4-aminobenzonitrile

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January - March 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-aminobenzonitrile

EC Number:

212-850-1

EC Name:

4-aminobenzonitrile

Cas Number:

873-74-5

Molecular formula:

C7H6N2

IUPAC Name:

4-aminobenzonitrile

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): 4-Aminobenzonitril
- Physical state: solid
- Stability under test conditions: not stated
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, 97633 Sulzfeld, Germany
- Age at study initiation: Approximately 8 weeks (males) and 12 weeks (females) at the time of administration.
- Weight at study initiation: 231 - 291 g
- Housing:Single caging in Makrolon cages type III (37.5 cm x 21.5 cm bottom area , 18 cm height). Wire mesh lids, Sanitation of cages once a week.
- Diet (e.g. ad libitum): Ssniff R/M-H maintenance diet for rats and mice (item V1534-300) ad libitum, supplied by Ssniff Spezialdiäten GmbH, 59494 Soest, Germany. Analysis of the feed for ingredients and contaminants is performed randomly by Ssniff.
- Water (e.g. ad libitum): Tap water, from an automatic watering system, ad libitum. Random samples of the water are analysed by the "AGES" 1226 Vienna, Austria, to check, if the water fulfils the requirements for drinking water for humans.
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Mean of 20.41 °C in the dose range finding study, mean of 19.54 °C in the main study, (continuous control and recording).
- Humidity (%): Mean of 50.53 % in the dose range finding study, mean of 39.13 % in the main study, (continuous control and recording).
- Air changes (per hr): 12 per hour.
- Photoperiod (hrs dark / hrs light): Artificial light from 6 a.m. to 6 p.m.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal thoracic region, an area of 6.5 cm x 8 cm (52 cm²) was marked on a relaxed animal.
- % coverage: 10 %
- Type of wrap if used: A cellulose patch (Pehazell, Hartmann AG) with the calculated amount of the test substance on the surface and soaked with deionised water to get optimal contact with the skin, was applied to the test site and held in place by fixing marginally with non irritating tape (Blanderm Wundpflaster, 3M). The test site was covered by a semi-occlusive dressing (Fixomull Stretch, Fa. Beiersdorf).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance was wiped off using wet cellulose tissue, if necessary.
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

Range Finding Study: 400, 894 and 2000 mg/kg bw
Main Study: 2000 mg/kg bw

No. of animals per sex per dose:

Range Finding Study: One male and one female per dose.
Main Study: Five male and five female per dose. (Both animals dosed with 2000 mg/kg bw in the preliminary test were included into the main study).

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were determined before administration, 7 and 14 days after the administration.
- Necropsy of survivors performed: yes
- Other examinations performed: Observations were performed 0 - 0.5, > 0.5 -1, > 1 - 2, > 2 - 4 and > 4 - 6 hours after administration of the test substance and then at least once a day for a total of 2 weeks. Observations included but were not limited to changes in skin, fur, eyes, the occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions. No skin examination of the administration site was possible during the exposure period while it was covered by the patch and wrappings.

Statistics:

not applicable

Results and discussion

Preliminary study:

In a range finding study three groups of one male and one female each were dosed with 400, 894 or 2000 mg per kg body weight. All animals survived for 7 days after administration. Therefore a limit-test with one dose of 2000 mg per kg body weight was performed.
Both animals dosed with 2000 mg/kg in the preliminary test, were included into the main study.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived until the scheduled termination of the study.

Clinical signs:

other: General findings: All animals did not show any clinical signs during the entire observation period. Observations of skin conditions: Exposed skin was not found to be altered by the test substance.

Gross pathology:

No abnormal findings were made in the animals at terminal necropsy.

Other findings:

No abnormal findings.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

No local or systemic test substance related effects were noted from clinical observations or post-mortem examination at a limit dose of 2000 mg 4-Aminobenzonitrile per kg body weight and no mortality occurred.

Executive summary:

In an acute dermal toxicity study according to OECD 402 ("Acute Dermal Toxicity") the test substance 4-Aminobenzonitrile was administered once topically on an area of approximately 6.5 cm x 8 cm on the dorsal thoracic region of five males and five female Spargue Dawley rats. The dose was 2000 mg per kg body weight. The test site was covered by a semi-occlusive dressing. The duration of the exposure was 24 hours.

No local or systemic toxic effects realted to the administration of 4-Aminobenzonitrile were noted from clinical observations or post-mortem examination at a limit dose of 2000 mg of the test substance per kg body weight and no mortality occurred.

Therefore the LD50(dermal) of 4-Aminobenzonitrile is > 2000 mg/kg body weigtht.