Effect, carcinogenic

Various solvents which occur in paints and varnishes exhibit a carcinogenic potential. Benzene and all isomers of dinitrobenzenes are particular examples (see also Chapter 20.1). This was confirmed by several extensive studies of occupational exposmes in paint manufacturing plants and in painters. These data show the risk of contracting cancer to be about 20% above the national average. 

In many studies, increased risks were described mainly for Ixmg cancer (about 40% above the national average), leukemia, bladder cancer, liver cancer, and childhood cancers where there has been parental exposme.  

It should be noted, however, that more critical risk factors such as smoking and alcohol can obscure such correlations. 

Although high risks for cancer resulting from occupational exposures were mentioned, no significant information concerning the occupation of painted rooms could be noted. This area has been inadequately studied. 

As mentioned above, lung cancer is a major concern. Painters, as opposed to those involved in paint manufacture were shown to be at greatest risk for contracting lung can-cer 25,48 evidence of increased risk in persons involved in the manufac- 

After in-vitro tests were developed for cell-mediated immune responses, Hanifin et al. 

There is no question that a cell-mediated immune response to beryllium is an impor- 

Further studies on the cell-mediated immune response have determined that mainly a subset of lymphocytes (i.e., 

In contrast to acute beryllium disease, chronic beryllium disease still occurs but is due to an immune response to beryllium that occurs in a minority of exposed vorkers (Eisenbud and Lisson 1983). Therefore, in this condition the determination of an immune response to beryllium has more important clinical utility than the determination of beryllium levels (US Department of Energy 1999). 

A variety of techniques have been employed to assess the immune response to beryllium. Ho vever, the ease, sensitivity, and specificity have made the lymphocyte proliferation assay using H-thymidine the standard technique (Rossman et al. 1988, Mroz et al. 1991). In the past, this technique has been referred to as the lymphocyte transformation test (LTT), but transformation is an older term that is no longer applicable. The cells respond by proliferating (a normal process) and are not transformed, which today implies a malignant process. Hence, the test is currently known as the lymphocyte proliferation test (LPT). 

Himors are caused by uncontrolled cell growth activated by increasing proliferation. Fundamentally, two different kinds of tumors have to be distinguished  

Tlimors are designated by the suffix -oma A fiber-forming tumor of the connective tissue is called n fibroma, a blood vessel tumor is an angioma, a gland tumor is an adenoma, and a benign tumor of the fatty tissue is a lipoma. 

Benign tumors grow in isolation, which means that they do not destroy the environmental tissue. 

Depending on the surrounding tissue in which the tumor grows, different types of tumors can be distinguished  

A cancer of the epithelium cells is referred to as a carcinoma. Epithelium cells form the inner and outer surfaces of the organs. Examples are the skin, the respiratory organs, the stomach-intestinal tract, and numerous glands, such as, for example, the mammary gland, the pancreas, and the thyroid gland. Most cancers (approx. 90 %) start from epithelium cells and thus are carcinomas. The suffix carcinoma is used to characterize them. A malignant tumor of the gland tissue is therefore called an adenocarcinoma. 

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Colorants. According to U.S. regulations, colorants are divided into two classes certified and exempt (see Colorants for foods, drugs, COSMETICS, AND MEDICAL DEVICES). Batch samples of certified colors must be sent to the FDA for analysis and confirmation that the colorants comply with estabhshed specifications. Color manufacturers pay a small fee for each batch of color that is analy2ed. The number of certified colors available to food technologists has declined. Several of the historical colorants were found to have carcinogenic effects. Table 1 shows the certified colors that are permissible for food use in the United States as of 1993. 

Vanillin has a low potential for acute and chronic toxicity, with a reported oral LD q in rats of 1580—3300 mg/kg. Dietary doses up to 20,000 ppm adrninistered to rats for two years resulted in no adverse toxicologic or carcinogenic effects. Vanillin is classified as a GRAS substance by EEMA. Consequently, at levels normally found in the human diet, vanillin would present no significant health or carcinogenic risk to humans. 

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. 

To.xicity values for carcinogenic effects can be e.xprcsscd in several ways. The slope factor is usually, but not always, the upper 95th percent confidence limit of the slope of the dose-response curve and is e.xprcsscd as (mg/kg-day). If the extrapolation model selected is the linearized multistage model, this value is also known as the ql. That is ... 

Toxicity alucs for carcinogenic effects also can be c.xprcsscd in terms of risk per unit concentration of the substance in the medium where human contact occurs. These measures, called unit risks, are calculated by dividing the slope factor by 70 kg and multiplying by the inhalation rate (20 m /day) or the water consumption rate (2 L/day), respecti ely, for risk associated with unit concentration in air or water. Where an absorption fraction less than 1.0 has been applied in deriving the slope factor, an additional conversion factor is necessary in the calculation of unit risk so that the unit risk will be on an administered dose basis. The standardized duration assumption for unit risks is understood to be continuous lifetime c.xposure. Hence, when there is no absorption conversion required ... 

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. 

To assess die overall potential for non carcinogenic effects posed by several exposure pathways, the total haziird index for each exposure duration (i.e., chronic, subchronic, and shorter-term) should be calculated separately. This equation is described below ... 

Tlie total cancer risk by inhalation is calculated from tlie arithmetic sum of individual cancer risks, assuming no interaction of pollutiuits in teniis of carcinogenic effects ... 

Dioxins are prominent members of the class of polychlorinated hydrocarbons that also includes diben-zofuran, biphenyls and others. Dioxins are highly toxic environmental contaminants. Like others small planar xenobiotics, some dioxins bind with high affinity to the arylhydrocarbon (Ah) receptor. Dioxins activate the receptor over a long time period, but are themselves poor substrates for the enzymes which are induced via the Ah-receptor. These properties of the dioxins and related xenobiotics may be important for the toxicity of these compounds. Dioxins like 2,3,7,8-tetrachloro-p-dibenzodioxin can cause persistent dermatosis, like chloracne and may have other neurotoxic, immunotoxic and carcinogenic effects. 

Second Generation Second generation SERMs were developed with the objective of obtaining ER-targeted pharmaceuticals that lacked the utero-trophic and carcinogenic effects of tamoxifen. The most well characterized second generation SERM is... 

To help public health professionals and others address the needs of persons living or working near hazardous waste sites, the information in this section is organized first by route of exposure (inhalation, oral, and dermal) and then by health effect (death, systemic, immunological, neurological, reproductive, developmental, genotoxic, and carcinogenic effects). These data are discussed in terms of three exposure periods acute (14 days or less), intermediate (15-364 days), and chronic (365 days or more). 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been made for methyl parathion. An MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. 

No studies were located regarding carcinogenic effects in humans or animals after inhalation exposure to methyl parathion. 

Saleh MA. 1980. Mutagenic and carcinogenic effects of pesticides. J Environ Sci Health B15 907-927. 

No studies were located regarding cancer in humans after oral exposure to endosulfan. Carcinogenic effects of endosulfan were investigated in a number of chronic animal bioassays with rats and mice the available data provide no evidence that endosulfan is carcinogenic. 

The U.S. EPA and the International Agency for Research on Cancer (lARC) have not classified endosulfan as to its carcinogenicity (lARC 1987,1998). Studies conducted by the National Toxicology Program (NTP) using rats and mice indicated inadequate and negative evidence, respectively, for carcinogenic effect from endosulfan (NTP 1991). No data were available for studies conducted for the metabolites of endosulfan. 

Named after its inventor, Bruce Ames, the test has become one of the common screening tests for measuring the potential carcinogenic effects of... 

Levels of exposure associated with carcinogenic effects (Cancer Effect Levels, CELs) of trichloroethylene are indicated in Tables 2-1 and 2-2 and Figures 2-1 and 2-2. 

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