Skin-bound residues

Signihcant Residues Associated with Protective Device 327 Signihcant Quantity of Residues Remaining Bound to the Skin 327 USE OF DATA 330 General Considerations 330 Tiered Approach 330 Tier 1 331 Tier 2 331 Tier 3 332... 

SIGNIFICANT QUANTITY OF RESIDUES REMAINING BOUND TO THE SKIN... 

Finally, although compounds with a high Kqw (i e. a high solubility in octanol relative to the solubility in water) may remain in the lipid layer of the skin (stratum comeum) and not become absorbed systemically, insufficient documentation exists to support exclusion of skin-bound residues from estimates of dermal absorption, based on the X ow of the test material alone. 

In search of possible reservoirs of flumequine and oxolinic acid in fish, several tissues of salmon treated with the drugs were analyzed (169). The results showed that residues of these drugs were present in the fish tissues for prolonged periods after the end of treatment. It was found, however, that even when residues in muscle and liver were at the low ppb level, there were still quite high residues left in bone and skin. Residues of oxolinic acid were especially bound to bone and skin, whereas flumequine was bound to bone. 

The use of sulfur mustard as a vesicant CW agent implies that proteins of the skin are a primary target. It was found that upon exposure of human callus to [14C]sulfur mustard, a significant part of the radioactivity was covalently bound to keratin (30). Most of the radioactivity (80%) bound to keratin could be removed by treatment with alkali, indicating the presence of adducts to glutamic and/or aspartic acid residues. 

When significant quantities of residues remain at the skin site, the conventional approach is to include these residues in the percentage of absorbed dose. Eor instance, as part of the North American Free Trade Agreement (NAFTA) Technical Working Group on Pesticides, there was agreement that bound skin residues are considered absorbed when the bioavailability of residues cannot be determined (NAFTA, 2000). This approach is considered conservative as it is unlikely that all... 

Table 9.1 Comparison of the percentage of dermal absorption - with and without direct addition of bound skin residues (from Thongsinthusak et al, 1999). Reprinted from Reg. Toxicol. Pharmacol, 29, T. Thongsinthusak, J.H. Ross, S.G. Saiz and R.I. Krieger, Estimation of dermal absorption using the exponential saturation model , pp. 37-43, Copyright (1999), with permission from Elsevier... 

CW/CW, cage wash/cage wipe BSR, bound skin residue DA, dermal absorption N/D, no data available. 

The skin is a primary target of sulphur mustard. Exposure of human callus to 14C-sulphur mustard showed that a significant part (15-20%) of the radioactivity was covalently bound to keratin (Van der Schans, G.P. et al., 2003). Approximately 80% of the bound radioactivity could be released by alkaline hydrolysis, indicating it to be bound as esters of glutamic and aspartic acid residues. 

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