Multiple exposures

Number of Exposures. Some toxic effects are produced in response to a single exposure of sufficient magnitude, while others require multiple exposures for their development (see Table 1). 

ACUTE TOXICITY Advcfse health effects occumng within a short time period of exposure to a single dose of a chemical or as a result of multiple exposures over a short time period, e.g. 24 hours. 

When the total hazard index for an exposed individual or group of indii iduals exceeds unity, dicrc may be concern for potential non cancer health effects. As indicated before, for multiple exposure pathways, the hazard index can exceed unity even if no single exposure padiway hazard index exceeds unity. If the total hazard index exceeds unity and if combining exposure... 

Multiple exposure photography is used to illustrate the movement oi a pole vaulter. tCorbis-Bettmann)... 

No studies were located regarding interactions with other substances in humans or animals after exposure to diisopropyl methylphosphonate. However, the potential for multiple chemical interactions does exist. Diisopropyl methylphosphonate has been identified in the RMA in the presence of many other chemicals (such as endrin, dieldrin, dicyclopentadiene, bicycloheptdiene, diethyl benzene, and diethyl disulfide). The nervous system is a target of many of these compounds found at the RMA, including diisopropyl methylphosphonate. Therefore, there is potential for interaction, and studies examining multiple exposures would be useful in predicting risk to humans. Workers at the RMA reported skin irritation after dermal exposure to diisopropyl methylphosphonate at concentrations around 11.3 ppm in water. However, several other chemicals were also in the area (NIOSH 1981). Therefore, it is not clear if diisopropyl methylphosphonate contributed to the effects. 

A potentiation of neuropathy has been observed in studies involving administration of -hexane or methyl -butyl ketone with O-ethyl-O-4-nitrophenyl phenylphosphonothioate (EPN) (Abou-Donia 1983 Abou-Doniaetal. 1985). Administration of each compound individually resulted in peripheral neuropathy. The peripheral neuropathy observed when /7-hexane or methyl n-butyl ketone was administered simultaneously with EPN was more severe and had an earlier onset (Abou-Donia et al. 1985). The potential interactive effect of multiple exposures to different organophosphorus pesticides on delayed neuropathy has not been characterized (Chemiack 1988). 

FUN tool is a new integrated software based on a multimedia model, physiologically based pharmacokinetic (PBPK) models and associated databases. The tool is a dynamic integrated model and is capable of assessing the human exposure to chemical substances via multiple exposure pathways and the potential health risks (Fig. 9) [70]. 2-FUN tool has been developed in the framework of the European project called 2-FUN (Full-chain and UNcertainty Approaches for Assessing Health Risks in FUture ENvironmental Scenarios www.2-fun.org). 

IRAP-h View Interface for conducting a comprehensive multipathway human health risk assessment. It simultaneously calculates risk values for multiple chemicals, from multiple sources, at multiple exposure locations. IRAP-h view implements the US EPA - OSW Human Health Risk Assessment Protocol (HHRAP) US EPA [15]... 

Aniline may be absorbed following inhalation, ingestion, and dermal exposures. The inhalation toxicity of aniline was studied in several animal species, but only one study that utilized multiple exposure concentrations for sublethal effects was located. Data from human studies lack specific details or exposures... 

Figure 8. TGA of cured films (cured by exposure to Fusion 600 D model lamp) of an equimolar MPBM/CHVE mixture ( —) and a HDDA film with 3 weight percent DMAP photoinitiator ( — ). Light intensity approximately same as for Figure 6 with multiple exposures for each system.

Modern site layouts require sufficient separation of plants within the site to minimize risks of multiple exposures. 

The period of the test depends on whether long- or short-term effects are of interest. Acute toxicity is the effect of a single exposure or a series of exposures close together in a short period of time. Chronic toxicity is the effect of multiple exposures occurring over a long period of time. Chronic toxicity studies are difficult to perform because of the time involved most toxicological studies are based on acute exposures. The toxicological study can be complicated by latency, an exposure that results in a delayed response. 

In general, from a clinical standpoint, the development of resistance to the quinolones has not emerged as a major problem. Recent reviews have placed this issue in appropriate perspective [40]. Resistance to the new quinolones, as the result of single-step mutation occurs at a very low frequency (< 10 9) high-level resistance may be obtained by in vitro multiple exposures of organisms... 

Caufield, C., Multiple Exposures Chronicles of the Radiation Age, University of Chicago, Chicago, IL, 1989. 

EROD activity is measured in the H411E cells as follows. The cells are seeded at 7,000 cells per well in 250 xL of Dulbecco s modified Eagles culture media (Tillitt et al., 1991). After an initial incubation period of 24 hours, the cells are dosed with 5 xL volumes of eiuiched SPMD extracts (cleanup of extracts generally includes dialysis and size exclusion chromatography [SEC]) and incubated for an additional 72 hours. Sample dose is typically expressed as g-equivalents triolein or whole SPMD per mg cellular protein. Multiple exposures are performed at each of six (typically) sample concentrations, using a dilution series. Afterwards, the microtiter plates are washed three times with distilled water to lyse the cells. EROD activity (pmol mg cellular protein per min) in each sample is measured... 

Owing to the very high intensity of SR, exposure times on nuclear plates are typically ten minutes, whereas for such a slow emulsion, exposures are of the order of days in the laboratory. This reduction in timescale is particularly important for multiple exposure topographs of deformed crystals. 

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