Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Pre-GLP study following a method equivalent to a recognised guideline at a limit dose, with some deviations not expected to affect the reliability of the study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Limit dose of 2000mg/kg bw applied single dose; no gross pathology completed.
Principles of method if other than guideline:
The principles of the method were in accordance with the US 16 CFR 1500.3 definitions.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Physical state: liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: at least 8 weeks old.
- Weight at study initiation: not reported
- Housing: The animals were housed 2/cage in suspended wire mesh cages.
- Diet: Rabbit chow ad libitum
- Water: ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: abdomen
- Type of wrap if used: The test material was applied once dermally to the prepared site under gauze patches. The patches were secured with adhesive tape and the trunks were wrapped with impervious material.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the exposure site was wiped, but not washed, to remove excess material.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
Duration of exposure:
24h
Doses:
2000 mg/kg
No. of animals per sex per dose:
4 males and 6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Dermal reactions were scored at 24 hours by the Draize scoring system. The rabbits were .observed daily for 14 days for signs of toxicity, pharmacological effects and mortality. Body weights were recorded pretest and in survivors at 14 days.
- Necropsy of survivors performed: no

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal died on day 10
Clinical signs:
Predeath signs included anorexia, diarrhea, mucus in stool, lethargy and ptosis. With the exception of diarrhea, all animals remained in generally good health.
Body weight:
no significant changes observed.
Gross pathology:
not examined
Other findings:
Very slight to well defined erythema and very slight to slight edema were noted at 24 hours.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: US CPSC / US FDA
Conclusions:
Under the conditions of this study the LD50 was determined to be > 2000 mg/kg and so the test material is not considerd to be toxic to New Zealand rabbits via the dermal route.
Executive summary:

The pre-GLP study was performed following a method similar to OECD 402 to assess the dermal toxicity of the test material to New Zealand White rabbit. The test substance was evaluated in 10 New Zealand white rabbits. A dose of 2000 mg/kg test substance (undiluted), was applied to intact and abraded clipped skin site under a occlusive dressing for 24 hours. Skin observations were made 24 hours after patch removal and then daily for 14 days for signs of toxicity, pharmacological effects and mortality. One test animal died on day ten; pre-death toxic signs included anorexia, diarrhoea, mucus in stool, lethargy, and ptosis. Isolated instances of diarrhoea were periodically noted in 3 animals. Six animals remained normal throughout the observation period. Very slight to well defined erythema and very slight to slight edema were noted at 24 hours. Under the conditions of this study the LD50 is considered to be greater than 2000 mg/kg.