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 1mug/kg
each of hexachlorobenzene and 1,2,4-trichlorobenzene via a gastric tube for 30, 60
or 90days. 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.