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PCBs Polychlorinated biphenyls

5. What are the effects of PCBs on laboratory animals?

  • 5.1 At what exposure levels do PCBs cause harmful effects?
  • 5.2 What are the effects of PCBs on reproduction?
  • 5.3 What other biological effects can PCBs have?
  • 5.4 Through what mechanisms do PCBs act?

5.1 At what exposure levels do PCBs cause harmful effects?

Single exposure: In laboratory tests, animals were fed a single dose of one of several different PCB mixtures available on the market. Those tests determined doses at which different mixtures would cause the death of half of the animals (LC50). This occurred in rats with a single dose between 1 010 and 4 250 mg PCBs per kg body weight and in minks with a single dose between 750 and 4 000 mg PCBs [750 000 000 - 4 000 000 000 ng] per kg body weight depending on the specific PCB mixture. Results may have been affected by factors such as animal breed, age, and sex, as well as by the purity of the PCB formulation.

For example, there is evidence that young rats (3–4 weeks old) are more vulnerable to PCB mixtures than adults. Effects of PCBs on rats include diarrhea, breathing difficulties, dehydration, decreased response to pain, and coma. PCBs were found to mainly damage the lungs, the stomach, and the pancreas.

Short-term exposure: Over a 7 day period, a small number of rats were given different daily doses of a commercial PCB mixture (Aroclor 1254). The lowest tested dose that has been reported to harm them was 2.5 mg/kg body weight per day (LOAEL), which caused a significant increase in relative liver weight and a decrease in the level of a thyroid hormone in the blood.

Cancer: Over a period of approximately 2 years, in twelve different experiments, male and female rats were given various concentrations of several commercial PCB mixtures in their food. The results showed that, in nine out of twelve studies, the number of rats that developed tumors of the liver increased significantly with the dose of PCB mixture ingested. The lowest PCB doses associated with the development of these tumors ranged from 1.4 to 5.4 mg/kg body weight/day depending on the type of PCB mixture tested, and on the strain and sex of the rats. It is possible that impurities in some of the PCB mixtures may have affected the findings. Other significant observed effects of exposure to PCB mixtures were a greater number of thyroid tumors in male rats, and fewer cases of mammary gland tumors in female rats.

In more limited studies, PCB mixtures have also been shown to induce liver tumors in different strains of mice.

In addition, studies have established that PCBs with relatively high chlorine content can ‘promote’ the formation of liver tumors in rats and mice and lung tumors in mice, if such tumors were previously ‘initiated’ by exposure of the animals to genotoxic carcinogens. Whether or not less highly chlorinated PCBs also promote the formation of tumors has not been evaluated.

Several studies on mice in which low doses (0.1 mg/mouse) of a relatively highly chlorinated PCB mixture (Aroclor 1254) were applied to the skin showed little or no effect on cancer formation.

In summary, PCBs, particularly the highly chlorinated mixtures, are associated with cancer of the liver in animals.

This text is a summary of: IPCS - WHO Polychlorinated biphenyls : Human health aspects. Concise international chemical assessment document 55
Section 8.1, Single exposure,  Section 8.2, Short-term exposure  and
Section 8.3, Long-term exposure and carcinogenicity 

5.2 What are the effects of PCBs on reproduction?

Harmful effects on fertility and reproductive organs have been seen in rats, mice, and monkeys exposed to PCBs through their food.

Rats that were fed relatively high doses of PCBs showed:

  • an increase in testes weight (at 3.5 mg/kg body weight per day),
  • a decreased fecundity (at 12.5 mg/kg body weight per day),
  • a reduced sperm count (at 25 mg/kg body weight per day), and
  • a decreased number of young per litter (at 35.4 mg/kg body weight per day).

Adverse reproductive effects have been observed in offspring of female rats exposed to a mixture of relatively highly chlorinated PCBs (Aroclor 1254) during lactation. This suggests that PCBs transferred during breast-feeding can have a long-lasting effect.

Exposure to a moderately chlorinated PCB mixture did not increase testicular weight in newborn male rats, when 0.4 mg/day was injected under their skin for 25 days (NOAEL).

Monkeys that were fed PCBs showed:

  • a prolonged menstruation (at 0.1 mg/kg body weight per day), and
  • a decreased fecundity (0.2 mg/kg body weight per day).

No adverse effects on fecundity were observed below 0.005 mg/kg body weight per day [i.e. a NOAEL for monkeys of 5 000 ng / kg body weight /day].

Effects on female hormonal activity, have been widely investigated in vivo and in vitro with rats and mice. The studies indicate that PCBs may increase or mimic estrogen activity or, alternatively in the case of dioxin-like PCBs, prevent estrogens from acting. Differences in the composition of the PCB mixtures tested probably account for the different results seen. Effects on estrogen activity stem from the fact that certain forms of PCBs are structurally similar to estrogen and can therefore bind to the same cellular receptors. Effects on female hormonal activity, have been widely investigated in vivo and in vitro with rats and mice. The studies indicate that PCBs may increase or mimic estrogen activity or, alternatively in the case of dioxin-like PCBs, prevent estrogens from acting. Differences in the composition of the PCB mixtures tested probably account for the different results seen. Effects on estrogen activity stem from the fact that certain forms of PCBs are structurally similar to estrogen and can therefore bind to the same cellular receptors.

Developmental effects of ingested PCBs have been tested on several animal species. Exposure to PCBs of females during pregnancy and lactation may interfere with the development of the fetus or offspring.

In monkeys, several behavior tests on the offspring of exposed females showed deficits such as a reduced ability to respond to changes in the rules which they needed to follow to obtain a reward (with a LOAEL of 0.03 mg/kg body weight per day). Newly born monkeys exposed to a mixture constructed to resemble the PCB composition in human milk showed behavioral impairment (with a LOAEL of 0.0075 mg [7 500 ng] /kg body weight per day ). In one study, deficits in the development of nervous system were observed after exposure to high levels of non-planar PCBs, but not after exposure to coplanar (dioxin-like) PCBs.

The effect of PCBs on the developing immune system of young rats was evaluated. Fifteen weeks after birth, the rats treated with high doses of PCBs had a smaller thymus gland and a reduced number of immune cells suggesting that PCBs had impaired the development of the immune system. The lowest dose at which no adverse effects on the development of the immune system of rats were observed (NOAEL) was 1 mg/kg body weight per day [1 000 000 ng/kg body weight/day]. It was noted that highly chlorinated PCBs were more immunosuppressive to mice than those with low chlorine content. Effects on the development of the liver, thyroid, and kidney have also been found.

This text is a summary of: IPCS - WHO Polychlorinated biphenyls : Human health aspects. Concise international chemical assessment document 55
Section 8.5.1, Effects on fertility, 
Section 8.5.2, Estrogen-related effects  and
Section 8.5.3, Developmental effects 

5.3 What other biological effects can PCBs have?

It appears that PCB mixtures do not directly damage genes, according to tests carried out in-vitro and in-vivo on many species, as well as on human white blood cells.

Two main effects have been observed; the reduced production of antibodies in response to an immunological challenge and changes in some of the organs of the lymphatic system such as the spleen and the thymus, of the. Observed effects of PCBs on the immune system included a reduction in the production of antibodies, an increased susceptibility to disease, and a decreased thymus weight.

Adult animals appear to be less sensitive than the fetus to the effects of PCBs. The effects of PCB exposure on the immune system of adult animals depend on the amount and specific type of PCB. These effects occur in all animal species examined at high doses, and only in some, such as the rhesus monkey, at low doses. For example, monkeys exposed for 55 months to a PCB mixture with relatively high chlorine content (Aroclor 1254) produced a weaker immune response than monkeys that had not been exposed (control group). The observed effect was even more pronounced at higher doses.

Certain PCB mixtures have been shown to affect the transmission of nerve impulses in different areas of the brain and the spinal cord in rats and monkeys.

This text is a summary of: IPCS - WHO Polychlorinated biphenyls : Human health aspects. Concise international chemical assessment document 55
Section 8.4, Genotoxicity and related end-points, 
Section 8.6, Immunotoxicity   and
Section 8.7, Neurochemical effects 

5.4 Through what mechanisms do PCBs act?

The shape of a particular PCB depends on the position of the chlorine atoms (see question 1.2) and determines the way it acts in an organism. The two phenyl rings that make up a PCB molecule can either lie approximately in the same plane (coplanar PCBs) or in different, more perpendicular planes (non-planar PCBs).

Planar PCBs are also called “dioxin-like”, because they can cause similar harmful effects in the body. They can bind strongly to a cellular receptor, the Ah receptor, and thereby affect the hormonal system and the way cells grow and develop. Those PCBs that bind strongly to the Ah receptor induce certain types of enzymes involved in energy production in the cell. A different set of enzymes of this family are induced by PCBs that have a less planar structure and therefore bind less strongly to the Ah receptor.

Non-planar PCBs do not act like dioxins, because they do not bind to the Ah receptor. However, at high doses, they do have effects on the development of the nervous system and on dopamine levels, and can contribute to tumor formation.

Estrogen-like PCBs can bind to cellular receptors for the estrogen hormone, and cause subtle hormonal disturbances and adverse effects on reproduction. Any hormonal effect is likely to depend on the species, tissue, and developmental stage.

In addition to the effects of the PCBs themselves, some of their break-down products may also be endocrine disruptors. They may for instance have a negative effect on thyroid hormone levels, inhibit enzyme activity in the adrenal glands, interact with estrogen receptors, alter cellular processes in the lung and affect the reproductive system.

This text is a summary of: IPCS - WHO Polychlorinated biphenyls : Human health aspects. Concise international chemical assessment document 55
Section 8.8, Mode of action 


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