Compatibility of a combination of tiamulin and chlortetracycline with salinomycin in feed during a pulsed medication program coadministration in broilers.

In an earlier study, the continuous medication of broiler feed with a combination of tiamulin (TIA; 20 mg/kg), chlortetracycline (CTC; 60 mg/kg), and the ionophore anticoccidial salinomycin (SAL; 60 mg/kg) caused an initial increase in BW and feed efficiency (FE; g of weight gain/kg of feed intake). However, as doses increased to combinations of 30 mg/kg of TIA and 90 mg/kg of CTC or 50 mg/kg of TIA and 150 mg/kg of CTC, there was a dose-related reduction in growth rate and FE. This was thought to be due to the interaction between TIA and SAL. In this study, using a protocol similar to the previous trial, broiler chicks were administered SAL at 60 mg/kg via the feed and the same inclusion rates of TIA + CTC. However, instead of feeding the birds continuously, considering the cost of TIA and possibly to compensate for the depressed growth attributable to the interaction with SAL, they were pulse-dosed for 1 to 10 d and again at 21 to 27 d, and the whole trial lasted 35 d to see if the intermittent pulses might reduce production losses. A total of 200 straight-run 1-d-old broiler chicks (Hubbard classic) were randomly distributed into 4 groups, with each group consisting of 5 cages containing 10 birds. The 20 cages were allocated to the 4 treatment groups on a random basis. The control diet, containing only SAL at 60 mg/kg, was fed to all birds throughout the 35-d trial, including the period during the gaps between dosing (i.e., d 11 to 20 and d 28 to 35). Feed and water were available for the whole trial period. Several serum enzymes (creatine kinase, lactate dehydrogenase, and aspartate aminotransferase) were determined from blood samples taken on d 35. Blood samples were also collected at 1, 19, and 35 d of age and were examined for antibody titers to Mycoplasma gallisepticum and Mycoplasma synoviae. Necropsy and histopathology of the birds (n = >or=4) were conducted during weekly intervals. There was no significant difference in weight gain, feed intake, and FE when the groups treated with TIA + CTC were compared with the control group (P > 0.05). There was no relationship between mortality and inclusion rates of the medication. No clinical signs of an interaction were exhibited during the trial, which was supported by necropsy and serum enzyme results. Maternally derived antibodies against M. gallisepticum were identified at the start of the trial but disappeared within 19 d, and infection with M. gallisepticum or M. synoviae was found neither serologically nor clinically during the trial. The results demonstrated that intermittent pulse administration of TIA at 50 mg/kg + CTC at 150 mg/kg from d 1 to 10 and d 21 to 27, along with continuous feeding of SAL (60 mg/kg), would be possible without altering performance and while maintaining the health status of the broilers. However, further research is required on the presence of artificial infections with Mycoplasma pathogens to determine the efficacy of the combination of TIA +CTC.

Pharmacokinetics of levamisole in broiler breeder chickens.

The pharmacokinetics of levamisole was studied in 20 broiler breeder chickens (chickens that give eggs to breed broilers). A single dose of levamisole (40 mg/kg) was administered orally or intravenously to chickens before the onset of egg production, prelay (age = 22 weeks), and repeated at the peak of egg production (age = 32 weeks). A high-pressure liquid chromatographic with ultraviolet detection method (HPLC-UV) was used for quantification of levamisole in plasma. Using compartmental analysis, levamisole followed a three-compartmental open model with mean values of alpha = 0.1224 and 0.4968, beta = 0.01663 and 0.01813, gamma = 0.002 and 0.002/min at the prelay and at the peak of egg production periods, respectively. The mean values for volume of distribution at steady state (V(ss)), determined by compartmental analysis, were significantly different for prelay and peak of egg production (8.358 and 13.581 mL/kg), respectively.

Levamisole residues in chicken tissues and eggs.

Levamisole is currently being used to treat capillaria infection in chickens even though there is no published withdrawal information available for levamisole in chickens. Tissue residue withdrawal of levamisole in chickens was studied in 32 healthy broiler breeder chickens at the age of 32 wk (peak of egg production). Levamisole residues in chicken tissues, eggs, and plasma were determined by HPLC with ultraviolet (UV) detection at 225 nm. The highest level of residue and longest withdrawal after oral administration of 40 mg/kg levamisole to chickens was in the liver. On d 3 the level of levamisole were undetectable in the plasma. On d 9, levamisole residue in eggs was 0.096 microg/g and on d 18 it was 0.06 microg/g or less in all the analyzed chicken tissues. Those levels were lower than the recommended maximum residue limit (MRL). The withdrawal time for levamisole in chickens was longer than for other species tested, which is due in part to a larger dose of levamisole being recommended for chickens. In conclusion from this research, 9 d are needed for levamisole in eggs to be less than the MRL, and 18 d of withdrawal are needed before medicated birds are slaughtered if their tissues are to be safe for human consumption.

Skin concentrations of thromboxane synthetase inhibitor after topical application with bioelastic membrane.

Elevated thromboxane levels are associated with a number of disease states, including dermal pressure ulcers. When dazmegrel was orally administered to greyhound dogs wearing leg casts, it resulted in a sparring effect on the skin areas of potential pressure ulcer development. The objective of this research was to determine if bioelastic matrices could provide controlled release of thromboxane A2 synthetase inhibitor (dazmegrel) at tissue concentrations sufficient for inhibition of thromboxane synthesis. The animal used for these studies was the greyhound, which has thin skin, angular conformation, limited body fat and is predisposed to pressure ulcers similar to those occurring in humans. In vivo skin penetration studies showed that epidermal exposure to bioelastic thromboxane synthetase inhibitor (TSI) matrix resulted in local tissue concentrations of TSI sufficient for thromboxane synthetase inhibition. There were no significant differences between dazmegrel in the skin layers (epidermis, dermis and subcutaneous layers) on 1, 7 and 14-day exposures.

Drinking water contaminants (arsenic, cadmium, lead, benzene, and trichloroethylene). 1. Interaction of contaminants with nutritional status on general performance and immune function in broiler chickens.

The objective of this study was to examine possible interactions between drinking water contaminants and suboptimal nutritional status for performance and immune function in male broiler chickens. Experimental drinking water contained a mixture of arsenic, benzene, cadmium, lead, and trichloroethylene (TCE) at low concentrations (0.80, 1.3, 5.0, 6.7, and 0.65 ppm) and high concentrations (8.6, 13, 50, 67, and 6.5 ppm). These chemicals were selected because they are among the most common contaminants found in ground water near hazardous waste sites. The experimental diets included feed containing 50% added vitamins and minerals (V&M) and feed without added V&M. Increasing levels of drinking water contaminants and decreasing levels of V&M in diet resulted in significantly (P < or = 0.05) decreased water and feed intake, decreased weight gain, and suppression of natural, humoral, and cell-mediated immune response. In a paired-water study, feed consumption, body weight, and immune function were decreased in chickens provided low and high concentrations of the chemical mixture in drinking water compared with chickens given control drinking water equal to the volumes consumed by the chickens given the low and high concentration of mixture, respectively. A deficiency of dietary V&M caused increased sensitivity to adverse effects of drinking water contaminants.

Drinking water contaminants (arsenic, cadmium, lead, benzene, and trichloroethylene). 2. Effects on reproductive performance, egg quality, and embryo toxicity in broiler breeders.

Broiler breeder hens were used to determine the effect of drinking water containing a low concentration of a chemical mixture (arsenic, 0.8 ppm; benzene, 1.3 ppm; cadmium, 5.1 ppm; lead, 6.7 ppm; and trichloroethylene, 0.65 ppm) and a high (10 times greater than the low concentration of the chemical mixture) levels of the chemical mixture. These chemicals are present in ground water near hazardous waste sites. Water consumption significantly decreased in chickens provided the high concentration of the chemical mixture, whereas feed consumption was not affected in any treatment. There was a linear relationship between increasing concentration of the chemical mixture in drinking water and decreasing body weight of hens. The low concentration of the chemical mixture significantly decreased egg production and egg weight, and increased percentage embryonic mortality. These results suggest that reproductive function in hens is sensitive to adverse effects of contaminated drinking water.

Effects of fusarium moniliforme isolates on tissue and serum sphingolipid concentrations in horses.

Disruption in sphingolipid (SL) metabolism is a biomarker of exposure to fumonisins. The role of altered SL metabolism in the pathogenesis of fumonisin toxicoses is not understood. A 27-d feeding trial in horses compared the toxic effects of 3 strains of Fusarium moniliforme: RRC 415, cultured from corn in MS; AU 2/3, cultured from feed associated with clinical signs of duodenitis-proximal jejunitis (DPJ) in horses in AL; and MRC 826, cultured from corn in South Africa and shown to cause equine leukoencephalomalacia (ELEM). These were cultured on corn and diluted with clean corn and grain mixed with molasses (sweet feed) to final concentrations of < 1, 65-130 and 200 mg fumonisin B1 (FB1)/kg, respectively. None of the horses developed DPJ, but horses fed MRC 826 had intestinal lesions consistent with DPJ and horses fed AU 2/3 and MRC 826 developed ELEM. Serum SL concentrations were analyzed in horses fed control and F moniliforme culture material, in brain and/or intestinal tissues in healthy horses (euthanized in AL and IL), and in horses fed AU 2/3 and MRC 826. Serum sphinganine (Sa): sphingosine (Szero) ratios were significantly elevated in horses fed AU 2/3 and MRC 826. Sphinganine concentrations were significantly elevated in the hypothalamus-dentate gyrus and brain stem in horses fed AU 2/3, compared to healthy horses. Sphingosine concentrations were significantly elevated in the proximal duodenum and ileum of MRC 826 horses compared to healthy horses. The brain and intestinal tissues in horses with and without pathological lesions did not have changed Sa:S(zero).

Toxicity of ochratoxin A, its opened lactone form and several of its analogs: structure-activity relationships.

Ochratoxin A (OA); its three natural analogs, ochratoxin C (OC), B (OB), and alpha (Oalpha); and its six synthetic analogs, the epimere of OA (d-OA), the ethylamide of OA (OE-OA), decarboxylated OA (DC-OA), O-methylated OA (OM-OA), lactone-opened OA (OP-OA), and the methyl ester of Oalpha (M-Oalpha) were assayed for their toxicities in prokaryotic (Bacillus brevis) and eukaryotic (HeLa cell) systems and in animals (mouse and rat). The LC50S (mM) for HeLa cells, were 0.005 (OA), 0.009 (OC), 0.163 (d-OA), 10.1 (OE-OA), 7.6 (DC-OA), 0.83 (OM-OA), 0.054 (OB), and 0.56 Oalpha). The minimum inhibitory doses (nmol/disc) for the growth of B. brevis (pH 6.5) were 8.7 (OA), 2.0 (OC), 5.5 (d-OA), 1.1 (OE-OA), 54 (OB), 390 (Oalpha), and 90 (M-Oalpha) while no inhibition of the bacterial growth was observed for OM-OA, DC-OA, and OP-OA at doses as high as 350 nmol/disc. The results indicate that the toxicities of OA were associated with its isocoumarin moiety but that neither the dissociation of the phenolic hydroxyl group nor the iron-chelating properties of OA were directly related to its toxicities. The lactone carbonyl group of OA, however, appears to be involved in OA toxicity as OP-OA is found in the bile of rats injected with OA and has similar toxicity to that of OA when administered intravenously to the rat. Overall, the structure-activity studies suggest that the toxicity of OA is attributable to its isocoumarin moiety and that the lactone carbonyl group may be involved in its toxicity.

Preliminary evaluation of in vitro prescreen assays for developmental toxicants based on cultured murine preimplantation embryos and a cell line developed from a bovine preimplantation embryo.

The purpose of this research was to evaluate in vitro assays and compare their efficiency in accurate prediction of the potential of chemicals to cause abnormal embryonic/foetal development. In vitro assays were based on cultured murine preimplantation embryos and a continuous cell line derived from a bovine preimplantation embryo. Preimplantation embryos collected from superovulated mice were cultured for 72 hr in the presence of 10-fold dilutions of coded compounds. In vitro embryonic development was considered normal if the embryos hatched from the zona pellucida (with normal-appearing inner cell mass and trophoblast cells) and attached to the culture plate at the end of the culture period. The embryonic cells were seeded in 96-well plates, cultured for 24 hr in control media, exposed to 10- and twofold dilutions of test compounds for 72 hr, and finally were stained and counted. The inhibitory concentration (IC(50)) and lethal concentration (LC(50)) were the concentrations (mm) that decreased embryonic development or cell viability by 50%, and were calculated for three model compounds and 10-12 coded compounds (known developmental toxicants and non-toxicants). The concordance between in vivo animal developmental toxicity data and the murine and bovine assays was 83 and 87%, respectively. These accuracies are similar to those of other available assays, and the bovine assay has the added advantage of being simple to perform and economical (about US$100 per assay).

An investigation of the role of Fusarium moniliforme in duodenitis/proximal jejunitis of horses.

Duodenitis/proximal jejunitis syndrome (DPJ) is a small intestinal disease of horses that is associated with depression and copious gastric reflux. Since an infectious cause for DPJ remains unsubstantiated, these studies were designed to investigate the possible role of Fusarium moniliforme toxins in this disease. Fusarium moniliforme was isolated by culturing 2 samples of feed that had been fed to horses with clinical signs of DPJ. These isolates (AU 2/3) were subsequently grown concurrently on autoclaved corn and their toxicity evaluated in a feeding trial utilizing horses. Isolates of F moniliforme known to be low and high producers (RRC 415 and MRC 826, respectively) of fumonisin B1 (FB1) were cultured individually on corn and each fed separately to other groups of horses. Control horses were fed autoclaved corn that was not inoculated with fungus. Production of FB1 by isolates RRC 415, MRC 826 and AU 2/3 were 19, 4360 and 1455 ppm, respectively. Each group contained 2 horses and the test diets were prepared by diluting culture material with sweet feed and clean corn. The test diets consisted of control corn that contained < 1 ppm FB1, RRC 415 diluted to < 1 ppm FB1, MRC 826 diluted to 200 ppm FB1, and AU 2/3 culture material diluted to contain 65 ppm FB1 on days 1-10 and 130 ppm on days 11-27. Horses fed either MRC 826 or AU 2/3 had elevated serum gamma-glutamyltransferase after 7 to 21 d exposure and elevated serum L-iditol dehydrogenase activity after 7 to 19 d exposure to test diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of in vitro and in vivo biological activity of mycotoxins.

In vitro assays developed to screen the cytotoxic activity of chemicals in murine (NIH/3T3) and bovine (BE 12-6) embryonic cells were used to determine the concentrations (microgram/ml) of mycotoxins which caused 50% lethality (LC50). Embryonic cells were seeded in 96 well plates, cultured for 72 hr with dilutions of each individual and combinations of mycotoxins, and stained and counted. Verrucarin A and roridin A had the strongest cytotoxic activity, and ergotamine tartrate was least toxic. Furthermore, results correlated with published values of in vivo activity, indicating this assay can be used for acute toxicity screening of compounds.

Comparison of the partition coefficient and skin penetration of a marine algal toxin (lyngbyatoxin A).

Lyngbyatoxin A is produced by marine algae, and causes local cutaneous toxicity in swimmers. The purpose of this research was (1) to determine the partition coefficient of lyngbyatoxin A in octanol/water and (2) to use methods in vitro to measure the penetration and distribution of lyngbyatoxin A in guinea pig and human skin. Discs of excised guinea pig and human skin were mounted in diffusion chambers that exposed the epidermal surface to air and bathed the dermis with HEPES-buffered Hanks' balanced salt solution with gentamicin sulphate. The epidermal surfaces were dosed with 26 micrograms lyngbyatoxin A/cm2 dissolved in 13 microliters dimethyl sulphoxide/cm2. The diffusion chambers were incubated at 36 degrees C for varying periods (1.0-24 hr). HPLC was used to quantify lyngbyatoxin A. Skin penetration was calculated by summing the amount of lyngbyatoxin A recovered from the dermis and receptor fluid. The mean partition coefficient for lyngbyatoxin A was 1.53. Penetration of lyngbyatoxin A (expressed as a percentage of dose, n = 3) in guinea pig and human skin was 23 and 6.2 (respectively) after 1 hr of topical exposure. The amount of lyngbyatoxin A in the dermis and receptor fluid did not change significantly over time.

Effect of vehicle on skin penetration and retention of a lipophilic red tide toxin (PbTx-3).

The purpose of this study was to determine the effect of carrier vehicle on the penetration of brevetoxin ([3H]PbTx-3) into skin layers and receptor fluid. Disks of guinea-pig skin were mounted on penetration chambers. Epidermal surfaces were dosed with 0.320 microgram/cm2 of PbTx-3 dissolved in 50 microliters of vehicle [water, methanol, or dimethylsulfoxide (DMSO)]. In vitro skin penetration by PbTx-3 during 24 hr of exposure was 6.2, 2.3 and 26% for water, methanol, and DMSO, respectively (expressed as % of dose applied).

Methods for in vitro skin absorption studies of a lipophilic toxin produced by red tide.

The penetration and distribution of [3H]PbTx-3 into pig skin was determined using in vivo and in vitro methods. The dose used in each topical study was 0.3-0.4 micrograms/cm2 skin, with dimethylsulfoxide as the vehicle. In the in vivo study, mean cutaneous absorption after 48 h (expressed as percentage of the dose) was 11.5% (n = 3). In the in vitro study, mean cutaneous absorption after 48 h was 1.6% (n = 12), when based on accumulation of radioactivity in receptor fluid, or 9.9% when based on receptor fluid and dermis. [3H]PbTx-3 readily penetrated through the epidermis into the dermis, reaching maximal dermal accumulation at 4 h (9.1% in vivo and 18% in vitro). At 24 h, the amount in the dermis decreased to 2.3% and 15% in vivo and in vitro, respectively and at 48 h the amount in the dermis decreased to 8.2% in vitro. These results demonstrate the important role of the dermis as a reservoir for a lipophilic compound in both in vivo and in vitro percutaneous absorption studies.

In vitro penetration of tritium-labelled water (THO) and [3H]PbTx-3 (a red tide toxin) through monkey buccal mucosa and skin.

The permeability coefficients (Kp) for tritium-labelled water (THO) were determined in human and monkey skin, and monkey buccal mucosa. Kp of human skin (0.47 x 10(-3) cm/h) correlated favorably with previous reports. Kp of hydrated monkey skin for THO (0.77 x 10(-3) cm/h) was not significantly different (P greater than 0.05) from Kp of hydrated human skin (0.88 x 10(-3) cm/h). Kp of monkey buccal mucosa for THO (6.15 x 10(-3) cm/h) was significantly greater than that for monkey skin. Penetration and disposition of [3H]PbTx-3 into layers of monkey buccal mucosa and skin was determined. [3H]PbTx-3 (5-7 microCi) dissolved in 2 ml of water was applied to epithelial/epidermal surface (2.8 cm2) at zero time. The relative percent dose recovered from the upper layers of buccal mucosa (epithelium) and skin (epidermis) varied, but at each time interval was less than 2.5% of the dose. At most of the time intervals (2-24 h), a larger percent of the dose was recovered from the inner layer of the buccal mucosa (lamina propria) than from the inner layer of skin (dermis). After 24 h, as much as 34 or 13% of the dose was recovered from lamina propria or dermis, respectively. At each time interval studied, less than 2% of dose of [3H]PbTx-3 penetrated into the receptor fluid which bathed the inner surfaces of the lamina propria or dermis. The results of this study demonstrate that monkey buccal mucosa is more permeable than skin to THO and PbTx-3.

Quantitative tritium exchange of [3H] aflatoxin B1 during penetration through isolated human skin.

Tritium labelled aflatoxin B1 ([G-3H]AFB1) underwent an almost total tritium exchange with water during penetration through isolated human skin. The process was not enzymatic and the site of exchange appeared to be within the epidermis. The mechanism which mediated this extensive exchange was not determined. However, the tritium in [G-3H]AFB1 was found to be very susceptible to chemical conditions which favored carbanion formation at the alpha-carbon of the cyclopentenone ring. The relative effectiveness of the various solvents in mediating the loss of the tritium label was 1 N3NaOH much greater than methanol greater than 1 N HCl greater than water. This work serves as a warning that [G-3H]AFB1 can easily undergo significant changes in specific activity in biological tissues and under relatively mild experimental conditions. It is possible that conditions within the skin favor carbanion formation.

Comparison of penetration and metabolism of [3H]diacetoxyscirpenol, [3H]verrucarin A and [3H]T-2 toxin in skin.

The purpose of this research was to determine the rate of cutaneous penetration and metabolism of [3H]diacetoxyscirpenol (DAS) and [3H]verrucarin A (VCA) and compare these values to previously determined values for [3H]T-2 toxin (T-2), to compare the cutaneous penetration and metabolism of DAS in human and guinea-pig skin, and to compare the effects of dose and of two vehicles, methanol and dimethylsulphoxide (DMSO), on penetration rates. DAS or VCA was applied to the epidermal surface of excised skin, and the receptor fluid bathing the dermal surface was sampled periodically for 48 hr. Whether the applied dose (581 ng/cm2) was dissolved in methanol or DMSO, the rate of penetration through human skin was lower for VCA than for DAS or T-2, the rates for the two latter compounds being similar at this dose. Metabolism of DAS occurred during penetration through excised human skin and did not occur in the receptor fluid as a result of enzymes leaching out of the skin. VCA appeared to be metabolized by human skin, but this conclusion is tentative because of the relative instability of this compound. DAS penetrated significantly (P less than 0.05) faster through excised guinea-pig skin than through human skin. Metabolism of DAS was greater in human skin than in guinea-pig skin. When compared with methanol, DMSO increased the penetration of DAS and VCA by factors of between 7 and 52. At the low dose (79 ng/cm2) DAS penetrated human and guinea-pig skin significantly (P less than 0.05) faster than T-2 using either vehicle.

In vitro percutaneous penetration and metabolism of [3H]T-2 toxin: comparison of human, rabbit, guinea pig and rat.

The purpose of this research was to determine which species of laboratory animal provided the best approximation of in vitro percutaneous penetration and metabolism of T-2 in humans. The [3H]T-2 which penetrated discs of skin after 48 hr (expressed as per cent of dose, 581 ng/cm2) was 1.0, 1.4, 2.8 and 9.7% for the human, rabbit, guinea pig and rat when the vehicle was methanol. The penetration was 29.2, 19.6, 51.9 and 52.6% for the human, rabbit, guinea pig and rat when the vehicle was DMSO. When 2 concentrations were compared, 79 ng/cm2 and 581 ng/cm2 (the vehicle was methanol), the higher dose caused a significant (P less than 0.05) increase in the per cent of dose which penetrated human and guinea pig skin. Metabolism was extensive in the human, rabbit, and rat, with the main metabolite being HT-2 toxin. Previous studies comparing human to monkey indicated penetration in these 2 species was different when methanol was the vehicle. This study indicates that the rabbit provides the best approximation of human skin, both in terms of penetration kinetics and metabolic activity.

Comparison of in vivo and in vitro percutaneous absorption of T-2 toxin in guinea pigs.

The fate and distribution of T-2 were examined in 6 guinea pigs. T-2 (1.2 micrograms/cm2), in methanol or DMSO, was painted onto the shaved backs of guinea pigs, a screen barrier was applied, urine and feces were collected daily and the guinea pigs were killed after 48 hr. Disks of skin (lateral to the in vivo site of application) were excised from the guinea pigs and used for in vitro penetration studies with static diffusion cells. Skin excised from 6 additional guinea pigs was used for penetration studies with flow-through diffusion cells. For in vitro studies, T-2 dissolved in methanol or DMSO was applied to the epidermal surfaces and the appearance of penetrant in receptor fluid bathing the dermal surfaces was monitored for 48 hr. Metabolism of T-2 was measured by using thin layer radiochromatography to identify metabolites. In the in vivo study, mean cutaneous absorption (n = 3) after 48 hr (expressed as per cent dose) was 22.5 and 51.9 for the methanol and DMSO groups, respectively. In vitro cutaneous penetration for static diffusion cells was 3.9 and 38.4 for the methanol and DMSO groups. For flow-through diffusion cells, mean penetration (n = 9) was 14.6 and 42.6 for the methanol and DMSO groups. Urinary metabolites of T-2 were T-2 triol, 3' OH-HT-2, T-2 tetraol, the glucuronide conjugate of HT-2 and several more polar metabolites. The main metabolite of T-2 in the receptor fluid bathing the dermal surfaces of excised skin was HT-2.

Evaluation of monkey skin as a model for in vitro percutaneous penetration and metabolism of [3H]T-2 toxin in human skin.

Discs of abdominal skin (obtained from humans and hybrid monkeys at autopsy) were mounted on diffusion cells. The epidermal surfaces were dosed with [3H]T-2 dissolved in dimethyl sulfoxide (DMSO). The rate of [3H]T-2 penetration (expressed as ng/cm2/hr) through human skin was 0.38 +/- 0.10 and 3.85 +/- 0.96 (means +/- 95% confidence limit) when dosed with 74 and 582 ng/cm2, respectively. [3H]T-2 penetrated through monkey skin at the rate of 0.37 +/- 0.14, 0.80 +/- 0.43, 4.13 +/- 1.71, and 6.55 +/- 3.45 when dosed with 70, 155, 555 and 1063 ng/cm2, respectively. Analysis of the receptor fluid bathing human skin revealed 15% of the radioactivity was associated with T-2, 71% with HT-2 toxin (HT-2), and 6.3% with an unknown metabolite more polar than HT-2. The radioactivity in the receptor fluid bathing monkey skin was associated with T-2 (87%) and HT-2 (1.0%). The results are consistent with the hypothesis that metabolism of T-2 occurred during penetration through the excised skin and did not occur in the receptor fluid due to enzymes leaching out of the skin. These findings indicate that excised monkey skin is a good model for T-2 penetration through human skin when DMSO is the vehicle, but that dermal metabolism of T-2 is different in these two species.