N-(3-(trimethoxysilyl)propyl)ethylenediamine

Endpoint summary

Description of key information

The key study for the inhalation route is a 90-day inhalation test (Charles River, 2017) conducted to OECD TG 413 and in compliance with GLP in which Sprague Dawley rats were exposed to an aerosol of N-[3-(trimethoxysilyl)propyl] ethylenediamine at concentration of 5, 15 or 45 mg/m3, 5 days per week. The NOAEC for local effects was 15 mg/m3, based on effects on the respiratory tract. There were no adverse systemic effects.

The key study for the oral route is a Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test conducted to OECD TG 422 and in compliance with GLP (Dow Corning Corporation, 2002a). The NOAEL from this study was at least 500 mg/kg bw/day as no adverse effects were observed at any dose tested.

A nine-day dermal toxicity study (Bushy Run Research Center, 1993) supported the finding of low repeated dose systemic toxicity. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

500 mg/kg bw/day

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

45 mg/m³

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

15 mg/m³

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Additional information

In the key study (Charles River, 2017), which is a 90-day repeated dose toxicity study conducted to OECD TG 413 and in compliance with GLP, exposure of Sprague-Dawley rats to an aerosol of N-[3-(trimethoxysilyl)propyl] ethylenediamine via nose-only inhalation for 6 hours per day on a 5-day basis for 13 weeks at target exposure concentrations of 5, 15, and 45 mg/m3 resulted in non-adverse test substance-related effects at 5 and 15 mg/m3. Adverse test substance-related clinical observations, lower body weights and body weight gains, macroscopic findings in the lungs, increased lung weights, and microscopic findings in the nasal cavity, larynx, trachea, and lungs were noted in the 45 mg/m3 group males and females at the end of the treatment period. At the recovery necropsy, many of the effects of test substance exposure, including higher lung weights, persisted in the nasal cavity, larynx, trachea, and lungs in the 45 mg/m3 group and were noted at generally a lower incidence and severity than that seen at the primary necropsy. Therefore, the NOAEC for the local effects on the lungs and respiratory tract was 15 mg/m3. There were no adverse systemic effects observed at any concentration.

The supporting study for this endpoint is an oral test conducted according to OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test), and to GLP (Dow Corning Corporation, 2002b) concluded a NOAEL of 500 mg/kg bw/day as no treatment-related adverse effects were observed at any dose. The earlier seven-day dose range-finding study (Dow Corning Corporation, 2002a), not conducted to GLP, also found the NOAEL to be at least 500 mg/kg bw/day.

 

A nine-day dermal study is also available (Bushy Run Research Center, 1993) which supports the finding of low repeated dose systemic toxicity. In this study, treatment of rats for nine cutaneous applications during an 11-day period produced transient clinical, necropsy and microscopic observations indicative of mild to moderate skin irritation in males treated with 772.5 and 1545 mg/kg bw/day and females treated with 257.5 mg/kg bw/day and above. Skin effects included barely perceptible erythema exfoliation and excoriation. Therefore the NOAEL for systemic effects is at least 1545 mg/kg bw/day in rats.

Justification for classification or non-classification

Based on the available information on the registered substance no classification is required for oral or dermal repeated exposure, in accordance with Regulation (EC) No 1272/2008.

Effects observed in the 90-day inhalation toxicity study are considered to reflect a local irritation response to exposure to aerosol droplets. The substance is therefore classified STOT SE 3: Respiratory tract; H335: May cause respiratory irritation. No separate classification for repeated dose toxicity is required.