downward into the front portion of the fan-shaped channel 301 of each of the exposure chambers 30, with its lower end adjacent to the air outlet of the exposure chamber branch pipe 235, and is used to provide drinking water for the experimental animals (the drinking water is pre-filled before the experiment begins). Feed is placed in the feed bin 305 and water is placed in the water bottle 24 to induce the experimental animals to actively move their mouths and noses close to the air outlet of the exposure chamber branch pipe 235 to improve the total exposure inhalation dose and accuracy.

[0031] The highly repeatable and high-precision animal exposure and poisoning experimental method provided in this embodiment is implemented using the aforementioned highly repeatable and high-precision animal exposure and poisoning experimental system. Figure 1 As shown in the figure, after connecting the various parts of the high repeatability and high precision animal exposure experiment system in sequence, the whole system can start working. Figure 18 System automatic control flow chart, in which the MFC reported flow is the dotted line, and the MCU controlled MFC flow is the solid line.

[0032] The operation control unit controls the collaborative operation of the animal exposure and poisoning experiment unit and the operation support unit. The main working process is as follows: experimental animals are selected according to the experimental design plan and placed in each poison exposure chamber. Then, the operation control unit controls the aerosol generator 6 and the air compressor 3 to respectively input aerosol and clean air into the mixing and dilution chamber 74 and mix them. After mixing in the mixing and dilution chamber, a poison exposure mixed gas is obtained. The two isolated exposure channels, the oral and nasal poison exposure channel A 25 and the whole body poison exposure channel B 26, are switched through the poison channel switching plug 20. The poison exposure mixed gas is independently input into each poison exposure chamber 30 through one of the exposure channels, and enters the poison exposure chamber 8 for the poison exposure experiment, thereby realizing a set of experimental systems to complete animal poison exposure experiments in oral and nasal exposure mode or whole body exposure mode, and obtain highly repeatable and high-precision exposure and poisoning animal experimental data. After the poison exposure experiment, the gas is discharged from the poison exposure chamber for waste gas sampling and waste gas treatment before being discharged (sucked out by a negative pressure vacuum pump). The aerosol of this embodiment can ensure the uniformity of its particle size and concentration distribution in each poison exposure chamber 30 through two uniquely designed exposure channels; during the experiment, the operation control unit can adjust the generation speed of the aerosol generator 6 or the clean air flow in real time based on the data feedback from the aerosol particle concentration sensor 16, the pressure difference sensor 15 and the oxygen concentration sensor 17 to control the concentration of the exposure aerosol.

[0033] See also Figure 18 , the closed-loop adjustment of the experimental process is performed with the single-chip controller 12 as the core, and the flow rate of the aerosol generator is usually kept unchanged. If the concentration of aerosol in the contaminated exposure mixed gas collected by the particle concentration sensor 16 is too high, the flow rate of clean air is increased to reduce the concentration of aerosol; conversely, if the concentration of aerosol in the contaminated exposure mixed gas collected by the particle concentration sensor 16 is too low, the flow rate of the aerosol generator is increased, or the flow rate of high clean air is reduced to increase the concentration of aerosol, and the aerosol concentration in the contaminated exposure chamber 8 is maintained stable during the experiment; similarly, if the concentration of oxygen in the contaminated exposure mixed gas collected by the oxygen concentration sensor 17 is too high, the flow rate of clean air is reduced, otherwise the flow rate of clean air is increased to maintain the oxygen concentration in the contaminated exposure chamber 8 stable during the experiment; if the pressure in the contaminated exposure chamber 8 collected by the differential pressure sensor 15 is too high, the exhaust flow rate is increased, otherwise the exhaust flow rate is reduced to maintain the pressure in the contaminated exposure chamber 8 stable during the experiment. The control computer 1 is used to remotely control the single-chip controller 2 to complete the complex closed-loop control process and send instructions to the single-chip controller 2. The single-chip controller 2 further controls the aerosol generator and each MFC to execute the instructions, so that the experiment proceeds smoothly.

[0034] Among them, when implementing the oral and nasal poison exposure experiment, it also includes restricting the body position of the experimental animal to the front of the fan-shaped channel 301 in the poison exposure chamber 30, with the head facing it and unable to turn around or jump, and then providing the experimental animal with drinking water and feeding rewards on the head, so that the animal's head is more in the smaller space near the air outlet of the exposure chamber branch pipe 235 during the experimental time, so as to complete the highly repeatable oral and nasal exposure method of exposure to poison animals and obtain high-precision exposure experimental data close to the conventional oral and nasal exposure method.

[0035] Among them, when implementing the whole-body poison exposure experiment, it also includes restricting the body position of the experimental animal within the entire space of the fan-shaped channel 301 of the poison exposure chamber 30, so that the experimental animal can move freely, and then providing the experimental animal with drinking water and feeding rewards on the head, so that the animal can move more in the space close to the feed bin 305 and with uniform aerosol concentration distribution during the experimental time, so as to complete highly repeatable exposure poison animal experiments and obtain high-precision exposure experimental data than conventional whole-body exposure methods.

[0036] The basic working principles of the embodiments of the present invention are dynamic circulation, toxicokinetic simulation (animals absorb poisons through breathing and skin contact, simulating real exposure routes) and quantitative exposure (calculating the inhalation dose through mathematical models, such as concentration × time × respiratory volume), etc. The specific connection of each part and the control method of flow rate, concentration, etc. can all adopt conventional technology and therefore will not be described in detail.

[0037] The highly repeatable and high-precision animal exposure experiment method provided in this embodiment is implemented using the aforementioned highly repeatable and high-precision animal exposure experiment system. By switching between two mutually isolated oral and nasal exposure channels A 25 and whole-body exposure channels B 26, one of which inputs the poison exposure gas into the poison exposure chamber 30, a set of experimental systems is used to complete animal poison exposure experiments in oral and nasal or whole-body exposure modes in a time-sharing manner, and obtain highly repeatable and high-precision animal exposure experiment data.

[0038] Example 2 The highly repeatable and high-precision animal exposure experiment system and method provided in this embodiment is based on Example 1, and specifically provides an animal exposure experiment system and method for oral and nasal exposure. It also specifically implements a highly repeatable and high-precision animal exposure experiment to study the respiratory and systemic toxicity of lunar dust simulated particulate aerosols on mice. The lunar dust simulated particulate matter (simulating the composition of the lunar regolith) is evaluated, and the toxic effects on the respiratory system, immune response and systemic organs (such as the lungs, liver, and brain) of mice are explored through oral and nasal exposure experiments to reveal its potential fibrosis, oxidative stress and genotoxicity mechanisms.

[0039] The highly repeatable and high-precision animal exposure experiment method and system used in this embodiment are basically the same as those in Example 1. When conducting the oral and nasal exposure experiment, the body position of the experimental animal (mouse) must first be strictly restricted to the fan-shaped channel 301 at the front of the exposure chamber 30 (passive control), with the head facing forward and the mouth and nose close to the air outlet of the exposure chamber branch 235. The animal cannot turn around or jump, and the body can only move forward and backward, not left and right. Then the experiment can be started. During the experiment, the experimental animal is provided with drinking water and feeding rewards (active enticement) on the head, so that the animal's head is more often in the smaller space near the air outlet of the exposure chamber branch 235 during the experimental time, so as to complete the highly repeatable animal exposure experiment and obtain high-precision exposure experiment data that is close to or the same as the conventional oral and nasal inhalation method.

[0040] This example uses the animal poison exposure experimental system of Example 1, and its experimental method further includes the following steps: S1. Experimental Design S1-1 Experimental Purpose To evaluate the toxic effects of lunar dust-simulated particles (simulating the composition of the lunar regolith) on the respiratory system, immune response and systemic organs (such as lungs, liver, and brain) of mice through a whole-body exposure poisoning device, and to reveal its potential fibrosis, oxidative stress and genotoxic mechanisms.

[0041] S1-2 Experimental Materials and Main Equipment Experimental animals: SPF-grade C57BL / 6 mice (half male and half female, 8 weeks old), randomly divided into the following groups: Control group: clean air exposure (n=10) Low-dose group: lunar dust particles 100 mg / m³ (simulating short-term lunar mission exposure, n=10) High-dose group: lunar dust particles 500 mg / m³ (simulating long-term or high-concentration exposure, n=10) Experimental materials: Lunar dust simulation particles: refer to NASA JSC-1A / 1AV standard formula (containing plagioclase, pyroxene, olivine, ilmenite, etc.), the particle size simulates real lunar dust (0.1-20 μm, irregular angular morphology).

[0042] Aerosolization treatment: Pretreatment is required to form completely dry particles.

[0043] The main equipment of the animal exposure experiment system includes: Aerosol generator (Venturi effect principle). During the experiment, lunar dust is directly sucked out through negative pressure and blown away by compressed air to form aerosol.

[0044] Real-time aerosol monitors (such as the Grimm 1.109 aerosol monitor, which monitors aerosol concentrations in real time); Auxiliary equipment: Air compressor and low-temperature dryer for simulating lunar low humidity control (simulating lunar dry environment, humidity <10%); Animal lung function tester (invasive lung function system); Laser scanning confocal microscopy (to observe the deposition of particles in lung tissue); S2. Experimental system preparation S2-1 First, according to Figure 1 As shown, first, the various parts of the exposure animal experiment system are connected to each other, and then the exposure channel switching plug A 20a is inserted into the plug slot 73 to connect the oral and nasal exposure channel A 25 with each exposure chamber 30, while the entrance of the whole body exposure channel B 26 is closed; In this embodiment, the contaminated exposure chamber 8 adopts a transparent wear-resistant shell, and the overall outer contour is a transparent, hollow structure in the shape of a shuttle. Among them, the conical upper cover 81, the middle cabin panel 82, and the lower cover 84 are all designed with wear-resistant PC plastic or glass to prevent erosion by simulated lunar dust particles; a sealing ring 811 is used to seal between the conical upper cover 2 and the columnar guide tube 222 of the trumpet-shaped upper guide tube 22.

[0045] The isolation cage 21 is divided into multiple independent poison exposure chambers 30. Each poison exposure chamber 30 is surrounded by a cage bottom plate 211, a cage cover plate 212, an outer cage enclosure plate 213, vertical partitions 214, and a lower guide tube wall 231. The cage cover plate 212 is an independent fan-shaped structure, and the cage cover plate 212 and vertical partitions 214 are both detachable structures. The cage bottom plate 211 and the outer cage enclosure plate 213 are provided with multiple slots (cylindrical openings). Each vertical partition 214 is inserted between the inner side of the outer cage enclosure plate 213 and the cage bottom plate 211 (which is an overall circular structure) through the slots, and evenly divides the space above the cage bottom plate 211. After the upper part is covered with the cage cover plate 212, a six-sided poison exposure chamber 30 is formed. The cage cover plate 212 is formed by splicing together a plurality of fan-shaped spliced cover plates 2121. After splicing, the overall shape of the spliced cover plate is an annular metal perforated plate. Each spliced cover plate 2121 covers the upper part of the fan-shaped channel 301 of the poison exposure chamber 30, thereby sealing the fan-shaped channel 301 of the poison exposure chamber 30 from above. According to the experimental design, the front and rear limit plates 302 are vertically inserted into the middle of the fan-shaped channel 301 of each poison exposure chamber 30, dividing the fan-shaped channel 301 of each poison exposure chamber 30 into two parts, front and rear. During the experiment, the experimental animal is placed in the front part, restricting the experimental animal to move only with its head forward and in the space in front of the fan-shaped channel 301; then the top lifting limit plate 303 is moved downward and the front and rear limit plates 302 are moved forward; during the experiment, the specific positions of the lifting limit plate 303 and the front and rear limit plates 302 are adjusted according to the size of the experimental animal, and the experimental animal is confined to the front of the fan-shaped channel 301 of the poison exposure chamber 30, so that the experimental animal always keeps its head forward, cannot jump or turn around, and can only move its body slightly forward and backward, forcing the mouth and nose of the experimental animal to passively approach the air outlet of the exposure chamber branch pipe 235 (semi-restraint); S2-2 connects the operation control unit and the operation support unit, respectively, to perform operation control and operation support. It controls the concentration and flow of the toxic exposure mixed gas according to the experimental design. Each sensor detects and feeds back the operation data in real time. The control computer 1 and the single-chip controller 2 of the operation control automatic unit calculate and adjust the input concentration and pressure to perform closed-loop control. At the same time, environmental control is performed during the experiment to maintain constant temperature and humidity to reduce animal stress. S2-3 Preparation of experimental animals and experimental materials Prepare experimental animals and experimental materials separately, and prepare lunar dust simulated particulate aerosol.

[0046] Particle activation: lunar dust simulating particles were prepared and then baked at high temperature (200°C for 2 hours) to remove organic matter and simulate the non-adsorption characteristics of the lunar vacuum environment; Aerosol preparation: Dry air is used to drive an aerosol generator (Venturi tube suction and spray generator) to disperse particles, controlling the mass concentration to 100-500 mg / m³ and the peak particle size to 1-3 μm (simulating the inhalable range); S3. Conduct oral and nasal exposure experiments on animals Toxic exposure protocols include: Exposure period: 4 hours per day for 4 consecutive weeks (simulating a long-term mission at a lunar base); Exposure chamber environment: temperature 25±1°C, humidity <10%, CO2 concentration maintained at 0.5% (simulating the risk scenario of space suit leakage).

[0047] Dynamic exposure control: monitors the particle concentration in the chamber every 15 minutes and automatically calibrates the airflow velocity when the deviation is >10%; Aerosol leakage risk control: The slightly positive pressure of the exposure chamber 8 allows precious samples to be more fully exposed to animals, but there is a risk of leakage. A three-stage HEPA+ULPA filter is connected in series at the outlet of the exposure chamber 8 to prevent the leakage of simulated lunar dust. The aerosol generator 6 and the exposure chamber 8 must be placed in a biological safety cabinet for experiments, and the experimenters must wear N95 masks. Animal welfare (ethics) protection: Experimental animals are semi-restrained and provided with free access to drinking water and feed during exposure, so that animal welfare is fully guaranteed.

[0048] S3-1 Set exposure parameters in the control software of the operation control unit, such as exposure aerosol concentration, exposure chamber pressure (slightly positive pressure), minimum ventilation volume, etc., and set environmental control parameters; S3-2: Under environmental control parameters, the experiment begins: the mice are grouped and placed in separate poison exposure chambers 30 in the isolation cages 21 within the poison exposure chamber 8. Each mouse is isolated within the poison exposure chamber 30, maintaining a constant temperature (22±2°C) and humidity (50±10%). Sufficient food is added to the feed bin 305, and sufficient clean drinking water is added to the drinking bottle 24 to ensure that the mice have their food and water needs for 6 hours. Each mouse is confined to a semi-restrained position within the narrow fan-shaped passages 301 of each poison exposure chamber 30 in the isolation cages 21, preventing them from turning around or running. S3-3: According to the set exposure parameters, the aerosol generator 6 introduces exposure aerosol gas (mixed with clean air to adjust its concentration) into the poison exposure chamber 8. Each concentration monitoring sensor feeds back the data in the poison exposure chamber 8 in real time and sends it to the operation control unit, which automatically adjusts the concentration of the input aerosol and oxygen to perform closed-loop control. At the same time, during the exposure experiment, the mice are provided with free drinking water and feed, so that the heads of the mice are located near the center of the poison exposure chamber 8, and the mouths and noses of the experimental animals are lured to actively approach the outlet of the exposure chamber branch 235 (the area with high concentration and uniform particle size distribution) to increase the total exposure inhalation dose and accuracy. The respiratory rate of the mice is also stabilized and close to the normal physiological value. The introduction of the exposure aerosol is stopped until the exposure time is reached. During the exposure experiment, the aerosol generator 6 sucks the gas in the poison exposure chamber 8 that has completed the exposure experiment out of the poison exposure chamber 8 at a set flow rate and a negative pressure after treatment to maintain the exposure aerosol concentration and pressure in the poison exposure chamber 8. After reaching the exposure time (4 hours per day for 4 consecutive weeks) in S3-4, the experimental mice were removed, samples were collected, and then tested; S4. Experimental Data Analysis The physiological data and activity data of the experimental animals collected during the experiment, as well as the data obtained from the animal samples, are summarized and analyzed to obtain the toxic effect data on the respiratory system, immune response and systemic organs of the experimental animals in the whole-body exposure experiment, including the following contents: S4-1 Respiratory system assessment: Pulmonary function: detect airway resistance (Raw) and lung compliance (Cchord).

[0049] Bronchoalveolar lavage fluid (BALF): analysis of total protein content, lactate dehydrogenase (LDH, a marker of lung injury), and differential inflammatory cell count.

[0050] Lung tissue pathology: Masson trichrome staining (collagen deposition), transmission electron microscopy (observation of lunar dust particles penetrating the alveolar barrier).

[0051] S4-2 Oral and nasal toxicity analysis: Oxidative stress: detection of MDA, SOD, and GSH-Px in lung and liver tissues; Systemic inflammation: serum IL-1β, IL-6, TNF-α (Luminex multifactor assay); Genotoxicity: peripheral blood lymphocyte comet assay (DNA damage degree); Brain tissue effects: immunohistochemistry for Iba-1, a marker of microglial activation; S4-3 Lunar dust removal dynamics analysis: Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify the contents of silicon (Si), iron (Fe), and titanium (Ti) in the lungs and spleen, and to evaluate the systemic migration patterns of lunar dust-simulated particles.

[0052] S4-4 Experimental analysis results The high-dose group of mice showed interstitial fibrosis in the lung tissue (collagen area increased by more than 30%), and LDH activity in BALF was significantly increased.

[0053] Increased serum IL-6 levels indicate a systemic inflammatory response.

[0054] The activation of brain microglia may be related to the penetration of lunar dust nanoparticles through the blood-brain barrier.

[0055] Through actual experiments, it was found that the technical solution and experimental results provided by this embodiment also have the following unique features: (1) Lunar dust-specific exposure simulation: The particulate aerosol generator 6 that adopts the principle of Venturi effect does not need to compress the lunar dust particles into powder cakes and then further scrape and blow them away to simulate the occurrence. It only needs to put the processed lunar dust into the disc of the aerosol generator 6 and directly form an aerosol through the Venturi tube suction and spray method, which can perfectly reproduce the electrostatic adsorption characteristics of particulate matter on the lunar surface.

[0056] (2) Aerosol uniformity: A reasonable design of the space of the poison exposure chamber 8 and its isolation cage 21 is adopted to optimize the particle size distribution and concentration uniformity of the aerosol inside it. For example, the poison exposure chamber 8 adopts a shuttle-shaped exposure chamber structure to reduce turbulence during the aerosol sedimentation process; the opening and closing of the upper cover 81 is adopted to load and remove experimental animals, which can minimize the height of the poison exposure chamber 8 and reduce the occupied internal volume; the oral and nose poison exposure channel A 25 with an overall trumpet-shaped structure in the center of the isolation cage 21 in the poison exposure chamber 8 is conducive to the uniform and rapid diffusion of the aerosol input from the top into each poison exposure chamber 30.

[0057] (3) Dose accuracy: The actual inhalation dose is calculated based on the exposure time and respiratory rate (about 150 times / minute for mice). In this device, the animals are restricted by the isolation cage 21 and cannot run freely. All mice are in almost the same position (the position is the center position of the most uniform concentration and particle size distribution in the poison exposure chamber 8), and the mice are in a semi-restrained state. In addition, they are provided with food and water. The respiratory rate of the animals is more stable and close to the normal physiological value during the whole experiment. The inhalation dose calculated in this way is more accurate and has a very high repeatability, which is close to the concentration deviation of the traditional oral and nasal inhalation exposure method (less than 10%).

[0058] (4) High-concentration exposure of trace samples: Since it is difficult to obtain lunar dust simulants, it is necessary to achieve high-concentration exposure experiments with minimum consumption. This requires that the volume of the animal exposure chamber 8 (especially each exposure chamber 30) be smaller while the particulate aerosol generator 6 can be stably generated, thereby reducing the probability of particle collision inside and achieving low-dose, high-concentration experiments. The system and method provided in this embodiment, through the combined design of the exposure chamber 8 and the experimental method, can fully meet these requirements and provide a feasible solution for high-precision exposure experiments on various precious materials.

[0059] (5) Multiple organ toxicity test: The health risks of lunar dust can be comprehensively assessed by combining local lung damage with systemic inflammation and neurotoxicity.

[0060] (6) Dose equivalence design: The human equivalent dose can be converted based on the mouse minute ventilation volume (MV=0.025 L / min).

[0061] Example 3 The highly repeatable and high-precision animal exposure and poisoning experimental system and method provided in this embodiment are basically the same as those in Example 1 and Example 2, except that a whole-body exposure animal exposure experimental system and method are provided, specifically, an experimental system and method for studying the toxicity of DEP dry powder particulate aerosol on the respiratory system of mice is provided.

[0062] The animal exposure and poisoning experimental system used in this embodiment is the same as that of Examples 1 and 2, with the difference being that, when conducting the whole-body poisoning exposure animal experiment, the body position of the experimental animal is restricted to a larger space of the poisoning exposure chamber 30 (not restrained), and there is no need to use the front and rear limit plates 302 and the top lifting limit plate 303. The experimental animal mice can move freely in the fan-shaped channel 301, including turning around, jumping, etc. Then, by providing drinking water and feeding rewards to the mice on their heads, the mice are allowed to move more in a smaller space close to the feed bin 305, where the aerosol concentration is evenly distributed, and close to the center of the isolation cage 21 during the experimental time, so as to complete a highly repeatable whole-body poisoning exposure animal experiment and obtain high-precision exposure experimental data compared to conventional whole-body poisoning methods.

[0063] The whole-body exposure to poison animal experimental system and method provided in this embodiment specifically include the following contents: S1. Experimental Design S1-1 Experimental Purpose To study the effects of DEP (Diesel Exhaust Particles) on the respiratory system of mice through whole-body exposure, evaluate its toxicity mechanisms (such as inflammatory response, oxidative stress, and histopathological changes), and understand the impact of motor vehicle exhaust emissions on human health.

[0064] S1-2 Experimental materials and main equipment Experimental animals: SPF male C57BL / 6 mice (8 weeks old, weighing 20-25 g) were randomly divided into a control group and an exposure group (n=10 in each group).

[0065] Experimental material: DEP dry powder particles, which need to be pre-treated to completely dry particles.

[0066] Main equipment of whole body exposure poisoning system: Aerosol generator 6 (Venturi effect principle), poison exposure chamber 8, real-time aerosol concentration monitor (such as laser particle counter), waste gas treatment, etc.

[0067] Auxiliary equipment: clean air compressor, biological safety cabinet.

[0068] S2. Experimental system preparation S2-1 Set up a whole-body exposure animal poisoning experimental unit, and connect the aerosol introduction device, poison exposure chamber device, and aerosol outlet device to each other through ventilation pipes; Insert the poison exposure and poison channel switching plug B 20b into the plug slot 73. The plum blossom-shaped through hole opens the whole-body poison exposure diffusion area 261 outside the columnar conduit 222, connecting the whole-body poison exposure channel B 26 with each poison exposure chamber 30. The poison exposure mixture of aerosol and clean air is evenly diffused in all directions from the hollow portion outside the horn wall 221 and the lower guide tube wall 231, especially along the curved slope of the horn wall 221, to the lower part, and quickly input into each poison exposure chamber 30 to carry out the whole-body poison exposure experiment. At the same time, the conduit channel 223 inside the columnar conduit 222 is closed, that is, the entrance of the oral and nasal poison exposure channel A 25 is closed. S2-2 sets the operating parameters of the operation control unit, which controls the operation of the aerosol generator 6, the exposure chamber 8, the exhaust gas outlet, etc. in the whole-body exposure animal poisoning experimental unit; Each sensor feeds back concentration monitoring data in real time, and the operation control unit automatically adjusts the input concentration to perform closed-loop control; During the experiment, the temperature and humidity were maintained constant to reduce animal stress.

[0069] S2-3 Preparation of experimental animals and experimental materials Prepare experimental animals and experimental materials separately, and prepare aerosols: use a dry powder aerosol generator to disperse DEP particles into stable aerosols, which are driven by compressed air and introduced into the mixing and dilution chamber 74 on the top of the exposure chamber 8; The operation control unit automatically adjusts the particulate matter mass concentration in the exposure chamber 8 to, for example, 100-500 μg / m³ through PID control. After the concentration reaches a stable value, the system automatically starts the experiment. During the experiment, the particle size distribution is monitored in real time, including controlling the median particle size of PM2.5 to ≤2.5 μm.

[0070] S3. Conduct whole-body exposure animal experiments S3-1 Set the exposure parameters in the control software of the operation control unit, such as exposure aerosol concentration, experimental chamber pressure (slightly positive pressure), minimum ventilation volume, etc.; also set the environmental control parameters, such as temperature, humidity, and oxygen concentration; S3-2: Under environmental control parameters, mice are grouped and placed in isolation cages 21 within the exposure chamber 8, specifically in individual exposure rooms 30, ensuring that each mouse is individually isolated. The exposure chamber 8 maintains a constant temperature (22±2°C) and humidity (50±10%). A sufficient amount of food is pre-filled into the feed bin 305, and sufficient clean drinking water is added to the drinking bottle 24 to ensure that the mice have their food and water needs for 6 hours. Each mouse is confined to the isolation cage and is not allowed to move freely. Exposure parameters: 6 hours per day for 5 consecutive days (simulating subacute exposure), the control group was exposed to filtered clean air; Real-time monitoring of the particle concentration in the cabin (e.g., Grimm 1.109 aerosol monitor) to ensure dosage consistency; S3-3 According to the set exposure parameters, the exposure aerosol is introduced into the poison exposure chamber 8 by the aerosol generator, and the particle concentration sensor 16 feeds back the data in the poison exposure chamber 8 in real time and sends it to the operation control unit, which automatically adjusts the input concentration, etc. to perform closed-loop control; at the same time, during the exposure experiment, the mice are provided with free drinking water through the water supply pipe 243 of the drinking bottle 24, and feed is provided through the feed bin 305, so that the head of the mouse is in a position close to the center of the poison exposure chamber 8 where the concentration and particle size distribution are uniform for a long time, and the respiratory rate of the mouse is stable and close to the normal physiological value; until the exposure time is reached, the introduction of the exposure aerosol is stopped; during the exposure experiment, the gas that has completed the exposure in the poison exposure chamber 8 is sucked out of the poison exposure chamber 8 for treatment at a set flow rate under negative pressure, and the concentration of the exposure aerosol in the poison exposure chamber 8 is maintained; Controlling the uniformity of aerosols: Through the combined optimized design of the poison exposure chamber 8, the isolation cage 21, the trumpet-shaped upper guide tube 22, and the cylindrical lower guide tube 23, the particle size distribution and concentration uniformity of the aerosol in each poison exposure chamber 30 are significantly enhanced; for example, the overall adoption of a shuttle-shaped exposure chamber structure in the poison exposure chamber 8 can reduce turbulence during aerosol sedimentation; a trumpet-shaped upper guide tube 22 is provided at the central position of the isolation cage 21 in the poison exposure chamber 8 to form each poison exposure chamber 30. The trumpet-shaped upper guide tube 22 at the upper portion can quickly guide the aerosol to the front (near the center) of each poison exposure chamber 30, and then diffuse it evenly from front to back, resulting in high aerosol uniformity and greatly improved aerosol utilization.

[0071] Controlling the accuracy of the exposure dose: The actual inhalation dose is calculated based on the exposure time and respiratory rate (approximately 150 times / minute for mice). During the experiment, the experimental animals are subject to the physical constraints of the various poison exposure chambers 30 in the isolation cages 21 and cannot run freely. All mice are in almost the same position (the front of the poison exposure chamber 30, where the concentration and particle size distribution in the poison exposure chamber 8 are most uniform, and the water and food supply position). The mice are not restrained, and are provided with food and water. The animals' respiratory rates are more stable and close to normal physiological values throughout the experiment. The inhalation dose calculated in this way is more accurate and has very high repeatability, which significantly reduces the concentration deviation of traditional whole-body exposure methods (less than 10%).

[0072] Guaranteeing animal welfare: Animals are not restrained during the experiment and are provided with free access to drinking water and feed during the exposure period, so animal welfare can be fully guaranteed.

[0073] S3-4 After the exposure duration (6 hours per day for 5 consecutive days) is reached, the experimental animals are removed and samples are prepared for testing; Precautions during animal exposure experiments: Aerosol leakage risk: The slightly positive pressure of the poison exposure chamber 8 allows precious samples to be more fully exposed to animals, but there is a risk of leakage. Therefore, the aerosol generator and the poison exposure chamber 8 need to be placed in a biosafety cabinet for experiments, and the experimenters must wear N95 masks.

[0074] Reduce particle collision losses: During the experiment, the connecting pipe from the aerosol generator to the exposure chamber 8 should be as short as possible (no more than 1 meter). Avoid using fans to dilute and mix particles in the exposure chamber 8 to avoid collisions. Use a shuttle airflow design to reduce turbulence during particle settling in the chamber.

[0075] Data comparability: The control group and the exposed group must be raised in the same environment at the same time to eliminate environmental interference.

[0076] S4. Experimental Data Analysis The physiological data, activity data of experimental animals collected during the experiment, as well as the data obtained from animal samples, were summarized and analyzed to obtain data on the toxic effects on the respiratory system, immune response and systemic organs of experimental animals in the whole-body exposure experiment.

[0077] S4-1 Respiratory function test: After the exposure, the lung function of mice (such as airway resistance and tidal volume) was detected by whole body plethysmography (WBP).

[0078] Bronchoalveolar lavage fluid (BALF) analysis was performed to detect inflammatory cell counts (neutrophils, macrophages) and inflammatory factors (IL-6, TNF-α).

[0079] Histopathological analysis: Lung tissues were collected for HE staining to observe alveolar structural destruction and inflammatory infiltration.

[0080] Analysis of oxidative stress indicators: detection of SOD, MDA, and GSH levels in lung tissue.

[0081] S4-2 Analysis results obtained from the experiment The lung function of mice in the exposure group decreased, and the inflammatory cells and factors in BALF increased significantly.

[0082] Lung tissue pathology showed alveolar wall thickening and inflammatory cell infiltration.

[0083] Oxidative stress markers (such as MDA) are increased, and the activities of antioxidant enzymes (such as SOD) are decreased.

[0084] The uniqueness of the technical solution and effects provided by this embodiment also includes the following parts: This embodiment, through the combined improvement of the system and method, focuses on overcoming the shortcomings of the existing whole-body exposure poisoning device structure and experimental methods. First, the aerosol at the top fills the entire space, resulting in uneven aerosol concentration distribution. Second, the same volume of aerosol distributed in a larger space will cause the concentration to decrease. Therefore, it can achieve highly repeatable exposure experiments, especially for some very precious whole-body exposure experiments of test substances. At the same time, high-precision experimental data under highly repeatable conditions can also be obtained.

[0085] The experimental systems and experimental methods provided in the aforementioned embodiments of the present invention, when combined, can reduce the coefficient of variation of aerosol concentration and particle size distribution between animals at different locations in two exposure methods to less than 10%. This allows for high-concentration exposure experiments with trace samples using either oral or whole-body exposure methods, significantly improving the accuracy and repeatability of animal exposure experiments. The oral or nasal method can replace conventional oral or nasal inhalation exposure experiments, freeing animals from the significant experimental stress associated with restraint during conventional oral or nasal inhalation experiments. Compared to conventional experimental systems and methods, the aforementioned embodiments of the present invention offer advantages such as high system utilization, low cost (equipment maintenance, consumables), and relatively low experimental material requirements, making them suitable for conducting trace material exposure experiments. They also provide greater uniformity in concentration and particle size distribution of the exposed material, a high degree of automation, and the ability to be placed in a biosafety cabinet for conducting experiments with highly toxic substances. Furthermore, they ensure the welfare of experimental animals and avoid ethical disputes, thus offering broad application prospects.

[0086] It should be noted that within the scope of the structures, steps, process parameters and conditions described in the present invention, other different schemes obtained by making specific selections can all achieve the technical effects described in the present invention, so the present invention will no longer list them one by one.

[0087] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Any person skilled in the art may, without departing from the scope of the present invention, utilize the methods and technical contents disclosed above to make many possible variations and modifications to the present invention, or modify them into equivalent embodiments with equivalent variations, all of which fall within the scope of protection of the present invention.

Claims

1. A highly repeatable and high-precision animal exposure experiment system, characterized in that: The animal exposure and poisoning experimental unit includes: an aerosol air inlet sleeve (7), a poisoning exposure chamber (8), an isolation mouse cage (21), a trumpet-shaped upper guide tube (22), and a cylindrical lower guide tube (23); The poison exposure chamber (8) is a closed chamber with a spindle-shaped overall outline and a hollow interior; The aerosol air inlet sleeve (7) is hollow inside, the upper section is a mixing and dilution chamber (74), and the lower section is arranged in the opening at the top of the poison exposure chamber (8); The isolation cage (21) is a cylindrical, air-permeable flat cage in an annular shape, and is disposed in the middle section of the spindle-shaped poison exposure chamber (8). The inner space of the isolation cage (21) is hollow near the center of the circle, forming a through groove (215), and the remaining part is divided into a plurality of centrally symmetrical, independent poison exposure chambers (30). The trumpet-shaped upper guide tube (22) is in the shape of a trumpet with an opening facing downward, and is disposed in the upper section of the spindle-shaped poison exposure chamber (8); the upper section of the trumpet wall (221) divides the internal space of the lower section of the aerosol air inlet sleeve (7) into two mutually isolated gas channels: the outer side surface of the trumpet wall (221) and the inner side surfaces of the aerosol air inlet sleeve (7) and the poison exposure chamber (8) together form a whole-body poison exposure diffusion zone (261), and the hollow space inside the trumpet wall (221) forms a trumpet inner tube channel (224); The cylindrical lower guide tube (23) is hollow and cylindrical in shape and is disposed in a through groove (215) in the middle of the isolation cage (21). The upper portion of the hollow cylindrical inner tube channel (234) is connected to the horn inner tube channel (224), and the bottom portion is provided with a plurality of exposure chamber branches (235) leading to the front of each contaminated exposure chamber (30). When the mixing and dilution chamber (74) is connected to the trumpet inner tube channel (224), the cylindrical inner tube channel (234), and the exposure chamber branch pipe (235), an exposure channel for inputting the poison exposure mixed gas into the independent poison exposure chamber (30) is formed, namely, the oral and nasal poison exposure channel A (25), which is used to implement oral and nasal poison exposure animal experiments; When the mixing and dilution chamber (74) is connected to the whole-body poison exposure diffusion zone (261), an exposure channel for inputting the poison exposure mixed gas into the independent poison exposure chamber (30) is formed, namely the whole-body poison exposure channel B (26), which is used to implement the whole-body poison exposure animal experiment.

2. The highly repeatable and high-precision animal exposure and poisoning experimental system according to claim 1, characterized in that: The aerosol inlet sleeve (7) is a hollow cylinder with a closed upper end surface and an open lower end surface. A plug slot (73) is horizontally provided on the side surface of the middle part of the hollow cylinder. The upper part of the plug slot (73) is the upper section, and the lower part of the plug slot (73) is the lower section. An aerosol connecting pipe (71) for connecting to an aerosol input pipeline is provided at the center of the upper end surface of the hollow cylinder; A clean air connecting pipe (72) for connecting to a clean air input pipeline is provided on the side surface of the upper section of the hollow cylinder; The aerosol connecting tube (71) and the air connecting tube (72) merge above the insert slot (73) to form a mixing and dilution chamber (74).

3. The highly repeatable and high-precision animal exposure and poisoning experimental system according to claim 1, characterized in that: The trumpet-shaped upper guide tube (22) comprises: a columnar guide tube (222), a trumpet tube wall (221), and a hollow horizontal support frame (225); The upper section of the horn wall (221) is a hollow columnar conduit (222), which is arranged at the center of the circle just above the horn-shaped horn wall (221). A conduit channel (223) is vertically provided inside the columnar conduit (222), which is connected to the horn inner tube channel (224) inside the horn wall (221); An annular hollow horizontal support plate (225) is also provided on the lower end surface of the horn wall (221); The horn wall (221) is entirely arranged inside the hopper-shaped upper cover (81), and the hollow horizontal support frame (225) is arranged on the outer surface of the bottom of the horn wall (221), horizontally extending outward and deep, surrounding the horn wall (221); The trumpet-shaped upper guide cylinder (22) is entirely arranged directly above the cylindrical lower guide cylinder (23) through its hollow horizontal support plate (225), so that the trumpet inner cylinder channel and the cylindrical inner cylinder channel are aligned with each other and connected to the isolation cage (21); The columnar conduit (222) is inserted upward into the interior of the aerosol air inlet sleeve (7), dividing the internal space of the lower section of the aerosol air inlet sleeve (7) into two mutually isolated gas channels: the outer side surface of the columnar conduit (222) and the inner side surfaces of the aerosol air inlet sleeve (7) and the poison exposure chamber (8) together form a whole-body poison exposure diffusion zone (261), i.e., a whole-body poison exposure channel B (26); the hollow conduit channel (223) inside the columnar conduit (222) forms the upper section of the trumpet inner tube channel (224), and is connected with the cylindrical inner tube channel (234) and the exposure chamber branch (235) to form an oral and nasal poison exposure channel A (25); After the external aerosol and clean air are mixed in the mixing and dilution chamber (74) at the upper section of the aerosol inlet sleeve (7), they are introduced into one of the two isolated gas channels to carry out the corresponding toxic exposure experiment.

4. The highly repeatable and high-precision animal exposure and poisoning experimental system according to claim 2, characterized in that: The animal exposure and poisoning experimental unit further includes: a poisoning and poisoning exposure channel switching plug (20); The poison exposure channel switching insert (20) is a sheet substrate with a semicircular end, and two switching inserts with through-hole structures are provided at different positions of the sheet substrate: Contamination channel switching insert A (20a): a central through hole (20a2) is provided at the center of the semicircular shape of the sheet substrate (20a1), and the sheet substrate portion surrounding the central through hole (20a2) is closed; Poison channel switching insert B (20b): The center position of the semicircular circle of the sheet substrate (20b1) is closed, and plum blossom-shaped through holes (20b2) are provided around the periphery of the center position; The poison exposure channel switching plug (20) is pluggably arranged in the plug slot (73) and is used to switch between the oral and nasal poison exposure channel A (25) and the whole body poison exposure channel B (26): When the poison channel switching plug A (20a) is inserted into the plug slot (73), the hollow conduit channel (223) inside the columnar conduit (222) is opened, so that the oral and nasal poison exposure channel A (25) is connected to the mixing and dilution chamber (74) upward and to each poison exposure chamber (30) downward. At the same time, the whole body poison exposure diffusion area (261) outside the columnar conduit (222) is closed, that is, the entrance of the whole body poison exposure channel B (26) is closed, and the poison exposure mixed gas after the aerosol and clean air are mixed in the mixing and dilution chamber (74) is input into each poison exposure chamber (30) from the opening of the exposure chamber branch pipe (235) to carry out the oral and nasal poison exposure experiment; When the poison channel switching plug B (20b) is inserted into the plug slot (73), the whole body poison exposure diffusion area (261) outside the columnar duct (222) is opened, so that the whole body poison exposure channel B (26) is connected to each poison exposure chamber (30), and at the same time, the internal duct channel (223) of the columnar duct (222) is closed, that is, the entrance of the oral and nasal poison exposure channel A (25) is closed, and the poison exposure mixed gas obtained by mixing the aerosol and clean air is input into each poison exposure chamber (30) from the whole body poison exposure diffusion area (261) inside the poison exposure chamber (8) and outside the horn wall (221) to carry out the whole body poison exposure experiment.

5. The highly repeatable and high-precision animal exposure and poisoning experimental system according to claim 1, characterized in that: The poison exposure chamber (8) comprises: a hopper-shaped upper cover (81), a cylindrical middle chamber coaming (82), and a funnel-shaped lower cover (84); The overall outline of the hopper-shaped upper cover (81) is conical, with an opening provided at the center of the top circle, the lower end surface of the opening, and the conical hollow portion inside the upper section as the upper section; the lower section of the aerosol air inlet sleeve (7) is embedded in the opening and extends into the interior of the hopper-shaped upper cover (81), and a sealing ring (811) is provided in the gap between the aerosol air inlet sleeve (7) and the opening at the joint surface; The mid-cabin coaming (82) is a vertically arranged cylindrical coaming, and the cylindrical hollow portion inside the mid-cabin coaming (82) is the middle section; The overall outline of the funnel-shaped lower cover (84) is funnel-shaped, and the conical hollow portion inside it is the lower section; The lower end surface of the inverted bucket-shaped upper cover (81) is buckled and sealed with the middle cabin coaming (82); the funnel-shaped lower cover (84) and the middle cabin coaming (82) are an integral structure; The three hollow sections of the upper section, the middle section and the lower section are connected to each other to form a closed structure inside the poison exposure chamber 8. The isolation cage (21), the trumpet-shaped upper guide tube (22) and the cylindrical lower guide tube (23) are all arranged in the closed structure as a whole.

6. The highly repeatable and high-precision animal exposure and poisoning experimental system according to claim 5, characterized in that: The isolation cage (21) is a semi-enclosed cage in the shape of an annular flat cylinder, wherein the side facing the center is open, and a cylindrical through groove (215) is formed in the hollow position around the center of the circle, which is connected to the cage. The cage comprises the following metal perforated plates that are interlocked: a cage bottom plate (211), a cage cover plate (212), an outer cage enclosure plate (213), and a plurality of vertical partitions (214); The cage bottom plate (211) is a ring-shaped metal perforated plate with a through hole in the center, and is arranged on a boss at the junction of the funnel-shaped lower cover (84) and the middle cabin coaming (82); The cage cover plate (212) is formed by splicing together a plurality of fan-shaped spliced cover pieces (2121), and the overall shape after splicing is a ring-shaped metal perforated plate; each spliced cover piece (2121) covers directly above the fan-shaped channel (301) of the poison exposure chamber (30), and closes the fan-shaped channel (301) of the poison exposure chamber (30) from the top; The outer cage enclosure plate (213) is a vertical plate arranged in a ring shape and connected end to end, and is arranged between the cage bottom plate (211) and the cage cover plate 212; The vertical partitions (214) are vertical plates, and multiple vertical partitions (214) are all centrally symmetrical and vertically arranged between the bottom plate (211), the cage cover plate (212) and the outer cage enclosure plate (213). The cylindrical lower guide tube (23) is arranged in the through groove (215), and together divides the internal space of the isolation mouse cage (21) into multiple independent poison exposure chambers (30). Each independent poison exposure chamber (30) is a fan-shaped channel (301) surrounded by six sides, and the fan-shaped channel (301) is narrow in front and wide in the back, and is used to place experimental animals.

7. The highly repeatable and high-precision animal exposure and poisoning experimental system according to claim 6, characterized in that: Each of the independent poison exposure chambers (30) is further provided with a top lifting limit plate (303) and front and rear limit plates (302) for limiting the body position of the experimental animal; the top lifting limit plate (303) is suspended on the cage cover (212) by means of lifting bolts (304), and moves up and down during use to limit the movement space of the experimental animal in the height direction within the fan-shaped channel (301); The front and rear limiting plug plates (302) are vertically inserted in the middle of the fan-shaped channel (301) of each poison exposure chamber (30), dividing the fan-shaped channel (301) of each poison exposure chamber (30) into two parts, front and rear, and restricting the experimental animals to move only in the space in front of the fan-shaped channel (301) with their heads facing forward; When conducting an animal poisoning mouth and nose exposure experiment, the top lifting limit plate (303) moves downward and the front and rear limit plug plates (302) move forward, restricting the experimental animal to the front of the fan-shaped channel (301) of the poisoning exposure chamber (30), so that the animal always keeps its head forward and cannot jump or turn around, forcing the mouth and nose of the experimental animal to passively approach the air outlet of the exposure chamber branch pipe (235); When conducting a whole-body exposure experiment on animals, the top lifting limit plate (303) is moved upward, and the front and rear limit plates (302) are moved backward or removed, so as to confine the experimental animals in the fan-shaped channel (301) and enable them to move freely, including jumping or turning.

8. The highly repeatable and high-precision animal exposure and poisoning experimental system according to claim 6, characterized in that: The cylindrical lower guide tube (23) comprises a lower guide tube wall (231) and a lower guide tube base (232); a plurality of parallel fins (233) are vertically provided on the outer surface of the lower guide tube wall (231); a cylindrical inner tube channel (234) is vertically provided inside the lower guide tube wall (231); the lower end of the cylindrical inner tube channel (234) is closed by the lower guide tube base (232); a plurality of exposure chamber branches (235) leading to the contaminated exposure chamber (30) are provided at a position close to the lower guide tube base (232) of the cylindrical inner tube channel (234); the inclined cavity between the outer side surface of the lower guide tube wall (231) and the fins (233) forms an exposure chamber diffusion guide groove (236), which is connected to each contaminated exposure chamber (30) from the outside of the lower guide tube wall (231); The upper end surfaces of the lower guide tube wall (231) and the fins (233) are respectively connected to the horn tube wall (221) and the hollow horizontal support frame (225), and the centers of the lower guide tube wall (231) and the horn tube wall (221) are located on a vertical line, and the cylindrical inner tube channel (234) of the cylindrical lower guide tube (23) is connected to the horn inner tube channel (224); When the cylindrical lower guide tube (23) is integrally arranged in the through groove (215) of the isolation cage (21), the upper and lower end surfaces of the lower guide tube wall (231) are flush with the cage bottom plate (211) and the cage cover plate (212), respectively, and the lower guide tube wall (231) and the fins (233) close the openings of each contaminated exposure chamber (30) toward the center of the circle.

9. The highly repeatable and high-precision animal exposure and poisoning experimental system according to claim 8, characterized in that: The exposure chamber diffusion guide groove (236) between the outer side surface of the lower guide tube wall (231) and the fin (233) and connected to the front end of each poison exposure chamber 30, and the lower part near the air outlet of the exposure chamber branch pipe (235) are used as a feed bin (305) for placing feed for experimental animals; The hollow horizontal support frame (225) is also provided with a plurality of drinking bottles (24) with the bottle mouth facing downward; the drinking bottles include a bottle body (241), a bottle cap (242) and a water supply pipe (243); the water supply pipe (243) extends downward into the front part (301) of the fan-shaped channel of each poison exposure chamber 30, and the lower end is close to the air outlet of the exposure chamber branch pipe (235), and is used to provide drinking water for the experimental animals; Feed is placed in the feed bin (305), and drinking water is placed in the drinking bottle (24), which are used to induce the experimental animals to actively move their mouths and noses close to the air outlet of the exposure chamber branch tube (235), so as to improve the total exposure inhalation dose and accuracy.

10. The highly repeatable and high-precision animal exposure and poisoning experimental system according to any one of claims 1 to 9, characterized in that: It also includes an operation support unit interconnected with the animal exposure and poisoning experimental unit; The operation support unit includes: an air compressor (3), an aerosol generator (6), an exhaust gas treatment module (10), and a negative pressure vacuum pump (14), which are connected to each other through a connecting pipe (19) and are ultimately connected to the poison exposure chamber (8); The first air path of the air compressor (3) passes through the generating MFC (4) and the aerosol generator (6) and is connected to the aerosol connecting pipe (71) of the aerosol air inlet sleeve (7); the second air path passes through the clean air MFC (5) and is connected to the clean air connecting pipe (72) of the aerosol air inlet sleeve (7); The waste gas treatment module (10) is connected to the lower section of the contamination exposure chamber (8) through the aerosol discharge pipeline interface (35), and then connected to the first gas path of the negative pressure vacuum pump (14) through the exhaust MFC (12); the second gas path of the negative pressure vacuum pump (14) is simultaneously connected to the impact sampler (9) and the particle size spectrometer (11) through the sampling MFC (13), and then connected to the lower section of the contamination exposure chamber (8) through the waste gas sampling pipeline interface (36).

11. The highly repeatable and high-precision animal exposure and poisoning experimental system according to claim 10, characterized in that: It also includes an operation control unit interconnected with the animal exposure and poisoning experimental unit and the operation support unit; The operation control unit includes an operation control group and a concentration monitoring group connected to each other via a connecting line (18) or a connecting pipeline (19); The operation control group is used to control the operation of each part in the exposure animal poisoning experimental unit and the operation support unit, which includes a control computer (1), a single-chip controller (2), a generating MFC (4), a clean air MFC (5), an impact sampler (9), a particle size spectrometer (11), an exhaust MFC (12), and a sampling MFC (13); The concentration monitoring group is used to provide real-time feedback data, which is automatically adjusted by the operation control group after calculation, and to perform closed-loop control on the exposed animal poisoning experimental unit and the operation support unit. It includes: a pressure difference sensor (15), a particle concentration sensor (16), an oxygen concentration sensor (17), an impact sampler (9), and a particle size spectrometer (11); The control computer (1) is connected to the single-chip microcomputer controller (2); the single-chip microcomputer controller (2) is respectively connected to the generating MFC (4), the clean air MFC (5), the aerosol generator (6), the particle size spectrometer (11), the exhaust MFC (12), the sampling MFC (13), and is also connected to the differential pressure sensor (15), the particulate matter concentration sensor (16), and the oxygen concentration sensor (17); One end of the pressure difference sensor (15), the particle concentration sensor (16), and the oxygen concentration sensor (17) are all connected to the single-chip controller (2), and the other end is connected to the aerosol inlet sleeve (7), so as to collect the pressure difference, particle concentration, and oxygen concentration of the contaminated exposure mixed gas of the aerosol and clean air in the mixing and dilution chamber (74); One end of the impact sampler (9) is connected to the exhaust gas sampling pipeline interface (36) through a gas path, and the other end is connected to the particle size spectrometer (11) and the sampling MFC (13) through a gas path; One end of the particle size spectrometer (11) is connected to the exhaust gas sampling pipeline interface (36) through a gas path, and the other end of the particle size spectrometer (11) is connected to the sampling MFC (13) through a gas path.

12. A highly repeatable and high-precision animal exposure experiment method, characterized in that: It is implemented by using the highly repeatable and high-precision animal exposure experiment system described in any one of claims 1 to 11. After the various parts of the highly repeatable and high-precision animal exposure experiment system are connected, the aerosol generator (6) and the air compressor (3) respectively input aerosol and clean air into the mixing and dilution chamber (74) and mix them. The two isolated exposure channels, the oral and nasal exposure channel A (25) and the whole-body exposure channel B (26), are switched through the poison channel switching plug (20). The poison exposure mixed gas is independently input into each poison exposure chamber (30) through one of the exposure channels, so that the animal poison exposure experiment of the oral and nasal exposure mode or the whole-body exposure mode can be completed by using a set of experimental systems, and the exposure animal experiment data with high repeatability and high precision can be obtained.

13. The highly repeatable and high-precision animal exposure experiment method according to claim 12, characterized in that: When conducting the oral and nasal poison exposure experiment, the body position of the experimental animal is also restricted to the front of the fan-shaped channel (301) in the poison exposure chamber (30), with the head facing it and unable to turn around or jump. Then, the experimental animal is provided with drinking water and feeding rewards on the head, so that the animal's head is more often in the smaller space near the air outlet of the exposure chamber branch pipe (235) during the experimental time, so as to complete the highly repeatable oral and nasal exposure method of exposure to poison animals and obtain high-precision exposure experimental data close to the conventional oral and nasal exposure method.

14. The highly repeatable and high-precision animal exposure experiment method according to claim 12, characterized in that: When implementing the whole-body poison exposure experiment, the body position of the experimental animal is also restricted to the entire space of the fan-shaped channel (301) of the poison exposure chamber (30), and the experimental animal can move freely. Then, the experimental animal is provided with drinking water and feeding rewards on the head, so that the animal is more likely to move in a space close to the feed bin (305) and with a uniform aerosol concentration distribution during the experimental time, so as to complete the highly repeatable poison exposure animal experiment and obtain high-precision exposure experimental data that is higher than that of conventional whole-body exposure methods.

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