Inhalation-dermal absorption

Dermal/Inhalation Absorption Correction. Since it is generally presumed that 100% of the Inhaled pesticide dose is absorbed, little work is being done to refine this. It has also been shown that in most agricultural applicators the dermal route is the predominant route of exposure. However, the patch methods which are used only... 

A case can often be made to omit studies as scientifically unnecessary, because it is possible to conduct an adequate risk assessment without them. This is most often the case if the substance decomposes to degradants of known hazardous properties. For example the substance may hydrolyse rapidly to non-toxic products, so the key issue is to establish that this happens rapidly in the stomach before the parent substance can be absorbed. There may then be a case for omitting the expensive long-term animal studies, providing it is also established that there is no dermal or inhalation absorption from these exposure routes. In a similar way, it may be justified to omit ecotoxicity studies on a substance which hydrolyses or otherwise decomposes in the aquatic environment to stable products that have already been tested. 

A clear influence of dermal absorption on the total absorption in addition to the oral or inhalation absorption... 

Human exposure to di(2-ethylhexyl) phthalate can occur via the dermal, inhalation, oral and intravenous routes. The high level of exposure has prompted many studies on the absorption, distribution, metabolism and excretion of di(2-ethylhexyl) phthalate in humans (Lawrence Tuell, 1979 Thomas Thomas, 1984 Burg, 1988 Albro Lavenhar, 1989 Kamrin Mayor, 1991 Huber et al., 1996 Doull et al., 1999). 

The relative contributions of dermal/ocular absorption, ingestion, and inhalation of silver compounds to the development of these ocular deposits and skin color changes are not known. However,... 

Studies were located for oral and dermal absorption in animals, but are lacking for absorption from inhalation exposure. Additional animal data would be useful in predicting the rate and extent of the inhalation absorption of various silver compounds in humans. 

At the completion of the study, the data obtained should be evaluated in relationship to exposure (dermal and inhalation), absorption (urinary metabolites), effects (ChE inhibited), acute, chronic, and metabolic studies in laboratory animals. These findings should then be evaluated and discussed in relation to existing or proposed labeling or regulations. 

Figure 11.6 illustrates a process to follow to assess a substance s absorption potential. The first step is to establish the types of individuals (i.e., workers, consumers, or general population) at greatest risk of exposure and the known or likely routes (dermal, inhalation, or oral) by which exposure will take place. The second step is to determine whether measured absorption data for the substance are available. Such data are often not available, but animal absorption data can be used as surrogates for human data in many cases. If no measured absorption data are available, toxicity data from studies involving humans or animals exposed to the substance may be useful. For example, if systemic toxic effects were noted in humans or animals following dermal (or oral or inhalation) exposure to a substance, especially at low doses, then obviously the substance is absorbed via this route. 

There is a wealth of literature showing significant differences in the acute toxicity values of chemicals (particularly pesticides) by oral and dermal routes of exposure. In a majority of instances, chemicals (particularly pesticides) are more toxic by ingestion than by skin absorption. However, it should be remembered that workers handling pesticides invariably can be affected through all three routes of exposure (oral, dermal, inhalation) and must exercise extreme caution (Table 2-9). 

The route of exposure is another aspect of exposure in which health-relevance must be considered. In Section One of this book, there is a detailed discussion of exposure assessment methodologies, including the importance of identification of the most prevalent route of exposure (dermal, inhalation or oral) and the necessity of knowing the absorption of the pesticide to allow calculation of the absorbed dose for risk assessment. For epidemiological purposes, exposure-assessment smdies are usually limited to assessing contact exposure levels. Since dermal absorption is not known for many pesticides or complex mixtures, uptake through the dermal route can often not be estimated and contact exposure data are a poor proxy of internal exposure (absorbed dose) (Schneider et al., 1999). 

Absorption from the gastrointestinal (GI) tract is poor (6% absorption in rats) with the remainder primarily eliminated in the feces. Oral diquat is transformed to a minimal degree within the intestines, with fecal elimination of metabolites. Complete elimination occurred within 4 days after oral dosing. Diquat was rapidly eliminated via the urine with dermal, inhalation, or intravenous dosing. With subcutaneous dosing, 90% was eliminated within 24 h via urine. Following intravenous administration in mice, diquat did not accumulate in lung or muscle. 

Absorption of TCE following inhalation exposure in humans is characterized by an initial rate of trichloroethylene uptake that is quite high. Retention of inhaled TCE has been measured at 37% and 75% of the amount inhaled. Absorption of TCE following oral exposure in both humans and animals is rapid and extensive. In animal studies, absorption from the gastrointestinal tract has been measured at 91-98%, and peak TCE blood levels are attained within a matter of hours. Dermal absorption of TCE in both humans and animals is slow, but dermal absorption studies are complicated by the fact that pure liquid TCE can act to defat the skin and thereby enhance its own absorption. 

Blancato, J. N., and Bischoff, K. B. (1993). The application of pharmacokinetic models to predict target dose. In Health Risk Assessment Dermal Inhalation Exposure and Absorption [Pg.610]

Vinyl monomer, many industrial uses. White powder, very soluble in water. Dermal, oral and inhalation absorption. Repeated exposure polyneuritis, sensory losses in limbs, weakness, ataxia. 

Moderately toxic by ingestion and inhalation absorption through skin may be very slow and, therefore, almost nontoxic by dermal route used as a herbicide, rather than as a pesticide toxic symptoms are those of other carbamate esters ... 

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. 

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). 

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). 

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. 

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... 

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