title: Estimation of health risk by using toxicokinetic modelling: a case study of polychlorinated biphenyl PCB153.
abstract: To assess potential PCB153-associated human health effects and risks, it is necessary to model past exposure. PCB153 blood concentrations, obtained from the AMAP biomonitoring programme, in Inuit women covering the years 1994-2006 at Disko Bay, 1999-2005 at Nuuk, and 1992-2007 at Nunavik were used to extrapolate body burden and exposure to the whole lifespan of the population by the one-compartment toxicokinetic model. By using risk characterisation modelling, calculated Hazard Quotients were higher than 1 between the years 1955 and 1987 for the 90th population percentile and during 1956-1984 for the 50th population percentile. Cancer risk for overall exposure of PCB153 ranged from 4.6×10(-5) to 1.8×10(-6) for the 90th percentile and 3.6×10(-5) to 1.4×10(-10) for the 50th percentile between 1930 and 2049, when central estimates or upper-bound slope factors were applied. Cancer risk was below 1×10(-6) for the same time period when a lower slope factor was applied. Significant future research requirements to improve health risk characterisation include, among others, larger sample sizes, better analytical accuracy, fewer assumptions in exposure assessment, and consequently, a better choice of the toxicity benchmark used to develop the hazard quotient.
authors.affiliation: Centre for Arctic Medicine, Thule Institute, University of Oulu, Finland. Electronic address: khaled.megahed@oulu.fi.
authors.forename: Khaled
authors.initials: K
authors.lastname: Abass
authors.forename: Antti
authors.initials: A
authors.lastname: Huusko
authors.forename: Pentti
authors.initials: P
authors.lastname: Nieminen
authors.forename: Päivi
authors.initials: P
authors.lastname: Myllynen
authors.forename: Olavi
authors.initials: O
authors.lastname: Pelkonen
authors.forename: Kirsi
authors.initials: K
authors.lastname: Vahakangas
authors.forename: Arja
authors.initials: A
authors.lastname: Rautio
mesh_terms: D000293:Adolescent; D000328:Adult; D004784:Environmental Monitoring; D005260:Female; D006116:Greenland; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood*; D008875:Middle Aged; D008895:Milk, Human / Q000378:metabolism; D008954:Models, Biological; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics* / Q000633:toxicity*; D011247:Pregnancy; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D008055:Lipids; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl
keywords: ADD; ADME; AMAP; AhR; Arctic Monitoring and Assessment Programme; BMDL; BMI; CAR; CR; CSF; Cancer risk; HQ; Hazard quotient; Health outcomes; IRIS; Integrated Risk Information System; LADD; POPs; PXR; RfD; Toxicokinetic modelling; US-EPA; United States Environmental Protection Agency; absorption, distribution, metabolism and excretion; aryl hydrocarbon receptor; average daily dose; benchmark dose level; body mass index; cancer risk; cancer slope factor; constitutive androstane receptor; hazard quotient; lifetime average daily dose; persistent organic pollutants; pregnane X receptor; reference dose