Organic solvent exposure, genes, and risk of neuropsychological impairment

Background: Subtle cognitive and neurological impairments have been found in some workers exposed to organic solvents. Whether these effects occur at or below current legal limits for occupational exposure is controversial. Aim: To determine whether occupational solvent exposure is associated with neuropsychological impairment and whether such risk is modified by polymorphisms in the genes for enzymes involved in detoxification. Design: Retrospective case-control analysis. Methods: We studied 78 former dockyard painters and 42 community controls. Individual respiratory and dermal exposures to solvents were estimated. Neuropsychological tests were administered, including paper and pencil tests, tests from the Neurobehavioural Evaluation System (NES2), together with a structured neurological examination and genotyping of polymorphic enzymes involved in detoxification: GSTM1, GSTT1, GSTP1, NAT1, NAT2, SOD1 and CYP1A1. Results: While initial case-control analyses failed to identify any significant differences between symptomatic and asymptomatic painters, in regression analyses increasing solvent exposure was associated with increasing risk of cognitive impairment, after adjustment for IQ (or age, where appropriate), smoking and alcohol. There was also an association between exposure and reduction in grip strength. There was limited evidence of risk modification by some enzyme polymorphisms. Discussion: This association between increasing intensity of solvent exposure and neuropsychological impairment may be important at current exposure levels in the UK.