Dermal routes

Care must be exercised in handling carbon disulfide because of both health concerns and the danger of fire or explosions. Occupational exposure potentially may involve as many as 20,000 workers in the United States (136). Ingestion is rare, but a 10 mL dose can prove fatal (137). Contact usually occurs by inhalation of vapor. However, vapor and Hquid can be absorbed through intact skin and poisoning may occur by the dermal route (138). 

Reproductive Toxicity. No data are available that impHcate either hexavalent or trivalent chromium compounds as reproductive toxins, unless exposure is by way of injection. The observed teratogenic effects of sodium dichromate(VI), chromic acid, and chromium (HI) chloride, adininistered by injection, as measured by dose-response relationships are close to the amount that would be lethal to the embryo, a common trait of many compounds (111). Reported teratogenic studies on hamsters (117,118), the mouse (119—121), and rabbits (122) have shown increased incidence of cleft palate, no effect, and testicular degeneration, respectively. Although the exposures for these experiments were provided by injections, in the final study (122) oral, inhalation, and dermal routes were also tried, and no testicular degeneration was found by these paths. 

Ocular Effects. One study reported that seven children exposed to methyl parathion by inhalation, oral, and possibly dermal routes exhibited pinpoint pupils (miosis) (Dean et al. 1984). This effect is a consequence of the effects on the autonomic nervous system. No other studies were located regarding ocular effects in humans or animals after inhalation exposure to methyl parathion. 

LD50 values for the dermal route of exposure to methyl parathion have been established in acute studies for rats 67 mg/kg for males and females (Gaines 1960), 110 mg/kg for males, and 120 mg/kg for females (EPA 1978e). The LD50 in male mice exposed by dermal application of methyl parathion to their hind feet (rather than shaved backs) was 1,200 mg/kg (Skinner and Kilgore 1982a). The mice were muzzled to prevent oral exposure from grooming. 

In a case-control study of pesticide factory workers in Brazil exposed to methyl parathion and formulating solvents, the incidence of chromosomal aberrations in lymphocytes was investigated (De Cassia Stocco et al. 1982). Though dichlorodiphenyltrichloroethane (DDT) was coformulated with methyl parathion, blood DDT levels in the methyl parathion-examined workers and "nonexposed" workers were not significantly different. These workers were presumably exposed to methyl parathion via both inhalation and dermal routes however, a dose level was not reported. The exposed workers showed blood cholinesterase depressions between 50 and 75%. However, the baseline blood cholinesterase levels in nonexposed workers were not reported. No increases in the percentage of lymphocytes with chromosome breaks were found in 15 of these workers who were exposed to methyl parathion from 1 week to up to 7 years as compared with controls. The controls consisted of 13 men who had not been occupationally exposed to any chemical and were of comparable age and socioeconomic level. This study is limited because of concomitant exposure to formulating solvents, the recent history of exposure for the workers was not reported, the selection of the control group was not described adequately, and the sample size was limited. 

Chromosome aberrations were detected in lymphocytes of individuals acutely intoxicated by methyl parathion by the inhalation route (Van Bao et al. 1974). Blood samples were taken 3-6 days after exposure and again at 30 and 380 days. A temporary but significant (p<0.05) increase was noted in the frequency of stable chromosomal aberrations in the exposed individuals. The study limitations include small sample size, absence of a control group, lack of quantification of exposure levels, and a possible concomitant exposure to other substances via the dermal route. 

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. 

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. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor approach. They are below levels that might cause adverse health effects in the people most sensitive to such chemical-induced effects. MRLs are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level above the MRL does not mean that adverse health effects will occur. 

Twenty-two cases of endosulfan poisoning were reported in people exposed while spraying cotton and rice fields the dermal route of exposure was assumed to be the primary route of exposure (Singh et al. 1992). The assumption was based on the fact that those spraying rice fields, and who suffered cuts over the legs with the sharp leaves on the rice plants exhibited the more severe toxicity. Three out of the 22 cases exhibited tremors and 11 presented convulsions all patients recovered. 

The data in animals are insufficient to derive an acute inhalation MRL because serious effects were observed at the lowest dose tested (Hoechst 1983a). No acute oral MRL was derived for the same reason. The available toxicokinetic data are not adequate to predict the behavior of endosulfan across routes of exposure. However, the limited toxicity information available does indicate that similar effects are observed (i.e., death, neurotoxicity) in both animals and humans across all routes of exposure, but the concentrations that cause these effects may not be predictable for all routes. Most of the acute effects of endosulfan have been well characterized following exposure via the inhalation, oral, and dermal routes in experimental animals, and additional information on the acute effects of endosulfan does not appear necessary. However, further well conducted developmental studies may clarify whether this chemical causes adverse developmental effects. 

Currently, MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end point considered to be of relevance to humans. Serious health effects (such as irreparable... 

Exposure to trichloroethylene can occur via the inhalation, oral, and dermal routes in people living in areas surrounding hazardous waste sites if evaporation occurs from contaminated soils or spill sites, or if contaminated water is ingested or used in bathing. Individuals who work in the vicinity of industries that use this substance may breathe trichloroethylene vapors or come into physical contact with spilled trichloroethylene. The group with the greatest likelihood for substantial exposure to trichloroethylene consists of those exposed to trichloroethylene in the workplace. 

Beliles et al. 1980 Land et al. 1981). Studies for oral exposure indicate no adverse reproductive effects (NTP 1985, 1986). More research on the reproductive effects of inhalation exposure to trichloroethylene, especially effects on miscarriage in humans is needed. Additional animal studies via the inhalation and dermal routes are needed to further characterize reproductive effects. 

Mineral Oil Hydraulic Fluids. There is limited information on the toxicity of mineral oil hydraulic fluids in humans. A single case report of a child accidentally ingesting a single dose of automotive transmission fluid provides limited information on death and systemic effects. A case-control study provides some information on the carcinogenicity of mineral oil hydraulic fluids. The study population was exposed via inhalation and dermal routes. An occupational exposure study provides information on neurotoxicity following chronic dermal exposure. Information on the toxicity of mineral oil hydraulic fluids is limited to a series of inhalation, oral, and dermal acute-duration exposures. These studies provide information on death, systemic effects, and neurotoxicity by inhalation, oral, and dermal routes, and immunotoxicity following dermal exposure. 

Information on polyalphaolefin hydraulic fluids is limited to a single study in rats orally exposed to MIL-H-83282 and MIL-H-83282LT (Mattie et al. 1993). Intermediate-duration inhalation or oral MRLs could not be derived based on a single study. Significant toxicity was not observed. Systemic toxicity studies in which animals were exposed via inhalation and dermal routes would be useful in identifying the end points of toxicity for humans living at or near hazardous waste sites and exposed for intermediate-durations. 

No information on the carcinogenic potential of polyalphaolefin hydraulic fluids was located. Studies designed to assess carcinogenicity in animals exposed via inhalation, oral, and dermal routes or a well-controlled cohort retrospective or prospective study would be useful for determining the carcinogenic potential of polyalphaolefin hydraulic fluids. 

Acute lethal concentrations (LC50s) for hydrogen sulfide in rats have been reported to range from 335 to 587 ppm (Prior et al. 1988 Tansy et al. 1981). There are no reports of fatalities in humans or animals exposed solely by the oral route or dermal routes. 

The relationship between exposure and internal dose is known only for a few pyrethroids. Human volunteer studies have shown that, after a single oral administration, pyrethroids and the respective metabolites are excreted in urine within 24 hr and do not accumulate in the body. In field workers exposed to cypermetrin through the dermal route, urine excretion of the intact compound and its metabolites peaked 36 hr after exposure had ceased (WHO, 1989). 

Doses for each volunteer were estimated by two methods. The first approach was to sum the contributions of the inhalation and dermal routes (whole body and hands). These contributions were estimated using calculations based on the air sampling data, the dislodgeable residue data, and the hand-rinse data. 

Table 4 summarizes the results of using physical techniques to estimate total chlorpyrifos doses of adults following activity on treated grass. Total doses ranged from 3.03 pg/kg to 5.04 pg/kg (mean, 3.88 pg/kg). Approximately 85% of the chlorpyrifos dose came from the whole body dermal route. About 15% came from the inhalation route. Hand exposure was insignificant. 

This study was conducted to evaluate and compare ADD determined using whole-body dosimetry with results of two situational exposure studies conducted following use of a flea fogger under natural conditions. Chlorpy-rifos was selected due to its general availability as a fogger for indoor flea control. Chlorpyrifos is poorly absorbed by the dermal route and readily cleared from the body in urine (Nolan et al., 1984). Trichloropyridinol was measured in 24-hr urine specimens of the volunteers and was converted to chlorpyrifos equivalents as a measure of absorbed dose. The study provided an opportunity to determine the relationship between intensive, high-contact dosimetry studies and the amounts of chlorpyrifos absorbed by two sets of adults who re-entered fogger-treated homes. 

Re-entry exposure will be predominantly via the dermal route. Exposure data indicate that, in general, inhalation exposure is only important during a relatively short period after application (e.g., in field crops only during the... 

The exposure value thus yielded provides a measure of the skin exposure with and without consideration of a protective garment and gloves (personal protective equipment = PPE), and may be taken directly for comparison with appropriate data from relevant toxicity studies for assessment of the risk via the dermal route. 

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