Alkanes, C10-13, chloro

Endpoint summary

Additional information

No studies have attempted to identify metabolites of SCCPs, although cytochrome P450 oxidation to CO2 has been demonstrated (cited in EU, 2000).

Oral absoprtion, excretion and distribution

In a good quality study, the tissue distribution and excretion of three C12 chlorinated paraffins, labelled with 14C in the terminal carbon atom, has been investigated in pregnant and non-pregnant female C57Bl mice following intravenous and gavage administration. Animals were given a single dose of either a monochlorinated dodecane (MCDD; 17.4% chlorinated), a polychlorinated dodecane (PCDD I; 55.9% chlorinated) or a second polychlorinated dodecane (PCDD II; 68.5% chlorinated) and the results compared with animals given the non-chlorinated analogue, 14C-labelled lauric acid. Tissue distribution was assessed qualitatively by autoradiography at between 1 h and 60 days post injection and excretion was followed by collecting urine, faeces and expired 14CO2 up to 12 h post administration (injection and oral dosing). In addition, the nature of the radioactivity present in liver and white fat after the oral administration of PCDD I and PCDD II was examined chemically. At early times after iv injection (up to 24 h), radioactivity was detected in liver, white fat and in tissues with a high metabolic activity/high cell turnover (e.g. intestinal mucosa, bone marrow, salivary glands and thymus). The accumulation was most pronounced for lauric acid and MCDD and least for PCDD II. Radioactivity was seen in urine and bile of all chlorododecane-treated animals but not in animals given lauric acid. At longer times (up to 30 days), activity was still prominent in liver, white fat, bile and urine and, except for PCDD II-treated animals, in the adrenal cortex and gonads. At 30 to 60 days post injection, radioactivity was still present in liver and white fat of chlorododecane-treated animals, but not in the fat of lauric acid treated mice. At this time, radioactivity was also seen in the central nervous system after all treatments except PCDD II. At 24 h after oral dosing, the distribution pattern of radioactivity was similar to that after iv injection. Autoradiograms from late-gestation pregnant females showed evidence for transplacental transfer of radioactivity with all treatments, the distribution within foetuses being similar to that in adult animals. The extent of labelling was greatest with MCDD and lauric acid, and weakest with PCDD II. A proportion of the radioactivity retained in the liver and fat 30 days after oral administration of the polychlorinated paraffins was heptane-extractable and probably represents unmetabolised parent compound. In fat from PCDD I-treated mice, 24% of the retained activity was heptane-extractable, whereas in PCDD II-treated animals 78% was extractable. About 32 and 21% of the administered dose of PCDD I was recovered in the urine and 14CO2, respectively, of mice in the 12 h post intravenous administration, and about 33 and 29% following oral administration (for the corresponding values). This compares with only about 8% as 14CO2 and 4 to 5% in urine for PCDD II. Recovery in faeces at 12 h post-dosing amounted to about 4 and 5% for PCDD I after iv and oral dosing, respectively, whereas for PCDD II the corresponding values were 9 and 21%, respectively. Mice treated with MCDD intravenously excreted 52% of the dose as 14CO2, 18% in urine and 3% in faeces; the corresponding values for lauric acid-treated animals being 71, 2 and 0.2%, respectively. Overall, this study suggests that significant absorption (possibly about 80 and 90% of the administered dose of PCDD II and PCDD I, respectively) can occurr within 12 h following single oral administration (Darnerud et al. 1982). A figure of 80% will be taken forward to the risk characterisation for oral absorption.

The kinetics of absorption, tissue distribution and excretion of a C10-12 chlorinated paraffin (59% chlorination) in male and female F344 rats, assessed using 14C-labelled material, was essentially linear over the dose range 10-625 mg/kg bw following gavage administration, and was unaffected by pretreatment of the animals with the SCCP for 13 weeks in the diet. The principal route of elimination was in faeces with only trace amounts expired as 14CO2. Tissue levels of radioactivity were highest in liver, kidney, gonads and fat initially, tending to be greater in naive animals. The overall elimination rate from adipose tissue was 'somewhat' lower than from other tissues (IRDC, 1984a).

Dermal absorption

The absorption rate of Cereclor 56L, a C10-13 chlorinated paraffin (56% chlorinated), through human epidermal membrane in vitro, assessed using the 14C-labelled analogue, chlorinated n-undecane (58% chlorinated) as a marker, was approximatley 0.04 µg/cm2/h. Thus, less than 0.01% of the applied dose was absorbed during the 54 hours continuous skin contact, demonstrating extremely poor dermal absorption (Scott, 1985). A value of 0.01% will be taken forward to the risk caharacterisation for dermal absorption.