What Is the Biologic Fate of PCBs in Humans?
Rates of PCB metabolism vary greatly with the degree of chlorination of the biphenyl rings and the positions of the chlorines on these rings.
In the environment, PCBs undergo environmental alterations through
- Chemical transformation, and
- Preferential bioaccumulation.
As a result, compositions of environmental PCB mixtures differ from commercial PCB mixtures (original Aroclors).
Humans can absorb PCBs by the:
- Oral, and
- Dermal routes of exposure.
Although PCBs are readily absorbed into the body, they are slowly metabolized and excreted.
PCBs initially distribute preferentially to the liver and muscle tissue.
PCBs, especially the highly chlorinated congeners, tend to accumulate in lipid-rich tissues due to their lipophilic nature. Greater relative amounts of PCBs are usually found in
- Adipose tissue,
- Breast milk,
- The liver, and
- Skin [ATSDR 2000; Matthews et al. 1984].
The liver is the primary site of metabolism of PCBs, which occurs via hydroxylation and conjugation with glucuronic acid and sulfates.
PCBs are metabolized by the microsomal monooxygenase system catalyzed by cytochrome P-450 to phenols (via arene oxide intermediates), which can be conjugated or further hydroxylated to form a catechol [Safe SH 2007]. Glucuronide and sulfate conjugates are excreted mainly in the urine, whereas hydroxylated metabolites are excreted mainly in the bile.
The rate of individual congener metabolism depends on the number and position of chlorine atoms. Steele et al. estimated the half-life in humans for lower chlorinated biphenyls (Aroclor 1242) as 6-7 months and the corresponding half-life for the more highly chlorinated biphenyls as 33-34 months [Steele et al. 1986]. Phillips et al. measured total PCBs in capacitor workers and calculated half lives of 2.6 and 4.6 years for the lower (Aroclor 1242) and higher (Aroclor 1254) chlorinated biphenyls, respectively [Phillips et al. 1989]. A more recent study, taking into account of high initial body burden, ongoing environmental exposure, low serum levels, and congeners with very long half-lives, has showed the estimated half-lives during a period of high internal dose were 1.74 years for Aroclor 1242 and 6.01 years for Aroclor 1254. Half-lives during a period of low internal dose were estimated to be 21.83 years and 133.33 years for Aroclor 1242 and Aroclor 1254, respectively [Hopf et al. 2013].
In general, less-chlorinated PCB congeners are more readily metabolized than are highly chlorinated congeners. As a result of this preferential metabolism, highly chlorinated congeners tend to remain in the body longer than do less-chlorinated congeners. Highly chlorinated congeners therefore tend to become more concentrated in adipose tissues, where they are stored in solubilized form.
PCBs are primarily excreted after they have been conjugated and transformed into more polar metabolites. The major routes of excretion of PCBs are fecal and urinary.
Environmental PCBs occur as mixtures whose compositions differ from the commercial mixtures. This is because after release into the environment, PCB mixture composition changes over time through chemical transformation and preferential bioaccumulation [Cogliano 1998].
Chemical transformation can occur through biodegradation of PCB mixtures in the environment. PCBs with higher chlorine content are extremely resistant to oxidation and hydrolysis.
Preferential bioaccumulation occurs in living organisms. Bioaccumulation through the food chain tends to concentrate congeners of higher chlorine content. In humans, bioaccumulated PCBs also appear to be more persistent in the body [Hovinga et al. 1992]. This is significant because bioaccumulated PCBs appear to be more toxic than original Aroclors in animals [Aulerich et al. 1986; Cogliano 1998].
- PCBs are stored in adipose tissues.
- The liver is the primary site of metabolism of PCBs.
- The slow metabolism and high lipid solubility of PCBs lead to bioaccumulation.
- Binding of PCB metabolites to nucleophilic cellular macromolecules may contribute to the toxic effects of PCBs.
- After release into the environment, PCBs occur as mixtures whose compositions differ from the commercial mixtures. Bioaccumulated PCBs also appear to be more persistent in the body.