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Replace the NOAEL and LOAEL with the BMDL01 and BMDL10

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Abstract

Although benchmark-dose methodology has existed for more than 20 years, benchmark doses (BMDs) still have not fully supplanted the no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) as points of departure from the experimental dose–response range for setting acceptable exposure levels of toxic substances. Among the issues involved in replacing the NOAEL (LOAEL) with a BMD are (1) which added risk level(s) above background risk should be targeted as benchmark responses (BMRs), (2) whether to apply the BMD methodology to both carcinogenic and noncarcinogenic toxic effects, and (3) how to model continuous health effects that aren’t observed in a natural risk-based context like dichotomous health effects. This paper addresses these issues and recommends specific BMDs to replace the NOAEL and LOAEL.

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References

  • Allen BC, Kavlock RJ, Kimmel CA, Faustman EM (1994a) Dose–response assessment for developmental toxicity II: comparison of generic benchmark dose estimates with no observed adverse effect levels. Fund Appl Toxicol 23: 487–495

    Article  CAS  Google Scholar 

  • Allen BC, Kavlock RJ, Kimmel CA, Faustman EM (1994b) Dose–response assessment for developmental toxicity III: statistical models. Fund Appl Toxicol 23: 496–509

    Article  CAS  Google Scholar 

  • Al-Saidy OM, Piegorsch WW, West RW, Nitcheva DK (2003) Confidence bands for low-dose risk estimation with quantal response data. Biometrics 59: 1056–1062

    Article  PubMed  Google Scholar 

  • Bailer AJ, Noble RB, Wheeler MW (2005) Model uncertainty and risk estimation for experimental studies of quantal responses. Risk Anal 25: 291–299

    PubMed  Google Scholar 

  • Barnes DG, Daston GP, Evans JS, Jarabek AM, Kavlock RJ, Kimmel CA, Park C, Spitzer HL (1995) Benchmark dose workshop: criteria for use of a benchmark dose to estimate a reference dose. Regul Toxicol Pharm 21: 296–306

    Article  CAS  Google Scholar 

  • Catalano PC, Scharfstein DO, Ryan LM, Kimmel CA, Kimmel GL (1993) Statistical model for fetal death, fetal weight, and malformation in developmental toxicity studies. Teratology 47: 281–290

    Article  PubMed  CAS  Google Scholar 

  • Crump KS (1984) A new method for determining allowable daily intakes. Fund Appl Toxicol 4: 854–871

    Article  CAS  Google Scholar 

  • Crump KS (1995) Calculation of benchmark doses for continuous data. Risk Anal 15: 79–89

    Article  Google Scholar 

  • Farland W, Dourson M (1992) Noncancer health endpoints: approaches to quantitative risk assessment. In: Cothern CR(eds) Comparative environmental risk assessment. Lewis Publishers, Boca Raton, pp 87–106

    Google Scholar 

  • Faustman EM, Allen BC, Kavlock RJ, Kimmel CA (1994) Dose–response assessment for developmental toxicity I: characterization of database and determination of no observed adverse effect levels. Fund Appl Toxicol 23: 478–486

    Article  CAS  Google Scholar 

  • Filipsson AF, Sand S, Nilsson J, Victorin K (2003) The benchmark dose method—review of available models, and recommendations for application in health risk assessment. Cr Rev Toxicol 35: 505–542

    Google Scholar 

  • Food Safety Council (1980) Proposed system for food safety assessment. Food Safety Council, Washington

  • Fowles JR, Alexeeff GV, Dodge D (1999) The use of benchmark dose methodology with acute inhalation lethality data. Regul Toxicol Pharm 29: 262–278

    Article  CAS  Google Scholar 

  • Gaylor DW (1983) The use of safety factors for controlling risk. J Toxicol Environ Health 11: 329–336

    Article  PubMed  CAS  Google Scholar 

  • Gaylor DW (1992) Incidence of developmental defects at the no observed adverse effect level (NOAEL). Regul Toxicol Pharm 15: 151–160

    Article  CAS  Google Scholar 

  • Gaylor DW (1996) Quantalization of continuous data for benchmark dose estimation. Regul Toxicol Pharm 24: 246–250

    Article  CAS  Google Scholar 

  • Gaylor DW, Slikker W (1990) Risk assessment for neurotoxic effects. NeuroToxicology 11: 211–218

    PubMed  CAS  Google Scholar 

  • Gift J (2003) EPA’s Benchmark Dose Software (BMDS), Version 1.3.2. Available at: http://www.epa.gov/ncea/bmds.htm

  • Haber LT, Allen BC, Kimmel CA (1998) Non-cancer risk assessment for nickel compounds: issues associated with dose–response modeling of inhalation and oral exposures. Toxicol Sci 43: 213–229

    PubMed  CAS  Google Scholar 

  • Kang S-H, Kodell RL, Chen JJ (2000) Incorporating model uncertainties along with data uncertainties in microbial risk assessment. Regul Toxicol Pharm 32: 68–72

    Article  CAS  Google Scholar 

  • Kavlock RJ, Allen BC, Faustman EM, Kimmel CA (1995) Dose–response assessments for developmental toxicity IV: benchmark doses for fetal weight changes. Fund Appl Toxicol 26: 211–222

    Article  CAS  Google Scholar 

  • Kimmel CA, Gaylor DW (1988) Issues in qualitative and quantitative risk analysis for developmental toxicity. Risk Anal 8: 15–20

    Article  PubMed  CAS  Google Scholar 

  • Kodell RL (2005) Managing uncertainty in health risk assessment. Int J Risk Assess Manage 5: 193–205

    Article  Google Scholar 

  • Kodell RL, Chen JJ, Gaylor DW (1995) Neurotoxicity modeling for risk assessment. Regul Toxicol Pharm 22: 24–29

    Article  CAS  Google Scholar 

  • Kodell RL, West RW (1993) Upper confidence limits on excess risk for quantitative responses. Risk Anal 13: 177–182

    Article  PubMed  CAS  Google Scholar 

  • Krewski D, Van Ryzin J (1981) Dose response models for quantal response toxicity data. In: Csorgo M, Dawson DA, Rao JNK, Saleh AKMdE(eds) Statistics and related topic: Proceedings of the international symposium on statistics and related topics. North-Holland, Amsterdam, pp 201–231

    Google Scholar 

  • Leisenring W, Ryan L (1992) Statistical properties of the NOAEL. Regul Toxicol Pharm 15: 161–171

    Article  CAS  Google Scholar 

  • Mohammed FK, St. Omer V (1986) Behavioral and developmental effects in rats following in utero exposure to 2,4-D/2,4,5-T mixture. Neurovbehav Toxicol Teratol 8: 551–560

    Google Scholar 

  • NRC (National Research Council) (2000) Methods for developing spacecraft water exposure. National Academy Press, Washington, p 151

  • NRC (National Research Council) (2004) Spacecraft water exposure guidelines for selected contaminants, vol 1. National Academy Press, Washington, p 354

  • NTP (National Toxicology Program) (1987) Toxicology and carcinogenesis studies of 1,4-Dichlorobenzene (CAS No. 106-46-7) in F344/N rats and B6C3F1 mice (gavage studies). Technical Report No. 319. U.S. Department of Health and Human Services, Research Triangle Park

  • Razzaghi M, Kodell RL (2004) Quantitative risk assessment for developmental neurotoxic effects. Risk Anal 24: 1673–1681

    Article  PubMed  Google Scholar 

  • Schlosser PM, Lilly PD, Conolly RB, Janszen DB, Kimbell JS (2003) Benchmark dose risk assessment for formaldehyde using airflow modeling and a single-compartment, DNA-protein cross-link dosimetry model to estimate human equivalent doses. Risk Anal 23: 473–487

    Article  PubMed  Google Scholar 

  • Tukey J, Ciminera J, Heyse JB (1985) Testing the statistical certainty of a response to increasing dose of a drug. Biometrics 41: 295–301

    Article  PubMed  CAS  Google Scholar 

  • West RW, Kodell RL (1999) A comparison of methods of benchmark dose estimation for continuous response data. Risk Anal 19: 453–459

    PubMed  CAS  Google Scholar 

  • West RW, Kodell RL (2005) Changepoint alternatives to the NOAEL. J Agric Biol Environ Stat 10: 197–211

    Article  Google Scholar 

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Correspondence to Ralph L. Kodell.

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Kodell, R.L. Replace the NOAEL and LOAEL with the BMDL01 and BMDL10 . Environ Ecol Stat 16, 3–12 (2009). https://doi.org/10.1007/s10651-007-0075-3

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  • DOI: https://doi.org/10.1007/s10651-007-0075-3

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