Registration Dossier

Administrative data

Endpoint:
one-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
other:
Rationale for reliability incl. deficiencies:
other: Body responsible for the test

Data source

Reference
Reference Type:
other: Body responsible for the test
Title:
Unnamed

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 415 (One-Generation Reproduction Toxicity Study)
Deviations:
not specified
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
other: SD rats
Strain:
not specified
Sex:
male/female

Administration / exposure

Route of administration:
oral: unspecified
Type of inhalation exposure (if applicable):
not specified
Vehicle:
not specified
Details on mating procedure:
no data
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
no data
Frequency of treatment:
Dosing regime (males): 7 days/week
Dosing regime (females): 7 days/week
Details on study schedule:
no data
No. of animals per sex per dose:
Male: 24 animals at 0 mg/kg or mg/L
Male: 24 animals at 100 mg/kg or mg/L
Male: 24 animals at 300 mg/kg or mg/L
Male: 24 animals at 1000 mg/kg or mg/L
Female: 24 animals at 0 mg/kg or mg/L
Female: 24 animals at 100 mg/kg or mg/L
Female: 24 animals at 300 mg/kg or mg/L
Female: 24 animals at 1000 mg/kg or mg/L

Results and discussion

Results: P0 (first parental animals)

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Sex:
not specified

Results: F1 generation

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
300 mg/kg bw/day
Sex:
not specified
Basis for effect level:
other: based on equivocal findings on pup survival in the high dose group

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Details on results (parental animals)

No clinical observations were related to the substance. No effects on the body weight or body weight gain were observed. Food consumption was not affected by the treatment. No effect of the treatment could be observed on mating and pregnancy rates.

Gross pathology findings occured sporadically, without any dose-response relationship and were not considered treatment

related.

Details on results (offspring)

Effects on F1 generation:

In the high and low dose group, the total number of dead/missing pups during lactation was significantly increased compared to the untreated controls. This was mainly due to the fact that in both groups all pups of one litter died to the lack of maternal care. This resulted in 17 dead pups in the low dose group and 13 in the high dose group. If the values are corrected for these numbers, this results in 8,10,6 and 10 dead/missing pups respectively. In addition, the relevance of this observation is strongly limited by the lack of any dose response relationship.

No effect of the test item treatment was found on pup weight or sex ratio. Clinical findings observed in pups were considered to be treatment related. The only remarkable finding was one pupshowing anuria in the high dose group.

Summarizing these findings, it seems most unlikely that any observation was substance related induced. However, a bordeline effectin the high dose group cannot be excluded with certainty.

The NOAEL is a very conservative value given that this finding is highly unlikely treatment related.

Applicant's summary and conclusion

Conclusions:
NOAEL = 1000mg/kg/d (parental animal)
NOAEL = 300 mg/kg/d (parental animal)
It seems most unlikely that any observation was substance related induced. However, a bordeline effect in the high dose group cannot be excluded
with certainty.