Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

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
853.38 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
The test was conducted in accordance with an appropriate OECD test guideline and in compliance with GLPand is therefore considered to be reliability 1. Read-across of the study itself is considered to be reliability 2.
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Studies were chosen as key when the available study was of relevance and of sufficient quality for classification and labelling and for risk assessment.

Read-across justification

Effects on toxicity to reproduction

There are no reproductive toxicity data for (3-chloropropyl) diethoxymethylsilane (CAS 13501-76-3) or its hydrolysis product, (3-chloropropyl) methylsilanediol, so good quality data for the related substance (3-chloropropyl) trimethoxysilane (CAS 2530-87-2) has been used to assess the reproductive toxicity of (3-chloropropyl) diethoxymethylsilane. (3-chloropropyl) diethoxymethylsilane and (3-chloropropyl) trimethoxysilane hydrolyse within 2.3 and 0.28 h at 37.5°C and pH 7, yielding similar silanol hydrolysis products, (3-chloropropyl) methylsilanediol and (3-chloropropyl) silanetriol. In addition, methanol and ethanol are generated. Hydrolysis will be faster at lower or higher pH values. Since neither methanol nor ethanol would contribute to general toxicity effects in rodents at the dose levels tested, it is considered that the observed toxicological effects are due to the action of the (3-chloropropyl) silyl moiety, although the specific toxicological mechanism cannot be determined from the available information. Both substances have log Kowin the range that is favourable for absorption across the respiratory tract (ethoxy log kow= 4.2 and methoxy log kow= 0.56). No acute inhalation toxicity data are available for either substance, but acute oral and dermal LD50values for both substances in rats are > 2000 mg/kg. It is therefore considered valid to read-across the results for the trimethoxy analogue to fill data gaps for the registered substance. Additional information is given in a supporting report (PFA, 2013s) attached in Section 13 of the IUCLID 5 dossier. The molecular weight difference between target and source chemical is 210.77/198.72 = 1.06. 

Ethanol

Rats and mice maintained on liquid diets containing 5 – 10% ethanol for 5 weeks or longer showed some adverse physical and functional effects on the testes. Some indications of toxicity to the foetus, including deaths, growth retardation and increased malformations have been noted in rats and mice given diets in which 15-35% of the calories were derived from ethanol. However in other studies, no effect on the foetuses were seen in mice and rabbits given drinking water containing up to 15% ethanol, or inhaling up to 20 000 ppm ethanol, during pregnancy.

Methanol

Information about the effects of methanol on fertility is limited. Slight increases in sperm abnormalities were noted in a study in mice (1000 mg/kg/day) although the effect on fertility was not investigated. In a rat 2-generation study there were no effects on fertility. In a cynomolgus monkey study no effects were noted. Where effects are noted they occur only at high doses.

Conclusion

The non-silanol hydrolysis products of these substances, ethanol and methanol, would not contribute to any reproductive toxicity (fertility) effects at the dose levels tested.

Further information on read-across is given in Section 5.6.3.

Discussion of results:

Effects on fertility: via oral route

No data available.

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). The molecular weight ratio of the submission substance (CAS 15267-95-5) and the test substance (CAS 2530-87-2) is: 212 g/mol/198.72 g/mol=1.07. Therefore, the NOAEC for the submission substance is: 810.32 mg/m³x1.07=867.05 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, a 2-generation reproductive toxicity test 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 fertility: via dermal route

No data available.

 


Short description of key information:
There are no measured data available to assess the reproductive toxicity potential of (3-chloropropyl)diethoxymethylsilane, however, data are available for the structural analogue substance (3-chloropropyl)trimethoxysilane (CAS: 2530-87-2). (MW ratio: target/source = 1.06).

Reproduction Screening Test (OECD 422): rat: NOAEC: ≥ 804.6 mg/m³ (99.7 ppm)
MW corrected NOAEC:≥ 853.38 mg/m³

Justification for selection of Effect on fertility via oral route:
Reliable data for a structural analogue are available for the inhalation route.

Justification for selection of Effect on fertility via inhalation route:
The key study was selected for assessment.

Justification for selection of Effect on fertility via dermal route:
Reliable data for a structural analogue are available for the inhalation route.

Effects on developmental toxicity

Description of key information
There are no measured data available to assess the developmental toxicity potential of (3-chloropropyl)diethoxymethylsilane, however, data are available for the structural analogue substances 3-chloropropyltrimethoxysilane (CAS 2530-87-2, MW ratio: target/source = 1.06) and (3-chloropropyl)triethoxysilane (CAS 5089-70-3). 
Inhalation (OECD 422, RA from CAS 2530-87-2): rat: NOAEC:≥ 804.6 mg/m³ (99.7 ppm), MW corrected NOAEC = ≥ 853.38 mg/m³
Oral (OECD 414, RA from CAS 5089-70-3, rat): NOAEL=300 mg/kg bw/day
Dermal: no data available
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 study was carried out in accordance with an appropriate OECD test guideline and in compliance with GLP. Since this is a read-across from the structural analogue substance CAS 5089-70-3, the reliability was set from RL1 to RL2.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
853.38 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
The test was conducted in accordance with an appropriate OECD test guideline and in compliance with GLPand is therefore considered to be reliability 1. Read-across of the study itself is considered to be reliability 2.
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

There are no studies available for the registered substance (3-chloropropyl)diethoxymethylsilane (CAS 13501-76-3). 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). Studies were chosen as key when the available study was of relevance and of sufficient quality for classification and labelling and for risk assessment. The read-across is justified as follows:

READ-ACROSS JUSTIFICATION

To reduce animal testing REACH recommends to make use of a read-across approach where appropriate based on the high accordance in properties relevant for the specific endpoint.  In the case of repeated dose toxicity relevant properties are structural similarity as well as physical-chemical and basic toxicological parameters in the same range. In the following paragraphs the read-across approach for (3-chloropropyl)diethoxymethylsilane (CAS 13501-76-3) is evaluated point by point.

Read-across hypothesis

After oral exposure, (3-chloropropyl)diethoxymethylsilane (CAS 13501-76-3), (3-chloropropyl)triethoxysilane (CAS 5089-70-3) and (3-chloropropyl)trimethoxysilane (CAS 2530-87-2) are supposed to hydrolyse rapidly to similar silanol hydrolysis products, namely (3-chloropropyl)methylsilanediol and (3-chloropropyl)silanetriol. The non-silanol hydrolysis products methanol and ethanol are not expected to contribute to any adverse effects for systemic toxicity at the relevant dose levels. This is discussed further below.

The half-lives of (3-chloropropyl)diethoxymethylsilane at 25°C are 3.8 h at pH 7(see Section 4.1.1.1). As the hydrolysis reaction may be acid or base catalysed, the rate of reaction is expected to be slowest at pH 7 and increases as the pH is raised or lowered.

Reaction rate increases with temperature therefore hydrolysis will be faster at physiologically relevant temperatures compared to standard laboratory conditions. Under ideal conditions, hydrolysis rate can be recalculated according to the equation:

DT50(X °C) = DT50(T) x e(0.08 (T-X))

Where T = temperature for which data are available and X = target temperature.

Thus, for (3-chloropropyl)diethoxymethylsilane the hydrolysis half-life at 37.5°C and pH 7 (relevant for lungs and blood) is 2.3 hours and 5 s at 37.5°C and pH 2 (relevant for stomach).

For the read-across substances, (3-chloropropyl)triethoxysilane (CAS 5089-70-3) and (3-chloropropyl)trimethoxysilane (CAS 2530-87-2), the corresponding half-lives are 35 h (25°C, pH 7), 12.9 h (37°C, pH 7), 5 s (37.5°C, pH 2) and 0.89 h (25°C, pH 7), 19.8 min (37°C, pH 7), 5 s (37.5°C, pH 2), respectively.

 

Analogue approach justification

(a) Structural similarity

Both, the registration and read-across substances are structurally similar, containing a 3-chloropropyl moiety and 2-3 alkoxy (-OX) groups. The substances hydrolyse rapidly to produce similar hydrolysis products (3-chloropropyl)methylsilanediol and (3-chloropropyl)silanetriol.

These substances are part of an analogue group of chloroalkoxysilanes. The read-across substances were selected as the most appropriate based on chemical structure.

Further information is given in a supporting report attached to Section 13 of the IUCLID5 dossier (PFA, 2013s).

 

(b) Similar physicochemical characteristics

A data matrix is attached in Section 13 of the IUCLID dossier, and the key physicochemical parameters are summarised below

CAS Number

13501-76-3

5089-70-3

2530-87-2

Chemical Name

(3-chloropropyl)diethoxymethylsilane

(3-chloropropyl)triethoxysilane

(3-chloropropyl)

trimethoxysilane

Si hydrolysis product

(3-chloropropyl)methylsilanediol

(3-chloropropyl)silanetriol

(3-chloropropyl)

silanetriol

Molecular weight (parent substance)

210.77 g/mol

240.8 g/mol

198.72 g/mol

log Kow (parent)

4.2

2.0

2.0

log Kow (silanol hydrolysis product)

0.8

-1.1

-1.1

Water sol (parent)

36 mg/l

483 mg/l

1100 mg/l at 20°C

Water sol (silanol hydrolysis product)

60 000  mg/l

1 000 000 mg/l

1 000 000 mg/l at 20°C

Vapour pressure (parent)

6.8 Pa

2.3 Pa

52 Pa at 20°C

Hydrolysis t1/2 at pH 7 and 20-25°C

3.8 h

35 h

0.89 h

Hydrolysis t1/2 at pH 2 and 37.5°C

5 s (prediction)

5 s (prediction)

5 s

Hydrolysis t1/2 at pH 7 and 37°C

2.3 h (prediction)

12.9 h (prediction)

19.8 min

(c) Similar toxicokinetics

(3-chloropropyl)diethoxymethylsilane, (3-chloropropyl)triethoxysilane and (3-chloropropyl)trimethoxysilane, have a low vapour pressure, thus inhalation as a vapour is rather unlikely. The predicted water solubility and the log Kowindicate that absorption from the respiratory tract epithelium by passive diffusion is possible. After oral exposure the parent substances may be absorbed based on their phys.-chem. data. It is supposed that a rapid hydrolysis will take place in the stomach and exposure will be mostly to the hydrolysis products. These may be well absorbed in the GI tract, distributed well in the body and excreted mainly via urine.

 

(d) Similar acute toxicity

A key acute oral limit test which was conducted in compliance with GLP and according to the now deleted OECD TG 401 is available on (3-chloropropyl)diethoxymethylsilane. Two out of five males died when dosed at 2000 mg/kg bw and the macroscopic examination of the two perished animals showed the most severe lesions in the stomach and the intestine. The mucosa of these tissues showed hyperaemia and haemorrhages. No macroscopic abnormalities were observed in animals killed on day 14. All animals showed severe clinical symptoms in the first six hours after treatment with the test substance. The symptoms seen were padding movements, gait abnormality; decreased activity and squatting position. 24 and 48 hours after treatment most of the animals showed still the described clinical signs. Only one male and one female showed these signs 72 hours after treatment with the test substance. Milder clinical signs like piloerection were observed until day 7. After 7 days until the end of the observation period there were no more signs of systemic reaction to treatment. The LD50 to rats of (3-Chloropropyl)diethoxymethylsilane was found to be > 2000 mg/kg bw.

A key acute dermal toxicity study which was conducted in compliance with GLP and according to OECD TG 402 is available on (3-chloropropyl)diethoxymethylsilane, there was no mortality or any systemic effects seen at 2000 mg/kg bw (24 hour exposure) (LD50> 2000 mg/kg bw). 

In an acute oral toxicity study with (3-chloropropyl)triethoxysilanethe LD50 (rat) was determined to be >2000 mg/kg day. No mortality was observed and no necropsy findings were reported.In addition theLD50 (rabbit) was determined to be >2000 mg/kg after dermal exposure. No mortality was observed and no necropsy findings were reported. Desquamation was observed at the treatment site.

In an acute inhalation toxicity study with (3-chloropropyl)trimethoxysilane no systemic toxicity was observed leading to a LC0≥ essentially saturated vapour concentration.

In conclusion, the described substances have low potential for acute toxicity.

 

 

(e) Discussion of repeated systemic toxicity of the non-silanol hydrolysis product

The repeated dose toxicity of the non-silanol hydrolysis products, methanol and ethanol, have been extensively studied. It is beyond the scope of this assessment to review all of the available data in detail. However, the key findings from the disseminated REACH dossier and OECD SIAR report are reported here to support read-across arguments.

Ethanol

Rats and mice maintained on liquid diets containing 5 – 10% ethanol for 5 weeks or longer showed some adverse physical and functional effects on the testes. Some indications of toxicity to the foetus, including deaths, growth retardation and increased malformations have been noted in rats and mice given diets in which 15-35% of the calories were derived from ethanol. However in other studies, no effect on the foetuses were seen in mice and rabbits given drinking water containing up to 15% ethanol, or inhaling up to 20 000 ppm ethanol, during pregnancy.

Methanol

In rats, foetal NOAELs have been defined up to 5000 ppm after inhaled exposure. A corresponding figure of 1000 ppm has been defined for mice, which are considered to be more sensitive. At higher concentrations litter resorptions and increased incidences of foetal variations, and in some cases, malformations e. g. exencephaly and encephalocoele have been noted at 20000 ppm in rats and 5000 ppm in mice.

Conclusion

The non-silanol hydrolysis product of these substances, methanol and ethanol, would not contribute to any developmental toxicity effects at the dose levels tested.

  

Discussion of results:

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 post-natally 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 postnatally 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. The molecular weight ratio of the submission substance (CAS 15267-95-5) and the test substance (CAS 2530-87-2) is: 212 g/mol/198.72 g/mol=1.07. Therefore, the NOAEC for the submission substance is: 810.32 mg/m³x1.07=867.05 mg/m³.

 

Effect on developmental toxicity: via dermal route

No data available.

 


Justification for selection of Effect on developmental toxicity: via oral route:
The key study was selected for assessment.

Justification for selection of Effect on developmental toxicity: via inhalation route:
The key study was selected for assessment.

Justification for selection of Effect on developmental toxicity: via dermal route:
Reliable data for a structural analogue are available for the oral and inhalation route.

Justification for classification or non-classification

The available data on reproduction and developmental toxicity via inhalation and oral route of the structural analogue substances, 3 -chloropropyltrimethoxysilane (CAS 2530-87-2) and (3-chloropropyl) triethoxysilane (CAS 5089-70-3) and do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification of the registered substance.

No information is available on effects via lactation.