A Simple Procedure for Estimating Pseudo Risk Ratios from Exposure to Non-Carcinogenic Chemical Mixtures

Details

• Alternative Title:
  Arch Toxicol
• Personal Author:
  Scinicariello, Franco ; Portier, Christopher
• Description:
  Background
  
  Non-cancer risk assessment traditionally assumes a threshold of effect, below which there is a negligible risk of an adverse effect. The Agency for Toxic Substances and Disease Registry (ATSDR) derives health-based guidance values known as Minimal Risk Levels (MRLs) as estimates of the toxicity threshold for non-carcinogens. Although the definition of an MRL, as well as EPA reference dose values (RfD and RfC), is a level that corresponds to “negligible risk,” they represent daily exposure doses or concentrations, not risks.
  
  Objectives
  
  To present a new approach to calculate the risk at exposure to specific doses for chemicals mixtures.
  
  Methods
  
  The assumption in this approach is to assign de minimis risk at the MRL. The assigned risk enables the estimation of parameters in an exponential model, providing a complete dose-response curve for each compound from the chosen point of departure to zero.
  
  Results
  
  We estimated parameters for 27 chemicals. The value of k, which determines the shape of the dose-response curve, was moderately insensitive to the choice of the risk at the MRL.
  
  Conclusions
  
  The approach presented here allows for the calculation of a risk from a single substance or the combined risk from multiple chemical exposures in a community. The methodology is applicable from point of departure data derived from quantal data, such as data from benchmark dose analyses (BMD) or from data that can be transformed into probabilities, such as lowest-observed-adverse effect level (LOAEL). The individual risks are used to calculate risk ratios that can facilitate comparison and cost-benefit analyses of environmental contamination control strategies.
  
  
• Subjects:
  Benchmarking Carcinogens Complex Mixtures Humans Models, Theoretical Probability Reference Values Risk Assessment
• Keywords:
  Acceptable Risk Benchmark Dose Lowest-observed-adverse Effect Minimal Risk Levels Point Of Departure Risk Assessment Toxicological Mixtures
• Source:
  Arch Toxicol. 90(3):513-523
• Pubmed ID:
  25667015
• Pubmed Central ID:
  PMC5700810
• Document Type:
  Journal Article
• Funding:
  CC999999/Intramural CDC HHSUnited States/
• Volume:
  90
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:ca3d746700ea6869aab09b0f065a24d2df5ab3a2ea3602ebd687af220b561b03
• Download URL:
  https://stacks.cdc.gov/view/cdc/49983/cdc_49983_DS1.pdf
• File Type:
  [PDF - 1009.88 KB ]