ARTICLE IN PRESS

Ecotoxicology and Environmental Safety 71 (2008) 260–266 www.elsevier.com/locate/ecoenv

Pentachlorobenzene, , and pentachlorophenol in children’s serum from industrial and rural populations after restricted use

Daniel Carrizoa, Joan O. Grimalta,Ã, Nuria Ribas-Fitob, Maties Torrentc, Jordi Sunyerb

aDepartment of Environmental Chemistry, Institute of Chemical and Environmental Research (IIQAB-CSIC), Jordi Girona 18, 08034 Barcelona, Catalonia, Spain bRespiratory and Environmental Health Research Unit, Institut Municipal Investigacio´ Me`dica (IMIM), Barcelona, Catalonia, Spain cA`rea de Salut de Menorca, IB-SALUT, Menorca, Spain

Received 24 October 2006; received in revised form 14 May 2007; accepted 29 August 2007 Available online 1 November 2007

Abstract

The study of a population of 4-year-old children born between 1997 and 1999 in an urban area under strong inputs of pentachlorobenzene (PeCB) and hexachlorobenzene (HCB) suggested that the measured concentrations of pentachlorophenol (PCP) in serum may essentially result from metabolism of these chlorinated . In contrast, examination of a rural population of children where the same compounds were present at relatively low levels points to other inputs besides transformation of PeCB and HCB being responsible for the measured PCP concentrations. In both populations, the results showed that a major proportion of the organochlorine compounds present in these children’s serum at 4 years of age was incorporated during the lactation period. r 2007 Elsevier Inc. All rights reserved.

Keywords: Pentachlorobenzene; Hexachlorobenzene; Pentachlorophenol; Preschoolers; Maternal feeding; Children serum; Gender differences; Chloro- alkali plant emissions

1. Introduction To-Figueras et al., 1995). Alterations of the thyroid metabolism have also been observed as a consequence of Pentachlorobenzene (PeCB) has been used as an inter- exposure to high HCB levels (Sala et al., 2001). In addition, mediate for the synthesis of several compounds such as human exposure to this compound has been related with . However, it is also a by-product porphyria (Cam and Nigogosyan, 1963), thyroid cancer of the synthesis of organochlorine compounds (OCs) in and soft tissue sarcoma (Grimalt et al., 1994), and chloro-alkali plants, and has been reported to have neurodevelopment delays in children (Ribas-Fito et al., deleterious effects in the human nervous system, liver, 2006). and kidneys (US-EPA, 2006). Pentachlorophenol (PCP) is a chlorinated compound Hexachlorobenzene (HCB) is a widespread environmen- that has been used as a herbicide, disinfectant, and tal pollutant previously used as a fungicide for seed antimicrobial agent. It has been added to adhesives, paints, treatment. At present, the major source of HCB contam- paper coatings, food cans, and storage containers, and has ination is the industrial manufacture of organochlorinated also been used in leather tanning, pulp and paper solvents, namely in chloro-alkali plants. HCB is highly production. Since the early 1980s PCP has almost lipophilic and frequently found in food. It accumulates in exclusively been used as a wood preservative to protect human tissues after ingestion (Gomez-Catalan et al., 1993; timber from wood-boring insects and fungal rot (Fisher, 1991; Seiler, 1991). Increased lymphocyte responses have ÃCorresponding author. Fax: +34932045904. been observed in patients with high PCP blood levels E-mail address: [email protected] (J.O. Grimalt). (Daniel et al., 2001). Adverse neurobehavioral effects such

0147-6513/$ - see front matter r 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.ecoenv.2007.08.021 ARTICLE IN PRESS D. Carrizo et al. / Ecotoxicology and Environmental Safety 71 (2008) 260–266 261 as decreased performance in visual short-term memory, Table 1 verbal memory, and incidental learning tasks were ob- Characteristics of the populations from Ribera d’Ebre and Menorca served in women exposed to above average PCP levels in a Ribera d’Ebre Menorca domestic environment (Peper et al., 1999). It has also been related with infertility in women since it may act centrally Sample size at age 4 70 285 on a hypothalamic or suprahypothalamic level resulting in Recruitment period 1997–1999 1997–1998 mild ovarian and adrenal insufficiency (Gerhard et al., Gender (%) 1999). In vitro experiments have also shown that PCP may Girls 54.9 48.5 affect thyroid hormone metabolism by competitively Boys 45.1 51.5 inhibiting iodothyronine sulfation (Schuur et al., 1999), Birth length (cm) 49 49 Birth weight (g) 3248 3186 while possible alteration of thyroid metabolism in infants Gestational age (weeks) 40 40 due to exposure to this compound has been reported Maternal age (years) 30 29 (Sandau et al., 2002). Maternal social class (%) In the last 20 years, the use of these OCs has been Professional 20.4 12.7 severely restricted in a large number of countries, including Skilled 15.3 51.4 those from the European Union. However, they are still Non-skilled 27.6 15.3 found in humans, as well as those from children. The Unemployed, husband professional 6.1 2.4 present study is therefore devoted to contribute to the Unemployed, husband skilled 7.1 14.8 Unemployed, husband non-skilled 23.5 3.4 elucidation of the origin of these compounds, namely PCP, in human tissues after implementation of the use Maternal education (%) restrictions. High 0.0 13.1 Secondary 51.0 28.5 For this purpose their concentrations in serum of 4-year- Primary 6.1 51.1 old preschoolers from two populations, one living in the Less primary 42.9 7.3 area of influence of the PeCB and HCB emissions of a Paternal education (%) chloro-alkali plant and the other in a rural environment, High 14.3 8.3 have been examined. The former is represented by a cohort Secondary 41.8 24.8 located in the county of Ribera d’Ebre (Catalonia, Spain; Primary 35.7 56.5 Table 1) in which a large factory producing organochlorine Less primary 8.2 10.4 solvents is located (Flix). The second is situated in Marital status at age 4 Menorca, a rural environment not exposed to high HCB With a stable partner 97.6 91.0 or PeCB inputs. This island is one of the Balearic Islands in Divorced or widow 2.4 9.0 the northwest Mediterranean Sea and does not have Maternal feeding (%) factories producing OCs. Thus, the participant children o2 weeks 24.7 20.3 were taken as an example of the background exposure to 2–15.9 weeks 36.6 26.2 these pollutants in western countries. 16–27.9 weeks 22.6 27.6 X28 weeks 16.1 25.9 Both cohorts recruited women presenting for antenatal Age at examination (years) 4.4 4.3 care from 1997 onwards. The recruitment period encom- passed between 1997 and 1999 in Ribera d’Ebre and between mid 1997 and 1998 in Menorca (where birth rate repeated, yielding a combined extract of 7 mL of n-hexane, to which 2 mL was higher). Thus, serum samples from the participant conc-H2SO4 was added, the sample mixed (vortex mixer, ca. 1500 rpm, children were collected between 2001 and 2003. The 90 s), centrifuged as before, and the supernatant transferred to a conical Menorcan cohort was set up within the Asthma Multi- bottomed, graduated tube. The combined extracts were then reduced to center Infants Cohort study (AMICS) (Polk et al., 2004). near dryness under a gentle stream of nitrogen and an injection standard (PCB 142 in iso-octane; 10 mL) was added. Then, the sample was quantitatively transferred to GC vials using four 25 mL rinses of iso- 2. Materials and methods octane. If an emulsion was formed at any stage of the extraction, 10–15 drops of MilliQ water were added before sample centrifugation. The Standards of PeCB, HCB, PCP, tetrabromobenzene (TBB), PCB 142 samples were derivatizated with diazomethane in diethyl ether (1:1) for and PCB 209 in iso-octane were purchased from Dr. Ehrenstoffer preparation of methylated PCP derivatives. The mixture was left to react (Augsburg, Germany). Analytical grade concentrated sulfuric acid overnight, the solvent was evaporated with nitrogen gas and the residue

(conc-H2SO4), acetonitrile (CH3CN), iso-octane, and n-hexane were all was dissolved in iso-octane (50 mL). purchased from Merck (Darmstadt, Germany). A gas chromatograph with electron capture detection (Hewlett Packard Serum samples (0.5 mL) were introduced into 10 mL centrifuge tubes 6890N GC-ECD) was used to quantify PeCB, HCB, and PCP. Samples and TBB and PCB 209 were added as recovery standards. Then, 2 mL of were injected (2 mL) in splitless mode onto a 60 m, DB-5 column with a conc-H2SO4 and 3 mL of n-hexane were added, mixed in a vortex retention gap (both from J&W/Agilent). Helium was the carrier gas (ca. 1500 rpm, 30 s) and then centrifuged (ca. 1500 rpm, 10 min). The (1.5 mL/min). The temperature program was 90 1C 2 min, 20 1C/min to supernatant n-hexane layer was aspirated into a second centrifuge tube 140 1C, 4 1C/min to 200 1C held for 13 min, 4 1C/min to 310 1C held for using a Pasteur pipette. Further n-hexane (2 mL) was added to the first 10 min. tube containing the H2SO4/serum mixture, stirred (vortex ca. 1500 rpm, Quantification was performed by external standards using PCB 142 30 s) and then centrifuged (ca. 1500 rpm, 10 min). This last step was injection standard to correct for volume. Recoveries of TBB and PCB 209 ARTICLE IN PRESS 262 D. Carrizo et al. / Ecotoxicology and Environmental Safety 71 (2008) 260–266 were used to correct results. Limits of detection (LOD) and quantification site due to the emissions of the chloro-alkali plant (Grimalt (LOQ) were calculated from blanks (LOD ¼ mean of all blanks plus three et al., 1994). The concentrations of PCP were also higher in times the standard deviation, LOQ ¼ mean plus five times the standard deviation) or from instrumental LOD using diluted standards if the Ribera d’Ebre than in Menorca, involving a difference of compound was absent from the blanks. LOD for PeCB, HCB, and PCP one order of magnitude. To the best of our knowledge no were 0.01, 0.02, and 0.2 ng/mL, respectively. LOQ were 0.02, 0.05, and specific sources of PCP are located in Ribera d’Ebre. The 0.3 ng/mL, respectively. higher levels of PeCB, HCB, and PCP in Ribera d’Ebre are This method performed satisfactorily in repeated international inter- consistent with a possible source–metabolite relationship calibration exercises within the Arctic Monitoring and Assessment Programme (AMAP 2004). between these compounds (Renner, 1988). However, Information on socioeconomic background, maternal diseases, ob- comparison of the concentrations of these three com- stetric history, parity, child’s gender, foetal exposure to alcohol (ever pounds in the individuals belonging to the population of exposure during pregnancy) and cigarette smoking (at least one cigarette a Ribera d’Ebre did not show any significant correlation, nor day during the last trimester), type and duration of maternal feeding, was a correlation observed when comparing the concentra- education, and social class was obtained through questionnaires adminis- tered in person after delivery and at 48 months. The United Kingdom tions of these compounds in the individuals from the Registrar General’s 1990 classification was used to group subjects by population of Menorca. social class according to maternal and paternal occupation coded using the International Standard Classification of Occupations (ISCO-88, 2006). Social class was grouped into six categories: four were created according 3.2. Feeding mode to maternal occupation (professional, skilled, nonskilled, and unem- ployed), and unemployed women were categorized into three groups Information on the maternal feeding periods of children according to their husband’s occupation. Information on birth weight, from the populations of Ribera d’Ebre and Menorca are birth length, and gestational age was obtained through medical records. Information on type and duration of maternal feeding was obtained shown in Table 1. The average concentrations of PeCB, from questionnaires at 6, 12, and 24 months and were categorized by two HCB, and PCP in children from these two populations fed groups, formula and maternal feeding, the former involving two weeks or either with maternal milk or formula are shown in Tables 3 less maternal feeding and the latter more than two weeks of this feeding and 4, respectively. PeCB was present in higher average mode. concentrations in maternally fed children. However, the This study was approved by the Ethics Committee of the Institut Municipal d’Investigacio´Me` dica and all mothers provided a signed differences are only statistically different in the population informed consent. of Ribera d’Ebre (po0.01) where higher concentrations were found. In both populations, HCB exhibited signifi- cantly higher concentrations in children that underwent 3. Results maternal rather than formula feeding (po0.01 or 0.0001). No statistically significant differences between the two 3.1. Average concentrations in both populations feeding groups were found for the average PCP concentra- tions. In Menorca, the average PCP levels were higher The characteristics of the two study populations are among those fed with formula than maternal milk. described in Table 1. Average birth length (49 cm) and weight (3.2 kg) were the same in both populations. Average gestational and maternal ages at delivery were also the 3.3. Gender differences same (40 weeks and 29–30 years, respectively) in both cases. Mean ages at examination were virtually the same in No significant differences in feeding mode, either both populations (4.3–4.4 years). Children from the Ribera maternal or formula, or period of lactation were found d’Ebre cohort were more likely to be an only child (data between the two gender groups of these two populations. not shown). Concentrations of PeCB and HCB were higher in male The average concentrations of PeCB, HCB, and PCP in than female children in Ribera d’Ebre (Table 3). In the two studied populations are summarized in Table 2. Menorca slightly higher levels of HCB were observed Concentrations of PeCB and HCB were higher in Ribera in female and PeCB was found at higher levels in males d’Ebre than in Menorca which is consistent with the high (Table 4). The concentrations of PCP are higher in male in airborne concentrations of these compounds in the former both populations (Tables 3 and 4). In any case, these

Table 2 Concentrations of pentachlorobenzene, hexachlorobenzene, and pentachlorophenol in serum of 4-year-old children from Ribera d’Ebre and Menorca (ng/mL)

PeCB HCB PCP

Mean7SD Min Max Mean7SD Min Max Mean7SD Min Max

Ribera d’Ebre 0.03770.059 0 0.25 1.470.97 0.17 5.8 6.476.0 1.5 35 (n ¼ 59) (n ¼ 69) (n ¼ 66) Menorca 0.02370.085 0 0.79 0.4270.43 0.067 2.1 0.6170.69 0 4.7 (n ¼ 250) (n ¼ 250) (n ¼ 131) ARTICLE IN PRESS D. Carrizo et al. / Ecotoxicology and Environmental Safety 71 (2008) 260–266 263

Table 3 Differences in the concentrations of pentachlorobenzene, hexachlorobenzene, and pentachlorophenol in serum of 4-year-old children from Ribera d’ Ebre associated to sex and feeding mode (ng/mL)

PeCB HCB PCP

Mean7SD Min Max Mean7SD Min Max Mean7SD Min Max

Lactation mode Maternal 0.04470.062 0 0.25 1.571.1 0.30 5.8 7.176.7 1.5 35 (n ¼ 47)* (n ¼ 47)* (n ¼ 47) Formula 0.009070.030 0 0.099 0.9970.52 0.17 2.05 4.874.1 1.6 17 (n ¼ 11)* (n ¼ 15)* (n ¼ 12) Sex Female 0.03670.057 0 0.20 1.270.61 0.17 2.6 6.376.3 1.7 35 (n ¼ 29) (n ¼ 37) (n ¼ 32) Male 0.03870.062 0 0.25 1.771.2 0.3 5.8 6.976.4 1.5 24 (n ¼ 29) (n ¼ 32) (n ¼ 28)

*Statistically significant differences (po0.01).

Table 4 Differences in the concentrations of pentachlorobenzene, hexachlorobenzene, and pentachlorophenol in serum of 4-year-old children from Menorca associated to sex and feeding mode (ng/mL)

PeCB HCB PCP

Mean7SD Min Max Mean7SD Min Max Mean7SD Min Max

Lactation mode Maternal 0.03370.058 0 0.24 0.4770.41* 0.067 2.1 0.5970.61 0 3.4 (n ¼ 74) (n ¼ 74) (n ¼ 112) Formula 0.03070.066 0 0.79 0.2370.11* 0.11 0.46 0.7371.1 0 4.7 (n ¼ 13) (n ¼ 15) (n ¼ 16) Sex Female 0.03170.046 0 0.16 0.4470.42 0.067 2.1 0.5470.73 0 4.7 (n ¼ 41) (n ¼ 43) (n ¼ 63) Male 0.03470.069 0 0.24 0.4270.36 0.11 2.1 0.6870.66 0 3.4 (n ¼ 46) (n ¼ 46) (n ¼ 68)

Statistically significant differences (po0.0001). average gender values do not exhibit statistically significant children from urban areas of Germany (3.7 ng/mL; differences when evaluated with the Student’s t-test. Heudorf et al., 2003), Stockholm (2.0 ng/mL; Guvenius et al., 2003), USA (0.61–1.3 ng/mL; Wilson et al., 2007)or 4. Discussion coastal populations from Quebec (1.8 ng/mL; Sandau et al., 2002). The average concentrations in children from 4.1. HCB and PCP concentrations in children from Ribera Menorca (0.61 ng/mL; Table 2) were lower than reported in d’Ebre, Menorca and other populations all the above cases. No correlation between body mass index (BMI) and PCP levels were observed in this cohort. The average HCB concentrations in children from The PCP concentrations of both cohorts are consistent Ribera d’Ebre (1.8 ng/mL; Table 2) were towards the with the general decline observed after implementation of higher end of previously reported cases. They are similar to restricted use regulations, e.g. from 70 ng/mL in the 1980s those found in Germany between 1984–1985 (2.0 ng/mL, to about 12 ng/mL in 1996 (Heudorf et al., 2003). However, Lackmann et al., 1996) but higher than those in later the high average concentrations of HCB and PCP in samples from Germany between 1994–1995 (0.61 ng/mL, Ribera d’Ebre stand out among the recent data of quoted Lackmann et al., 1996), Norway (1.0 ng/mL, Skaare et al., literature sites. 1988) or Canada (0.04 ng/mL, Rhainds et al., 1999). The Examination of potential PCP sources for present- average concentrations in Menorca (0.43 ng/mL; Table 2) day general population suggests emissions from pulp, were lower than those reported in all these reference sites paper, and sawmill industries (Mussalo-Rauhamaa et al., except Canada (Rhainds et al., 1999). 1989) or emissions from municipal waste incinerators The average PCP concentrations in Ribera d’Ebre (Angerer et al., 1992; Paasivirta et al., 1985). However, (6.4 ng/mL; Table 2) were higher than those reported in there are not paper mill industries or municipal waste ARTICLE IN PRESS 264 D. Carrizo et al. / Ecotoxicology and Environmental Safety 71 (2008) 260–266 incinerators in Ribera d’Ebre neither in its vicinity. Menorca, where the average PeCB values in the whole Homes having wood ceilings treated with PCP have population were lower than in Ribera d’Ebre, no sig- also been described to lead to high levels of contamination nificant differences in the average values of maternal and by this compound (Gerhard et al., 1999) but the ceilings of formula feeders was found, although maternal feeders also the houses and apartments of the population living in exhibited higher concentrations (Table 4). Ribera d’Ebre are made of plaster, stone, or other In the populations of Ribera d’Ebre and Menorca, inorganic materials. Specific contaminations associated maternal feeding is the major route of incorporation of with leather jackets impregnated with PCP or as a HCB into 4-year-old children (Tables 3 and 4), which is in consequence of travel abroad have also been described agreement with previous observations from other studies, (Heudorf et al., 2003). These particular cases, if any, e.g. HCB (Karmaus et al., 2001). A full account of the cannot be representative of the general population in the maternal characteristics influencing the intake of HCB and cohort of Ribera d’Ebre. PeCB in the population of Menorca is given in Carrizo Another aspect to be considered is the fast excretion rate et al. (2006). of PCP, having half-lives in the order of 40–90 h (Seiler, PCP concentrations in children from Ribera d’Ebre were 1991), several days up to 2 weeks (Heudorf et al., 2003)or also higher among maternal than formula feeders. The about 17 days (Pecari et al., 1991; Uhl et al., 1986). Thus, relative difference between the two groups is similar to the the PCP concentrations found in the 4-year-old children difference observed in HCB concentrations (Table 3). from Ribera d’Ebre must be related to recent inputs. However, in the case of PCP, the higher standard Metabolization of HCB is also another possible source deviations meant that the average differences between of PCP in humans (Renner, 1988; van Ommen et al., 1985). maternal and formula feeders were not significant. In the Excretion of HCB through bile in adults (414 years old) case of Menorca, where the overall values of these from Flix has been observed to be mainly related with compounds were lower, there was no higher average PCP glutathion conjugation (To-Figueras et al., 1997, 2000). concentration among maternal feeders. In this cohort, no However, the same studies also showed a correlation correlations between BMI of the mothers at birth and PCP between HCB and PCP when comparing the concentra- or PeCB concentrations were observed. In contrast, HCB tions of these two compounds in serum and bile of and maternal BMI exhibited a statistically significant individuals from this population (To-Figueras et al., correlation (po0.05). 1997). The present study shows a correspondence between The concentrations of PeCB and HCB in the population high HCB and PCP values in the cohort of Ribera d’Ebre of Ribera d’Ebre indicated that the main input of these which is consistent with a precursor–metabolite relation- compounds for 4-year-old children was associated with ship. Thus, the accumulated HCB in the body of these maternal feeding. This maternal contribution stands out 4-year-old children could constitute the reservoir stock of among the inputs of these compounds that children PCP since the former compound has been calculated to received in their first 4 years. In the case of PCP, the data have half lives of 6 years in humans (To-Figueras et al., are also consistent with transformation of the HCB (and 2000). HCB could be incorporated into children as a possibly PeCB) accumulated by maternal feeding into PCP consequence of the air concentrations of this compound as main source of this compound. However, as mentioned due to the factory emissions in Flix. These results are above, this phenol is more water soluble than the precursor consistent with other studies involving preschooler children OCs having short half lives in humans (Heudorf et al., from general population in which inhalation was found to 2003; Pecari et al., 1991; Seiler, 1991; Uhl et al., 1986). represent about 70–99% of the main dietary ingestion of Thus, it is likely that this compound has lower degree of OCs (Wilson et al., 2007). retention in fat which may explain the higher dispersion of The cohort of Menorca constitutes a different case since values and the lack of degree of statistical significance children have PCP concentrations close to baseline between the means observed in maternal and formula concentrations (Wilson et al., 2007). This cohort has also feeding groups. In any case, in this population higher background HCB levels. A precursor–metabolite relation- average concentrations of PeCB and HCB in both feeding ship between these two compounds is also possible but modes are in correspondence with higher PCP levels these low levels could also reflect contributions from other (Table 3). environmental inputs. Furthermore, as mentioned in the In the case of Menorca, the lower levels of PeCB and introduction, no specific HCB industrial source is located HCB may have likely resulted in lower PCP concentrations in Menorca. (Table 4). These results are also consistent with a precursor–metabolite correspondence between HCB (and 4.2. Maternal feeding possibly PeCB) and PCP. Thus, the low concentrations of the apolar OCs and the short half lives of PCP in humans Maternal feeding is a major route for the incorporation may explain the lack of concentration differences between of PeCB in the population of Ribera d’Ebre where the maternal and formula feeding. However, the baseline concentration averages of this compound in maternal and concentrations of these compounds in this cohort does formula feeders were significantly different (po0.01). In not allow excluding other inputs. ARTICLE IN PRESS D. Carrizo et al. / Ecotoxicology and Environmental Safety 71 (2008) 260–266 265

4.3. Gender differences Angerer, J., Heinzow, B., Reimann, D.O., Knorz, W., Lehnert, G., 1992. Internal exposure to organic substances in a municipal waste PeCB, HCB, and PCP were higher in male than female incinerator. Int. Arch. Occup. Environ. Health 64, 265–273. Cam, C., Nigogosyan, G., 1963. Acquired toxic Porphyria Cutanea Tarda children of the cohort of Ribera d’Ebre (Table 3). The due to hexachlorobenzene. JAMA 183, 88–91. differences were not statistically significant (po0.05) but Carrizo, D., Grimalt, J.O., Ribas-Fito, N., Sunyer, J., Torrent, M., 2006. were consistent with the above mentioned precursor– Physical-chemical and maternal determinants of the accumulation of metabolite differences between these compounds. Thus, organochlorine compounds in four-year-old children. Environ. Sci. males have higher levels of the apolar OCs and also of PCP. Technol. 40, 1420–1426. Daniel, V., Huber, W., Bauer, K., Suesal, C., Conradt, C., Opelz, G., In the cohort of Menorca, PeCB and PCP were also 2001. Associations of blood levels of PCB, HCHS, and HCB with higher in male than female and HCB had virtually the same numbers of lymphocyte subpopulations, in vitro lymphocyte response, concentrations in both groups (Table 4). As mentioned plasma cytokine levels, and immunoglobulin autoantibodies. Environ. above, the lower concentrations of these compounds in this Health Perspect. 109, 173–178. cohort make it more difficult to determine the source Fisher, B., 1991. Pentachlorophenol: toxicology and environmental fate. associations between them. In a previous study on 7-year- J. Pesticide Reform 11, 2–5. Gerhard, I., Frick, A., Monga, B., Runnebaum, B., 1999. Pentachlor- old children from the Federal State of Hessen (Germany), ophenol exposure in women with gynaecological and endocrine the concentrations of HCB in both genders were virtually dysfunction. Environ. Res. Sect. A 80, 383–388. the same (Karmaus et al., 2001). Gomez-Catalan, J., Planas, J., To-Figueras, J., Camps, M., Corbella, J., 1993. Organochlorine pesticide residues in the population of Catalonia (Spain). Bull. Environ. Contam. Toxicol. 51, 160–164. 5. Conclusions Grimalt, J.O., Sunyer, J., Moreno, V., Amaral, O.C., Sala, M., Rosell, A., Anto, J.M., Albaiges, J., 1994. Risk excess of soft-tissue sarcoma and The children from the two cohorts considered for study thyroid cancer in a community exposed to airborne organochlorinated exhibit low PCP concentrations which is consistent with the compound mixtures with a high hexachlorobenzene content. Int. J. observed decrease in human levels after implementation of Cancer 56, 200–203. Guvenius, D.M., Aronsson, A., Ekman-Ordeberg, G., Bergman, A., the regulatory use restrictions of this compound. In this Noren, K., 2003. Human prenatal and postnatal exposure to context, the PCP concentrations found in the cohort of polybrominated diphenyl ethers, polychlorinated biphenyls, polychlor- Ribera d’Ebre seem to originate from transformation of the obiphenols, and pentachlorophenol. Environ. Health Perspect. 111, HCB (and PeCB) incorporated into children as a conse- 1235–1240. quence of atmospheric emissions of these apolar OCs due to Heudorf, U., Angerer, J., Drexler, H., 2003. Current international exposure to pesticides in children and adolescents in Germany: blood the industrial activities in the area. The low concentrations plasma levels of pentachlorophenol (PCP), lindane (g-HCH), and of PeCB, HCB, and PCP in the cohort of Menorca do not dichloro(diphenyl)ethylene (DDE), a biostable metabolite of dichlor- allow to assess this precursor–metabolite association in this o(diphenyl)trichloroethane (DDT). Int. J. Hyg. Environ. Health 206, case although the distribution of concentrations could also 485–491. / S be interpreted following this approach. ISCO-88, 2006. http://www.warwick.ac.uk/ier/isco/isco88.html . Karmaus, W., deKoning, E.P., Kruse, H., Witten, J., Osius, N., 2001. The higher concentrations of PeCB, HCB, and PCP in Early childhood determinants of organochlorine concentrations in maternally fed than formula fed children in Ribera d’Ebre school-aged children. Pediatric Res. 50, 331–336. at 4 years of age are consistent with generation of PCP Lackmann, G.M., Goe¨n, T., To¨llner, U., Schaller, K.H., Angerer, J., 1996. from a standing stock of the apolar OCs accumulated in PCBs and HCB in serum of full-term German neonates. Lancet 348, the breastfeeding period. 1035. Mussalo-Rauhamaa, H., Pyysalo, H., Antervo, K., 1989. The presence of chlorophenols and their conjugates in Finnish human adipose and liver Acknowledgments tissues. Sci. Total Environ. 83, 161–172. Paasivirta, J., Knuutila, M., Paukku, R., 1985. Study of organo- This research was supported by the Instituto de Salud pollutants in snow at north pole and comparison to the Carlos III. Red de Grupos INMA (G03/176) and projects snow at north, central and south Findland. Chemosphere 14, 1741–1748. PI041666 and PI051987. Pecari, K., Luotamo, M., Ja¨rvisalo, J., Lindroos, L., Aitio, A., 1991. Funding: This manuscript has been sponsored by the Urinary excretion of chlorinated phenols in saw-mill workers. Int. Spanish Research Network ‘‘Infancia y Medio Ambiente’’ Arch. Occup. Environ. Health 63, 57–62. (G03/176) from the Spanish Health Funding Agency Peper, M., Ertl, M., Gerhard, I., 1999. Long-term exposure to wood- (Instituto de Salud Carlos III) and also by projects preserving chemicals containing pentachlorophenol and lindane is related to neurobehavioral performance in women. Am. J. Ind. Med. PI041666 and PI051987 from the same organization. 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