Endocrine Disruptors

Characteristics

Fate and Transport in the Environment

Methods for Monitoring in the Environment

Methods for Measuring Human Exposure

Exposure Pathway

Strategies for Preventing or Controlling Exposure


PCBs - Harmful Effects

PCBs - Dose Response

Sites of Toxicity

Mechanisms of Toxicity

Toxicokinetics

Biomarkers

Risk Assessment

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BIOMARKERS

Of Exposure:

The preferred biomarkers of exposure are generally the substance itself or its metabolite in readily obtainable body fluids or excretory products. However, confounding can limit the use and interpretation of biomarkers of exposure. For example, body burden of a substance can be from multiple sources. The substance being monitored can be a metabolite of a different xenobiotic substance. Nonetheless, highly chlorinated PCBs or congeners that lack unsubstituted meta-para carbons yield the most reliable biomarkers of PCB exposure because they are resistant to metabolism and accumulate in tissues. However, OH-PCBs and Methyl Sulfone PCBs bioaccumulate as well. .

  • Since PCBs are lipophilic, they are generally stored in adipose tissue. However, they are also present in serum, blood plasma, and human milk. Both serum and plasma PCB levels can be significantly affected by serum lipid content (total cholesterol, free cholesterol, triglycerides, and phospholipids) because of partitioning between adipose tissue and serum lipids. Therefore, serum or plasma lipid PCB levels are a better biomarker for body burden than serum or plasma PCB levels without lipid content corrections. Correction factors can be obtained by measuring PCB serum levels while fasting and while not fasting. Non-fasting levels tend to be higher.
  • Due to bioaccumulation in adipose tissue, PCB levels can be measured from tissue samples. PCB levels in adipose tissue will normally display different compositions when compared to the original PCB source. Therefore, body burdens of PCBs should be based on the levels of individual congeners or groups of congeners, not on the commercial PCB mixtures
  • Accumulation of PCBs also occurs in human milk. High resolution analytical techniques such as gas chromatography can be used to compare the congeneric composition of PCBs in human milk with commercial mixtures.
  • Chloroacne and other dermal conditions are relevant biomarkers of exposure to PCBs. These conditions are typically found in subjects occupationally exposed to PCBs. Chloracne appears when serum PCB levels are ten to twenty times greater than the levels found in the general population. However, interindividual variability is great and reduces the sensitivity of this biomarker.

An important issue regarding exposure biomarkers of PCB’s is whether or not serum and adipose tissue samples yield similar information regarding body burden. Convincing positive serum to adipose correlation coefficients have been reported suggesting that either serum or adipose tissue samples may be used

Of Effects:

Biomarkers that test the effects of PCBs have attempted to correlate PCB levels with health indices.

  • Correlations between serum PCB levels with serum levels of liver-related enzymes (e.g., AST, ALT) and serum lipid levels (cholesterol, triglycerides) have been reported. However, correlation between serum PCBs and lipid levels depend on the partitioning of PCBs between lipids and adipose tissue. Therefore, serum lipid levels are better for correcting serum PCB levels, as in exposure biomarkers. Additionally, altered liver-associated enzyme levels may be nonspecific and may be within normal ranges. Nonetheless, animal tests suggest that liver enzyme induction may be the most sensitive biomarker of PCB effects.
  • The Caffeine Breast Test has also been used to observe the effects of PCBs. 13C-methyl caffeine is ingested and the activity of a particularenzyme, hepatic cytochrome P4501A2-dependent caffeine 3-N-demethylase, is monitored by measuring the quantity of caffeine exhaled as radiolabeled CO2. This biomarker is also responsive to PCDFs and PCDDs that also induce the cytochrome P4501A.
  • A specific human hepatoma cell line, HcpG2, has been used to determine dose response characteristics of a mixture of related PCBs (Aroclor’s). The human CYP1A1 gene was engineered to produce luciferase instead of P-45050 upon induction by PCBs and the product levels were monitored.

REFERENCES:

New Types of Persistent Halogenated Compounds (Ed. by J. Paasivirta). The Handbook of Environmental Chemistry Vol 3. Part K. Springer-Verlag, Berlin Heidelberg. 2000

Wolf MS. 1985. Occupational Exposure to Polychlorinated Byphenyls (PCBs). Environmental Health Perspective 60: 133-138.

Schlummer M, Moser GA, McLachlan MS. 1998. Digestive tract absorption of PCDD/Fs, PCBs, and HCB in humans: Mass balances and mechanistic considerations. Toxicol Appl Parmacol 152: 128-137.


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