Haber's rule duration adjustments should not be used systematically for risk assessment in public health decision-making

Human health risk assessment can be used to support decisions for public health regulations and actions. Characterizing the hazards of inhaled toxicants generally includes extrapolation from observations on experimental animals, subjected to intermittent or subchronic exposures, to a human environmental context with exposure that is usually continuous and long-term. The extrapolation is usually based on a simple linear relationship derived from Haber's rule which assumes that, for a given chemical compound, multiplying the same concentration by the same duration of exposure will yield the same biological response. This study assessed the reliability of this assumption. The p-power in the equation C × tp = k was calculated for 21 chemicals, based on a comparison of LOAELs for subacute, subchronic and chronic durations. A bibliographic survey was then carried out to study the reliability of the intermittent-to-continuous exposure adjustment factors currently used in risk assessment. The results showed that the value of p, assumed to be 1 in risk assessment methodology, was not in fact equal to 1 for any of the selected chemicals. Moreover, in the case of respiratory tract irritation, the value of p varied from 0 to 0.44, as confirmed by experimental studies. These results suggest that a more in-depth and case-by-case approach is required for regulatory toxicology, based on toxicokinetics and toxicodynamic data analysis for each toxicant before applying a temporal-adjustment factor.

► This paper address the issue of appropriate duration adjustment based on Haber's law in risk assessment. ► The p-power in the equation C × tp = k was calculated for 21 substances for different durations of exposure. ► We also include in depth reviews for formaldehyde, benzene, trichloroethylene and carbon tetrachloride. ► Based on comparison of the of p values, we conclude that Haber's law is generally not applicable for effects on respiratory tract.