Exposure routes, toxicants

The toxicity of common acryhc monomers has been characterized in animal studies using a variety of exposure routes. Toxicity varies with level, frequency, duration, and route of exposure. The simple higher esters of acryhc acid are usually less absorbed and less toxic than lower esters. In general, acrylates are more toxic than methacrylates. Data appear in Table 5. 

Human and animal studies indicate that inorganic manganese compounds have a very low acute toxicity by any route of exposure. The toxicity values for a given Mn compound are shown in Table 20 to depend on the species of test animal as well as the route of exposure. Manganese concentrations as high as 2000 ppm were found to be tolerated by test animals over a six-month period without any ill effects (208). 

Ha2ard is the likelihood that the known toxicity of a material will be exhibited under specific conditions of use. It follows that the toxicity of a material, ie, its potential to produce injury, is but one of many considerations to be taken into account in assessment procedures with respect to defining ha2ard. The following are equally important factors that need to be considered physicochemical properties of the material use pattern of the material and characteristics of the environment where the material is handled source of exposure, normal and accidental control measures used to regulate exposure the duration, magnitude, and frequency of exposure route of exposure and physical nature of exposure conditions, eg, gas, aerosol, or Hquid population exposed and variabiUty in exposure conditions and experience with exposed human populations. 

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. 

Route Dependent Toxicity. The toxicity of trichloroethylene does not seem to be heavily dependent upon its route of entry. Inhalation and ingestion are the primary exposure routes, and the liver, heart, and central nervous system are the primary targets for both routes (Candura and Faustman 1991). Renal toxicity results principally from oral exposure, and dermal exposure generally confines its toxic effects to the skin, although broad systemic effects can be induced imder conditions of high exposure (Bauer and Rabens 1974). Attributing such effects solely to dermal exposure, however, is difficult because inhalation exposure is often a factor in these cases as well. 

Recycling of printer circuit boards is deemed as the most important source of heavy metals to the ambient environment. These heavy metals may be entering into human body from various exposure routes such as ingestion, inhalation, and dermal absorption. Exposure to high levels of heavy metals can lead to acute and chronic toxicity, such as damage to central and peripheral nervous systems, blood composition, lungs, kidneys, liver, and even death [14],... 

Chronic-Duration Exposure and Cancer. No studies were located in humans following chrome-duration exposure to hexachloroethane for any exposure route. No chronic animal studies were conducted using the inhalation route of exposure. In oral studies with rats, the kidney was identified as a primary target organ in males and females (NTP 1989). The kidney damage in male rats was the result of hyaline droplet nephropathy and, accordingly, was not suitable as the basis for an oral MRL. In contrast to acute- and intermediate-duration oral exposure, liver toxicity was not evident in rats following chronic oral exposure. There were no studies of chronic dermal exposure to hexachloroethane. 

Ballantyne, B. 1983. The influence of exposure route and species on the acute lethal toxicity and tissue concentrations of cyanide. In Developments in the Science and Practice of Toxicology. Elsevier Science Publishers, New York, pp. 583- 586. 

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. 

Effect of Dose and Duration of Exposure on Toxicity. The severity of neurological effects in humans and animals after acute oral exposure to cyanide is dose-related (Chen and Rose 1952 Lasch and El Shawa 1981). Central nervous system effects have been observed following acute-duration exposures (Levine and Stypulkowski 1959a) and chronic-duration exposures (Hertting et al. 1960), via the inhalation and oral routes. Necrosis is the most prevalent central nervous system effect following acute-duration exposure to high concentrations of cyanide, whereas demyelination is observed in animals that survive repeated exposure protocols (Bass 1968 Ibrahim et al. 1963). 

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