| Title: | A proposal for calculating the no-observed-adverse-effect level (NOAEL) for organic compounds responsible for liver toxicity based on their physicochemical properties |
| Author(s): | Jakubowski M; Czerczak S; |
| Address: | "Department of Chemical Safety, Nofer Institute of Occupational Medicine, Lodz, Poland" |
| Journal Title: | Int J Occup Med Environ Health |
| DOI: | 10.2478/s13382-014-0277-5 |
| ISSN/ISBN: | 1896-494X (Electronic) 1232-1087 (Linking) |
| Abstract: | "OBJECTIVES: Both environmental and occupational exposure limits are based on the no-observed-adverse-effect level (NOAEL), lowest-observed-adverse-effect level (LOAEL) or benchmark dose (BMD) deriving from epidemiological and experimental studies. The aim of this study is to investigate to what extent the NOAEL values for organic compounds responsible for liver toxicity calculated based on their physicochemical properties could be used for calculating occupational exposure limits. MATERIAL AND METHODS: The distribution coefficients from air to the liver (log K(liver)) were calculated according to the Abraham solvation equation. NOAEL and LOAEL values for early effects in the liver were obtained from the literature data. The descriptors for Abraham's equation were found for 59 compounds, which were divided into 2 groups: 'non-reactive' (alcohols, ketones, esters, ethers, aromatic and aliphatic hydrocarbons, amides) and 'possibly reactive' (aldehydes, allyl compounds, amines, benzyl halides, halogenated hydrocarbons, acrylates). RESULTS: The correlation coefficients between log-log K and log NOAEL for non-reactive and reactive compounds amounted to r = -0.8123 and r = -0.8045, respectively, and were statistically significant. It appears that the Abraham equation could be used to predict the NOAEL values for compounds lacking information concerning their liver toxicity. CONCLUSIONS: In view of the tendency to limit animal testing procedures, the method proposed in this paper can improve the practice of setting exposure guidelines for the unstudied compounds" |
| Keywords: | "Chemical Phenomena Humans Liver/*drug effects *Models, Theoretical No-Observed-Adverse-Effect Level Occupational Exposure/adverse effects/*analysis Risk Assessment/*methods Volatile Organic Compounds/adverse effects/*analysis;" |
| Notes: | "MedlineJakubowski, Marek Czerczak, Slawomir eng Research Support, Non-U.S. Gov't Poland 2014/07/25 Int J Occup Med Environ Health. 2014 Aug; 27(4):627-40. doi: 10.2478/s13382-014-0277-5. Epub 2014 Jul 24" |
