Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Oral: no data available
Inhalation (OECD 422, RA from CAS 2530-87-2, rat): NOAEC=810.32 mg/m³
Dermal: no data available

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.
Reason / purpose:
read-across source
Dose descriptor:
NOAEC
Remarks:
systemic
Effect level:
>= 100 ppm (nominal)
Based on:
test mat.
Remarks:
equivalent to 810.32 mg/m³
Sex:
male/female
Basis for effect level:
other: No adverse effects observed up to the highest dose tested.
Dose descriptor:
NOEC
Remarks:
reproduction
Effect level:
>= 100 ppm (nominal)
Based on:
test mat.
Remarks:
equivalent to 810.32 mg/m³
Sex:
male/female
Basis for effect level:
other: No adverse effects observed up to the highest dose tested.
Critical effects observed:
no
Dose descriptor:
NOEC
Generation:
F1
Effect level:
>= 100 ppm (nominal)
Based on:
test mat.
Remarks:
equivalent to 810.32 mg/m³
Sex:
male/female
Basis for effect level:
other: No effects observed up to the highest dose tested.
Critical effects observed:
no
Reproductive effects observed:
no
Conclusions:
Exposure to the source substance (3-Chloropropyl)trimethoxysilane up to and including the high concentration of 100 ppm did not result in any signs of general or reproductive toxicity of the test item. Based on these results the NOEC (no observed effect concentration) was established as ≥100 ppm (nominal concentration, corresponding to 99.7 ppm mean analytical concentration and equivalent to 810.32 mg/m³). As explained in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in reproduction toxicity potential.
Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
810.32 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
The available information comprises an adequate, reliable (Klimisch score 1) and consistent study, from a reference substance with similar structure and intrinsic properties. Read-across is justified based on similarities in PC/ECO/TOX properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

There are no studies available for the registered substance (chloromethyl)triethoxysilane (CAS 15267-95-5). However, reliable data are available for the structural analogue substance (3-chloropropyl)trimethoxysilane (CAS 2530-87-2).

Effects on fertility: via inhalation route

In the available key study (RCC, 2005) the test substance (3-chloropropyl)trimethoxysilane (CAS 2530-87-2) was investigated for effects on fertility in a Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test, conducted according to OECD 422, and in compliance with GLP. Groups of 10 Sprague-Dawley rats per sex per dose were exposed to the vapour in a whole body inhalation system at doses of 5, 25 and 100 ppm. Untreated animals served as controls. Treatment was carried out for 6 hours daily to male rats for 28 days and to female rats throughout the 14-day pre-pairing, pairing and gestation period until the individual day 19 post coitum. During the pairing period, rats were housed overnight with one male and one female in Makrolon pairing cages. The female was placed with the same male until mating occurred or two weeks elapsed. Animals were observed for mortalities and clinical signs, and detailed clinical observations were performed once per week. A Functional Observational battery (modified Irwin screen test) was performed once during the test (males: shortly before sacrifice; females: on day 3 post-partum). Body weights and food consumption was recorded. Parental generation males were sacrificed after they had been treated for 28 days, parental generation females were sacrificed on day 4 post-partum. A complete gross necropsy was performed on all adult animals. The litters were examined for litter size, live birth, stillbirth and any gross anomalies. The sex ratio of the pups was recorded. Pups were weighed individually on day 0, 1 and 4 post-partum. The pups were observed daily for survival and behavioural abnormalities in nesting and nursing. Dead pups and pups killed on day 4 post-partum were examined macroscopically.

The fertility rate was high resulting in at least 9 litters per group for evaluation of reproduction data. At all concentrations, there were no treatment-related effects on precoital time, fertility indices, mean duration of gestation, number of implantations, post-implantation loss through to scheduled sacrifice on day 4 post-partum. The mean number of corpora lutea per dam (determined at necropsy) was similar in all groups and gave no indication of a test item-related effect. There were no findings, which distinguished test item-treated animals from controls. In particular, no treatment-related histopathological findings were observed in the reproductive organs of either sex from the parental generation. The assessment of the integrity of the spermatogenetic cycle did not provide any evidence of impaired spermatogenesis.

At all concentrations, there were no treatment-related effects on pup survival or litter size from birth through to scheduled sacrifice on day 4 post-partum. No abnormal findings were noted for pups at first litter check or during the first 4 days post-partum. Sex ratios at first litter check and on day 4 post-partum were unaffected by treatment with the test item. Mean pup weights on day 0 and day 1 post-partum were unaffected by treatment with the test item. Mean pup weight development during the first 4 days post-partum lactation was unaffected by treatment with the test item.

In summary, exposure to (3 -chloropropyl)trimethoxysilane (CAS 2530-87-2) up to and including the high concentration of 100 ppm did not result in any signs of general or reproductive toxicity of the test item. Based on these results the NOEC (no observed effect concentration) was established as ≥100 ppm (nominal concentration, corresponding to 99.7 ppm mean analytical concentration and equivalent to 810.32 mg/m³).

This data is further supported by a 90-day inhalation study (Dow Corning Corporation, 1993), conducted according to OECD 413, and in compliance with GLP. Groups of 10 Sprague-Dawley rats per sex were exposed to the test item (3-chloropropyl)trimethoxysilane (CAS 2530-87-2) in a whole-body inhalation system at target concentrations of 0.5, 5, and 100 ppm for 6 hours/day, 5 days/week for 13 weeks. No treatment-related effects were observed in testes and ovaries when examined histopathologically and with regard to organ weights.

In accordance with Section 8.7.3 of REACH Annex IX, Column 1, an extended one-generation reproductive toxicity study does not need to be conducted if the 28-day or 90-day study does not indicate adverse effects on reproductive organs or tissues. As no adverse effects on the reproductive organs and on the reproductive performance were observed in a subchronic inhalation study (RA from the structural analogue substance CAS 2530-87-2) and in a Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test via the inhalation route (RA from CAS 2530-87-2). Therefore, further testing according to Section 8.7.3 of REACH Annex IX, Column 1 is not required.

Effects on developmental toxicity

Description of key information
Oral (OECD 414, RA from CAS 5089-70-3, rat): NOAEL=300 mg/kg bw/day
Inhalation (OECD 422, RA from CAS 2530-87-2, rat): NOAEC=810.32 mg/m³
Dermal: no data available
Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Dose descriptor:
NOAEL
Remarks:
oral
Effect level:
300 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Remarks on result:
other: CAS 5089-70-3, OECD 414
Dose descriptor:
NOAEC
Remarks:
inhalation
Effect level:
>= 100 ppm
Based on:
test mat.
Basis for effect level:
other: no adverse effects observed up to the highest dose
Remarks on result:
other: CAS 2530-87-2, OECD 422
Abnormalities:
no effects observed
Dose descriptor:
NOAEL
Remarks:
oral
Effect level:
300 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: teratogenicity
Remarks on result:
other: CAS 5089-70-3, OECD 414
Dose descriptor:
NOEC
Remarks:
inhalation
Effect level:
>= 100 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects observed up to the highest dose tested
Remarks on result:
other: CAS 2530-87-2, OECD 422
Abnormalities:
effects observed, treatment-related
Description (incidence and severity):
delayed skeletal ossification
Developmental effects observed:
yes
Lowest effective dose / conc.:
1 000 mg/kg bw/day (actual dose received)
Treatment related:
yes
Relation to maternal toxicity:
developmental effects as a secondary non-specific consequence of maternal toxicity effects
Dose response relationship:
not specified
Relevant for humans:
not specified
Conclusions:
An oral developmental toxicity study according to OECD 414 for the source substance (3-chloropropyl)(triethoxy)silane (CAS 5089-70-3) is available Administration of (3-chloropropyl)(triethoxy)silane at doses of 0, 100, 300 or 1000 mg/kg bw/day by oral gavage to pregnant female Wistar rats from gestation days 5 to 19 resulted in lower body weight, body weight gain and food consumption at 1000 mg/kg bw/day and were considered to be adverse. Lower terminal body weight, uterus weight and mean total litter weight were also noted at this dose.
Increased incidences of skeletal findings such as delayed ossification and lower litter weight recorded at 1000 mg/kg bw/day were considered to be attributable to the maternal effects and not adverse. An increased incidence of wavy ribs and bent scapula was also noted at this dose and these findings are recognised as part of chondrodystrophy syndrome in rats and have been demonstrated to be post-natally reversible and therefore also not adverse. However, the increased incidence of skeletal variations noted together with the lower litter weight was considered to be adverse at 1000 mg/kg bw/day.
Therefore the maternal and foetal NOAEL were both considered to be 300 mg/kg bw/day.

In addition, a screening study according to OECD 422 via inhalation route is available for the source substance (3-chloropropyl)(trimethoxy)silane (CAS 2530-87-2). Exposure to (3-Chloropropyl)trimethoxysilane up to and including the high concentration of 100 ppm did not result in any signs of general or reproductive toxicity of the test item. Based on these results the NOEC was established as ≥100 ppm (nominal concentration, corresponding to 99.7 ppm mean analytical concentration and equivalent to 810.32 mg/m³).
As explained in the read across justification, the differences in the molecular structure between the target and the source substances are unlikely to lead to differences in the developmental toxicity that are higher than the typical experimental error of the test method.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
The available information comprises an adequate, reliable (Klimisch score 1) and consistent study, from a reference substance with similar structure and intrinsic properties. Read-across is justified based on similarities in PC/ECO/TOX properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
810.32 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
The available information comprises an adequate, reliable (Klimisch score 1) and consistent study, from a reference substance with similar structure and intrinsic properties. Read-across is justified based on similarities in PC/ECO/TOX properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

There are no studies available for the registered substance (chloromethyl)triethoxysilane (CAS 15267-95-5). However, reliable data are available for the structural analogue substances (3-chloropropyl)trimethoxysilane (CAS 2530-87-2) and (3-chloropropyl)triethoxysilane (CAS 5089-70-3).

Effect on developmental toxicity: via oral route

In the available key study (BSL, 2014) the test substance (3-chloropropyl)triethoxysilane (CAS 5089-70-3) was investigated for effects on prenatal developmental toxicity study after repeated oral administration conducted according to OECD 414, and in compliance with GLP.

Groups of 24 pregnant female Crl:WI(Han) rats per dose were administered doses of 100, 300 and 1000 mg/kg bw/day via oral gavage. Animals treated with the vehicle (corn oil) served as controls. Treatment was carried out once daily during the gestation period between day 5 to day 19. Animals were observed for mortalities and clinical signs, and detailed clinical observations were performed twice daily (except weekends). Body weights and food consumption was recorded. Upon sacrifice on gestation day 20 macroscopic examination for structural abnormalities or pathological changes were performed. Fetuses were subjected to external and either, soft tissue or, skeletal and head examination. 

Group mean body weight at 1000 mg/kg bw/day was slightly reduced compared to the control group on gestation day 20. Body weight gain was also slightly lower in this group compared to the control group on various intervals within the study period. In correlation with the body weight and body weight change, food consumption in the 1000 mg/kg bw/day group was noted to be slightly lower compared to the control group after the beginning of the treatment. A slightly, statistically significantly lower terminal body weight was observed in the 1000 mg/kg bw/day group when compared to the control group. A slightly but statistically significantly lower mean litter weight was observed in the 1000 mg/kg bw/day group, mean litter weight was marginally lower in the 300 mg/kg bw/day group but not statistically significant compared to the control group. No external, visceral or craniofacial abnormalities attributable to treatment were noted. Delayed ossification was evident in litters of dams treated with 1000 mg/kg bw/day. A statistically significant increase in litter incidences of incomplete ossification of interparietal bone, frontal bone, parietal bone, supraoccipital bone and zygomatic arch was observed in the 1000 mg/kg bw/day group when compared to the concurrent control group. For interparietal and frontal bones, incidences in this group were also higher compared to historical control data. Furthermore, a statistically significant increase in non-ossified 4th sternebrae was observed in the 1000 mg/kg bw/day group compared to the concurrent control group. Values were within the range of historical control data, but due to the clear dose-dependency this finding was considered related to the treatment with the test item. In each litter of the 1000 mg/kg bw/day group several fetuses were observed with non-ossified cervical vertebra centra. The incidence of this finding was statistically significant compared to the control group and was considered to be test item-related due to the dose-dependency.There were a few findings of bent scapula body and of incompletely ossified 4th sacral arch which were only observed at 1000 mg/kg bw/day without statistical significance. Wavy ribs were seen in most litters of the 1000 mg/kg bw/day group showing a higher incidence than in the concurrent control group. Though this finding was not statistically significant, it can be considered treatment-related, as the incidence of this group was higher compared to historical control data.

The observed reduced ossification of those bones that normally exhibit rapid ossification in the last days of gestation indicates a generalized skeletal delay in this group. This delayed ossification was considered to be associated with the observed maternal toxicity (lower body weight and food consumption) and reduced fetal body weight of the 1000 mg/kg bw/day group. Generally delayed ossification is not regarded to persist postnatally and not associated with long term consequences on survival, general growth and development and therefore not considered to be adverse.

In summary, administration of (3-chloropropyl)triethoxysilane (CAS 5089-70-3) at doses of 0, 100, 300 or 1000 mg/kg bw/day by oral gavage to pregnant female Wistar rats from gestation days 5 to 19 resulted in lower body weight, body weight gain and food consumption at 1000 mg/kg bw/day. Lower terminal body weight, uterus weight and mean total litter weight were also noted at this dose. Increased incidences of skeletal findings such as delayed ossification and lower litter weight recorded at 1000 mg/kg bw/day were considered to be attributable to the maternal effects and not adverse. An increased incidence of wavy ribs and bent scapula was also noted at this dose and these findings are recognized as part of chondrodystrophy syndrome in rats and have been demonstrated to be post-natally reversible and therefore also not adverse. Therefore the maternal and fetal No-Observed-Adverse-Effect-Levels (NOAEL) were both considered to be 300 mg/kg bw/day.

 

 

Effect on developmental toxicity: via inhalation route

In the available key study (RCC, 2005) the test substance (3-chloropropyl)trimethoxysilane (CAS 2530-87-2) was investigated for effects on fertility in a Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test, conducted according to OECD 422, and in compliance with GLP. Groups of 10 Sprague-Dawley rats per sex per dose were exposed to the vapour in a whole body inhalation system at doses of 5, 25 and 100 ppm. Untreated animals served as controls. Treatment was carried out for 6 hours daily to male rats for 28 days and to female rats throughout the 14-day pre-pairing, pairing and gestation period until the individual day 19 post coitum. During the pairing period, rats were housed overnight with one male and one female in Makrolon pairing cages. The female was placed with the same male until mating occurred or two weeks elapsed. Animals were observed for mortalities and clinical signs, and detailed clinical observations were performed once per week. A Functional Observational battery (modified Irwin screen test) was performed once during the test (males: shortly before sacrifice; females: on day 3 post-partum). Body weights and food consumption was recorded. Parental generation males were sacrificed after they had been treated for 28 days, parental generation females were sacrificed on day 4 post-partum. A complete gross necropsy was performed on all adult animals. The litters were examined for litter size, live birth, stillbirth and any gross anomalies. The sex ratio of the pups was recorded. Pups were weighed individually on day 0, 1 and 4 post-partum. The pups were observed daily for survival and behavioural abnormalities in nesting and nursing. Dead pups and pups killed on day 4 post-partum were examined macroscopically.

The fertility rate was high resulting in at least 9 litters per group for evaluation of reproduction data. At all concentrations, there were no treatment-related effects on precoital time, fertility indices, mean duration of gestation, number of implantations, post-implantation loss through to scheduled sacrifice on day 4 post-partum. The mean number of corpora lutea per dam (determined at necropsy) was similar in all groups and gave no indication of a test item-related effect. There were no findings, which distinguished test item-treated animals from controls. In particular, no treatment-related histopathological findings were observed in the reproductive organs of either sex from the parental generation. The assessment of the integrity of the spermatogenetic cycle did not provide any evidence of impaired spermatogenesis.

At all concentrations, there were no treatment-related effects on pup survival or litter size from birth through to scheduled sacrifice on day 4 post-partum. No abnormal findings were noted for pups at first litter check or during the first 4 days post-partum. Sex ratios at first litter check and on day 4 post-partum were unaffected by treatment with the test item. Mean pup weights on day 0 and day 1 post-partum were unaffected by treatment with the test item. Mean pup weight development during the first 4 days post-partum lactation was unaffected by treatment with the test item.

In summary, exposure to (3-chloropropyl)trimethoxysilane (CAS 2530-87-2) up to and including the high concentration of 100 ppm did not result in any signs of general or reproductive toxicity of the test item. Based on these results the NOEC (no observed effect concentration) was established as ≥100 ppm (nominal concentration, corresponding to 99.7 ppm mean analytical concentration and equivalent to 810.32 mg/m³.

Justification for classification or non-classification

The available data are reliable and suitable for classification. Based on these data, classification for toxicity to reproduction according to EC/1272/2008 is not warranted.

No information is available on effects via lactation.