3,3'Dichlorobenzidine [factsheet]

3,3'-DICHLOROBENZIDINE

Please Note: The main sources of information for this fact sheet are EPA's Integrated Risk Information System (IRIS), which contains information on the carcinogenic effects of 3,3'-dichlorobenzidine including the unit cancer risk for oral exposure, and the Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile for 3,3'-Dichlorobenzidine. Other secondary sources include the Hazardous Substances Data Bank (HSDB), a database of summaries of peer-reviewed literature and the Registry of Toxic Effects of Chemical Substances (RTECS), a database of toxic effects that are not peer reviewed.

Environmental/Occupational Exposure

* 3,3'-Dichlorobenzidine has not been detected in ambient air, and has only been detected at very low levels (<10 ppb) in water. (1)

* The general public may be exposed to 3,3'-dichlorobenzidine from the use of pressurized spray containers of paints, lacquers, and enamels containing benzidine yellow, an azo dye derived from 3,3'-dichlorobenzidine. (1)

* Occupational exposure to 3,3'-dichlorobenzidine may occur for workers involved in the synthesis of azo dyes, and for workers in the garment, leather, printing, paper, and homecraft industries where benzidine-based dyes are used. (1)

Assessing Personal Exposure

* No data were located regarding the measurement of personal exposure to 3,3'-dichlorobenzidine.

Health Hazard Information

Acute Effects:

* No information is available on acute (short-term) exposure to 3,3'-dichlorobenzidine in humans.

* Tests involving acute exposure of animals, such as the LD₅₀ test in rats, have shown 3,3'-dichlorobenzidine to have low to moderate toxicity from oral exposure and moderate toxicity from dermal exposure. (2)

Chronic Effects (Noncancer):

* Chronic (long-term) exposure to 3,3'-dichlorobenzidine via dermal exposure results in dermatitis in humans. Gastrointestinal upset and upper respiratory tract infections have also been noted in humans, but the length and conditions of exposure were not reported. (1,3)

* Animal studies have reported mild liver injury from oral exposure to 3,3'-dichlorobenzidine. (1)

* EPA has not established an RfD for 3,3'-dichlorobenzidine. (4)

* EPA has determined that the data are inadequate to establish an RfC for 3,3'-dichlorobenzidine. (4)

Reproductive/Developmental Effects:

* No information is available on the reproductive or developmental effects of 3,3'-dichlorobenzidine in humans.

* Animal studies have reported abnormal growth in the kidneys of the fetuses of pregnant mice treated subcutaneously with 3,3'-dichlorobenzidine. No data were reported on maternal effects. (1)

Cancer Risk:

* Three epidemiologic studies have found no association between 3,3'-dichlorobenzidine exposure and bladder cancer. However, these studies are limited due to their small cohort size, limited statistical power, brief exposure periods, and incomplete followup. (1,4)

* Animal studies have shown an increased incidence of tumors at a variety of sites in rats, mice, and dogs exposed orally to 3,3'-dichlorobenzidine. (1,4)

* EPA has classified 3,3'-dichlorobenzidine as a Group B2, probable human carcinogen. (4)

* EPA uses mathematical models, based on animal studies, to estimate the probability of a person developing cancer from ingesting water containing a specified concentration of a chemical. EPA calculated an oral unit risk estimate of 1.3 H 10^-5 (m g/L)^-1. EPA estimates that, if an individual were to ingest water containing 3,3'-dichlorobenzidine at 0.08 Fg/L* over his or her entire lifetime, that person would theoretically have no more than a one-in-a-million increased chance of developing cancer as a direct result of breathing air containing this chemical. Similarly, EPA estimates that ingesting water containing 0.8 Fg/L would result in not greater than a one-in-a-hundred thousand increased chance of developing cancer, and water containing 8.0 Fg/L would result in not greater than a one-in-ten-thousand increased chance of developing cancer. (4)

* EPA's Office of Air Quality Planning and Standards, for a hazard ranking under Section 112(g) of the Clean Air Act Amendments, has ranked 3,3'-dichlorobenzidine in the nonthreshold category. The 1/ED₁₀ value is 7.5 per (mg/kg)/d and this would place it in the medium category under Superfund's ranking for carcinogenic hazard. (5)

Physical Properties

* 3,3'-Dichlorobenzidine is a gray or purple crystalline solid. (6,7)

* The chemical formula for 3,3'-dichlorobenzidine is C₁₂H₁₀Cl₂N₂and the molecular weight is 253.13 g/mol. (7)

* The vapor pressure for 3,3'-dichlorobenzidine is 1.15 H 10^-7 mm Hg at 25 EC and it has an octanol/water partition coefficient (log K_ow) of 3.64. (2)

* The odor threshold for 3,3'-dichlorobenzidine has not been established.

Uses

* The major uses for 3,3'-dichlorobenzidine are in the manufacture of pigments for printing ink, textiles, plastics, and crayons and as a curing agent for solid urethane plastics. (7)

Health Data from Oral Exposure

Concentration (mg/kg/d)	Health numbers^a	Regulatory, advisory numbers^b	Reference
10.0
_ _ _ _ 1.0
_ _ _ _ 0.1
_ _ _ _ 0.01
_ _ _ _ 0.001
_ _ _ _ 0.0001
_ _ _ _ 0.00001	* EPA Cancer Risk Level (1-in-a-million excess lifetime risk) = 8 H 10^-5 mg/L		4

^a Health numbers are toxicological numbers from animal testing or risk assessment values developed by EPA.

^b Regulatory numbers are values that have been incorporated in Government regulations, while advisory numbers are nonregulatory values provided by the Government or other groups as advice.

References

1. Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for 3,3-Dichlorobenzidine (Draft). U.S. Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA. 1989.

2. U.S. Department of Health and Human Services. Registry of Toxic Effects of Chemical Substances (RTECS, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.

3. U.S. Department of Health and Human Services. Hazardous Substances Data Bank (HSDB, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. 1993.

4. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on 3,3-Dichlorobenzidine. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, Cincinnati, OH. 1993.

5. U.S. Environmental Protection Agency. Technical Background Document to Support Rulemaking Pursuant to the Clean Air ActCSection 112(g). Ranking of Pollutants with Respect to Hazard to Human Health. EPAB450/3-92-010. Emissions Standards Division, Office of Air Quality Planning and Standards, Research Triangle Park, NC. 1994.

6. The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. 11th ed. Ed. S. Budavari. Merck and Co. Inc., Rahway, NJ. 1989.

7. M. Sittig. Handbook of Toxic and Hazardous Chemicals and Carcinogens. 2nd ed. Noyes Publications, Park Ridge, NJ. 1985.