Furans human exposure

PCBs Dioxins and Furans Human Exposure and Health Effects... 

PCBS, DIOXINS AND FURANS HUMAN EXPOSURE AND HEALTH EFFECTS... 

PCBS, DIOXINS AND FURANS HUMAN EXPOSURE AND HEALTH EEEECTS TABLE 19.2 Toxic Equivalency Factors (TEFs) for Dioxins, Furans and DioxinTike PCBs. ... 

General considerations. Nitroaromatic compounds, such as nitro-furans and nitrobenzenes are commercially important chemicals used as drugs, food additives or synthetic intermediates. Since there is widespread human exposure to these chemicals, their metabolism has been studied extensively. Nitroaromatic compounds are reduced by both hepatic cytosol and microsomes. The microsomal activity... 

Although these reservoirs may be highly contaminated with PCDD/PCDFs, the chemical and physical properties of these compounds imply that dioxins and furans will stay adsorbed to organic carbon in soils or other particles. On the other hand, mobilization can occur in the presence of lipophilic solvents (leaching into deeper layers of soils and/or groundwater) or in cases of erosion or run-off from topsoil (translocation into the neighbourhood). Experience has shown that transport of PCDD/PCDFs due to soil erosion and run-off does not play a major role in environmental contamination and human exposure (Fiedler 1995, 1999). 

Wild SR, Harrad SJ, Jones KC. 1993. The influence of sewage sludge applications to agricultural land on human exposure to polychlorinated dibenzo-p-dioxins (PCDDs) and -furans (PCDFs). Environ Pollution 357-369. 

For risk assessment purposes, an important objective in evaluating the environmental fate of PCDD/Fs is predicting the major pathways of human exposure. It is well established that the food chain, especially meat and dairy products, accounts for more than 90% of human exposure to PCDD/Fs and perhaps as much as 99% of human exposure to 2,3,7,8-TCDD.34 In industrialized countries, the average daily intake via food (the major route of exposure to dioxins and furans) ranges from 1.5 to 2.5 pg TEQ kg-1 body weight. 

The dioxin toxic equivalency factor (TEF) approach is currently used worldwide for assessing and managing the risks posed by exposure to mixtures of certain dioxin-like compounds (DLCs). World Health Organization-TEF (WHO-TEE) values have been established for humans and mammals, birds, and (For new, refined values, see Ref. 12g.) It should be mentioned that 16 PCBs, the coplanar isomers with nonortho, monoortho, and diortho substitution by chlorine (overall, there are 209 isomers for this class of compounds) show dioxin-like toxic behavior. I-TE values are smaller, in the range of 0.0001-0.1. The most toxic isomers is 3,3, 4,4, 5-pentachlorodiphenyl with I-TE of 0.1. Polybrominated dibenzodioxins and furans with the 2,3,7,8 pattern also show dioxin-like toxicity, but their I-TE values are lower compared to PCDD/F. 

No studies were located regarding metabolism of 2,3-benzofuran in humans or animals. However, the metabolism of several other substituted furans has been shown to involve oxidation by P-450, with the unsubstituted double bond of the furan ring converted either to an epoxide (Boyd 1981) or to a dialdehyde (Ravindranath et al. 1984). Pretreatment with inducers and inhibitors of P-450 modified the toxicity of a single intraperitoneal injection of 2,3-benzofuran to male mice (McMurtry and Mitchell 1977). Oral exposure to 2,3-benzofuran altered the activity of P-450 and other enzymes in the livers of female mice (Heine et al. 1986). These experiments indicate that cytochrome P-450 may be involved in the toxicity of 2,3-benzofuran, but do not provide a clear picture of 2,3-benzofuran metabolism. 

Pluim HJ, deVijlder JJM, Olie K, et al. 1993c. Effects of pre and postnatal exposure to chlorinated dioxins and furans on human neonatal thyroid hormone concentrations. Environ Health Perspect 101 504-508. 

Chloracne has been reported in chronic occupational exposure to pentachlorophenol. However, commercial preparations are commonly contaminated with dioxins and furans, and chloracne may be linked to these compounds. In addition, hemolytic and aplastic anemia and weight loss have been reported in humans. Pentachlorophenol is classified as a probable human carcinogen (group 2B). 

Application of this 1/100 safety factor to the NOAEL (1 ng/kg/day or 1000 pg/kg/day) defined in the lifetime rat study (30) that is considered most definitive by essentially all of the regulatory agencies was the basis for the Ontario MOE expert panel to recommend a Maximum Daily Intake for 2,3,7,8-TCDD (or its toxic equivalent of other chlorinated dioxins and furans) of 10 pg/kg B.W./day for humans (38). This more recent approach used by these four non-U.S. groups demonstrate the manner in which carcinogenicits based lifetime exposure control limit recommendations for humans can be realistically derived from the data available from the animal cancer bioassays when interpreted in concert with the data available regarding the likely mechanism of action by which the carcinogenic response occurred in the animal bioassays. 

The heterocyclic compounds of oxygen that are largely used as solvents, tetrahydro-furan and 1,4-dioxane, are an irritant to the eyes and respiratory tract, a depressant to the central nervous system, and exhibit a low order of toxicity. Exposure to high concentrations, however, may cause injury to the kidney and liver in humans. 

Dioxins are a family of the most toxic chlorinated organic compounds known to science, numbering around 75 dioxins and 135 related furans. These can cause cancer and are ECD for humans, even at very low exposure levels, since minute amounts, can bio-accumulate due to their ease of solubility in body fat (dioxins are hydrophobic, water-hating and lipophilic, fat-loving ). Number and position of chlorine atoms in the molecule has a considerable effect on toxicity, and 17 dioxins are classed as highly toxic. These include polychlorinated dioxins (PCDD) and dibenzofurans (PCDF) which are by-products of the chlorine bleaching of paper, the burning of chlorinated hydrocarbons (such as pentachlorophenol, PCB, and PVC) and the incineration of municipal/medical... 

Based on toxicological studies in rodents, the lARC classified furan as a potential human carcinogen of Group 2B. The existing experimental data show the relationship between Hver cancer and the exposure dose. As is apparent from the EFSA documents, it is necessary to collect additional data for the critical risk assessment of dietary furan and to clarify the toxicity of intermediates produced by furan bio transformation. 

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