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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
chronic toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD 451
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
IUCLID4 Test substance: as prescribed by 1.1 - 1.4

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female

Administration / exposure

Details on exposure:
Route of Administration: dermal
Duration of treatment / exposure:
89 weeks females, 105 weeks males
Frequency of treatment:
Twice a week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 13.8, 138 mg/animal or approximately 575 mg/kg or 5750 mg/kg per week
Basis:

Control animals:
yes

Results and discussion

Results of examinations

Details on results:
CLINICAL SIGNS AND MORTALITY
No data.

BODY WEIGHT AND WEIGHT GAIN and FOOD CONSUMPTION
No treatment related changes in food consumption were noted, but there were occasional statistically significant changes in the high dose males, which consumed more food in weeks 3/4, 10/11, 25/26, and 97/98. During week 49/50, these animals had slightly lower food consumption. The low dose group had slightly lower food consumption in week 65/66. The high dose females had marginally higher food consumption in weeks 3/4, 11/12, 13/14, 65/66 to 73/74. Low dose females had slightly increased food consumption in weeks 3/4, 11/12 and 81/82. The overall food consumption was 3.3% higher in low dose females and 6.6 in high dose females. These changes were considered to reflect biological variation since they were marginal, less than 10 % overall.

No treatment related body weight changes were observed during the study. The body weight of low dose males was slightly higher during weeks 11 to 21 (max. 6.5 %) 57, to 61 (5.0 %) and in the week 73 (6.1 %). The body weight of low and high dose females was slightly higher in week 65 (7.4 % in low and 7.7% in high dose).

OPHTHALMOSCOPIC EXAMINATION;
HAEMATOLOGY;
CLINICAL CHEMISTRY;
URINALYSIS;
NEUROBEHAVIOUR;
ORGAN WEIGHTS
No data

GROSS PATHOLOGY
In the pathological examination, a small but statistically significant decrease of left testis absolute (0.223 g control, 0.214 g low dose (-4%) and 0.192 g high dose (-14%)) and organ weight relative to body weight (0.488 control, 0.477 (-2%) low dose and 0.414 high dose (-15%)) was seen in the high dose male mice. The female mice of the high dose group had an increased absolute and relative weight of the liver and adrenals. The absolute weight of the right kidney was increased in the high dose females.

HISTOPATHOLOGY: NON-NEOPLASTIC
In histopathology, the microscopical examination revealed a slight dose-related increase in the incidence of minimal to mild focal acanthosis and hyperkeratosis at the application site.

HISTOPATHOLOGY: NEOPLASTIC (if applicable)


HISTORICAL CONTROL DATA (if applicable)


OTHER FINDINGS

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
575 other: mg/kg bw/wk
Dose descriptor:
LOAEL
Effect level:
5 750 other: mg/kg bw/wk

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

There were no significant treatment related differences between the test substance and control group animals. No treatment related changes in 

food consumption were noted, but there were occasional statistically significant changes in the high dose males, which consumed more food in 

weeks 3/4, 10/11, 25/26, and 97/98. During week 49/50, these animals had slightly lower food consumption. The low dose group had slightly lower 

food consumption in week 65/66. The high dose females had marginally higher food consumption in weeks 3/4, 11/12, 13/14, 65/66 to 73/74. Low 

dose  females had slightly increased food consumption in weeks 3/4, 11/12 and 81/82. The overall food consumption was 3.3% higher in low dose 

females and 6.6 in high dose females. These changes were considered to reflect biological variation since they were marginal, less than 10 % 

overall. No treatment related body weight changes were observed during the study. The body weight of low dose males was slightly higher during 

weeks 11 to 21 (max. 6.5 %) 57, to 61 (5.0 %) and in the week 73 (6.1 %). The body weight of low and high dose females was slightly higher in 

week 65 (7.4 % in low and 7.7% in high dose). In the pathological examination, a small but statistically significant decrease of left testis absolute 

(0.223 g control, 0.214 g low dose (-4%) and 0.192 g high dose (-14%))  and organ weight relative to body weight (0.488 control, 0.477 (-2%) low 

dose and 0.414 high dose (-15%)) was seen in the high dose male mice. The  female mice of the high dose group had an increased absolute 

and relative weight of the liver and adrenals. The absolute weight of the right kidney was increased in the high dose females. In histopathology, the  

microscopical examination revealed a slight dose-related increase in the incidence of minimal to mild focal acanthosis and hyperkeratosis at the  

application site.

Applicant's summary and conclusion