IN-VITRO DERMAL ABSORPTION OF PESTICIDES .6. IN-VIVO AND IN-VITRO COMPARISON OF THE ORGANOCHLORINE INSECTICIDE DDT IN RAT, GUINEA-PIG, PIG,HUMAN AND TISSUE-CULTURED SKIN

In vitro dermal absorption tests were conducted with the C-14-ring-lab elled pesticide, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) d issolved in acetone and applied to dermatomed skin (0.5 mm) of a numbe r of species at dose rates of 16-27 mu g/cm(2). Skin absorption was de termined for 48 hr after exposure using in vitro Row-through cells. Sk in absorption was calculated from the sum of the percentage recovery o f C-14 activity in the receiver solution added to the percentage recov ery for the methanol washes of the skin at 48 hr and the skin digest s amples. Two receiver solutions, Ringer's saline (used with Moody alumi nium cells), and Hanks' HEPES buffered saline with 4% serum albumin (u sed with Bronaugh Row-through cells) were used. Listed in decreasing o rder, the total percentage in vitro dermal absorptions obtained by 48 hr after exposure for the five skin types were: 42 +/- 2.6% [hairless guinea pig: Hanks' receiver (HR)], 34 +/- 10.5% (rat; HR), 28 +/- 13.2 % [Testskin; Ringer's receiver (RR)], 28 +/- 2.9% (human; HR), 22 +/- 3.3% (Testskin; HR), 18 +/- 6.2% (pig; RR) and 14 +/- 2.1% (pig; HR). The percentage C-14 activity recovered in soapy water rinses of the sk in specimens at 24 hr, and for methanol skin washes and skin digests a t 48 hr, and of C-14-labelled volatiles collected in air traps are rep orted. Data obtained with pig and Testskin for DDT using the Moody flo w-through permeation cell was compared with that obtained using the Br onaugh cell. Significantly greater (P < 0.05) percentage recovery was obtained for the soap washes at 24 hr of the skin following the Bronau gh procedure than was obtained with the Moody method. Comparative in v ivo studies demonstrated urinary recovery was 2 +/- 0.5 and 15 +/- 1.7 % for rats (dose rate; 6 mu g/cm(2)) and guinea pigs (dose rate: 9 mu g/cm(2)), respectively. Total faecal recovery was 20 +/- 1.9 and 44 +/ - 2.75% for rats and guinea pigs, respectively. Analysis of tissue tak en at autopsy 14 days after dosing demonstrated total tissue recovery of 51 +/- 5.6% in rats but of only 3 +/- 0.7% in guinea pigs. Includin g the C-14 activity extracted from the skin removed from the dose site at 14 days after exposure, the total recovery of dermally absorbed re sidues was 73 +/- 5.9 and 62 +/- 4.1% for rats and guinea pigs, respec tively. Recovery of C-14 from soapy water skin washes conducted at 24 hr after exposure was 3 +/- 1.4 and 14 +/- 1.8% for rats and guinea pi gs, respectively, and this was significantly less than that obtained b y both the Bronaugh and Moody in vitro procedures. Skin patch recovery was 24% for both rats and guinea pigs. In summary, the in vitro data underestimed the degree of dermal absorption observed in vivo for both rats and guinea pigs, and this was thought to be due to an overly vig orous removal of the pesticide skin deposit by the soap washing proced ures used in vitro in comparison with the in rico washing procedure.