Allyl acetoacetate

Endpoint summary

Key value for chemical safety assessment

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

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.