WORK PLANS - Laserfiche WebLink

Home Browse Search

biologically significant effect of concern, often called the "critical toxic effect." For certain substances, only a Lowest Observed Adverse Effect Level (LOAEL) has been determined. This is the lowest dose of a substance that produces either a statistically or biologically significant indication of the critical toxic effect. The NOAEL or the -- LOAEL may be used to calculate the RfD of a particular contaminant (EPA 1988). RfDs are calculated by dividing the NOAEL (or LOAEL) by uncertainty factors, which generally range from 10 to 1,000. For example, uncertainties include variations in the sensitivity of individuals within a population and the extrapolation of data from experimental animals to humans. The RfD is expressed in units of milligrams of contaminant per kilogram of body weight per day (mg/kg-day) for oral exposure. Reference Air Concentrations (RfCs) expressed in milligrams of contaminant per cubic meter of air (mg/m3) may be available to evaluate inhalation exposure. A body weight of 70 kg and a respiration rate of 20 m3/day are used to convert the RfC to a dose (mg/kg-day). The methodology for deriving RfDs is more fully described in the EPA's current human health risk assessment guidance (EPA 1989b). The majority of toxicological knowledge of chemicals comes from experiments on laboratory animals. Experimental animal data have historically been relied upon by regulatory agencies and other expert groups to assess the hazards of human contaminant exposures. Although this reliance has been greatly supported by empirical observations, there are known interspecies differences in contaminant absorption, metabolism, excretion, and toxic responses. There are also uncertainties concerning the relevance of animal studies using exposure routes that differ from the human exposure routes under consideration. Additionally, the extrapolation of results of short-term or subchronic animal studies to long-term exposures in humans has inherent uncertainty (EPA 1988). Despite the limitations of experimental animal data, such information is essential for contaminant toxicity assessment, especially in the absence of human epidemiological evidence. The uncertainty factors used in the derivation of RfDs are intended to compensate for data limitations. This approach is conservative by design and is meant to avoie the underestimation of protective RfD values (EPA 1989b). S:\LDC\YELLO.RPr May 4,1995 5-3