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Description of key information

LD50 oral (rat): > 2000 mg/kg bw [Kurth 2007]
LD50 dermal (rat): > 2000 mg/kg bw [Kurth 2009a]

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Aug to Nov 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: 2.0 mg carboxymethyl cellulose ad 1.0 mL Aqua dest.
Doses:
2000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.

No animal died in the course of the study. A single oral (gavage) application of 2000 mg/kg was tolerated without compound-related clinical findings. The body weight gain on days 8, 15 and 21 was within the normal range for rats of this age and strain, which are routinely used in the laboratory. Autopsy revealed no compound-related findings.

Executive summary:

A single oral administration of the test substance by gavage to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, clinical signs, effects on body weight gain and gross pathological findings. According to OECD TG 423 the oral LD50 of ZK 37877 is therefore > 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
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
Reason / purpose for cross-reference:
reference to same study
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
Species:
rat
Strain:
Wistar
Sex:
male/female
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
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)

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.

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

A single oral administration of the test substance by gavage to male and female rats at the limit-dose 2000 mg/kg was tolerated without mortalities, clinical signs, effects on body weight gain and gross pathological findings (Kurth, 2007). According to OECD TG 423 the oral LD50 of ZK 37877 is therefore > 2000 mg/kg body weight.

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 (Kurth, 2009a). 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.


Justification for classification or non-classification

Based on the study results a classification according to Regulation (EC) No. 1272/2008 (CLP) is not required.