3,5,5-trimethylcyclohex-3-en-1-one

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Reference 2

Reference Type:

other: OECD SIDS

Title:

3,5,5-Trimethylcyclohex-2-enone (Isophorone), CAS No. 78-59-1

Author:

OECD SIDS

Year:

2003

Bibliographic source:

SIDS Initial Assessment Report for SIAM 16

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,5,5-trimethylcyclohex-2-enone

EC Number:

201-126-0

EC Name:

3,5,5-trimethylcyclohex-2-enone

Cas Number:

78-59-1

IUPAC Name:

3,5,5-trimethylcyclohex-2-en-1-one

Details on test material:

- Analytical purity: approx. 96.8 %
- Name of test material (as cited in study report): MRD-83-237, Isophorone
- Physical state: pale yellow liquid
- Analytical purity: approximately 96.8%
- Storage condition of test material: room temperature, under nitrogen

Test animals

Species:

rat

Strain:

Fischer 344

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure (if applicable):

whole body

Vehicle:

unchanged (no vehicle)

Details on exposure:

Vehicle: no vehicle.
Concentrations: 0, 25, 50, 115 ppm (corresponds to 0.144, 0.289, 0.664 mg/L; low mid and high dose).
Type or preparation of particles: vapor.
Pregnant rats were dosed on days 6 through 15 of gestation (G).

Analytical verification of doses or concentrations:

yes

Details on mating procedure:

- Impregnation procedure: cohoused
- Length of cohabitation: until confirmed to have mated
- Proof of pregnancy: vaginal plug or sperm in vaginal smear

Duration of treatment / exposure:

gestation day 6 - gestation day 15

Frequency of treatment:

6 hours/day

Duration of test:

Section on gestation day 20

Doses / concentrations

Remarks:

Doses / Concentrations:
0.144; 0.289 and 0.664 mg/L (corresponds to 25; 50 and 115 ppm)
Basis:
nominal conc.

No. of animals per sex per dose:

22 mated female rats per dose level

Control animals:

other: yes, concurrent conditioned air

Details on study design:

- Dose selection rationale: based on results of probe study

Examinations

Maternal examinations:

PARAMETERS ASSESSED DURING STUDY
Body weight gain: each 3rd day.

Food consumption: 3 day intervals.

Clinical observations: each 3rd day.

Ovaries and uterine content:

PARAMETERS ASSESSED DURING STUDY
Examination of uterine content: identified as live fetuses, dead fetuses, late resorptions, and early resorptions at the end of the study (day 20 of gestation). The uterus of each animal was stained in 10 % aqueous ammonium sulfide and further examined for confirmation of implantation sites. Corpora lutea were counted.

Fetal examinations:

PARAMETERS ASSESSED DURING STUDY
Examination of fetuses: Live and dead fetuses were weighed, examined externally for gross abnormalities, and crown-rump distances were determined.
Further examinations: skeletal malformations and ossification variations.

Statistics:

Bartlett's test of homogeneity of variance: body weight, body weight change, food consumption, number of implantation sites, ratio of live fetuses to implantation sites, ratios of resorptions to implant sites, malformations per litter. Kruskal-Wallis test if variances were not equivalent. Standard nested analysis of variance for fetal weights.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Details on maternal toxic effects:
MATERNAL TOXIC EFFECTS BY DOSE LEVEL
Mortality and day of death: no mortalities.

Number pregnant per dose level: 22

Body weight: reduced on days 12G (-6.1 %) and 15G (-6.8 %) in high dose group.

Food/water consumption: reduced food consumption in high dose group.

Clinical signs: alopecia and cervical or anogenital staining (each dose-related).

No statistically significant differences between treated and control groups: Number of resorptions, number of implantations, number of corpora lutea, duration of pregnancy.

Conclusion:
The test material elicited a clinical effect in the pregnant dams in the form of decreased food consumption (high dose, days 6 -20 and 0 -20), lower body weights (high dose, days 12G and 15G), and dose related increases in alopecia and staining of the cervical and anogenital areas.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

0.289 mg/L air

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Details on embryotoxic / teratogenic effects:
FETAL DATA
No statistically significant differences between treated and control groups:
Litter size and weights, number viable, sex ratio, grossly visible abnormalities, external abnormalities, soft tissue abnormalities, skeletal abnormalities.

Conclusion:
During the conduct of the study there was one instance of exencephaly noted in a rat fetus.
Based on the observations made in this study the authors do not believe that this anomaly was related to the test material.
Within the framework of the dose levels and test methods used, the test material was not teratogenic or fetotoxic.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

0.664 mg/L air

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified