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Biological monitoring for pesticide exposure —the role of human volunteer studies

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Summary

Predictions of human pesticide metabolism which are needed for the interpretation of biological monitoring data are frequently made from animal studies. Consequently, assumptions have to be made about the relationship between absorbed dose and metabolite excretion. The results from two human volunteer studies highlight the problems associated with extrapolating from animal studies in this way. The pyrethroid insecticide cypermethrin shows markedly different metabolite patterns when administered orally or dermally in man. Following dermal dosing the ratio of translcis cyclopropane acids is approximately 1:1, compared to 2:1 after oral administration. The ratio of total cyclopropane acids to phenoxybenzoic acids also differs depending on the route (dermal 1:4, oral 1:0.8). A knowledge of human metabolism by these two routes enables a much more meaningful interpretation of biological monitoring measurements. The herbicide molinate forms a mercapturate conjugate as a major urinary metabolite in the rat (35%). In volunteers at low dose levels this metabolite is present at insignificant levels (<1%) and 4-hydroxymolinate is a much more abundant metabolite (39%). This shows that extrapolation between species can be very misleading. It is concluded that the benefits of using human volunteers for metabolism studies at low doses far outweigh the minimal risks involved. As a basis for biological monitoring such studies can lead to a greatly improved risk assessment for pesticides in use.

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References

  • Carmichael NG, Nolan RJ, Perkins JM, Davies R, Warrington SJ (1989) Oral and dermal pharmacokinetics of triclopyr in human volunteers. Human Toxicol 8: 431–437

    Google Scholar 

  • CPMP Working Party on Efficacy of Medicinal Products (1990) EEC Note for Guidance: Good Clinical Practice for trials on medicinal products in the European Community. Pharmacol Toxicol 67: 361–372

    Google Scholar 

  • De Baun J, Bova DL Tseng CK, Menn JJ (1978) Metabolism of [ring 14C] Ordram (molinate) in the rat. 2. Urinary metabolites. J Agric Food Chem 26: 1098–1104

    PubMed  Google Scholar 

  • Eadsforth CV, Bragt PC, Van Sittert NJ (1988) Human dose excretion studies with cypermethrin and alphacypermethrin: relevance to biological monitoring. Xenobiotica 18: 603–61

    PubMed  Google Scholar 

  • Harris SA, Solomon KR (1992) Percutaneous penetration of 2,4 dichlorophenoxyacetic acid and 2,4-D dimethylamine salt in human volunteers. J Toxicol Environ Health 36: 233–2540

    PubMed  Google Scholar 

  • Hayes WJ (1983) Ethical considerations involving studies of pesticides and other xenobiotics in man. In: Miyamoto J (ed) IUPAC Pesticide chemistry: Human welfare and environment. Volume 3. Mode of action, metabolism and toxicity. Pergamon, London, pp 387–394

    Google Scholar 

  • Meuling WJA, Bragt PC, Leenheers LH, Kort WLAM de (1992) Dose excretion studies with the pesticide propoxur in volunteers. In: Scott RC, Guy RH, Hadgraft J, Boddé HE (eds) Prediction of percutaneous penetration, volume 2. IBC Technical Services, London, pp 13–19

    Google Scholar 

  • Miyamoto J, Kaneko H, Hutson DH, Esser HO, Gorbach S, Dom E (1988) IUPAC. Pesticide metabolism: Extrapolation from animals to man. Blackwell Scientific Publications, London

    Google Scholar 

  • Moody RP, Wester RC, Melandres JL, Maibach HI (1992) Dermal absorption of the phenoxy herbicide 2,41) Dimethylamine in humans: Effect of DEET and anatomic site. J Toxicol Environ Health 36: 241–250

    PubMed  Google Scholar 

  • Nolan RJ, Rick DL Freshour NL Saunders JH (1984a) Chlorpyrifos: Pharmacokinetics in human volunteers. Toxicol Appl Pharmacol 73:8–15

    Article  PubMed  Google Scholar 

  • Nolan RJ, Freshour NL Kastl PE, Saunders JH (1984b) Pharmacokinetics of picloram in male volunteers. Toxicol Appl Pharmacol 76: 264–269

    Article  PubMed  Google Scholar 

  • Ramsey JD, Woollen BH, Auton TR, Batten PL, Leeser JE (1992) Pharmacokinetics of fluazifop-butyl in human volunteers:II. Dermal dosing. Human Exp Toxicol 11: 247–254

    Google Scholar 

  • Woollen BH, Hart TB, Batten PL Laird WJD, Davies DS, Dollery CT (1991) Oral pharmacokinetics of fluazifop-butyl in human volunteers. Human Exp Toxicol 10: 39–43

    Google Scholar 

  • Woollen BH, Marsh JR., Laird WJD, Leeser JE (1992) The metabolism of cypennethrin in man: differences in metabolite profiles following oral and dermal administration. Xenobiotica 22: 983–993

    PubMed  Google Scholar 

  • World Medical Assembly (1964) Declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. Adopted by the 18th World Medical Assembly, Helsinki, Finland June 1964, amended by the 29th World Medical Assembly, Tokyo, Japan, October 1975, the 35th World Medical Assembly, Venice, Italy, October 1983, and the 41st World Medical Assembly, Hong Kong, September 1989

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Wilkes, M.F., Woollen, B.H., Marsh, J.R. et al. Biological monitoring for pesticide exposure —the role of human volunteer studies. Int. Arch Occup Environ Heath 65 (Suppl 1), S189–S192 (1993). https://doi.org/10.1007/BF00381338

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