4,4',4''-triaminotrityl alcohol

Endpoint summary

Description of key information

Acute oral toxicity: 

LD50 was considered to be 2376 mg/kg bw when male rats were orally exposed with 4,4',4''-Triaminotrityl alcohol.

Acute Dermal toxicity: 

LD50 was considered to be 2841.1 mg/kg bw, when female New Zealand White rabbits were treated with 4,4',4''-Triaminotrityl alcohol by dermal application.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR Toolbox 3.4.0 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material : 4,4',4''-Triaminotrityl alcohol
- Molecular formula : C19H19N3O
- Molecular weight : 305.379 g/mol
- Smiles notation : C(c1ccc(N)cc1)(c1ccc(N)cc1)(c1ccc(N)cc1)O
- InChl : 1S/C19H19N3O/c20-16-7-1-13(2-8-16)19(23,14-3-9-17(21)10-4-14)15-5-11-18(22)12-6-15/h1-12,23H,20-22H2
- Substance type: Organic
- Physical state: Solid

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: unspecified

Vehicle:

not specified

Details on oral exposure:

not specified

Doses:

2376 mg/kg bw

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male

Dose descriptor:

LD50

Effect level:

2 376 mg/kg bw

Remarks on result:

other: 50% mortality

Mortality:

not specified

Clinical signs:

not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" or "b" or "c" or "d" or "e" or "f" )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and "s" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) AND Dianilines by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after nitrenium ion formation AND SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) AND Benzyl Alcohols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Addition of an Acyl Halide OR Acylation >> Direct Addition of an Acyl Halide >> Alkyl carbamyl halides OR Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR No alert found OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after nitrenium ion formation AND SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR No alert found OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Diazenes and Azoxyalkanes OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Direct nucleophilic attack on diazonium cation (DNA alkylation) OR SN1 >> Direct nucleophilic attack on diazonium cation (DNA alkylation) >> Diazenes and Azoxyalkanes OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.4

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 16 - Sulfur S OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to the quinoid type structures OR AN2 >> Michael addition to the quinoid type structures >> Substituted Anilines by Protein binding alerts for Chromosomal aberration by OASIS v.1.2

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Primary aromatic amine, hydroxyl amine and its derived esters by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.08

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.53

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 2376 mg/kg bw when male rats were orally exposed with 4,4',4''-Triaminotrityl alcohol.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 4,4',4''-Triaminotrityl alcohol. The LD50 was estimated to be 2376 mg/kg bw when male rats were orally exposed with 4,4',4''-Triaminotrityl alcohol.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 376 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from Hazardous Substances Data Bank

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

Data is predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material : 4,4',4''-Triaminotrityl alcohol
- Molecular formula : C19H19N3O
- Molecular weight : 305.379 g/mol
- Smiles notation : C(c1ccc(N)cc1)(c1ccc(N)cc1)(c1ccc(N)cc1)O
- InChl : 1S/C19H19N3O/c20-16-7-1-13(2-8-16)19(23,14-3-9-17(21)10-4-14)15-5-11-18(22)12-6-15/h1-12,23H,20-22H2
- Substance type: Organic
- Physical state: Solid

Species:

rabbit

Strain:

New Zealand White

Sex:

female

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

occlusive

Vehicle:

not specified

Details on dermal exposure:

not specified

Duration of exposure:

24 hrs

Doses:

2841.1 mg/kg bw

No. of animals per sex per dose:

Total = 3 Female
3 Female - 2841.1 mg/kg

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

2 841.1 mg/kg bw

Remarks on result:

other: 50% mortality

Mortality:

not specified

Clinical signs:

not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

(((((("a" or "b" or "c" or "d" or "e" or "f" )  and ("g" and ( not "h") )  )  and "i" )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and "o" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Anilines (Acute toxicity) AND Dianilines by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Radical AND Radical >> Radical mechanism via ROS formation (indirect) AND Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines AND SN1 AND SN1 >> Nucleophilic attack after nitrenium ion formation AND SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Nitrenium Ion formation AND SN1 >> Nitrenium Ion formation >> Primary aromatic amine by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Strong binder, NH2 group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Michael-type addition to quinoid structures  AND AN2 >> Michael-type addition to quinoid structures  >> Substituted Anilines by Protein binding by OASIS v1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Anilines (Unhindered) AND Benzyl Alcohols by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 16 - Sulfur S OR Group 17 - Halogens Cl OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "i"

Similarity boundary:Target: Nc1ccc(C(O)(c2ccc(N)cc2)c2ccc(N)cc2)cc1
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aromatic amines by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Phenols by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by rtER Expert System ver.1 - USEPA

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as 4-Alkylanilines by rtER Expert System ver.1 - USEPA

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.709

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.02

Interpretation of results:

other: Not Classified

Conclusions:

LD50 was estimated to be 2841.1 mg/kg bw, when female New Zealand White rabbits were treated with 4,4',4''-Triaminotrityl alcohol by dermal application.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 4,4',4''-Triaminotrityl alcohol. The LD50 was estimated to be 2841.1 mg/kg bw, when female New Zealand White rabbits were treated with 4,4',4''-Triaminotrityl alcohol by dermal application.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 841.1 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from Hazardous Substances Data Bank

Additional information

Acute oral toxicity:

In different studies, 4,4',4''-Triaminotrityl alcohol (CAS no 467-62-9) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats for 4,4',4''-Triaminotrityl alcohol along with the study available on structurally similar read across substance 4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride (CAS no 632-99-5) and 6-dimethylamino-3,3-bis(4-dimethylaminophenyl)phthalide (CAs No.1552-42-7). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 4,4',4''-Triaminotrityl alcohol. The LD50 was estimated to be 2376 mg/kg bw when male rats were orally exposed with 4,4',4''-Triaminotrityl alcohol.

In experimental study done on 7-methyloctyl acetate by Commission of the European Communities (Directorate-General Environment, Consumer Protection and Nuclear Safety- Commission of the European Communities- Brussels Luxembourg, 1988), the acute oral toxicity study was conducted by using 4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride in rat at the concentration of 12000 mg/kg bw orally in 40% suspension in carboxymethylcellulose. No mortality was observed at 12000 mg/kg bw. Therefore, LD50 was considered to be > 12000 mg/kg when rats were treated with 4-(4-aminophenyl)(4-iminocyclohexa-2,5-dienylidene)methyl)-2-methylaniline hydrochloride) orally.

In another experimental study supported by Ministry of Health, Labour and Welfare, Ministry of the Environment and National Institute of Technology and Evaluation (J-CHECK Japan Chemicals Collaborative Knowledge database, 2010), the acute oral toxicity study was conducted by using 6-dimethylamino-3,3-bis(4-dimethylaminophenyl)phthalide in rat. Test substance 3,3-bis (p-dimethylaminophenyl) -6-dimethylaminophthalide taken from Yamada Chemical Industry Co., Ltd. (Kyoto), has Lot No. 010327, and purity 99.5%. Male and female SD rats [Crj: CD (SD) IGS, SPF] obtained from Charles River Japan Co., Ltd. Were quarantined and acclimatized for 6 days and then subjected to the test. On the day before administration, each group was divided into 5 males and 5 females per group so that the average body weight of each group was almost uniform by the weight stratification random sampling method. The age at the administration day was 5 weeks old, the body weight ranged from 124 to 129 g for males and 113 to 121 g for females. Throughout the whole quarantine and acclimatization period, rearing automatically controlled at a temperature of 22 ± 2 ° C., relative humidity of 55 ± 15%, ventilation at about 12 times / hour, lighting 12 hours / day (7: 00-19: 00). Five animals (same sex) were housed and raised in polycarbonate cages spread with experimental animal bedding (Beta chip, Nippon Charles River Co., Ltd.). For the animals, a solid feed for experimental animals (MF, Oriental Yeast Industry Co., Ltd.) and filtering with 5 μm, freely ingested tap water irradiated with ultraviolet light. Rats fasted for about 18 hours from the day before administration were forcibly orally administered using a stomach probe and no feed was given for about 3 hours after administration. Mortality, general condition was observed for 14 days immediately after administration, 4 times 1, 3 and 6 hours after administration, once a day for 14 days thereafter. All the cases were measured using an electronic balancing balance on days 4, 8 and 15 immediately before administration. After completion of the observation, the abdominal aorta was exsanguinated under anesthesia by intraperitoneal administration of thiopental sodium, euthanized and necropsied after euthanasia. After 14 days of observation, no abnormalities were observed in any of the animals including death.Both males and females showed the same body weight as in the control group. No abnormal findings were found in any of the animals. Based on above observation, LD50 was considered to be > 2000 mg/kg when rats were treated with 6-dimethylamino-3,3-bis(4-dimethylaminophenyl)phthalide orally.

Thus, based on the above studies on 4,4',4''-Triaminotrityl alcohol (CAS no 467-62-9) and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4,4',4''-Triaminotrityl alcohol can be classified as category V of acute oral toxicity.

Acute Dermal toxicity:

In different studies, 4,4',4''-Triaminotrityl alcohol (CAS no 467-62-9) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats and rabbits for 4,4',4''-Triaminotrityl alcohol along with the study available on structurally similar read across substance 4,4'-oxydianiline (CAS no 101-80-4) and 4,4'-methylenedianiline (CAS no 101-77-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 4,4',4''-Triaminotrityl alcohol. The LD50 was estimated to be 2841.1 mg/kg bw, when female New Zealand White rabbits were treated with 4,4',4''-Triaminotrityl alcohol by dermal application.

In experimental study done on 4,4'-oxydianiline by U.S. Environmental Protection Agency (Robust Summaries & Test Plans: Oxydianiline: Revised Summaries, U.S. Environmental Protection Agency, 201-16479C, JAN -8-2007), the acute dermal toxicity study was conducted by using 4,4'-oxydianiline in Rabbit. Albino Rabbit was taken for the dermal study at a dose of 5000 mg/kg. The test substance (4,4’-Oxydianiline, purity approximately 100%) was applied to the shaved skin of 1 rabbit as a 50% ointment in Carbowax 1500. The maximum feasible dose was 5000 mg/kg, but absorption of the test substance was poor. The animal was wrapped in moisture-proof cellophane and bandage for 24 hours. The rabbit was euthanized 12 days after the dermal application of the test substance. No mortality was observed. Loss of appetite and weight loss for 5 days were observed. No pathological changes were observed. Hence, LD50 was considered to be > 5000 mg/kg bw, when rabbit was treated with 4,4'-oxydianiline by dermal application to shaved skin.

In another experimental studies supported by EUROPEAN COMMISSION – European Chemicals Bureau (IUCLID Dataset, EUROPEAN COMMISSION – European Chemicals Bureau, 18 - FEB - 2000), the acute dermal toxicity study was conducted by using 4,4'-methylenedianilinein Rats. The Tif RAIf (SPF), were used in 2 groups of 6 rats, each containing 3 males and 3 females and there were 2 dose levels, 2150 or 3170 mg/kg at a formulation concentration of 50%.The Source of the test substance was Bayer AG Leverkusen. The test substance (4,4’–Dimethylenedianiline (MDA), suspended in dimethyl sulphoxide, or 70% ethyl alcohol, or with carboxymethyl–cellulose. The animals were kept at22 ± 1°Cand 55 ± 5% RH with a 14 hr light–cycle day. They received, ad libitum, water and the rat food NAFAG, Gossan SG. They were acclimatized for at least 4 days, and the initial body weight was 180–200 g. They were observed for 14 days after treatment. The MDA suspensions were homogenized, and during treatment stability was maintained by stirring. The applications were maintained under occlusion for 24 hr. None of the animals died, and there were no local reactions. Animals at each dose level, in each vehicle, exhibited dypsnoea, exophthalmos, ruffled fur, and a curved body position. Autopsy after 14 days did not reveal any gross effects (Fairhurst). From the above observation, LD50 was considered to be > 3100 mg/kg bw, when rats were treated with 4,4'-methylenedianiline by dermal application to the skin.

In addition to this, another result was supported by EUROPEAN COMMISSION – European Chemicals Bureau (IUCLID Dataset, EUROPEAN COMMISSION – European Chemicals Bureau, 18 - FEB - 2000). In which, the acute dermal toxicity study was conducted by using4,4'-methylenedianilinein Rats. 10 Male and female, Sprague Dawley rats, of average weight 155 g, were taken and given a proprietary feed, and water ad libitum.The test substance 4,4’-Diaminodiphenylmethane (MDA) was distilled (having >98% strength) as a 50% milling in distilled water and applied to about 50 cmEXP2 of the shaved back, or flank, in the maximum possible doses of 2500 mg/kg and 1000 mg/kg. The Source of the test substance was Bayer AG Leverkusen. The method employed was that of Noakes. Mortality and resorptive poisoning symptoms were observed, and the animals were dissected after sacrifice using carbon dioxide. There were no deaths during the 14 day observation period, and there were no poisoning symptoms. Macroscopic examination of the internal organs did not reveal any effects caused by the test substance. Hence, LD50 was considered to be > 2500 mg/kg bw, when rats were treated with 4,4'-methylenedianiline by dermal application to the shaved back, or flank.

Further supported by experimental study given by EUROPEAN COMMISSION – European Chemicals Bureau (IUCLID Dataset, EUROPEAN COMMISSION – European Chemicals Bureau, 18 - FEB - 2000), the acute dermal toxicity study was conducted by using4,4'-methylenedianilinein Rats. 10 Male and female, Sprague Dawley rats, of average weight 155 g, were taken and given a proprietary feed, and water ad libitum. The test substance 4,4’-Diaminodiphenylmethane (MDA) was distilled (having >98% strength) as a 50% solution in dimethyl sulphoxide and applied to about 50 cmEXP2 of the shaved back and flank, in the maximum possible doses of 500, 1000, 1250, 2000, 2500 mg/kg. The Source of the test substance was Bayer AG Leverkusen. The method employed was that of Noakes. Mortality was recorded after 1hr, and then 1, 2, 7, and 14 days. After being unbound all the animals at all doses displayed marked apathy, hyper chromodacryorrhea, and intensely yellow urine. At the dose level of 2500 mg/kg, there was observed after 4 days from the beginning of the test a general jaundice which was fading after 14 days. At the dose levels of 500–2000 mg/kg, poisoning symptoms were no longer observed 6–9 days after the beginning of the test. The dead rats, and those sacrificed with carbon dioxide, were dissected. Dissection showed that the animals which died, and some of those sacrificed after 14 days, exhibited a bright, clay–coloured to yellowish colour change of the liver parenchyma. In the case of the 2500 mg/kg dose group, some of the 10 animals which died displayed an extreme, general jaundice, and some displayed a slimy to bloody enteritis, as well as bleeding stomach ulcers. Therefore, LD50 was considered to be 2080 mg/kg bw, when rats were treated with 4,4'-methylenedianiline by dermal application to the shaved back and flank.

Thus, based on the above studies on 4,4',4''-Triaminotrityl alcohol (CAS no 467-62-9) and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4,4',4''-Triaminotrityl alcohol can be classified as category V of acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies on 4,4',4''-Triaminotrityl alcohol (CAS no 467-62-9) and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 4,4',4''-Triaminotrityl alcohol can be classified as category V of acute oral and dermal toxicity.