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Manuel Posada de la Paz,¹ Rossanne M. Philen,² Fredric Gerr,³ Richard Letz,⁴ Maria José Ferrari Arroyo,¹ Lydia Vela,⁵ Maravillas Izquierdo,¹ Concepción Martín Arribas,¹ Ignacio Abaitua Borda,¹ Alejandro Ramos,¹ Cristina Mora,¹ Gloria Matesanz,¹ Maria Teresa Roldán,¹ and Juan Pareja⁵

¹Instituto de Salud Carlos III, Centro de Investigación sobre el Síndrome del Aceite Tóxico y Enfermedades Raras, Madrid, Spain; ²Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ³Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa, USA; ⁴Emory University, Atlanta, Georgia, USA; ⁵Hospital Fundación Alcorcón, Servicio de Neurología, Alcorcón, Madrid, Spain

Abstract
Toxic oil syndrome (TOS) resulted from consumption of rapeseed oil denatured with 2% aniline and affected more than 20,000 persons. Eighteen years after the epidemic, many patients continue to report neurologic symptoms that are difficult to evaluate using conventional techniques. We conducted an epidemiologic study to determine whether an exposure to toxic oil 18 years ago was associated with current adverse neurobehavioral effects. We studied a case group of 80 adults exposed to toxic oil 18 years ago and a referent group of 79 adult age- and sex-frequency-matched unexposed subjects. We interviewed subjects for demographics, health status, exposures to neurotoxicants, and responses to the Kaufman Brief Intelligence Test (K-BIT) , Programa Integrado de Exploracion Neuropsicologica (PIEN) , and Goldberg depression questionnaires and administered quantitative neurobehavioral and neurophysiologic tests by computer or trained nurses. The groups did not differ with respect to educational background or other critical variables. We examined associations between case and referent groups and the neurobehavioral and neurophysiologic outcomes of interest. Decreased distal strength of the dominant and nondominant hands and increased vibrotactile thresholds of the fingers and toes were significantly associated with exposure to toxic oil. Finger tapping, simple reaction time latency, sequence B latency, symbol digit latency, and auditory digit span were also significantly associated with exposure. Case subjects also had statistically significantly more neuropsychologic symptoms compared with referents. Using quantitative neurologic tests, we found significant adverse central and peripheral neurologic effects in a group of TOS patients 18 years after exposure to toxic oil when compared with a nonexposed referent group. These effects were not documented by standard clinical examination and were found more frequently in women. Key words: case-referent study, environmental food epidemic, exam, long-term effects, neurobehavioral tests, toxic oil syndrome. Environ Health Perspect 111:1326-1334 (2003) . doi:10.1289/ehp.6098 available via http://dx.doi.org/ [Online 9 April 2003]