Carcinogenicity probable carcinogens

Formaldehyde 1,3-Butadiene Probable carcinogen Probable carcinogen... 

Information listed within this section is synopsis of current knowledge of the physiological effects of cadmium and is not intended to be used as the basis for OSHA policy. lARC classifies cadmium and certain of its compounds as Group 2A carcinogens (probably carcinogenic... 

Since 1979 the use of 24 5 T has been regu lated in the United States It is likely that the United States Environmental Protection Agency will classify some dioxins as known and others as probable human carcinogens and recommend further controls be placed on processes that produce them It appears from decreasing dioxin levels in some soils that exist mg regulations are having some effect ... 

Formaldehyde is classified as a probable human carcinogen by the International Agency for Research on Cancer (lARC) and as a suspected human carcinogen by the American Conference of Governmental Industrial Hygienists (ACGIH). This is based on limited human evidence and on sufficient evidence in experimental animals (136). Lifetime inhalation studies with rodents have shown nasal cancer at formaldehyde concentrations that overwhelmed cellular defense mechanisms, ie, 6 to 15 ppm. No nasal cancer was seen at 2 ppm or lower levels (137). 

Sihca and aluminosihcate fibers that have been exposed to temperatures above 1100°C undergo partial conversion to mullite and cristobaUte (1). Cristobahte is a form of crystalline siUca that can cause siUcosis, a form of pneumoconiosis. lARC has deterrnined that cristobaUte should be classified as 2A, a probable carcinogen. The amount of cristobahte formed, the size of the crystals, and the nature of the vitreous matrix in which they are embedded are time- and temperature-dependent. Under normal use conditions, refractory ceramic fibers are exposed to a temperature gradient, thus only the hottest surfaces of the material may contain appreciable cristobahte. Manufacturers Material Safety Data Sheets (MSDS) should be consulted prior to handling RCF materials. 

Group 2A The agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. 

Group 4 The agent (mixture, or exposure circumstance) is probably not carcinogenic to humans. Table 5.17 lists only Groups 1 and 2. 

A. Probably carcinogenic ro humans Limited evidence on carcinogenicity in humans and sufficient evidence on carcinogenicity in experimental animals and other relevant evidence... 

Probably not carcinogenic in Evidence both in humans and experimental... 

A slope factor is generated in the second part of the evaluation. Based on the evaluation that the chemical is a known or probable human carcinogen, a toxicity value that defines quantitatively the relationship between dose and response (i.e., the slope factor) is calculated. Slope factors are typically calculated for potential carcinogens in classes A, Bl, and B2. Quantitative estimation of slope factors for the chemicals in class C proceeds on a case-bycase basis. 

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. 

B1 orB2 Probable human carcinogen B1 indicates that limited human data are available B2 indicates sufficient evidence in animals and inadequate or no evidence in human... 

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. 

Because the slope factor is often an upper 95 percentile confidence limit of the probability of response based on experimental animal data used in tlie multistage model, tlie carcinogenic risk estimate will generally be an upper-bound estimate. Tliis means tliat tlie EPA is reasonably confident tliat tlie true risk will not exceed the risk estimate derived tlirough use of tliis model and is likely to be less than tliat predicted. 

The cancer risk equation described below estimates tlie incremental individual lifetime cancer risk for simultaneous exposure to several carcinogens and is based on EPA s risk assessment guidelines. Tliis equation represents an approximation of the precise equation for combining risks wliich accounts for tlie joint probabilities of tlie same individual developing cancer as a consequence of exposure to two or more carcinogens. The difference between tlie precise equation and tlie approximation described is negligible for total cancer risks less tlian 0.1. Thus, tlie simple additive equation is appropriate for most risk assessments. The cancer risk equation for multiple substances is given by ... 

For carcinogens, risks are estimated as the incremental probability of an indii idual developing ameer o er a lifetime as a result of exposure to the potential carcinogen. The slope factor (SF) converts estimated daily intakes averaged over a lifetime of exposure directly to incremental risk of an individual developing cancer. 

Chemicals which are probably carcinogenic in humans Substance Site affected (human)... 

---