2,4-1 , dermal absorption

Health and Safety Factors. Neopentanoic acid possesses low toxicity, either by ingestion (oral LD q in rats is 2.0 g/kg) or by skin absorption (dermal LD q in rabbits is 3.16 g/kg). The principal ha2ards associated with neopentanoic acid at ambient temperatures are from eye and skin irritation. At elevated temperatures, where concentrations of the vapor are significant, irritation of the respiratory tract can also occur. Contact with the material should be avoided. 

The major routes through which the toxic chemicals enter the body under normal workplace conditions are by inhalation (respiratory route), through skin absorption (dermal route), or through ingestion (oral route). Many chemicals are known to cause the most severe health effects and rapid responses to test chemicals as soon as they enter directly into the blood circulation of animals. Several routes are used to evaluate and determine the toxicity and safety of chemical substances using species of laboratory animals in experimental toxicology studies. These routes of exposure include ... 

Dermal absorption (dermal penetration) Movement of a pesticide into and through the skin includes that taken up into the systemic circulation and that retained in the skin compartment (OECD, 1997). 

Applicability Individual compound absorption Dermal absorption data... 

Health and Safety Factors. Animal-feeding studies of DMPPO itself have shown it to be nontoxic on ingestion. The solvents, catalyst, and monomers that are used to prepare the polymers, however, should be handled with caution. Eor example, for the preparation of DMPPO, the amines used as part of the catalyst are flammable toxic on ingestion, absorption, and inhalation and are also severe skin and respiratory irritants (see Amines). Toluene, a solvent for DMPPO, is not a highly toxic material in inhalation testing the TLV (71) is set at 375 mg/m, and the lowest toxic concentration is reported to be 100—200 ppm (72). Toxicity of 2,6-dimethylphenol is typical of alkylphenols (qv), eg, for mice, the acute dermal toxicity is LD q, 4000 mg/kg, whereas the acute oral toxicity is LD q, 980 mg/kg (73). The Noryl blends of DMPPO and polystyrene have PDA approval for reuse food apphcations. 

Dermal Toxicity. Fatty alkylamines are not considered especially toxic with regard to skin penetration and systemic absorption into the body certain polyamines may be absorbed through the skin to a much greater degree. The acute dermal LD q of decylamine in rabbits has been reported to be... 

Toxicology. Isoquinoline is a poison when ingested or injected intraperitoneally. Even in cases of skin contact it is moderately toxic. As in the case of quinoline, its vapors are irritating to the eyes, nose, and throat. Exposure causes headaches, dizziness, and nausea. Rapid absorption through the skin makes it a dangerous chemical. Its toxicity is oral LD q (i t)> mg/kg, and dermal LD q (rabbit), 590 mg/kg (65,66,182,183). 

The dermal adsorption of DEBT in humans has been studied in the Netherlands by appHcation of DEBT as undiluted technical material or as 15% solutions in alcohol. Labeled material was recovered from the skin, and absorption of DEBT was indicated by the appearance of label in urine after two hours of skin exposure. About 5—8% of the appHed treatments was recovered as metaboHtes from urine, and excretion of metaboHtes in the urine came to an end four hours after exposure ended. DEBT did not accumulate in the skin, and only a small (less than 0.08%) amount ended up in feces. Curiously, less has been absorbed through skin from 100% DEBT appHcation (3—8%, mean of 5.6%) than from 15% alcohol appHcation (4—14%, mean of 8.4%). These results have been described as consistent with previous absorption/metaboHsm studies using guinea pigs, rats, and hairless dogs. Other pubHcations on DEBT toxicology have been cited (92). 

The water solubiUty of glutaric acid fosters its toxicity. Glutaric acid is a known nephrotoxin. Renal failure has been documented ia rabbits adruinistered sodium glutarate subcutaneously (124). Dibasic ester (Du Pont), which contains primarily dimethyl glutarate, has low acute toxicity by inhalation and by ingestion, and is moderately toxic via dermal absorption. The acid is both a dermal and ocular irritant of humans. The ester is a severe skin irritant and may cause a rash ia humans (120). 

Diglycidyl Ether of Bisphenol A. The Hquid DGEBPA-based resins exhibit low acute toxicity with a single-dose oral LD q value in rats of >2000 mg/kg (40). The potential for absorption of DGEBPA through the skin in acutely toxic amounts is low. LD q values of >800 mg/kg for acute dermal toxicity have been obtained from studies using both the pure and commercial DGEBPA (41,42). 

Carcinogenicity of DGEBPA or DGEBPA-based resins, as measured by topical appHcation, has not been shown by a majority of the studies (45). Advanced DGEBPA resins exhibit low systemic toxicity either by dermal or oral routes and inhalation of these resins is unlikely because of low volatihty. The acute oral LD q in rats has been reported to be >2000 mg/kg (46). Acute dermal studies show these materials have alow potential for absorption through the skin in acutely toxic amounts. No evidence of carcinogenicity has been found in animals or humans for advanced DGEBPA resins (47,48). 

Absorption via the skin depends on the lipid- and water-solubility of the compound, its polarity, and the molecular size. Dermal absorption is also markedly affected by the size of the exposed skin area. - ... 

Generally, the main pathways of exposure considered in tliis step are atmospheric surface and groundwater transport, ingestion of toxic materials that luu c passed tlu-ough the aquatic and tcncstrial food chain, and dermal absorption. Once an exposure assessment determines the quantity of a chemical with which human populations nniy come in contact, the information can be combined with toxicity data (from the hazard identification process) to estimate potential health risks." The primary purpose of an exposure assessment is to... 

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. 

Health effects in humans and animals provide indirect evidence of absorption of endosulfan following oral, inhalation, and dermal exposures. Endosulfan and metabolites have been detected in tissues of humans and animals following various exposures to endosulfan, providing qualitative evidence that... 

Indirect evidence indicates that dermal absorption occurs in animals. Calves dusted with a 4% dust formulation of endosulfan had neurological symptoms (tremors, twitching, convulsions) and died within a day after exposure (Nicholson and Cooper 1977). Neurological effects have also been reported in preclipped rabbits and rats after repeated application of endosulfan to the skin (Dikshith et al. 1988 Gupta and Chandra 1975). Dikshith et al. (1988) reported levels of a-, [3-, and total endosulfan in liver, kidney, brain, testes, fatty tissue, and blood 30 days after dermal application of endosulfan. 

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