title: An exposure-response curve for copper excess and deficiency.
abstract: There is a need to define exposure-response curves for both Cu excess and deficiency to assist in determining the acceptable range of oral intake. A comprehensive database has been developed where different health outcomes from elevated and deficient Cu intakes were assigned ordinal severity scores to create common measures of response. A generalized linear model for ordinal data was used to estimate the probability of response associated with dose, duration and severity. The model can account for differences in animal species, the exposure medium (drinking water and feed), age, sex, and solubility. Using this model, an optimal intake level of 2.6 mg Cu/d was determined. This value is higher than the current U.S. recommended dietary intake (RDI; 0.9 mg/d) that protects against toxicity from Cu deficiency. It is also lower than the current tolerable upper intake level (UL; 10 mg/d) that protects against toxicity from Cu excess. Compared to traditional risk assessment approaches, categorical regression can provide risk managers with more information, including a range of intake levels associated with different levels of severity and probability of response. To weigh the relative harms of deficiency and excess, it is important that the results be interpreted along with the available information on the nature of the responses that were assigned to each severity score.
authors.affiliation: Institute of Population Health, McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada. acham035@uottawa.ca
authors.forename: Andrea
authors.initials: A
authors.lastname: Chambers
authors.forename: Daniel
authors.initials: D
authors.lastname: Krewski
authors.forename: Nicholas
authors.initials: N
authors.lastname: Birkett
authors.forename: Laura
authors.initials: L
authors.lastname: Plunkett
authors.forename: Richard
authors.initials: R
authors.lastname: Hertzberg
authors.forename: Ruth
authors.initials: R
authors.lastname: Danzeisen
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Aggett
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Starr
authors.forename: Scott
authors.initials: S
authors.lastname: Baker
authors.forename: Michael
authors.initials: M
authors.lastname: Dourson
authors.forename: Paul
authors.initials: P
authors.lastname: Jones
authors.forename: Carl L
authors.initials: CL
authors.lastname: Keen
authors.forename: Bette
authors.initials: B
authors.lastname: Meek
authors.forename: Rita
authors.initials: R
authors.lastname: Schoeny
authors.forename: Wout
authors.initials: W
authors.lastname: Slob
mesh_terms: D000328:Adult; D000367:Age Factors; D000818:Animals; D003300:Copper / Q000172:deficiency* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018673:Nutrition Policy; D051381:Rats; D012016:Reference Values; D012737:Sex Factors; D013045:Species Specificity
chemical_list: D003300:Copper