Acute toxicity exposure factors

Health, Safety, and Environmental Factors. Sulfur dioxide has only a moderate acute toxicity (183). The lowest pubHshed human lethal concentration is 1000 ppm for 10 months. The lowest pubHshed human toxic concentration by inhalation is 3 ppm for 5 days or 12 ppm for 1 hour. The lowest pubHshed human lethal concentration is 3000 ppm for 5 months. In solution (as sulfurous acid), the lowest pubHshed toxic dose is 500 flg/kg causing gastrointestinal disturbances. Considerable data is available by other modes of exposure and to other species NIOSH standards are a time-weighted average of 2 ppm and a short-term exposure limit of 5 ppm (183). 

Intraspecies Because the species used was the most sensitive to monomethylhydrazine toxicity and the most closely related to humans, an uncertainty factor of 3 is justified. A factor of 3 was used. Although the mechanism of toxicity is uncertain and sensitivity among individuals may vary, the exposure-response relationship is steep, suggesting limited variability in the toxic response to methylhydrazine. Furthermore, it is likely that acute toxic responses are, at least initially, a function of the extreme reactivity of methylhydrazine. The interaction of the highly reactive monomethylhydrazine with tissues (e.g., pulmonary epithelium) is not likely to greatly vary among individuals. 

The following factors have been suggested as alternatives to consider when presented with a potential case of exposure to carbon monoxide diabetic ketoacidosis, hypothyroidism and myxedema coma, labyrinthitis, and lactic acidosis toxic exposures resulting in methemoglobinemia ingestion of alcohols or narcotics and diseases that cause gastroenteritis, encephalitis, meningitis, and acute respiratory distress syndrome. 

Persons with a history of convulsive disorders would be expected to be at increased risk from exposure to endrin. Children may be more sensitive than adults to the acute toxic effects of endrin. In an endrin poisoning episode in Pakistan, children 1-9 years old represented about 70% of the cases of convulsions (Rowley et al. 1987). The causative factor responsible for the outbreak was not identified, however, and the age distribution of cases could be explained by age-specific exposure situations. In general, following oral administration, female animals appear to be more susceptible to endrin toxicity than males (Gaines 1960 Treon et al. 1955). The difference may be due to the more rapid excretion of endrin by male versus female rats (Hutson et al. 1975 Klevay 1971 Korte et al. 1970). A sex-related difference in toxicity was not apparent following dermal exposure (Gaines 1960, 1969). No sex-based differences in endrin-related... 

A Dutch smdy (Wilschut et al. 1998, as reviewed in Vermeire et al. 1999) has evaluated route-to-route extrapolation on the basis of absorption or acute toxicity data. Data were collected primarily on dermal and inhalation repeated dose toxicity. An extrapolation factor, defined as the factor that is applied in route-to-route extrapolation to account for differences in the expression of systemic toxicity between exposure routes, was determined for each substance by using data on absorption and acute toxicity data. As experimental data on absorption often were not available, default values for absorption were also used to determine an extrapolation factor. Despite a rather large overall database, relatively few data could be used for the evaluation and the selection criteria were modified in order to include data that initially were considered less suitable for data analysis interspecies extrapolation based on caloric demands was introduced, and a factor of 3 was applied in case a LOAEL instead of a NOAEL was available. The choice of NOAELs for different exposure routes known for a substance suitable for analysis was based primarily on the same effect, but this criterion could not be maintained. 

Arsenic, Cobalt, Copper TT assessment of relationships between acute toxicity and various experimental variables (e.g., metal concentration in water, time of exposure, bioconcentration factor) with two fish species. F,F (Liao and Lin, 2001)... 

The most important factor is the dose-time relationship. The dose-time relationship forms the basis for distinguishing between two types of toxicity acute and chronic. Acute toxicity of a chemical refers to its ability to inflict systemic damage as a result (in most cases) of a one-time exposure to relative large amounts of the chemical. In most cases, the exposure is sudden and results in an emergency situation. 

Skin. The skin may become contaminated accidentally or, in some cases, materials may be deliberately applied. Skin is a principal route of exposure in the industrial environment. Local effects that are produced include acute or chronic inflammation, allergic reactions, and neoplasia. The skin may also act as a significant route for the absorption of systemically toxic materials. Factors influencing the amount of material absorbed include the site of contamination, integrity of the skin, temperature, formulation of the material, and physicochemical characteristics, including charge, molecular weight, and hydrophilic and lipophilic characteristics. Determinants of percutaneous absorption and toxicity have been reviewed (32—35,42,43,46—49). 

The most important factor is the dose-time relationship. The amount of a substance that enters or contacts a person is called a dose. An important consideration in evaluating a dose is body weight. Dose is the quantity of a chemical substance that a surface, plant, or animal is exposed to. Time means how often one is exposed to or the duration of exposure to a chemical substance. In simple terms, the dose-time relationship provides information on how much of the test substance is involved and how often the exposure to the test substance occurs. This relationship gives rise to two different types of toxicity of a chemical substance—namely, acute toxicity and chronic toxicity. 

The principal study involved a non-oral exposure route (intraperitoneal) and required route-to-route extrapolation using acute toxicity data. Because of uncertainties associated with the use of this nonstandard methodology, a Modifying Factor of 3 was applied to the RfD. 

Studies of occupational exposures to sulfur mustard indicate an elevated risk of respiratory tract and skin tumors following long-term exposure to acutely toxic concentrations. Overall, several factors are important regarding the assessment of the carcinogenicity of sulfur mustard. Increased cancer incidence in humans appears to be associated only with exposures that caused severe acute effects, and occupational exposures tended to involve repeated exposures and repeated injury of the same tissues. Because the therapeutic use of the sulfur mustard analog nitrogen mustard is associated with an increased incidence of CML, the reports of CML in HD-exposed individuals appear to be relevant to the eareinogenicity of sulfur mustard. 

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