Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 10, 1979 - May 2, 1979
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline 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)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Inc., Pennsylvania
- Housing: Stainless steel, wire mesh cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum of 7 days

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

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: ca. 10
- Type of wrap if used: impervious elastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was wiped clean with a soft cloth and tap water
- Time after start of exposure: 24 hours

Duration of exposure:
24 hours
Doses:
20000 mg/kg
No. of animals per sex per dose:
Two rabbits, 1 male and 1 female were used in the range finding study and six rabbits, 3 male and 3 female were used in the LD50 determination.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each rabbit was observed 24 hours following dermal application of the test material and daily thereafter. Individual body weights were determined on the day of dosing, day 7 and day 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 20 000 mg/kg bw
Mortality:
Three deaths, two male (day 10 and 13) and one female (day 8), occurred during the study.
Clinical signs:
Twenty-four hours after administration of the test material, all rabbits exhibited erythema with three of the eight rabbits also exhibiting oedema. The irritation on all dose application sites returned to normal by day three and remained so throughout the study. Seven of the eight rabbits exhibited one or more of these clinical signs: diarrhoea, decreased locomotor activity, nasal discharge and salivation.
Body weight:
The weekly mean body weights of both males and females decreased on day seven; increasing on day 14. The mean body weights on day 14, however, were still not as high as the body weights on day 0.
Gross pathology:
Gross necropsies of animals deceased during the study revealed salivation, diarrhoea, injection of the stomach, small intestines, cecum and colon, dark red areas of the lungs, numerous white masses in the liver and numerous white masses throughout the body cavity. The gross necropsies of the rabbits which survived the 14 day study period revealed diarrhoea, nasal discharge, dark red spots on the lungs, numerous small white masses on the liver, colon distended by gas enlargement and discolouring of the gall bladder.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
An LD50 value of >20000 mg/kg bw is reported in a reliable study conducted according to GLP.