4,4'-Thiodianiline

Nitrogen Compounds -> Other Aromatics (Nitrogen)

Carcinogens

less than 0.1 mg/mL at 68 °F (NTP, 1992)

Very soluble in ethanol, diethyl ether, benzene; soluble in trifluoroacetic acid

Soluble in aqueous hydrochloric acid

Slightly soluble in water

226 to 228 °F (NTP, 1992)

108.5 °C

4,4'-thiodianiline appears as needles or brown powder. (NTP, 1992)

Brown solid; [CAMEO] Fine slightly violet crystals; [MSDSonline]

Danger

H302: Harmful if swallowed [Warning Acute toxicity, oral]

P203, P264, P270, P273, P280, P301+P317, P318, P330, P391, P405, and P501 (click each P-code to see the statement)

Danger

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P264, P270, P273, P280, P301+P317, P318, P330, P391, P405, and P501 (click each P-code to see the statement)

Hazard Traits - Carcinogenicity

The New Jersey Worker and Community Right to Know Act requires public and private employers to provide information about hazardous substances at their workplaces. (N.J.S.A. 34:5A-1 et. seq.)

DHEW/NCI; Bioassay of 4,4'-Thiodianiline for Possible Carcinogenicity (1978) Technical Rpt Series No. 47 DHEW Pub No. (NIH) 78-847

National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. 4,4'-Thiodianiline (139-65-1) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s173thio.pdf]

4,4'-THIODIANILINE is incompatible with acids, diazo and azo compounds, halocarbons, isocyanates, aldehydes, alkali metals, nitrides, hydrides, and other strong reducing agents. May generate heat with these materials and hydrogen gas or hydrogen sulfide gas. May liberate hydrogen sulfide if heated to decomposition or mixed with an acid. Also incompatible with peroxides, phenols (acidic), epoxides, anhydrides, and acid halides.

Acute Tox. 4 (100%)

Carcinogenicity - category 1B

Acute toxicity (Oral) - Category 4

Acute toxicity (Oral) - Category 4

Carcinogens

Carc. 1B

SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

SMALL SPILLS AND LEAKAGE: Should a spill occur while you are handling this chemical, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with 60-70% ethanol and transfer the dampened material to a suitable container. Use absorbent paper dampened with 60-70% ethanol to pick up any remaining material. Seal the absorbent paper, and any of your clothes, which may be contaminated, in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for 4,4'-THIOBISBENZENAMINE (6 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... Clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for 4,4'-THIOBISBENZENAMINE (9 total), please visit the HSDB record page.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

Male Wistar rats were divided into two groups. Rats of group 1 were fed basal powdered diet containing 610 ppm 2,4- diaminoanisole sulfate (DAAS), 46 ppm 4,4'-thiodianiline (TDA) and 200 ppm N,N'-diethylthiourea (DETU) for 52 wk (DTD treatment). Rats of group 2 were maintained on basal diet throughout the experiment as controls. At 52 wk all surviving rats were sacrificed and subjected to an autopsy. Thyroid, lungs, stomach, liver, spleen, kidneys, testes, and all gross lesions suspected of being a tumor were removed. After DTD treatment, the incidence of thyroid hyperplasia and papillary thyroid carcinoma was 59% (10/17) and 65% (11/17), respectively. Hepatocellular adenoma was induced in 2 of 17 rats (12%). Papillary thyroid carcinoma metastasis was found in the lung of 1 rat. No neoplastic tumors were found in kidney, spleen, stomach and testis tissue.

Three thyroid carcinogens, 2,4-diaminoanisole sulfate, N,N'-diethylthiourea and 4,4'-thiodianiline, were simultaneously administered in the diet to male F344 rats at one-third the concentration of the reported TD50 levels (610, 200 and 46 ppm respectively) for 52 weeks. The resultant incidence of thyroid adenocarcinomas in the combined treatment group (18/18: 100%) was significantly higher than those in each individual treatment group (2,4- diaminoanisol sulfate, 0/21; N,N'-diethylthiourea, 1/21; 4,4'-thiodianiline, 2/20). Hepatocellular carcinomas (9/18, 50%) and lung adenomas (6/18, 33%) were also induced by the combined treatment, the incidences being higher than in the TDA group (3/20, 15% and 4/20, 20% respectively) to which these tumors were limited in the three groups treated with single chemicals. Thus, the results indicated that the three carcinogens exert apparent synergism in thyroid carcinogenesis when administered simultaneously.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2,100(SRC), determined from a structure estimation method(2), indicates that bis(4-aminophenyl) sulfide is expected to have slight mobility in soil(SRC). Volatilization of bis(4-aminophenyl) sulfide from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.9X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(3). bis(4-Aminophenyl) sulfide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-5 mm Hg(SRC), determined from a fragment constant method(4). A half-life of 10 to 12 hours using activated sludge under aerobic conditions and a half-life of 30 to 32 hours under anaerobic conditions(5) suggests that biodegradation may be an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2,100(SRC), determined from a structure estimation method(2), indicates that bis(4-aminophenyl) sulfide is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.9X10-12 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 13(SRC), from its log Kow of 2.18(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Hydrolysis of bis(4-aminophenyl) sulfide is not expected based on measured half-lives at 25 °C of 11.11, 11, and 10.73 years at pH values of 2.96, 7, and 10.95, respectively(8). A half-life of 10 to 12 hours using activated sludge under aerobic conditions and a half-life of 30 to 32 hours under anaerobic conditions(8) suggests that biodegradation may be an important environmental fate process in water(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 4,4'-thiobisbenzenamine, which has an estimated vapor pressure of 1.1X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase 4,4'-thiobisbenzenamine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 2.9 hours(SRC), calculated from its rate constant of 1.3X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase 4,4'-thiobisbenzenamine may be removed from the air by wet or dry deposition(SRC). 4,4'-Thiobisbenzenamine does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical.[Available from: http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=139-65-1]

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

Using a structure estimation method based on molecular connectivity indices(1), the Koc of bis(4-aminophenyl) sulfide can be estimated to be 2,100(SRC). According to a classification scheme(2), this estimated Koc value suggests that bis(4-aminophenyl) sulfide is expected to have slight mobility in soil.

AEROBIC: bis(4-Aminophenyl) sulfide exhibited a half-life of 10 to 12 hours in activated sludge, at an incubation temperature of 35 °C, pH of 6.9 and starting concentration of 50 ug/L in a 7 day test(1).

ANAEROBIC: bis(4-Aminophenyl) sulfide exhibited a half-life of 30 to 32 hours in activated sludge adjusted to anaerobic conditions (by passing nitrogen through the system for one hour) at an incubation temperature of 35 °C, pH of 6.9 and starting concentration of 50 ug/L in a 7 day test(1).

4,4'-Thiodianiline

Group 2B: Possibly carcinogenic to humans

Volume 27: (1982) Some Aromatic Amines, Anthraquinones and Nitroso Compounds, and Inorganic Fluorides Used in Drinking-water and Dental Preparations

1987

1987

4,4'-Thiodianiline

An estimated BCF of 13 was calculated in fish for bis(4-aminophenyl) sulfide(SRC), using a log Kow of 2.18(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for bis(4-aminophenyl) sulfide is estimated as 3.9X10-12 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that bis(4-aminophenyl) sulfide is expected to be essentially nonvolatile from water surfaces(2). bis(4-Aminophenyl) sulfide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-5 mm Hg(SRC), determined from a fragment constant method(3).

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In 45-day subchronic feeding studies with male Sprague-Dawley rats and male Swiss mice, all animals that received diets containing 3% (rats) or 2.5% (mice) or more 4,4'-thiodianiline died.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In an experiment designed to screen carcinogens that act on the mammary gland of young female Sprague-Dawley rats, 20 animals, 40 days of age, were given 10 doses of 40 mg/animal 4,4'-thiodianiline in 1 mL sesame oil every 3 days by gastric intubation (total dose, 400 mg); a further group of 10 females received a total dose of 300 mg/rat; 140 control rats received the vehicle alone. All surviving animals were killed after 9 mo. Of 12 surviving rats given 400 mg and which were autopsied, 3 developed mammary carcinomas; of those that received 300 mg/animal, 1/8 developed a mammary carcinoma. Among 132 controls autopsied, of which 127 survived 9 mo, 3 had mammary carcinomas and 1a mammary fibroadenoma. (The IARC Working Group noted the inadequate duration of the experiment.).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ 20 female Sprague-Dawley rats ... were given 10 doses of 40 mg/animal ... in 1 mL sesame oil every 3 days by gastric intubation ... /and/ killed after 9 mo; of 12 surviving rats, ... 3 had ... mammary carcinomas ... Incr incidence of tumors ... in treated animals ... is statistically significant.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Under the conditions of this bioassay, 4,4'-thiodianiline was carcinogenic for Fischer 344 rats, inducing tumors in the liver, thyroid, colon, and ear canal of male rats, and the thyroid, uterus, and the ear canal of female rats. 4,4'-Thiodianiline was carcinogenic for B6C3F1 mice, inducing tumors in the liver and thyroid of both males and females.

For more Non-Human Toxicity Excerpts (Complete) data for 4,4'-THIOBISBENZENAMINE (11 total), please visit the HSDB record page.

Used to make dyes; Also used as an antiparasitic drug (antiplatyhelmintic agent and fasciolicide for sheep); [HSDB]

Appears to be used almost exclusively as a dye intermediate. Three dyes can be prepared from it. Only Mordant Yellow 16 has been produced commercially in the US.

Substance listed with specific concentration in tattoo ink and/or permanent make up according to EU Commission Regulation 2020/2081. The concentration limit (by weight) is 0.0005%.

Prepared by Merz and Weith in 1871 by boiling sulfur with aniline for several days. No information was available on the methods used for its commercial production.

Probably by reaction of aniline with sulfur

Benzenamine, 4,4'-thiobis-: ACTIVE

Thiodianiline was used almost exclusively as a chemical intermediate in the production of three dyes: C.I. mordant yellow 16, milling red G, and milling red FR. C.I. mordant yellow 16 has been used as an indicator in the United States government's nerve gas detector program. However, no uses of either thiodianiline or C.I. mordant yellow 16 since the early 1990s have been reported.

4,4'-Thiodianiline can be used as intermed in production of three dyes: CI mordant yellow 16, Milling red G, and Milling red FR ... Only the 1st is believed to be of commercial significance in USA.