Project Details
Projekt
Human biomonitoring and toxicological evaluation of hazardous substances in silicone production
Subject Area
Toxicology, Laboratory Medicine
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 502906636
Di-(2,4-dichlorobenzoyl)-peroxide (DCIBP) is a reactive chemical substance used as an initiator and reducing agent in the plastics and rubber industry. DCIP decomposes into 2,4-dichlorobenzoic acid (main product) as well as 1,3-dichlorobenzene during the hot crosslinking of silicone rubbers. Via a radical recombination of two 1,3-dichlorophenyl radicals, the low-chlorinated polychlorinated biphenyls (PCBs) PCB-47, PCB-51 and PCB-68 are formed. The examination of a small collective of workers from the silicone production in the laboratories of the applicants showed partly alarmingly high values (max. value: 2.56 µg/L plasma) of mainly PCB47 in the blood. This illustrates the urgency of further investigations in order to be able to classify and evaluate the measured values toxicologically. The aim of this project is to detect not only the ingested PCB47 and its OH metabolites, but also the 2,4-dichlorophenylmercapturic acid of 1,3-DCB and the corresponding metabolites 3,5-dichlorophenol and 3,5-dichlorocatechol produced by oxidation in exposed workers and to characterise them with regard to their toxic potency. A decisive advantage for the planned human biomonitoring of 1,3-DCB in silicone production is the short half-life of the corresponding metabolites in urine. With the repeated detection of these metabolites in the post-shift urine of exposed workers, the effectiveness of exposure-reducing measures at the workplace can be checked much better than by analysing persistent PCBs in plasma. Thus, this new analytical method to be developed makes a decisive contribution to prevention in the handling of DCBP. In addition, the cytochrome P450 enzymes which contribute to the formation of reactive OH metabolites from 1,3-dichlorobenzene and PCB-47 are to be determined. Transgenic cell lines expressing appropriately identified CYPs will be used to study the ability of PCB47 and 1,3-DCB to cause DNA damage. Thus, this proposal makes an important contribution to research into the metabolism of PCB-47 and 1,3-DCB in humans. The results will also allow conclusions to be drawn about the carcinogenic potential that 1,3-dichlorobenzene and PCB-47 represent for humans. Furthermore, by studying the phenols and OH-PCBs produced by oxidative pathways, parameters will be established that are closer to the ultimate health risk posed by 1,3-dichlorobenzene and PCBs than those previously studied. This is of great interest for the assessment and prevention of cancer risks in occupational and environmental medicine.
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