The hepatotoxicity of PCBs in rats is reasonably well characterized for acuteduration oral exposure, but it is unclear if the liver is the mostsensitive target organ for acute exposure. Other targets appear to include the kidneys, stomach, and thyroid, but insufficient informationexists to determine if effects in these or other tissues occur at lower doses or are more critical than effects in the liver.
PCBs are well absorbed after exposure by all routes, and distribution to and retention by adipose tissue has been observed in humans afterinhalation, oral, and/or dermal exposure. Mobilization of PCBs from adipose tissue to target organs is likely to be similar regardless of theroute of exposure.
The table below presents short summary of LD50 value studies for technical PCB, Aroclor 1254. U.S. National Toxicology Program acute toxicity studies for Aroclor 1254
U.S National Toxicology Program acute toxicity studies for Aroclor 1254
|Study type ||Route ||Species ||Result ||Units |
The preponderance of toxicity data for PCBs is available from animals exposed to PCBs in the diet in intermediateduration studies. Studies havebeen performed with various species, but the rat, monkey, and mink have been tested most extensively. The liver, skin, and stomach areunequivocal targets, but existing studies do not identify NOAELs for effects in these organs in monkeys and minks. Anaemia consistently occursin monkeys at doses similar to those producing other effects, but a NOAEL and the relative importance of this effect is not known. There isevidence suggesting that effects occur in the thyroid and adrenal glands of rats at doses lower than those producing effects in other tissues inmonkeys and minks, but these doses are in proximity to those producing developmental toxicity in monkeys. A series of intermediatedurationstudies in infant monkeys found neurodevelopmental effects of a low dose of a congener mixture that simulated the congener composition of humanbreast milk. The single dose level tested was a LOAEL that was used as the basis for the intermediate MRL.
Some information is available on effects of PCBs in animals by inhalation or dermal exposure for intermediate durations. Although limited byvarious study inadequacies including insufficient numbers of animals, dose levels, end points and NOAEL data, this information is essentiallyconsistent with the oral data in indicating that the liver, kidneys, thyroid and skin are main targets of toxicity.
Some epidemiological studies of PCBexposed workers, which involve inhalation and dermal exposure, have provided evidences that PCBs wereassociated with adverse health effects, including hepatic and dermal changes. Reported effects on the respiratory system and gastrointestinaltract in these workers are suggestive.
There is growing evidence that immunologic, reproductive, and thyroid effects are effects of concern in PCBexposed populations. Relatively fewtoxicity studies of animals with chronic oral exposure to PCBs have been performed, and chronic inhalation and dermal toxicity studies withanimals, which could support or refute the findings of occupational studies, are lacking. Although limited in quantity, the available chronicanimal oral toxicity data essentially corroborate the results of intermediateduration studies with respect to effects in the liver, skin,stomach, blood, and thyroid, but provide no information on renal effects.
Limited information is available on reproductive effects of PCBs in humans. In women, there was no apparent effect of occupational exposure tovarious Aroclor mixtures on mean number of pregnancies. Due to study limitations and lack of information on gravidity in other studies, theeffect of PCBs on human conception is unclear.
Oral studies with animals provide conclusive evidence for reproductive toxicity of PCBs in females of various species and some evidence foreffects in male rats. Effects that have been induced in female animals include estrus changes and reduced implantation rate in adult rats and/ortheir offspring, decreased conception in mice, partial or total reproductive inhibition in minks, and menstrual alterations and decreasedfertility in monkeys. Monkeys (Rhesus) and minks are the most sensitive species tested, although reproductive effects were not induced at dosesquite as low as those inducing the critical neurobehavioral, immunological, and dermal/ocular effects used to derive the intermediate andchronic MRLs. In male animals, shortterm exposure to high oral doses of Aroclor 1254 induced no changes in the weight or histology of thetestes or accessory glands in adult rats, although seminal vesicle weights and caudal epididymal weights and sperm counts were reduced in ratsthat were exposed for several months as weanlings. No studies in male mice or rats evaluated reproductive capability. There is limited evidenceof hypoactivity of the seminiferous tubules in monkeys that were chronically exposed to a dose of Aroclor 1248 that also caused clinical signsof toxicity. In contrast to the limited evidence for reproductive effects in male adult animals, fertility was markedly reduced in maleoffspring of rats that were lactationally exposed to relatively high doses of Aroclor 1254, and results of oral and subcutaneous studies withsingle congeners have also shown that gestational and neonatal exposures can adversely affect morphology and production of sperm and fertilityin male rats and mice. Effects on male reproductive organs appear to involve postnatal developmentallyspecific vulnerable periods ofresponsiveness.