Diethoxy(methyl)silane

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Screening study for reproductive/developmental toxicity (RA-A CAS 78 -62 -6, OECD 422, oral, rat): NOAEL systemic toxicity and fertility = 300 mg/kg bw/day

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 for cross-reference:

read-across source

Description (incidence and severity):

There were no ophthalmoscopic findings in any of the animals of this study.

Dose descriptor:

NOAEL

Remarks:

systemic

Effect level:

300 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

mortality

body weight and weight gain

food consumption and compound intake

organ weights and organ / body weight ratios

histopathology: non-neoplastic

Dose descriptor:

NOAEL

Remarks:

reproductive toxicity

Effect level:

300 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

reproductive function (sperm measures)

reproductive performance

Critical effects observed:

yes

Lowest effective dose / conc.:

1 000 mg/kg bw/day (actual dose received)

System:

male reproductive system

Organ:

testes

Treatment related:

yes

Dose response relationship:

no

Relevant for humans:

not specified

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

300 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

viability

clinical signs

body weight and weight gain

Critical effects observed:

no

Reproductive effects observed:

yes

Lowest effective dose / conc.:

1 000 mg/kg bw/day (actual dose received)

Treatment related:

yes

Relation to other toxic effects:

reproductive effects as a secondary non-specific consequence of other toxic effects

Dose response relationship:

no

Relevant for humans:

not specified

Conclusions:

A combined repeated dose toxicity study with a reproductive/developmental toxicity screening test was performed with the source substance diethoxy(dimethyl)silane according to OECD TG 422 and GLP at dose levels of 100, 300 and 1000 mg/kg bw/day. The NOAEL for general systemic toxicity and reproductive toxicity can be established at 300 mg/kg bw/day. General systemic toxicity was based on increased mortality, adversely reduced body weight, food consumption, and histopathology effects to the kidney and testes at the highest dose level. Developmental toxicity was based on an increase of still births, a prolonged gestation period, reduced delivery index, higher postimplantation loss, decreased litter weight, and a reduced viability index at the highest dose. 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:

adverse effect observed

Dose descriptor:

NOAEL

300 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Hazard assessment is conducted by means of read-across based on a read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

No data on the reproductive toxicity of diethoxy(methyl)silane (CAS 2031-62-1) are available. Therefore, the risk assessment was performed based on the available data from the source substance diethoxy(dimethyl)silane (CAS 78-62-6). In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and in accordance with the Read across assessment framework (RAAF, ECHA 2017) read across from the analogue substance has been applied to support the human health hazard assessment of diethoxy(methyl)silane (CAS 2031-62-1). Details on read across justifications can be found in the attached justification in the respective target entry and in the overall justification for grouping of substances attached in IUCLID Section 13.

A key study (combined repeated dose toxicity study with reproductive/developmental toxicity screening test (oral)) with diethoxy(dimethyl)silane (CAS 78-62-6) is available and was performed according to OECD TG 422 and in compliance with GLP (Eurofins, 2018). The test substance was administered daily in graduate doses (100, 300, and 1000 mg/kg bw/day) to 3 groups of test animals per gavage, one dose level per group for a treatment period of up to 54 days, i.e. during 14 days of pre-mating and maximum 14 days of mating in both males and females, during gestation period and up to post-natal day 3 in females. Males were dosed after the mating period until the minimum total dosing period of 28-29 days was completed. Animals of an additional control group were handled identically as the dose groups but received corn oil, the vehicle used in this study.

 

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 following the last administration. Animals in the recovery groups were not mated and dosed for 28 days (males) or until the first scheduled euthanasia of dams (females).

 

As described in the repeated dose toxicity chapter systemic toxicity was observed in the highest dose group based on mortality, reduced body weight and food consumption and histopathological findings in the kidney and testes. With regard to reproductive toxicity effect, there was a moderate tubular degeneration which correlated with reduced weight in testes of high-dose males. The elongated and round spermatids of stages V-VII were mainly affected. More mature spermatids and spermia appeared to be almost unaffected. In some tubules, there were reabsorbed apoptotic bodies or Sertoli cell vacuolation. In the epididymides, only a minimal severity of cellular detritus (shedded epithelia and/or pyknotic sperm cells) was recorded in most 1000-mg/kg bw/day males. Therefore, it is deemed that the sperm became damaged late during the study period, and hence, fertility was not affected during the mating period. While these findings were still present after the recovery period, a partial recovery cannot be judged since the recovery time was much too short (i.e., sperm cycle in rats takes between 56-58 days) for recovery.

Treatment-related effects also were observed in offspring at 1000 mg/kg bw/day. Still births were seen in 6/8 dams at 1000 mg/kg bw/day with an increased mean number of 5.00 still births when compared to 0.11 in controls. In relation to the increase in still births, gestation period was noted to be prolonged. The delivery index was shown to be markedly reduced (56%) when compared to 100% in the control group. Accordingly, percentage of post-implantation loss was markedly higher (51.31%) when compared to the control group (6.57%).

 

No adverse effects of diethoxy(dimethyl)silane were found at the lower dose levels tested. Thus, the NOAEL for reproductive toxicity could be established at 300 mg/kg body weight/day.

Taking into consideration the above results generated from the structurally analogue substance the target substance is expected to show similar toxicity after repeated exposure.

Effects on developmental toxicity

Description of key information

Screening study for reproductive/developmental toxicity (RA-A CAS 78 -62 -6, OECD 422, oral, rat): NOAEL systemic toxicity and developmental toxicity = 300 mg/kg bw/day

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:

Hazard assessment is conducted by means of read-across based on a read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose.

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

For assessment of the developmental toxicity properties of diethoxy(methyl)silane (CAS 2031 -62 -1) read-across was applied using the structural analogue substance, diethoxy(diemthyl)silane (CAS 78 -62 -6). In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and in accordance with the Read across assessment framework scenario 2 (RAAF, ECHA 2017) read across from an analogue substance has been applied to support the human health hazard assessment of diethoxy(methyl)silane (CAS 2031 -62 -1). Details on read across justifications can be found in the attached justification in the respective target entry and in the overall justification for grouping of substances attached in IUCLID Section 13.

A key study (combined repeated dose toxicity study with reproductive/developmental toxicity screening test (oral)) with diethoxy(dimethyl)silane (CAS 78-62-6) is available and was performed according to OECD TG 422 and in compliance with GLP (Eurofins, 2018). The test substance was administered daily in graduate doses (100, 300, and 1000 mg/kg bw/day) to 3 groups of test animals per gavage, one dose level per group for a treatment period of up to 54 days, i.e. during 14 days of pre-mating and maximum 14 days of mating in both males and females, during gestation period and up to post-natal day 3 in females. Males were dosed after the mating period until the minimum total dosing period of 28-29 days was completed. Animals of an additional control group were handled identically as the dose groups but received corn oil, the vehicle used in this study.

Test item-related mortality occurred at the highest dose level of 1000 mg/kg bw/day. Beforehand, both affected adult females were seen with general signs of reduced health condition and were found dead or were euthanised for animal welfare shortly after delivery of still born pups. Mortality was related to renal tubular necrosis. One further female dosed with 1000 mg/kg bw/day was also observed with reduced health condition after delivery of still births.

Treatment-related effects were observed in offspring at 1000 mg/kg bw/day. Still births were seen in 6/8 dams at 1000 mg/kg bw/day with an increased mean number of 5.00 still births when compared to 0.11 in controls. Total litter weight at 1000 mg/kg bw/day was also affected based on the lower number of live pups.Test item-related, adverse effects were also noted for pup survival. At 1000 mg/kg bw/day a reduced viability index of 75.56% was seen when compared to 100.00% in the control group.

 

No adverse effects of diethoxy(dimethyl)silane were found at the lower dose levels tested. Thus, the NOAEL for reproductive toxicity could be established at 300 mg/kg body weight/day.

Taking into consideration the above results generated from the structurally analogue substance the target substance is expected to show similar toxicity after repeated exposure.

Justification for classification or non-classification

Based on the information from an adequate read-across substance, it is concluded that the available information on reproductive toxicity does not meet the criteria for classification according to Regulation (EC) No. 1272/2008, and is therefore conclusive but not sufficient for classification.