Influence of exposure time on toxicity—An overview

Abstract

Data on toxicity of chemicals is usually reported as the LD50, or LC50, with the exposure time from experimental testing in the laboratory reported. But the exposure time is not considered to be a quantifiable variable which can be used to evaluate its importance in expressed toxicity, often described in general terms such as acute, chronic and so on. For the last hundred years Habers Rule has been successfully used to extrapolate from reported exposure times to other exposure times which may be needed for setting standards, health risk assessments and other applications. But it has limitations particularly in environmental applications where exposure levels are low and exposure times are relatively long. The Reduced Life Expectancy (RLE) model overcomes these problems and can be utilised under all exposure conditions. It can be expressed as ln(LT50)=-a (LC50)(ν)+b where the constants ν, a and b can be evaluated by fitting the model to experimental data on the LC50, and corresponding LT50, together with the Normal Life Expectancy (NLE) of the organism being considered as a data point when the LC50 is zero. The constant, ν, at a value of unity gives a linear relationship and where ν<1 the relationship has a concave shape. In our extensive evaluations of the RLE model for fish, invertebrates and mammals involving 115 data sets and with a wide range of organic and inorganic toxicants the RLE model gave correlation coefficients of >0.8 with 107 sets of data. The RLE model can be used to extrapolate from a limited data set on exposure times and corresponding LT50 values to any exposure time and corresponding LT50 value. The discrepancy between Haber's Rule and RLE model increases as the exposure time increases.

Relationship between magnitude of body weight effects and exposure duration in mammalian toxicology studies and implications for ecotoxicological risk assessment

“…[14]) and an exposure time dependence of toxicity has also been described for aquatic organisms (e.g. [2,10,12]). Hence, the exposure time dependence is an important and so far often neglected aspect of the regulatory ecotoxicological risk assessment, in particular for the long-term assessment.…”

Reduced Life Expectancy Model Analyses of Exposure Time Effects of Endocrine Disruptors to Teleost Fishes Based on Effect Concentration of Hepatic Biomarkers

“…Other researchers also reached the same conclusion while studying the toxic effects of organic pollutants to fish [12]. The transfer of compounds from water to fish is the first step in the development of toxic effects [26].…”

“…It was noted that the relationship between natural logarithm of exposure time (lnET 50 ) and EC 50 for zebrafish was linear. The RLE model allows the normal life expectancy (NLT) to be calculated from the toxicity data [12]. In previous study, the reported NLT and calculated NLT obtained were in general agreement [5].…”

“…The results show that the correlation between reported NLT and calculated NLT is better. The NLT introduces a fixed limiting point for a teleost fish and it is a reference point for the reduced life expectancy in fish exposed to the compound [12]. In Figure 1, Figure 2, from the cross point of regression line and x-axis to the roported NLT range, the trend changes of toxic effects based on the EC 50 of hepatic biomarkers can be predicted by the RLE model when no data available for these extended exposure times.…”

“…Many toxicological studies usually focus on concentration-response relationship based on biomarker in risk assessments. Relatively fewer studies exposure time has been studied as a quantifiable variable of toxic effects [12]. Reduced life expectancy (RLE) model which is based on the influence of exposure time has been developed to study time-response relationship [13].…”