Dermal exposure development

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been made for methyl parathion. An MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. 

Although human data are not extensive, the data suggest that dermal effects may be a concern for some humans exposed to trichloroethylene, particularly through bathing with contaminated water however, it is unlikely that exposure to trichloroethylene in the air or soil at hazardous waste sites would be irritating to human skin. Some people may develop immunological sensitivity to trichloroethylene which may manifest as a dermal response following inhalation, oral, or dermal exposure to trichloroethylene. 

It is therefore advisable to group the various crop habitats and maintenance activities into "re-entry scenarios" and to determine whether standard values for the initial DFR shortly after the first application and generic transfer factors for the level of dermal exposure for each scenario can be developed. Investigations to this end have been carried out over the last two decades, primarily in the U.S. The generic transfer factors for a number of... 

Acute-Duration Exposure. Information is available regarding the effects of acute-duration inhalation exposure of humans to acrylonitrile and the effects are characteristic of cyanide-type toxicity. Quantitative data are limited but are sufficient to derive an acute inhalation MRL. Further studies of humans exposed to low levels of acrylonitrile in the workplace would increase the confidence of the acute MRL. Studies in animals support and confirm these findings. No studies are available on the effects of acute-duration oral exposure in humans however, exposure to acrylonitrile reveals neurological disturbances characteristic of cyanide-type toxicity and lethal effects in rats and mice. Rats also develop birth defects. Animal data are sufficient to derive an acute oral MRL. Additional studies employing other species and various dose levels would be useful in confirming target tissues and determining thresholds for these effects. In humans, acrylonitrile causes irritation of the skin and eyes. No data are available on acute dermal exposures in animals. 

Dermal toxicity due to JP-8 may also be attributed to increased free radical formation that may be involved in the development of skin sensitization [45], Following dermal exposure to JP-8, increasing levels of oxidative species are observed [46], In vitro studies with rat lung epithelial cells demonstrated that JP-8-induced cell death is inhibited by exogenous glutathione or the thiol-containing antioxidant N-acetyl-cysteine... 

Modified Buehler. Buehler (1964) developed the first test system to use an occlusive patch to maximize dermal exposure and to increase the test sensitivity (Buehler, 1964). Although, this assay is still insensitive for some xenobiotics that may not sufficiently traverse the epidermis, it is particularly useful for compounds that are either highly irritating by intradermal injection or cannot be dissolved or suspended in a form that is conducive to injection. Other advantages are that the test produces few false positives, rarely overpredicts the potency of sensitizers, and is less likely to produce limiting system toxicity or ulceration at the induction sites. Figure 15.4 shows the test design in its current (OECD) form. 

The available data were not sufficient for the development of acute-duration inhalation or oral MRLs. Additional data are necessary to further define the dose response of phenol following inhalation, oral, and dermal exposure. Because the oral toxicity of phenol varies with the concentration of the dose, studies using varying concentrations would be useful. 

BPA can occur due to an incomplete polymerization, followed by migration into the food or environment [200], Furthermore, BPA monomer is used as color developer in thermal paper and is consequently also present in recycled paper and paperboard which can be used as food packaging material [201]. Human exposure to BPA is believed to occur mainly through contaminated food, although recently dermal exposure and absorption have gained attention [202-204]. 

Renal Effects. Acute renal failure occurred in a man who washed his hair with an unknown amount of diesel fuel (Barrientos et al. 1977). In addition, he had oliguria biopsy revealed mitosis and vacuolization in renal cells, tubular dilation, and some cellular proliferation in the glomerulus. Another man developed acute tubular renal necrosis after washing his hands with an unspecified diesel fuel over several weeks (Crisp et al. 1979). Specifically, patchy degeneration and necrosis of the proximal and distal tubular epithelium with preservation of the basement membranes were noted. Also, increased blood urea nitrogen and serum creatinine levels were noted in this individual. Effects resulting from inhalation versus dermal exposure could not be distinguished in these cases. 

Some case studies suggest that dermal exposure to the vapor of diesel fuel may also result in absorption via the skin. The studies identify one individual with only vapor exposure and two others with vapor and/or direct dermal contact with diesel fuel individuals developed acute renal failure or renal necrosis (Barrientos et al. 1977 Crisp et al. 1979 Reidenberg et al. 1964). Also, dermal exposures to marine diesel fuel and JP-5 in mice induced renal damage (Basely et al. 1982). No studies were located that directly tested dermal absorption of fuel oil vapor. 

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