title: Percutaneous absorption of 14C-labelled 2-chlorobenzaldehyde in rats. Metabolism and toxicokinetics.
abstract: 2-Chlorobenzaldehyde might be produced when a moist skin is exposed to the riot control agent CS. CS-hydrolysis to 2-chlorobenzaldehyde and malononitrile occurs both in vitro and in vivo. No quantitative data have thus far been reported with respect to the percutaneous absorption and the cutaneous biotransformation of 2-chlorobenzaldehyde. Percutaneous absorption, biotransformation and elimination of 14-C-labelled 2-chlorobenzaldehyde was investigated in the rat. Following IV (25 microliters/kg) and IP (37.5 microliters/kg) 14C-2-chlorobenzaldehyde administration to rats, the plasma radioactivity declined rapidly over a 24 h period with similar plasma radioactivity-time profiles. Following cutaneous administration (75 microliters/kg) in a closed glass-cup on the skin a slow skin penetration occurred as indicated by plasma radioactivity levels. A slow increase in plasma radioactivity was followed by a slow decline of radioactivity in plasma over a 3-day period. Most of the radioactivity was found in the urine with low levels in faeces and exhaled air. The cutaneously administered radioactivity was also partly recovered from the glass-cup. For the qualitative and quantitative determination of metabolites in urine, a thin layer chromatography-radioautography method was used. The metabolic patterns of urinary excreted metabolites following cutaneous application and systemic administration of 14C-2-chlorobenzaldehyde to rats were very similar. No parent compound was recovered from the rat urine. 2-Chlorohippuric acid was the principal urinary metabolite. Quantitatively, the urinary excretion of 14C-2-chlorobenzyl alcohol following cutaneous application differed substantially from that after the systemic administration. There was no evidence of storage in the skin or skin toxicity of 2-chlorobenzaldehyde following cutaneous application.
authors.affiliation: Department of Pharmacology, Catholic University of Nijmegen, The Netherlands.
authors.forename: E C
authors.initials: EC
authors.lastname: Rietveld
authors.forename: R M
authors.initials: RM
authors.lastname: Hoet
authors.forename: F
authors.initials: F
authors.lastname: Seutter-Berlage
authors.forename: J M
authors.initials: JM
authors.lastname: Van Rossum
mesh_terms: D000818:Animals; D001547:Benzaldehydes / Q000493:pharmacokinetics*; D001711:Biotransformation; D002250:Carbon Radioisotopes; D002855:Chromatography, Thin Layer; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption
chemical_list: D001547:Benzaldehydes; D002250:Carbon Radioisotopes; C059341:2-chlorobenzaldehyde