Dichloromethyl(3,3,3-trifluoropropyl)silane

Endpoint summary

Description of key information

There are no repeated dose toxicity data available for dichloromethyl(3,3,3-trifluoropropyl)silane. The the hazard profile of dichloromethyl(3,3,3-trifluoropropyl)silane is solely driven by the hydrolysis product HCl and can be assessed qualitatively and quantitatively by considering the amount of HCl produced by hydrolysis. Thus, a worst case assessment for inhalation toxicity was performed with data from a subchronic study with hydrogen chloride. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEC

15 mg/m³

Study duration:

subchronic

Species:

rat

Quality of whole database:

The study was well documented and meets generally accepted scientific principles, and conducted in compliance with GLP. The relevance of these data for hazard assessment of dichloromethyl(3,3,3-trifluoropropyl)silane is discussed in the endpoint summary. Since this is a read-across from hydrogen chloride, the reliability was set from RL1 to RL2.

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are no repeated dose toxicity data on dichloromethyl(3,3,3-trifluoropropyl)silane.

Dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7) is a highly moisture-sensitive liquid that hydrolyses rapidly in contact with water (half-life of 8 to 12 seconds at pH 4, 7 and 9 at 1.5°C) to methyl(3,3,3-trifluoropropyl)silanediol and hydrogen chloride (HCl). As the substance is corrosive, risk management measures are in place at industrial sites to prevent the potential for human exposure to dichloromethyl(3,3,3-trifluoropropyl)silane. Due to the corrosive nature of the substance it is considered not to be either ethical or scientifically justified to perform repeated dose toxicity testing with dichloromethyl(3,3,3-trifluoropropyl)silane by any route of exposure. As an example, following repeated oral dosing, the corrosive nature of the product could affect the lining of the stomach, giving rise to hyperplasia and a subsequent reduced food intake. This would make the interpretation of any systemic findings difficult.

A guideline-compliant repeated-dose inhalation study should elicit systemic toxicity at the highest test concentration. Since the local corrosive effects of dichloromethyl(3,3,3-trifluoropropyl)silane would be significant, it is unlikely that any systemic effects would be seen at dose levels made sufficiently low (< 10 ppm) to prevent the known corrosive effects and/or distress in the test species. This has been confirmed in a 28-day inhalation study with another chlorosilane, dichloro(dimethyl)silane (CAS 75-78-5, WIL, 2014) in which there were no effects of treatment on clinical signs, body weight or food consumption that would indicate a systemic effect. Furthermore, the histopathology in the study indicated that the effects in the upper respiratory tract were similar to HCl. It is therefore concluded that the hydrolysis product HCl will dominate the inhalation toxicity profile of dichloromethyl(3,3,3-trifluoropropyl)silane. Local effects from hydrogen chloride are addressed by good quality data for that substance (Toxigenics Inc, 1983) and the 4-week dichloro(dimethyl)silane study (WIL, 2014). With regard to the dermal route, due to the known corrosive effects of dichloromethyl(3,3,3-trifluoropropyl)silane, appropriate H-phrases and P-statements are included in the labelling, meaning that repeated skin contact can be excluded.

Thus, the hazard profile of dichloromethyl(3,3,3-trifluoropropyl)silane is solely driven by the hydrolysis product HCl and can be assessed qualitatively and quantitatively by considering the amount of HCl produced by hydrolysis. Further repeated-dose animal studies should be omitted due to animal welfare.

Hydrogen Chloride

In a 90-day repeated dose inhalation study in rats and mice (Toxigenics, 1983), 31 males and 21 females of each species/strain were exposed to test concentrations of 0, 10, 20 and 50 ppm hydrogen chloride gas (HCl). Treatment was whole-body exposure for six hour per day, 5 days per week.15 males and 10 females from each group were sacrificed after four exposures and the nasal turbinates, trachea, lung and gross lesions were examined microscopically. In general, all animals in the high dose group showed adverse findings after 4-days exposure.One female high dose mouse was found dead on study day 12, and four low dose male mice were found dead on study day 92. In addition, one high dose female mouse was sacrificedin extremison study day 20. One high dose female Sprague-Dawley rat was found dead on study day 4. However, the study authors noted that the deaths did not appear to be related to exposure to HCl. Clinical signs were consistent with the irritant/corrosive properties of HCl (appendage, tail or lip injury in the form of toe missing/swollen/open/gelatinous, scabbed/deformed/lesion, crusty nose, tissue mass, mouth injury, scabbed nose, crusty muzzle, red stained fur, nasal discharge, crusty eye, poor coat quality);some of the observed injuries may have been mechanical and not related to test material exposure.90-days exposure to 50 ppm HCl resulted in decreased body weights in all four strains after four exposures. Following 90 days of exposure B6C3F1 male and female mice and male Sprague-Dawley rats exposed to 50 ppm had biologically significant decreases in body weight. After four days of exposure there were statistically significant decreases in food consumption for high dose male Sprague-Dawley rats and male Fischer 344 rats. After 90 days high dose mice had the largest reduction in food consumption. The rats did not show a consistent reduction in food consumption that could be deemed expsoure-related. There were no treatment-related effects on the haematology, clinical chemistry or urinalyis parameters that were examined. Decreased liver weights were observed in high dose male and female mice and Fischer 344 female rats. The authors noted that this might have been due to the overall reduced body weights. Animals exposed to all concentrations of HCl had minimal to mild rhinitis, which occurred in the anterior portion of the nasal cavity and was dose and time related. Mice also developed varying degrees of cheilitis with accumulations of haemosiderin-laden macrophages involving the perioral tissues at 50 ppm. At all exposure concentrations mice developed oesinophilic globules in epithelial cells lining the nasal turbinates after 90 days of exposure.

The No Observed Adverse Effect Concentration (NOAEC) for systemic effects was determined to be 20 ppm (ca. 30 mg/m³) based on decreased body weight following exposure to 50 ppm. No NOAEC for local effects was established as irritant/corrosive effects were observed at all dose levels tested.

 

Dichloro(dimethyl)silane

In a 4-week repeated dose study (WIL, 2014) inhalation administration of dichloro(dimethyl)silane at targeted concentrations of 5 or 25 ppm (26 or 132 mg/m³) or hydrogen chloride at 50 ppm to rats for 5 days per week for 4 weeks resulted in subacute inflammation, hyperplasia and/or hyperkeratosis of the squamous epithelium and mucous cell hyperplasia of the respiratory epithelium in the anterior nasal cavity, with a clear dose-relationship in incidence and severity between the 5 and 25 ppm dichloro(dimethyl)silane groups for the majority of findings. Exposure to 25 ppm (132 mg/m³) dichloro(dimethyl)silane or 50 ppm hydrogen chloride was also associated with interstitial edema and respiratory epithelial degeneration within the anterior nasal cavity and acute inflammation in the larynx. Generally the incidence and severity of effects were similar in the 25 ppm dichloro(dimethyl)silane and 50 ppm hydrogen chloride groups, or greater in the hydrogen chloride group. The incidence and severity of the effects in the hydrogen chloride exposed group were generally comparable to those noted in the 90-day inhalation study with hydrogen chloride (Toxigenics, 1983). Overall, the histopathology observations in the nasal cavity did not suggest a greater irritant effect for the 25 ppm dichloro(dimethyl)silane group compared with the 50 ppm HCl group.

 

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Dichloromethyl(3,3,3-trifluoropropyl)silane (CAS 675-62-7) is a highly moisture-sensitive liquid that hydrolyses rapidly in contact with water (half-life of 8 to 12 seconds at pH 4, 7 and 9 at 1.5°C) to methyl(3,3,3-trifluoropropyl)silanediol and hydrogen chloride (HCl). As the substance is corrosive, risk management measures are in place at industrial sites to prevent the potential for human exposure to dichloromethyl(3,3,3-trifluoropropyl)silane. Due to the corrosive nature of the substance it is considered not to be either ethical or scientifically justified to perform repeated dose toxicity testing with dichloromethyl(3,3,3-trifluoropropyl)silane by any route of exposure. As an example, following repeated oral dosing, the corrosive nature of the product could affect the lining of the stomach, giving rise to hyperplasia and a subsequent reduced food intake. This would make the interpretation of any systemic findings difficult.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
A guideline-compliant repeated-dose inhalation study should elicit systemic toxicity at the highest test concentration. Since the local corrosive effects of dichloromethyl(3,3,3-trifluoropropyl)silane would be significant, it is unlikely that any systemic effects would be seen at dose levels made sufficiently low (< 10 ppm) to prevent the known corrosive effects and/or distress in the test species.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
Only one study available.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
In accordance with Column 2 of REACH Annex VIII (Section 8.6.1) testing for repeated dose dermal toxicity using a validated test method and relevant guidelines will be omitted. Due to the known corrosive effects of dichloromethyl(3, 3, 3-trifluoropropyl)silane appropriate H-phrases and P-statements are included in the labelling, meaning that repeated skin contact would be unlikely to occur. Any accidental skin contact could cause severe local effects but would be unlikely to cause any systemic effects.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
Due to the known corrosive effects of dichloromethyl(3, 3, 3-trifluoropropyl)silane appropriate H-phrases and P-statements are included in the labelling, meaning that repeated skin contact would be unlikely to occur.

Justification for classification or non-classification

In the absence of appropriate measured data, the substance is not classified for repeat dose toxicity.