Environ. Sci. Technol. 2010, 44, 2876–2883
Distribution of PCBs, Their Hydroxylated Metabolites, and Other Phenolic Contaminants in Human Serum from Two European Countries†
mechanism of HO-PCB metabolite formation (HO-direct insertion vs. 1,2-shift of a chlorine atom) could be highlighted for investigated samples. The main chlorinated phenolic compound found in the Belgian samples was pentachlorophenol (PCP) which accounted for up to 85% of the total quantified phenolics, whereas in the Romanian samples, PCP accounted for only 35%.
A L I N C . D I R T U , ‡,§ VEERLE L. B. JASPERS,| ROBERTA CERNAT,§ HUGO NEELS,‡ AND A D R I A N C O V A C I * ,‡,⊥ Toxicological Center, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium, Department of Chemistry, “Al. I. Cuza” University of Iasi, Carol I Bvd. No 11, 700506 Iasi, Romania, Department of Biology, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Antwerp (Wilrijk), Belgium, and Laboratory for Ecophysiology, Biochemistry and Toxicology, Department of Biology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium
Polychlorinated biphenyls (PCBs) are one of the most studied classes of contaminants since they were discovered in the environment over 30 years ago (1). Even when they were banned in most countries in the late 1970s, PCBs usually dominated the burden of organohalogen contamination in humans (2). PCBs are biotransformed by cytochrome P-450 mono-oxygenases and the major metabolic pathways lead to the formation of hydroxylated PCBs (HO-PCBs) and methyl-sulfone PCBs (3). Even the most persistent PCBs in the environment, such as CB 153, are biotransformed both in vitro and in vivo forming a number of hydroxylated metabolites (3). The mechanism of PCB metabolism to HOPCBs involves the insertion of a HO-group on a biphenyl via arene oxide formation (possibly followed by 1,2 shift or NIH shift) (4, 5) or via direct insertion of the hydroxyl group (6). Therefore, theoretically the metabolism of PCBs results in the formation of a relatively large number of HO-PCB congeners (3, 7-9). In biological organisms, only HO-PCBs with HO- group in para- (chemical structure resembling prohormone thyroxine (T4)) or meta- position to the phenyl-phenyl bond and that possess adjacent chlorine atoms, have a greater in vitro binding affinity for transthyretin (TTR) than the natural ligand T4 (10-12). Therefore, their presence may lead to thyroid hormone metabolism disruption (10-13). HO-PCBs are selectively retained in plasma and this is a presumed mechanism of PCB toxicity (7). Therefore, it is possible that human exposure to different PCB mixtures may lead to formation of different profiles of HO-PCBs, this being a consequence of dissimilar metabolism of parental contaminants. As a consequence, it becomes necessary to investigate whether the human exposure to PCB congeners with a different degree of chlorination may lead to the formation of significantly different metabolite profiles, presenting different risks for independent populations. The present study investigates the presence of PCBs and their hydroxylated metabolites in human serum samples collected from (a) the Eastern part of Romania (Iasi), an area highly contaminated with organochlorine pesticides (14), and (b) Belgium, with relatively low levels of organohalogenated contaminants in human serum (15). The differences in the pathways and magnitude of exposure to organohalogenated contaminants for humans living in different areas were therefore investigated. Additionally, differences between the levels of other phenolic contaminants, such as pentachlorophenol (PCP) and tetrabromobisphenol-A (TBBP-A) were also assessed.
Received July 17, 2009. Revised manuscript received September 30, 2009. Accepted October 1, 2009.
Human exposure to mixtures of polychlorinated biphenyls (PCBs) may result in the formation of different profiles of hydroxylated PCBs (HO-PCBs), as a consequence of different exposures or dissimilar metabolism of parent compounds. Therefore, we investigated the levels and profiles of PCBs and HO-PCBs in human serum samples collected from two European countries with different degrees of pollution. There was no significant difference between the levels of sum PCBs measured in each set of samples, with a median concentration of 3100 pg/mL for Romanian samples (n ) 53) and 3380 pg/mL for Belgian samples (n ) 22). However, the median concentrations recorded for sum HO-PCBs were almost double in Belgian (310 pg/mL) compared to Romanian (175 pg/mL) samples. The detection frequency recorded for HO-PCBs in Belgian samples was also significantly higher compared to Romanian samples. The main contributors to the sum HO-PCBs in the Belgian samples were 4HO-CB107 > 4HO-CB146 > 4HO-CB187 (76% from the sum HO-PCBs) and 4HO-CB187 > 4HO-CB146 > 3′HO-CB138 (66% from the sum of HO-PCBs) in the Romanian samples. The HO-PCB profile showed that the higher chlorinated HO-PCBs had a higher contribution in the Romanian samples compared to the Belgian ones. This suggests that differences in the PCB profiles between populations can lead to the formation of different HO-PCB metabolite profiles presenting thus different risks for populations. No clear preferential † Part of the special section “Sources, Exposures, and Toxicities of PCBs in Humans and the Environment”. * Corresponding author tel: +32 3 265 2498; fax: +32 3 265 2722; e-mail:
[email protected]. ‡ Toxicological Center, Department of Pharmaceutical Sciences, University of Antwerp. § “Al. I. Cuza” University of Iasi. | Department of Biology, University of Antwerp. ⊥ Laboratory for Ecophysiology, Biochemistry and Toxicology, Department of Biology, University of Antwerp.
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ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 44, NO. 8, 2010
Introduction
Materials and Methods Samples Collection. Human serum samples were obtained in December 2006-January 2007 from individuals visiting the Clinical Hospital of Pneumology from lasi, Eastern Romania. Belgian samples were obtained in 2000 through the Public Health Institute from Brussels. In total, 53 persons, of which 22 were females, were sampled from Romania and 20 individuals, of which 4 were females, were sampled from 10.1021/es902149b
2010 American Chemical Society
Published on Web 10/13/2009
TABLE 1. Median Concentrations, Range (pg/mL Wet Weight), and Detection Frequencies (%) of Neutral and Phenolic Organic Compounds in Human Serum Samples from Romania and Belgium (Values for Method LOQs for Each Analyte Are Also Presented) Romanian samples (N ) 53)
Belgian samples (N ) 20)
range (pg/mL) compound total lipids (g/L) PCP 3HO-CB118 4HO-CB107 3HO-CB153 4HO-CB146 4′HO-CB127 3′HO-CB138 4′HO-CB130 4HO-CB163 4HO-CB187 3′HO-CB180 4′HO-CB172 4HO-CB193 ΣHO-PCBs TBBP-A
method LOQ (pg/mL)
DF (%)
range (pg/mL) a
min
max
median (pg/mL)
3.5
