Neurological and Neurophysiological Findings in Workers with Chronic 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Intoxication 50 Years After Exposure

Basic Clin Pharmacol Toxicol. 2018 Feb;122(2):271-277. doi: 10.1111/bcpt.12899. Epub 2017 Sep 27.

Abstract

The last eight survivors of 80 workers accidentally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during production of herbicides based on trichlorophenoxyacetic acid in 1965-1967 in a chemical factory were followed. All were men, mean age 72.4 ± 1.3 years. Their current median TCDD blood level was 112 (46-390) pg/g lipids. Neurological examination revealed central nervous system impairment in all individuals and signs of polyneuropathy in 87.5%, which was confirmed by a nerve conduction study (NCS) in 75%. A Lanthony test demonstrated acquired dyschromatopsia in 87.5% of the patients, with deterioration of mean colour confusion index (CCI) from 1.52 ± 0.39 in 2010 to 1.73 ± 0.41 in 2016. Single-photon emission computer tomography (SPECT) of the brain showed focal reduction of perfusion in various brain locations in all patients and worsening in six patients. Visual-evoked potentials (VEP) was abnormal in 62.6% of individuals. Most patients complained of psychological problems. The neuropsychological test battery showed most positive impairments in the Trail Making Test evaluating processing speed (average level in the range of mild neurocognitive impairment), which correlated with mean CCI (p < 0.05).

Conclusion: Fifty years after exposure, blood levels of TCDD are still 10 times higher than the general population. NCS, VEP, Lanthony test and SPECT findings deteriorated from examination of these patients in 2004 and in 2010. The total of abnormal tests per patient in 2016 is very high. Minor differences among patients and their reduced count may explain why the number of impairments in 2016 does not correlate with TCDD blood level.

MeSH terms

  • Accidents, Occupational*
  • Aged
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / physiopathology
  • Cerebrovascular Circulation / drug effects
  • Chemical Industry*
  • Cognition / drug effects
  • Color Vision / drug effects
  • Evoked Potentials, Visual / drug effects
  • Herbicides / adverse effects*
  • Herbicides / blood
  • Herbicides / chemical synthesis
  • Humans
  • Male
  • Neural Conduction / drug effects
  • Neurologic Examination
  • Neuropsychological Tests
  • Neurotoxicity Syndromes / diagnosis
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / physiopathology
  • Neurotoxicity Syndromes / psychology
  • Occupational Exposure / adverse effects*
  • Occupational Health*
  • Perfusion Imaging / methods
  • Polychlorinated Dibenzodioxins / adverse effects*
  • Polychlorinated Dibenzodioxins / blood
  • Polychlorinated Dibenzodioxins / chemical synthesis
  • Polyneuropathies / chemically induced*
  • Polyneuropathies / diagnosis
  • Polyneuropathies / physiopathology
  • Time Factors
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Herbicides
  • Polychlorinated Dibenzodioxins