Absorption, Distribution and Excretion
Between 1980 and 1982, liver samples were collected from 19 cormorants (Phalacrocorax carbo), 3 grey herons (Ardea cinerea), and 1 great crested grebe (Podiceps crisatus) in the Netherlands. The livers of these fish-eating birds were analyzed for polychlorinated dibenzo-p-dioxins (PCBs) and dibenzofurans. The results showed that only homologues with a 2,3,7,8-chloro-substituted pattern were present in the livers. The main component was 2,3,4,7,8-pentachlorodibenzofuran, and also 1,2,3,6,7,8-hexachlorodibenzo-p-dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxins, and 1,2,3,7,8-pentachlorodibenzo-p-dioxins. A mixed sample of six eel (Anquilla anquilla) samples also showed the same homologue chemical composition pattern as these birds. In eels, the levels of 2,3,4,7,8-pentachlorobenzofuran and 1,2,3,6,7,8-hexachlorodibenzodioxins are typically in the range of 1–5 ng/kg. Given that eels are a primary food source for cormorants, this suggests a strong bioaccumulation of these two homologues in cormorant livers. Polychlorinated dibenzodioxins and polychlorinated dibenzofurans are primarily stored in fat but are also excreted in milk and through the placenta. They are also present in lower concentrations in blood and vital organs. /Polychlorinated dibenzodioxins/ Polychlorinated dibenzodioxins and dibenzofurans in human adipose tissue samples obtained from autopsies in five cities in the Great Lakes Basin of Canada were analyzed using gas chromatography-high resolution mass spectrometry (GC-HR-MS). The mean homologue levels in male and female donors from each city were comparable to previously reported data. No significant differences in homologue levels were found between males and females or between different cities. Several homologues, as well as the total homologues expressed as toxic equivalents of 2,3,7,8-tetrachlorodibenzo-p-dioxin, showed a positive correlation with age. Tissue distribution analysis of 2,3,7,8-chloro-substituted dibenzo-p-dioxins was performed on 11 patients who died of cancer. Octachlorodibenzo-p-dioxin had the highest concentrations in all organs and tissues, followed by heptachlorodibenzo-p-dioxin, which had a relatively high concentration. The spleen showed the highest concentrations of 1,2,3,7,8-pentachlorodibenzo-p-dioxin and 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin. 2,3,7,8-tetrachlorodibenzo-p-dioxin was also detected, with the highest concentrations (0.8–3.2 pg/g) in the gonads. The highest equivalent value for toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxins was obtained from a 54-year-old woman who died of cancerous goiter. Among 11 patients, this patient had the highest concentrations of 2,3,7,8-substituted pentachlorodibenzo-p-dioxins and hexachlorodibenzo-p-dioxins. For more complete data on the absorption, distribution, and excretion of 1,2,3,6,7,8-hexachlorodibenzo-p-dioxins (a total of 8), please visit the HSDB record page.

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Metabolism / Metabolites
In rats, primary hydroxylation of dibenzodioxins occurs only at positions 2, 3, 7, or 8. This study investigated the metabolism of seven polychlorinated dibenzofuran isomers in female Sprague Dawley rats. Bile samples were collected from surgically implanted bile duct cannulas 2 hours after administration of the corresponding polychlorinated dibenzofuran isomer, continuing for 3 to 7 days. Administration was via intravenous injection or gavage. Metabolites were isolated from the bile, and their hydroxylation products were analyzed by gas chromatography-mass spectrometry (GC/MS). The tetrachlorodibenzofuran isomer underwent rapid biotransformation. No ring-opening products were observed; both isomers were metabolized to hydroxylated tetrachlorodibenzofuran, trichlorodibenzofuran, and dihydroxytrichlorodibenzofuran. The metabolites of pentachlorodibenzofuran isomers exhibit quantitative differences in distribution. 1,2,3,4,8-Pentachlorodibenzofuran is primarily metabolized to hydroxypentachlorodibenzofuran, 1,2,3,7,8-pentachlorodibenzofuran to dihydroxypentachlorodibenzofuran, while 2,3,4,7,8-pentachlorodibenzofuran produces diverse metabolites, mainly resulting from ether bond cleavage. Neither 1,2,3,6,7,8-hexachlorodibenzofuran nor 1,2,3,4,6,7,8-heptachlorodibenzofuran produced identifiable concentrations of metabolites. Therefore, it can be concluded that the metabolism of polychlorinated dibenzofurans (PCBs) in rat liver primarily occurs through oxidation, hydrolysis, or reductive dechlorination; ether bond cleavage is a relatively minor metabolic mechanism; chlorine substitution patterns affect metabolism; and the metabolism of PCBs decreases when the number of chlorine atoms on each ring exceeds two. PCBs can be absorbed via oral, inhalation, and dermal routes. CDDs are carried in the blood plasma by lipids and lipoproteins, and are mainly distributed in the liver and adipose tissue. CDDs are metabolized slowly in the microsomal monooxygenase system, producing polar metabolites that can bind to glucuronic acid and glutathione. They can increase their metabolic rate by inducing phase I and phase II enzymes. The main excretion routes of CDDs are bile and feces, with small amounts also excreted in urine and breast milk. (L177)

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Biological Half-Life
The half-life of 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin was calculated to be approximately 3.5 years. This estimate is based on the analysis of an adipose tissue biopsy sample from a 14-year-old girl who was exposed to industrial-grade pentachlorophenol for approximately 2–3 years. The two biopsy samples were collected 28 months apart. In a study of 48 workers at a pesticide factory in Germany, researchers estimated the elimination half-life of several chlorodibenzo-p-dioxin homologues. The half-life of 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin was estimated to be 13.1 years.

Toxicity Summary
CDDs exert toxic effects by binding to aryl hydrocarbon receptors, thereby altering the transcription of certain genes. Their affinity for aryl hydrocarbon receptors depends on the specific CDD's structure. Alterations in gene expression may result from direct interactions between the aryl hydrocarbon receptor and its heterodimer-forming chaperone—the aryl hydrocarbon receptor nuclear translocase—and gene regulatory elements, or from the initiation of a phosphorylation/dephosphorylation cascade that activates other transcription factors. Affected genes include various oncogenes, growth factors, receptors, hormones, and drug-metabolizing enzymes. These alterations in gene transcription/translation are considered the cause of most CDD toxicities. (L177)

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Non-Human Toxicity Values
Male rats: Oral LD50: 1.8 mg/kg body weight / 31% 1,2,3,6,7,8- and 67% 1,2,3,7,8,9-hexachlorodibenzo-dioxin mixture / Female rats: Oral LD50: 0.8 mg/kg body weight / 31% 1,2,3,6,7,8- and 67% 1,2,3,7,8,9-hexachlorodibenzo-dioxin mixture / Male mice: Oral LD50: 0.75 mg/kg body weight / 31% 1,2,3,6,7,8- and 67% 1,2,3,7,8,9-hexachlorodibenzo-dioxin mixture / Female mice: Oral LD50: 0.5 mg/kg body weight / 31% 1,2,3,6,7,8- A mixture of 1,2,3,7,8,9-hexachlorodibenzo-dioxin and 67% 1,2,3,7,8,9-hexachlorodibenzo-dioxin/
Guinea pig oral LD50 70 μg/kg

[1]. PCDD/Fs levels in indoor environments and blood of workers of three municipal waste incinerators in Taiwan. Chemosphere. 2004 Apr;55(4):611-20.

[2]. Feed as a source of dioxins and PCBs. Chemosphere. 2022 Dec;308(Pt 1):136243.

[3]. A rapid and reagent-free bioassay for the detection of dioxin-like compounds and other aryl hydrocarbon receptor (AhR) agonists using autobioluminescent yeast. Anal Bioanal Chem. 2018 Feb;410(4):1247-1256.

[4]. Suppression of humoral antibody production by exposure to 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin. J Pharmacol Exp Ther. 1984 Dec;231(3):518-26.

1,2,3,6,7,8-Hexachlorodibenzo-P-dioxin is a fluffy white solid. (NTP, 1992) 1,2,3,6,7,8-Hexachlorodibenzo-P-dioxin is a polychlorinated dibenzo-p-dioxin. 1,2,3,6,7,8-Hexachlorodibenzo-P-dioxin is an isomer of chlorodibenzo-p-dioxin (CDD). CDDs are a class of synthetic chemicals composed of a dioxin skeleton and chlorinated substituents. They are also persistent organic pollutants (POPs), and their production is regulated in most regions. Sources of dioxins include organochlorination production, paper bleaching, chlorination treatment in wastewater and drinking water plants, municipal solid waste and industrial incinerators, and natural sources such as volcanoes and forest fires. (L177, L178) Pentachlorophenol pollutants

C12H2CL6O2

390.86

389.816

57653-85-7

1,2,3,6,7,8-Hexachloro dibenzo-p-dioxin-13C12;109719-81-5

42540

Typically exists as solids at room temperature

1.777 g/cm3

478ºC at 760 mmHg

545 to 547 °F (NTP, 1992) ; 285-286 °C ; 285 °C

182.9ºC

7.505

0

2

0

20

338

0

C1=C2C(=C(C(=C1Cl)Cl)Cl)OC3=CC(=C(C(=C3O2)Cl)Cl)Cl

YCLUIPQDHHPDJJ-UHFFFAOYSA-N

InChI=1S/C12H2Cl6O2/c13-3-1-5-11(9(17)7(3)15)20-6-2-4(14)8(16)10(18)12(6)19-5/h1-2H

1,2,3,6,7,8-hexachlorodibenzo-p-dioxin

1,2,3,6,7,8-HxCDD

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)