2,3,7,8-Tetrachlorodibenzo-p-dioxin

CAS RN: 1746-01-6

Health Effects

0.2.1 SUMMARY OF EXPOSURE
  • 0.2.1.1 ACUTE EXPOSURE
    • A) USES: Dioxins have no intended commercial use; exposure is through their presence as a byproduct or contaminant of certain herbicides. However, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxan (TCDD) is produced in small quantities for use as a research chemical. Dioxins are released into the environment through incineration and combustion, chemical manufacturing processes, processes involving chlorine bleaching or municipal sludge, and recirculation of environmental reservoirs. At present, a significant route of exposure is through the atmospheric fallout of particles and gases contaminated with TCDD.
    • B) TOXICOLOGY: Dioxins bind to the aryl hydrocarbon receptor protein in cytoplasm, forming a heterodimer with nuclear proteins and inducing transcription of multiple genes. They are mutagenic and act as human carcinogens.
    • C) EPIDEMIOLOGY: Low-level environmental exposure to dioxins is common. Dioxins have been responsible for several environmental disasters, but exposures rarely produce significant acute toxicity. Deliberate poisoning with dioxins is rare but may cause caustic injury and systemic symptoms.
    • D) WITH POISONING/EXPOSURE
      • 1) MILD TO MODERATE TOXICITY: Acute early signs and symptoms include chemical burns of the skin, irritation of the mucous membranes and eyes, abdominal pain, nausea, vomiting, headache, dizziness, blurred vision, irritability, dyspnea, and severe muscle pains. TCDD affects various hormone systems, particularly sex steroids, corticosteroids, and thyroid hormones. It disrupts normal feedback mechanisms of the pituitary gland. Cardiovascular disorders such as atherosclerosis and myocardial infarction have been suggested but not conclusively shown to be related to TCDD exposure.
      • 2) SEVERE TOXICITY: After a latent period of several weeks, chloracne, an acne-like eruption of the skin, porphyria, cutaneous tarda, hirsutism, and hyperpigmentation may occur. Symptoms (itching, swelling, redness) may occur weeks or months before the eruptions appear and may last a few months or up to 15 years. Polyneuropathies and hepatotoxicity are frequently noted. Increased blood lipids are common and may persist. Pancreatitis, diabetes mellitus, and reduction in cognitive performance have also been noted. There are no known cases of human fatalities from acute exposure to dioxins.
      • 3) CARCINOGENIC EFFECT: TCDD is considered a human carcinogen by IARC.
      • 4) REPRODUCTIVE EFFECT: Dioxins may be human teratogens, specifically for ectodermal dysplasia, CNS, cardiac, and skeletal defects.
  • 0.2.1.2 CHRONIC EXPOSURE
    • A) Little is known about potential human health effects (if any) of long-term exposure to low concentrations. The US EPA considers dioxin (TCDD) to be probably carcinogenic to humans (Group B2). IARC classifies TCDD as Group 1 (carcinogenic to humans), but places other dioxins in Group 3 (not classifiable as to their carcinogenicity to humans).
0.2.20 REPRODUCTIVE HAZARDS
  • A) Dioxins have not been proven to produce adverse reproductive effects in humans. However, low birth weights, ectodermal dysplasia, and growth and neurological deficits have been associated with dioxin exposure. Data on spontaneous abortions, decreased sperm quality and feminizing alterations of sex hormones have been mixed. TCDD accumulates in breast milk, and neurological deficits and increases in T4 and TSH have been associated with lactational exposure. TCDD is considered an animal teratogen.
  • B) The US EPA has been re-evaluating the health effects of dioxins. In its current report version ("Draft Final" of May 2000), it is concluded that TCDD is a likely developmental and reproductive toxin.
0.2.21 CARCINOGENICITY
  • 0.2.21.1 IARC CATEGORY
    • A) IARC Carcinogenicity Ratings for CAS1746-01-6 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
      • 1) IARC Classification
        • a) Listed as: 2,3,7,8-Tetrachlorodibenzo-para-dioxin
        • b) Carcinogen Rating: 1
      • 1) The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.
  • 0.2.21.2 HUMAN OVERVIEW
    • A) Dioxins are probable human carcinogens; TCDD is a known human carcinogen. Results are conflicting regarding increased overall cancer morbidity and mortality, and for an association with soft tissue sarcomas, non-Hodgkin and Hodgkin lymphoma. There is limited evidence of an association with myeloma and pulmonary, prostate, gastric, and breast carcinoma. The upper limit for overall risk in the general population may be as high as 1:1000.
  • 0.2.21.3 ANIMAL OVERVIEW
    • A) TCDD is the most potent known animal carcinogen and tumor promoter.
0.2.22 GENOTOXICITY
  • A) TCDD is not directly genotoxic and usually produces negative results in most genotoxicity assays. However, the TCDD-aryl hydrocarbon receptor complex can bind to specific DNA enhancer sequences. This induces a pleiotropic sequence of genetic expression whose products may activate pro-mutagens.
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