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Information is available from one reliable bacterial mutagenicity study for (3-chloropropyl)dimethoxymethylsilane (CAS 18171-19-2). No further data are available for the registered substance, however, reliable data are available for the related substances dichloro(3-chloropropyl)methylsilane (CAS 7787-93-1) and (3-chloropropyl) diethoxymethylsilane (CAS 13501-76-3).

(3-Chloropropyl)diethoxymethylsilane and dichloro(3-chloropropyl)methylsilane are both close structural analogues of the registered substance,

(3-chloropropyl)dimethoxymethylsilane. All three substances hydrolyse to (3-chloropropyl)methylsilanediol and ethanol, hydrochloric acid and methanol respectively. (3-chloropropyl)dimethoxymethylsilane has a hydrolysis half-life of around 1 h at 25°C and pH 7; the rate for the dichloro analogue (7787-93-1) is <1 min at pH 4, 7 and 9 and 25°C (category read-across), that for (3-chloropropyl)diethoxymethylsilane is slower (estimated to be around 20-30 hours, based on read-across from related alkoxysilanes). As hydrolysis is likely to occur during testing and following ingestion, and the other products of hydrolysis are not genotoxic (OECD (2002), OECD (2004a), OECD (2004b)), it is considered that read-across between the three substances is appropriate. Additional information is given in a supporting report (PFA 2013aa) attached in Section 13 of the IUCLID 5 dossier.

(3-Chloropropyl)diethoxymethylsilane and dichloro(3-chloropropyl)methylsilane were chosen as read-across substance as they have the same silanol hydrolysis product as (3-chloropropyl)dimethoxymethylsilane and none of the substances have any functional groups that are associated with genetic toxicity.

The genetic toxicity data available for the other substances in the analogue group are summarised in Table 5.7.2. The positive results observed with structural analogues were not read-across to the registered substance as there is a reliable bacterial mutagenicity study available for the registered substance, in which no evidence of mutagenicity was observed. In addition, the final conclusions from the studies on the structural analogue substances were negative, as the potential for genetic toxicity observed bacterial cells was found in only one of two in vitro mammalian mutagenicity assays, and no evidence for genetic toxicity was observed in in vivo micronucleus assays.

In a reliable bacterial mutagenicity assay, no increase in the number of revertants was observed in Salmonella typhimurium strains (TA 98, TA 100, TA 102, TA 1535 and TA 1537) tested with and without metabolic activation in either of two independent experiments, the first using the plate incorporation method and the second using the pre-incubation method. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test (Leuschner 2002; rel 1). The study was conducted in compliance with OECD 471 and under GLP conditions.

In a reliable in vitro cytogenicity assay in Chinese hamster fibroblasts, under GLP and following OECD 473, dichloro(3-chloropropyl)methylsilane (CAS 7787-93-1) did not induce a biologically significant increase in chromosomal aberration frequency and was found not to be clastogenic (Hüls AG 1997). The original study was considered reliability 1. Read-across to the registered substance is considered scientifically justified and is reliability 2.

In a reliable in vitro mutagenicity assay in Chinese hamster ovary cells, under GLP and following OECD 476, dichloro(3-chloropropyl)methylsilane (CAS 7787-93-1) showed no mutagenic potential of the test material (Hüls AG 1997). The original study was considered reliability 1. Read-across to the registered substance is considered scientifically justified and is reliability 2.

In a reliable in vivo mammalian micronucleus assay, no evidence of substance mediated induction of micronuclei was apparent after the administration of 1600 mg/kg bw of (3-chloropropyl)diethoxymethylsilane (CAS 13501-76-3) by intraperitoneal injection. The test was carried out in accordance with EU method B.12 under GLP (Hüls AG 1996). The original study was considered reliability 1. Read-across to the registered substance is considered scientifically justified and is reliability 2.

The results of all the studies are in agreement. The most recent and reliable available studies were chosen as key.


Short description of key information:
Information is available from one reliable bacterial mutagenicity study for (3 -chloropropyl)dimethoxymethylsilane (CAS 18171 -19 -2). No further data are available for the registered substance, however, reliable data are available for the related substances dichloro(3-chloropropyl)methylsilane (CAS 7787-93-1) and (3 -chloropropyl)diethoxymethylsilane (CAS 13501 -76 -3).

In vitro:
Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in Salmonella typhimurium strains (TA 98, 100, 102, 1535, 1537) (OECD TG 471) (Leuschner 2002; rel 1).

Cytogenicity in mammalian cells: read across from analogous substance dichloro(3-chloropropyl)methylsilane (CAS 7787-93-1): negative in Chinese hamster fibroblast cells (OECD TG 473) (Hüls 1997).

Mutagenicity in mammalian cells: read-across from analogous substance dichloro(3-chloropropyl)methylsilane (CAS 7787-93-1): negative in Chinese hamster ovary cells (OECD 476) (Hüls 1997).

In vivo:
read-across from analogous substance (3-chloropropyl)diethoxymethylsilane (CAS 13501-76-3): negative in mammalian micronucleus assay (intraperitoneal administration) (EU method B 12 (Hüls 1996).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available information on (3 -chloropropyl)dimethoxymethylsilane (CAS 18171 -19 -2) and its structural analogues, no classification is required in accordance with EU Regulation (1272/2008).