Siloxanes - Consumption, Toxicity and Alternatives - Miljøstyrelsen
Siloxanes - Consumption, Toxicity and Alternatives - Miljøstyrelsen
Siloxanes - Consumption, Toxicity and Alternatives - Miljøstyrelsen
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haematological serum chemistry <strong>and</strong> organ weight <strong>and</strong> a transient increase in<br />
liver to body weight <strong>and</strong> thymus to body weight at 160 ppm. NOEL (histopathological<br />
changes) was determined at 10 ppm, NOEL (systemic toxicity)<br />
was determined at 75 ppm <strong>and</strong> NOEL (immunosuppression) was determined<br />
at 160 ppm (EPA DCN 86970000385 1996).<br />
Subchronic toxicity studies in rats exposed over three months at doses up to<br />
224 ppm show that the lung is the primary target organ following D5 inhalation<br />
(Burns et al. 1998).<br />
Rats exposed to inhalation of HMDS for one month in concentrations between<br />
0.9 <strong>and</strong> 59.2 mg/l showed moderate increase in focal inflammatory lesions<br />
in the lungs in the highest dose group, increase in incidence <strong>and</strong> severity<br />
of renal tubule regeneration in male rats exposed to 12.7 <strong>and</strong> 59.2 mg/kg,<br />
hyaline droplet accumulation, protein casts <strong>and</strong> granular casts were present in<br />
kidneys in several males in the highest 59.2 mg/kg dose group. Other signs of<br />
toxicity included minimal hepatocellular hypertrophy in males of the two<br />
highest dose groups <strong>and</strong> a slight increase in pigment accumulation in bile<br />
ducts in the high dose group males (EPA DCN 869000048 1997).<br />
Exposure of rats for three months to HMDS in concentrations between 0.33<br />
<strong>and</strong> 33.3 mg/kg showed also similar histological lesions in the kidneys of males<br />
in the three highest dose groups; 4.0, 10.0 <strong>and</strong> 33.3 mg/kg. NOEL was determined<br />
at 1.3 mg/kg for male rats <strong>and</strong> 33.0 mg/kg for female rats (EPA<br />
DCN 86980000182 1998; Cassidy 2001).<br />
Multifocal, subpleural, subacute to subchronic interstitial inflammation were<br />
seen in lungs of all groups of rats exposed for three months to inhalation of<br />
concentrations between 0.9 <strong>and</strong> 13.64 mg/kg HMDS. After the recovery period<br />
an increase of these finding were still seen in the high dose group (EPA<br />
DCN 86980000048 1997).<br />
3.2.5 Genetic toxicity<br />
Both D4 <strong>and</strong> HMDS have been tested in a number of in vitro studies including<br />
Ames test in different strains (with <strong>and</strong> without metabolic activation),<br />
DNA damage <strong>and</strong> repair test in E. Coli, cytogentic assay in Chinese Hamster<br />
Ovary cells, chromosome aberration assay <strong>and</strong> sister chromatide exchange<br />
assay in mouse lymphoma cells, all with <strong>and</strong> without activation with negative<br />
result. In vivo tests have included cytogenetic assay in rat (HMDS) <strong>and</strong><br />
dominant lethal assay in rat (D4). Both tests were negative (European Commission,<br />
2000). An in vivo chromosome aberration test in rats exposed to 700<br />
ppm D4 was also negative (Vergnes et al. 2000).<br />
The results gave no indication of a genotoxic potential - neither for D4 nor<br />
HMDS.<br />
3.2.6 Carcinogenicity<br />
Very little information is available on carcinogenicity of siloxanes. The only<br />
information identified is a report from Dow Corning received by EPA with<br />
preliminary results from a two-year chronic toxicity <strong>and</strong> carcinogenicity study<br />
in rats exposed to vapour concentrations of 0, 10, 40 or 160 ppm of D5 for 6<br />
hours per day, 5 days per week, for 24 months. The preliminary results show<br />
that female rats in the highest dose group had a statistically significant increase<br />
of uterine tumours. These findings may indicate that there is a potential car-