Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July to Nov 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
- 3 instead of 5 animals/sex used
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
17 alpha-Cyanomethyl-17 ß-hydroxy-5(10)-estren-3-one
IUPAC Name:
17 alpha-Cyanomethyl-17 ß-hydroxy-5(10)-estren-3-one
Test material form:
semi-solid (amorphous): gel
Remarks:
migrated information: paste

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Type of coverage:
occlusive
Vehicle:
physiological saline
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: test substance (technical quality including impurities)

Any other information on results incl. tables

No animal died in the course of the study.

After administration of 2000 mg/kg ZK 37877 focal to total hairless areas were found in one male animal (both fore- and hind limbs, inguinal region, abdomen) from day 15 onwards and in one female animal (both hind limbs, abdomen) on day 13 to day 16 of the study. This female animal showed focal to moderate thinning of fur on both fore- and hind limbs and the abdomen from day 17 onwards. These findings were suspected to be compound-related. Additionally punctiform to focal scab formation occurred on the back of one male animal and on the back of the neck of another male animal on the last days of the study. Because of the time-point and localization, these findings were considered to be spontaneous findings. No compound-related findings were observed in the other animals over the whole study period.

After administration of 2000 mg/kg ZK 37877 three animals (two males and one female) showed a decreased body weight in the first week of the study, which was reversible in the second week. One female animal showed a slight decrease in body weight in the last week of the study. No compound-related effect on body weight gain was observed in the other two animals.

Autopsy revealed no compound-related findings, because the observed lesions (scab formation) in the skin are considered to be not substance related.

Applicant's summary and conclusion

Executive summary:

A single dermal administration of the test substance (technical quality including impurities) to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities and gross pathological findings. After administration of 2000 mg/kg ZK 37877 single animals showed hairless areas and thinning fur in the course of the study. These findings are suspected to be compound-related because they are known findings in rats after treatment with hormones. Additionally, a slight decrease in body weight was observed in some animals on day 8. This effect was reversible on day 15 of the test.

According to OECD TG 402 the dermal LD50 of ZK 37877 is therefore > 2000 mg/kg body weight.