Carcinogenic effects evaluation

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. 

The measure used to describe the potential for noncarcinogenic toxicity to occur in an individual is not expressed as tlie probability of an individual suffering an adverse effect. The EPA does not at tlie present time use a probabilistic approach to estimate tlie potential for noncarcinogenic healtli effects. Instead, tlie potential for non carcinogenic effects is evaluated by comparing an exposure level over a specified time period (e.g., lifetime) witli a reference dose derived for a similar exposure period. Tliis ratio of exposure to toxicity is called a liazard quotient and is described below. (The reader is referred to Chapter 11 for additional details on tlie material tliat follows). The noncancer liazard quotient assumes tliat tliere is a level of exposure (i.e., RfD) below which it is unlikely for even sensitive populations to experience adverse healtli effects. 

The evaluation of risk has underlined the possible adverse effects both on human health after the exposure to drinking water contaminated by landfill leachate and on small rodents and aquatic species at the hypothesized condition for humans, the estimated toxic effects of the raw leachate are mainly due to the levels of ammonia and cadmium and carcinogenic effects are induced by arsenic first and then by PCBs and PCDD/Fs while ecological potential risk is mainly attributable to the concentration of inorganic compounds, in particular ammonia for small rodents, cadmium, ammonia, and heavy metals for fishes. 

Additional information on hepatic lesions in species other than the rat and mouse would be useful in evaluating the risk to humans for both noncarcinogenic and carcinogenic effects from hexachloroethane exposure. 

It is, therefore, important to realize that the incidence of cancer in man today reflects exposure of 15 or more years ago similarly, any increase of carcinogenic contaminants in man s environment today will reveal its carcinogenic effect some 15 or more years from now. For this reason it is urgent that every effort be made to detect and control sources of carcinogenic contamination of the environment well before damaging effects become evident in man. Similar concepts may apply to the need for evaluation of other chronic toxicity hazards. Environmental cancer remains one of the major disease problems of modern man. 

Substances, which give rise to concerns due to possible carcinogenic effects on humans, but which caimot be evaluated definitively due to insufficient information. Knowledge exists on the basis of suitable animal testing, but this is not sufficient to classify the... 

Term Tests for Carcinogens and Data on Genetic Effects in Carcinogenic Hazard Evaluation. LARC Scientific Publication No. 146. Lyon LARC, 1999 309-54. 

McGregor, D.B., Rice, J.M. Venitt, S., eds (1999) The Use of Short- and Medium-term Tests for Carcinogens and Data on Genetic Effects in Carcinogenic Hazard Evaluation (LARC Scientific Pubhcations No. 146), Lyon, lARCBres s... 

Hazard identification qualitative evaluations of the agent s ability to produce carcinogenic effects and the relevance to humans. 

The toxicity of chlorobenzene has been studied in animals by oral and inhalation exposures, but there are no data on dermal exposures. Oral studies have focused on systemic toxicity (liver and kidney) and genotoxic and carcinogenic effects. There are inhalation studies evaluating neurologic, developmental, and reproductive effects. 

In a limited evaluation of carcinogenicity, tributyltin fluoride was applied to the shaved backs of male white mice 3 times per week for a period of 6 months. Treated mice received 15 mg of 5% or 10% of the compound in propylene glycol. Hyperplastic skin changes were observed in the 5% but not in the 10% group (Sheldon 1975). Carcinogenic effects were not observed in this study, which was only of intermediate duration. No other studies were located regarding cancer effects in animals after dermal exposure to organotin compounds. 

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