Inhalants statistics

A comprehensive study of fire (and nonfire) fatalities associated with carbon monoxide showed that carbon monoxide inhalation statistically tracks fire fatalities.199 200 203... 

The eombined ineidence of stomach, liver, prostate, and lymphohematopoeitic cancers was increased among 2,050 male and 1,924 female Finnish workers occupationally exposed primarily to trichloroethylene (Antilla et al. 1995). The workers were exposed principally through inhalation, although there was some dermal contact. The statistical power of this study was low. 

Lethal concentration 50 (LC50) is the vapour concentration of a substance in air, which kills 50% of the animals exposed. This estimate comes from a protocol that was statistically controlled. This value depends on the animal chosen for the experiments and exposure time. The three animals that are most commonly used are in descending order rat, mouse and rabbit. It is a parameter that estimates risk level by inhalation, which is the most important means of penetration involving toxic substances in the work place. 

Mineral Oil Hydraulic Fluids. No information on hematological effects in humans after inhalation, oral, or dermal exposure to mineral oil hydraulic fluids is available. In another animal study, a statistically significant reduction of 16% was reported in the percentage of lymphocytes in whole blood in rats receiving 1,000 mg/kg/day MIL-H-5606 by gavage for 26 days (Mattie et al. 1993). 

Another case of multimedia fate modeling may be exemplified by human inhalation exposure estimates for PCB spills. The spill size is estimated considering both spread and soil infiltration. Volatilization calculations were carried out to get transfer rates into the air compartment. Finally, plume calculations using local meteorological statistics produced ambient concentration patterns which can be subsequently folded together with population distributions to obtain exposures. 

The hemolytic potential of arsine is considerable. Arsine at 0.1-0.5 mM may cause significant hemolysis (Hatelid et al. 1995 Pernis and Magistretti 1960). Inhalation exposure of mice to arsine at 9 ppm for only 1 h resulted in a statistically significant decrease in hematocrit levels at 24 h to 11 d after exposure (Peterson and Bhattacharyya 1985). The practical significance of this finding is demonstrated by a simple calculation provided by Klimecki and Carter (1995) showing an arsine concentration of 0.26 mM resulting from a 4-h exposure to arsine at a concentration of 30 ppm. This calculation assumed a minute alveolar... 

It is not entirely clear whether the acetone co-exposure in the Sanagi et al. (1980) study contributed to the observed effects. Indirect evidence from an occupational study (Cardona et al. 1996) showed that workplace acetone concentrations had a statistical correlation with the ratio of urinary -hexane metabolites to /i-hcxanc air concentration, although it did not correlate with measured urinary metabolites. No animal studies are available describing the effects of inhalation co-exposure to acetone and -hexane, although there are several studies which report interactions between acetone and the neurotoxic metabolite of -hexane 2,5-hexanedione (See Section 2.4, Mechanisms of Action). Oral administration of acetone has been reported to potentiate the neurotoxicity caused by oral exposure to the neurotoxic u-hexane metabolite 2,5-hexanedione in rats (Ladefoged et al. 1989, 1994). Oral exposure to acetone alone in rats at 650 mg/kg/day resulted in a statistically significant decrease in motor nerve conduction velocity after 6 weeks co-exposure to acetone and 2,5-hexanedione resulted in greater effects... 

The interaction of /2-hexane with toluene and trichloroethylene has also been examined in volunteers (Baelum et al. 1998). Exposure in these experiments was via a gastric feeding tube at controlled rates equivalent to what the authors stated would be delivered to the liver by inhalation exposure at Danish occupational exposure limits (50 ppm /7-hexane. 50 ppm toluene, and 30 ppm trichloroethylene). Coexposure to toluene and trichloroethylene slightly increased the area under the curve (AUC) representing concentration versus time for end exhaled /2-hexane air concentration, but urinary excretion of 2,5-hexanedione was unchanged. The only statistically significant interaction observed with /2-hexane was an 18% decrease in the urinary excretion of hippuric acid, a toluene metabolite. 

To evaluate inhalation toxicity in situations where workers are exposed to various concentrations and durations of a drug vapor, aerosol, or powder in the work environment during manufacturing or packaging, a more comprehensive determination of E(COso or L(Ct)so values are used. The E(Ct)50 or L(Ct)so values are statistically derived values that represent the magnitude of exposure, expressed as a function of the product of C and t, that is expected to affect or kill less than 50% and more than 50% of the animals. The other curve represents exposures that kill 50% or more than 50% of each group of animals (Irish and Adams, 1940). 

Hematological Effects. Intermediate and chronic inhalation exposure of humans to mixtures of heptachlor, chlordane, and other chemicals has been associated with leukemia and aplastic and hemolytic anemias. These exposures were either occupational or followed the use of termiticides in homes. These exposures were probably primarily inhalation combined with dermal. There are oral animal studies that confirm that the hematopoietic system, specifically the white cells, can be affected by heptachlor exposure. Rats fed 0.5 mg/kg/day heptachlor in the diet showed a statistically significant increase in total white blood count (Enan et al. 1982). It appears that although the hematopoietic system is not a primary target for heptachlor or heptachlor epoxide, it can be measurably affected. 

The animal studies for oral exposure to heptachlor and heptachlor epoxide are almost all limited to some extent by the number of doses used, the lack of appropriate statistics, or the small number or lack of controls. No information was located regarding the health effects of inhalation or dermal exposure, with the exception of a dermal LDso in rats. Exposure of the general population via the inhalation and dermal routes may result from contaminated soil or vapors from treated houses. Some exposures from contaminated soil or water may occur in populations located near hazardous waste sites in which these chemicals have been stored or from food grown in contaminated soil. 

Intermediate-Duration Exposure. Because the human studies do not report quantitative information on dose or duration, it is not possible to know with certainty whether the combined inhalation and dermal exposures were of intermediate duration. There are intermediate-duration oral exposure data from animal studies that indicate that the liver and the hematologic systems are affected by heptachlor exposure (Enan et al. 1982 Halacka et al. 1974 Pelican 1971). The liver is probably the more sensitive of the two. No intermediate-duration oral or inhalation MRLs for heptachlor or heptachlor epoxide have been determined because of limitations in the studies, including lack of statistical comparisons, insufficient number of dose levels, no identification of NOAELs, and the description of effects that may be considered adaptive and not adverse. 

In a report on a research project quantification of extrapolation factors (Kalberlah and Schneider 1998), it is noted that extrapolation factors are intended to replace lack of knowledge by a plausible assumption, and that instimtions with responsibihty for establishing the mles must decide which level of statistical certainty, e.g., applicable for 50% or for 90% of a representative selection of substances, is desired for the selection of a standard value. It is furthermore noted that extrapolation factors are required for (1) time extrapolation, e.g., from a subchronic to a chronic duration of exposure (2) extrapolation from the LOAEL to the NAEL (3) interspecies extrapolation, i.e., from experimental animals to humans and (4) intraspecies extrapolation, i.e., from groups of persons with average sensitivity to groups of persons characterized by special sensitivity. In addition to these extrapolations, route-to-route extrapolation, e.g., oral-to-inhalation or dermal-to-oral must also be discussed. 

The US-EPA Child Specific Exposure Factors Handbook (US-EPA 2006), first published in 2002, consolidates all children s exposure factors data into one document. The document provides a summary of the available and up-to-date statistical data on various factors assessing children s exposures. These factors include drinking water consumption soil ingestion inhalation rates dermal factors including skin area and soil adherence factors consumption of fruits, vegetables, fish, meats, dairy products, homegrown foods, and breast milk activity patterns body weight consumer products and life expectancy. 

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