Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: only secondary literature (handbook)

Data source

Reference
Reference Type:
review article or handbook
Title:
Patty's Industrial Hygiene and Toxicology
Author:
Rowe and McCollister
Year:
1982
Bibliographic source:
Clayton and Clayton (eds.), Vol.2C, 3rd ed. (1982), John Wiley & Sons, New York, 4604 - 4605, 4608, 4701

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Repeated dermal toxicity
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
not specified
Sex:
male/female

Administration / exposure

Details on exposure:
Route of Administration: dermal, half of the dose was applied to the clipped backs of the rabbits twice a day.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0.344 or 3440 mg/kg bw/day
Basis:
no data
No. of animals per sex per dose:
5 males and 5 females
Control animals:
yes, concurrent vehicle

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Dermal irritation:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
344 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: systemic toxicity
Dose descriptor:
LOAEL
Effect level:
344 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: local effects

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

No adverse effects were detected in those animals that received the low dose other than the expected local effects to the skin at the site of application. These included erythema, drying, thickening, cracking and induration. The high dose caused similar but more extensive injury to the skin and caused serious systemic effects. Three animals of each sex became comatose and died or were sacrified in a moribund condition after a few applications. Gross and histopathologic examinations failed to reveal morphologic lesions that would account for the condition of these animals. With the exception of decreases in body size, adipose reserves, and glycogen of hepatocytes, all other parameters were within the normal range.

Applicant's summary and conclusion

Conclusions:
The repeated dermal toxicity of the test item to rats was tested in a subacute study. The NOEAL was determined to be 344 mg/kg bw/day.
Executive summary:

The repeated dermal toxicity of the test item to rabbits was tested in a subacute study. The animals were exposed over a period of 4 weeks with a frequency of 5 days per week. The test item was administrated by applying half of the doses to the clipped backs of the rabbits twice a day. 5 males and 5 females were exposed to a dose of 3440 mg/kg bw/day. Control animals were used, treated with the concurrent vehicle. The NOAEL (basis for effect level systemic toxicity) was determined to be 344 mg/kg bw/day. The LOAEL (basis for effect level local effects) was determined to be 344 mg/kg bw/day. No adverse effects were detected in those animals that received the low dose other than the expected local effects to the skin at the site of application. These included erythema, drying, thickening, cracking and induration. The high dose caused similar but more extensive injury to the skin and caused serious systemic effects. Three animals of each sex became comatose and died or were sacrified in a moribund condition after a few applications. Gross and histopathologic examinations failed to reveal morphologic lesions that would account for the condition of these animals. With the exception of decreases in body size, adipose reserves, and glycogen of hepatocytes, all other parameters were within the normal range.