[Human neurotoxicity of ethylene-bis-dithiocarbamates (EBDC)]. / La neurotoxicité des éthylène-bis-dithiocarbamates (EBDC) chez l'homme.

Ethylene-bis-dithiocarbamates (EBDC) (maneb, mancozeb,...) are fungicides which rarely cause acute toxicity reactions, but may have a severe long-term toxic effect. Twelve cases reported to the Bordeaux Anti-Poison Center over a 10-year period generally exhibited short-term neurological symptoms of variable severity. Cases of acute intoxication reported in the literature have involved various neurological signs including headache, dizziness and confusion, and a few cases of seizures, all of which were rapidly reversible. Long-term exposure has been associated with parkinsonism and epidemiological studies have found an increased risk of neurocognitive impairment associated with long-term exposure to pesticides in general and to EBDC specifically. Experimentally, EBDC increases the neurotoxicity of MPTP and paraquat. Their metabolite, ethylene thiourea (ETU), is neurotoxic in utero. There are indications that EBDC and/or ETU may increase sensitivity to genetic and environmental risk factors for cell death and apoptosis. Occupational or accidental exposure to EBDC and its possible long-term consequences require adequate studies concerning their mechanism, surveillance and prevention.

Acute and chronic effects of aminoglycosides on cochlear hair cells.

The first detectable effect on the auditory system after a single high-dose injection of an aminoglycosidic antibiotic (AA) like gentamicin (GM) is the reversible blockade of medial efferent function, probably via blockade of calcium channels at the base of the outer hair cells (OHC). The kinetics of this effect are compatible with that of the molecule in perilymph. In the course of chronic treatment with lower doses, however, ototoxicity develops only after several days of treatment. Still GM can be observed inside the OHCs as soon as 24 hours after the first injection, and will be still present in some OHCs as long as 11 months after a chronic, nonototoxic 6-day treatment. In vitro, the short-term viability of isolated OHCs is not affected by exposure to AAs, but their transduction channels and their response to acetylcholine are reversibly blocked. However, developing organs of Corti in culture are highly and rapidly affected by exposure to AAs. Yet during direct intracochlear perilymphatic perfusion of GM, 2-mM solutions are not ototoxic, and with perfusion with a 20-mM solution ototoxicity develops only after several days of perfusion. From these various observations one can describe some aspects of the mechanisms of ototoxicity of AAs, from their access to perilymph and endolymph, to penetration in the hair cells, likely via endocytosis at their apical pole, and intracellular cytotoxic events.