Cumulative exposure

Cumulative risk is the combined risk resulting from exposures that accumulate over time, pathways, sources, or routes for a number of agents or stressors. This concept of cumulative risk addresses the fact that individuals are not usually exposed to a single environmental contaminant by means of a single exposure pathway. Multiple contaminants are released from sources as chemical mixtures. Environmental fate and transformation processes affect the nature, pathways, and extent of human exposure. Exposures by different pathways may result in differential absorption, metabolism, and toxic response, even for the same chemical. Cumulative risks are 

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Action levels for cumulative exposures within a 12 week period ... 

Calculation of the occupational exposure concentration (OEC) depends on the type of OEL. For example, when the limit value has been set as an eight-hour time-weighted average, the cumulative exposure for an eight-hour work shift should be computed as follows ... 

If workers are exposed simultaneously or successively to more than one chemical agent, the risk shall be assessed on the basis of the risk presented by all such chemical agents in combination. Usually, additive effects are assumed for the mixture of chemical agents, so the cumulative exposure is calculated as follows ... 

To comply with the OEL, the value of the cumulative exposure index shall not exceed unity. 

This policy seems to be rational and would be of tremendous help to registrants in getting more uses registered for their products. This would be especially useful when new uses (worth millions of dollars to the registrant) were to be added to the label in cases where no detectable residues were found in the food product and the risk cup (cumulative exposure risk) was nearly full. The following example highlights this point ... 

DNA - deoxyribonucleic acid, dosage - cumulative exposure equivalent to the concentration of chemical agent to which an individual is exposed integrated over the time of exposure, dose - quantity of agent having entered the body. 

However, some measures of cumulative exposure may be better predictors of impaired performance in workers with current PbB levels <40 pg/dL. 

Effects on Other Neurological End Points in Adults. Recent studies have provided evidence that exposure to lead affects postural balance. For example, Chia et al. (1996b) evaluated the possible association between postural sway parameters and current PbB concentration, cumulative PbB at different years of exposure, and an index of total cumulative exposure to lead in a group of 60 workers ... 

Balbus-Komfeld JM, Stewart W, Bolla KI, et al. 1995. Cumulative exposure to inorganic lead and neurobehavioural test performance in adults an epidemiological review. Occup Environ Med 52(1) 2-12. 

Lindgren KN, Masten VL, Ford DP, et al. 1996. Relation of cumulative exposure to inorganic lead and neuropsychological test performance. Occup Environ Med 53(7) 472-477. 

A worktable that can be used to calculate a cumulative exposure estimate on a site-specific basis is provided in Table 2. To use the table, environmental levels for outdoor air, indoor air, food, water, soil, and dust are needed. In the absence of such data (as may be encountered during health assessment activities), default values can be used. In most situations, default values will be background levels unless data are available to indicate otherwise. Based on the U.S. Food and Drug Administration s (FDA s) Total Diet Study data, lead intake from food for infants and toddlers is about 5 pg/day (Bolger et al. 1991). In some cases, a missing value can be estimated from a known value. For example, EPA (1986) has suggested that indoor air can be considered 0.03 x the level of outdoor air. Suggested default values are listed in Table 3. 

Up to 100 WLM of cumulative exposure, lung cancer risk shows... 

The cumulative exposure to such activity can be expressed as the amount of activity in WL multiplied by time. In past analyses of occupational exposure by miners, this cumulative exposure has been given in WLM assuming 170 hours in a working month and is calculated as... 

Acute lethality data for several laboratory species are summarized in the following sections. Lethal concentrations for various species are shown in Table 2 4. Cumulative exposures (C t) exhibit notable variability even within species. 

Several reports identified nonlethal effects in humans acutely exposed to arsine. These reports, however, lacked definitive exposure data but verified hematologic disorders leading to renal failure as critical effects of arsine exposure. Bulmer et al. (1940) (as cited in Elkins 1959) reconstructed an exposure incident at a gold extraction facility and estimated that subchronic (up to 8 mon) exposure to 0.12 ppm arsine resulted in jaundice and anemia (see Section 2.2.1). The lack of definitive exposure data for humans necessitates the use of animal data for quantitative estimation of AEGL values. Derivation of AEGL-2 values based upon limited human data (Flury and Zernik 1931) was considered but rejected because the data were poorly documented and inconsistent with other data showing lethality at lower cumulative exposures. 

Consistent with the human responses to arsine exposure, observations in several animal species (rats, mice, and hamsters) indicated hematologic involvement. Cumulative exposures of 540-1,800 ppm-min produced decreases in hematocrit levels, RBC counts, packed cell volumes, and increases in absolute and relative spleen weights (consistent with erythrocyte damage). For acute exposures, the exposure-response curve is steep generally less than a 10-fold difference between no-effect and lethality exposures. 

Lethality data are available for several animal species including rats, mice, monkeys, dogs, and cats. Cumulative exposures producing lethality range from 525 to 11,520 ppm-min, with the highest value representing a 24-h exposure to only 8 ppm. 

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