Registration Dossier

Diss Factsheets

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: In a dose range finding study according to OECD412 pregnant rats were used.
Reason / purpose for cross-reference:
reference to same study

Data source

Reference Type:
study report
Report date:

Materials and methods

Principles of method if other than guideline:
Report presented some data on developmental toxicity in the frame of a sub-acute inhalation toxicity study in pregnant rats according to OECD TG412.
GLP compliance:
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
Isobutyl vinyl ether
EC Number:
EC Name:
Isobutyl vinyl ether
Cas Number:
Molecular formula:
Details on test material:
lsobutylvinylether, clourless liquid
Batch No.: 03/0186-1 or 03/0186-2
Purity 99.56%
The stability under storage conditions over the exposure of the study period was guaranteed by the sponsor

Test animals

Details on test animals or test system and environmental conditions:
Time-mated Wistar rats (CrlGlxBrIHan :Wl) were supplied by Charles River Laboratories (Germany)
age 70 - 84 days and bw 144.1- 176.1 g at arrival
Acclimatisation: rats arrived at gestation day 1 and exposure starts gestation day 6.
housed singly
certified diet and tap water ad libitum
temperature 20 - 240C and relative humidity in the range of 30 - 70%
A light/dark rhythm of 12 hours

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
other: air
Details on exposure:
For each concentration the test substance was supplied to a thermostated vaporizer at a constant rate by means of the metering pump. The animals were kept singly in wire cages located in a glass-steel inhalation chamber, volume of 1.4 m³
Analytical verification of doses or concentrations:
Details on analytical verification of doses or concentrations:
determined analytically using gas chromatography
Details on mating procedure:
time pregnant rats used
Duration of treatment / exposure:
gestation day 6-20, sacrifice the day following the last exposure
Frequency of treatment:
once daily, 6 h/day
Duration of test:
sacrifice the day following the last exposure
Doses / concentrationsopen allclose all
Doses / Concentrations:
0, 500, 2000, 5000 ppm (0, 2080, 8300, 33200 mg/m³)
nominal conc.
Doses / Concentrations:
0, 2070+-118, 8352+-385, 33607+-2314 mg/m³
analytical conc.
No. of animals per sex per dose:
Control animals:
yes, concurrent vehicle


Maternal examinations:
Clinical signs
Body weight
Ovaries and uterine content:
Uterus weight at termination
Fetal examinations:
no further data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Even at the low dose level local effects in the nasal cavity were reported (hyperplasia of the respiratory epithelium, mucous cell reduction, and degeneration of the olfactory epithelium) but no other effects. At the mid dose level additional adaptive or secondary (to local effects) effects were seen (increased absolute and relative liver weights, decreased absolute and relative spleen weights, decreased absolute and relative thymus weights, starry sky appearance and decreased cellularity of the thymus cortex). At 8000 ppm (33200 mg/m³) clinical signs, reduced body weight, increased alkaline phosphatase and total bilirubin were found.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
Effect level:
2 000 ppm
Basis for effect level:
other: developmental toxicity
Dose descriptor:
Effect level:
8 000 ppm
Basis for effect level:
other: developmental toxicity
Dose descriptor:
Effect level:
500 ppm
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
Decreased uterus weight and reduced number of pups and resorptions in 2 dams were reported.
No further details available.

Fetal abnormalities

not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Developmental toxicity (reduced number of pups, resorptions, reduced uterus weight) was found in rats exposed to 8000 ppm (33200 mg/m³) during gestation day 6-20 (6 h/day, whole body) but not at a dose level of 2000 ppm. Local effects in the nasal cavity of dams were seen even at 500 ppm (2080 mg/m³); clinical signs and reduction in maternal body weight were obvious at the high dose level (reliability 3).