DIOXIN CANCER RISK — EXAMPLE OF HORMESIS?

A recent case-control study implied an inverse correlation between the measured body burden of dioxins (polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans, PCDD/F) and the risk of soft tissue sarcoma in normal population exposed to dioxins mainly via food. The surprising result could not be explained by biases or confounding. There is no a priori confounding by occupational chemicals in a random sample from general population, but exposures to other lipid soluble chemicals with similar sources might be expected to associate with that of dioxins. One such group is polychlorinated biphenyls (PCB). Therefore three most relevant dioxin-like PCB compounds PCB 77, PCB 126, and PCB 169 were now analyzed from the same patients. Cases were 110 soft-tissue sarcoma patients undergoing surgery for their disease, and referents were 227 patients operated for appendicitis. Dioxin and PCB concentrations were analyzed from subcutaneous fat samples by high-resolution gas chromatography–mass spectrometry and TCDD equivalent concentrations (WHO-TEq) were calculated by using toxicity equivalency factors of WHO. The highest risk of sarcoma was found in the septile with the lowest body burden of sum WHO-TEq, and the differences of septiles 2 and 6 from septile 1 were statistically significant. If soft sarcoma risk is true at high occupational levels of dioxins, the provocative result suggests that a possibility of a J-shaped dose-response curve should be taken into consideration and studied further. This is also supported by the similar J-shaped dose responses in animal studies

Estimated PCDD/F TEQ and total TEQ concentrations in the serum of 7-10 year old Finnish children

Polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are persistent organic pollutants that have detrimental health effects. As people are exposed to them mainly through the diet, EU has set maximum food dioxin and PCBs levels. EFSA CONTAM Panel made new risk assessment in 2018 that lowered the tolerable weekly intake (TWI) from 14 pg-TEQ/kg bw/week to 2 pgTEQ/kg bw/week. Critical effect was decreased semen count at the age of 18-19 years if serum total TEQ at the age of 9 years exceeded the No Observed Adverse Effect Level (NOAEL) of 7 pg/g lipid. However, it is largely unknown to what extent NOAEL is exceed in European boys currently. We thus measured PCBs from small volume of serum in 184 Finnish children 7-10 years of age. To estimate the TEQ levels of children from measured PCB levels, we used our existing human milk PCDD/F and PCB concentrations to create a hierarchical Bayesian regression model that was used to estimate TEQs from measured PCBs. For quality control (QC), three pooled blood samples from 18 to 20 year old males were measured for PCDD/Fs and PCBs, and estimated for TEQs. In QC samples measured and estimated TEQs agreed within 84% -106%. In our estimate for 7-10 year old children, PCDD/F TEQ exceeded NOAEL only in 0.5% and total TEQ in 2.7% of subjects. Risk management following the decreased TWI proposed by the CONTAM Panel should be carefully considered if total TEQ in children is already largely below the NOAEL. (C) 2020 Elsevier Ltd. All rights reserved.Peer reviewe

Comparison of questionnaire data and analyzed dioxin concentrations as a measure of exposure in soft-tissue sarcoma studies

Soft-tissue sarcoma is one of the few specific tumors thought to be caused by polychlorinated dibenzo-pdioxins and dibenzofurans (PCDD/Fs) and specifically TCDD. Evidence is, however, based on questionnaire-based case-control studies, and on very few cancer cases in cohort studies at high occupational exposures to chlorophenols or chlorophenoxy acid herbicides with dioxin impurities. Recall bias has been suspected to influence the reporting of exposure, but this possibility has never been adequately put to test. In the present study 87 cancer patients and 308 controls answered a questionnaire asking their exposure to wood preservatives, fungicides and herbicides, and insecticides, and their PCDD/ F concentrations were also measured. After matching for age and area 67-69 sarcoma patients and 153156 controls were available for the study depending on the chemical group, 1-3 controls for each sarcoma patient. Sarcoma patients reported exposure to these chemicals significantly more often than controls did, odds ratios were 6.7 for wood preservatives (p = 0.02), 16 for fungicides and herbicides (p = 0.01), and 4.9 for insecticides (p = 0.06). There was no association, when the analysis was based on measured PCDD/ F concentrations (odds ratios close to 1). Although it is not possible to exclude the role of the main chemical as the cause with certainty, the results indicate that recall bias is very likely in previous studies. Thus the causality between contaminant PCDD/Fs and soft tissue sarcoma cannot be considered proven. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe