Non-carcinogenic effects

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 ... 

Table 8.4 provides a few examples of these various protective limits. Recall that RfD is for non-carcinogenic effects only benzene is regulated as a carcinogen (see later). 

The oral reference dose (Oral RfD) is an estimate of the daily exposure of a person to a contaminant that is likely to be without appreciable risk of a deleterious non-carcinogenic effect during a lifetime (USEPA http //www.epa.gov/iris/). Oral RfD values for POP concentrations in seafood types are presented in Table 16.5, together with the daily intake of POPs from seafood consumed in Singapore. Daily intakes of POPs from seafood are below the oral RfD. The cancer benchmark concentration (Dougherty et al., 2000) represents the exposure concentration at which a lifetime cancer risk equates to one excess cancer death in one million persons. This level is defined as the public health protective concentration in the Congressional House Report to the Food Quality Protection Act of 1996 in the USA. Cancer benchmark concentrations were exceeded for DDTs, heptachlor, and PCBs (See Table 16.5). The cancer hazard ratio is the ratio of the MDI for a specific contaminant relative to the cancer benchmark concentration. The cancer hazard ratio represents the extent to which average daily exposure exceeds the benchmark concentration. The cancer hazard ratio of seafood consumption... 

Table 1 Carcinogenic and non-carcinogenic effects associated with human exposures to PCDDs/PCDFs...

Figure 9.32. Dose-response relationship for non-carcinogenic effects.

Historically speaking, the acceptable daily intake (ADI) procedure has been used to calculate permissible chronic exposure levels for humans, based on non-carcinogenic effects. The ADI is the amount of a chemical to which a person can be exposed each day for a long time (usually for a lifetime) without suffering harmful effects. It is determined by applying safety factors that account for the uncertainty in the data, to the highest dose used in human or animal studies which has been shown not to cause toxicity (i.e., the NOAEL). 

The contamination levels at which non-carcinogenic effects are likely to occur are also evaluated. Total dose is compared to a dose that is considered likely to be safe (exposure criteria e.g., RfD). In a quantitative assessment the site-related dose is divided by the criteria and the resulting fraction is defined as the hazard quotient. This simply indicates whether the hypothetical dose exceeds the... 

Birnbaum LS, Tuomisto J. Non-carcinogenic effects of TCDD in animals. FoodAddit Contam 2000 17(4) 275—88. 

MRLs and Cancer Endpoints. One panelist wondered if ATSDR will derive an MRL or some other advisory limit that reflects carcinogenic endpoints. Other panelists and ATSDR scientists explained that the MRLs, by definition, are based strictly on non-carcinogenic effects and that ATSDR, as per policy, does not derive advisory limits for cancer effects. Rather, the Agency simply defers to EPA s cancer slope factors for such limits, if appropriate. 

Risk Characterization. Once a quantitative exposure assessment has been made, Risk Assistant allows the user to automatically calculate lifetime excess cancer risk and/or a hazard index for toxic non-carcinogenic effects of chronic exposure for any agent included in the toxicity databases which currently include about 300 compounds. The appropriate hazard values (slope-potency factors and reference doses) for the relevant routes of exposure are automatically retrieved from the databases. The uncertainty calculations in the exposure assessment can also be retrieved to assess the range of risks associated with a given exposure situation. 

Oncologic This model is used to predict carcinogenic potential in humans. Other non-carcinogenic effects (e.g., acute toxicity, developmental toxicity) cannot be modeled at the present time and, therefore, conventional SAR and read-across methods must be used to predict these endpoints. 

The main adverse health effects associated with cadmium overexposure are lung cancer and kidney dysfunction. It is not yet known how to adequately biologically monitor human beings to specifically prevent cadmium-induced lung cancer. By contrast, the kidney can be monitored to provide prevention and early detection of cadmium-induced kidney damage. Since, for non-carcinogenic effects, the kidney is considered the pri-... 

---