Isobutyl vinyl ether

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: In a dose range finding study according to OECD412 pregnant rats were used.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

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:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Isobutyl vinyl ether

EC Number:

203-678-8

EC Name:

Isobutyl vinyl ether

Cas Number:

109-53-5

Molecular formula:

C6H12O

IUPAC Name:

1-(ethenyloxy)-2-methylpropane

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

Species:

rat

Strain:

Wistar

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

Vehicle:

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:

yes

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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 500, 2000, 5000 ppm (0, 2080, 8300, 33200 mg/m³)
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 2070+-118, 8352+-385, 33607+-2314 mg/m³
Basis:
analytical conc.

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Examinations

Maternal examinations:

Clinical signs
Body weight

Ovaries and uterine content:

Uterus weight at termination
resorptions

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)

1

Dose descriptor:

NOAEC

Effect level:

2 000 ppm

Basis for effect level:

other: developmental toxicity

2

Dose descriptor:

LOAEC

Effect level:

8 000 ppm

Basis for effect level:

other: developmental toxicity

3

Dose descriptor:

LOAEC

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

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

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).