Utilizing uncertainty factors in minimal risk levels derivation.

The Agency for Toxic Substances and Disease Registry (ATSDR) utilizes chemical-specific minimal risk levels (MRLs) to assist in evaluating public health risks associated with exposure to hazardous substances. During MRL derivation, uncertainty factors (UF) are used. Under current ATSDR methodology, default UFs of 10 are applied to extrapolate from a lowest-observed-adverse-effect level (LOAEL) to a no-observed-adverse-effect level (NOAEL), for interspecies extrapolation and for intraspecies variability. However, chemical-specific toxicity information has sometimes made it necessary and appropriate to deviate from using the standard UF of 10. Since its inception in January 1993 until December 1994, ATSDR's Inter-agency MRL Workgroup has derived 46 inhalation and 67 oral MRLs. When the substance-specific data permitted, the workgroup departed from the default UFs of 10 in 30 specific cases. Specific examples and rationales are presented in this paper.

[1]  W. Tseng,et al.  Prevalence of skin cancer in an endemic area of chronic arsenicism in Taiwan. , 1968, Journal of the National Cancer Institute.

[2]  R. Zielhuis,et al.  The use of a safety factor in setting health based permissible levels for occupational exposure , 1979, International archives of occupational and environmental health.

[3]  K. A. Andrewartha,et al.  Effects of changes in nutritional copper on erythrocyte superoxide dismutase activity in sheep. , 1980, Research in veterinary science.

[4]  O. Novakova,et al.  Role of time and concentration on carbon tetrachloride toxicity in rats , 1981, International archives of occupational and environmental health.

[5]  D. Goodenberger.  Clinical management of poisoning and drug overdose , 1983 .

[6]  M L Dourson,et al.  Regulatory history and experimental support of uncertainty (safety) factors. , 1983, Regulatory toxicology and pharmacology : RTP.

[7]  J. Burg,et al.  Effects on the peripheral nervous system of workers' exposure to carbon disulfide. , 1983, Neurotoxicology.

[8]  F C Lu.  Toxicological evaluations of carcinogens and noncarcinogens: pros and cons of different approaches. , 1983, Regulatory toxicology and pharmacology : RTP.

[9]  D W Gaylor,et al.  The use of safety factors for controlling risk. , 1983, Journal of toxicology and environmental health.

[10]  K S Crump,et al.  A new method for determining allowable daily intakes. , 1984, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[11]  G. Shopp,et al.  Naphthalene toxicity in CD-1 mice: general toxicology and immunotoxicology. , 1984, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[12]  O F Pedersen,et al.  Response of solvent-exposed printers and unexposed controls to six-hour toluene exposure. , 1985, Scandinavian journal of work, environment & health.

[13]  D. Everett,et al.  HMX: 13 Week Toxicity Study in Mice by Dietary Administration , 1985 .

[14]  E J Calabrese,et al.  Uncertainty factors and interindividual variation. , 1985, Regulatory toxicology and pharmacology : RTP.

[15]  K. P. Lee,et al.  Inhalation toxicity study on rats exposed to titanium tetrachloride atmospheric hydrolysis products for two years. , 1986, Toxicology and applied pharmacology.

[16]  D Hattis,et al.  Human variability in susceptibility to toxic chemicals--a preliminary analysis of pharmacokinetic data from normal volunteers. , 1987, Risk analysis : an official publication of the Society for Risk Analysis.

[17]  D. Barnes,et al.  Reference dose (RfD): description and use in health risk assessments. , 1988, Regulatory toxicology and pharmacology : RTP.

[18]  Use of short-term toxicity data for prediction of long-term health effects , 1988 .

[19]  G. Nise,et al.  Neurasthenic complaints and psychometric function of toluene-exposed rotogravure printers. , 1989, American journal of industrial medicine.

[20]  H. Tryphonas,et al.  Immunotoxicity studies of PCB (Aroclor 1254) in the adult rhesus (Macaca mulatta) monkey--preliminary report. , 1989, International journal of immunopharmacology.

[21]  M. K. Yadrick,et al.  Iron, copper, and zinc status: response to supplementation with zinc or zinc and iron in adult females. , 1989, The American journal of clinical nutrition.

[22]  Jessilynn Taylor,et al.  Toxicological profile for carbon tetrachloride , 2005 .

[23]  Life Systems.  Toxicological profile for zinc , 1989 .

[24]  R. Coulombe,et al.  Evaluation of toluene exposure via drinking water on levels of regional brain biogenic monoamines and their metabolites in CD-1 mice. , 1990, Ecotoxicology and environmental safety.

[25]  M. Luster,et al.  Effect of chronic exposure of PCB (Aroclor 1254) on specific and nonspecific immune parameters in the rhesus (Macaca mulatta) monkey. , 1991, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[26]  A G Renwick,et al.  Safety factors and establishment of acceptable daily intakes. , 1991, Food additives and contaminants.

[27]  M. Erdos,et al.  Effects of PCB (Aroclor 1254) on non-specific immune parameters in rhesus (Macaca mulatta) monkeys. , 1991, International journal of immunopharmacology.

[28]  M L Dourson,et al.  On Reference Dose (RFD) and Its Underlying Toxicity Data Base , 1992, Toxicology and industrial health.

[29]  T. Archer,et al.  Behavioural effects of neonatal metallic mercury exposure in rats. , 1992, Toxicology.

[30]  D. H. Taylor,et al.  Developmental neurotoxicity following premating maternal exposure to hexachlorobenzene in rats. , 1992, Neurotoxicology and teratology.

[31]  B D Beck,et al.  Does the animal-to-human uncertainty factor incorporate interspecies differences in surface area? , 1992, Regulatory toxicology and pharmacology : RTP.

[32]  E J Calabrese,et al.  Lack of total independence of uncertainty factors (UFs): implications for the size of the total uncertainty factor. , 1993, Regulatory toxicology and pharmacology : RTP.

[33]  Michigan.,et al.  Toxicological profile for dichloropropenes , 2008 .