Parathion dermal absorption

Dermal Absorption. To determine the toxicity of parathion following dermal application, the method of Draize, Woodard, and Calvery (3) was followed. Variables considered in the design of these experiments were concentration as a factor of area, solvent, exposure time, and number of exposures. In some cases the wettable powder was applied in the dry form, while in other cases sufficient water was added to produce a viscid paste. All doses in the table are presented as milligrams per kilogram of parathion, regardless of the concentration or solvent. 

Parathion is efficiently absorbed through any route of exposure. Signs of toxicity due to parathion generally appear within several hours following dermal exposure. The rate of dermal absorption in rabbits was found to be 0.059 pg min cm There is considerable individual variation in dermal absorption rates in animals and humans. About 0.1-2.8% of the applied compound was absorbed through skin in... 

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. 

Often, absorption occurs by multiple routes in humans. Dean et al. (1984) reported deaths and toxic effects as well as lowered blood cholinesterase levels and excretion of urinary 4-nitrophenol in several children who were exposed by inhalation, oral, and possibly dermal routes after the spraying of methyl parathion in a house. In the same incident (Dean et al. 1984), absorption was indicated in adults who also excreted 4-nitrophenol in the urine, though at lower levels than some of the children, and in the absence of other evidence of methyl parathion exposure. In this study, the potential for age-related differences in absorption rates could not be assessed because exposure levels were not known and the children may have been more highly exposed than the adults. Health effects from multiple routes are discussed in detail in Section 3.2. 

Although the extent of absorption was not measured, the above evidence suggests that absorption in humans occurs rapidly following dermal exposure to commercial pesticide formulations of methyl parathion. 

Based on the rapid appearance of clinical signs and cholinesterase inhibition, methyl parathion appears to be readily absorbed by humans and animals following inhalation, oral, and dermal exposure. Following oral administration of methyl parathion to animals, the extent of absorption was at least 77-80% (Braeckman et al. 1983 Hollingworth et al. 1967). No studies were located regarding the extent of absorption following inhalation and dermal exposure, or the mechanism of absorption. 

Procedures that have been used to reduce absorption of methyl parathion include the following. In inhalation and dermal exposures, the exposed person is first removed from the source of exposure. 

Absorption, Distribution, Metabolism, and Excretion. Evidence of absorption comes from the occurrence of toxic effects following exposure to methyl parathion by all three routes (Fazekas 1971 Miyamoto et al. 1963b Nemec et al. 1968 Skiimer and Kilgore 1982b). These data indicate that the compound is absorbed by both humans and animals. No information is available to assess the relative rates and extent of absorption following inhalation and dermal exposure in humans or inhalation in animals. A dermal study in rats indicates that methyl parathion is rapidly absorbed through the skin (Abu-Qare et al. 2000). Additional data further indicate that methyl parathion is absorbed extensively and rapidly in humans and animals via oral and dermal routes of exposure (Braeckman et al. 1983 Flollingworth et al. 1967 Ware et al. 1973). However, additional toxicokinetic studies are needed to elucidate or further examine the efficiency and kinetics of absorption by all three exposure routes. 

Obviously, ambient temperature will influence the absorption of parathion and the rapidity with which cholinesterase enzyme decline will occur. Funckes et al. (5) showed the temperature dependence of urinary PNP in volunteers dermally exposed to parathion. In our study, while temperature recordings were not documented, the impression was gained that in the month of August, the hottest and most humid month, higher weekly PNP levels were obtained and more cholinesterase declines observed. 

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. 

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. 

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