China
Africa
Explore chapters and articles related to this topic
Hazard Characterization and Dose–Response Assessment
Published in Ted W. Simon, Environmental Risk Assessment, 2019
Traditionally, the US Environmental Protection Agency, Health Canada, and other regulatory agencies have developed two types of quantitative toxicity criteria for oral exposure: reference doses (RfDs) or tolerable daily intakes (TDIs), and cancer slope factors (CSFs). RfDs are also known as toxicity reference values. Reference doses are developed for non-cancer effects and embody the concept of a threshold in which a biological factor must be depleted or overcome for disruption of normal homeostatic mechanisms and resulting adverse effects. Cancer slope factors are developed based on the presumption that cancer responses lack a threshold. The non-threshold approach of a cancer slope factor is used because EPA presumes that any level of exposure, even as small as a single molecule, poses finite probability of generating a carcinogenic response. Right or wrong, this presumption has enjoyed wide acceptance and has had a significant effect on environmental regulation throughout the history of risk assessment. This assumption is known as the linear no-threshold (LNT) hypothesis, and will be discussed at length later in the chapter.
Quantitative Cancer Risk Assessment
Published in Peter G. Shields, Cancer Risk Assessment, 2005
The underlying default assumption for dose-response has been that the low-dose portion of the curve is linear unless proven otherwise. The original justification for this assumption was mathematical and derived from the multistage model of carcinogenesis. Animal tumor data is analyzed by the linearized multistage (LMS) procedure, which provides a first-order cancer potency factor at low dosage levels. The cancer slope factor (q1*) is the linear extrapolation line of the dose-response data and is expressed in units of risk per dosage (mg/kg b.w./day)–1. The q1* represents the 95% upper confidence limit on that slope.
A review of mammalian in vivo genotoxicity of hexavalent chromium: implications for oral carcinogenicity risk assessment
Published in Critical Reviews in Toxicology, 2021
Chad M. Thompson, Marilyn J. Aardema, Melissa M. Heintz, James T. MacGregor, Robert R. Young
The quantitative differences in safety criteria derived by linear and nonlinear extrapolations approaches and their implications for public health are large. Following the release of the NTP (2008) cancer bioassay, when targeted intestinal genotoxicity data were not available, several agencies developed similar oral cancer slope factors for Cr(VI) based on the small intestine tumors in mice (Stern 2010; U.S. EPA 2010; OEHHA 2011). The cancer slope factor of 0.5 (mg/kg-day)−1 in these assessments result in a 1E-6 extra risk of cancer at 2E-6 mg/kg (1E-6 ÷ 0.5). Assuming a typical 70 kg adult consuming 2 L of water per day, the de minimis risk dose equates to a water concentration of 7E-5 mg/L or 0.00007 ppm (0.07 ppb). This value is 14-fold lower than the mean U.S water concentration of 0.001 ppm and ∼1400-fold lower than the current MCL of 0.1 ppm. The California EPA Office of Environmental Health Hazard Assessment (OEHHA) public health goal (PHG) for Cr(VI) is still lower at 0.02 ppb (OEHHA 2011). As a result of linear low-dose extrapolation, such standards imply that the Cr(VI) present in many U.S. drinking water sources (whether natural or anthropogenic) poses an increased cancer risk. The critical question is whether the available scientific data (including genotoxicity studies) support such safety criteria or whether the proposed standards overestimate risk.
Health risk assessment of heavy metals content in cocoa and chocolate products sold in Saudi Arabia
Published in Toxin Reviews, 2019
The oral cancer slope factor used in this study was downloaded from the US EPA’s Regional Screening Level’s Generic Tables of May 2016 (US-EPA 2016). The oral cancer slope factor for As, Ni, and Cr are 1.5, 1.7, and 0.5 mg/kg/d, respectively. The TCR values for As, Ni, and Cr are calculated and presented in Table 8. The values of TCR for As, Ni, and Cr were ranged from 3.40 × 10−5 to 2.11 × 10−5, 9.31 × 10−4 to 3.15 × 10−3, and 8.22 × 10−5 to 1.41 × 10−4, respectively. Following on publications using 10−6 to 10−4 as the range for acceptable risk of developing cancer (US-EPA 1991), 10−4 was accepted as the upper limit for acceptable risk of developing cancer. No TCR result for any food type analyzed exceeded 10−4, except TCR for Ni in cocoa products which exceeding the limit for acceptable risk of developing cancer indicating some concern about the consumption of this foodstuff.
Dose-response for assessing the cancer risk of inorganic arsenic in drinking water: the scientific basis for use of a threshold approach
Published in Critical Reviews in Toxicology, 2019
Joyce S. Tsuji, Ellen T. Chang, P. Robinan Gentry, Harvey J. Clewell, Paolo Boffetta, Samuel M. Cohen
In a subsequent draft reevaluation based on internal tumors, USEPA (2005b) again relied upon the linear default approach for low dose extrapolation and the same data, stating that it lacked a full understanding of the arsenic modes of carcinogenic action. In a review of these analyses (USEPA 2007), the Science Advisory Board (SAB) recommended reconsideration of the evidence from inorganic arsenic animal toxicology, pharmacokinetics, and pharmacodynamics research that suggested other than a linear bladder cancer dose response. Another draft IRIS assessment was then completed (USEPA 2010, 2011) which provided an extensive literature search on the mode of action data spanning a three-year period (2005–2007). However, there was no structured mode of action analysis with pre-defined criteria to evaluate causality in an explicit weight-of-evidence process and no attempt to integrate the relevant understanding into the dose-response assessment, which was still based principally on a linear dose-response from Morales et al. (2000). The resulting combined lung and bladder cancer slope factor in this revised assessment was considerably higher (the higher slope factor of 25.7 per mg/kg/day for females was recommended) than previously based on revised model selection, exposure assumptions, and use of more recent U.S. mortality and incidence data (USEPA 2010, 2011). Following a request from Congress for an independent review, the draft risk assessment was withdrawn by the USEPA in early 2012.