Registration Dossier

Administrative data

Description of key information

In one acute oral toxicity study (BRRC, 1988), which was similar to the now deleted 401, trimethoxysilane was administered to rats (strain not given) by oral gavage. Signs of toxicity included sluggishness, lacrimation, an unsteady gait, distended abdomens, head and body twitches, piloerection, prostration, a moribund appearance, red crust around nose and eyes, diarrhea, an unkempt appearance and emaciation. At necrospy the animals that died had gas-filled stomachs and intestines, red and/or thick stomachs, a hard white material in the stomach, red intestines and red liquid-filled abdominal cavities. In survivors, the only macroscopic finding was mottled and tan to dark red appearance of several kidneys. The LD50 was 2361.6 mg/kg bw in males and 1497.6 mg/kg bw in females (based on a density of 0.96 g/cm3). In a number of additional studies, the LD50 for both males and females was >2000 mg/kg.
In the key dermal study (BRRC, 1988), which was similar to OECD 402, rabbits (strain not given) were exposed under occlusive conditions to trimethoxysilane. Clinical signs were sluggishness, salivation, prostration, emaciation, and a clear or red discharge around the nose. There were also signs of skin corrosion.
For inhalation, the key study (BRRC, 1988) was conducted according to OECD 403. Sprague-Dawley rats were exposed whole body to a vapour of the test substance for four hours. Clinical signs were blepharospasm, abdominal breathing, decreased motor activity, ataxia, slow surface-righting reflex, unkempt fur, decreased respiration rate and motor activity. The LC50 was 60 ppm.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
Value:
299.88 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
Value:
6 048 mg/kg bw

Additional information

The studies with the highest reliability score (1 or 2) were selected as key studies. In the case of the oral route an overall LD50 of >2000 mg/kg bw (the limit dose) was selected as the key parameter because only one study gave a value less than this for females. All other acute oral studies gave LD50s greater than 2000 mg/kg bw in both males and females. Hence, on a weight-of-evidence the oral LD50 is greater than 2000 mg/kg bw. There were three reliability score 2 studies for the dermal route. The study selected as the key study was not the most recent, but unlike the most recent study, was able to identify an LD50 value rather than a range. Overall, for all routes the findings in the non-key studies were in agreement with the findings of the key study.

Justification for classification or non-classification

The evidence suggests that trimethoxysilane does not need be classified for acute oral or dermal toxicity.

Trimethoxyslane is labelled as 'R26: Very toxic by inhalation' according to Directive 67/548/EEC, and the proposed labelling under Regulation 1272/2008 is 'Acute toxic1 (vapour)'. This is based on the criteria LC50 0.5 mg/l. In addition, due to the corrosive effects observed in the respiratory tract, the substance is additional classified for Specific Target Organ Toxicity (Single Exposure) Category 3 under Regulation 1272/2008.