Chronic toxicity focus

A carcinogenicity study is more focused than a chronic toxicity study fewer endpoints are evaluated, and as such it is a simpler study. The key endpoints are actually few. 

The immediate future in risk assessment will focus on the difficult but necessary task of integrating experimental data from all levels into the risk assessment process. A continuing challenge to toxicologists engaged in hazard or risk assessment is that of risk from chemical mixtures. Neither human beings nor ecosystems are exposed to chemicals one at a time, yet logic dictates that the initial assessment of toxicity start with individual chemicals. The resolution of this problem will require considerable work at all levels, in vivo and in vitro, into the implications of chemical interactions for the expression to toxicity, particularly chronic toxicity. 

Quality assurance efforts within this phase will focus on four types of studies conducted for safety evaluation (a) safety studies on regulated products, (b) safety studies that encompass the full scope of laboratory operations, (c) studies that are significant to safety assessment, e.g., carcinogenicity, reproduction, chronic toxicity studies, and (d) studies that encompass operations for several species of animals. 

Management Based on Intrinsic Properties The complex life cycles of many substances prevent proper estimations of exposure. Therefore, precautionary policies primarily focus on intrinsic hazardous properties, i.e. assume that critical exposure is the case. Since hazardousness (e.g. chronic toxicity) is difficult to estimate, also substances classified as persistent and liable to bioaccumulate should be treated as hazardous and as action targets. 

There are considerable data on the subchronic and chronic toxicity of BPA in laboratory animals. For decades, BPA has been shown to produce weak but consistent responses in uterotrophic assays. The focus of these investigations has typically been evaluation of the potential reproductive and developmental effects of BPA, due to its ability to modulate estrogen... 

There are considerable data on the chronic toxicity of NP in laboratory animals. The focus of these investigations has typically been evaluation of the potential reproductive and developmental effects of NP, due to its ability to modulate estrogen receptor-mediated responses. Many endpoints are not consistently observed across studies. Some of this variability may be due to differences in the conditions, design, and other test-specific variables of the toxicity tests. For example, since phytoestrogens are abundant in most laboratory animal feeds (such as found in soy and alfalfa) and are known to modulate estrogen receptor-mediated responses, phytoestrogens may be confounding factors as a result of the feed selection. 

At the lower tiers, acute and chronic toxicity parameters are determined for the active substance and a representative formulated product, and are then compared to exposure concentrations from FOCUS steps 1, 2, and 3 in an iterative process. Results from lower tier effects assessments are compared in either step 3 or step 4 exposure calculations and similarly results from higher tier effect assessments are compared in either step 3 or step 4 exposure calculations. At higher tiers, all the options for effects and exposure refinement, along with mitigation options, are considered in order to select the most appropriate path for further risk refinement at step 4. 

Public concern has focused on the possible carcinogenic effects of drugs and other chemicals. Long-term chronic toxicity studies in a variety of species have been started in the hope of minimizing potential risk of cancer in man. However, the results of such studies are difficult, sometimes impossible, to interpret. Yet their economic impact can be enormous, as shown by the withdrawal of cyclamates when bladder cancer was observed in a limited number of rodents. Inevitably drugs will be affected too already the safety of certain oral contraceptives has been questioned because of possible carcinogenic effects in the breasts of dogs after extended use. 

Separate from the acute toxicity endpoints described above, one must be concerned about the long-term effects of exposure to chemicals. Chronic toxicity is particularly insidious because effects may not be felt by the individual(s) for years (or even decades) before serious effects such as cancer become apparent, which may by then be too late to treat. Cancer can result from many sources, cigarette smoking and genetic disorders being notable examples, but the public is also very concerned about cancer and other serious health effects which may result from exposure to synthetic chemicals. Repeated or continuous exposure to low levels of chemicals over an extended period ( chronic exposure ) is of primary concern and therefore a focus of the EPA under the TSCA. 

Somani et al. 1992 Watson et al. 1989b). This review focuses primarily on the available subchronic or chronic toxicity data that may be useful for deriving an oral RfDg. 

The system provides a method of ranking one risk relative to another. It is not intended to define a particular containment system as safe or unsafe but provides a way of comparing toxic hazards. It deals with acute, not chronic, releases. The procedure focuses on the... 

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