Behavioural effects in female rats of postnatal exposure to sub-toxic doses of polychlorinated biphenyl congener 153.

Polychlorinated biphenyls (PCBs) are widespread environmental contaminants that are also present in human tissues and breast milk. Behavioural disturbances have been reported in both children and animals exposed perinatally to PCBs. The present study assessed the behavioural consequences in female rats of postnatal exposure to the di-ortho-substituted 2,2',4,4',5,5'-hexachlorobiphenyl (IUPAC no. 153), which is one of the PCB congeners most frequently detected in human milk. The different groups of mothers were dosed via gavage with 5 mg/kg bodyweight of PCB 153 in corn oil or 5 ml/kg bodyweight corn oil vehicle every second day from day 3 to day 13 after delivery. The exposure did not affect the bodyweight of the dams nor the physical development of the pups. Operant behavioural testing of the female offspring by two different schedules of reinforcement was performed. First, the animals were tested by a multiple schedule with two components: fixed interval (FI) and extinction (EXT), which has proved sensitive in revealing changes in activity level. There were no statistically significant differences in frequency or interresponse times of lever pressing between the PCB-exposed female rats and the controls. These results were in contrast to a previous, analogous study where PCB 153 produced an increased frequency of lever presses during the FI in male rats, indicating a sex-specific behavioural effect of PCB 153. The female offspring was also tested by a conjunctive schedule with two components: variable interval (VI) and differential reinforcement of low rate (DRL). This schedule revealed slower acquisition of time discrimination in the PCB 153-exposed females as compared with the controls. The VI-DRL results showed that PCB 153 may also produce long-lasting behavioural effects in female rats following postnatal exposure through the mother's milk.

Behavioural hyperactivity in rats following postnatal exposure to sub-toxic doses of polychlorinated biphenyl congeners 153 and 126.

Rats were exposed through mother's milk either to the di-ortho-substituted polychlorinated biphenyl (PCB) congener 2,2',4,4',5,5'-CB (IUPAC no. 153) or to the non-ortho-substituted PCB congener 3,3',4,4',5-CB (IUPAC no. 126). The different groups of mothers were dosed via gavage with corn oil vehicle, 5 mg/kg b.w. of PCB 153 or 2 microg/kg b.w. of PCB 126 every second day from day 3 to 13 after delivery. The exposure did not affect the body weight (b.w.) of the dams or the physical development of the pups. A two-component schedule of reinforcement was used to study behavioural effects of the PCB exposures in male offspring. One component was operating when the house light was turned on. Then a reinforcer, a drop of water, was delivered every 2-min. This component is called a 2-min fixed interval (FI) schedule of reinforcement. The other component was in effect when the house light was turned off. Then no reinforcer was ever delivered. This is called an extinction (EXT) component. It was shown that the PCB-exposed offspring were hyperactive as they had an increased frequency of lever presses. In addition, the PCB 153-exposed male pups showed a behavioural pattern similar to that observed in spontaneously hypertensive rats (SHR), an animal model of attention-deficit hyperactivity disorder (ADHD). This behaviour is characterized by 'burst' of lever presses with short interresponse times (IRT) just before the next reinforcer is given. These results show that both PCBs 153 and 126 may produce significant neurotoxic effects following postnatal exposure through mother's milk.

Functional aspects of developmental toxicity of polyhalogenated aromatic hydrocarbons in experimental animals and human infants.

A scientific evaluation was made of functional aspects of developmental toxicity of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in experimental animals and in human infants. Persistent neurobehavioral, reproductive and endocrine alterations were observed in experimental animals, following in utero and lactational exposure to PCBs, PCDDs and PCDFs. The lowest observable adverse effect levels (LOAELs) for developmental neurobehavioral and reproduction endpoints, based on body burden of TCDD-toxic equivalents (TEQs) in animals, are within the range of current background human body burdens. Relatively subtle adverse effects on neurobehavioral development and thyroid hormone alterations have also been observed in infants and children exposed to background levels. Exclusive use of the toxic equivalency factor (TEF) approach may underestimate the risk of neurodevelopmental effects, because both Ah receptor dependent and independent mechanisms may be involved in these effects. The use of marker congeners and/or bioassays based on Ah receptor mediated mechanisms are rapid, low cost pre-screening alternatives for expensive and time consuming gas chromatographic-mass spectrometric analysis.