Chlorpyrifos: Pharmacokinetics in human volunteers

Biomonitoring and whole body cotton dosimetry to estimate potential human dermal exposure to semivolatile chemicals

“…On the day following exposure, 11 of 21 exceeded the 100th percentile, dropping back to 8 of 21 on the third day following exposure. This pattern of maximum excretion at 24 ± 48 h following exposure was also observed with human volunteers in the dermal pharmacokinetic study conducted by Nolan et al ( 1984 ) . None of the individuals that wore WBD during exposure exceeded the Hill et al ( 1995 ) 100th percentile on any day of the study.…”

“…Adjusting AD for the 25% of skin covered by the swimsuit and assuming uniform dermal distribution of dose, the whole body estimate was increased to 3.3 3.3 g/ kg. An additional adjustment that could be rationalized to account for the recovery of CP equivalents in urine (70% of an oral dose ) was not applied because of the substantially higher dosages (about 400 and 4000 g/cm 2 ) and route of exposure ( oral ) used by Nolan et al (1984 ). If that adjustment was made and an additional modification was made for the fact that 60% of the absorbed dose would be recovered after 3 days in urine (clearance t 1 / 2 =27 h ), the final adjusted AD would be about 8 g CP equivalents /kg.…”

“…Chlorpyrifos (CP ), a well -studied organophosphate insecticide of moderate mammalian toxicity, was selected for this study, since its principal metabolite, 3,5,6 -trichloro -2 -pyridinol ( TCP ) , is stable, readily cleared in urine ( t 1 / 2 = 27 h ) after oral and dermal doses, and its general pharmacokinetics have been studied in humans ( Nolan et al, 1984 ). Dermal absorption of 9.6% per 24 h is assigned based upon review of studies submitted by the registrant ( Nolan et al, 1984 ), other human studies ( Feldman and Maibach, 1974 ) , and U.S. EPA guidelines ( Zendzian, 1989 ) .…”

“…Dermal absorption of 9.6% per 24 h is assigned based upon review of studies submitted by the registrant ( Nolan et al, 1984 ), other human studies ( Feldman and Maibach, 1974 ) , and U.S. EPA guidelines ( Zendzian, 1989 ) . These factors and regulatory considerations, particularly the excessive dermal dose ( 400 to 4000 g/cm 2 ) relative to expected dermal loading (10 g/cm 2 ), are the basis of the 9.6% 24 -h dermal absorption estimate as summarized by Thongsinthusak ( 1991 ) .…”

Design strategy for assessing multi-pathway exposure for children: the Minnesota Children's Pesticide Exposure Study (MNCPES)

“…A complementary approach to testing the primary hypotheses involves adapting pharmacokinetic models developed for adults ( e.g., predict oral and dermal dose of chlorpyrifos and TCPy ) to assess children's pesticide exposure and absorbed dose (Nolan et al, 1984 ). The Diet Diary and food residue measurements will be used to determine the amount and timing of dietary exposures and to estimate ranges of expected urinary metabolite concentrations.…”