Use of antioxidants for reducing and / or preventing toxicity of rubber compositions

Abstract

The present invention relates to the use of at least one antioxidant in a rubber composition for reducing and / or preventing the toxicity of said rubber composition, said at least one antioxidant comprising at least one oligomer and / or polymer having at least one diphenylamine repeat unit.

Description

Technical Field

[0001] The present invention relates to the field of antioxidant additives used in rubber compositions, i.e., elastomeric compositions (natural or synthetic high molecular weight substances with rubber elasticity). Specifically, the present invention relates to the use of specific polymeric antioxidants in rubber compositions to reduce and / or prevent their toxicity. Background Art

[0002] The application of rubber compositions covers a wide range of uses in everyday life, such as seals, pipes, the automotive industry (tyres, seat belts and various rubber parts: hoses, etc.), the medical field, the clothing industry (shoe soles) and high-performance uses (aerospace and offshore applications).

[0003] In known manner, rubber compositions generally contain one or more additives, including antioxidants.

[0004] Antioxidants are also used in a wide range of applications and everyday products, and their supply is essential for the longevity and maintenance of the physicochemical and mechanical properties of these everyday products, despite their relatively small content in the materials in which they are contained. In the case of plastics, or more specifically in the case of rubber used in pipes (e.g. under-the-hood components), cables or tires, their presence preserves the mechanical properties of the materials, in particular by avoiding their hardening by oxidation in air or in ozone (e.g. in the case of tires subjected to the action of ozone generated by the heating of the air in contact with catalytic converters associated with road traffic).

[0005] Until now, aromatic amines, such as diphenylamine monomer (DPA) or p-phenylenediamine (PPD), have been very widely used in rubber hoses, cables or tires. The more recent family (PPD) has now become the choice of a series of additives due to its antioxidant and anti-ozone properties, which are necessary for tires that are subject to these two aging phenomena. For example, the compound N,N'-bis(1,4-dimethylpentyl)-p-phenylenediamine (hereinafter referred to as 77PD, CAS 3081-14-9) is often used in rubber coatings for cables. It is also estimated that in 2009, China consumed 100,000 tons of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (hereinafter referred to as 6PPD) per year in the production of rubber for various purposes.

[0006] Unfortunately, recent studies have shown that the toxicological profile of standard antioxidants (e.g. those based on aromatic amines or diamines) is changing for the worse and in a drastic and worrying way, creating established dangers for humans and their environment (carcinogenicity, mutagenicity or reproductive toxicity, known as "CMR", aquatic toxicity / ecotoxicity, bioaccumulation, substances classified as persistent, bioaccumulative and toxic, known as "PBT"). This trend is accelerating under the influence of international regulatory agencies requiring increasingly precise and in-depth characterization of chemical materials produced in large quantities. For example, the European Chemicals Agency (ECHA) reports the apparent hazard of the main antioxidants, in particular those belonging to the family of diphenylamine (DPA) or p-phenylenediamine (PPD) monomers, which are widely used in the chemical industry for liquids, plastics or rubbers.

[0007] Specifically, standard antioxidants and their proven toxicity are listed in Table 1 below:

[0008] Table 1

[0009]

[0010] In particular, recent scientific studies have confirmed this standard antioxidant toxicity, such as Tian et al., Science, 2021, 371(6525), 185-189 or W. Huang et al., Environ. Sci. Technol. Lett. 2021, 8, 381-385, indicating that the main antioxidants used to date are toxic to humans and / or the environment.

[0011] The publication by Tian et al. focused on the effects of antioxidants on Pacific coho salmon (Oncorhynchus kisutch) (Northeastern United States). The authors found that in this salmon, exposure to rainwater led to unexplained acute mortality when adult salmon migrated to urban rivers every year for reproduction. By studying this phenomenon, they found a highly toxic 6PPD transformation product, namely 6PPD-quinone, in the water. As mentioned above, 6PPD is an antioxidant of tire rubber that is ubiquitous in the world. Therefore, this study shows that 6PPD-derived oxidation products are even more toxic than 6PPD itself. Specifically, a retrospective analysis of representative highway runoff and stormwater streams on the west coast of the United States showed that 6PPD-quinone (<0.3 to 19 micrograms per liter) was widely present at toxic concentrations (median lethal concentration of 0.8±0.16 micrograms per liter). Therefore, this publication shows that the compound 6PPD and its oxidation products are highly ecotoxic and that tire rubber residues scattered in nature are a real ecological challenge.

[0012] The publication by W. Huang et al. also demonstrated that tire wear particles containing these toxic antioxidants are widely present throughout the environment, i.e. on roads, parking lots, and even in cars and houses. These antioxidants include 6PPD, IPPD, CPPD or DPPD. Specifically, 6PPD-quinone was detected in motor vehicles.

[0013] A study on air quality in major Chinese cities in the publication Zhang et al., Environ. Sci. Technol. 2021 ("p-Phenylenediamine Antioxidants in PM2.5: The Underestimated Urban Air pollutants") showed that a large amount of antioxidants commonly used in rubber compositions, such as compounds 6PPD and 77PD, as well as oxidation products IPPD-quinone and DPPD-quinone, are present in the fine particles of urban ambient air.

[0014] FR 2156392 discloses antioxidant products for materials such as rubber (page 6, lines 1-4), such as 2-(4,4'-di-tert-octyldiphenylamine)-4,4'-di-tert-octyldiphenylamine. The document only refers to rubber in general, as it does to plastics, but does not describe the rubber and demonstrate the effect of antioxidants in such rubber compositions, which are solid, unlike lubricant compositions, and the document only shows performance in the field of fluids and lubricants.

[0015] CN 107540559 discloses a method for preparing 4,4'-bis(α,α-dimethylbenzyl)diphenylamine. According to the document (paragraph 0031), it has a non-toxic effect. However, there are no experimental tests in the document to illustrate this property. There is no description or suggestion of any method to prove its non-toxicity. The inventor only cites the benefits of this compound in a very subjective way, and even its effectiveness is not proven. On the contrary, the applicant proves that the compound is highly toxic, whether in terms of reproductive toxicity, mutagenicity or carcinogenicity (see compound 25 in Table 5 below).

[0016] EP 2842995 relates to a special material for manufacturing explosion-proof tire rubber for wheeled military combat vehicles. As far as the applicant is aware, the rubber industry uses only monomeric compounds (substances) as antioxidants, but not polymers / oligomers.

[0017] WO 2009 / 071857 relates to a process for preparing a lubricating oil antioxidant and / or corrosion inhibitor comprising diphenylamine and phenyl-α-naphthylamine units.

[0018] Therefore, there is a great need in the prior art to develop antioxidants, or even anti-ozonant additives, to replace the above-mentioned standard antioxidants for making better rubber compositions.

[0019] Specifically, there is an urgent need in the prior art to develop alternative antioxidant additives for rubber compositions, which have satisfactory antioxidant effects in target application areas (automobiles, clothing, etc.) while being able to improve the safety level (reduce the risk to humans) and reduce the environmental impact of the rubber composition to which the antioxidant is added.

[0020] Invention Disclosure

[0021] In this context, the applicant is committed to developing antioxidants that have antioxidant properties while preventing and / or reducing the toxicity of rubber compositions containing them compared to standard antioxidants (for example, specifically, the above-mentioned standard antioxidants belonging to the diphenylamine (DPA) or p-phenylenediamine (PPD) monomer family). For example, CN 107540559 describes the compound 4,4'-bis(α,α-dimethylbenzyl)diphenylamine, which is a diphenylamine monomer (DPA), which is toxic. As mentioned above, this effect is by no means what the present disclosure is intended to demonstrate. However, on the contrary, the compound is toxic in terms of reproductive toxicity, mutagenicity and / or carcinogenicity as demonstrated by the applicant's toxicity QSAR testing.

[0022] As described in the experimental section below, the applicant has demonstrated, particularly surprisingly and unexpectedly, that upon oligomerization and / or polymerization, the toxicity of the diphenylamine monomer is significantly reduced. Thus, it is possible to form oligomers and / or polymers comprising at least one diphenylamine repeating unit, which have both antioxidant and ozone resistance properties, are suitable for various fields of application of rubber compositions (tires, cables, etc.), and are less toxic or not toxic at all to humans and / or the environment.

[0023] In fact, the experimental tests below show that the antioxidants selected by the applicant according to the present invention are not arbitrarily selected and have a technical effect different from other antioxidant compounds (specifically, diphenylamine (DPA) or p-phenylenediamine (PPD) monomers), namely they reduce / prevent / avoid the toxicity of the rubber composition.

[0024] Although the use of oligomeric and / or polymeric compounds comprising at least one diphenylamine repeating unit as antioxidant additives has been considered in the prior art, in particular for the purpose of forming antioxidants for lubricant compositions (which, as the name implies, are liquid), to the best of the applicant's knowledge, no studies have been conducted to demonstrate that they are non-toxic and therefore useful for preventing and / or reducing, or even avoiding, toxicity, let alone for use in solid and crosslinked rubber compositions.

[0025] It is indeed unexpected and unknown that oligomers / polymers (i.e. macromolecules) could have an antioxidant effect similar to that of monomers or substances which, by definition, are theoretically more fluid and active in solid rubber compositions. It is important to distinguish solid cross-linked materials from fluids, through which the effect of soluble antioxidants is more easily achieved. To date, to the best of the applicant's knowledge, the high performance technical benchmark for antioxidants in rubber compositions (tires) is the compound disclosed in CN 107540559, namely 4,4'-bis(α,α-dimethylbenzyl)diphenylamine (CAS 10081-67-1, Product 445). However, as mentioned above, this compound is toxic, unlike the compounds of the present invention. Other substances commonly used in this field are 6PPD (Comparative Compound 22) and IPPD (Comparative Compound 23). These two compounds are also toxic, and one of them is even a CMR compound according to the applicable European regulations. Therefore, under the teachings of the prior art, it is not possible to predict the specific technical effects of the compounds according to the present invention.

[0026] Furthermore, the applicant believes that testing the toxicity of antioxidants is not an obvious measure for a person of ordinary skill in the art. This is why the applicant has developed an effective and in-depth method based on four models (C: carcinogenicity, M: mutagenicity, R: reproductive toxicity and N: neurotoxicity) in order to comprehensively test the toxicity of the compounds in an indisputable manner. In particular, the method highlights the greatly reduced toxicity of the diphenylamine oligomers / polymers according to the present invention compared to other conventional antioxidant compounds. To date, in compliance with increasingly stringent applicable regulatory requirements (e.g. European Chemicals Agency (ECHA) etc.), the classification of many antioxidants is evolving, generally in the wrong direction. For example, the Irganox L57 product (as described in Table 1 below) is also classified as a CMR compound.

[0027] In conclusion, it is not easy, or even impossible, for a person skilled in the art to combine high technical performance and high antioxidant capacity (at the level of the highest standards in the art, such as Naugard 445) with greatly reduced overall toxicity. Summary of the invention

[0028] In view of this, the present invention relates to the use of at least one antioxidant in a rubber composition for reducing and / or preventing the toxicity of the rubber composition, the at least one antioxidant comprising at least one oligomer and / or polymer comprising at least one diphenylamine repeating unit of formula (I):

[0029]

[0030] Wherein R1 to R10 are each independently selected from: a hydrogen atom, an alkyl group (a saturated, straight-chain or branched hydrocarbon group containing 1 to 24 carbon atoms) and an aralkyl group (an alkyl group as described above, wherein at least one carbon atom is substituted by a monocyclic aromatic hydrocarbon or polycyclic aromatic group containing 5 to 14 carbon atoms).

[0031] Of course, the different features, variants and embodiments of the invention can be combined with one another according to various combinations, as long as they are not incompatible or mutually exclusive.

[0032] In the present invention, unless otherwise specified, the term "comprise" and its derivatives should be understood as non-restrictive and do not exclude the existence of other components or steps. In some specific embodiments, the term "comprise" can be understood as "essentially composed of..." or "consisting of...".

[0033] Unless otherwise stated, the intervals mentioned in the present invention include the end values. DETAILED DESCRIPTION

[0034] The present invention therefore relates to the use of at least one antioxidant in a rubber composition, said at least one antioxidant comprising at least one oligomer and / or polymer comprising at least one diphenylamine repeating unit of formula (I):

[0035]

[0036] Wherein R1 to R10 are each independently selected from:

[0037] Hydrogen atoms,

[0038] an alkyl group which is a saturated, straight-chain or branched hydrocarbon group containing 1 to 24 carbon atoms, and

[0039] Aralkyl, which is an alkyl group as described above, wherein at least one carbon atom is substituted by a monocyclic aromatic hydrocarbon or polycyclic aromatic group containing 5 to 14 carbon atoms,

[0040] Used to reduce and / or prevent toxicity of the rubber composition, the toxicity coming from antioxidants belonging to the diphenylamine (DPA) or p-phenylenediamine (PPD) monomer family.

[0041] By antioxidants, it is meant specific chemical additives that are added to a composition and block oxidation-related degradation processes in the composition, in this case a rubber composition.

[0042] According to the present invention, the "toxicity" of a substance and / or composition means that the substance and / or composition has at least one, preferably at least two, specifically at least three, generally at least four, for example at least five, at least six, or even all of the following toxicities:

[0043] - reproductive toxicity, corresponding to impairment of fertility or damage to mammals / unborn organisms,

[0044] - Mutagenicity, i.e. the tendency of a substance to cause genetic mutations,

[0045] - acute toxicity, i.e. toxicity induced within a short period of time (e.g. 24 hours) by application or contact (topical application) with a single dose (optionally a large dose) or with multiple doses of a toxic product or mixture (natural or chemical) obtained within this period,

[0046] - Ecotoxicity, i.e. all imbalances or hazards caused by industrial activities or the introduction of foreign substances or products into the natural environment, usually as a result of human activities,

[0047] - neurotoxicity, i.e. the ability of a substance or compound to induce harmful effects in the nervous system of mammals / organisms (e.g. humans or planarians),

[0048] - carcinogenicity, i.e. the tendency of a substance to cause / induce the development of cancer or to contribute to its progression,

[0049] - Toxicity to the synthesis, degradation, transport and mode of action of hormones, such as in the case of endocrine disruptors (indirect toxicity through the physiological changes they induce).

[0050] Therefore, compounds with CMR properties (carcinogenicity, mutagenicity or reproductive toxicity) have various toxicities.

[0051] Thus, according to features of the present invention, toxicity includes one or more of the following toxicities: neurotoxicity, reproductive toxicity, mutagenicity, acute toxicity, carcinogenicity, toxicity to the synthesis, degradation, transport and mode of action of hormones, and ecotoxicity.

[0052] By "reducing" the toxicity of the rubber composition, it is meant that the at least one antioxidant according to the present invention (i.e. comprising at least one oligomer and / or polymer comprising at least one diphenylamine repeating unit of formula (I)) is capable of and / or is configured to reduce the toxicity of the rubber composition containing it, i.e. by its presence, the at least one antioxidant according to the present invention comprising at least one oligomer and / or polymer comprising at least one diphenylamine repeating unit of formula (I) reduces / reduces the toxicity of the rubber composition, in particular relative to other possible standard antioxidant compounds that are typically toxic, and provides a non-toxic rubber composition or a rubber composition with at least reduced toxicity.

[0053] By "preventing" the toxicity of the rubber composition, it is meant that the at least one antioxidant according to the invention (the antioxidant comprising at least one oligomer and / or polymer comprising at least one diphenylamine repeating unit of formula (I)) prevents the rubber composition from being considered toxic and / or prevents the mammal or any other organism (e.g., a human or animal) that comes into contact with the rubber composition from developing symptoms of poisoning. For example, neurotoxic symptoms may affect the central nervous system (CNS) and have the following effects: headache, loss of appetite, drowsiness, mood and personality disorders, cognitive disorders (difficulties in learning and concentrating), or affect the peripheral nervous system (SNP) and have the following effects: movement disorders (e.g., weakness, tremor, ataxia, convulsions, etc.), or sensory disorders (e.g., hearing loss, color vision loss, tinnitus, loss of balance, etc.); these effects may or may not be reversible, depending on the degree of acute or chronic exposure of the mammal. For example, acute toxic symptoms may be skin irritation, allergic skin reactions, vomiting, etc.

[0054] In general, the at least one antioxidant according to the present invention (i.e. comprising at least one oligomer and / or polymer comprising at least one diphenylamine repeating unit of formula (I)) is capable of and / or is configured to reduce and / or prevent the toxicity of the rubber composition at various stages of its life (i.e. its implementation, its use and its end of life, including its diffusion in the environment, such as wear of particles or tires made from said composition).

[0055] According to a particular embodiment, the oligomer and / or polymer comprising at least one diphenylamine repeating unit of formula (I) further comprises at least one phenyl α-naphthylamine repeating unit of formula (II):

[0056]

[0057] Wherein R11 to R22 are each independently selected from:

[0058] hydrogen atoms, and

[0059] Alkyl, which is a saturated, straight-chain or branched hydrocarbon group containing 1 to 24 carbon atoms.

[0060] In the present invention, a "polymer" of at least one diphenylamine and optionally at least one phenyl alpha-naphthylamine refers to a compound comprising a recurrence of at least two diphenylamine units and optionally at least one phenyl alpha-naphthylamine unit.

[0061] In the present invention, an "oligomer" of at least one diphenylamine and optionally at least one phenyl α-naphthylamine refers to a polymer of at least one diphenylamine and optionally at least one phenyl α-naphthylamine containing 2 to 15 repeating units, or a mixture of these compounds. This may include dimers, trimers, tetramers, pentamers, hexamers, heptamers, octamers, nonamers, decamers and / or any mixture of these compounds. Preferably, the oligomer contains (in terms of relative mass percentage) at least 70%, preferably 80%, in particular 90% of dimers, trimers, tetramers, pentamers or mixtures of these compounds. In general, the oligomer is a dimer and / or a trimer.

[0062] "Repeating units" of diphenylamine or phenyl α-naphthylamine mean that in the final structure of the oligomer or polymer obtained according to the invention, at least one diphenylamine unit and at least one phenyl α-naphthylamine unit, or at least two diphenylamine units and optionally at least one phenyl α-naphthylamine unit are present.

[0063] In the polymer or oligomer structure according to the invention, the diphenylamine and phenyl α-naphthylamine repeating units may be positioned in any manner relative to one another. Thus, the polymer or oligomer may comprise, at least over a portion of its structure, a regular alternation of diphenylamine and phenyl α-naphthylamine repeating units. At least over a portion of its structure, it may comprise a random distribution of diphenylamine and phenyl α-naphthylamine repeating units. Finally, at least over a portion of its structure, it may comprise blocks containing a single type of diphenylamine or phenyl α-naphthylamine repeating unit.

[0064] In one embodiment, the polymers and / or oligomers according to the invention comprise only diphenylamine and phenyl alpha-naphthylamine repeating units in their structure. In another embodiment, the polymers and / or oligomers according to the invention comprise only diphenylamine repeating units in their structure.

[0065] "Diphenylamine" refers to a compound of formula (I):

[0066]

[0067] Wherein R1 to R10 are each independently selected from: a hydrogen atom, an alkyl group (a saturated, straight-chain or branched hydrocarbon group containing 1 to 24 carbon atoms) and an aralkyl group (an alkyl group as described above, wherein at least one carbon atom is substituted by a monocyclic aromatic hydrocarbon or polycyclic aromatic group containing 5 to 14 carbon atoms).

[0068] In one embodiment, at least one diphenylamine of formula (I) is an alkylated diphenylamine, which means that at least one of R1 to R10 is an alkyl or aralkyl group. In another embodiment, at least one of R1 to R5 is an alkyl or aralkyl group, and at least one of R6 to R10 is an alkyl or aralkyl group.

[0069] In general, R1 to R10 are each independently selected from: a hydrogen atom or an alkyl group, wherein the alkyl group is a saturated, straight-chain or branched hydrocarbon group containing 1 to 24 carbon atoms, preferably 1 to 15 carbon atoms, specifically 3 to 12 carbon atoms, and generally 3 to 10 carbon atoms. For example, the at least three substituents may be independently tert-butyl or tert-octyl or n-nonyl.

[0070] Generally, at least one, specifically at least two, generally at least three substituents of R1 to R10 are alkyl groups (as defined below), and the other substituents are hydrogen atoms. Usually less than nine, specifically less than six, generally less than four substituents of R1 to R10 are alkyl groups, and the other substituents are hydrogen atoms. According to the present invention, "at least one" includes the following numbers and all intervals therebetween: 1; 2; 3; 4; 5; 6; 7; 8; 9; 10. In addition, in the context of the present invention, "less than 9" includes the following numbers and all intervals therebetween: 9; 8; 7; 6; 5; 4; 3; 2; 1. For example, one or two substituents of R1 to R10 are alkyl groups, and the other substituents are hydrogen atoms.

[0071] In the present invention, "alkyl" refers to a saturated, straight-chain, branched or cyclic hydrocarbon group containing 1 to 24 carbon atoms. Preferably, the alkyl group contains 1 to 12 carbon atoms. Therefore, according to the present invention, "alkyl containing 1 to 24 carbon atoms" includes the following carbon numbers and all intervals therebetween: 1; 2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 18; 19; 20; 21; 22; 23; 24. Specifically, the alkyl group includes methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, n-pentyl, isopentyl, n-hexyl, cyclohexyl, n-heptyl, n-octyl, tert-octyl, isooctyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl and isododecyl. In a specific embodiment, the alkyl group is selected from the group consisting of tert-butyl and tert-octyl or n-nonyl (nC9), and may be selected from the group consisting of tert-butyl and tert-octyl.

[0072] In the present invention, "aralkyl" refers to an alkyl group in which at least one carbon atom is substituted by an aryl group. Examples of aralkyl groups include 1-methyl-1-phenylethyl, styryl (C6H5-CH=CH-) or methylstyryl moieties.

[0073] In the present invention, "aryl" refers to a monocyclic or polycyclic aromatic hydrocarbon group. Each polycyclic aromatic hydrocarbon or aromatic ring contains 5 to 14 atoms. Examples of aryl include phenyl.

[0074] In one embodiment, the diphenylamine of formula (I) is selected from the group consisting of N,N-diphenylamine, N,N-di-(p-tert-butylphenyl)amine, N,N-di-(p-tert-octylphenyl)amine, N-(p-tert-butylphenyl)-N-aniline, N-(p-tert-octylphenyl)-N-aniline, N-(p-tert-butylphenyl)-N-(p-tert-octylphenyl)amine, tert-butylated diphenylamine and / or tert-octylated diphenylamine, nonylated diphenylamine and any mixture thereof.

[0075] In a specific embodiment, the polymers and oligomers according to the present invention contain only diphenylamine units. Therefore, the oligomers according to the present invention containing at least one diphenylamine repeating unit of formula (I) can be dimers, trimers, tetramers, pentamers of the diphenylamines of one or more of the above-mentioned formulas (I), for example, can be dimers or trimers of di-(p-tert-octylphenyl)amine (DODPA).

[0076] Specifically, according to the present invention, when the oligomer comprising at least one diphenylamine repeating unit of formula (I) is a dimer, at least three, generally at least four, of all substituents R1 to R10 of the repeating units of formula (I) forming the dimer are not hydrogen atoms (thus the other substituents are hydrogen atoms). According to the present invention, "at least three substituents of R1 to R10 of the repeating units of formula (I) forming the dimer" include the following numbers: 3; 4; 5; 6; 7; 8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 18; 19; 20, and may correspond to, for example, three or four substituents of all substituents R1 to R10 forming the dimer. Generally speaking, each of the at least three substituents is preferably an alkyl group, i.e., a saturated, straight-chain or branched hydrocarbon group containing 1 to 24 carbon atoms, preferably 3 to 15 carbon atoms, specifically 5 to 12 carbon atoms, generally 6 to 9 carbon atoms. For example, the at least three substituents can be independently tert-butyl or tert-octyl or even n-nonyl. Typically, the at least three substituents are independently distributed in two diphenylamine repeating units of formula (I) of the dimer. Typically, each repeating unit comprises at least one of the three substituents. For example, a dimer repeating unit comprises at least one substituent that is not a hydrogen atom (preferably an alkyl group as defined above) in R1 to R10, and another dimer unit comprises at least two substituents that are not a hydrogen atom (preferably an alkyl group as defined above) in R1 to R10.

[0077] In general, according to the present invention, when the oligomer comprising at least one diphenylamine repeating unit of formula (I) is a trimer, at least one, preferably at least two, substituents of all substituents R1 to R10 of the repeating units of formula (I) forming the trimer are not hydrogen atoms (and thus the other substituents are hydrogen atoms). According to the present invention, “at least one substituent of all substituents R1 to R10 of the repeating units of formula (I) forming the trimer” comprises the following numbers: 1; 2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 12; 13; 14; 15; 16; 17; 18; 19; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29; 30, and may correspond to, for example, five or six substituents of all substituents R1 to R10 forming the trimer. In particular, each of the at least one, preferably five or even six substituents is usually an alkyl group, that is, a saturated, straight-chain or branched hydrocarbon group containing 1 to 24 carbon atoms, preferably 3 to 15 carbon atoms, specifically 5 to 12 carbon atoms, and generally 6 to 9 carbon atoms. For example, the substituents can be independently tert-butyl or tert-octyl or n-nonyl, generally tert-octyl. Generally, the at least one, preferably five or six substituents are independently distributed in the three diphenylamine repeating units of formula (I) forming the trimer. Generally, each repeating unit of the trimer contains at least one or even two substituents of alkyl as defined above in R1 to R10 (the other substituents are hydrogen atoms). Generally, the alkyl substituents are independently distributed in the three diphenylamine repeating units of formula (I) of the trimer. Generally, each repeating unit of the trimer contains at least one or even two alkyl substituents (the other substituents are hydrogen atoms).

[0078] The diphenylamines according to the present invention may be in separated form or mixed together. For example, they may be in the form of a mixture of N,N-diphenylamine, N,N-di-(p-tert-butylphenyl)amine, N,N-di-(p-tert-octylphenyl)amine, N-(p-tert-butylphenyl)-N-aniline, N-(p-tert-octylphenyl)-N-aniline and N-(p-tert-butylphenyl)-N-(p-tert-octylphenyl)amine, tert-butylated diphenylamine and / or tert-octylated, nonylated diphenylamine.

[0079] The oligomers and / or polymers comprising at least one diphenylamine repeating unit of formula (I) may correspond to the compounds exemplified below.

[0080] According to the present invention, phenyl α-naphthylamine refers to a compound of formula (II):

[0081]

[0082] Wherein R11 to R22 are each independently selected from:

[0083] hydrogen atoms, and

[0084] Alkyl, which is a saturated, straight-chain or branched hydrocarbon group containing 1 to 24 carbon atoms.

[0085] In one embodiment, at least one of R11 to R22 is an alkyl group. In one embodiment, only one of R11 to R22 is an alkyl group, specifically a tert-octyl group.

[0086] In a specific embodiment, the phenyl α-naphthylamine is N-(4-tert-octylphenyl)-1-naphthylamine, CAS No. 4572-51-4 (OPAN).

[0087] In an embodiment of the present invention, at least one diphenylamine is in the form of a mixture of N,N-diphenylamine, N,N-di-(p-tert-butylphenyl)amine, N,N-di-(p-tert-octylphenyl)amine, N-(p-tert-butylphenyl)-N-aniline, N-(p-tert-octylphenyl)-N-aniline and N-(p-tert-butylphenyl)-N-(p-tert-octylphenyl)amine, and at least one phenyl α-naphthylamine is N-(4-tert-octylphenyl)-1-naphthylamine (OPAN).

[0088] In another embodiment of the present invention, at least one diphenylamine is di-(p-tert-octylphenyl)amine (DODPA), and at least one phenyl α-naphthylamine is N-(4-tert-octylphenyl)-1-naphthylamine (OPAN). Therefore, the oligomer forming the antioxidant according to the present invention can be a trimer 2DODPA / 1OPAN, 1DODPA / 2OPAN, 3DODPA. According to one embodiment, the at least one oligomer can be a mixture of trimers, such as a mixture of 2DODPA / 1OPAN, 1DODPA / 2OPAN and 3DODPA. Specifically, in this mixture, the oligomer 2DODPA / 1OPAN is dominant. Generally speaking, the at least one oligomer comprises a mixture of trimers (e.g., 2DODPA / 1OPAN, 1DODPA / 2OPAN, 3DODPA), tetramers, pentamers and hexamers.

[0089] The relative mass ratio of the two types of diphenylamine and phenyl α-naphthylamine units in the polymer or oligomer can vary in a wide range from 0 / 100 to 100 / 0. Preferably, the relative mass ratio of diphenylamine / phenyl α-naphthylamine is between 100 / 0 and 10 / 90, in particular between 100 / 0 and 30 / 70 (e.g. 50 / 50 or 80 / 20), specifically between 100 / 0 and 90 / 10, generally between 100 / 0 and 95 / 5.

[0090] The polymer or oligomer according to the invention forming at least one antioxidant according to the invention can in particular be prepared according to the method described in patent application FR 2010199 filed by the applicant company, i.e. in a continuous reactor. A person skilled in the art will be able to adjust the amount of diphenylamine and phenyl α-naphthylamine introduced into the reactor, depending on the desired structure and the desired thermal properties of the oligomer or polymer to be synthesized. The polymer or oligomer according to the invention forming at least one antioxidant according to the invention can in particular also be prepared according to the method described in US 2019 / 0127526 or WO 2008 / 022028.

[0091] For the present invention, the applicant conducted QSAR simulation tests on neurotoxicity, reproductive toxicity, mutagenicity and carcinogenicity, and proved the non-toxicity of the at least one antioxidant according to the present invention, wherein the at least one antioxidant comprises at least one oligomer and / or polymer, and the oligomer and / or polymer comprises at least one diphenylamine repeating unit of formula (I) and optionally at least one phenyl α-naphthylamine repeating unit of formula (II).

[0092] In particular, oligomers and / or polymers comprising at least one diphenylamine repeating unit of formula (I) and optionally at least one phenyl α-naphthylamine repeating unit of formula (II) have QSAR values ​​for measuring each of the following toxicities: neurotoxicity (neurotoxicity QSAR), reproductive toxicity (reproductive toxicity QSAR), mutagenicity (mutagenicity QSAR) and carcinogenicity (carcinogenicity QSAR), the QSAR value for each toxicity corresponding to subtracting a statistical threshold value (%) from a delta value of at least 30%, the statistical threshold value for each of the toxicities being determined by the QSAR (Quantitative Structure Activity Relationship) model according to the method described in the experimental part below.

[0093] According to the present invention, "at least 30% of the delta value" used for the QSAR model includes the following values ​​and intervals therebetween: 30; 31; 32; 33; 34; 35; 36; 37; 38; 39; 40; 41; 42; 43; 44; 45; 46; 47; 48; 49; 50; 51; 52; 55; 60; 65; 70; 75; 80; 85; 90; 91; 92; 93; 94; 95; 96; 97; 98; 99; 100 (at least 30% of the range applies to each toxicity).

[0094] According to one embodiment, generally, the statistical threshold percentage for the neurotoxicity QSAR is 55%.

[0095] Preferably, for neurotoxicity QSAR measurements, the delta value is at least 45%, preferably at least 55%, typically at least 53%.

[0096] In general, for neurotoxicity measurements (neurotoxicity QSAR), oligomers and / or polymers comprising at least one diphenylamine repeating unit of formula (I) and optionally at least one phenyl α-naphthylamine repeating unit of formula (II) have a QSAR model percentage (%) value less than or equal to 10%, preferably less than or equal to 5%, typically less than or equal to 2%.

[0097] According to the present invention, for the neurotoxicity QSAR model, values ​​less than or equal to 10% include the following values ​​and all intervals therebetween: 10; 9; 8; 7; 6; 5; 4; 3; 2; 1; 0.9; 0.8; 0.70; 0.69; 0.68; 0.67; 0.66; 0.65; 0.64; 0.63; 0.62; 0.61; 0.60; 0.59; .058; 0.57; 0.56; 0.55; 0.54; 0.53; 0.52; 0. 51;0.50;0.49;0.48;0.47;0.46;0.45;0.44;0.42;0.40;0.38;0.36;0.34;0.32;0.30;0.28;0.26;0.24;0.22;0.20;0.18;0.16;0.14;0.12;0.10;0.09;0.08;0.07;0.06;0.05;0.04;0.03;0.02;0.01;0.00.

[0098] According to another embodiment, the reproductive toxicity QSAR statistical threshold percentage is generally 90%.

[0099] Preferably, for reproductive toxicity QSAR measurements, the delta value is at least 41%, preferably at least 43%, typically at least 46%.

[0100] In general, for reproductive toxicity measurements (reproductive toxicity QSAR), oligomers and / or polymers comprising at least one diphenylamine repeating unit of formula (I) and optionally at least one phenyl α-naphthylamine repeating unit of formula (II) have a QSAR model percentage (%) value less than or equal to 65%, preferably less than or equal to 50%, typically less than or equal to 45%.

[0101] According to the present invention, for the reproductive toxicity QSAR model, values ​​less than or equal to 65% include the following values ​​and all intervals therebetween: 65; 64; 63; 62; 61; 60; 59; 58; 57; 56; 55; 54; 53; 52; 51; 50; 49; 48; 47; 46; 45; 44; 43; 42; 41; 40; 39; 38; 37; 36; 35; 34; 33; 32; 31; 30; 29; 28; 27; 26; 25; 24; 23; 22; 21 ;20;15;10;5;3;1;0.50;0.49;0.48;0.47;0.46;0.45;0.44;0.42;0.40;0.38;0.36;0.34;0.32;0.30;0.28;0.26;0.24;0.22;0.20;0.18;0.16;0.14;0.12;0.10;0.09;0.08;0.07;0.06;0.05;0.04;0.03;0.01;0.00.

[0102] According to another embodiment, the mutagenicity QSAR statistical threshold percentage is typically 58%.

[0103] Preferably, for the mutagenicity QSAR measurement, the delta value is at least 48%, preferably at least 53%, typically at least 56%.

[0104] In general, for mutagenicity measurements (mutagenicity QSAR), oligomers and / or polymers comprising at least one diphenylamine repeating unit of formula (I) and optionally at least one phenyl α-naphthylamine repeating unit of formula (II) have a QSAR model percentage (%) value less than or equal to 10%, preferably less than or equal to 5%, typically less than or equal to 2%.

[0105] According to the present invention, for the mutagenicity QSAR model, a value less than or equal to 10% includes the following values ​​and all intervals therebetween: 10; 9; 8; 7; 6; 5; 4; 3; 2; 1; 0.9; 0.8; 0.70; 0.69; 0.68; 0.67; 0.66; 0.65; 0.64; 0.63; 0.62; 0.61; 0.60; 0.59; .058; 0.57; 0.56; 0.55; 0.54; 0.53; 0.52; 0.5 1;0.50;0.49;0.48;0.47;0.46;0.45;0.44;0.42;0.40;0.38;0.36;0.34;0.32;0.30;0.28;0.26;0.24;0.22;0.20;0.18;0.16;0.14;0.12;0.10;0.09;0.08;0.07;0.06;0.05;0.04;0.03;0.02;0.01;0.00.

[0106] According to another embodiment, the carcinogenicity QSAR statistical threshold percentage is generally 85%.

[0107] Preferably, for the carcinogenicity QSAR measurement, the delta value is at least 77%, preferably at least 82%, typically at least 85%.

[0108] In general, for carcinogenicity measurements (carcinogenicity QSAR), oligomers and / or polymers comprising at least one diphenylamine repeating unit of formula (I) and optionally at least one phenyl α-naphthylamine repeating unit of formula (II) have a QSAR model percentage (%) value less than or equal to 10%, preferably less than or equal to 5%, typically less than or equal to 2%.

[0109] According to the present invention, for the carcinogenicity QSAR model, values ​​less than or equal to 10% include the following values ​​and all intervals therebetween: 10; 9; 8; 7; 6; 5; 4; 3; 2; 1; 0.9; 0.8; 0.70; 0.69; 0.68; 0.67; 0.66; 0.65; 0.64; 0.63; 0.62; 0.61; 0.60; 0.59; .058; 0.57; 0.56; 0.55; 0.54; 0.53; 0.52; 0.5 1;0.50;0.49;0.48;0.47;0.46;0.45;0.44;0.42;0.40;0.38;0.36;0.34;0.32;0.30;0.28;0.26;0.24;0.22;0.20;0.18;0.16;0.14;0.12;0.10;0.09;0.08;0.07;0.06;0.05;0.04;0.03;0.02;0.01;0.00.

[0110] "Rubber composition" generally refers to an elastomeric composition, which, as the name implies, includes natural or synthetic macromolecular substances and has elasticity similar to rubber. Specifically, elastomer refers to a polymer having elasticity obtained by cross-linking.

[0111] "Rubber / elastomer" refers to an elastic, impermeable and durable substance obtained by coagulating the latex of certain plants, trees or vines of equatorial forests, or prepared synthetically by polymerizing various unsaturated hydrocarbons.

[0112] Common classifications include the division of rubber into three main categories (the abbreviations used are those recommended by the 1995 ISO 1629 standard):

[0113] - General purpose rubber, represented by natural rubber (NR) and synthetic isoprene rubber (IR), styrene butadiene rubber (SBR) and polybutadiene rubber (BR);

[0114] - rubbers for special purposes, namely ethylene propylene and diene polymers or terpolymers (EPM and EPDM), chlorinated or brominated isobutylene isoprene polymers (IIR, BIIR, CIIR), butadiene acrylonitrile polymers (NBR) and polychloroprene (CR);

[0115] - Rubbers for very special purposes, including silicone rubber (VMQ, FVMQ), fluorinated elastomers (FKM), chlorinated or chlorosulfonated polyethylene (CM, CSM), polyacrylates (ACM), ethylene-vinyl acetate copolymers (EVM) and ethylene methyl acrylate (AEM), hydrogenated nitrile rubber (HNBR) and epichlorohydrin rubber (CO, ECO, GECO), plastic polyurethane (AU, EU).

[0116] Thermoplastic elastomers, which form a separate category in their own right, can be added to this classification. In fact, in contrast to the previously mentioned rubbers, these elastomers do not require vulcanization and can be processed in the same way as thermoplastics.

[0117] In a known manner, natural rubber (NR) is produced by coagulating the latex of several plants, mainly from the rubber tree, Hevea brasiliensis, of the Euphorbiaceae family, native to the Amazon. The latex is collected by cutting the bark of the trunk, allowing it to flow from the latex ducts into a barrel placed below. The harvested latex is transferred to containers, filtered and can then be stabilized with ammonia (flake precipitation), then pressed to reduce its water content, or coagulated in a more or less controlled manner and dried by fire smoke (the tar prevents corruption), to obtain rubber pellets.

[0118] For example, synthetic rubbers can be made by polymerizing various monomers including isoprene (2-methyl-1,3-butadiene), 1,3-butadiene, chloroprene (2-chloro-1,3-butadiene), and isobutylene (methpropylene), with a low percentage of isoprene used for crosslinking. These monomers and other monomers can be copolymerized in various desired proportions to obtain a wide range of physical, mechanical, and chemical properties. The monomers can be pure products, and the addition of impurities and additives can be controlled by design to provide optimal properties. The polymerization of pure monomers can be better controlled to obtain the desired ratio of cis and trans double bonds. Other rubber compositions are known, such as butadiene-acrylonitrile, also known as "nitrile rubber" (NBR), or ethylene acrylate rubber (AEM).

[0119] In the present invention, rubber composition or elastomeric composition (synonyms) refers to a composition mainly comprising rubber, ie a composition comprising at least 60%, preferably at least 70%, in particular at least 80%, usually at least 90% rubber by mass.

[0120] Typically, the rubber composition and / or the at least one antioxidant additive do not substantially comprise, preferably do not comprise, diphenylamine monomer (DPA) or p-phenylenediamine (PPD) or any other standard antioxidant (having toxicity and / or ecotoxicity) mentioned in the above prior art description. In some embodiments, the rubber composition used according to the invention or the antioxidant used according to the invention do not substantially comprise, preferably do not comprise, antioxidant additives other than oligomers and / or polymers comprising at least one diphenylamine repeating unit of formula (I) according to the invention and optionally at least one phenyl α-naphthylamine repeating unit of formula (II).

[0121] In general, based on the total mass of antioxidants in the rubber-based composition, the antioxidant additive according to the present invention is 50% to 100% by mass, preferably 80% to 100% by mass, specifically 90% to 100% by mass, and usually 100% by mass. According to the present invention, "50% to 100%" refers to the following values ​​or any intervals therebetween: 50; 55; 60; 65; 70; 75; 80; 85; 90; 95; 100.

[0122] The at least one antioxidant and the at least one oligomer and / or polymer generally comprising at least one diphenylamine repeating unit of formula (I) and optionally at least one phenyl α-naphthylamine repeating unit of formula (II) are present in the rubber-based composition used in the present invention in amounts such as conventionally used in the art. For example, they can be used in an amount of 0.1 wt % to 10 wt %, preferably 0.5 wt % to 5 wt %, typically 1 wt % to 4 wt %, based on the total weight of the rubber composition.

[0123] The rubber composition may also contain other additives, such as mineral solid fillers for enhancing mechanical properties, carbon black, plasticizers, vulcanizing agents (such as elemental sulfur or polythiol), vulcanization accelerators, crosslinking retarders, silanes and other agents capable of increasing the degree of crosslinking, etc. These other additives will not be described in more detail below, because their composition and conditions of use (mass content, etc.) are known to those of ordinary skill in the art, depending on the intended use of the rubber-based composition.

[0124] The present invention is also applicable to a method for maintaining the physicochemical and mechanical properties of a rubber-based composition, comprising:

[0125] - preparing the rubber composition, which preferably does not contain diphenylamine (DPA) monomer or p-phenylenediamine (PPD),

[0126] - adding to said rubber-based composition an effective amount of at least one antioxidant comprising an oligomer and / or a polymer comprising at least one diphenylamine repeating unit of formula (I) as defined above and optionally at least one phenyl α-naphthylamine repeating unit of formula (II) as defined above,

[0127] The at least one antioxidant is capable of reducing and / or preventing the toxicity of the rubber-based composition.

[0128] Of course, the various embodiments described above for preventing and / or reducing the toxicity of the rubber-based composition using the at least one antioxidant are also applicable to this method and will not be repeated below.

[0129] According to the present invention, unless otherwise stated, the percentages shown in this application are percentages by mass.

[0130] In the present invention, the term "about" a value V refers to the interval between 0.9xV and 1.1xV. In some embodiments, it refers to the interval between 0.95xV and 1.05xV, specifically the interval between 0.99xV and 1.01xV.

[0131] Example

[0132] Example 1: Toxicity studies

[0133] Les oligomers and / or polymers according to the invention comprising at least one diphenylamine repeating unit of formula (I) and optionally at least one phenyl α-naphthylamine repeating unit of formula (II) were studied and compared with other standard antioxidant compounds with respect to QSAR models for neurotoxicity, reproductive toxicity, mutagenicity and carcinogenicity.

[0134] QSAR modeling scheme

[0135] The degree of toxicity of the various compounds used according to the invention and other standard antioxidants was evaluated by means of the QSAR model (Quantitative Structure Activity Relationship).

[0136] Selection of training and validation sets

[0137] The set of test molecules is defined with chemical structures compiled from several publicly available sources, such as: HSBD (Hazardous Substances Database), EPA (US Environmental Protection Agency), ECHA (European Chemicals Agency) and NTP (US National Toxics Program). The project selected about 34,000 molecules, including: 3245 compounds classified as neurotoxic compounds, 12609 compounds classified as reproductive toxic compounds, 4084 compounds classified as mutagenic compounds, 12158 compounds classified as carcinogenic compounds, and 1953 compounds that are said to be non-toxic, classified as neither neurotoxic nor reproductive toxic nor mutagenic nor carcinogenic.

[0138] Based on this set of test molecules, two groups of molecules were defined: a training set and a validation set. For this purpose, the "leave one out" method was used. The set of test molecules was divided into two groups, one containing 90% of the test molecules and forming the training set, and the other containing the remaining 10% of the test molecules and forming the validation set.

[0139] Performance of QSAR Models

[0140] The generalized linear model (GLM) approach was chosen for quantitative structure-activity relationship (QSAR) analysis. Based on the training set, GLM models were trained to distinguish the chemical structures of (i) neurotoxic and non-neurotoxic compounds, (ii) reproductive toxic and non-reproductive toxic compounds, (iii) mutagenic and non-mutagenic compounds, and (iv) carcinogenic and non-carcinogenic compounds, respectively. This approach resulted in four GLM models with 328, 313, 327, and 330 significant descriptors in the neurotoxic, reproductive toxic, mutagenic, and carcinogenic training sets, respectively. During the training period, the performance of the QSAR models was tested by ROC (receiver operating characteristic) curves, and the area under the curve (AUC) values ​​of 0.8831 for neurotoxicity prediction, 0.7967 for reproductive toxicity prediction, 0.8444 for mutagenicity prediction, and 0.8333 for carcinogenicity prediction were obtained.

[0141] To validate the robustness of the QSAR models, they were then used to predict (i) the neurotoxicity category of the validation set compounds (i.e., neurotoxic / non-neurotoxic category), (ii) the reproductive toxicity category of the validation set compounds (i.e., reproductive toxicity / non-reproductive toxicity category), (iii) the mutagenicity category of the validation set compounds (i.e., mutagenic and non-mutagenic categories), and (iv) the carcinogenicity category of the validation set compounds (i.e., carcinogenic and non-carcinogenic categories). During the validation process, the performance of the QSAR models was measured by the area under the curve (AUC) value, which provided significant values ​​of 0.76 and above for the prediction of neurotoxicity, mutagenicity, and carcinogenicity, and provided a significant value of 0.70 for the prediction of reproductive toxicity.

[0142] The GLM-based QSAR model was then used to study the compounds according to the present invention.

[0143] Results

[0144] Once the model is built on the training set, it is then validated using a validation set, which is based on a statistical threshold percentage mathematically determined on a statistical basis.

[0145] The QSAR statistical thresholds for various toxicity tests are shown in Table 2 below:

[0146] [Table 2]

[0147] Non-toxic and moderately toxic molecules (%) Toxic molecules (%) Neurotoxicity QSAR <55％ ≥55％ Reproductive toxicity QSAR <90％ ≥90％ Mutagenicity QSAR <58％ ≥58％ Carcinogenicity QSAR <85％ ≥85％

[0148] This statistical threshold is a preliminary overview for distinguishing non-toxic, moderately toxic and toxic molecules. However, it does not completely exclude toxic molecules from non-toxic molecules (i.e., there is an error range for the probability of toxic risk). Therefore, the applicant improved its research and determined that the delta value of the statistical threshold for each model (neurotoxicity QSAR, reproductive toxicity QSAR, etc.) was reduced by 30%, providing a reliable guarantee that the tested molecule is toxic or non-toxic. In fact, this new threshold (30% reduction in the statistical threshold) indisputably separates moderately toxic and residual toxic molecules from non-toxic molecules. In addition, an intermediate range (non-zero toxicity probability) including moderately toxic and / or toxic molecules was established in order to establish a more precise classification.

[0149] The classification improved by the applicant is shown in Table 3 below.

[0150] [Table 3]

[0151] Slight toxicity (%) Moderate toxicity (median value) (%) High toxicity (%) Neurotoxicity QSAR <25 25≤QSAR<55 55≤QSAR≤100 Reproductive toxicity QSAR <60 60≤QSAR<90 90≤QSAR≤100 Mutagenicity QSAR <28 28≤QSAR<58 58≤QSAR≤100 Carcinogenicity QSAR <55 55≤QSAR<85 85≤QSAR≤100

[0152] The compound numbers tested are as follows (Table 4 below):

[0153] [Table 4]

[0154]

[0155]

[0156]

[0157]

[0158]

[0159] Thus, the examples designated A to I are according to the invention and the examples designated 1 to 26 are comparative examples (standard antioxidant and antiozonant).

[0160] The results of the QSAR model are shown in Table 5 below:

[0161] [Table 5]

[0162]

[0163]

[0164] As shown in Table 5 above, the antioxidants according to the present invention comprising oligomers and / or polymers (which comprise at least one diphenylamine repeating unit and optionally at least one phenyl α-naphthylamine repeating unit) have very low neurotoxicity, reproductive toxicity, mutagenicity and low carcinogenicity. In contrast, the compounds that make up standard ozone-resistant antioxidants are generally highly toxic, whether in terms of neurotoxicity, reproductive toxicity, mutagenicity and / or carcinogenicity.

[0165] Thus, this QSAR model test demonstrates that the oligomers and / or polymers according to the present invention comprising at least one diphenylamine repeating unit and optionally at least one phenyl α-naphthylamine repeating unit prevent and / or reduce the toxicity of the rubber-based composition.

[0166] Protocol for toxicity assessment using in vivo assays

[0167] To complete the QSAR model testing, the applicant conducted in vivo experiments on the so-called planarian model, an invertebrate microorganism that lives in water and has a cephalic sphere and a distinct neuronal system, which is used in the literature to evaluate the neurotoxicity, neurodevelopmental and reproductive toxicity of relevant compounds (such as pesticides and other toxic organophosphorus compounds) (Poirier et al., Médecine / Sciences (Paris) 2019; 35(6-7): 544-8 "Le planaire, un modèleanimal original pour la toxicologie"; Collins et al. US-2020209223-A1; D. Hagstrom et al., Archives of toxicology, 201791(8), 2837-2847; Zhang et al., TOXICOLOGICAL SCIENCES, 2018, 1-19; Ireland et al., Chemosphere, 2020, 253, 126718). The tests were performed under conditions similar to those reported in the above-mentioned publication (Zhang et al., TOXICOLOGICAL SCIENCES, 2018, 1-19).

[0168] The operating conditions used were as follows:

[0169] - Test concentration value for each chemical product: 5;

[0170] -Concentration range: 0.22mg / L-22mg / L, increasing in half-log increments;

[0171] -Study organisms: intact adult planarians;

[0172] - Test duration: 12 days, with control points assessed on the 7th and 12th days;

[0173] - Control points: lethality, adhesion (the skin produces a sticky mucus that makes the worm stick to the wall instead of floating), movement speed, rest (ratio of rest time to movement time), phototropism and "huddle" (a specific movement pattern adopted by the nominal worm in dangerous situations (here, overheating));

[0174] -Number of repetitions: 3.

[0175] The method used is described below:

[0176] - All compounds are available in powder form;

[0177] - Add the appropriate volume of 100% DMSO (Sigma) as indicated on the tube to obtain a 200-fold 4.4 mg / ml broth;

[0178] - Screening was performed in triplicate plates following the same plate assembly procedure described in Zhang et al., Neurotoxicology and Teratology, 2019.

[0179] [Table 6]

[0180]

[0181] **Behavioral questions registered: Adhesion (skin produces a sticky mucus that allows the worm to stick to walls instead of floating), movement speed, resting (ratio of resting time to moving time), phototropism, and “huddling” (the nominal worm adopts a specific movement pattern in the event of a dangerous situation (here, overheating).

[0182] This test shows that the antioxidant according to the invention (mixture of compounds A and B) is not toxic in vivo, especially compared to the comparative antioxidants PANα and 6PPD.

[0183] Example 2: Antioxidant properties of oligomeric and / or polymeric compounds used according to the invention

[0184] Tested recipes:

[0185] For this test, two types of rubber were prepared and evaluated: HNBR rubber (a hydrogenated nitrile rubber), and AEM rubber ( An ethylene acrylate rubber).

[0186] For each rubber, three formulations were used, varying only the antioxidant, which were:

[0187] - a standard antioxidant of the prior art, namely bis[4-(2-phenyl-2-propyl)phenyl]amine, CAS 10081-67-1 (corresponding to the commercial product Naugard The high performance and high temperature benchmark for rubber additives),

[0188] - or a mixture of the standard antioxidant and the antioxidant according to the invention (corresponding to sample C in Table 4),

[0189] - or an antioxidant according to the invention (Sample C).

[0190] HNBR type rubbers were formulated according to the compositions summarized in Table 7 below (proportions expressed as phe: parts per hundred parts of elastomer):

[0191] [Table 7]

[0192]

[0193] AEM type rubbers were formulated according to the compositions summarized in Table 8 below (proportions expressed as phe: parts per hundred parts of elastomer):

[0194] [Table 8]

[0195]

[0196] The six mixtures (i.e. without the vulcanization system) were 3 The mixture was prepared in a HAAKE internal mixer, and then the accelerator system was added in a drum mixer. Rheological tests were performed on each mixture at 180°C. 150*150*2mm HNBR rubber sheets were pressed after 98min at 180°C. 150*150*2mm EAM rubber sheets were pressed after 98min at 180°C, and then post-vulcanized in an oven at 150°C for 4h.

[0197] result

[0198] The mechanical properties of these six formulations were evaluated in the initial state (Table 9) and after aging at 130°C for 10 days (Table 10). The results are as follows:

[0199] [Table 9]

[0200] Initial state

[0201]

[0202] [Table 10]

[0203] After aging at 130°C for 10 days

[0204]

[0205] Thus, this test shows that, for two different rubber compositions (i.e.: HNBR and AEM), the mechanical properties and aging levels of the rubber compositions obtained with the antioxidant additive according to the invention are at the same or even higher levels compared to the same compositions made with comparative antioxidants recognized on the market (high performance and high temperature market benchmarks).

[0206] Of course, various other modifications may be made to the invention within the scope of the appended claims.

Claims

1. Use of at least one antioxidant in a rubber composition for reducing and / or preventing the toxicity of the rubber composition, the at least one antioxidant comprising at least one oligomer and / or polymer comprising at least one diphenylamine repeating unit of formula (I) Wherein R1 to R10 are each independently selected from: Hydrogen atoms, an alkyl group which is a saturated, straight-chain or branched hydrocarbon group containing 1 to 24 carbon atoms, and Aralkyl, which is an alkyl group as described above, wherein at least one carbon atom is substituted with a monocyclic aromatic hydrocarbon or polycyclic aromatic group containing 5 to 14 carbon atoms.

2. The use according to claim 1, wherein the toxicity comprises one or more of the following toxicities: neurotoxicity, reproductive toxicity, mutagenicity, acute toxicity, carcinogenicity, toxicity to the synthesis, degradation and mode of action of hormones, and ecotoxicity.

3. The use according to claim 1 or 2, wherein the oligomer and / or polymer further comprises at least one phenyl α-naphthylamine repeating unit of formula (II): wherein R11 to R22 are each independently selected from a hydrogen atom and an alkyl group, and the alkyl group is a saturated, linear or branched hydrocarbon group containing 1 to 24 carbon atoms.

4. The method according to claim 1, wherein the at least one diphenylamine of formula (I) is an alkylated diphenylamine in which at least one, preferably two, of R1 to R10 are alkyl or aralkyl, for example tert-butyl or tert-octyl or n-nonyl.

5. The method according to claim 1 , wherein the at least one diphenylamine of formula (I) is an alkylated diphenylamine, wherein at least one, preferably two, of R1 to R5 are alkyl or aralkyl, such as tert-butyl or tert-octyl, and at least one, preferably two, of R6 to R10 are alkyl or aralkyl, such as tert-butyl or tert-octyl.

6. The use according to any one of the preceding claims, wherein the diphenylamine of formula (I) is selected from the group consisting of N,N-diphenylamine, N,N-di-(p-tert-butylphenyl)amine, N,N-di-(p-tert-octylphenyl)amine, N-(p-tert-butylphenyl)-N-aniline, N-(p-tert-octylphenyl)-N-aniline, N-(p-tert-butylphenyl)-N-(p-tert-octylphenyl)amine, tert-butylated diphenylamine and / or tert-octylated diphenylamine, nonylated diphenylamine and any mixtures thereof.

7. The method according to claim 3 , wherein the oligomers and / or polymers comprising at least one diphenylamine repeating unit are selected from one or more of the following compounds: di-tert-octyldiphenylamine dimers, di-tert-octyldiphenylamine trimers, trimers comprising two di-tert-octyldiphenylamine units and one N-(4-tert-octylphenyl)-1-naphthylamine unit, and oligomers of a mixture of N,N-diphenylamine, N,N-di-(p-tert-butylphenyl)amine, N,N-di-(p-tert-octylphenyl)amine, N-(p-tert-butylphenyl)-N-aniline, N-(p-tert-octylphenyl)-N-aniline, N-(p-tert-butylphenyl)-N-(p-tert-octylphenyl)amine.

8. The use according to any one of claims 3 to 7, wherein the phenyl α-naphthylamine is N-(4-tert-octylphenyl)-1-naphthylamine.

9. Use according to any one of the preceding claims 3 to 9, wherein the polymer and / or oligomer comprises in its structure only diphenylamine repeating units and optionally phenyl alpha-naphthylamine repeating units.

10. The use according to any one of the preceding claims 3 to 9, wherein the oligomers and / or polymers comprising at least one diphenylamine repeating unit of formula (I) and optionally at least one phenyl α-naphthylamine repeating unit of formula (II) have QSAR values ​​for measuring each of the following toxicities: neurotoxicity (neurotoxicity QSAR), reproductive toxicity (reproductive toxicity QSAR), mutagenicity (mutagenicity QSAR) and carcinogenicity (carcinogenicity QSAR), the QSAR value for each toxicity corresponding to subtracting a statistical threshold value (%) from a delta value of at least 30%, the statistical threshold value for each of the toxicities being determined by the QSAR model according to the method described in the experimental part.

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