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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

In an oral OECD 422 study in rats (Hashima Labs, 2005), trimethoxyvinylsilane was administered by gavage at doses up to 1000 mg/kg bw/day. A low number of estrous cases was detected in females and based on this effect, a NOAEL of 250 mg/kg bw /day was determined. The value used for CSA might change depending on the outcome of the planned Extended One-Generation Reproductive Toxicity study.

Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
2 425 mg/m³
Study duration:
subchronic
Species:
rat
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

A reliable oral screening study for reproductive toxicity is available (Hashima 2005). The NOAELs for reproductive performance of parental animals were estimated to be 1000 mg/kg bw/day for males and 250 mg/kg bw/day for females. The NOAEL for offspring was 1000 mg/kg bw/day. Regarding reproductive toxicity, a low number of estrous cases was noted in the 1000 mg/kg bw/day group. No changes attributable to the test article were noted for the copulation index, number of conceiving days, number of pregnant females, fertility index, gestation length, gestation index, delivery conditions, nursing conditions, number of corpora lutea, number of implantation sites, or the implantation rate. No effects were noted for the offspring.

 

In a fourteen week vapour inhalation study in rats which does not meet current guideline requirements for reproductive toxicity (BRRC 1993), the reproductive organs of male and female animals were examined microscopically in response to treatment with test article. In the 400 ppm group after 14 weeks exposure the absolute testes weight was statistically significantly lower when compared to control mean values. When expressed as a percentage of body weight, the testes weights were equivalent to control values. There was no effect on absolute testes weight in the 400 ppm recovery group animals. There were no histopathological lesions reported for any of the reproductive organs examined in any group. No effect was noted on male reproductive organs in the study.




Effects on developmental toxicity

Description of key information

Exposure of pregnant rats during organogenesis to trimethoxyvinylsilane by inhalation resulted in slight maternal toxicity at 100 and 300 ppm as evidenced by concentration-dependent reductions in gestational body weight gain (gestation days 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 (BRRC, 1993). The observed variations are not considered toxicologically relevant, particularly in the presence of maternal toxicity, and therefore the NOAEC is greater than or equal to 300 ppm (approximately 1730 mg/m3). A combined repeated dose toxicity study with the reproduction/developmental toxicity screening test via the oral route is also available (Hashima 2005).  No changes to any developmental parameters were noted during the study in response to the test article, and the  NOAEL for developmental toxicity was therefore determined to be the highest test concentration of 1000 mg/kg bw/day.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
1 730 mg/m³
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

In a reliable inhalation study conducted according to EPA OTS 798.4350 and GLP (BRRC 1993) 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 gestation day 14 due to trauma unrelated to exposure. Another 300 ppm female delivered early on gestation day 21, and was therefore 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.  Assessment of the various reproductive endpoints did not reveal any differences among the groups. Foetal 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 foetal body weight/litter were not different among control and treated groups. The NOAEC for maternal toxicity was concluded to be 25 ppm based on concentration-dependent reductions in gestational body weight gain and the NOAEC delayed development is greater than or equal to 300 ppm based on evidence of slightly delayed development in foetuses from the 300 ppm group as indicated by delayed ossification in several skeletal districts, but only in the presence of maternal toxicity.

 

In a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test via the oral route, conducted according to current guideline and in compliance with GLP (Hashima, 2005) a low number of estrous cases was noted in the 1000 mg/kg group. No changes attributable to the chemical were noted in the copulation index, number of conceiving days, number of pregnant females, fertility index, gestation length, gestation index, delivery conditions, nursing conditions, number of corpora lutea, number of implantation sites, or implantation rate. The NOAELs for reproductive performance of parental animals were estimated to be 1000 mg/kg/day for males and 250 mg/kg/day for females. No changes attributable to treatment were noted in the number of pups, number of stillbirths, number of pups born, sex ratio, delivery index, birth index, live birth index, general signs, and number of live pups on Day 4 of lactation, viability index of pups on Day 4 of lactation, appearance, body weight, or necropsy findings. The NOAEL for pups was estimated to be 1000 mg/kg/day.


Justification for classification or non-classification

Based on the available data, trimethoxy(vinyl)silane does not require classification for reproductive or developmental toxicity according to Regulation (EC) No 1272/2008.