Registration Dossier

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation

Data source

Reference
Reference Type:
publication
Title:
European Union Risk Assessment Report (CAS No: 98-82-8):Cumene
Author:
European Chemicals Bureau
Year:
2001
Bibliographic source:
European Commission, Joint Research Centre, Institute for Health and Consumer Protection, European Chemicals Bureau. Office for Official Publications of the European Communities; Luxembourg. 1st Priority List (PL1), Vol. 6.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
Sex: Female

Administration / exposure

Route of administration:
inhalation: vapour
Duration of treatment / exposure:
6 hrs/day on gestational days 6 through 15
Duration of test:
Scheduled sacrifice performed at day 21
Doses / concentrationsopen allclose all
Dose / conc.:
0 ppm
Dose / conc.:
100 ppm
Dose / conc.:
500 ppm
Dose / conc.:
1 200 ppm
No. of animals per sex per dose:
25

Examinations

Maternal examinations:
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 21
- Organs examined: wide range of investigations of the reproductive tract

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
- perioral wetness and perioral encrustation following daily exposures at all 3 exposure levels
- hypoactivity and blepharospasm during exposures at all 3 exposure levels
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
- 20% reduction in body weight gain at all 3 exposure levels
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
- decreased food consumption during the exposure period at all 3 exposure levels
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
- increased relative liver weight at all 3 exposure levels

Maternal developmental toxicity

Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Description (incidence and severity):
- number of viable implantations per litter was unaffected by exposure
Dead fetuses:
no effects observed
Description (incidence and severity):
- all pregnant dams had live litters
Changes in pregnancy duration:
no effects observed
Changes in number of pregnant:
not specified
Description (incidence and severity):
3 dams at 500 ppm and 2 dams each at 100 and 0 ppm were not pregnant

Effect levels (maternal animals)

Key result
Dose descriptor:
NOEL
Effect level:
100 ppm
Based on:
test mat.
Remarks:
cumene
Basis for effect level:
clinical signs
body weight and weight gain
food consumption and compound intake
organ weights and organ / body weight ratios

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
- fetal body weights per litter unaffected by exposure
Changes in sex ratio:
no effects observed
Description (incidence and severity):
- sex ratio (% males) unaffected by exposure
External malformations:
no effects observed
Description (incidence and severity):
- no significant increases in the incidences of individual malformations or of pooled external malformations at any exposure level
Skeletal malformations:
no effects observed
Description (incidence and severity):
- no significant increases in the incidences of individual malformations or of pooled skeletal malformations at any exposure level
- 81 skeletal variations were recorded but none showed statistically increased incidences related to exposure. Three skeletal variations exhibited significantly reduced incidences: 1) a reduction in 11th bilobed thoracic centrum at 100 ppm; 2) reductions in poorly ossified parietal bones at 100 and 1200 (but not 500) ppm; and 3) a reduction in 5th sternebra bilobed ossification sites at 500 ppm. However, there was no significant difference in the incidence of these malformations compared with controls.
Visceral malformations:
no effects observed
Description (incidence and severity):
- no significant increases in the incidences of individual malformations or of pooled external malformations at any exposure level
- significantly reduced incidences of bilateral dilated ureters and distension of the urinary bladder at 1200 ppm. However, there was no significant difference in the incidence of these malformations compared with controls.

Effect levels (fetuses)

Key result
Dose descriptor:
NOEL
Effect level:
> 1 200 ppm
Based on:
test mat.
Sex:
male/female

Applicant's summary and conclusion

Conclusions:
Based on the study conditions, the NOEL for maternal toxicity was determined to be 100 ppm. The NOEL for developmental toxicity (including teratogenicity) was greater than the highest dose tested, 1200 ppm. It was concluded that cumene was not teratogenic.
Executive summary:

Based on the study conditions, the NOEL for maternal toxicity was determined to be 100 ppm. The NOEL for developmental toxicity (including teratogenicity) was greater than the highest dose tested, 1200 ppm. It was concluded that cumene was not teratogenic.