Reference Dose —

For carckiogen pesticides (70,71), animal testkigs are subject to maximum tolerated doses (M I L)). M I D is the maximum amount of a substance that can be administered to an experimental animal without causkig extreme health consequences, such as death, to occur but while continuing to produce some measurable toxic effects. Current regulatory theory holds that carckiogen effects do not have a threshold and caimot be related to reference doses. 

Oral reference doses by chemical name for 535 substances EPA s IRIS (Integrated Risk Information. System) http //www.epa.gOv/ngispgm3/iri.s/... 

Provides information on how levels of exposure of hazardous chemicals affect human health. Covers levels of exposure to hazardous chemicals below which no adverse health effects are expected to occur in various segments of the human population. The reference dose and carcinogenicity assessments on IRIS can sen>e as guides in e >aluating potential health hazards and selecting response to alleviate a potential risk to human health. Hours 8 00 a.m. to 4 40 p.m. EST, Monday - Friday. 

Oral Reference Dose (RfD) An estimate (with an uncertainty spanning perhaps an order of magnitude) of the daily exposure of the human population to a chemical, through ingestion, that is likely to be without risk of deleterious effects during a lifetime. 

Development of subchronic RfDs parallels the development of chronic reference doses in concept the distinction is one of e.xposurc duration. Appropriate studies are evaluated and a subchronic NOAEL is identified. The RfD is derived from the NOAEL by the application of the UFs and MF, as outlined above. When experimental data arc available only for shorter e.xposurc durations than desired, an additional uncertainly factor is applied. This is similar to the application of the uncertainly factor for duration differences when a chronic RfD is estimated from subchronic animal data. On the other hand, if subchronic data are missing and a chronic oral RfD derived from chronic data exists, the chronic oral RfD is adopted as the subchronic oral RfD. Ill this instance, there is no application of an uncertainly factor to account for differences in exposure duration. 

Dcri c appropriate reference doses for each discrete set of conditions. 

RfD, the Reference Dose, is an estimate of a daily e.xposure level for the human population that will not produce an adverse effect. 

The drinking water maximum contaminant level (MCL) set by the USEPA for altrazine is 0.003 mg/L and its Reference Dose (RfD) is 3.5 ingAcg-d. How many liters of water containing atrazine at its MCL would a person have to drink each day to e.xceed the RfD for this triazine herbicide ... 

This large volume indicates that there is cither no health problem or there is considerable uncertainty (i.e., the product of the uncertainty factors is large) in estimating a reference dose for atrazine. 

Describe and illustrate the process of setting a reference dose (RfD) using a schematic dose response curve. Correctly label the axis and all other important information. 

The measure used to describe the potential for noncarcinogenic toxicity to occur in an individual is not expressed as tlie probability of an individual suffering an adverse effect. The EPA does not at tlie present time use a probabilistic approach to estimate tlie potential for noncarcinogenic healtli effects. Instead, tlie potential for non carcinogenic effects is evaluated by comparing an exposure level over a specified time period (e.g., lifetime) witli a reference dose derived for a similar exposure period. Tliis ratio of exposure to toxicity is called a liazard quotient and is described below. (The reader is referred to Chapter 11 for additional details on tlie material tliat follows). The noncancer liazard quotient assumes tliat tliere is a level of exposure (i.e., RfD) below which it is unlikely for even sensitive populations to experience adverse healtli effects. 

RfD = reference dose E and Rfd are expressed in tlie same units... 

For each clironic exposure padiway (i.e., seven years to lifetime exposure), calculate a sepmate clironic hazard index from die rados of the clironic daily intake (GDI) to die clironic reference dose (RfD) for individual chemicals as described below ... 

There are several limitations to tliis approach that must be acknowledged. As mentioned earlier, tlie level of concern does not increase linearly as the reference dose is approached or exceeded because the RfDs do not luive equal accuracy or precision and are not based on the same severity of effects. Moreover, luizm-d quotients are combined for substances with RfDs based on critical effects of vaiy ing toxicological significance. Also, it will often be the case that RfDs of varying levels of confidence Uiat include different uncertainty adjustments and modifying factors will be combined (c.g., extrapolation from animals to hmnans, from LOAELs to NOAELs, or from one exposure duration to anoUier). 

The potential for noncarcinogcnic health effects is evaluated by comparing iui exposure level over a specified lime period (c.g., lifetime) with a reference dose derived for a similar exposure period. The ratio of exposure to toxicity in called a liazard quotient and, when it is greater tlien unity tlierc is a higher level of concern for potential noncancer effects. 

EL = emissions level ERA = Environmental Protection Agency HSDB = Hazardous Substances Data Bank lARC = International Agency for Research on Cancer IRIS = Integrated Risk Information System NIOSH = National Institute of Occupational Safety and Health OEL = occupational exposure limit OSHA = Occupational Safety and Health Administration PEL = permissible exposure limit RAC = reference air concentration REL = recommended exposure limit RCRA = Resource Conservation and Recovery Act RfD = reference dose TLV = threshold limit value TWA = time-weighted average WHO = World Health Organization... 

Bames DG, Dourson M. 1988. Reference dose (RfD) description and use in health risk assessments. Regul Toxicol Pharmacol 8 471-486. 

EPA. 1988d. Reference dose (RfD) Description and use in health risk assessment. Vol. I, Appendix A Integrated risk information system supportive documentation. U.S. Environmental Protection Agency, Office of Health and Environmental Assessment. EPA 600/8-86-032a. 

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious effects during a lifetime. The RfD is operationally derived from the no-observed-adverse-efifect level (NOAEL-from animal and human studies) by a consistent application of uncertainty factors that reflect various types of data used to estimate RfDs and an additional modifying factor, which is based on a professional judgment of the entire database on the chemical. The RfDs are not applicable to nonthreshold effects such as cancer. 

MRL users should also understand the MRL derivation methodology. MRLs are derived using a modified version of the risk assessment methodology the Environmental Protection Agency (EPA) provides (Barnes and Dourson 1988) to determine reference doses for lifetime exposure (RfDs). 

EPA s Integrated Risk Information System (IRIS) lists an oral reference dose (RfD) of 0.006 mg/kg/day for endosulfan (IRIS 2000). No reference concentration (RfC) for chronic inhalation exposures to endosulfan was reported. 

RfD = reference dose, 0.00005 mg/(kg-day) for alpha-, beta-endosulfan, and endosulfan sulfate FCR = fish consumption rate, set at 0.030 kg/day... 

The oral reference dose (RfD) for trichloroethylene is currently imder review by an EPA workgroup (IRIS 1996). No inhalation reference concentration (RfC) has been derived (IRIS 1996). The National Center for Environmental Assessment, EPA has begun an effort to reassess the health risks associated with trichloroethylene. 

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