Parathion percutaneous absorption

Qiao, G.L. Chang, S.K. Riviere, J.E. Effects of anatomical site and occlusion on the percutaneous absorption and residue pattern of 2,6-[ring- C]parathion in vivo in pigs. Toxicol. Appl. Pharmacol. 1993, 121, 131-138. 

Gyrd-Hansen, N. Brimer, L. Rasmussen, R. Percutaneous absorption and recovery of parathion in pigs. Acta Vet. Scand. Suppl. 1991, 87, 410-412. 

One in vivo Study on pigs (Qiao et al.. 1997) demonstrated that occlusion significantly enhanced pen-tachlorophcnol (PCP) absorption in a soil-based mixture from 29 to 85% of dose and changed the shape of the absorption profile in blood and plasma. The study also suggested that occlusion enhanced metabolism of PCP and resultantly the partitioning between plasma and red blood cells. Occlusion was kinctically linked to modification of cutaneous biotransformation of topical parathion (Qiao and Riviere, 1995). Occlusion enhanced cutaneous metabolism of parathion to paraoxon and to p-nitrophenol as well as the percutaneous absorption and penetration of both parathion and p-nitrophenol, This probably resulted in the... 

Carver, M. P., Levi. P. E., and Riviere, J, E. (1990). Parathion metabolism during percutaneous absorption in perfused porcine. skin. Pest. Biochem. Physiol. 38,245-254. 

Chang, S, K., and Riviere, J, E. (1991). Percutaneous absorption of parathion in vivo in porcine skin. Effects of dose, temperature, humidity and perfusate composidon on absorptive flux. Fundam Appl. Toxicol, 17,494—504. 

Qiao, G. L., Brooks, J. D., Bayne.s, R. E., Monteiro-Rivierc, N. A., Williams, P. L and Riviere, J. E. (1996). The use of inccha-nistieally defined chemical mixtures (MDCM) to assess component effects on the percutaneous absorption and cutaneous disposition of topically-exposed chemicals. I. Studies with parathion mixtures in isolated perfused porcine. skin. Toxicol. Applied. Pharmacol. 141, 473 86. 

Fredriksson, T. (1961). Percutaneous absorption of parathion and paraoxon. IV, Decontamination of human skin from parathion. Art ll. Environ. Health 185-189. 

Chang, S.K., Williams, P.L., Dauterman, W.C., and Riviere, J.E., 1994, Percutaneous absorption, dermatopharmacokinetics, and related biotransformation studies of carbaryl, lindane, malathion and parathion in isolated perfused porcine skin. Toxicology, 91 269-280. 

The mass balance approach was used to develop an in vivo animal model for skin penetration of topically applied dmgs in hairless rats (Simonsen et al., 2002). Two dmgs, C-sahcylic acid and C-butyl salicylate were topically applied for the assessment of the model. Rapid and differentiated percutaneous absorption of both compounds was indicated by urinary excretion data. Total mass balance on the applied radioactivity was performed, and 90% recovery was achieved. Carver and Riviere (1989) conducted an extensive mass balance study with " C-labeled xeno-biotics after topical and intravenous administration to pigs. These authors reported that dermal absorption of C-benzoic acid, caffeine, malathion, parathion, progesterone, and testosterone was 25.7, 11.8, 5.2, 6.7, 16.2, and 8.8%, respectively, following topical administration to pigs. 

Percutaneous absorption measurements of a limited number of pesticides have previously been reported. Permeation of DDT, lindane, parathion, uld meilathlon was measured in human volunteers by Maibach and coworlcers ( , ] ). In vivo absorption values for the same compounds were obtained for monkey, pig, and rabbit (11). The dermeil penetration of lU pesticides in mice (12) end three pesticides in rats ( ) was measured by Shah and coworkers using in vivo techniques. 

Dermal dose-ChE response and percutaneous absorption studies were conducted with parathion, carbaryl, and thiodicarb in the rat. Parathion and thiodicarb inhibited 50% of the red cell cholinesterase activity at dose levels of 3.2 and 33 mg/kg of bw. Carbaryl at the highest dose level tested (417 mg/kg of bw) produced no detectable red cell cholinesterase Inhibition. 

The rapid inhibition of red cell cholinesterase in workers der-mally exposed to parathion suggested that parathion was rapidly absorbed from skin. In the rat dermal dose response study (J a period of 72 hr was required for a single topical dose of parathion (32 mg/kg) to inhibit 50% of the red cell cholinesterase activity. Studies by Fredriksson (18) in he c t showed that parathion was absorbed slowly (0.35 ug hr cm ) and that parathion was unsuitable as a model substance for studying percutaneous absorption. The rate of absorption was determined by serial skin stipping and by measuring the disappearance of parathion over a period of 5 hr using a GM tube. 

Maibach et al., (19) conducted percutaneous absorption studies in man and Shah et al. (22) in the mouse. Carbaryl was absorbed more readily than parathion in these studies. The relationship between the dose and the adverse health effect (OiE inhibition) was not examined. According to the skin loss and plasma elimination data of Knaak et al. (iL) reviewed in this paper, carbaryl was not absorbed more rapidly than parathion in the adult male rat. More carbaryl residues were found in skin (penetrated) than were found in the case of parathion. The difference (2X) may be related to the ability of the rat skin to metabolize these pesticides prior to their absorption into blood. Fredriksson (22) showed that parathion was not metabolized to any extent in rat skin. Studies by Chin et al. (24) suggest that carbaryl may be partially metabolized in skin to water soluble products prior to their absorption into blood. 

Thlodicarb is a new insecticide being marketed by Union Carbide as Larvin for the control of insects on cotton. Thiodicarb is metabolized in the rat to acetamide, acetonitrile, CO, methomyl, and methomyl metabolites. No illnesses have been reported among applicators or field workers coming in contact with this carbamate insecticide. Thiodicarb is somewhat more persistent on crops than methomyl and is less toxic dermally in rabbit studies. The dermal dose-CliE response study showed that a dose of 33 mg/kg produced 50% ChE inhibition 24 hr. after the application of the dose, while a dose of 87 mg/kg of thiodicarb did not produce more inhibition than a dose of 44 mg/kg. The poor solubility of this carbamate in water/lipid most likely prevented the absorption of additional quantities of thiodicarb, thereby reducing its toxicity. Thiodicarb was found in lower concentrations in skin than either parathion or carbaryl during the percutaneous absorption studies. The concentrations in plasma. 

The effect of a topically applied dose of parathion, carbaryl, and thiodicarb on red blood cell cholinesterase activity in the rat was reviewed along with pharmacokinectic data developed on their percutaneous absorption. Parathion and thiodicarb inhibited 50% of the red cell cholinesterase activity at dose levels of 3.2 and 33 mg/kg of bw, while no inhibition was detected with carbaryl at dose levels as high as 417 mg/kg of w. Parathion and carbaryl were absorbed at 0.33 and 0.18 ug/hr/cm, while thiodicarb was absorbed at rates varying from 0.27 to 0.042 ug/hr/cm of skin. Skin loss and plasma elimination data were used to calculate the values. The topically applied pesticides slowly penetrated skin and were available for absorption into blood and redistribution to other tissues. Recovery data suggested that evaporative losses occurred during the course of the 5-day study. The pesticides may be removed from skin by washing, thus reducing the amount available for absorption. 

The effect on skin absorption of several insecticides was tested after in vivo pretreatment of the skin with either a 3% fenvalerate or 3% parathion in ethanol solution (Chang et al. 1995). The insecticides tested were carbaryl, fenvalerate, lindane, and parathion and their absorption was studied using a pig skin in vitro approach. Concentrations of 40 or 400 pg cm of carbaryl, fenvalerate, lindane, and parathion were used. Pretreatment with an ethanol control, or fenvalerate and parathion increased the total absorption of these insecticides proportionally with dose. In a study by Hotchkiss et al. (1992), ethanol was again shown to increase the percutaneous absorption of chemicals. 

Knaak JB, Leung H-W, Stott WT, Busch J, Bilsky J (1997) Toxicology of mono-, di-, and triethanolamine. Rev Environ Contam Toxicol 149 1-86 Knaak JB, Dary C, Patterson GT, Blancato J (2002) The worker hazard posed by reentry into pesticide-treated foliage reassessment of reentry levels/intervals using foliar residue transfer-percutaneous absorption PBPK/PD models, with emphasis on isofenphos and parathion. In Paustenbach D (ed) Human and ecological risk assessment theory and practice. Wiley, New York, pp 673-731... 

I. Boudry, O. Blanck, C. Cruz, M. Blanck, V. Vallet, A. Bazire, A. Capt, D. Josse and G. Lallement, Percutaneous penetration and absorption of parathion using human and pig skin models in vitro and human skin grafted onto nude mouse skin model in vivo,/. Appl Toxicol, 2008, 28, 645-657. 

---