Background According to the EU-REACH legislation; all registered substances that are manufactured, imported and used in quantities of 10 tons or more per year should have a health benchmark defined as the DNEL. Registrants under REACH (“industry”) are to develop these DNELs which in turn are registered at the ECHA website (http://echa.europa.eu). Values for both workers and the general population (including certain sensitive populations) are available. The only statement on asthmatics in the ECHA guidance 1 is related to when use of a lower assessment factor than 10, i.e. 1-2, is justified; “…if the NOAEL is obtained from a study where a susceptible group of people has been specifically addressed (e.g. the registration of respiratory effects in a group of persons with asthma or hyper-reactive airways)…” (p.160) The main focus in this study was on DNELs for local effects from acute/short-term inhalation exposure because of relevance to the airway affecting disease asthma. Other DNELs were also included if no such DNELs were available. Previous indicative SCOEL STEL values can under certain circumstances be used as DNELs. This project was performed within the Swedish National Center for Disaster Toxicology (KcC). Financial support was received from the Swedish National Board of Health and Welfare (SoS), the Swedish Civil Contingencies Agency (MSB) and the Swedish Research Council for Health, Working Life and Welfare (Forte). A travel grant was received from the Swedish Chapter of International Society of Indoor Air Quality and Climate (SWESIAQ). References: 1) ECHA. 2012. Guidance in information requirements and chemical safety assessment. Chapter R.8: Characterization of dose [concentration]-response for human health. ECHA. Helsinki, Finland 2) Johansson M., Johanson G., Öberg M. (2012) How are asthmatics included in the derivation of guideline values for emergency planning and response? Reg. Toxicol. Pharmacol. 63 pp. 461-470 Does Industry Take the Sensitive Subpopulation of Asthmatics into Account when Setting DNELs under REACH? Conclusions Available data on asthmatics are often not included in the derivation of Derived No-Effect Levels (DNELs). Several respiratory irritants with available experimental data on asthmatics lack DNEL values. DNEL values are often close to LOAELs in asthmatics suggesting absence of or a low safety margin. Availability of data on asthmatics should be carefully examined in the development of DNELs, and that the lack of such data should be explicitly noted for respiratory irritants. Omission of asthmatics may interfere with trustful and efficient health protective actions. Mia Johansson 1 , Gunnar Johanson 1 , Mattias Öberg 1 , Linda Schenk 1,2 1 Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2 Department of Philosophy and History, Royal Institute of Technology, Stockholm, Sweden Substances Worker-DNEL and SCOEL STEL Asthma considered in SCOEL document SCOEL document published Asthma study available at the time Ammonia 36 No 1992 Yes Chlorine 1.5 Yes Dec 1998 Yes Hydrogen chloride 15 No 1994 Yes Hydrogen sulfide 14 Yes (only text) 2007 Yes Nitric acid 2.6 No Jun 2001 Yes Sulfur dioxide 2.7 Yes Dec 2009 Yes Sulfuric acid 0.1 (a) Yes (only text) Jan 2007 Yes Table 2. Consideration of asthma studies in SCOEL documents for substances with STEL values identical to inhalation worker-DNELs (local effects from acute/short-term exposure). a) STEL was not established but 0.1 mg/m 3 was stated to be “a desirable value”. Table 1. Inclusion of relevant experimental data on asthmatic subjects in ECHA and in other risk assessment documents. LOAEL and NOAEL values are derived from experimental studies on asthmatics. Inhalation DNEL values are for local effects from acute/short-term exposure if not otherwise specified. (L-L) Local effects from Long-term exposure; (S-S) Systemic effects from Short-term exposure; (S-L) Systemic effects from Long-term exposure Results 14 of the 15 substances found in ECHAs database were classified as respiratory irritants. Only 8 included studies on asthmatics as references (Table 1). One additional substance (chlorine), with a SCOEL STEL value identical to the DNEL, included asthma data in the SCOEL document (Table 2). Inhalation DNELs for workers and/or the general population were missing for 6 substances. In addition, several substances did not have inhalation DNELs for local effects from short-term exposure. Available inhalation DNELs were generally close to the LOAEL values for asthmatics, suggesting absence of or a low safety margin (Table 1). DNELs for seven respiratory irritants were identical to the SCOEL STEL values. SCOEL did not consider asthmatics for 3 although data was available (Table 2). Abstract #643 Mia Johansson M.Sc. Eng., PhD student Work Environment Toxicology E-mail: mia.johansson@ki.se Phone: +468 524 874 11 Website: http://ki.se/IMM Nobels väg 13 Box 201 SE-171 77 Stockholm Substances Experimental studies on asthmatics Based on asthma data DNEL value (mg/m 3 ) Respiratory irritant (from EU- CLP) Number found in the literature Used in other RA documents 2 Cited by registrant (”industry”) LOAEL NOAEL General population Workers Acetaldehyde 11 Yes No 15.8 13 - - Yes Ammonia 2 Yes No - 11.3-40 7.2 36 Yes Ammonium sulfate 7 No RA Yes 1 0.1 1.7 (S-L) 11.2 (S-L) Yes Chlorine 1 Yes No 2.9 1.16 1.5 1.5 Yes Ferric sulfate 1 Yes Yes - 0.075 0.5 (S-S) 2.01 (S-S) Yes Formaldehyde 12 Yes Yes 3.72 2.5 0.1 (L-L) 1 Yes Hydrogen chloride 1 Yes No - 2.68 - 15 Yes Hydrogen sulfide 1 Yes Yes - 2.8 - 14 Yes Methyl methacrylate 1 No Yes - - 104 (L-L) 208 (L-L) Yes Nitric acid 4 Yes Yes 0.13 - 1.3 2.6 Yes Sodium bisulfate 3 No RA No 1 0.1 - - No Sodium nitrate 3 No RA No - 7 10.9 (S-L) 36.7 (S-L) Yes Sulfur dioxide 66 Yes Yes 0.57 0.286 0.53 (L-L) 2.7 Yes Sulfuric acid 38 Yes Yes 0.1 0.075 - 0.1 Yes 2,4-toluendiisocyanate 2,6-toluendiisocyanate 2 Yes No - 0.142 - 0.14 Yes Methods Data from a previous study 2 and further literature searches for asthma data were used to identify substances at the ECHA website and to perform analyzes. 15 out of 22 substances with asthma data were found in the ECHA database. Inclusion of experimental data on asthmatics for the 15 substances was compared to results from analyzing 10 other sets of short-term values 2 . LOAEL and NOAEL values were identified from experimental studies on asthmatics and compared to the DNELs. Indicative SCOEL STELs were compared to the DNELs. SCOEL documents for identical values were investigated in detail regarding consideration of asthmatics. Questions 1) Are available experimental data on asthmatic subjects considered in the DNEL setting process? 2) Are asthmatic subjects adequately protected by the short-term inhalation DNELs? Abbreviations CLP: Classification, Labelling & Packaging regulation DNEL: Derived No-Effect Level EU: European Union REACH: Registration Evaluation Authorization & Restriction of Chemicals ECHA: European Chemicals Agency RA: Risk assessment SCOEL: Scientific Committee on Occupational Exposure Limits STEL: Short-Term Exposure Limits View publication stats View publication stats