Registration Dossier

Administrative data

Endpoint:
repeated dose toxicity: dermal
Remarks:
other: No data
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Summary study report
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
review article or handbook
Title:
ROBUST SUMMARY OF INFORMATION ON LUBRICATING OIL BASESTOCKS
Author:
American Petroleum Institute
Year:
2003
Bibliographic source:
ROBUST SUMMARY OF INFORMATION ON LUBRICATING OIL BASESTOCKS pag 45-46

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Undiluted API 83-12 (cas 64742-53-6) was applied at doses of 200, 1000 and 2000 mg/kg/day to the shorn dorsal skin of groups of five male and five female rabbits. The test material was applied to the skin 3 times each week for 4 weeks (12 applications total). The applied material was covered with an occlusive dressing for 6 hours, which was then removed and the skin was wiped with a dry gauze to remove any residual material. A group of five rabbits of each sex served as sham controls.
The test skin site of each animal was examined and scored for irritation prior to each application of test material.
Mortality and moribundity checks were performed twice daily and body weights were recorded weekly.
At termination, blood samples were taken for a range of hematological and clinical chemical measurements. Urine samples were also collected and frozen for possible future examination.
A complete gross necropsy was performed on all animals.
Major organs were weighed and tissues were processed for subsequent histopathological examination
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female

Administration / exposure

Type of coverage:
occlusive
Vehicle:
not specified
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
6 hours each day, 3 times each week
Doses / concentrations
Remarks:
Doses / Concentrations:
200, 1000, 2000 mg/Kg
Basis:
no data
No. of animals per sex per dose:
5
Control animals:
yes

Results and discussion

Effect levels

Basis for effect level:
other: Result are explained in "Any other information incl tables"
Remarks on result:
not measured/tested
Remarks:
Effect level not specified (migrated information)

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

No deaths occurred during the study. Skin irritation occurred to varying degrees in all animals treated with API 83-12. There was moderate irritation in the high dose males and females. In the mid dose group moderate irritation occurred in the females and slight irritation in the males. In the low dose group minimal irritation occurred in both sexes. The overall mean irritation scores were:

 Dose level (mg/kg)  Males  Females
 Control
 200 0.1  0.4 
 1000 2.0  2.2 
 2000 2.6  3.1 

Soft stool was also observed in several animals but this also occurred in a control male was not considered to be dose related. All high dose females appeared thin and this was considered to be treatment related. Body weight gains were reduced in the high dose males and females and in the mid dose females when compared to their respective controls. Overall weight changes (kg) are shown in the following table:

 Dose level (mg/kg) Males  Females 
 Contrl +0.5 +0.3 
 200 +0.3  +0.4 
 1000 +0.3  +0.0 (*)
 2000 +0.1 (*) -0.2 (*)

* statistically significant (p ≤ 0.05)

Clinical chemical and hematological values were considered to be unaffected by treatment. A low value for white cell count in the low dose female group was considered incidental since the value was within a normal range and was not a dose-related effect. Although there were some organ weight differences, they were considered incidental to treatment. The exception was for the absolute testis weights, which were lower in the high dose males and the relative weights of the right testis which were also lower than controls. At gross necropsy, findings for the skin consisted of dry, scaly, rough, fissured, crusted and/or thickened skin. This was a common finding in all treatment groups. Histopathological examination revealed slight to moderate proliferative changes in the skin in all rabbits in the high dose group. These changes were accompanied by an increased granulopoeisis of the bone marrow. The testes of 3 of the 5 males in the high dose group had bilateral diffuse tubular hypoplasia accompanied by aspermatogenesis and atrophy of the accessory sex organs. There were no changes observed in either the testes or epididymes of the male rabbits in the mid or low dose groups. No other treatment-related histopathological changes were recorded.

Applicant's summary and conclusion