Serum Concentrations Of Organochlorine Compounds Research Articles

Serum concentrations of organochlorine compounds and predictors of exposure in children living in agricultural communities from South-Eastern Spain

BackgroundInformation on exposure levels to organochlorine compounds (OCs) in child population is limited, despite their greater vulnerability to the adverse health effects of these chemicals. ObjectiveTo determine serum concentrations of 10 OCs (including organochlorine pesticides and polychlorinated biphenyls –PCBs–) in children living in agricultural communities from Almería (South-Eastern Spain), and to identify the main predictors of exposure related to socio-economic characteristics, diet and lifestyle. MethodsA cross-sectional study was conducted on 133 children aged 6–11 years selected from public schools of the study area. OCs compounds were determined in serum samples by GC/ECD. Anthropometric measures were obtained during sample collection. Information on sociodemographic characteristics, parental occupation, residential history, lifestyle and frequency of food consumption, among other relevant factors, was obtained by questionnaires administered to the mothers. ResultsGeometric means of serum concentrations (ng/ml) were 0.11 for β-hexachloro-cyclohexane (β-HCH), 0.09 for endosulfan, 0.20 for endosulfan-ether, 0.51 for hexachorobenzene (HCB), 0.08 for mirex, 0.06 for oxychlordane, 0.36 for p,p'-DDE, 0.20 for PCB 138, 0.36 for PCB 153, and 0.45 for PCB 180. Percentage of samples above the limit of detection (0.05 ppb) ranged from 32 (β-HCH) to 100 (HCB). A high variability in OC levels depending on the compound was observed between our results and others found in similar studies carried out in children. Variables related to fish consumption were found to be the major dietary determinant of PCB 138, p,p´-DDE, endosulfan-α, β-HCH, mirex and oxychlordane levels. ConclusionsChildren participating in this study showed detectable levels of many OC, despite these compounds are no longer used. Their presence in children serum can be explained by their high lipophilicity and environmental persistence, leading to contamination of fatty food. In this line, fish consumption seemed to be the most relevant determinant of OC levels found in our study.

Gestational diabetes and offspring birth size at elevated environmental pollutant exposures

BackgroundGestational diabetes mellitus (GDM) is associated with increased availability of glucose and macronutrients in fetal circulation and macrosomia. Therefore, the role of GDM in the association between metabolism-disrupting chemicals and birth size deserves attention. ObjectiveWe examined whether GDM may mediate or modify the associations between maternal environmental pollutant exposures and offspring birth size measures. MethodsWe analyzed 604 Faroese pregnant women and their offsprings born in 1997–2000. Maternal pregnancy serum concentrations of organochlorine compounds (OCs: polychlorinated biphenyl (PCB) congeners and dichlorodiphenyldichloroethylene (DDE)), and five perfluoroalkyl substances (PFASs), and hair and cord blood mercury concentrations were measured. We used regression (single-pollutants) and structural equation models (SEMs) (multiple-pollutant analyses using latent constructs of OCs, PFASs and mercury) to estimate the associations with GDM and birth size measures, accounting for mediation and/or effect modification by GDM. ResultsSerum-DDE and hair-mercury concentrations were associated with GDM (adjusted OR per concentration doubling: 1.29; 95% CI: 0.94, 1.77 for DDE, and 0.79; 95% CI: 0.62, 0.99 for mercury), but in multiple pollutant-adjusted SEMs only a positive association between OC exposure and GDM remained significant (change in GDM odds per OC doubling: 0.45; 95% CI: 0.05, 0.86). PCB and overall OC exposure were positively associated with head circumference (SEM; mean change per OC doubling: 0.13cm; 95% CI, 0.01. 0.25). Overall PFAS exposure was inversely associated with birth weight (SEM; mean change per PFAS doubling: −169g; 95% CI: −359, 21), and for many single-PFASs we found a pattern of inverse associations with birth weight and head circumference in boys, and positive or null associations in girls. None of the environmental pollutants was associated with offspring length. GDM neither modified nor mediated the associations with birth size measures. ConclusionsWe found associations with GDM and offspring birth size to be specific to the environmental pollutant or pollutant group. Associations with birth size measures appear to be independent of GDM occurrence.

The association of serum trans-nonachlor levels with atherosclerosis

ABSTRACTRecent epidemiological studies suggest a strong association between exposure to environmental contaminants, including organochlorine (OC) insecticides or their metabolites, and development of pathologies, such as atherosclerosis, in which oxidative stress plays a significant etiological role. Biomarkers of systemic oxidative stress have the potential to link production of reactive oxygen species (ROS), which are formed as a result of exposure to xenobiotic toxicants, and underlying pathophysiological states. Measurement of F2-isoprostane concentrations in body fluids is the most accurate and sensitive method currently available for assessing in vivo steady-state oxidative stress levels. In the current study, urinary concentrations of F2-isoprostanes and serum levels of persistent OC compounds p,p’-dichlorodiphenyldichloroethene (DDE), trans-nonachlor (a component of the technical chlordane mixture), and oxychlordane (a chlordane metabolite) were quantified in a cross-sectional study sample and the association of these factors with a clinical diagnosis of atherosclerosis determined. Urinary isoprostane levels were not associated with atherosclerosis or serum concentrations of OC compounds in this study sample. However, occurrence of atherosclerosis was found to be associated with serum trans-nonachlor levels. DDE and oxychlordane were not associated with atherosclerosis. This finding supports current evidence that exposure to environmental factors is a risk factor for atherosclerosis, in addition to other known risk factors.

Review of the state of the art of human biomonitoring for chemical substances and its application to human exposure assessment for food safety

Review of the state of the art of human biomonitoring for chemical substances and its application to human exposure assessment for food safety

Adjusting serum concentrations of organochlorine compounds by lipids and symptoms: A causal framework for the association with K-ras mutations in pancreatic cancer

In clinically aggressive diseases, patients experience pathophysiological changes that often alter concentrations of lipids and environmental lipophilic factors; such changes are related to disease signs and symptoms. The aim of the study was to compare the effects of correcting for total serum lipids (TSL) and other clinical factors on the odds of mutations in the K-ras oncogene by organochlorine compounds (OCs), in logistic models, in 103 patients with exocrine pancreatic cancer (EPC) using a causal directed acyclic graph (DAG) framework. Results and likelihood of bias were discussed in the light of possible causal scenarios. The odds of K-ras mutated EPC was associated with some TSL-corrected OCs, including p,p′-DDT (p-value: 0.008) and polychlorinated biphenyl 138 (p-trend: 0.024). When OCs were not corrected by TSL, the OR of a K-ras mutation was significant for p,p′-DDT (p-trend: 0.035). Additionally adjusting for cholestatic syndrome increased the ORs of TSL-corrected OCs. When models were adjusted by the interval from first symptom to blood extraction (ISE), the ORs increased for both TSL-corrected and uncorrected OCs. Models with TSL-corrected OCs and adjusted for cholestatic syndrome or ISE yielded the highest ORs. We show that DAGs clarify the covariates necessary to minimize bias, and demonstrate scenarios under which adjustment for TSL-corrected OCs and failure to adjust for symptoms or ISE may induce bias. Models with TSL-uncorrected OCs may be biased too, and adjusting by symptoms or ISE may not control such biases. Our findings may have implications as well for studying environmental causes of other clinically aggressive diseases.

Serum concentrations of persistent organic pollutants (POPs) in the inhabitants of a Sicilian city

BackgroundPolychlorinated biphenyls (PCBs) and organochlorine pesticides are common environmental contaminants that have been associated with human health problems. ObjectivesTo assess serum concentrations of several organochlorine contaminants in general population living in a city with an ancient agricultural tradition and to identify possible exposure sources in Sicily. MethodsA cross-sectional study was conducted on 101 individuals. Each participant answered a face-to-face questionnaire submitted by well-trained personnel and provided a serum sample which was analyzed for the concentrations of PCBs, HCB, HCHs and DDTs by using gas-chromatography coupled with mass spectrometry. ResultsHCB, p,p′-DDE, PCB 138, PCB 153 and PCB 180 were detected in more than 80% of the study participants. The ngg−1 lipid median concentrations were: 18.6 for HCB; 175.1 for p,p′-DDE; 22. for PCB 138; 32.5 for PCB 153 and 23.0 for PCB 180. PCB 153 and PCB 138, PCB 138 and PCB 180, PCB 153 and PCB 180, and p,p′-DDE and HCB showed a high correlation each other (p<0.05). HCB and p,p′-DDE concentrations were significantly higher in subjects >49years old (adj-p=0.03 in 50–69years old and adj-p<0.001 in >69years old, respectively) whereas PCB 138, PCB 153 and PCB 180 concentrations were higher in males (adj-p=0.03), in subjects >69years old (adj-p=0.04) and in current smokers (adj-p=0.04). ConclusionsThe present study shows that serum concentrations of organochlorine compounds detected in subjects living in a small Sicilian city with ancient agricultural tradition are similar to those found in subjects living in urban areas of other countries. However, further investigations are needed to compare data from rural/urban areas in the same country, assessing correlations between serum concentrations of several chemical compounds and potential health effects in general population.

Relationships between occupational history and serum concentrations of organochlorine compounds in exocrine pancreatic cancer

BackgroundPrevious studies investigating associations between occupational history and risk of exocrine pancreatic cancer (EPC) did not use biomarkers of exposure. The only two studies that measured internal concentrations of organochlorine...

The relative influence of diet and serum concentrations of organochlorine compounds on K- ras mutations in exocrine pancreatic cancer

Background In exocrine pancreatic cancer (EPC) mechanistic relationships may exist among some organochlorine compounds (OCs) and mutations in the K- ras oncogene, as well as among the latter and dietary factors. Objective To analyze (1) the relationship between food intake and serum concentrations of OCs in EPC patients and (2) the relative influence of food and OCs on the frequency of K- ras mutations in EPC. Patients and methods Incident cases of EPC were prospectively identified, and interviewed face-to-face during hospital admission ( N = 135 patients with data on OCs and diet, and N = 97 with additional information on K- ras status). OCs were measured by high-resolution gas chromatography with electron-capture detection. Results Consumption of milk and other dairy products was positively associated with concentrations of p,p′-DDT, PCB 138 and PCB 153 (log-transformed βs = 0.652, 0.588 and 0.317, respectively; all p < 0.05). When adjusted by OCs, dairy products were no longer associated with K- ras. By contrast, after adjusting by consumption of dairy products, patients with the highest concentrations of p,p′-DDT and some PCBs remained more likely to have a K- ras-mutated EPC than patients with lower concentrations (OR for upper tertile of PCB 138 = 5.5, 95% CI: 1.3–23.4). Conclusions Dairy products were a source of OCs. The association between dairy products and K- ras mutations was not independent of OCs. By contrast, the association between OCs and K- ras was not confounded by dairy products. OCs may be more likely to contribute to the occurrence of K- ras mutations than nutrients contained in dairy products.

An evaluation of the sexual differences in the accumulation of organochlorine compounds in children at birth and at the age of 4 years

This study of the body burden and serum concentrations of organochlorine compounds (OCs), represents a general population in a cohort from Menorca Island (birth 1997-1998) of children at birth and at 4 years of age; the study has shown that the concentrations of hexachlorobenzene (HCB), 4,4'-DDE, 4,4'-DDT, polychlorobiphenyl (PCB) congeners #153, #138 and #180 and total PCBs in sera collected at 4 years are much higher in breastfed children than in those fed with formula, e.g. HCB 0.48 vs 0.21 ng/ml, beta-HCH 0.32 vs 0.24 ng/ml, total DDTs 2.2 vs 0.57 ng/ml and total PCBs 1.4 vs 0.52 ng/ml. Comparison of gender differences in 4 years old children shows higher concentrations of all examined OCs in females than in males with the exception of HCB and PeCB in breastfed children, which are higher in males than in females, e.g. beta-HCH 0.34 vs 0.28 ng/ml, total DDTs 2.6 vs 1.7 ng/ml and total PCBs 1.6 vs 1.0 ng/ml for breastfed children and beta-HCH 0.23 vs 0.19 ng/ml, total DDTs 0.59 vs 0.48 ng/ml and total PCBs 0.58 vs 0.45 ng/ml for formula fed children. Gender comparison of the body burden between children fed with breastmilk or formula also shows higher concentrations in females than in males, e.g. beta-HCH 0.47 vs 0.35 microg, total DDTs 3.0 vs 1.8 microg and total PCBs 1.9 vs 1.2 microg for breastfed children, and beta-HCH 0.39 vs 0.17 microg, total DDTs 0.48 vs 0.27 microg and total PCBs 0.66 vs 0.55 microg for formula fed children. The results may suggest a higher capacity in female children for the retention of OCs incorporated through breastfeeding. However, these results should be taken with caution because the differences of the gender averages have low statistically significance when evaluated with the Student test.

Pre-Diagnostic Serum Concentrations of Organochlorine Compounds and Risk of Testicular Germ Cell Tumors

Pre-Diagnostic Serum Concentrations of Organochlorine Compounds and Risk of Testicular Germ Cell Tumors

Correcting serum concentrations of organochlorine compounds by lipids: Alternatives to the organochlorine/total lipids ratio

Introduction When studying the effects of organochlorine compounds (OCs) on human health it is common to correct serum concentrations of OC by total lipids (TL). However, the relationship between serum OCs and serum TL is far from established in many diseases, including several cancers. Our aim was to analyze the relationship between serum OC and TL in patients with pancreatic ductal adenocarcinoma (PDA), and to explore several alternatives to perform the OC lipid correction. Methods Incident cases of PDA were interviewed and had blood drawn soon around hospital admission ( n = 144). Serum concentrations of OCs were analysed by high-resolution gas chromatography with electron-capture detection. Results Most patients with high TL had moderate or low concentrations of OCs. By contrast, the variability of OC values among patients with normal TL was large. Correlations were of a similar magnitude between OC and TL and between OC and total cholesterol; while these correlations were weak (all Spearman's ρ < 0.3 and R 2 < 0.11), no OC were significantly correlated with triglycerides. Although all alternatives to the OC/TL linear ratio were statistically significant for at least one OC, their R 2 was always below 10%. Conclusions In patients with severe diseases as PDA, linear correction of OC by TL as commonly performed in epidemiologic studies may be inappropriate. Results contribute to the scant literature on the rationale to correct serum concentrations of OC by lipids. They suggest that it is unwarranted to routinely correct OC by TL, offer ways to assess such need, and present alternatives as no TL correction, correction by total cholesterol only or use of different statistical models.

Influence of tumor stage, symptoms, and time of blood draw on serum concentrations of organochlorine compounds in exocrine pancreatic cancer

Knowledge is scant on the relationships between pathophysiologic processes common during cancer progression and changes in blood concentrations of organochlorine compounds (OCs). To analyze the influence of tumor stage, cancer symptoms, and time of blood extraction on serum concentrations of OCs in exocrine pancreatic cancer (EPC). Subjects were 144 incident cases of EPC prospectively recruited in eastern Spain. Blood was drawn and face-to-face interviews with patients were conducted during hospital admission. Information on signs and symptoms was obtained from medical records and patient interviews. OCs were analyzed by high-resolution gas chromatography with electron-capture detection. General linear models were applied to analyze log-transformed OCs corrected for total lipids. Lower concentrations of six of the seven OCs analyzed (p,p'-DDE, three polychlorinated biphenyls, hexachlorobenzene, and β-hexachlorocyclohexane) were observed in patients with cholestatic syndrome (jaundice, hypocholia, and choluria). The constitutional syndrome increased only p,p'-DDT. The lowering effect of the cholestatic syndrome was stronger than the increasing effect of the constitutional syndrome (fatigue, anorexia, and weight loss), except for p,p'-DDT. When symptoms were considered, stage had only weakly inverse relationships with OC levels. The effects of symptoms on p,p'-DDE, p,p'-DDT, and the three PCBs remained significant after adjusting by the interval from blood extraction to first symptom of EPC, and even when further adjusting by stage. Restriction or adjustment by stage and timing of blood draw may be insufficient to prevent biases associated with cancer progression. Symptoms may enable investigators to assess disease-induced changes in lipophilic exposure biomarkers.

Prediagnostic Serum Concentrations of Organochlorine Compounds and Risk of Testicular Germ Cell Tumors

BackgroundRecent findings suggest that exposure to organochlorine (OC) compounds, chlordanes and p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) in particular, may increase the risk of developing testicular germ cell tumors (TGCTs).ObjectiveTo further investigate this question, we conducted a nested case–control study of TGCTs within the Norwegian Janus Serum Bank cohort.MethodsThe study was conducted among individuals with serum collected between 1972 and 1978. TGCT cases diagnosed through 1999 (n = 49; 27–62 years of age at diagnosis) were identified through linkage to the Norwegian Cancer Registry. Controls (n =51) were matched to cases on region, blood draw year, and age at blood draw. Measurements of 11 OC insecticide compounds and 34 polychlorinated biphenyl (PCB) congeners were performed using gas chromatography/high-resolution mass spectrometry. Case–control comparisons of lipid-adjusted analyte concentrations were performed using the Wilcoxon signed-rank test. Odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles of analyte concentration were calculated using conditional logistic regression.ResultsTGCT cases had elevated concentrations of p,p′-DDE (tertile 3 vs. tertile 1 OR (ORT3) 2.2; 95% CI, 0.7–6.5; pWilcoxon = 0.07), oxychlordane (ORT3 3.2; 95% CI, 0.6–16.8; pWilcoxon = 0.05), trans-nonachlor (ORT3 2.6; 95% CI, 0.7–8.9; pWilcoxon = 0.07), and total chlordanes (ORT3 2.0; 95% CI, 0.6–7.2; pWilcoxon = 0.048) compared with controls, although no ORs were statistically significant. Seminoma cases had significantly lower concentrations of PCB congeners 44, 49, and 52 and significantly higher concentrations of PCBs 99, 138, 153, 167, 183, and 195.ConclusionsOur study provides additional but qualified evidence supporting an association between exposures to p,p′-DDE and chlordane compounds, and possibly some PCB congeners, and TGCT risk.

Differences in serum concentrations of organochlorine compounds by occupational social class in pancreatic cancer

Background The relationships between social factors and body concentrations of environmental chemical agents are unknown in many human populations. Some chemical compounds may play an etiopathogenic role in pancreatic cancer. Objective To analyze the relationships between occupational social class and serum concentrations of seven selected organochlorine compounds (OCs) in exocrine pancreatic cancer: dichlorodiphenyltrichloroethane (p,p′-DDT), dichlorodiphenyldichloroethene (p,p′-DDE), 3 polychlorinated biphenyls (PCBs), hexachlorobenzene, and β-hexachlorocyclohexane. Methods Incident cases of exocrine pancreatic cancer were prospectively identified, and interviewed face-to-face during hospital admission ( n=135). Serum concentrations of OCs were analyzed by high-resolution gas chromatography with electron-capture detection. Social class was classified according to occupation. Results Multivariate-adjusted concentrations of all seven compounds were higher in occupational social classes IV–V (the less affluent) than in classes I–II; they were higher as well in class III than in classes I–II for four compounds. Concentrations of six OCs were higher in manual workers than in non-manual workers ( p<0.05 for PCBs). Social class explained statistically between 3.7% and 5.7% of the variability in concentrations of PCBs, and 2% or less variability in the other OCs. Conclusions Concentrations of most OCs were higher in the less affluent occupational social classes. In pancreatic cancer the putative causal role of these persistent organic pollutants may not be independent of social class. There is a need to integrate evidence on the contribution of different social processes and environmental chemical exposures to the etiology of pancreatic and other cancers.

The influence of lipid and lifestyle factors upon correlations between highly prevalent organochlorine compounds in patients with exocrine pancreatic cancer

We aimed to analyse the influence of cholesterol and triglycerides, and of tobacco, coffee and alcohol consumption upon correlations between serum concentrations of organochlorine compounds (OCs) in patients with exocrine pancreatic cancer (EPC). Incident cases of EPC diagnosed in eastern Spain were prospectively identified (N=144). OCs were analysed by high-resolution gas chromatography with electron-capture detection. A strong correlation was observed between hexachlorobenzene (HCB) and β-hexachlorocyclohexane (β-HCH) (Spearman's ρ=0.758). β-HCH showed ρ>0.4 with p,p′-DDT, p,p′-DDE, PCB138 and PCB153 (all p<0.001). Some correlations among compounds were slightly affected by tobacco, coffee or alcohol consumption. We observed a striking diversity of correlation patterns by strata of cholesterol and triglycerides. Most correlations were higher in the lowest category of triglycerides than in the lowest category of cholesterol. Most coefficients above 0.7 were seen in the lowest category of triglycerides (e.g., OC pairs p,p′-DDT and HCB, p,p′-DDT and β-HCH, p,p′-DDE and β-HCH, or HCB and β-HCH). Correlations among OCs may be stronger when concentrations of triglycerides are low than when they are high. This is compatible with a dilution in the early phases of cancer and with a concentration effect as triglycerides become lower in the advanced phases of the disease.

Determinants of serum concentrations of organochlorine compounds in Swedish pregnant women: a cross-sectional study.

BackgroundWe performed a cross-sectional study of associations between personal characteristics and lipid-adjusted serum concentrations of certain PCB congeners and chlorinated pesticides/metabolites among 323 pregnant primiparous women from Uppsala County (age 18–41 years) sampled 1996–1999.MethodsExtensive personal interviews and questionnaires about personal characteristics were performed both during and after pregnancy. Concentrations of organochlorine compounds in serum lipids in late pregnancy were analysed by gas chromatography. Associations between personal characteristics and serum levels of organochlorine compounds were analysed by multiple linear regression.ResultsParticipation rate was 82% (325 of 395 women). Serum concentrations of PCB congeners IUPAC no. 28, 52, 101, 105 and 167, and o, p'-DDT and -DDE, p, p'-DDT and -DDD, oxychlordane, and γ- and α-HCH were in many cases below the limit of quantification (LOQ). No statistical analysis of associations with personal characteristics could be performed for these substances. Concentrations of PCB congeners IUPAC no. 118, 138, 153, 156 and 180, HCB, β-HCH, trans-nonachlor and p, p'-DDE increased with increased age and were highest in women sampled early during the 4 year study period. This shows that older women and women sampled early in the study had experienced the highest life-time exposure levels, probably mainly during childhood and adolescence. The importance of early exposures was supported by lower PCB concentrations and higher β-HCH and p, p'-DDE concentrations among women born in non-Nordic countries. Moreover, serum concentrations of certain PCBs and pesticide/metabolites were positively associated with consumption of fatty fish during adolescence, and concentrations of CB 156, CB 180 and p, p'-DDE increased significantly with number of months women had been breast-fed during infancy. Short-term changes in bodily constitution may, however, also influence serum concentrations, as suggested by negative associations between concentrations of organochlorine compounds and BMI before pregnancy and weight change during pregnancy.ConclusionAlthough some of the associations could be caused by unknown personal characteristics confounding the results, our findings suggest that exposures to organochlorine compounds during childhood and adolescence influence the body burdens of the compounds during pregnancy.

Serum Concentrations of Organochlorine Compounds and Mammographic Density in a Highly Exposed Population in Triana, Alabama

Serum Concentrations of Organochlorine Compounds and Mammographic Density in a Highly Exposed Population in Triana, Alabama

Serum concentrations of organochlorine compounds and K-ras mutations in exocrine pancreatic cancer

Organochlorine compounds such as 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane (p,p'-DDT), 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE), and some polychlorinated biphenyls (PCBs) are carcinogenic to animals and possibly also to human beings. Occupational exposure to DDT may increase the risk of pancreas cancer. The high frequency of K-ras mutations in pancreatic cancer remains unexplained. We analysed the relation between serum concentrations of selected organochlorine compounds and mutations in codon 12 of the K-ras gene in patients with exocrine pancreatic cancer. Cases were prospectively identified in five hospitals. Mutations in K-ras were analysed by PCR and artificial restriction fragment length polymorphism. Cases of pancreatic cancer with wild-type K-ras (n=17) were frequency matched for age and sex to cases of pancreatic cancer with a K-ras mutation (n=34, case-case study). These 51 cases were further compared with 26 hospital controls (case-control comparison). Serum organochlorine concentrations were measured by high-resolution gas chromatography with electron-capture detection and negative ion chemical ionisation mass spectrometry. Serum concentrations of p,p'-DDT were significantly higher in pancreatic cancer cases with a K-ras mutation than in cases without a mutation (odds ratio for upper tertile 8.7 [95% CI 1.6-48.5], p for trend=0.005). For p,p'-DDE the corresponding figures were 5.3 (1.1-25.2, p for trend=0.031). These estimates held after adjusting for total lipids, other covariates, and total PCBs. A specific association was observed between a glycine to valine substitution at codon 12 and both p,p'-DDT and p,p'-DDE concentrations (odds ratio 15.9, p=0.044 and odds ratio 24.1, p=0.028; respectively). A similar pattern was shown for the major di-ortho-chlorinated PCBs (congeners 138, 153, and 180), even after adjustment for p,p'-DDE, but without a specific association with spectrum. Concentrations of p,p'-DDT and p,p'-DDE were similar among wild-type cases and controls, but significantly higher for K-ras mutated cases than for controls (p<0.01). Organochlorine compounds such as p,p'-DDT, p,p'-DDE, and some PCBs could play a part in the pathogenesis of exocrine pancreatic cancer through modulation of K-ras activation. The results require replication, but they suggest new roles for organochlorines in the development of several cancers in human beings.

Polycyclic Aromatic Hydrocarbons in Carcinogenesis

Polycyclic Aromatic Hydrocarbons in Carcinogenesis

Serum concentrations of organochlorine compounds during pregnancy and the newborn

The widespread use of organochlorine compounds as insecticides during the past few decades has led to their ubiqitous presence in the environment. The polychlorinated biphenyls (PCBs) were produced for use as coolant and insulator fluids for transformers and capacitors, as heat transfer fluids and as fire retardants for wood products; heavy industrial usage has led to widespread contamination of the environment with the PCBs. Organochlorine insecticides (OCIs) and PCBs are highly lipid soluble and are resistant to environmental degradation. In human beings these compounds are stored in adipose tissue and are resistant to metabolism. These substances are present in women and the fetus is exposed during utero development by transplacental transfer. Relatively high serum levels of OCIs and PCBs have been found in women with premature delivery. Also, DDT and PCB residue levels were higher in California sea lions which gave birth prematurely than in those with full-term pups. OCIs may disturb the hormonal balance of pregnancy and perhaps precipitate labor. Some DDT analogs are reported to have estrogenic effects and PCBs were also estrogenically active. Limited data exist on the levels and kinetics of OCIs and PCBs during pregnancy and in newborns.