The passage of trimethylamine across rat and human skin.
Trimethylamine is a volatile low molecular weight tertiary aliphatic amine that has known toxicity and the potential for human exposure from industrial and environmental sources is considerable. It is generally believed that absorption across the skin is an unimportant route of entry but there is little, if any, supporting evidence for this assumption. Passage across rat and human skin has been investigated employing excised skin circles in an in vitro diffusion cell apparatus. Trimethylamine was found to penetrate readily when applied to the epidermal surface of skin at three different dose levels (0.1, 1.0 and 10 mg per skin membrane 0.32 cm2). The apparent dermal flux was calculated as 3.40 +/- 1.60, 58.3 +/- 30.6 and 265.0 +/- 155.0 microg/cm2/h for rat and 0.98 +/- 0.75, 9.21 +/- 3.06 and 92.7 +/- 31.9 microg/cm2/h for human at the three dose levels, respectively. Both rat and human skin was able to act as a reservoir, with the trimethylamine not remaining in the stratum corneum but passing through. When presented to the underneath of rat and human skin circles, both [U-14C]-trimethylamine and [U-14C]-trimethylamine N-oxide were able to pass from the dermis to the epidermis. Small but detectable amounts of trimethylamine were oxidised to its N-oxide during passage through the skin.
Kenyon
S
S
Biological Chemistry, Division of Biomedical Sciences, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, UK.
Carmichael
P L
PL
Khalaque
S
S
Panchal
S
S
Waring
R
R
Harris
R
R
Smith
R L
RL
Mitchell
S C
SC
D000818:Animals; D020405:Dermis / Q000378:metabolism; D015194:Diffusion Chambers, Culture; D004817:Epidermis / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008744:Methylamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption
D008744:Methylamines; C023336:trimethylamine