Automated In Vitro Dermal Absorption (AIVDA): predicting skin permeation of atrazine with finite and infinite (swimming/bathing) exposure models.

The Automated In Vitro Dermal Absorption (AIVDA) HPLC method developed in our laboratory for finite dose tests was developed further for infinite dose swimming/bathing exposure tests and for monitoring skin viability during the permeation assay. Skin absorption of the herbicide atrazine was tested under both finite and infinite dose conditions and the data compared to that obtained using the Bronaugh flow-through cell. Confirmation that skin viability was maintained throughout the AIVDA 24-hr infinite dose tests without phenol was obtained using a novel Radio-HPLC method that was developed to monitor glycolytic 14C-lactic acid formation in 14C-glucose spiked receiver solution. Advantages of the AIVDA method (e.g. rapid, sensitive, versatile, cost-effective analysis) together with its disadvantages (e.g. need for manual dexterity, lack of receiver albumin, compound retention time, limit of sampling interval) are discussed.

In vitro dermal absorption of two commercial formulations of 2,4-dichlorophenoxyacetic acid dimethylamine (2,4-D amine) in rat, guinea pig and human skin.

In vitro dermal absorption studies with rat, hairless guinea pig and human skin were conducted employing Bronaugh flow-through cells for two commercial formulations of the herbicide, 2,4-dichlorophenoxyacetic acid dimethyl amine (2,4-D amine) and in vivo studies were conducted with rats. The Clean Crop (CC) and Wilbur-Ellis (WE) 2,4-D amine formulations gave similar absorption values, ranging from 21 to 30% in vitro in all three species, except for absorption from WE in guinea pig skin [16 +/- 4.7% (n = 4)], which was significantly less (Student's t-test; P < 0.05) than absorption from WE formulation for human skin [28 +/- 2.6% (n = 4)]. A profound 'washing-in' effect of the soap wash conducted at 24 hr post-treatment was observed for all three species in vitro, and this effect was much more pronounced than in previous studies with 2,4-D where more dilute topical doses were employed. Dermal absorption of both 2,4-D amine formulations was significantly less for rats tested in vivo (16-17%) than for the skin from the same rats tested in vitro (26-30%). The lower percentage absorption observed in vivo was thought to be due to 'rub-off' of the dose application, as 68-78% of the dose was detected in the foam rubber patches used to protect the dose site. The inability to demonstrate greater permeability of animal skin to skin from the one human subject tested, the observation of a soap 'washing-in' effect, and the apparent overprediction of field exposure by both the in vivo and in vitro data were all factors considered to have important implications for accurate assessment of occupational exposure to 2,4-D.

Dermal exposure to environmental contaminants in the Great Lakes.

This paper reviews the literature to determine the importance of the dermal route of exposure for swimmers and bathers using Great Lakes waters and summarizes the chemical water contaminants of concern in the Great Lakes along with relevant dermal absorption data. We detail in vivo and in vitro methods of quantifying the degree of dermal absorption and discuss a preference for infinite dose data as opposed to finite dose data. The basic mechanisms of the dermal absorption process, routes of chemical entry, and the environmental and physiological factors affecting this process are also reviewed, and we discuss the concepts of surface slick exposure to lipophilic compounds and the adsorption of contaminants to water sediment. After presenting mathematical constructs for calculating the degree of exposure, we present in vitro data concerning skin absorption of polyaromatic hydrocarbons adsorbed to Great Lakes water sediment to show that in a worst-case scenario exposure via the dermal route can be equally important to the oral route. We have concluded that prolonged exposure of the skin, especially under conditions that may enhance dermal absorption (e.g., sunburn) may result in toxicologically significant amounts of certain water contaminants being absorbed. It is recommended that swimming should be confined to public beaches, people should refrain from swimming if they are sunburned, and skin should be washed with soap as soon as possible following exposure. Future studies should be conducted to investigate the importance of the dermal exposure route to swimmers and bathers.

In vivo and in vitro dermal absorption of benzo[a]pyrene in rat, guinea pig, human and tissue-cultured skin.

Cross-species in vitro dermal absorption tests were conducted with 14C-labelled benzo[a]pyrene dissolved in acetone and applied to dermatomed skin (0.5 mm thickness) at comparable dose rates (8-13 micrograms/cm2). Skin absorption was determined using the Bronaugh in vitro flow-through procedure. The percentage (%) dermal absorption included the % 14C-activity detected persisting in the skin added to that detected in the receiver solution. Listed in decreasing order, total % in vitro dermal absorption obtained by 48 h postexposure was: 95 +/- 9.6% (rat), 51 +/- 3.0% (hairless guinea pig), 43 +/- 8.7% (human; 50-year-old), 34 +/- 12.4% (Testskin) and 23 +/- 5.3% (human; 32-year-old). Comparative in vivo studies demonstrated urinary recovery of 8 +/- 1.8% and 25 +/- 5.0% for rats (dose rate: 6 micrograms/cm2) and hairless guinea pigs (dose rate: 9 micrograms/cm2), respectively. Total faecal recovery was 61 +/- 6.0% and 43 +/- 6.1% for rats and guinea pigs, respectively. Necropsies conducted at 14 days postexposure demonstrated total 14C-activity tissue recoveries of 0.5 +/- 0.13% and 0.6 +/- 0.17% in rats and guinea pigs, respectively. Including the 14C-activity extracted from the skin removed from the dose site at 14 days postexposure, the total % in vivo dermal absorbtion was 70 +/- 7.6% and 68 +/- 9.3% for rats and guinea pigs, respectively. In summary, the in vitro data was consistent with the in vivo data in demonstrating that 14C-benzo[a]pyrene was well absorbed through skin.

In vitro dermal absorption of pesticides: IV. In vivo and in vitro comparison with the organophosphorus insecticide diazinon in rat, guinea pig, pig, human and tissue-cultured skin.

In vitro skin absorption tests are currently being developed as an alternative to in vivo animal tests for predicting the degree of occupational exposure to pesticides. In the study reported here, in vitro percutaneous absorption tests were conducted with the (14)C-ring-labelled pesticide, diazinon, dissolved in acetone and applied to the dermatomed skin (0.5 mm) of a number of species at a dose rate of 9.5-16.7 mug/cm(2). Skin permeation was determined for 48 hr after exposure using an in vitro flow-through system. Skin permeation was calculated from the sum of the percentage recovery of (14)C activity in the receiver solution and the percentage recovery obtained in methanol washes of the skin at 48 hr and in skin digests. Listed in decreasing order, the total percentage in vitro dermal absorptions (mean +/- SD) obtained by 48 hr after exposure for the five skin types were: 47 +/- 3.4% (rat), 36 +/- 0.9% (tissue cultured Testskin), 33 +/- 2.8% (hairless guinea pig), 20 +/- 3.1% (human) and 15 +/- 13.1% (pig). The percentage recoveries in soapy water skin washes at 24 hr, in methanol washes and skin digests at 48 hr and of (14)C-labelled volatiles collected in air traps at 48 hr after exposure are reported. Comparative in vivo studies demonstrated 37 +/- 0.8 and 24 +/- 5.7% recovery of (14)C in the urine of rats (dose rate, 6 mug/cm(2)) and hairless guinea pigs (dose rate, 5 mug/cm(2)), respectively, by 14 days after exposure. Total faecal recovery 14 days after exposure was 18 +/- 0.4 and 4 +/- 0.9% for rats and guinea pigs, respectively. Analysis of tissue taken at autopsy 14 days after exposure demonstrated a total tissue recovery of 0.6 +/- 0.1% [(14)C]diazinon in rats and 1 +/- 0.2% in hairless guinea pigs. The total recovery in skin removed from the dose site at 14 days after exposure was 0.2 +/- 0.02% and 0.1 +/- 0.05% in rats and hairless guinea pigs, respectively. Recovery of radioactivity from soapy water skin washes conducted at 24 hr after exposure was 21 +/- 3.8% for rats and 2 +/- 0.1% for hairless guinea pigs. Recovery in skin patches was 23 +/- 5.4% and 73 +/- 2.9% in rats and hairless guinea pigs, respectively. The in vitro data for dermal absorption of [(14)C]diazinon for rats (47 +/- 3.4%) and hairless guinea pigs (33 +/- 2.8%) were in good agreement with the data observed for rats (56 +/- 1.03%) and hairless guinea pigs (28 +/- 6.0%) in vivo. This study supported the use of in vitro skin absorption tests as an alternative to in vivo animal testing.

In vitro dermal absorption of pesticides: VI. 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 (14)C-ring-labelled pesticide, 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) dissolved in acetone and applied to dermatomed skin (0.5 mm) of a number of species at dose rates of 16-27 mug/cm(2). Skin absorption was determined for 48 hr after exposure using in vitro flow-through cells. Skin absorption was calculated from the sum of the percentage recovery of (14)C activity in the receiver solution added to the percentage recovery for the methanol washes of the skin at 48 hr and the skin digest samples. Two receiver solutions, Ringer's saline (used with Moody aluminium cells), and Hanks' HEPES buffered saline with 4% serum albumin (used with Bronaugh flow-through cells) were used. Listed in decreasing order, 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 (14)C activity recovered in soapy water rinses of the skin specimens at 24 hr, and for methanol skin washes and skin digests at 48 hr, and of (14)C-labelled volatiles collected in air traps are reported. Data obtained with pig and Testskin for DDT using the Moody flow-through permeation cell was compared with that obtained using the Bronaugh cell. Significantly greater (P < 0.05) percentage recovery was obtained for the soap washes at 24 hr of the skin following the Bronaugh procedure than was obtained with the Moody method. Comparative in vivo studies demonstrated urinary recovery was 2 +/- 0.5 and 15 +/- 1.7% for rats (dose rate; 6 mug/cm(2)) and guinea pigs (dose rate: 9 mug/cm(2)), respectively. Total faecal recovery was 20 +/- 1.9 and 44 +/- 2.75% for rats and guinea pigs, respectively. Analysis of tissue taken 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. Including the (14)C activity extracted from the skin removed from the dose site at 14 days after exposure, the total recovery of dermally absorbed residues was 73 +/- 5.9 and 62 +/- 4.1% for rats and guinea pigs, respectively. Recovery of (14)C from soapy water skin washes conducted at 24 hr after exposure was 3 +/- 1.4 and 14 +/- 1.8% for rats and guinea pigs, respectively, and this was significantly less than that obtained by 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 vigorous removal of the pesticide skin deposit by the soap washing procedures used in vitro in comparison with the in vivo washing procedure.

In vitro dermal absorption of pesticides: V. In vivo and in vitro comparison of the herbicide 2,4-dichlorophenoxyacetic acid in rat, guinea pig, pig, human and tissue-cultured skin.

In vitro dermal absorption tests were conducted with the (14)C-ring-labelled herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), dissolved in acetone and applied to dermatomed skin (0.5 mm) of a number of species at dose rates of 7-8 mug/cm(2). Skin absorption was determined for 48 hr after exposure using an in vitro flow-through system. Skin absorption was calculated from the sum of the percentage recovery of (14)C activity in the receiver solution and the percentage recovery in the methanol washes of the skin at 48 hr and the skin digest samples. Two receiver solutions, Ringer's saline, and Hanks' HEPES buffered saline with 4% serum albumin were used. Listed in decreasing order, the total percentage in vitro dermal absorptions obtained by 48 hr after exposure for the five skin types were: 47 +/- 4.3% [tissue cultured Testskin; Hanks' receiver (HR)], 40 +/- 4.5% (rat; HR), 19 +/- 1.8% (human; HR), 14 +/- 2.3% (hairless guinea pig; HR), 14 +/- 8.8% (pig; Ringer's receiver). The percentage recovery of the radiolabel in soapy water skin washes at 24 hr, methanol washes and skin digests at 48 hr, and of (14)C-labelled volatiles collected in air traps at 48 hr after exposure are reported. Comparative in vivo studies were conducted for 14 days after exposure and demonstrated 32 +/- 3.9 and 28 +/- 7.8% recovery of (14)C in the urine of rats (dose rate, 3 mug/cm(2)) and guinea pigs (dose rate, 4 mug/cm(2)), respectively. Total faecal recovery was 2 +/- 0.3 and 9 +/- 3.5% for rats and guinea pigs, respectively. Analysis of tissue taken at autopsy 14 day after dosing demonstrated a total tissue recovery of (14)C activity of 1 +/- 0.1 and 2 +/- 0.5% in rats and guinea pigs, respectively. Including the (14)C activity extracted from the skin removed from the dose site at 14 days after exposure, the total recovery of dermally absorbed residues was 49 +/- 10.4 and 40 +/- 9.9% in rats and guinea pigs, respectively. Recovery of (14)C activity from soapy water skin washes conducted at 24 hr after exposure was 28 +/- 8.1 and 43 +/- 9.0% for rats and guinea pigs, respectively. Recovery in skin patches was 18% (guinea pigs) and 26% (rats). In summary, the in vitro/in vivo concordance for the rat dermal absorption data was good but the in vitro data for hairless guinea pigs underestimated the in vivo absorption, and therefore for 2,4-D, rat skin may provide a better model of percutaneous absorption.

An automated in vitro dermal absorption procedure: III. In vivo and in vitro comparison with the insect repellent N,N-diethyl-m-toluamide in mouse, rat, guinea pig, pig, human and tissue-cultured skin.

Cross-species in vitro dermal absorption tests were conducted with the (14)C-ring-labelled insect repellent, DEET (N,N-diethyl-m-toluamide), dissolved in acetone and applied to skin sections (0.5 mm) from a dermatome at a dose rate of about 30 mug/cm(2). Skin permeation was determined using an automated in vitro dermal absorption procedure, and was calculated from the percentage recovery of (14)C-activity in the receiver solution. Listed in decreasing order, the total percentage of in vitro dermal absorption obtained by 48 hr post-exposure for the six skin types (n = 4) was: 36 +/- 27.5% (rhino mouse), 28 +/- 4.2% (human), 21 +/- 2.2% (rat), 15 +/- 0.8% (pig), 13 +/- 9.6% (tissue cultured Testskin) and 11 +/- 1.4% (hairless guinea pig). Lag times for DEET in vitro dermal absorption in the six skin types ranged from 0.6 hr (human) to 1.9 hr (rat). The (14)C-activity recovered in soapy water rinses of the skin specimens at 24 hr post-exposure ranged from 4% (rat) to 18% (mouse). The percentage recovery in methanol skin washes, skin digests, and of (14)C-volatiles collected in air traps at 48 hr post-exposure are reported. The total mass balance recovery ranged from 70% (Testskin) to 93% (human). Comparative in vivo studies demonstrated 38 +/- 10.3% (n = 4) and 26 +/- 5.4% (n = 4) urinary recovery in rats and guinea pigs, respectively, by 14 days post-exposure. Total faecal percentage recovery 14 days post-exposure was 1 +/- 0.5% for rats and 3 +/- 0.8% for guinea pigs. A tissue autopsy conducted at 14 days post-exposure demonstrated a total tissue recovery of 2 +/- 0.4% (14)C-DEET in rats and 1 +/- 0.3% in guinea pigs. Total percentage recovery in skin removed from the dose site at 14 days post-exposure was 0.2 +/- 0.11% and 0.1 +/- 0.06% in rats and guinea pigs, respectively. Soapy water skin washes conducted at 24 hr post-exposure had 8 +/- 0.5% recovery for rats and 5 +/- 2.8% recovery for guinea pigs. Total mass balance recovery was 84 +/- 9.2% and 108 +/- 2.9% for rats and guinea pigs, respectively. In summary, the in vitro data underestimated the dermal absorption observed in vivo and tentative explanations for this lack of agreement are discussed.

Effect of the mosquito repellent DEET and long-wave ultraviolet radiation on permeation of the herbicide 2,4-D and the insecticide DDT in natural rubber gloves.

Studies were conducted to determine the effect of a commonly used insect repellent, DEET (N,N-diethyl-m-toluamide), on the permeability of rubber gloves used as chemical protective clothing (CPC) by pesticide applicators. Glove permeation analysis was conducted with an automated in vitro diffusion analysis (AIDA) method employing an in-house, flow-through permeation cell design. Permeation of 14C-ring-labeled 2,4-D (2,4-dichlorophenoxyacetic acid) in natural rubber glove material was 2.4 +/- 1.81% at 48 hr after treatment of the glove with 2,4-D applied with DEET; this was not significantly different (Student's t-test; p less than 0.05) from 3.2 +/- 3.46% permeation of 2,4-D observed without DEET. Similarly, there was no significant difference between the permeation of pp'-DDT (1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane) applied with DEET (11.7 +/- 5.02%) and without DEET (11.4 +/- 4.86%) to natural rubber glove material. Scanning electron microscopy of the natural rubber glove material, however, demonstrated disruption of the surface ultrastructure following a 24-hr treatment with DEET. The AIDA analysis also suggested that exposure of the glove material to long-wave ultraviolet (UVA) radiation enhanced the glove permeability to 2,4-D (6.2 +/- 0.73% [+UVA]; 0.3% +/- 0.14% [-UVA]) but had no effect on the permeation of DDT. Because the CPC of pesticide applicators is commonly exposed to solar UVA, this finding may raise concerns about the efficacy and safety of CPC in general.

Dermal absorption of the phenoxy herbicide 2,4-D dimethylamine in humans: effect of DEET and anatomic site.

Percutaneous absorption of the 14C-ring-labeled phenoxy herbicide 2,4-D-amine (2,4-dichlorophenoxyacetic acid dimethylamine) was examined following topical applications of the herbicide to the palm and forearm of human volunteers. The effect of two vehicles (water and acetone) and the mosquito repellent DEET (N,N-diethyl-m-toluamide) on dermal absorption of 2,4-D-amine also was investigated. The total percent dermal absorption was calculated from the mean percent urinary recoveries and was not corrected for nonurinary excretion. The data revealed 14 +/- 4.5% (standard deviation) and 10 +/- 11.5% palmar absorption of 2,4-D-amine applied in water, with and without DEET, respectively, and 7 +/- 6.2% and 13 +/- 5.0% forearm absorption of the herbicide applied in water or acetone, respectively. Soap-and-water skin washes conducted at 24 h posttreatment removed up to 34% of the applied dose. Successive tape strips of skin taken at 24 h posttreatment demonstrated generally decreasing herbicide levels in the outer layers. The data bring into question the complete validity of the rhesus monkey model to predict human dermal absorption.

An automated in vitro dermal absorption procedure: II. Comparative in vivo and in vitro dermal absorption of the herbicide fenoxaprop-ethyl (HOE 33171) in rats.

Dermal absorption of the (14)C-ring-labelled herbicide fenoxaprop-ethyl (FPE; ethyl 2-[4-[(6-chloro-2-benzoxazolyl)oxy]phenoxy]propanoate) was examined after topical applications of the herbicide in either acetone or in field formulation (Excel) to the shaved backs of rats (n = 6) according to our standard in vivo procedure. The total percentage dermal absorption was determined from the mean percentage recoveries of (14)C in the urine after correction for incomplete urinary excretion using the recovery figures obtained from intramuscular (im) dose studies (49 +/- 17.7% recovery). The mean percentage dermal absorption of FPE applied in acetone at a dose of 1.8 mug/cm(2) was 32 +/- 6.8% and was significantly greater than that obtained at the same dose of FPE applied in the Excel formulation (18 +/- 4.5%). Increasing the applied dose of FPE had no effect on dermal absorption within the dose-range 1.8 to 100 mug/cm(2); when doses of 10 and 100 mug/cm(2) were applied in Excel, 20 +/- 6.7% and 21 +/- 4.5% was absorbed, respectively. Mass balance studies with the total percentage recovery in urine (im-corrected) added to recovery from foam patches covering the dose site, and from gauze swabs moistened with soapy water taken of dosed skin 24 hr after treatment, demonstrated only 56 +/- 3.7%, 54 +/- 3.8%, 56 +/- 5.4% and 53 +/- 3.9% total recovery for the acetone 1.8 mug/cm(2) and Excel 1.8, 10 and 100 mug/cm(2) treatments, respectively. Significantly less residual (14)C activity was detected in the skin swabs taken for the acetone (8 +/- 3.5%) than for the Excel treatments (21 +/- 6.0%, 27 +/- 4.0% and 25 +/- 5.8% for the 1.8, 10 and 100 mug/cm(2) dose rates, respectively). Comparative studies conducted at a dose rate of 1.4 mug/cm(2) with our automated in vitro dermal absorption (AIDA) procedure demonstrated no significantly different total percentage dermal absorption in dermatomed skin taken from the same rats tested in vivo at a dose rate of 1.8 mug/cm(2). There was no significant difference between the total percentage dermal absorption obtained for AIDA analysis of fresh rat skin (27 +/- 9.3%; n = 20) compared with that for rat skin frozen for 7 days in liquid nitrogen (25 +/- 7.6%; n = 19) and the implications of this for tissue storage are discussed.

Pesticide glove permeation analysis: comparison of the ASTM F739 test method with an automated flow-through reverse-phase liquid chromatography procedure.

The results of two methods of analysis for measuring glove permeability to pesticides are reported. The standard ASTM F739-85 testing procedure was used to determine breakthrough times and permeation rates for four protective glove materials for two commercially available pesticide formulations. The same glove materials and pesticides then were tested using an in-house developed automated in-vitro diffusion analysis (AIDA) procedure. The ASTM and AIDA procedures both demonstrated no detectable breakthrough of Sevin 50W or 2,4-D Amine 96% for nitrile butyl rubber and polyvinyl chloride gloves. Although no breakthrough of Sevin 50W or 2,4-D Amine 96 was detected for natural rubber or neoprene gloves following the ASTM procedure, permeation was observed in 2 of 3 replicate tests for both rubber and neoprene gloves when using the AIDA method. The observed discrepancy may have been caused by a longer sampling duration for the AIDA method (16 hr) than the ASTM procedure (8 hr). Advantages of the AIDA procedure are discussed.

Dermal absorption of the phenoxy herbicides 2,4-D, 2,4-D amine, 2,4-D isooctyl, and 2,4,5-T in rabbits, rats, rhesus monkeys, and humans: a cross-species comparison.

Dermal absorption of the 14C-ring-labeled phenoxy herbicides 2,4-D [(2,4-dichlorophenoxy)acetic acid], 2,4-D amine (2,4-dichlorophenoxyacetic acid dimethylamine), 2,4-D isooctyl (2,4-dichlorophenoxyacetic acid isooctyl ester), and 2,4,5-T amine (2,4,5-trichlorophenoxyacetic acid trimethylamine) was examined following topical applications of the herbicides to the back of rabbits, the back and tail of rats, the forearm and forehead of rhesus monkeys, and the forehead of human volunteers. The effect of three pesticide vehicles (water, acetone, and Esteron LV96) was also investigated. The total percent dermal absorption was calculated from the mean percent urinary recoveries from the animal tests and corrected for nonurinary excretion of the radiolabel using data from intramuscular (im) injections. The human data are reported without im correction. The reliability of animal data for modelling human dermal absorption of pesticides is highlighted.

An automated in vitro dermal absorption procedure: I. Permeation of (14)C-labelled N,N-diethyl-m-toluamide through human skin and effects of short-wave ultraviolet radiation on permeation.

An automated in vitro dermal absorption (AIDA) analysis procedure is reported together with a novel design for an AIDA cell chamber for measuring the permeation of pesticides through human skin and other membranes. Tests to determine the permeation of the insect repellent N,N-diethyl-m-toluamide (DEET) through fresh, frozen and heat-separated split-thickness human breast skin demonstrated permeation of 48.0 ± 10.18, 24.0 ± 7.76 and 42.4 ± 8.57% (mean ± SD), respectively, by 48 hr. permeation through nitrile butyl rubber glove material was not detected whereas 47.2 ± 3.16% permeation through a dialysis membrane was observed. Short-wave ultraviolet (UV) radiation had no significant effect on DEET permeation. The merits of AIDA in facilitating the precise simulation of environmental conditions during permeation testing are discussed.

Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) in rats and rhesus monkeys: effect of anatomical site.

Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) was determined in rats and rhesus monkeys. Lindane is in widespread use as a 1% cream or lotion scabicide formulation and as a 1% miticide shampoo for body lice control in humans. Results obtained following our in vivo dermal absorption procedure demonstrated that 18 +/- 4.1%, 34 +/- 5.2%, and 54 +/- 26.3% of the applied dose was absorbed following topical applications at a rate of 1.5 micrograms/cm2 (6.2 micrograms/100 microliters of acetone) of the 14C-labeled pesticide to 4.2-cm2 regions of the forearm (n = 8), forehead (n = 7), and palm (n = 4) of rhesus monkeys, respectively. Dose sites were washed with soapy water 24 h posttreatment. Comparative studies in rats (n = 5) dosed middorsally demonstrated 31 +/- 9.5% absorption. Statistical analysis of the 14C excretion kinetics demonstrated slower clearance of lindane from rats than monkey forearm, forehead, or palm. Intramuscular (im) injections of 14C-lindane gave 52 +/- 7.1% recovery in monkey (n = 8) and 64 +/- 5.9% in rats (n = 5), suggesting body storage of this lipophilic chemical.

Evaluation of the rat tail model for estimating dermal absorption of lindane.

Dermal absorption of the insecticide lindane was determined following topical application of ring 14C-labeled lindane to the tail of Sprague-Dawley rats. The tail was tested as a practical alternative to the rat mid-dorsal (back) region, and the data obtained were compared to those with rat back and with those of rhesus monkeys in our previous reports. There was no significant difference between total percentage urinary 14C recovery for rats dosed on the tail with occlusive tail covers (52 +/- 6.2%; t1/2 = 2.7 d) compared to those with nonocclusive covers (55 +/- 4.4%; t1/2 = 2.9 d). Neither the total percentage urinary recovery nor the t1/2 values obtained for the rat tail and rat back models differed significantly. Carbon-14 activity was still detectable in urine samples taken after 72 d post-treatment. However, an extensive tissue analysis failed to demonstrate 14C activity persisting at 72 d, with the exception of trace levels detected in blood serum and tail tissue. Advantages of the rat tail model are highlighted.