2,3,7,8-Tetrachlorodibenzofuran

2,3,7,8-Tetrachlorodibenzofuran

Names
IUPAC name IUPAC 4,5,11,12-tetrachloro-8-oxatricyclo[7.4.0.0²,⁷]trideca-1(13),2,4,6,9,11-hexaene
Other names 2,3,7,8-tetrachlorodibenzofuran 2,3,7,8-Tetrachloro-dibenzofuran 2,3,7,8-Tetrachlorodibenzo[b,d]furan 2,3,7,8-Tetrapolychlorinated dibenzofuran
Identifiers
CAS Number	207-31-9
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL136710
ChemSpider	36507
ECHA InfoCard	100.223.045
KEGG	C18104
PubChem CID	39929
CompTox Dashboard (EPA)	DTXSID3052147
InChI InChI=1S/C12H4Cl4O/c13-7-1-5-6-2-8(14)10(16)4-12(6)17-11(5)3-9(7)15/h1-4H Key: KSMVNVHUTQZITP-UHFFFAOYSA-N
SMILES ClC1=C(Cl)C=C2C(OC3=CC(Cl)=C(Cl)C=C23)=C1
Properties
Chemical formula	C12H4Cl4O
Molar mass	305.96 g·mol−1
Appearance	Colorless Crystals
Melting point	227 °C (441 °F; 500 K)
Solubility in water	6.92e-07 mg/mL at 26 °C
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

2,3,7,8-tetrachlorodibenzofuran (TDCF) is a polychlorinated dibenzofuran with a chemical formula of C₁₂H₄Cl₄O. 2,3,7,8-tetrachlorodibenzofuran is part of the chlorinated benzofuran (CDF) family that contain 1-8 chlorines attached to the parent dibenzofuran chain. The CDF family includes 135 compounds of which only a few have been studied.

TCDF was discovered in the mid- 20th century along with other CDFs. It was found to be an unwanted by-product in the manufacturing of chlorinated compounds; it is not commercially used or produced itself. TDCF is directly released into the environment via emissions of waste incineration, fires with PCB transformers, vehicle exhausts using leaded fuel, and bleaching of industrial products.

TDCF and other CDFs are known to have a lasting impact on the environment. TDCF can exist as both a gas and particles in the atmosphere, which result in deposition in the soil. It has an estimated half-life of around 60 days in the soil and atmosphere. This molecule can easily accumulate in the food chain leading to potential human exposure. TDCF is listed as a hazardous air pollutant in the Clean Air Act of the 1990s. Monitoring programmes are established to keep track of the levels on TDCF in various environmental compartments to avoid damaging ecosystems.

Synthesis

TDCF is not purposefully manufactured. It is formed as a by-product of industrial manufacturing processes involving organic compounds with chlorine atoms present. In certain favorable reaction conditions like alkaline medium with a temperature over 150°C, UV light and radical forming substances. In the production of chlorinated pesticides CDFs are formed as byproducts by intermolecular condensation of ortho-chlorophenols. Intramolecular cyclization reactions of predibenzofurans also result in CDFs. In thermal waste treatment processes CDFs are produced by combustion and pyrolysis (non)organochlorine compounds in the presence of chlorides. The recycling of metal cables also leads to the formation of CDFs as chlorine is formed by burning the insulator polyvinylchloride which causes new CDFs. From PCBs, the production of CDFs happen by loss of two ortho clorines, loss of ortho as well as chlorine, loss of an ortho hydrogen and chlorine with an additional shift of chlorine from the 2 to 3 position, and loss of two ortho hydrogens.

Available forms

TCDF is not made industrially and there are no commercial uses for it. TCDF can be found in the environment as an unwanted by-product therefore it can be found in the soil, water, sediments but also airborne. It is released into the air as vapour after burning of hazardous waste, gas exhausts using leaded gasoline, fires involving PCB mixtures and a byproduct of bleaching pulp. Some of this vapour remains in the air as particles but some of it gets deposited into the soil as well as water. Most of the exposure and available forms is through the air and the consumption of high fat meats that were exposed to the 2,3,7,8-Tetrachloro-dibenzofuran (National Center for Biotechnology Information, 2024).

Toxicity

TCDF is one of the most toxic congeners (naturally occurring compounds other than ethanol after the process of distilling and fermentation) of the polychlorinated dibenzofurans (Weber, et al 1984) Its toxicity is associated with fatty liver disease (Yuan, et al., 2020). Mainly the toxicity of TCDF has been recorded through testing of breast milk, adipose tissue and blood serum. It is at this moment not yet classifiable as to its carcinogenicity to humans, classified therefore as type 3 of the IARC (International Agency for Research on Cancer classification). Toxicity levels and baselines are not yet known in humans but are being tested on animals, more on this at Effects on Animals (The Metabolomics Innovation Centre, 2014).

Effects on animals

The recorded effects on animals are most commonly investigated in the house mouse as well as male guinea pigs. Exposure to TCDF has led to problems in multiple organs within mice such as its liver, jejunum, cecum, small intestine and the general intestines. In general, the liver is the main target of TCDF, which leads to induced hepatic lipogenesis (Yuan, et al 2020). When testing on female mice, the effects on embryos were recorded, showing that TCDF has the strongest effect on fetal kidneys and leads to 100% of fetuses to be teratogenic at toxicity levels which are not fatal for the mother (Weber, et al 1984). The exposure to TCDF leads to a decrease in glucose homeostasis leading to an abundance of glucose in the mouse body. It also promotes the increment in bile acid metabolic processes which leads to an increase in multiple acids such as Deoxycholic acid, Glycocholic Acid, Taurochenocdeoxycholic Acid, Tauromuricholic acid, Lithocholic acid, Chenodeoxycholic acid, Taurolithocholic acid and an abundance of bile acids and salts. As mentioned previously, it affects the liver as it results in a positive regulation of lipid biosynthetic processes leading to an abundance of unsaturated fatty acids. The baseline toxicity levels for TCDF are known for the mouse, the guinea pig and monkey, being at LD50 Guinea pig (Hartley, male, 3-4 wk old) oral 5-10 ug/kg, LD50 Mouse (C57B1/6, male, 6 wk old) oral >6,000 ug/kg and LD50 Monkey (Macaca mulatta, female, 2.0-3.7 kg) oral 1,000 ug/k (WHO, 1989).

References

Ioannou, Y. M., Birnbaum, L. S., & Matthews, H. B. (1983). Toxicity and distribution of 2,3,7,8-tetrachlorodibenzofuran in male guinea pigs. Journal of toxicology and environmental health, 12(4-6), 541–553. https://doi.org/10.1080/15287398309530448 Matsumura, F. (1995). Mechanism of action of dioxin-type chemicals, pesticides, and other xenobiotics affecting nutritional indexes. The American Journal of Clinical Nutrition, 61(3). https://doi.org/10.1093/ajcn/61.3.695s National Center for Biotechnology Information. (2024, March 12). 2,3,7,8-tetrachlorodibenzofuran. National Center for Biotechnology Information. PubChem Compound Database. https://pubchem.ncbi.nlm.nih.gov/compound/2_3_7_8-Tetrachlorodibenzofuran#section=Probable-Routes-of-Human-Exposure National Center for Biotechnology Information (2024). PubChem Annotation Record for , 2,3,7,8-TETRACHLORODIBENZOFURAN, Source: Hazardous Substances Data Bank (HSDB). Retrieved March 10, 2024 from https://pubchem.ncbi.nlm.nih.gov.

National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 39929, 2,3,7,8-Tetrachlorodibenzofuran. Retrieved March 10, 2024 from https://pubchem.ncbi.nlm.nih.gov/compound/2_3_7_8-Tetrachlorodibenzofuran.

Pope, C. N., & Liu, J. (202AD). Chapter 10 - Microbiome in toxicity and its modulation. In An Introduction to interdisciplinary toxicology: From molecules to man (pp. 127–138). essay, Academic Press. Tai, H. L., Mcreynolds, J. H., Goldstein, J. A., Eugster, H. P., Sengstag, C., Alworth, W. L., & Olson, J. R. (1993). Cytochrome-p4501a1 mediates the metabolism of 2,3,7,8-tetrachlorodibenzofuran in the rat and human. Toxicology and Applied Pharmacology, 123(1), 34–42. https://doi.org/10.1006/taap.1993.1218 The Metabolomics Innovation Centre (TMIC). (n.d.). 2,3,7,8-tetrachlorodibenzofuran (T3D0207). T3DB. http://www.t3db.ca/toxins/T3D0207#identification The Metabolomics Innovation Centre (TMIC). (2014, December 24). 2,3,7,8-tetrachlorodibenzofuran (T3D0207). T3DB. http://www.t3db.ca/toxins/T3D0207

Weber, H., Lamb, J. C., Harris, M. W., & Moore, J. A. (1984). Teratogenicity of 2.3.7.8-tetrachlorodibenzofuran (tcdf) in mice. Toxicology Letters, 20(2), 183–8.)

WHO; Environ Health Criteria 88: Polychlorinated Dibenzo-para-dioxins and Dibenzofurans p.276 (1989)

Yuan, P., Dong, M., Lei, H., Xu, G., Chen, G., Song, Y., Ma, J., Cheng, L., & Zhang, L. (2020). Targeted metabolomics reveals that 2,3,7,8-tetrachlorodibenzofuran exposure induces hepatic steatosis in male mice. Environmental Pollution (Barking, Essex : 1987), 259, 113820–113820. https://doi.org/10.1016/j.envpol.2019.113820