Standard Approach to Reproductive Toxicity Assessment Hazard Quotients

Although not expressly stated in ERA guidance, reproduction is rather clearly the toxicological endpoint of greatest concern in ERA work. Aside from reproduction being an essential biological function that allows for perpetuation of a species, reproduction's popularity may reflect the myriad ways in which this function can be compromised. A partial list of reproductive biology elements that can be impaired to some degree in chemically exposed terrestrial receptors includes: behavior (e.g., mate recognition, courtship displays), spermatogenesis and oogenesis, litter/clutch/brood number, litter/clutch/ brood size, mating frequency, birth/neonatal weight, spontaneous abortion rate, and dam weight. In the interest of having available tools with which to assess the potential for reproductive effects cropping up at contaminated sites, toxicologists scour the peer-reviewed scientific literature for toxicity studies where one or more reproductive effects are the endpoints. If the toxicity databases are lacking, new studies are conducted to furnish the required data. From these studies, that are almost always conducted with laboratory species, safe- and/or effect-level chemical-specific 'doses' (in units of milligrams of the chemical ingested/kilograms of body weight of the test species/day) are derived. The doses, termed toxicity reference values (TRVs), serve as the denominators of the simple ratios of desktop ERAs, termed hazard quotients (HQs), where a receptor's supposed potential for risk is calculated:

Estimated daily chemical intake through

Toxicity reference value (mg/kg/day)

The numerator of the HQ, in the same units as the denominator, is the receptor's estimated chemical intake. A simplified example will illustrate the calculation. If one wanted to calculate the HQ for mercury for red fox at a contaminated site, one would first determine how many milligrams of mercury a fox consumes in a given day. If we approximate a fox's daily diet to consist of field mice only (in actuality, a red fox has an omnivorous diet), the mercury concentration in one field mouse would first be determined either through modeling or by actual measure. This figure would then be multiplied by the number of mice a fox likely consumes in a given day. The total milligrams of mercury consumed per day would then be normalized to the fox's body weight, to render an estimated daily mercury dose in mg/kg/day - the HQ's numerator. This figure would then be divided by the reproduction-based mercury TRV, and the resultant unitless ratio is the HQ. For all of their popularity and ease in construction and use, the commonly computed reproduction-based HQs are crude measures of reproductive toxicity. As unitless metrics, they do not express risk, the probability of there being a negative effect, in this case, the probability of a receptor developing a compromised reproductive condition. One other problem (of many) with HQs, is that the values generated almost always exceed 1.0, indicating that receptors are consuming more than a safe chemical dose, and suggesting that the receptors are likely exhibiting reproductive effects.

Much of the inexactitude of the above reproductive toxicity assessment scheme stems from the manner in which the laboratory exposures of the test species radically differ from the actual exposures of receptors in the wild. By way of example, nearly all the laboratory studies with mammals are conducted with mice or rats, but the mammalian species that are of concern in ERAs are the larger, higher-trophic-level, and wider-ranging species, such as fox, deer, raccoon, and coyote. Aside from this key species difference, the form of the chemical tested with is rarely the one that the receptor in the wild encounters. Even in the rare case of the chemical form being the same, the chemical in the outdoors has been subjected to numerous environmental factors over the decades since the site became contaminated (temperature extremes, precipitation, photoincident light, ionizing radiation, etc.), and these have likely served to significantly alter the chemical's toxicity. The laboratory studies also occur under fixed temperature and lighting conditions, quite unlike the variable environments of the site receptors. Several other significant departures from the site condition may throw into question the utility of the chemical concentrations or doses that are deemed to be safe or harmful to ecological receptors. The laboratory studies almost always test a singular chemical's effect, but at contaminated sites, there are commonly a dozen or more chemicals of concern. Although a well-controlled lab study can essentially prove causation (i.e., that the administered chemical, alone, produced an effect), the utility of the study information is compromised because of the likely operating synergistic or antagonistic properties of the collective chemical mixture presented to the receptor in the wild. One other key difference is that almost all laboratory toxicity studies are of single-generation exposures (i.e., the exposure occurred during a portion of the lifetime of a cohort of test animals), while the receptors at contaminated sites have been exposed for tens of generations.

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