Noncarcinogens

After the critical study and toxic effect liave been selected, the USEPA identifies the experimental exposure level representing the highest level tested at which no adverse effects (including the criiical toxic effect) were demonstrated. This highest no-obser cd-adversc-effcct-lever (NOAEL) is the key datum obtained from the study of the dose-response relationship. A NOAEL obser ed in an animal study in which the exposure was intermittent (such as five days per week) is adjusted to reflect continuous exposure. 

The NOAEL is selected based in part on the assumption that, if the critical toxic effect is prevented, then all toxic effects are prevented. The NOAEL for the critical toxic effect should not be coniiised with the no-obscr cd-cffcct-lcver (NOEL). In some studies, only LOAEL rather than a NOAEL is a ailablc. The use of a LOAEL. however, requires the use of an additional uncertainty factor (as seen below). 

The RID is derived from the NOAEL (or LOAEL) for the critical toxic effect by consistent application of uncertainty factors (UFs) and a modifying factor (MF). The uncertainty factors generally consist of multiples of 10 (although values less than 10 are sometimes used), with each factor representing a specific area of uncertainty inherent in the extrapolation from the available data. The bases for application of different uncertainty factors are explained below. 

A UF of 10 is used to account for variation in the general population and is intended to protect sensitive subpopulations (e.g.. the elderly and children). 

A UF of 10 is used when extrapolating from animals to humans. This factor is intended to account for the interspccies variability between humans and other m unmals. 

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Eor high value food packaging appHcations, minimal migration of contaminants into food products is critical. Currently the PDA requirement is a maximum 0.5 parts per biUion (ppb) of noncarcinogenic compounds by dietary exposure (22). 

The NIOSH recommended exposure limit for carcinogenic hexavalent chromium is 1 lg/m Cr(VI) as a 10-h TWA, and for noncarcinogenic Cr(VI) the 10-h TWA is 25 lg/m Cr(VI), including a 15-min maximum exposure of 50 lg/m Cr(VI). According to NIOSH, the noncarcinogenic Cr(VI) compounds are chromic acid and the chromates and dichromates of sodium, potassium, lithium, mbidium, cesium, and ammonia. NIOSH considers any hexavalent chromium compound that does not appear on the preceding Hst carcinogenic (145). 

The classification as to whetlier a chemical agent is a carcinogen or a noncarcinogen can help identify whetlier it is a healtli liazard. Both topics are briefly reviewed in this section. More extensive information is provided in Chapter 15. 

Noncarcinogenic elTects include all toxicological responses except tumors. Toxicological responses and iiicchanisins vary widely, and e.xamples of these include interference with normal cell processes by displacing elements out of the cell and binding with a cell to reduce membrane penneability. However,... 

Acceptable Intake for Chronic Exposure (AIC) An estimate similar in concept to the RfD but derived using a less strictly defined methodology. Chronic RfDs have replaced AICs as the Agency s preferred values for use in evaluating potential noncarcinogenic health effects resulting from chronie exposure to a chemical. 

Due to contamination from a metal plating facility, the water from a nearby community water supply well was shown to contain cyanide at a concentration of 20 pg/L, nickel at 95 pg/L, and chroniium(IIl) at 10,200 pg/L. If the daily water intake is assumed to be 0.2L, and the body weight of an adult is 70kg, do these noncarcinogenic chemicals pose a health hazard ... 

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 tlie overall potential for noncarcinogenic effects posed by more dian one chemical, a liazard index (HI) approach has been developed based on EPA s Guidelines for Healdi Risk Assessment of Chemical Mixtures. This approach assumes that simultaneous subtlu eshold exposures to several chemicals could result in an adverse healtli effect. It also assumes tliat tlie magnitude of the adverse effect will be proportional to tlie sum of the ratios of the subtlireshold exposures to acceptable exposures. The non cancer hazard index is equal to tlie sum of the hazard quotients, as described below, where E and tlie RfD represent the same exposure period (e.g., subclironic, clironic, or shorter-term). 

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. 

The FDA [51] has used the MDL QSAR software [19] to develop QSARs for the carcinogenic potential of pharmaceuticals and organic chemicals. These were validated using a test set of 108 compounds, with 72% correct prediction of carcinogens and 72% correct prediction of noncarcinogens. 

The final performance standard is for toxic metals. For RCRA combustion units, both carcinogenic and noncarcinogenic metals are regulated under the same type of tiered system as chlorine. The facility determines an appropriate tier for each regulated metal and assures that the facility meets these feed rate and emission standards. A different tier may be selected for each metal pollutant. 

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