Carcinogenic Chemicals exposure estimates

The evaluation of the carcinogenic potential of a chemical exposure in humans must be based on analyses of all relevant data. Human epidemiologic and cfinical smdies, as well as accidental-exposure reports are considered and used to evaluate the carcinogenic potential of a substance. In the absence of human data, long-term bioassay data from controlled animal studies are used to derive theoretical excess carcinogenic risk estimates for exposed humans. The selection of data for estimating risk is based on the species and strain considered to resemble the human response most closely to provide the most accurate estimates. 

In a manner analogous to the hazard index approach for noncarcinogens, hazard quotients for carcinogenic mixture components can be estimated by dividing chemical exposure levels by doses (DR) associated with a set level of cancer risk the HI is the sum of the HQ values [9,16] ... 

Sixty to eighty percent of all human cancers are associated with our environment and environmental agents. The environment is a complex mixture of chemicals that originate from industrial and technological development and, most importantly, natural sources. Many industrial chemicals, pesticides, insecticides and food additives have exhibited carcinogenic properties in various animal model systems, and occupational and drug exposure has led to human cancers. However, estimates attribute the majority of human cancers associated with the environment not to intentional or accidental chemical exposure, but to the vast number of naturally occurring chemicals in our environment (Doll and Peto, 1981). 

Slope factors can be used to compare the relative cancer potencies of toxic chemicals. That is because when the CDI is arbitrarily set equal to 1 mg/kg/day, cancer incidence is equal to the slope factor (Equation 8.5). Another way to say this is that the slope factor gives the cancer incidence per unit (mg/kg/day) of exposure. This level of cancer risk, i.e., the risk from exposure to 1 mg/kg/day of a carcinogenic chemical averaged over a lifetime, is called the unit risk. Unit risks are numerically equal to slope factors. They provide a convenient way to compare the estimated carcinogenic potencies of different chemicals. 

For certain chemicals, levels of exposure associated with carcinogenic effects may be indicated in the figures. These levels reflect the actual doses associated with the tumor incidences reported in the studies cited. Because cancer effects could occur at lower exposure levels, the figures also show estimated excess risks, ranging from a risk of one in 10,000 to one in 10,000,000 (10 to 10 ), as developed by EPA. 

In the debate about the toxic effects of dyes and chemicals, there is no doubt that carcinogenic effects are perceived by the general public as the most threatening. Chemicals remain a focus for this concern in spite of the weight of evidence that they make only a minor contribution to the incidence of cancer [60,67,83]. The generally accepted estimate of cancer causation, based on mortality statistics, indicates that only 4% of all cancer deaths are attributable to occupational exposure. Another 2% are considered to arise from environmental causes and 1% from other forms of exposure to industrial products. 

Cumulative distributions of the logarithms of NOELs were plotted separately for each of the stmcmral classes. The 5th percentile NOEL was estimated for each stmctural class and this was in mrn converted to a human exposure threshold by applying the conventional default safety factor of 100 (Section 5.2.1). The stmcmre-based, tiered TTC values established were 1800 p,g/person/ day (Class I), 540 pg/person/day (Class II), and 90 pg/person/day (Class III). Endpoints covered include systemic toxicity except mutagenicity and carcinogenicity. Later work increased the number of chemicals in the database from 613 to 900 without altering the cumulative distributions of NOELs (Barlow 2005). 

Risk characterization for non-threshold effects, e.g., for chemicals that are both genotoxic and carcinogenic, generally proceeds by comparing the acceptable risk level (Section 6.2.4) with the actual or estimated total daily intake. An alternative, new approach is the margin of exposure approach (Section 6.4). 

According to the 1981-83 National Occupational Exposure Survey (NOES, 1999), as many as 30 000 workers in the United States were potentially exposed to ortho-toluidine and its hydrochloride salt (see General Remarks). Occupational groups included workers in the chemical industry, laboratory workers, machine operators and cleaners and janitors. Ninety laboratory workers, health-care workers and university teachers were identified as exposed to ort/20-toluidine or its salts in the Finnish Register of Employees Exposed to Carcinogens in 1997 (Savela et a/., 1999). National estimates of workers exposed were not available from other countries. 

For assessing the risks of chemicals, the approach is similar to that used with radiation in those cases where human data are available, but the data are rarely as complete as with radiation. Furthermore, estimation of the dose is usually more difficult with chemicals because of the lack of good monitoring data and other sources of uncertainty (see Section 5). For example, the dose is not usually well quantified even at levels of exposure where carcinogenic effects are conspicuous. 

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