Risk assessment potential carcinogens

Farris GM, Miller GK, Wollenberg GK, Molon-Noblot S, Chan C, Prahalada S. Recombinant rat and mouse growth hormones risk assessment of carcinogenic potential in 2-year bioassays in rats and mice. Toxicol Sci 2007 97 548-61. 

It was recommended by the MCRA Working Group that for risk assessments, the carcinogenic potential of lewisite degradation products be considered. 

The first section of this chapter provides a discussion of hazard assessment, classification of potentially dangerous substances, and the process of risk assessment. A summary of the mandatory and voluntary initiatives for regulating chemicals and biocides in the United States and Europe is also included together with information on the regulatory aspects of hazard communication. The second section deals with the scientific aspects of hazard identification and risk assessment of carcinogenic chemicals within the regulatory context. 

This section describes how the tj pes of to.xicity inforniation arc considered in the to.xicity assessment for carcinogenic effects. A slope factor and the accompanying weight of evidence determination are the toxicity data most commonly used to evaluate potential human carcinogenic risks. The methods the USEPA uses to derive these values arc outlined below. 

Generally, the slope factor is a plausible upper bound estimate of the probability of a response per unit intake of a ehemieal over a lifetime. The slope factor is used in risk assessments to estimate an upper-bound lifetime probability of an individual developing cancer as a result of e.xposure to a particular level of a potential carcinogen. Slope factors should always be accompanied by the weight-of-evidence classification to indicate the strength of the evidence that the agent is a human carcinogen. Calculational details are presented below. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer potency or perform cancer risk assessments. Minimal risk levels (MRLs) for noncancer end points (if derived) and the end points from which they were derived are indicated and discussed. 

Cancer. The information available on the carcinogenicity of lead in occupationally exposed humans is limited in its usefulness because the lead compound(s), the route(s) of exposure, and the levels of exposure were not always reported. Furthermore, concurrent exposure to other chemical (including arsenic, particularly in lead smelters) and confounding variables, such as smoking, were often not evaluated. Therefore, the data currently available do not support an assessment of the potential carcinogenic risk of lead in humans. 

The potential for a compound to induce carcinogenicity is a crucial consideration when establishing hazard and risk assessment of chemicals and pharmaceuticals in humans [53]. To date, the standard approach to assess carcinogenicity at a regulatory level is the 2-year bioassay in rodents. According to the recent REACH... 

Toxicity and exposure studies indicate PFOA is immunosuppressive and can cause developmental problems and other adverse effects in laboratory animals, such as rodents [Lau et al (2004), Lau et al (2006)]. In 2005 the US Environmental Protection Agency (EPA) released a draft risk assessment of its potential human health effects [U S. EPA (2005)]. A subsequent review by the EPA science advisory board concluded that there is sufficient evidence to classify PFOA as likely human carcinogenic. 

R40 (Care. Cat. 3) was proposed. The tumors occurred in mice exposed to bifenthrin on multiple sites (urinary bladder, leukemia), and therefore without robust mechanistic data the carcinogenic potential of bifenthrin could not be excluded. It was noted the tumors did not impact on the risk assessment [65],... 

Tennant, R.W., French, J.E. and Spalding, J.W. (1995). Identification of chemical carcinogens and assessing potential risks in short-term bioassays using transgenic mouse models. Environ. Health Perspect. 103 942-950. 

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