Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
15
Absorption rate - dermal (%):
0.03

Additional information

 A well reported study (Dow Corning Corporation, 2004) conducted according to an EPA guideline and GLP found that a single oral dose of labelled D6 (1000 mg/kg bw/day) given to male and female rats was largely excreted as D6 in the faeces within 48 h, with less than 12% having been absorbed. Radioactivity recovered in the urine (0.3-0.4% of the administered dose) was present exclusively as polar metabolites; two major metabolites were identified (methylsilanetriol (50-70%) and dimethylsilanediol (30-50%); females tended to show more of the latter). Whole body autoradiography and mass balance data indicate that the majority of the administered dose remained in the gastrointestinal tract. Low levels of radioactivity were present in organs and tissues (liver, fat, bone marrow) indicating some absorption. Some metabolites were present in the blood. However, considerabe variability was seen in radioactivity levels in expired volatiles (from 3.86% to 25.28% of administered dose) may be due to off gassing from the fecal pellets that were not collected as intended but remained inside the cage. This phenomenon could potentially give some false high values for expired volatiles and absorption due to partitioning from the faecal matter into the air. The entire radioactivity in the expired volatiles was attributed to parent D6. Metabolic profile evaluation of urine and faeces showed that the entire radioactivity in the urine consisted of polar metabolites, whereas in the faeces the majority was parent D6 with a trace non-polar metabolite.

 

A well conducted guideline in vitro study (Dow Corning Corporation, 2003) found no penetration by D6 through samples of human skin following 24-hour semi-occluded contact. Of the applied dose, 46.4% of D6 was found on the skin; 40% was volatilised; 3% was found in the skin; virtually none (0.003%) penetrated the skin. A further wash at 24 hours indicated that D6 present in the skin did not penetrate the skin but continued to evaporate.

 

There are no data regarding the absorption of D6 following inhalation; however, inhalation is likely to be a minor route of exposure due to the low vapour pressure (4.7 Pa at 25°C) of D6. This highly lipophilic substance (log Kow= 8.87) might be taken up by micellar solubilisation, particularly as it has poor water solubility (0.005 mg/l). Based on the available sub-acute and sub-chronic toxicity studies for D6, it can be concluded that D6 has no tendency to accumulate after repeated dosing. While D6 is very lipophilic (log Kow= 8.87), it is readily eliminated by biotransformation to polar metabolites. No genotoxicity was detected in any in vitro mutagenicity tests in absence or presence of metabolising enzymes or in anyin vivo tests and no indication of the importance of the metabolism of the registered substance was obtained from these studies.Therefore, it can be concluded that D6 has low bioaccumulation potential.

 

In a single oral dose (450 mg/kg bw) KMD study conducted via gavage, administered to groups of female rabbits, absorption, metabolism, and excretion of14C-D6 was investigated (The Dow Chemical Company, 2018).The Group A rabbit was administered 12C-D6 (non-radiolabeled; cold dose) on Gestation day (GD) 19 to determine the time point for maximum concentration (Cmax) in plasma and to give preliminary information for analytical method validation. The second group of animals (Group 1, n=2) was administered 14C-D6 (radiolabeled) on GD 26 to obtain samples for the definitive portion of the study. Only one of the two rabbits was confirmed to be pregnant as the other rabbit showed no signs of implantation (received non-pregnant from the supplier). The Group 2 rabbit (received non-pregnant from the supplier) was cold-dosed with12C-D6 on GD 26. The samples collected from this animal were stored as contingency samples, but were not analysed.

D6 derived-radioactivity was: 1) slowly absorbed and Cmax was at 48 hours (last blood collection), 2) metabolised (based on comparison of 14C-activity and parent plasma AUCs and 2% of the dose in urine) and 3) eliminated in the feces with 56% of the administered dose recovered within 48 hours post-dosing. Absorption and elimination rates could not be calculated from this study and plasma profiling of metabolites was not possible due to low levels of radioactivity in plasma samples.