Over the past several months numerous clients of Certified Environmental Management, Ltd. (CEM) have been contacting us to ask questions about ECHA, DNELs, and NOAELs. To answer many of these questions, we are providing some critical information based on our team's continuing education training through ACGIH in 2010. Please view the PDF link below to see a presentation given by ACGIH on these issues. You may also contact our staff at 800-252-2236 to discuss and ask any other questions.

What are NOAELs/NOELs?

The Agency for Toxic Substances and Disease Registry (ATSDR) is a federal public health agency with headquarters in Atlanta, Georgia, and 10 regional offices in the United States. ATSDR's mission is to serve the public by using the best science, taking responsive public health actions, and providing trusted health information to prevent harmful exposures and diseases related to toxic substances. ATSDR is not a regulatory agency, unlike the U.S. Environmental Protection Agency (EPA), which is the federal agency that develops and enforces environmental laws to protect the environment and human health. NOAELs (no observed adverse effect level) and NOELs (no observed effect level) describe the highest tested dose of a substance that has been reported to have no harmful (adverse) health effects on people or animals. This can apply to a particular study, species (e.g. rat, dog), or all studies on a particular substance. The difference between NOAEL and NOEL rests on the definition of adverse effect only, that is, an experimental study that produced a NOAEL will have stated the adverse effect to be observed before initiation.

What is REACH?

In the November 2006 Newsletter the Europeans previewed the new European Regulation on Registration Evaluation and Control of Chemicals (REACH). REACH was passed by the European Parliament on 13 December 2006 and entered into force in June 2007. It heralds the largest shake-up of occupational hygiene practice since the introduction of COSHH. Not least among the changes will be the creation of Derived No-Effect Levels (DNELs).

What is a DNEL?

The Derived No-Effect Level (DNEL) is defined in Annex 1 of REACH as the level of exposure above which humans should not be exposed. Manufacturers and importers are required to calculate DNELs as part of their Chemical Safety Assessment (CSA) for any chemicals used in quantities of 10 tons or more per year. The DNEL is to be published in the manufacturer’s Chemical Safety Report and, for hazard communication, in an extended Safety Data Sheet (SDSs). The DNEL is used in the risk characterization part of the CSA as a benchmark to determine adequate control for specified exposure scenarios. Risk to humans can be considered to be adequately controlled if the exposure levels estimated do not exceed the appropriate DNEL.

REACH specifies that DNELs shall reflect the likely routes, duration and frequency of exposure. If more than one route of exposure is likely to occur, (oral, dermal or inhalation), then a DNEL must be established for each route of exposure and for the exposure from all routes combined. It may also be necessary to identify different DNELs for each relevant human population (e.g. workers, consumers and humans liable to exposure indirectly via the environment) and possibly for certain vulnerable sub-populations (e.g. children, pregnant women).

Manufacturers and importers must give a full justification for the DNEL, explaining their choice of the information used, the route of exposure, and the duration and frequency of exposure to the substance for which the DNEL is valid. They must take into account the uncertainty arising from the variability in the experimental data, intra- and inter-species variation, the nature and severity of the effect and the sensitivity of the human (sub-) population to which the quantitative and/or qualitative information on exposure applies. The resulting value can be considered as an overall NOAEL/NOEL for a given chemical based on an integration of all available and relevant human health hazard data.

REACH then requires the manufacturer or importer to perform a risk characterization (RC) for the leading health effect, i.e. for the toxicological effect that results in the most critical DNEL. The exposure/DNEL ratio in principle presents a simple tool for RC, especially for downstream users who do not have the hazard data at their disposal. For any exposure scenario the risk to humans can be considered to be adequately controlled if exposure levels do not exceed the appropriate DNEL.

For some endpoints, especially mutagenicity and carcinogenicity, the available information may not enable a threshold, and therefore a DNEL, to be established. This is the case when the available data do not allow reliable identification of a threshold, or when a substance exerts its effect by a non-threshold mode of action. In such cases it is assumed that even at very low levels of exposure, residual risks cannot be excluded.

What Are the implications of DNELs?

The DNEL methodology is intended to harmonize the approach to occupational health risk assessment with those used for other types of risk. It can be compared, for example, with the Predicted No-Effect Concentration (PNEC) used to assess environmental risks. This is important under REACH, as manufacturers must assess not only human health risks but environmental and physical safety risks as well. However, HSE’s WATCH committee has looked at the comparability of risk assessment approaches for different purposes and has concluded that there are good reasons for the OEL process being different.

DNELS are more precautionary than conventional Occupational Exposure Limits (OELs). The calculation of DNELs follows a rule-based approach in which a series of standardized assessment factors are applied to the toxicological endpoints to allow for uncertainties and inter-/intra -species differences. This can result in a very conservative figure, perhaps one or two orders of magnitude lower than that from the traditional OEL setting process. While the extra margin of safety in DNELs will be welcomed by some, it raises the question of practicability. How would industry handle, say, a 10-fold reduction in exposure limits?

Some people hope, and expect, that DNELs will eventually replace OELs because they are more stringent. The European process for setting Indicative Occupational Exposure Limit Values (IOELVs) is well established, involving experts from member countries on a scientific committee (SCOEL) and providing an opportunity for stakeholders in industry and government to comment on the proposals. In contrast, these democratic safeguards will not be there under REACH. DNELs calculated by individual manufacturers and importers are not subject to any requirement for consultation or opportunity for input by interested parties.

Debate is also underway to decide what to do when a DNEL cannot be established. Is it possible to set a Derived Minimum Effect Level (DMEL), based on some concept of acceptable or negligible risk, (such as the “Threshold of Toxicological Concern”), or should such materials automatically be banned because they cannot be adequately controlled?

The methodologies, tools and technical guidance needed for REACH are currently being developed by the European Chemicals Bureau through a series of REACH Implementation Projects (RIPs). RIP 3.2 is focused on technical guidance for preparing the Chemical Safety Report and has a sub-group tasked with looking at the derivation of DNELs. Further information can be found on the ECB website at www.ecb.jrc.it/reach.