STP989

    Dose Response of Skin Absorption in Young and Adult Rats

    Published: Jan 1988


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    Abstract

    The effect of skin dosage on percutaneous absorption was determined in young and adult rats using 14 pesticidal chemicals. Young (33-day old) and adult (82-day old) female Fischer 344 rats, with previously clipped mid-dorsal skin, were treated with three dosages of labeled pesticides in acetone and sacrificed 72 h following application. The treated area was 2.3% of the body surface area and was protected by a perforated plastic blister. Skin penetration was determined by dividing the radioactivity in the body plus excreta by the total radioactivity recovered. The dosages used were 0.02 to 0.35, 0.54, and 2.68 µmol/cm2 for the low, medium, and high dosage levels, respectively.

    Skin penetration of the pesticides in young animals ranged from 2.9 to 81.5%, 2.0 to 84.4%, and 0.9 to 90.1% at the low, medium, and high dosage levels, respectively. In the adult, it ranged from 7.7 to 86.4%, 2.7 to 90.5%, and 1.0 to 93.3% at the low, medium, and high dosage levels, respectively.

    Chlorpyrifos, dinoseb, mono- and disodium methanearsonate did not show a significant effect of dosage on dermal penetration. Dinoseb, mono- and disodium methanearsonate displayed constant fractional penetration in both young and adult animals over the dosage range examined. The other compounds showed dose-dependent dermal absorption although the total amount absorbed usually increased with dose. Dose-response curves for young and adult animals were not parallel in 8 of the 14 pesticides studied.

    Eleven of the 14 pesticides showed significant age-dependent differences in skin penetration. Four of these eleven compounds had greater absorption in the young than adult at some dose. The highest and lowest significant young/adult penetration ratios were 1.53 and 0.19, respectively.

    In summary, dermal absorption of the majority of the pesticides studied was found to be dependent on dose and age of the animal. With this heterogeneous group of chemicals, the correlation between skin penetration and octanol/water partition coefficients was marginal. Stratum corneum thickness did not appear to be a factor in the penetration differences between young and adult.

    Keywords:

    protective clothing, pesticides, skin, dose, absorption, rats, age


    Author Information:

    Hall, LL
    Toxicologist, biophysicist, and toxicologist, Perinatal Toxicology Branch, Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park,

    Fisher, HL
    Toxicologist, biophysicist, and toxicologist, Perinatal Toxicology Branch, Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park,

    Sumler, MR
    Scientist and toxicologist, Northrop Services Inc., Environmental Sciences, Research Triangle Park, NC

    Monroe, RJ
    Emeritus professor, North Carolina State University, Raleigh, NC

    Chernoff, N
    Toxicologist, biophysicist, and toxicologist, Perinatal Toxicology Branch, Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park,

    Shah, PV
    Scientist and toxicologist, Northrop Services Inc., Environmental Sciences, Research Triangle Park, NC


    Paper ID: STP26284S

    Committee/Subcommittee: F23.96

    DOI: 10.1520/STP26284S


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