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Effects on fertility

Link to relevant study records
Reference
Endpoint:
one-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Principles of method if other than guideline:
Data is from ACToR and HSDB database.
GLP compliance:
not specified
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
other: Not applicable
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Males were treated for 7 weeks; females were treated from 14-days prior to mating through day-3 of lactation.
Frequency of treatment:
Daily
Remarks:
Doses / Concentrations:
100, 300, and 1000 mg/kg/day
Basis:
no data
No. of animals per sex per dose:
Males, 12; females, 12
Paternal/maternal toxic responses by dose: There were no treatment related effects noted in estrous cycle, number of corpora lutea and implantations, copulation or fertility indices for males or females.
Dose descriptor:
NOEL
Effect level:
> 1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Fetal toxic responses by dose: There were no treatment related effects noted on gestational days, litter and live born numbers, gestation index, stillborn index, birth index, sex ratio, body weights of offspring at birth and at day 4 post birth, or viability index on day 4. No external abnormalities were observed.
Remarks on result:
not measured/tested
Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Conclusions:
The NOEL of methyl acetoacetate is considered to be more than 1000 mg/kg/day for reproductive performance of parents in rat (male/female).
Executive summary:

Methyl acetoacetate was studied for reproductive toxicity by oral route in Crj:CD(SD) rats with doses of 0, 100, 300 and 1000 mg/kg. There were no premature deaths during the study.No clinical signs observed were considered to be as a result of treatment with the test substance. There were no notable intergroup body weight, food or water consumption differences in either sex. There were no effects noted in hemotology or clinical chemistries considered to be toxicologically significant in either sex. There were no intergroup differences in either organ weights, necropsy or histological findings that were considered to be treatment related in either sex. In terms of reproductive/developmental toxicity, there were no effects related to the test article on reproductive performance of parents and development of the next generation. There were no treatment related effects noted in estrous cycle, number of corpora lutea and implantations, copulation or fertility indices for males or females.There were no treatment related effects noted on gestational days, litter and live born numbers, gestation index, stillborn index, birth index, sex ratio, body weights of offspring at birth and at day 4 post birth, or viability index on day 4. No external abnormalities were observed. The NOEL is considered to be more than 1000 mg/kg/day for reproductive performance of parents and for development of offspring.Thus,the chemical would not induce reproductive toxicity.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Study duration:
subacute
Species:
rat
Quality of whole database:
The study is from an authoritative database.
Additional information

The toxicity to reproduction studies can be summarised as follows :

Sr.No

End point

Generation

Species

Effect level

1

LOEL

F2

Rattus norvegicus

 

155.9256 mg/kgbw/day

2

NOEL

P

Rat

>1000 mg/kg bw/day

Thus from the above studies it can be interpreted that the chemical would not induce reproductive toxicity.

Justification for selection of Effect on fertility via oral route:

The above selection is from an experimental study that gives a NOEL value of > 1000 mg/kg body weight per day.  

Justification for classification or non-classification

As evident from the weight of appraoch using predicted data from the target as well as study conducted on related chemical; it is concluded that the chemical allyl acetoacetate shall not exhibit toxicity to the reproductive system within the doses mentioned in the study end points.