Behavioral and endocrine effects of chronic exposure to low doses of chlorobenzenes in Wistar rats

Chlorobenzenes have often been applied to study persistent organic pollutants with endocrine disruptor effects (POP/EDCs), but with the focus mainly on physiological aspects. Few data exist on the effects of chlorobenzenes and most POP/EDCs on anxiety or other arginine-vasopressin (AVP)- and oxytocin (OXT)-mediated behavior, albeit exposure to POP/EDCs or their ambient mixtures, even in low doses, may pose health risks for subjects living in contaminated areas and/or consuming polluted food. Our primary aim was therefore to demonstrate behavioral effects of longterm exposure to a discrete dose of a chlorobenzene mixture, and to draw attention to the results of subtoxic oral exposure on anxiety-related elements and the possible underlying endocrine processes. Adult male Wistar rats were treated daily with a mixture (ClB) of 1 μg/kg each of hexachlorobenzene and 1,2,4-trichlorobenzene via a gastric tube for 30, 60 or 90 days. After exposure, anxiety-related behavioral elements were determined in open-field and elevated plus maze tests. At euthanasia, the plasma levels of AVP, OXT and adrenocorticotrophic hormone (ACTH) were measured. Simultaneously, pituicytes from subjects were cultured to study the levels of basal and serotonin- or norepinephrinestimulated AVP and OXT secretion. Various anxiety-related behavioral elements were observed to be increased in both tests. The plasma AVP, OXT and ACTH concentrations were increased, to extents depending on the duration of exposure. The basal and monoamine-stimulated levels of AVP and OXT secretion of pituicytes prepared from the ClB-exposed rats were also elevated. Thus, certain anxietyrelated behavioral and endocrine elements were modulated by long-term exposure to ClB. As adult subjects were involved, which are generally less susceptible to toxic agents, it may be concluded that discrete doses of POP/EDC chlorobenzenes that are low enough to fall below the range of legal regulation may exert anxiogenic effects, which suggests that certain anxiogenic disorders may be induced environmentally in exposed human populations.

► Long-term, subtoxic exposure of adult rats to a chlorobenzene mixture given orally.
► Alterations in anxiety-related behavioral elements of exposed subjects.
► Alterations in the release of the related hormone vasopressin and oxytocin.