Exposure duration dermal absorption

Duration and route of exposure can influence the interpretation of biological markers for instance, in some cases, pesticides that are inhaled remain in systemic circulation longer than those that are ingested. Compounds characterized by a slow process of dermal absorption can give rise to prolonged kinetics if compared to the kinetics following ingestion or inhalation of the same compounds. 

Animal data include an inhalation study in rabbits that resulted in an increased incidence of retroesophageal right subclavian artery in the fetuses (Hayes et al. 1985), and an oral study in rats that resulted in an increased incidence of an extra rib (NTP 1987). The data were considered sufficient to derive an acute-duration inhalation MRL of 0.8 ppm, based on a NOAEL of 300 ppm for lack of developmental effects in rabbits. It would be useful to have additional information on the developmental effects of 1,4-dichlorobenzene by inhalation and oral exposure in relation to maternal toxicity. There are currently no data available for the dermal route. Information on the developmental effects of dermal exposures would be useful if dermal absorption and systemic distribution of 1,4-dichlorobenzene could be demonstrated in toxicokinetic studies. 

Absorption, Distribution, Metabolism, and Excretion. Levels of cresols in blood were obtained from a single case report of a dermally exposed human (Green 1975). Data on the toxicokinetics of cresols in animals were contained in two acute oral studies that provided only limited quantitative information on the absorption, metabolism, and excretion of cresols (Bray et al. 1950 Williams 1938). A more complete oral toxicokinetics study, in addition to studies using dermal and inhalation exposure, would provide data that could be used to develop predictive pharmacokinetic models for cresols. Inclusion of several dose levels and exposure durations in these studies would provide a more complete picture of the toxicokinetics of cresols and allow a more accurate route by route comparison, because it would allow detection of saturation effects. Studies of the tissue distribution of cresols in the body might help identify possible target organs. 

Information on toxic effects of acute-duration exposure to PBBs by routes other than oral are limited to data on hepatic, renal, dermal, and ocular effects of inhalation and dermal exposure in rats or rabbits (Millischer et al. 1980 Needham et al. 1982 Norris et al. 1975a Waritz et al. 1977), but these data may not be reliable due to study limitations and possible delayed lethality. Quantitative data for inhalation and dermal absorption of PBBs are lacking. Studies of inhalation and dermal absorption following exposure to soil containing PBBs (i.e., bioavailability studies) would be useful for assessing risk at a hazardous waste... 

Okrent and Xing (1993) estimated the lifetime cancer risk to a future resident at a hazardous waste disposal site after loss of institutional control. The assumed exposure pathways involve consumption of contaminated fruits and vegetables, ingestion of contaminated soil, and dermal absorption. The slope factors for each chemical that induces stochastic effects were obtained from the IRIS (1988) database and, thus, represent upper bounds (UCLs). The exposure duration was assumed to be 70 y. Based on these assumptions, the estimated lifetime cancer risk was 0.3, due almost entirely to arsenic. If the risk were reduced by a factor of 10, based on the assumption that UCLs of slope factors for chemicals that induce stochastic effects should be reduced by this amount in evaluating waste for classification as low-hazard (see Section 7.1.7.1), the estimated risk would be reduced to 0.03. Either of these results is greater than the assumed limit on acceptable risk of 10 3 (see Table 7.1). Thus, based on this analysis, the waste would be classified as high-hazard in the absence of perpetual institutional control to preclude permanent occupancy of a disposal site. 

Intermediate-Duration Exposure. No human data were located concerning intermediate-duration exposures of humans to DEHP by any route. No data were located from animal studies after inhalation or dermal exposures. Therefore, MRL values cannot be determined for intermediate-duration exposures by the inhalation route. Due to the low vapor pressure of DEHP and its poor dermal absorption, and the fact that the contribution of the inhalation and dermal routes of exposure to body burden is considered minimal, specific studies of intermediate-duration exposures and dose-response pattern by the inhalation and dermal routes do not appear justified. 

DNOC is rapidly absorbed by the respiratory tract in humans and animals. A serum DNOC concentration of 1,000 pg/mL was detected in a spray operator 24-36 hours after inhaling a dense DNOC mist for an acute duration (van Noort et al. 1960). The worker subsequently died. Because the spray operator had previous dermal exposure to DNOC, the acute inhalation of dense DNOC mist probably caused the serum DNOC level to spike to lethal levels. A blood DNOC concentration of 60 pg/g was detected in a spray operator who had periodically inhaled an unknown amount of DNOC for 5 weeks (Pollard and Filbee 1951). The blood sample was collected after a 2-day period of no exposure. In addition, a DNOC peak urinary level of 22 mg was detected on the third day after the patient was admitted to the hospital, and a total of 89.9 mg DNOC was eliminated in the urine over 20 days. While these data indicate absorption after inhalation exposure, there was also possible dermal absorption. In an occupational exposure study involving DNOC manufacturers, winter-washer sprayers, and cereal-crop sprayers, a correlation between blood DNOC levels and the symptoms and signs of poisoning was observed (Bidstrup et al. 1952). Blood DNOC levels <10-20 p g/g were not generally associated with signs of toxicity, while concentrations greater than 44 pg/g resulted in several illnesses. 

In the risk assessment, some steps are not well described. For example, subchronic toxicity studies and not chronic toxicity studies are used in the risk assessment. Exposure duration and frequency considerations are not discussed. Route-to-route extrapolation is considered acceptable implicitly, without further evaluation of the various issues involved. The rationale for using a dermal absorption default of 10 %, in the absence of data is also not discussed. 

This model has a straightforward structure and is simple to use. It is based on studies carried out in part for the specific purpose of model development. However, not all of the required information is publicly available. The databases are not described at the study level the exposure data are only available in classes, although more detailed information is available on request. The choice of the statistics is not discussed. In the risk-assessment approach, some steps are not clearly presented. Sub-chronic toxicity studies, and not chronic toxicity studies, are used in the risk assessment. Exposure duration and frequency considerations are not discussed. Route-to-route extrapolation is considered acceptable implicitly, without further evaluation of the various issues involved. The rationale for using a dermal absorption default of 10 %, in the absence of data, is not discussed. 

This chapter provides an overview of factors affecting dermal absorption. Factors influencing absorption are among others related to the skin (e.g. anatomical site, difference between species, metabolism, etc.) and the exposure conditions (e.g. area dose, vehicle, occlusion and exposure duration). In order to provide relevant information for the risk assessment of pesticides, dermal absorption studies should take these aspects into account. With respect to the methods being used nowadays for the assessment of dermal absorption, it is important to realize that neither in vitro nor in vivo animal studies have been formally validated. Available data from various in vitro studies, however, indicate that the use of the total absorbed dose (i.e. the amount of test substance in the receptor medium plus amount in the skin) could be used in a quantitative manner in risk assessment. Tape stripping of the skin can be adequate to give a good indication of test chemical distribution, and hence its immediate bioavailability. 

Active ingredient E - 55% water-dispersible granule groundboom application to soybean (E-1, E-2) and corn (E-3, E-4) farmer and custom applicator dermal absorption <30% exposure duration, short-term for farmer and intermediate-term for custom applicator... 

Alachlor is absorbed orally. Dermal absorption may be linear over time for the duration of exposure. Excretion via kidneys is the major route of elimination. 

No quantitative data regarding absorption in humans after dermal exposure to chlordane were located. Kazen et al. (1974) reported that chlordane tends to persist on the hands of pest control operators (exposure duration not reported) for at least 2 years after exposure to the pesticide has... 

No acute-duration inhalation MRL could be derived for mirex because no inhalation data could be located. No acute-duration oral MRL was derived for mirex because serious effects (heart block and arrhythmias in fetuses from dams exposed during gestation) were observed at the lowest dose tested (Grabowski 1983a). Studies examining the effects of mirex and chlordecone after acute-duration dermal exposure would be helpful since persons at hazardous waste sites may be exposed dermally to mirex. Additional dermal studies are certainly necessary because skin absorption of chlordecone appears to be an important route of exposure (Taylor et al. 1978). However, populations at hazardous waste sites are unlikely to be exposed via inhalation since these substances are virtually nonvolatile, so future studies using this route of exposure are not essential. 

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