No. 1031 - Miljøstyrelsen

48
haematological serum chemistry and organ weight and a transient increase in
liver to body weight and thymus to body weight at 160 ppm. NOEL (histopathological
changes) was determined at 10 ppm, NOEL (systemic toxicity)
was determined at 75 ppm and NOEL (immunosuppression) was determined
at 160 ppm (EPA DCN 86970000385 1996).
Subchronic toxicity studies in rats exposed over three months at doses up to
224 ppm show that the lung is the primary target organ following D5 inhalation
(Burns et al. 1998).
Rats exposed to inhalation of HMDS for one month in concentrations between
0.9 and 59.2 mg/l showed moderate increase in focal inflammatory lesions
in the lungs in the highest dose group, increase in incidence and severity
of renal tubule regeneration in male rats exposed to 12.7 and 59.2 mg/kg,
hyaline droplet accumulation, protein casts and granular casts were present in
kidneys in several males in the highest 59.2 mg/kg dose group. Other signs of
toxicity included minimal hepatocellular hypertrophy in males of the two
highest dose groups and a slight increase in pigment accumulation in bile
ducts in the high dose group males (EPA DCN 869000048 1997).
Exposure of rats for three months to HMDS in concentrations between 0.33
and 33.3 mg/kg showed also similar histological lesions in the kidneys of males
in the three highest dose groups; 4.0, 10.0 and 33.3 mg/kg. NOEL was determined
at 1.3 mg/kg for male rats and 33.0 mg/kg for female rats (EPA
DCN 86980000182 1998; Cassidy 2001).
Multifocal, subpleural, subacute to subchronic interstitial inflammation were
seen in lungs of all groups of rats exposed for three months to inhalation of
concentrations between 0.9 and 13.64 mg/kg HMDS. After the recovery period
an increase of these finding were still seen in the high dose group (EPA
DCN 86980000048 1997).
3.2.5 Genetic toxicity
Both D4 and HMDS have been tested in a number of in vitro studies including
Ames test in different strains (with and without metabolic activation),
DNA damage and repair test in E. Coli, cytogentic assay in Chinese Hamster
Ovary cells, chromosome aberration assay and sister chromatide exchange
assay in mouse lymphoma cells, all with and without activation with negative
result. In vivo tests have included cytogenetic assay in rat (HMDS) and
dominant lethal assay in rat (D4). Both tests were negative (European Commission,
2000). An in vivo chromosome aberration test in rats exposed to 700
ppm D4 was also negative (Vergnes et al. 2000).
The results gave no indication of a genotoxic potential - neither for D4 nor
HMDS.
3.2.6 Carcinogenicity
Very little information is available on carcinogenicity of siloxanes. The only
information identified is a report from Dow Corning received by EPA with
preliminary results from a two-year chronic toxicity and carcinogenicity study
in rats exposed to vapour concentrations of 0, 10, 40 or 160 ppm of D5 for 6
hours per day, 5 days per week, for 24 months. The preliminary results show
that female rats in the highest dose group had a statistically significant increase
of uterine tumours. These findings may indicate that there is a potential car-