What Is the Biological Fate of the PAHs in the Body?
Course: WB 1519
CE Original Date: July 1, 2009
CE Renewal Date: July 1, 2011
CE Expiration Date: July 1, 2013
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Once PAHs enter the body, several things occur:
- PAHs are metabolized in a number of organs and excreted in bile and urine
- PAHs are excreted in breast milk and stored to a limited degree in adipose tissue.
Not much data for humans exists regarding the metabolic fate of PAHs. However, information on absorption, distribution, and elimination of these substances is available from animal studies.
Pyrene is commonly found in PAH mixtures, and its urinary metabolite, 1-hydroxypyrene, has been used as an indicator of exposure to PAH chemicals [Becher and Bjorseth 1983; Granella and Clonfero 1993; Popp 1997; Santella et al. 1993, CDC 2005]. The ACGIH recommends measurement of 1-hydroxypyrene in the end-of-shift, end-of-work-week urine samples as a biological exposure index (BEI) for assessment of exposure to mixtures containing PAHs.
Measurements of 22 PAH hydroxylated urinary metabolites were taken as part of the Third National Report on Human Exposure to Environmental Chemicals from a subsample of the National Health and Nutrition Examination Survey (NHANES) from participants aged 6 years and older during 1999–2002. These data provide physicians with a reference range so that they can determine whether people have been exposed to higher levels of PAHs than are found in the general population [CDC 2005].
PAHs are absorbed through ingestion, inhalation, and dermal contact, according to animal study data. The percent absorbed varies in these studies for several reasons, including the vehicle (transport medium) in which the PAHs are found [Kawamura et al. 1988]. In general, PAHs not bound to particulate matter may be absorbed in the lungs better than the same dose found on the surface of airborne particulate matter [Cresia et al. 1976; Seto 1993].
Once absorbed, PAHs
- enter the lymph,
- circulate in the blood, and
- are metabolized primarily in the liver and kidney.
PAHs differ with respect to distribution patterns and lipophilic properties [Busbee et al. 1990]. Because of their lipophilic nature, PAHs can accumulate in breast milk and adipose tissue. However, biliary and urinary excretion of PAHs is relatively efficient because of the wide distribution of enzymes that transform PAHs into polar metabolites.
PAHs are predominantly metabolized via CYP enzymes (enzymes in the P-450 mixed-function oxidase system) in the liver [Kapitulnik et al. 1977; Keifer et al. 1988; Monteith et al. 1987].
In addition to the liver and kidneys, metabolism of PAHs occurs in the adrenal glands, testes, thyroid, lungs, skin, sebaceous glands, and small intestines [ATSDR 1995].
PAHs are transformed initially to epoxides, which are converted to dihydrodiol derivatives and phenols. Glucuronide and sulfate conjugates of these metabolites are excreted in the bile and urine. Glutathione conjugates are further metabolized to mercapturic acids in the kidney and are excreted in the urine.
The hydroxylated metabolites of the PAHs are excreted in human urine both as free hydroxylated metabolites and as hydroxylated metabolites conjugated to glucuronic acid and sulfate [CDC 2005]. A commonly measured urinary metabolite is 1-hydroxypyrene [Becher and Bjorseth 1983; Granella and Clonfero 1993; Popp 1997; Santella 1993].
Metabolism is a prerequisite for hepatobiliary excretion and elimination through the feces, regardless of route of entry.
Excretion half-lives in feces and urine have been reported in animal studies as 22 hours and 28 hours, respectively [Becher and Bjorseth 1983].
- Absorption by route varies in animal studies.
- PAH distribution patterns vary due to differences in lipophilic properties.
- Metabolism via CYP liver enzymes (enzymes in the P-450 mixed-function oxidase system) is the predominant mechanism of PAH metabolism.
- PAHs are transformed to epoxides, then to dihydrodiol derivatives and phenols.
- Excretion occurs via the bile or urine after metabolite conjugation to glucuronides and sulfates.
- 1- Hydroxypyrene is a commonly measured urine metabolite.