Registration Dossier

Toxicological information

Developmental toxicity / teratogenicity

Currently viewing:

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995

Materials and methods

Test guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
Gestation days 6-15
Frequency of treatment:
once per day
No. of animals per sex per dose:
25 mated female rats
Control animals:
yes, concurrent vehicle

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
750 mg/kg bw/day (actual dose received)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
350 mg/kg bw/day (actual dose received)
Basis for effect level:
other: developmental toxicity

Results (fetuses)

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

Details on embryotoxic / teratogenic effects:
Reduced foetal body weight described as follows:
Increased incidence of the external skeletal malformation filamentous tail (3 foetuses had filamentous tail, this was statistically significant and outside historical control incidence) Incidence concurrent controls 0%, historical controls (0.6% foetal basis 9.1% litter basis), 750 mg/kg/day VEHA (1% foetal, 13% litter).
Increased incidence of several skeletal developmental variations (14th rudimentary ribs, 27 presacral vertebrae, bent ribs, 7th cervical ribs)
Reduced ossification (vertebral arches), sternebrae 5 and/or 6 unossified
Reduced number of ossified cervical centrum no. 1 among

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
350 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
skeletal malformations

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
NOEL maternal toxicity 750 mg/kg/day
NOEL developmental toxicity 350 mg/kg/day
Executive summary:

In the main study, groups of 25 mated female rats received oral doses (gavage) of 0, 100, 350 and 750 mg/kg/day on days 6-15 of gestation administered in corn oil. There was no evidence of maternal toxicity at any dose level. Developmental toxicity was observed at 750 mg/kg/day. Vinyl 2 -ethylhexanoate is a developmental toxicant in rats in the absence of maternal toxicity causing a slight increase in the external malformation filamentous tail together with various skeletal variants, reduced ossification and reduced foetal body weight indicative of developmental retardation. The NOEL for maternal toxicity was 750 mg/kg/day and the NOEL for developmental toxicity was 350 mg/kg/day.