Biological thresholds

The Chemical Substances Threshold Limit Values Committee classifies certain substances found in the occupational environment as either confirmed or suspected human carcinogens. The present listing of substances that have been identified as carcinogens takes two forms those for which a TLV has b n assigned and those for which environmental and exposure conditions have not been sufficiently defined to assign a TLV. Where a TLV has been assigned, it does not necessarily imply the existence of a biological threshold however, if exposures are controlled to this level, we would not expect to see a measurable increase in cancer incidence or mortality. 

Keywords biological monitoring biological threshold limit value body fluids ... 

In order to fill in these blanks and to give a more real reflection of the picture of exposure, the biological monitoring of harmful substances should be carried out and, especially its kinetic properties in the body should be established. Toxicokinetic models allow to estimate the Biological Threshold Limit Values (Reference Values), which serve to protect the individuals effectively from chemical-induced health risks. 

It has been shown that all doses of arsenic trioxide are characterized by different toxicokinetics parameters. Arsenic compounds have long half-times and the tendency to accumulate in the body. The excretion rate decreased with decreasing blood concentration. The present study confirms the ability of toxicokinetic models to improve the study of various toxic substances and to estimate the Biological Threshold Limit Values. 

What most influences this is the model chosen to describe the relationship and the model for the extrapolation. Biological thresholds and low-exposure hormesis may affect the outcome of the extrapolation. 

H. Roels, J.P. Gennart, R. Lauwerys, J.P. Bucher, J. Malchaire, and S. Bernard, Surveillance of workers exposed to mercury vapor Validation of a previously proposed biological threshold limit value for mercury concentration in urine. Am. J. Ind. Med. 7 45, 1985. 

Some aspects of degree of concern currently can be considered in a quantitative evaluation. For example, EPA considers human and animal data in the process of calculating the RfD, and these data are used as the critical effect when they indicate that developmental effects are the most sensitive endpoints. When a complete database is not available, a database UF is recommended to account for inadequate or missing data. The dose-response nature of the data is considered to an extent in the RfD process, especially when the BMD approach is used to model data and to estimate a low level of response however, there is no approach for including concerns about the slope of the dose-response curve. Because concerns about the slope of the dose-response curve are related to some extent to human exposure estimates, this issue must be considered in risk characterization. (If the MOE is small and the slope of the dose-response curve is very steep, there could be residual uncertainties that must be dealt with to account for the concern that even a small increase in exposure could result in a marked increase in response.) On the other hand, a very shallow slope could be a concern even with a large MOE, because definition of the true biological threshold will be more difficult and an additional factor might be needed to ensure that the RfD is below that threshold. 

Biological threshold A measureable concentration of chemical below which no damage is produced because of the chemical s inahUity to undergo the necessary biochemical reactions. 

Sofuni, T, Hayashi, M., Nohmi, T, Matsuoka, A., Yamada, M., and Kamata E. (2000). Semiquantitative evaluation of genotoxic activity of chemical substances and evidence for a biological threshold of genotoxic activity. Mutat Res 464, 97-104. 

For risk assessment in the case of vanadium uptake urine is the matrix of choice. The collection of urine is non-invasive and is practical under routine conditions. Moreover this parameter is more sensitive for diagnostic purposes than the vanadium concentration in blood. A tentative biological threshold limit value of 50 mg/kg creatinine has been proposed for urinary vanadium (Lauwerys, 1983). 

It is to be noted that the decision on a threshold and a non-threshold mode of action may not always be easy to make, especially when, although a biological threshold may be postulated, the data do not allow identification of it. If not clear, the assumption of a non-threshold mode of action would be the prudent choice. 

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