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Key value for chemical safety assessment

Effects on fertility

Description of key information

In the Combined Repeated Dose Oral Toxicity Study with the Reproduction / Developmental Toxicity Screening Test, conducted according to an appropriate OECD test guideline and in compliance with GLP,  the reported NOAEL value for reproductive toxicity for [2-(perfluorohexyl)ethyl]triethoxysilane was 125 mg/kg bw/day (the highest dose tested; Eurofins, 2017).

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

In the Combined Repeated Dose Oral Toxicity Study with the Reproduction / Developmental Toxicity Screening Test, conducted according to an appropriate OECD test guideline and in compliance with GLP,  the reported NOAEL value for reproductive toxicity for [2-(perfluorohexyl)ethyl]triethoxysilane was 125 mg/kg bw/day (Eurofins, 2017).

The test item was administered daily in graduated doses (50, 100 and 150 mg/kg bw/day) to 4 groups of 10 male and 10 female test animals and additional 6 male and 6 female rats in the control and high dose recovery group, one dose level per group for a treatment period of up to 54 days. In order to allow a detection of possible delayed occurrence or persistence of or recovery from toxic effects, additional animals in recovery groups were observed for a period of 14 days (males) or 16 days (females) following the last administration. Animals of the HD group were treated with the higher initial dose of 150 mg/kg bw/day from the start of treatment. Due to observed morbidity and mortality surviving HD animals were treated with a reduced dose of 125 mg/kg bw/day from the respective premating day 14 / mating day 1 onwards. After 14 days of treatment of both males and females, animals of the main groups were mated (1:1) for a maximum of 14 days. The subsequent morning onwards the vaginal smears of females were checked to confirm the evidence of mating. After the confirmation of mating, females were separated and housed individually. Each litter was examined as soon as possible after delivery of the dam to establish the number and sex of pups, stillbirths, live births, runts and the presence of gross abnormalities. Live pups were counted, sexed and litters weighed within 24 hours of parturition and on day 4 post-partum. Non-pregnant females of the main groups were sacrificed on study day 26 using the sperm-positive vaginal smear. The number of implantation sites and corpora lutea was recorded for each parental female at necropsy. Dead pups and all surviving pups on post-natal day 4 were carefully examined for gross external abnormalities before terminal sacrifice. The copulation index was markedly reduced in the HD group (43 %) when compared to controls (100%), 100 % in the LD group and 90 % in the MD group. Reduced copulation index in the HD group was assumed to be related to the reduced health condition and/or observed neuromuscular impairments of the females and/or their male pairing partners. Mean length of precoital interval was within the normal range of variation for animals of this age and strain in the dose groups and the control group. Mean duration of gestation was comparable between the LD, the MD group and the controls. Marginally but statistically significantly lower gestation length of 21.00 days was observed in the HD group compared to 22.10 days in the control group. As data of the HD group were derived from only two females and the value was within historical control data, this was not considered as an adverse effect. No effects of toxicological relevance were noted on fertility. The fertility index (number of pregnant females/number of copulated females x 100) was 100 % in the LD group, 78 % in the MD group and 100 % in the HD group when compared to 100 % in the control group. There were no microscopic findings in reproductive organs that could be related to the negative breeding success of single non-mating animals. Sperm staging did not reveal abnormalities in maturation. There were no toxicologically relevant effects on the number of corpora lutea and number of implantation sites in the dose groups when compared to the control group. Percentage of pre- and post-implantation loss was within the normal range of biological variation for all groups. No effects of toxicological relevance were noted on litter data. Litters were delivered by 10 dams of the control, 9 of the LD, 7 of the MD and 3 of the HD group (secondary to increased mortality in the HD group). The delivery index (no. of dams with live pups born / no. of pregnant dams x 100) was comparable between the groups with 90 % in the LD group, 100 % in the MD group and 100 % in the HD group when compared to 100 % in the control group. One female of the LD group could not deliver because of its prescheduled death.

Effects on developmental toxicity

Description of key information

In the Combined Repeated Dose Oral Toxicity Study with the Reproduction / Developmental Toxicity Screening Test, conducted according to an appropriate OECD test guideline and in compliance with GLP,  the reported NOAEL value for developmental toxicity for triethoxy [2-(perfluorohexyl)ethyl]triethoxysilane was 125 mg/kg bw/day (the highest dose tested; Eurofins, 2017).

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

In the Combined Repeated Dose Oral Toxicity Study with the Reproduction / Developmental Toxicity Screening Test, conducted according to an appropriate OECD test guideline and in compliance with GLP,  the reported NOAEL value for developmental toxicity for [2-(perfluorohexyl)ethyl]triethoxysilane was 125 mg/kg bw/day (Eurofins, 2017).

The test item was administered daily in graduated doses (50, 100 and 150 mg/kg bw/day) to 4 groups of 10 male and 10 female test animals and additional 6 male and 6 female rats in the control and high dose recovery group, one dose level per group for a treatment period of up to 54 days. In order to allow a detection of possible delayed occurrence or persistence of or recovery from toxic effects, additional animals in recovery groups were observed for a period of 14 days (males) or 16 days (females) following the last administration. Animals of the HD group were treated with the higher initial dose of 150 mg/kg bw/day from the start of treatment. Due to observed morbidity and mortality surviving HD animals were treated with a reduced dose of 125 mg/kg bw/day from the respective premating day 14 / mating day 1 onwards.

After 14 days of treatment of both males and females, animals of the main groups were mated (1:1) for a maximum of 14 days.

The subsequent morning onwards the vaginal smears of females were checked to confirm the evidence of mating. After the confirmation of mating, females were separated and housed individually. Each litter was examined as soon as possible after delivery of the dam to establish the number and sex of pups, stillbirths, live births, runts and the presence of gross abnormalities.

Live pups were counted, sexed and litters weighed within 24 hours of parturition and on day 4 post-partum.

Non-pregnant females of the main groups were sacrificed on study day 26 using the sperm-positive vaginal smear.

The number of implantation sites and corpora lutea was recorded for each parental female at necropsy.

Dead pups and all surviving pups on post-natal day 4 were carefully examined for gross external abnormalities before terminal sacrifice.

No effects of toxicological relevance were noted on litter data. Litters were delivered by 10 dams of the control, 9 of the LD, 7 of the MD and 3 of the HD group (secondary to increased mortality in the HD group). The delivery index (no. of dams with live pups born / no. of pregnant dams x 100) was comparable between the groups with 90 % in the LD group, 100 % in the MD group and 100 % in the HD group when compared to 100 % in the control group. One female of the LD group could not deliver because of its prescheduled death. There were no effects of toxicological relevance on number of pups (live and dead) delivered and sex ratio of pups.

There were no toxicologically relevant effects on mean pup weight and litter weight. Values were within the normal range of variation, so that slight differences between the groups were considered as incidental and not within a toxicologically relevant range.

There were no toxicologically relevant effects on viability of pups. All pups survived from PND 0 to PND 4 except for cannibalism of one pup of a control dam, which was considered as incidental. There were no remarkable, toxicologically relevant external abnormalities.

Justification for classification or non-classification

Based on the available data for [2-(perfluorohexyl)ethyl]triethoxysilane, no classification for reproductive or developmental toxicity is required according to Regulation (EC) No 1272/2008.