Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes
Remarks:
Research & Consulting Company AG
Test type:
standard acute method
Limit test:
yes

Test material

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

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG CH 4414 Fuellinsdorf/Switzerland
- Age at study initiation: 9 to 11 weeks
- Weight at study initiation: males 211 to 229 g, females 193 to 212 g
- Fasting period before study: no data
- Housing: housed individually in Makrolon type-2 cages with standard softwood bedding
- Diet (e.g. ad libitum): Pelleted standard Kliba 343, ad libitum
- Water (e.g. ad libitum): Community tap water, ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40 to 70
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: Jun 5, 1986 To: Jun 26, 1986

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: 4% solution of carboxymethylcellulose sodium salt in distilled water
Details on dermal exposure:
TEST SITE
- % coverage: 10 %
- Type of wrap if used: Test article was applied evenly on the skin with a syringe and covered with an occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated skin was washed with luke-warm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 hours after application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL/kg bw.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
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: Each animal had an examination for changes in appearance and behavior four times during Day 1, and daily during Days 2 to 15. Individual body weight measurements were recorded on Days 1, 8, and 15.
- Necropsy of survivors performed: yes
Statistics:
Statistical analysis was not performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: An LD50 could not be established as no deaths were observed from the single dose administration.
Mortality:
No deaths were observed.
Clinical signs:
Erythema was observed in both sexes. The male rats had recovered within 5 days, whereas the females showed erythema until termination of observation. No systemic symptoms mere observed.
Body weight:
Body weight gain was unaffected during the observation period (see table 1 for details).
Gross pathology:
No pathological changes were observed.

Any other information on results incl. tables

Table 1. Body weights and standard deviations

Dose (mg/kg bw)

Males

Females

Day 1

Day 7

Day 14

Day 1

Day 7

Day 14

2000

219 ± 6.9 g

246 ± 12.0 g

265 ± 12.0 g

199 ± 7.7 g

204 ± 6.4 g

212 ± 9.0 g

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of this experiment, the LD50 after dermal application to rats was determined to be greater than 2000 mg/kg bw.
Executive summary:

In a dermal acute toxicity study according to OECD guideline 402 and in compliance with GLP, five male and five female Wistar rats were treated occlusively with the test article in a 4% solution of Carboxymethylcellulose sodium salt for 24 hours and observed for 14 days thereafter. There were no deaths. Erythema formation was observed in all animals. The male rats had recovered within 5 days, whereas the females showed erythema until termination of observation. No systemic symptoms were observed. Body weight gain was unaffected during the observation period. All animals appeared normal at necropsy. Under the conditions of this study, the LD50 is greater than 2000 mg/kg bw in male and female rats when topically applied.