Chronic reference dose

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. 

Due to the high doses necessary for acute effects as observed in short-term toxicity tests and to the lack of effects seen at earlier time-points in long-term studies, only chronic reference doses are used in conjunction with exposure for the calculation of triazine dietary risk. Therefore, the remainder of this discussion is limited to chronic exposure and risk. 

The UEL for reproductive and developmental toxicity is derived by applying uncertainty factors to the NOAEL, LOAEL, or BMDL. To calculate the UEL, the selected UF is divided into the NOAEL, LOAEL, or BMDL for the critical effect in the most appropriate or sensitive mammalian species. This approach is similar to the one used to derive the acute and chronic reference doses (RfD) or Acceptable Daily Intake (ADI) except that it is specific for reproductive and developmental effects and is derived specifically for the exposure duration of concern in the human. The evaluative process uses the UEL both to avoid the connotation that it is the RfD or reference concentration (RfC) value derived by EPA or the ADI derived for food additives by the Food and Drug Administration, both of which consider all types of noncancer toxicity data. Other approaches for more quantitative dose-response evaluations can be used when sufficient data are available. When more extensive data are available (for example, on pharmacokinetics, mechanisms, or biological markers of exposure and effect), one might use more sophisticated quantitative modeling approaches (e.g., a physiologically based pharmacokinetic or pharmacodynamic model) to estimate low levels of risk. Unfortunately, the data sets required for such modeling are rare. 

Several assessments were conducted to illushate the impact of different procedures on dietary risk assessment. In all cases, consumption data from the UK surveys were used. One of the differences between the US and the EU is the food consumption data. However, conducting assessments with both US and UK food consumption data will confound the comparisons, so the assessments will be run using only the UK food consumption data. All exposure estimates are presented as percent of the chronic Reference Dose (cRiD) of 0.005 mg/kg bw/day or the acute Reference Dose (aRfD) of 0.01 mg/kg bw/day (both toxicity values are hypothetical for illushative purposes). 

Subcommittee on Chronic Reference Doses for Selected Chemical Warfare Agents, National Research Council... 

SUBCOMMITTEE ON CHRONIC REFERENCE DOSES FOR SELECTED CHEMICAL-WARFARE AGENTS... 

In this report, the Subcommittee on Chronic Reference Doses for Selected Chemical-Warfare Agents of the National Research Council s (NRC s) Committee on Toxicology reviews the scientific validity of the Army s interim values for the six chemical-warfare agents—GA, GB, GD, VX, sulfur mustard, and lewisite. The NRC report is intended to be useful to the Army in making site-specific cleanup decisions. 

For the derivation of an oral RfD, chronic or snbchronic hnman oral exposnre data are preferred however, the only available hnman dose-response data for VX pertain to acnte exposnres. Although such data can be used to establish short-term exposure limits, they are generally not used for establishing subchronic or chronic reference doses (for comparative purposes, an RfD for VX was derived using short-term human exposure data see Appendix D). 

National Research Council (NRC), Committee on Toxicology, Subcommittee on Chronic Reference Dose for Chemical Warfare Agents (1999). Review of the US Army s Health Risk Assessment for Oral Exposure to Six Chemical Warfare Agents. National Academy Press, Washington, DC. 

NRC (National Research Cormcil) (2003). Acute Exposure Guideline Levels for Selected Airborne Chemicals. Suhcommittee on Chronic Reference Doses for Selected Chemical-Warfare Agents, Committee on Toxicology, Board on Environmental Studies and Toxicology, Commission on Life Sciences, National Research Cormcil. National Academy Press, Washington, DC. 

The chronic reference dose for di-N-octylphthalate is 0.02 mg kg day No other regulatory or health-based guideline values are currently available for di-N-octylphthalate. Neither the US Environmental Protection Agency nor International Agency for Research on Cancer have evaluated the carcinogenicity of di-N-octylphthalate. 

The acute reference dose is 0.001 mg kg and the chronic reference dose is 0.0001 mgkg day ... 

Methyl parathion is a restricted use pesticide. The chronic reference dose for methyl parathion is 0.000 02 mg kg day ... 

US Environmental Protection Agency has established an acute reference dose of 0.000 25 mg kg day and a chronic reference dose of 0.0000 33 mg kg day for parathion. 

House dust serves as a reservoir for pesticides in households [85]. Dust ingestion scenarios show that exposures could also exceed the diazinon chronic reference dose [115]. Support for the thesis that household dust may not only be a direct exposure path but may serve as an indicator for all indoor exposure paths can be concluded from correlations between pesticides in dust and in samples of human origin. Regarding PCP, a semivolatile pesticide, concentrations in urine of women and children corresponded well with indoor dust samples from vacuum cleaner bags [13,136]. 

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