Exposure limits variations

In animal experiments exposures can be carefully controlled, and dose-response curves can be formally estimated. Extrapolating such information to the human situation is often done for regulatory purposes. There are several models for estimating a lifetime cancer risk in humans based on extrapolation from animal data. These models, however, are premised on empirically unverified assumptions that limit their usefulness for quantitative purposes. While quantitative cancer risk assessment is widely used, it is by no means universally accepted. Using different models, one can arrive at estimates of potential cancer incidence in humans that vary by several orders of magnitude for a given level of exposure. Such variations make it rather difficult to place confidence intervals around benefits estimations for regulatory purposes. Furthermore, low dose risk estimation methods have not been developed for chronic health effects other than cancer. The... 

TLV The TLV or Threshold Limit Value refers to a safe level of exposure by inhalation. The definition was established by the American Conference of Governmental Hygienists. There are several variations or criteria levels for the TLV. As an example, hydrogen sulfide has a TLV for short-term exposure limits (STEL) of 15 minutes of only 5 ppm. Comparing this to the TLV-STEL of 400 ppm for carbon monoxide provides an indication of the need to be extremely careful when H2S is suspected. Under OSHA Standards, and particularly on MSDS (Material Safety Data Sheets) compounds are associated with a time weighted average (TWA) TLV, which is the allowable concentration for an 8-hour continuous exposure period. For firefighting purposes, the short-term exposure is likely more realistic. 

As results vary with species (strains), lamps, detectors, doses, distances, time (exposure chemical to exposure light) chemical routes, endpoint (biological, erythema, edema, ear thickness) a somewhat structured method has been proposed to limit variation. To apply this method, at four skin sites apply 0.05 ml test chemical alone, under radiation, opaque cover, vehicle alone, and positive control at intervals of 5 min to 24 h. Irradiate all skin sites simultaneously for up to 40 min at a distance of up to 15 cm from the source. Adjust the exposure time so that 10Jcm UVA and 0.1 JemUVB using ... 

While cotinine functions fairly well as a marker of nicotine intake, it is not perfect due to individual variation in metalxtlism as discussed previously. As described earlier in this chapter, cotinine metabolism is affected by factors such as race, gender, age, genetic variation in the liver enzyme CYP2A6, and/or by the presence of pregnancy, liver or kidney disease. Another limitation to the use of cotinine is that, given an average half-life of 16 h, cotinine levels reflect relatively short-term exposure to tobacco (that is, over the past 3 days). 

The principal effects of carbon tetrachloride in humans are on the liver, the kidneys and the central nervous system. These effects are apparent following either oral or inhalation exposure, and limited data indicate they can occur after dermal exposure as well. All of the effects seen in humans except renal injury are demonstrable at roughly comparable exposure levels in animals, although there are some variations in susceptibility between species that are likely to be related to differences in metabolism. No studies were located regarding reproductive and developmental effects in humans after exposure to carbon tetrachloride. In rats, carbon tetrachloride was not shown to adversely affect reproduction or development. Studies with both mice and rats suggest that sufficiently high doses of carbon tetrachloride may increase the risk of liver tumors in exposed humans. 

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