Human equivalent dose , animal testing

Data from epidemiological studies, of sufficient quality, are generally preferred for estimating risks. When the evaluation is based on animal studies, the estimation of a human-equivalent dose should utilize toxicokinetic data for cross-species dose scaling if adequate data are available. Otherwise, a default procedure should be applied. The aim of the cross-species dose scaling is to define exposure levels for humans and animals that are expected to produce the same degree of effect, taking into account differences in scale between test animals and humans, such as size and life span. 

For extrapolation to humans, the U.S. EPA has adopted a convention of applying an uncertainty factor of 10 to the dose tested in animals. This is equivalent to assuming that the chemical is ten times more toxic in humans than in the test animal. Although this factor was not based on science when it was developed in the 1950s,... 

Species The test species, whether animal or human, are identified in this column. Chapter 2, "Relevance to Public Health," covers the relevance of animal data to human toxicity and Section 3.4, "Toxicokinetics," contains any available information on comparative toxicokinetics. Although NOAELs and LOAELs are species specific, the levels are extrapolated to equivalent human doses to derive an MRL. 

The AEGL-1 concentration was based on a 1-hour (h) no-effect concentration of 8,000 parts per million (ppm) in healthy human subjects (Emmen et al. 2000). This concentration was without effects on pulmonary function, respiratory parameters, the eyes (irritation), or the cardiovascular system. Because this concentration is considerably below that causing any adverse effect in animal studies, an intraspecies uncertainty factor (UF) of 1 was applied. The intraspecies UF of 1 is supported by the absence of adverse effects in therapy tests with patients with severe chronic obstructive pulmonary disease and adult and pediatric asthmatics who were tested with metered-dose inhalers containing HFC-134a as the propellant. Because blood concentrations in this study approached equilibrium following 55 minutes (min) of exposure and effects are determined by blood concentrations, the value of 8,000 ppm was made equivalent across all time periods. The AEGL-1 of 8,000 ppm is supported by the absence of adverse effects in experimental animals that inhaled considerably higher concentrations. No adverse effects were observed in rats exposed at 81,000 ppm for 4 h (Silber and Kennedy 1979) or in rats exposed... 

The LLNA is the preferred method when compared to the GPMT because (a) it can equivalently predict human contact dermatitis, (b) a dose-response can be obtained, and (c) it is in line with current animal welfare efforts. Nevertheless, several situations exist where the GPMT is advantageous, depending predominantly on the choice of test substances. The LLNA is known for less powerful detection of the sensitization potential of metallic compounds, high molecular weight proteins, strong irritants, and for substances with low adhesion to the skin surface (skin wettability is a prerequisite for the successful application of LLNA) [136-140],... 

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