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Evaluation of potential neurotoxic effects of occupational exposure to (L)-Lactates

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Author: Clary, J.J. · Feron, V.J. · Velthuijsen, J.A. van
Type:article
Date:2001
Institution: TNO Voeding
Source:Regulatory Toxicology and Pharmacology, 1, 33, 21-28
Identifier: 236029
doi: doi:10.1006/rtph.2000.1439
Keywords: Toxicology · Chronic neurotoxicity · Chronic toxic encephalopathy · Lactate esters · Organo psycho syndrome · Solvents · 2 ethylhexanol · 2 propanol · alcohol · butanol · isobutanol · lactic acid derivative · methanol · propanol · animal experiment · article · brain disease · disease association · hydrolysis · mouse · neurotoxicity · nonhuman · occupational exposure · priority journal · rat · risk assessment · toxicity testing · Alcohols · Animals · Esters · Humans · Hydrolysis · Lactates · Neurotoxicity Syndromes · No-Observed-Adverse-Effect Level · Occupational Exposure · Solvents · Toxicity Tests · Volatilization

Abstract

Organo psycho syndrome (OPS) or chronic toxic encephalopathy (CTE) is a neurotoxic condition reported following long-term exposure to paints containing organic solvent and to other solvents. Lactate esters are finding wider use as solvents. Lactate esters have been well studied in standard toxicity tests, but specific neurotoxicity studies have not been conducted. No clinical signs of chronic neurotoxicity have been observed in standard toxicity tests. Lactate esters are rapidly hydrolyzed in the body to lactic acid and the corresponding alcohol. Alcohols have been reported to have acute neurotoxic effects, usually following high levels of ingestion. The literature on alcohols was reviewed to establish the no-observed-adverse-effect level (NOAEL) for acute neurotoxicity and to look for any evidence of chronic neurotoxicity from the alcohols produced by hydrolysis of the lactate esters. The NOAELs were compared with the potential amounts of alcohol produced by hydrolysis of different lactate esters at 200 mg/m3 (the NOAEL for most of the lactate esters). In all cases neither acute nor chronic neurotoxicity would be expected based on the amounts of alcohol produced by hydrolysis of the lactate esters at their NOAELs. L-Lactic acid is a normal metabolite in the body and is not considered neurotoxic. Based on this information there is no evidence to suggest that L-lactate esters can cause any chronic neurotoxicity, OPS, or CTE. © 2001 Academic Press.