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Administrative data

Description of key information

An oral OECD 422 screening test (Dow Corning Corporation, 2005) in rats is available for the substance trimethoxy(methyl)silane. The NOAEL for systemic effects was determined to be 50 mg/kg/day, based on findings in a number of organs including the liver and thymus gland. The key study (Dow Corning Corporation, 2007) for repeated dose toxicity via the inhalation route, is a 90-day whole-body inhalation study, in which trimethoxy(methyl)silane was administered to rats six hours per day, five days per week. The NOAEC of 100 ppm (0.56 mg/l) was based on an increased incidence of grossly observed urinary bladder calculi along with kidney dilation at the 400 ppm exposure concentration.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
50 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
560 mg/m³
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

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

The key studies for the oral and inhalation routes are the only guideline studies available for the repeated dose toxicity endpoint (Dow corning Corporation, 2005 and Dow Corning Corporation, 2007). Both were conducted in accordance with the relevant OECD test guidelines and in compliance with GLP, and were therefore assigned Reliability 1. Range-finding studies are also available for both routes.

The key study for repeated dose via the oral route found that exposure to trimethoxy(methyl)silane was associated with organ weight and/or histomorphological changes in males (liver, thymus, thyroid, duodenum, jejunum, and red blood cell) and females (liver, thyroid, duodenum, jejunum, and adrenal gland) at dose levels at or above 250 mg/kg bw/day (Dow Corning Corporation 2005). A marked increase in prothrombin time was observed for males at 250 and 1000 mg/kg bw/day whereas females were unaffected.

Exposure was also associated with increased blood platelet concentration for males and females at 1000 mg/kg bw/day.

These data support a NOAEL for the toxicity phase of the study of 50 mg/kg bw/day.

The key study for repeated dose toxicity via the inhalation route reports the NOAEC of 560 mg/m3 (Dow Corning Corporation 2007). Test article-related clinical signs included decreased activity, soiling around muzzle, abdomen and urogenital regions with gross pathological findings including dilation of kidneys and urinary bladder with calculus in bladder. Test article-related clinical signs included soiling of the urogenital and abdominal regions of both sexes.

Mean body weights trended lower than controls over the exposure period for test anmals. This difference persisted through the completion of exposures and into week one of the post exposure recovery period. There were no differences in food consumption for either sex, in any of the 90-day exposure groups.

Test article-related gross necropsy included moderate dilation of the kidney, decreased soft testes, and calculi in the urinary bladder. Histomorphologic changes included minimal to moderate urinary bladder hyperplasia and inflammation. Kidney changes were characterized by hyperplasia of the pelvic epithelium and/or granulomatous inflammation. One male animal found dead on study day 72, demonstrated an apparent urinary obstruction possibly leading to acute uremia, with calcification of the aorta and pulmonary hemorrhagic edema as secondary effects. Additional changes included prostatic inflammation in moderate or severe degrees in two 1600 ppm exposure group rats.

Minimal to moderate hyperplasia of urinary bladder epithelium persisted in most rats, and exposure-related urinary bladder calculi were observed in several. Chronic or granulomatous inflammation in the renal pelvis was observed in several female rats. In male rats, there was no histomorphological evidence of a residual effect on the kidneys after the recovery period. In females, the incidence of pelvic epithelial hyperplasia and inflammation was modestly increased over controls. There were no indications of a residual effect on the prostate gland following the recovery period. No animals had more than mild inflammation of the prostate gland, and the incidence of inflammation was higher in control animals.

In females, absolute adrenal gland weights were statistically increased but without histological correlate and the finding was not present in males or in recovery group females. In males, increases in kidney weight were observed.

Also in males, the weights of testes and epididymides were statistically decreased in recovery group rats exposed to 1600 ppm. This finding correlated histologically with two recovery group males showing marked testicular seminiferous tubule degeneration and corresponding epididymal oligospermia (one unilateral, one bilateral). In regular study (90-day) rats, seminiferous tubule degeneration was observed only in one control and one low-exposure (25 ppm) rats. These findings were considered to be common spontaneous findings in young Sprague-Dawley rats and not test article-related. There were no test article-related changes in clinical pathology or serum chemistry.


Justification for classification or non-classification

Based on the available data trimethoxy(methyl)silane does not require classification for repeated dose toxicity according to Regulation (EC) 1272/2008.