| 1. |
|
|
| 2. |
- Schenk, Linda, 1980-, et al.
(författare)
-
A quantitative comparison of the safety margins in the European indicative occupational exposure limits and the derived no-effect levels for workers under REACH
- 2011
-
Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 121:2, s. 408-416
-
Tidskriftsartikel (refereegranskat)abstract
- The new European Union (EU) REACH legislation requires Derived No-Effect Levels (DNEL) to be calculated for substances produced in quantities above 10 tonnes/year. Meanwhile, the setting of occupational exposure limits (OEL) continues both at the member state and the EU level. According to REACH, Indicative OEL Values (IOELVs) from the Commission may under some circumstances be used as worker-DNELs. On the other hand, worker-DNELs will be derived for several thousand substances, far more than the roughly 100 substances for which IOELVs have been established. Thus, the procedure to set health-based OELs may become influential on that of DNELs and vice versa. In this study, we compare the safety margins of 88 SCOEL recommendations with those of the corresponding worker-DNELs, derived according to the default approach as described in the REACH guidance document. Overall, the REACH safety margins were approximately six times higher than those derived from the SCOEL documentation but varied widely with REACH/SCOEL safety margin ratios ranging by two orders of magnitude, from 0.3 to 58 (n=88). The discrepancies may create confusion in terms of legal compliance, risk management and risk communication. We also found that the REACH guidance document, although encompassing detailed advice on many issues, including default assessment factors for species and route extrapolation, gives no quantitative guidance on when and how to depart from defaults.
|
|
| 3. |
- Schenk, Linda, 1980-, et al.
(författare)
-
How consistent are the Derived No-Effect Levels (DNELs) in the European REACH legislation?
- 2013
-
Konferensbidrag (refereegranskat)abstract
- The new European REACH regulation places more responsibility than hitherto on manufacturers and importers of chemicals (“industry”) to provide safety information. An important part of the development of a REACH Chemical Safety Report is derivation of Derived No-Effect Levels (DNELs) which represent “the level of exposure above which humans should not be exposed”. In order to study the consistency, we compared DNELs presented by industry at the website of the European Chemicals Agency (ECHA) with those derived by us in our interpretation of the REACH guidance (Chapter R.8: Characterisation of dose [concentration]-response for human health, http://echa.europa.eu/documents/10162/13632/information_requirements_r8_en.pdf). There are various DNELs, e.g. representing short-term, long-term, inhalation and dermal exposure, as well as workers and the whole population. We limited our study to “worker-DNELs long-term” for inhalation route as they resemble occupational exposure limits (OELs). We found 24 substances for which (1) such DNELs were given in the ECHA chemical database (http://echa.europa.eu/web/guest/information-on-chemicals/registered-substances) and (2) a scientific basis for OEL had been published by the Swedish Criteria Group within the last 15 years in the serial Arbete och Hälsa (https://gupea.ub.gu.se/handle/2077/3194?locale=en). The results were startling, as the DNELs given by industry were 2.4 to 1,100 times higher than ours for 23 substances and 260,000 times higher for trimellitic anhydride. Some of the discrepancy is explained by different choice of key studies/points of departure (PODs). However, the choice of assessment factors (AFs) also differed markedly, as industry’s total AFs (calculated implicitly from the POD and the DNEL) were 1-230 times lower than ours. We conclude that although the REACH guidance is relatively detailed, many arbitrary choices remain that will influence the DNEL. A major problem is that little advice is given on when and how to depart from default AFs.
|
|
| 4. |
- Schenk, Linda, et al.
(författare)
-
Use of Uncertainty Factors by the SCOEL in their derivation of health-based Occupational Exposure Limits
- 2010
-
Ingår i: Critical reviews in toxicology. - : Informa UK Limited. - 1040-8444 .- 1547-6898. ; 40:9, s. 791-798
-
Forskningsöversikt (refereegranskat)abstract
- The aim of this study was to investigate how the Scientific Committee on Occupational Exposure Limits (SCOEL) of the European Commission uses uncertainty factors when proposing health-based indicative occupational exposure limit values (IOELVs). In total, 75 IOELVs in 62 summary documents published from 1991 to 2003 were analyzed. For 31 of the IOELVs, no explicit uncertainty factor (EUF) was stated. For these, we calculated an implicit safety margin (ISM) as the ratio between the point of departure (POD, derived from the NOAEL or LOAEL of the critical effect) and the proposed IOELV. We further analysed whether date of recommendation, type of critical effect, nature of POD or amount of available data influenced the magnitude of the EUFs and ISMs. The ISMs varied little (range 1-5), while the EUFs showed more variability (range 1-50). The EUFs remained unaffected over time and the ISMs decreased slightly. Significant differences in the magnitude of the EUFs, but not ISMs, were found between critical effects, however, contrary to expected the average EUFs and ISMs for irritation were similar to those for more severe systemic effects. The nature of the POD affected the ISMs and EUFs only slightly and less than expected. Both EUFs and ISMs showed a weak but significant negative correlation with the amount of available toxicological data, measured as the number of relevant publications in PubMed, whereas SCOEL statements on data sufficiency had no influence. Overall, the most striking difference was that between EUFs and ISMs, the former being on average 2.1 times higher.
|
|
| 5. |
|
|
| 6. |
- Stamyr, Kristin, et al.
(författare)
-
Swedish forensic data 1992-2009 suggest hydrogen cyanide as an important cause of death in fire victims
- 2012
-
Ingår i: Inhalation Toxicology. - : Informa Healthcare. - 0895-8378 .- 1091-7691. ; 24:3, s. 194-199
-
Tidskriftsartikel (refereegranskat)abstract
- Between 60 and 80% of all deaths related to fire are attributed to toxic fumes. Carbon monoxide (CO) is commonly thought to be the major cause. However, hydrogen cyanide (HCN) is also formed. Still, the exact contribution of HCN to fire-related fatalities is unknown. The aim of the study was to investigate the impact of HCN in relation to CO as a cause of death in fire victims. Data on carboxyhemoglobin (COHb) and blood cyanide from deceased fire victims in the period 1992-2009 were collected from two Swedish nationwide forensic databases (ToxBase and RattsBase). The databases contain data on COHb and/or cyanide from 2303 fire victims, whereof 816 on both COHb and cyanide. Nonparametric statistical tests were used. Seventeen percent of the victims had lethal or life-threatening blood cyanide levels (andgt;1 mu g/g) and 32% had lethal COHb levels (andgt;50% COHb). Over 31% had cyanide levels above 0.5 mu g/g, an indication of significant HCN exposure. The percentages may be underestimates, as cyanide is quickly eliminated in blood also after death. Our results support the notion that HCN contributes more to the cause of death among fire victims than previously thought.
|
|
