1,4-bis(p-tolylamino)anthraquinone

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary source.

Data source

Reference

Reference Type:

other: seconary source

Title:

DERMAL, EYE, AND ORAL TOXICOLOGICAL EVALUATIONS

Author:

Indu A. Muni, Elliot B. Gordon,Jane B. Goodband

Year:

1986

Bibliographic source:

U.S. Army Medical Bioengineering Research and Development Laboratory

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute dermal toxicity study was conducted by using the given test chemical.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,4-bis(p-tolylamino)anthraquinone

EC Number:

204-909-5

EC Name:

1,4-bis(p-tolylamino)anthraquinone

Cas Number:

128-80-3

Molecular formula:

C28H22N2O2

IUPAC Name:

1,4-bis[(4-methylphenyl)amino]-9,10-anthraquinone

Test material form:

solid

Details on test material:

- Name of test material (IUPAC name): 1,4-Bis(p-tolylamino)anthraquinone
- Common name: C.I. Solvent Green 3
- Molecular formula: C28H22N2O2
- Molecular weight: 418.4938 g/mol
- Smiles notation: c12c(c(Nc3ccc(cc3)C)ccc1Nc1ccc(cc1)C)C(=O)c1c(C2=O)cccc1
- InChl: 1S/C28H22N2O2/c1-17-7-11-19(12-8-17)29-23-15-16-24(30-20-13-9-18(2)10-14-20)26-25(23)27(31)21-5-3-4-6-22(21)28(26)32/h3-16,29-30H,1-2H3
- Substance type: Organic
- Physical State: Solid

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Rabbits were received from Pine Acres Rabbi try, West Brattleboro, Vermont
- Age at study initiation: These animals were 8-15 weeks old when obtained.
- Housing: The rabbits were individually housed in stainless steel cages,
- Diet (e.g. ad libitum): Fed Charles River Rabbit Formula (Agway) ad libitum and
- Water (e.g. ad libitum): provided untreated municipal water via water bottles
- Acclimation period: They were quarantined for two weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Animals were maintained at a temperature range of 67°F to 72°F
- Humidity (%): relative humidity range of 35% to 65%
- Air changes (per hr): Rooms are provided 12-16 air changes per hour
- Photoperiod (hrs dark / hrs light): Fluorescent lighting was controlled to provide a 12-hour
light cycle (1 AM to 7 PM).

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: 0.9% sodium chloride

Details on dermal exposure:

TEST SITE
- Area of exposure: The hair was carefully removed from the back and sides of each animal prior to testing. Oster animal clippers were used for this procedure.
- % coverage: 6 in. x 6 in
- Type of wrap if used: The trunk of the animal was wrapped in plastic wrap and then stockinette to prevent removal of the patches by the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the wrappings and patches were removed.
- Time after start of exposure:24 hour

Duration of exposure:

24 hour

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

five male and five female

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed 3 times on the day of dosing and twice daily thereafter for signs of toxicity. Body weights were determined twice weekly.
- Necropsy of survivors performed: yes, necropsies were performed on animals dying intercurrently, as well as those surviving treatment and sacrificed on day 14.
- Other examinations performed: Histopathological examination of treated and untreated skin application sites was performed on animals dying during the test period and on 2 animals per sex necropsied at the end of the test period.

Statistics:

No data

Results and discussion

Preliminary study:

No data

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed at 2000 mg/kg bw during the 14 day observation period.

Clinical signs:

other: The only overt sign of toxicity observed during the study was mild diarrhea displayed by female rabbit 8850 in the afternoon of day 1. This mild diarrhea subsided completely by the morning of day 2.

Gross pathology:

There were no gross visible lesions detected upon necropsy of all 10 rabbits at the termination of the study.

Other findings:

No data

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Conclusions:

The acute dermal LD50 value was considered to be >2000 mg/kg bw, when 10 male and female New Zealand White rabbits were treated with the given test chemical by dermal application.

Executive summary:

The acute dermal toxicity study was conducted by using the given test chemical in 10 male and female New Zealand White rabbits at the dose concentration of 2000 mg/kg bw. The hair was carefully removed from the back and sides of each animal prior to testing. Oster animal clippers were used for this procedure. The powdered test material for the single dose trials was applied uniformly to a 6 in. x 6 in. pad at a dose of 2000 mg/kg, moistened with 0.9% sodium chloride, and secured with surgical tape to the previously clipped and abraded test site. The trunk of the animal was wrapped in plastic wrap and then stockinette to prevent removal of the patches by the animal. After a 24 hour exposure period, the wrappings and patches were removed. All animals were observed 3 times on the day of dosing and twice daily thereafter for signs of toxicity. Body weights were determined twice weekly, and necropsies were performed on animals dying intercurrently, as well as those surviving treatment and sacrificed on day 14. Histopathological examination of treated and untreated skin application sites was performed on animals dying during the test period and on 2 animals per sex necropsied at the end of the test period. No mortality was observed at 2000 mg/kg bw during the 14 day observation period. The only overt sign of toxicity observed during the study was mild diarrhea displayed by female rabbit 8850 in the afternoon of day 1. This mild diarrhea subsided completely by the morning of day 2. The body weights of 3 male and 4 female rabbits either remained constant or increased during the study. Male rabbit 8828 lost approximately 100 grams between days 0 and 3, but regained weight by day 7. Female rabbit 8861 and male rabbit 8810 decreased in weight by 200 grams between days 10 and 14. There were no gross visible lesions detected upon necropsy of all 10 rabbits at the termination of the study.

Hence, the acute dermal LD50 value was considered to be >2000 mg/kg bw, when 10 male and female New Zealand White rabbits were treated with the given test chemical by dermal application.