Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an appropriate OECD test guideline and in compliance with GLP, using a closely related test substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OTS 798.4350 (Inhalation Developmental Toxicity Screen)
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: CD(R)

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure (if applicable):
whole body
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The analytically determined concentrations of A-171 vapor were 24.6, 96.7 and 312.0 ppm for target concentrations of 25, 100 and 300 ppm, respectively.
Details on mating procedure:
Mating not performed; timed-pregnant CD® rats were exposed during gestation
Duration of treatment / exposure:
gestation days 6-15
Frequency of treatment:
6 hours/day
Duration of test:
Up to gestation day 21
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
25, 100 and 300 ppm
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
24.6, 96.7 and 312.0 ppm
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
ca. 0.15, 0.60, and 1.8 mg/L
Basis:
other: conversion of analytical concentration to mg/L
No. of animals per sex per dose:
25 timed-pregnant CD® rats/dose level
Control animals:
yes
Details on study design:
Four groups, each consisting of 25 timed-pregnant CD® rats, were exposed to A-171 (vinyltrimethoxysilane; CAS No. 2768-02-7) vapor or filtered air for 6 hours/day on gestational days (gd) 6 through 15. Target concentrations of A-171 were 0 (control), 25, 100, and 300 ppm. The dams were sacrificed on gestation day 21.

Examinations

Maternal examinations:
Clinical observations were made daily. In addition, each group of dams was observed from outside their respective exposure chambers for overt clinical signs during the actual exposures. Body weights were measured on gd 0, 6, 9, 12, 15, 18 and 21. Maternal food consumption was measured at
3-day intervals throughout gestation. At scheduled sacrifice on gd 21, the dams were evaluated for body weight, liver and kidney weights, and gravid uterine weight, . Maternal liver, kidneys, and the upper and lower respiratory tract were retained in 10% neutral buffered formalin.
Ovaries and uterine content:
The number of corpora lutea, and number and status of implantation sites (including early and late resorptions, dead fetuses, and live fetuses) were evaluated.
Fetal examinations:
All live and dead fetuses were dissected from the uterus, weighed and examined externally for malformations, variations, and gender determinations.
Approximately one-half of the live fetuses in each litter were examined for visceral and craniofacial malformations and variations. The remaining one-half of the fetuses were stained with alizarin red S and were examined for skeletal malformations and variations.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
The pregnancy rate was equivalent for all groups and ranged from 96 to 100%. No treatment-related mortality occurred during the study. One dam from the 300 ppm group was removed from the study on gd 14 due to trauma unrelated to exposure. Another 300 ppm female delivered early on gd 21, and therefore, was removed from the study and all data summaries with the exception of pregnancy calculations. Two females, one each from the 25 and 300 ppm groups, had only non-viable implants and one female each from the 25 and 100 ppm groups were not pregnant. There were no
treatment-related effects on gestational body weight, food consumption or clinical signs. However, on gd 6 to 9 body weight gain was decreased by 28 and 34% in the 100 and 300 ppm groups, respectively. Macroscopic assessment of the dams and organ weights measured at necropsy did not reveal any treatment-related effects. Assessment of the various reproductive endpoints did not reveal any differences among the groups.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
25 ppm
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
100 ppm
Basis for effect level:
other: other:

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Fetal examinations indicated no evidence of treatment-related embryolethality or teratogenicity. Developmental delay in the 300 ppm group was indicated by an increase in the incidence of delayed skeletal ossification of the anterior arch of the atlas, thoracic centra, interparietal, matatarsals, and phalanges. A statistical increase in the number of litters at 100 ppm with unossified anterior arch of the atlas was not considered to be biologically significant because no other endpoints were similarly affected and the incidence (79.2%) was close to that observed in historical controls (29.2-73.9%). Mean fetal body weight/litter were not different among control and treated groups.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Exposure of pregnant CD® rats during organogenesis to A-171 by inhalation resulted in slight maternal toxicity at 100 and 300 ppm as evidenced by concentration-dependent reductions in gestational body weight gain (gd 6-9). There was evidence of slightly delayed development in fetuses from
the 300 ppm group as indicated by delayed ossification in several skeletal districts. No exposure-related embryotoxicity or teratogenicity was observed in this study.