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Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984
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

Constituent 1
Chemical structure
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
Molecular formula:
C9H14O
IUPAC Name:
3,5,5-trimethylcyclohex-2-enone
Details on test material:
Purity > 90%

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 / concentrationsopen allclose all
Dose / conc.:
25 ppm
Remarks:
corresponds to 0.144 mg/L
Dose / conc.:
50 ppm
Remarks:
corresponds to 0.289 mg/L
Dose / conc.:
115 ppm
Remarks:
corresponds to 0.664 mg/L
No. of animals per sex per dose:
22 mated female rats per dose level
Control animals:
yes, concurrent no treatment
Details on study design:
- Dose selection rationale: based on results of preliminary 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

General toxicity (maternal animals)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
dose related increases in alopecia and staining of the cervical and anogenital areas
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
reduced on gestation days 12 (-6.1 %) and 15 (-6.8 %) in high dose group
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
reduced food consumption in high dose group (days 6-20 and 0-20)
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined

Maternal developmental toxicity

Number of abortions:
not examined
Pre- and post-implantation loss:
not examined
Total litter losses by resorption:
no effects observed
Early or late resorptions:
not examined
Dead fetuses:
no effects observed
Changes in pregnancy duration:
no effects observed
Changes in number of pregnant:
no effects observed
Details on maternal toxic effects:
No statistically significant differences between treated and control groups: Number of resorptions, number of implantations, number of corpora lutea, duration of pregnancy.

Effect levels (maternal animals)

Dose descriptor:
NOAEC
Effect level:
0.289 mg/L air
Based on:
test mat.
Basis for effect level:
body weight and weight gain
food consumption and compound intake

Maternal abnormalities

Abnormalities:
no effects observed

Results (fetuses)

Fetal body weight changes:
not examined
Reduction in number of live offspring:
no effects observed
Changes in sex ratio:
no effects observed
Changes in litter size and weights:
no effects observed
Changes in postnatal survival:
not examined
External malformations:
no effects observed
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Details on embryotoxic / teratogenic effects:
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.

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.

Effect levels (fetuses)

Dose descriptor:
NOAEC
Effect level:
0.664 mg/L air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no adverse effects observed up to and including the highest tested concentration

Fetal abnormalities

Abnormalities:
no effects observed

Overall developmental toxicity

Developmental effects observed:
no

Applicant's summary and conclusion

Conclusions:
The test material elicited a clinical effect in the pregnant dams in the form of decreased food consumption, lower body weights and dose related increases in alopecia and staining of the cervical and anogenital areas.
Within the framework of the dose levels and test methods used, the test material was not teratogenic or fetotoxic.