M.M. Leijs

Effects of Dioxins, PCBs, and PBDEs on Immunology and Hematology in Adolescents

Dioxins and PCBs are environmental pollutants, proven to be immunotoxic. In the period 1987-1991 a cohort of mother-baby pairs was initiated to detect abnormalities in relation to dioxin levels in the mothers milk. At birth and at follow-up at 8-12 years, immunological and hematological effects were seen, prompting us to perform a new follow-up during adolescence. In addition, we assessed the immunological and hematological parameters in relation to current levels of PBDEs and PCBs. In the Netherlands, the pre- and postnatal exposure to dioxins have been studied prospectively since 1987. Venapuncture was performed to assess hematological (Hemoglobin, thrombocytes, thrombopoietin) and immunological (leukocytes, leukocyte differentiation) parameters and the current serum levels of dioxin, dioxinlike (dl)-PCBs and PBDEs. A decrease in the number of polymorphic neutrophils was found in adolescents with higher dl-PCBs in their serum (p = 0.021). No relation with total leukocytes, thrombocytes, hemoglobin, or thrombopoietin levels was seen. Similarly, we found no relation between prenatal, nor current dioxin levels and the hematological and the immunological parameters determined. The SigmaPBDEs were negatively associated with the number of lymphocytes (p = 0.01) and positively associated with the hemoglobin concentration (p = 0.003). These effects on the innate immunity by current levels of dl-PCBs and on the adaptive immunity by PBDEs are disconcerting, especially as the dl-PCB (0.04-7.8 WHOTEQ pg/g lipid, mean: 2.2 WHOTEQ pg/g lipid) and SigmaPBDE levels (mean 14.0 ng/g lipid, including one outlier with a sum of 73.6 ng/g lipid) were not high.

The influence of perinatal and current dioxin and PCB exposure on puberty: a review

Abstract Over the last two decades much has been written about the consequences of perinatal dioxin and PCB exposure in humans. In this paper we strive to elucidate the data on puberty in relation to these endocrine disruptive compounds in human populations. Effects in PCB/dioxin-exposed human populations on puberty are seen, not only in highly exposed cohorts, but also in average populations with background exposures. Study showed effects like increased weight, a delay in pubic hair growth and male genital development in boys, sex-hormone homeostasis, reduced penile length, and delayed age at first ejaculation after PCB exposure. Effects seen after dioxin exposure include retarded initiation and stage of breast development in girls, earlier menarche, disruption of sex hormone homeostasis, reduced testicular volume and reduced penile length in boys. The data published by different studies were inconclusive as a result of different methodological setup as well as because of multiple exposure settings. Populations were exposed to different mixtures of dioxin/PCB congeners or mixtures with other endocrine disrupters, and therefore synergistic and antagonistic effects with PCBs and dioxins are possible. Dioxinlike compounds disturb the hormonal balance mainly through interaction with the Ah receptor, which may influence the synthesis of hormones or their transport proteins. However, we have to keep in mind that hormonal balance during puberty could also be altered by disruption of the thyroid homeostasis. Another important possible mechanism is the induction of epigenetic changes or effects on genetic polymorphism. The fact that exposure to background concentrations of dioxin-like compounds and PCBs also has effects on the reproductive development is disconcerting and warrants further research and long term follow-up studies.

POPs and Skin

Persistent organic pollutants (POPs) is the name of a group of ubiquitous man-made toxic environmental pollutants which have adverse effects on the environment and human health. The skin is a major target organ of toxic effects of POPs as well as signalling organ for the toxicity of these compounds. Chloracne is the most obvious signs of systemic contact with higher levels of POPs with chloracnegenic potential. First we will discuss chemical and toxicological properties of POPs and finally the pathophysiology of cutaneous diseases derived from POPs including acne, cancerogenesis, porphyria and others.

Hyperpigmentation and higher incidence of cutaneous malignancies in moderate-high PCB- and dioxin exposed individuals

&NA; Polychlorinated biphenyls (PCB) are well known persistent and toxic environmental pollutants. Our aim was to identify effects of moderate‐high exposure to dioxin‐like (dl) and non‐dioxin‐like (ndl)‐PCBs on the skin in order to provide more insight in the pathophysiological effects of these compounds. We performed a dermatological examination on 92 former workers from a transformer recycling company with known elevated serum PCB and/or dioxin (polychlorinated dibenzo‐p‐dioxin/polychlorinated dibenzo‐p‐furan (PCDD/F)) levels. In addition, we performed a skin cancer screening over a period of seven years (2010–2016) on resp. 268, 271, 210, 149, 92, 129 and 79 participants. We found a higher incidence of acne and malignancies of the skin (malignant melanoma, basal cell carcinoma and mycosis fungoides) in the workers compared to normal population. The probability of having hyperpigmentation on the skin was statistically significantly higher in workers with higher sumPCBs‐ (OR:1.09(1.12–2.17)), dioxin‐like (dl)‐PCBs‐ (OR:1.56(1.12–2.17)) and dioxin (PCDD/Fs) (OR:1.09(1.02–1.16)) levels. Age was a confounding factor in this model. Formation of hyperpigmentation could be an indicator for (moderate‐high) exposure to toxic compounds like PCBs. The higher incidence of cutaneous malignancies found in the workers might be associated with PCB‐ and dioxin exposure, warranting further investigation on larger cohorts. HighlightsElevated blood levels of PCBs and dioxins were found in workers of a transformer recycling company.Higher incidence of acne and malignancies of the skin in PCB‐ and dioxin exposed workers.A correlation between hyperpigmentation on the skin and exposure levels in the workers.

Expression of CYP1A1, CYP1B1 and IL-1β in PBMCs and skin samples of PCB exposed individuals

Polychlorinated biphenyls (PCBs) are well- known man-made persistent environmental pollutants and endocrine disruptors. As a result of mass production in the past, background levels of these compounds can be measured in human blood worldwide. In 2010 high internal levels of PCBs were discovered in workers of a transformer-recycling company in Germany. Our aim was to measure, whether the expression of CYP1A1, CYP1B1, and IL-1β is dysregulated in peripheral blood mononuclear cells (PBMCs) of the exposed individuals (n = max 308). Further, we measured the regulation of CYP1A1, CYP1B1, AHRR (aromatic hydrocarbon receptor repressor) and IL-1β in skin samples of 25 workers with elevated plasma PCB levels using quantitative PCR (q-RT-PCR). We found a significant correlation between the regulation of IL-1β in skin samples and lipid adjusted PCB levels. In the PBMCs, the expression levels of CYP1A1, CYP1B1 and IL-1β decreased over time with decreasing PCB plasma levels. The upregulation of the cytokine IL-1β in exposed individuals with higher PCB plasma levels warrants further investigation in order to examine its role in the pathophysiology of autoimmune disorders and tumor promotion.