Toluol-4-sulfonamid

log Kow = 0.82

0.82

Monoclinic plates (w+2)

White leaflets

In water, 3.16X10+3 mg/L at 25 °C

Slightly soluble in water

Soluble in alcohol

Slightly soluble in ether; soluble in ethanol

Solubility in water, g/100ml at 25 °C: 0.316

202 °C (396 °F) Closed cup

202 °C c.c.

Hazardous decomposition products formed under fire conditions - Carbon oxides, nitrogen oxides (NOx), sulfur oxides.

When heated to decomposition it emits very toxic fumes of /nitrogen oxides and sulfur oxides/.

138 °C

MP: 105 °C (Hydrated)

138 °C

0.000096 [mmHg]

Vapor pressure at 25 °C: negligible

0.000096 [mm Hg] @25 °C

Dry Powder; Liquid

White solid; [Hawley] White powder; [MSDSonline]

WHITE CRYSTALS.

This chemical does not meet GHS hazard criteria for 57% (146 of 256) of all reports.

Warning

H319 (36.3%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

P264+P265, P280, P305+P351+P338, and P337+P317 (click each P-code to see the statement)

Aggregated GHS information provided per 256 reports by companies from 12 notifications to the ECHA C&L Inventory.

Chemical: Benzenesulfonamide, 4-methyl-

Benzenesulfonamide, 4-methyl- is listed on the EPA's Chemical Data Reporting (CDR) system. Manufacturers and importers of Benzenesulfonamide, 4-methyl- are required to report information about their production and use of this chemical to the EPA under the Toxic Substances Control Act (TSCA). (40 eCFR Part 711)

Status: Active Update: 27-05-2020 https://echa.europa.eu/registration-dossier/-/registered-dossier/10745

p-Toluenesulfonamide: Does not have an individual approval but may be used under an appropriate group standard

Used therapeutically, sulfonamides can cause a range of hypersensitivity reactions including rashes and injury to the liver and kidneys; Methemoglobinemia has been reported after sulfonamide poisoning; [HSDB] An eye irritant; [ICSC] Causes somnolence and weakness in subcutaneous lethal-dose studies of guinea pigs; [RTECS] An irritant; [MSDSonline]

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.

Personal protection: particulate filter respirator adapted to the airborne concentration of the substance. Sweep spilled substance into covered containers. If appropriate, moisten first to prevent dusting.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

SRP: 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 air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contaminated packaging: Dispose of as unused product.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Avoid breathing dust. Environmental precautions: Do not let product enter drains.

Precautions for safe handling: Avoid formation of dust and aerosols.Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 35(SRC), determined from a log Kow of 0.82(2) and a regression-derived equation(3), indicates that p-toluenesulfonamide is expected to have very high mobility in soil(SRC). Volatilization of p-toluenesulfonamide from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.7X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(3). p-Toluenesulfonamide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.6X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). A 3% of theoretical BOD using activated sludge in the Japanese MITI test(4) suggests that biodegradation is not an important environmental fate process in soil(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 35(SRC), determined from a log Kow of 0.82(2) and a regression-derived equation(3), indicates that p-toluenesulfonamide is not expected to adsorb to suspended solids and sediment(SRC). Volatilization of p-toluenesulfonamide from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.7X10-7 atm-cu m/mole(SRC), using a fragment constant estimation method(3). According to a classification scheme(4), an estimated BCF of 3.2(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). A 3% of theoretical BOD using activated sludge in the Japanese MITI test(5) suggests that biodegradation is not 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), p-toluenesulfonamide, which has an estimated vapor pressure of 9.6X10-5 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 p-toluenesulfonamide 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 13 days(SRC), calculated from its rate constant of 1.2X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(2). Particulate-phase p-toluenesulfonamide may be removed from the air by wet and dry deposition(SRC). p-Toluenesulfonamide does not absorb light at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight, since sunlight consists of wavelengths above 290 nm(SRC).

IDENTIFICATION AND USE: p-Toluenesulfonamide is a solid. It is used in organic synthesis, in plasticizers and resins, and as a fungicide and mildewicide in paints and coatings. It has been used as experimental therapy. HUMAN STUDIES: It is known as a common contact allergen. ANIMAL STUDIES: No treatment-related effects were observed in a 90 day feeding study on dogs exposed to doses up to 3000 mg/kg feed of a mixture of p-toluenesulfonamide (68%) and ortho-toluenesulfonamide (32%), equivalent to 75 mg/kg bw/day. In a 90 day feeding study, rats were exposed to diets containing 0, 300, 1000 or 3000 mg/kg feed of mixture of p-toluenesulfonamide (68%) and ortho-toluenesulfonamide (32%), equivalent to approximately 15, 50 or 150 mg/kg bw/day. A slight reduction of weight gain and food consumption was present at 3000 mg/kg feed as the only treatment-related effects. Pregnant rats were treated by gavage on gestational days 6-15 with 0, 50, 250, or 500 mg/kg bw of a mixture of p-toluenesulfonamide (68%) and ortho-toluenesulfonamide (32%). At 250 and 500 mg/kg bw maternal weight gain was significantly reduced during the treatment period. At the same dose levels, postimplantation loss demonstrated a dose-related increase and fetal weight was reduced. No teratogenic effect was observed. p-Toluenesulfonamide was studied for mutagenic potential with Salmonella typhimurium/microsome test, basic-test in Drosophila melanogaster, and micronucleus test in mice. No test revealed mutagenic activity.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of November 16, 2017: http://actor.epa.gov/dashboard/]

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for p-toluenesulfonamide is available.[Available from, as of November 3, 2017: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

p-Toluenesulfonamide has been identified in the effluent from the nonferrous metals industry (22 ng/uL extract) and the printing and publishing industry at 19 and 841 ng/uL, respectively(1). p-Toluenesulfonamide was identified, not quantified, as a contaminant found in advanced treatment water in Pomona, CA on 9/24/74(2). p-Toluenesulfonamide was identified in runoff samples from 6 crop fields irrigated with treated effluent and effluent-dominated stream water; concentrations reported in the runoff were <650 ng/L, WWTP effluent 115-184 ng/L, and effluent-dominated stream water <630 ng/L(3).

... The presence of benzosulfonamides (BeSAs) has been evaluated during seven consecutive days in influent and effluent samples from the wastewater treatment plant of Athens, Greece. o-TSA and p-TSA were detected in 100% of the samples, while BSA was detected in all the influents and in 43% of the effluents. All three compounds were determined in relevant concentrations (up to 1.4 ug/L in the case of p-TSA), constituting the first evidence of the presence of these compounds in Greece, and contributing to the scarce occurrence data. Removal efficiencies of BeSAs during wastewater treatment was also assessed and discussed. In this regard, different behaviors were observed: while BSA and p-TSA were removed in different rates, o-TSA was formed during wastewater treatment. A daily load of 0.48 kg of o-TSA and 0.47 kg of p-TSA was discarded in the receiving Saronikos Gulf.

The Koc of p-toluenesulfonamide is estimated as 35(SRC), using a log Kow of 0.82(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that p-toluenesulfonamide is expected to have very high mobility in soil.

/HUMAN EXPOSURE STUDIES/ Common contact allergen. /Toluene sulfonamide resins, from table/

/ALTERNATIVE and IN VITRO TESTS/ Para-toluenesulfonamide (PTS) has been implicated with anticancer effects against a variety of tumors. In the present study, we investigated the inhibitory effects of PTS on tongue squamous cell carcinoma (Tca-8113) and explored the lysosomal and mitochondrial changes after PTS treatment in vitro. High-performance liquid chromatography showed that PTS selectively accumulated in Tca-8113 cells with a relatively low concentration in normal fibroblasts. Next, the effects of PTS on cell viability, invasion, and cell death were determined. PTS significantly inhibited Tca-8113 cells' viability and invasive ability with increased cancer cell death. Flow cytometric analysis and the lactate dehydrogenase release assay showed that PTS induced cancer cell death by activating apoptosis and necrosis simultaneously. Morphological changes, such as cellular shrinkage, nuclear condensation as well as formation of apoptotic body and secondary lysosomes, were observed, indicating that PTS might induce cell death through disturbing lysosomal stability. Lysosomal integrity assay and western blot showed that PTS increased lysosomal membrane permeabilization associated with activation of lysosomal cathepsin B. Finally, PTS was shown to inhibit ATP biosynthesis and induce the release of mitochondrial cytochrome c. Therefore, our findings provide a novel insight into the use of PTS in cancer therapy.

AEROBIC: p-Toluenesulfonamide, present at 100 mg/L, reached 3% of its theoretical BOD in 4 weeks using an activated sludge inoculum at 30 mg/L in the Japanese MITI test(1). Three sulfonamides -para-toluenesulfonamide (p-TSA), ortho-toluenesulfonamide (o-TSA) and benzenesulfonamide (BSA) - have recently been detected in groundwater within a catchment area (Lake Muegglesee, Berlin, Germany) of the Frierichshagen drinking water treatment plant (DWTP), which is located downstream of a former sewage farm. The degradation pathways of p-TSA, o-TSA and BSA were investigated during drinking water treatment with incubation experiments and an experimental filter. Incubation experiments showed that p-TSA is removed during the treatment by microbiological processes. Removal of p-TSA is performed by adapted microorganisms only present in polluted groundwater. The elimination in an experimental filter of 1.6 m length applying filtration velocities from 2 to 6 m/hr was approximately 93% of p-TSA. The microbial degradation rates in the incubation experiment were approximately 0.029 ug/L-hr (zero order reaction). In the experimental filter, the reaction rate constants were around 0.0063/sec for all filtration velocities (1st order reaction). Drinking water treatment did not reduce the concentration of o-TSA and BSA under conditions encountered. p-TSA, o-TSA and BSA were only measured in the low ug/L concentrations range in the purified water(2).

ANAEROBIC: In a biodegradation study using aquifer microorganisms under anaerobic conditions, p-toluenesulfonamide was not degraded to any extent under sulfate reducing conditions, while 20% disappeared from methanogenic aquifer slurries after 13 months; however, this depletion could not be correlated with methane production over background controls(1).

An estimated BCF of 3.2 was calculated for p-toluenesulfonamide(SRC), using a log Kow of 0.82(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).

L - Antineoplastic and immunomodulating agents

QL - Antineoplastic and immunomodulating agents

Fingerlings and juvenile trout were exposed to 20 mg/L (twice the therapeutic concentration) of ring UL-14C-tosylchloramide sodium (purity 93.7%, specific activity 1.2 uCi/uM) for up to 1 hr and then transferred to fresh water for recovery to assess tissue accumulation and distribution of resulting residues. The temperature of the well water was 11.6 to 12.2 °C. The estimated half-life of para-toluenesulfonamide equivalents in fingerlings was 27.3 hours whereas determined by HPLC the half-life of para-toluenesulfonamide residues in whole-body homogenates was 36.3 hours. The estimated half-life of residues in juvenile fish was 32.6 hours, based on radiometric data, while determined by HPLC the half-life for para-toluenesulfonamide residues in whole body samples was 40.3 hours.

/The purpose of this study was/ to study the in vivo and in vitro metabolism and the effect of para-toluene-sulfonamide (PTS) on cytochrome P450 enzymes (CYP450). Total CYP450 and microsome protein content were determined after iv pretreatment of rats with PTS. CYP-specific substrates were incubated with rat liver microsomes. Specific CYP isoform activities were determined by using HPLC. CYP chemical inhibitors added to the incubation mixture were used to investigate the principal CYP isoforms involved in PTS metabolism. The effect of PTS on CYP isoforms was investigated by incubating PTS with specific substrates. The groups treated with 33 and 99 mg/kg per d PTS, respectively, had a total CYP content of 0.66+/-0.17 and 0.60+/-0.12 nmol/mg. The K(m) and V(max) were 92.2 umol/L and 0.0137 nmol/min per mg protein. CYP2C7, CYP2D1 and CYP3A2 might contribute to PTS metabolism in the rat liver. The inhibitory effects of sulfaphenazole and ketoconazole on PTS metabolism were shown to have a mixed mechanism, whereas PTS metabolism was inhibited noncompetitively by quinidine. PTS had little effect on the activities of the selected CYP isoforms. Generally speaking, it is relatively safe for PTS to be co-administered with other drugs. However, care should be taken when administering PTS with CYP inhibitors and the substrates of CYP2C, CYP2D and CYP3A.

Aim of this study was to investigate liver metabolism of with regard to para toluene-sulfonamide (PTS), CYP isoforms, P-glycoprotein (P-gp), and drug interactions. Known substrates, inducers and inhibitors of CYP and inhibitor of P-gp were employed and metabolites were determined with HPLC. Male Wistar rats were pretreated with ip phenobarbital (PB), ketoconazole (Ket), or verapamil (Ver) for 3 days and in situ liver perfusion of PTS was conducted in a recirculation system. Rats were also pretreated with ip PTS (33 mg/kg/day or PTS 99 mg/kg/day) for 4 days before liver perfusions with dextromethorphan (Dex) and phenacetin (Phe) preparations were conducted. Microsome incubation was used to investigate PTS effect on five CYP isoforms and PTS-drug interactions probability with phyllotoxin and 5-fluorouracil (5-FU) in vitro. PTS at 60 min perfusates had areas of 61.4% and 133.6% of the blank control in PB group and Ket group, respectively. The result that PTS metabolism was enhanced by PB and inhibited by Ket treatments suggested liver CYP was attributed to PTS metabolism. PTS mg/kg/day pretreatment slowed down the metabolism of Dex and Phe while in vitro incubations did not show a PTS (0-160 umol/L) effect on CYP activities. PTS metabolite formation when co-incubated with phyllotoxin was 50.7% of the negative control. The potent inhibitory ability of phyllotoxin to PTS requires further clinical investigation regarding in concomitant administration.

Fifteen adult rainbow trout were exposed to water solution of (14)C-tosylchloramide sodium (purity 93.7%, specific activity 1.2 ugCi/uM) at a concentration of 20 mg/L (twice the proposed treatment concentration) for a period of 1 hour and then transferred to fresh water. The temperature of the well water was 11 to 13 °C. ... tosylchloramide sodium was rapidly reduced to the primary metabolite para-toluenesulfonamide, but the levels were not quantified.

...50% of admin ortho- and para-toluenesulfonamides excreted in urine had been metabolized to ortho- and para-sulfamoylbenzoic acids, respectively.

For more Metabolism/Metabolites (Complete) data for p-Toluenesulfonamide (6 total), please visit the HSDB record page.

Urinary excretion of administration p-toluenesulfonamide in rats was approx 80% with half of original compound being oxidized to p-sulfamoylbenzoic acid. More than 90% of /the p-sulfamoylbenzoic acid metabolite/ was excreted unchanged, but urine to feces ratios varied considerably among individual animals.

After oral administration of (14)C-labeled compound to rats the label was rapidly eliminated largely in urine (66-89% of dose), with little in feces (2-8% of dose). (14)C in feces was 4-sulfamoylbenzoic acid, which probably originated in tissues.

Used to retard growth of fungi and mildew in paints, plasticizers, and resins; Also used as a plasticizer for hot-melt adhesives (commonly found in commercial mixtures with o-isomer); [HSDB] Used as intermediate for pesticides; [eChemPortal: SIDSUNEP]

Painting (Pigments, Binders, and Biocides) [Category: Paint]

Organic synthesis, plasticizers and resins, fungicide and mildewicide in paints and coatings.

Used in production of chloroamines, e.g., chloramine T and dichloramine T.

... carrier in fluorescent pigments. /Ortho- and para-toluenesulfonamide mixture/

The ortho- and para-toluenesulfonamide mixture is used as a reactive plasticizer in hot-melt adhesives to improve the flow properties of thermosetting resins (e.g., melamine, urea and phenolic resins) and to impart flexibility to coatings based on resins made from casein, shellac, zein and soya protein. /Ortho- and para-toluenesulfonamide mixture/

(1979) 8.22X10+7 GRAMS (PRINCPL CUSTMS DISTS)

(1981) 4.50X10+5 GRAMS (PRINCPL CUSTMS DISTS)

2023: 1,000,000 - <2,500,000 lb

(1979) MORE THAN 2.27X10+6 G (O-, P- MIXTURE)

(1981) MORE THAN 2.27X10+6 G (O-, P- MIXTURE)

Non-confidential 2016 Chemical Data Reporting (CDR) information on the production and use of chemicals manufactured or imported into the United States. Chemical: 4-Methylbenzenesulfonamide:

By amination of para-toluene sulfonchloride.

Produced from the sulfonyl chloride with aqueous ammonia.

Plastics Material and Resin Manufacturing

Benzenesulfonamide, 4-methyl-: ACTIVE