Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline Study performed under GLP like quality controlled conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
no
Remarks:
QAU statement included
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: Off-white powder
- Storage condition of test material: room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown, PA
- Age at study initiation: 2-4 months
- Weight at study initiation: 2.0 - 2.4 kg
- Fasting period before study:
- Housing: 1/cage in suspended wire cages. Bedding was placed beneath the cages and changed at least three times per week.
- Diet: Fresh Purina Rabbit Chow (Diet #5321) was provided daily.
- Water: ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature: controlled
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Remarks:
The patch and test article were moistened with saline to enhance contact of the test article with the dose site.
Details on dermal exposure:
TEST SITE
- Area of exposure: trunk
- % coverage: 10% of the body surface
- Type of wrap if used: The test article was applied under a 4 layered surgical gauze patch measuring 10 x 15 cm. The torso was wrapped with plastic which was secured with nonirritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test article was removed by gentle washing with distilled water.
- Time after start of exposure: 24 hours
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed 1,2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for 14 days for mortality. Body weights were recorded pretest and on days 3,7 and 14 or at death.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived the 2000 mg/kg dermal application.
Clinical signs:
Instances of mucoid diarrhea, diarrhea and anogenital soiling were the only abnormal systemic signs noted during the study.
Body weight:
Body weight changes were normal in 8/10 animals. Two animals lost weight during the second week of the observation period.
Gross pathology:
Necropsy results were normal in 8/10 animals. Soiling of the anogenital area was noted in one animal and lung abnormalities in another.
Other findings:
Dermal Observations: There were no abnormal dermal responses at any observation period up to and including 72 hours. Thereafter, observations were discontinued.

Applicant's summary and conclusion

Conclusions:
Based on this study, the dermal LD50 in rabbits was determined to exceed 2000 mg/kg.
Executive summary:

In an acute dermal toxicity study following OECD guideline 402, 5 male and 5 female New Zealand White rabbits were dermally exposed to the test item for 24 hours at a limit dose of 2000 mg/kg body weight. The test article was moistened with saline and applied to the clipped trunk of the animals under a 4 layered surgical gauze patch measuring 10 x 15 cm. The torso was wrapped with plastic which was secured with nonirritating tape. After 24 hours the wrapping was removed and residual test article was washed off with distilled water. All animals were observed 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for 14 days for mortality. Body weights were recorded pretest and on days 3, 7 and 14 or at death. All animals were examined for gross pathology. All animals survived the 2000 mg/kg dermal application. Body weight changes were normal in 8/10 animals. Two animals lost weight during the second week of the observation period. There were no abnormal dermal responses at any observation period up to and including 72 hours. Thereafter, observations were discontinued. Instances of mucoid diarrhea and diarrhea were the only abnormal systemic signs noted during the study. Necropsy results were normal in 8/10 animals. Soiling of the anogenital area was noted in one animal and lung abnormalities in another. Based on these observations, the dermal LD50 value of the test item was greater than 2000 mg/kg bw.