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Toxicological information

Developmental toxicity / teratogenicity

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 500, 2000, 5000 ppm (0, 2080, 8300, 33200 mg/m³)
Basis:
nominal conc.
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)

open allclose all
Dose descriptor:
NOAEC
Effect level:
2 000 ppm
Basis for effect level:
other: developmental toxicity
Dose descriptor:
LOAEC
Effect level:
8 000 ppm
Basis for effect level:
other: developmental toxicity
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).