DERIVED NO EFFECT

Routine genotoxicity tests are not designed in order to derive no-effect levels. However, the magnitude of the lowest dose with an observed effect (i.e., the LOEL) may, on certain occasions, be a helpful tool in the hazard assessment. Specifically, it can give an indication of the potency of the test substance. Modified studies, with additional dose levels and improved statistical power may be useful in this regard. 

The most frequently used POD for threshold effects (Section 4.2) is the NOAEL (Section 4.2.4). This NOAEL is generally obtained from studies in experimental animals. If reliable human data are available to derive the NOAEL, this value is preferable to the NOAEL from experimental animals. Where a NOAEL cannot be derived, a LOAEL, if available, can be used. An alternative POD to the NOAEL/LOAEL is the benchmark dose (BMD) (Section 4.2.5). The tolerable intake can also, in some cases, form the basis as the POD. In this chapter, the POD will be denoted as a derived no-effect level (DNEL) in order to provide a general term for the various types of PODs that can form the basis for the risk characterization. 

It should be noted that MOS ratios are no absolute measure of risks. Nobody knows the real risks of chemicals where the exposure exceeds the derived no-effect level (DNEL). The risk assessor only knows that the likelihood of adverse effects increases when the DNEL/E ratios decrease or the E/DNEL ratios increase. Thus, such ratios are internationally accepted only as substitutes for risks. 

The second objective of the hazard assessment concerns characterization of the identified hazards of a particular substance. Under REACH this means that the registrant must define so-called derived no-effect levels., abbreviated DNELs. With respect to human health, these values constitute exposure levels above which humans should not be exposed and below which risks for humans are considered controlled. The DNEL derivation is a complex process which comprises several conversion steps and the application of different assessment factors. In the case of reproductive toxicity, the registrant derives separate DNELs with respect to developmental toxicity on the one hand and to impairment of sexual function and fertility on the other hand. 

REACH uses the terms derived no-effects level (DNEL) for hazards to human health and predicted no-effect concentration (PNEC) for hazards to the environment. 

Gromiec J. (2008) Problems concerning the integration of derived-no-effect-levels (DNELS) into occupational safety and health regulations. In Polish. Medycyna Pracy 59(1) 65-73. 

Ultimately a derived no-effect level (DNEL) (in humans) or a predicted no-effect concentration (PNEC)20 (in ecosystems) is calculated for a substance, group of substances or chemical mixture. Assessment factors (AF) - sometimes referred to as uncertainty factors or safety factors - compensate for lack of data and assumptions resulting from dose spacing and other test model parameters (adapted from [124]) ... 

The European-Commission definition of the precautionary principle should be distinguished from the use of uncertainty factors during risk assessment or margins of safety during risk management46 [255]. Assessment factors account for assumptions made during the risk assessment process, such as when deriving no-effect levels. 

The genotoxic substances acrylamide, DMS and 1,4-dioxane and one substance with a very low derived no effect level (DNEL), AA, require specific restrictions to control direct exposures for professional uses and potential diffuse environmental emissions from high total volumes of use in professional products. 

Commission, exposure of humans and the environment can be considered to be adequately controlled if the Derived No Effect Levels (DNEL) or the Predicted No Effect Concentrations (PNEC) are not exceeded [199]. 

DNEL Derived no-effect level mum tolerated dose... 

In order to assess the human health hazard appropriate, a Derived No-EfFect Level (DNEL) has to be established. The assessment should comprise the following steps ... 

A DNEL is a Derived No-Effect Level and a DMEL is a Derived Minimal Effect Level. A DNEL applies to non-genotoxic substances and a DMEL to genotoxic carcinogens and substances sensitising by inhalation. Note the principal difference between the two approaches that is reflected in the terminology a DNEL is connected with absence of effect a DMEL is connected with a (low and accepted) effect level. 

The European Union s chemical management law known as REACH requires chemical manufacturers and importers to assess risks and describe conditions under which their chemical substances can be safely used. Although REACH is required in Europe, data generated under the law has global impact. Among the data generated for a chemical substance is a Chemical Safety Assessment, Derived No Effect Level (DNEL),... 

The derived no-effect level, or DNEL, is the level of exposure to a substance above which humans should not be exposed. Risk assessors use... 

Cormor, K.T. 2013. Differences between US EPA iris inhalation reference concentrations (RfCs) and European Chemicals Agency (ECHA) long-term inhalation derived no effect levels (DNELs) for the general population. Toxicologist. 132(1) 418. 

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