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Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 September 1992 to 30 September 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Benzenamine, reaction products with aniline hydrochloride and nitrobenzene
EC Number:
309-912-6
EC Name:
Benzenamine, reaction products with aniline hydrochloride and nitrobenzene
Cas Number:
101357-15-7
Molecular formula:
This is a UVCB substance. See section 1.2 for individual components.
IUPAC Name:
Benzenamine, reaction products with aniline hydrochloride and nitrobenzene
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston , Kent, UK
- Age at study initiation: 10 - 14 weeks
- Weight at study initiation: males: 208 - 231g; females: 211 - 235 g
- Fasting period before study: None
- Housing:suspended polypropylene cages furnished with softwood sawdust, individually for 24 h exposure, followed by groups of 5 by sex for remainder of study.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22 °C
- Humidity (%): 60 - 75%. On two occasions the humidity was above the limit specified in the protocol (70%). This was considered not to have affected the purpose or integrity of the study.
- Air changes (per hr): ca. 15/hr
- Photoperiod (hrs dark / hrs light): 12 h continuous light, 12 h continuous dark

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 5 cm x 4 cm. The appropriate amount of the test material was applied uniformly to the shorn skin which had previously been moistened with arachis oil B.P.
- % coverage: ca. 10% of total body surface
- Type of wrap if used: surgical gauze measuring 7 cm x 4 cm was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage (HYPERTIE). The bandage was further secured with a piece of BLENDERM wrapped around each end.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cotton wool moistened with acetone
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg


Duration of exposure:
24 h
Doses:
2000 mg/kg bodyweight
No. of animals per sex per dose:
5 male, 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed 0.5, 1, 2, and 4 hours after dosing and subsequently once daily for 14 days for deaths, overt signs of toxicity and any adverse dermal reactions. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology
At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
Data evaluations include the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities (behavioural, clinical observations, gross lesions, bodyweight changes, mortality and other toxicological effects). Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths.
Clinical signs:
other: No signs of systemic toxicity were noted. Black coloured staining of fur was commonly noted.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified according to EU criteria.
Conclusions:
The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 402 "Acute Dermal Toxicity". A group of ten animals (five males and five females) was given a single 24-hour, semi-occluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of treatment and then subjected to gross pathological examination. There were no deaths. No signs of systemic toxicity or skin irritation were noted during the study. All animals showed expected gain in bodyweight during the study. No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight.