2-MERCAPTOBENZOTHIAZOLE 1. Exposure Data 1.1.3 Physical and chemical properties of the pure substance 1.1 Identification of the agent Description: Yellowish crystals or powder 1.1.1 Nomenclature with a characteristic sulfurous odour (IFA, 2015) Chem. Abstr. Serv. Reg. No.: 149-30-4 Melting point: 180–182 °C (HSDB, 2015) Chem. Abstr. Serv. Name: Density (at 20 °C): 1.42 g/cm3 (HSDB, 2015) 2-Mercaptobenzothiazole Octanol/water partition coefficient: log Kow, IUPAC Systematic Name: 2.41 (HSDB, 2015) 3H-1,3-Benzothiazole-2-thione Water solubility: Moderately soluble Synonyms: Benzothiazole-2-thiol; 1,3-benzo- (100–1000 mg/L) (ECHA, 2015) thiazole-2-thiol; 2-benzothiazolethiol; 3H- Dissociation constant: pKa 7.0 at 20 °C (HSDB, benzothiazole-2-thione; 2-sulfanylbenzo- 2015) thiazole Volatility: Vapour pressure, 2.25 × 10−8 mm Acronyms: MBT; 2-MBT. Hg at 20 °C (HSDB, 2015) Flash point: 243 °C (GESTIS, 2015) 1.1.2 Structure and molecular formula, and Conversion factor: 1 ppm = 6.83 mg/m3 relative molecular mass (HSDB, 2015). S S SH S 1.2 Production and use N N H 1.2.1 Production (a) Production process (tautomers in crystals and aqueous solutions) Molecular formula: C H NS 2-Mercaptobenzothiazole is produced by 7 5 2 reacting aniline, carbon disulfide, and sulfur at Relative molecular mass: 167.25 high temperature and pressure; the product is then purified by dissolution in a base to remove the dissolved organics. Re-precipitation is achieved by the addition of acid (Kirk-Othmer, 1982; NTP, 1988). 73 IARC MONOGRAPHS – 115 (b) Production volume (Azam & Suresh, 2012), and sodium and zinc 2-Mercaptobenzothiazole is listed as a salts of 2-mercaptobenzothiazole are approved chemical with high production volume by the for use as pesticides by the EPA (1994). Organisation for Economic Co-operation and Development (OECD, 2004) and in the USA 1.3 Measurement and analysis (Federal Register, 2000; HSDB, 2015). Several analytical methods are available for In 2006, the inventory-aggregated national the determination of 2-mercaptobenzothiazole production volume for 2-mercaptobenzothi- in environmental samples (e.g. air, water, and azole in the USA was between 10 and < 50 food), in rubber products (e.g. disposable medical million pounds [~4536 to < 22 680 tonnes]. The gloves), in products that come into contact with United States Environmental Protection Agency rubber materials (e.g. medical drug solutions or (EPA) noted that 500 000–1 000 000 pounds/year industrial coolant solutions), and in the urine [~227–454 tonnes/year] of 2-mercaptobenzothi- of exposed persons (Table 1.1). Generally, the azole were produced, imported, and used in the use of stable isotope-labelled surrogate stand- USA in 2012 (EPA, 2012). In 2012, three facili- ards is recommended for the specific analysis of ties in three states were listed as manufacturing 2-mercaptobenzothiazole (Wick et al., 2010). A 2-mercaptobenzothiazole in the USA (HSDB, single method has been described for the deter- 2015). mination of 2-mercaptobenzothiazole in dietary 2-Mercaptobenzothiazole is registered with products (Barnes et al., 2003). the European Chemicals Agency, and prod- uction was stated to be 1000–10 000 tonnes per 1.4 Occurrence and exposure year from three manufacturers in three coun- tries, one each in Belgium, Spain, and the United Due to its use as an accelerant in rubber Kingdom (ECHA, 2012). vulcanization, 2-mercaptobenzothiazole can A commercial website identified a larger be found as a contaminant in rubber products. number of suppliers: 225 in China, 13 in the Sensitization to 2-mercaptobenzothiazole is USA, five in India, two in Hong Kong Special common in occupational and non-occupational Administrative Region, and one each in Canada, settings and can be used as an indicator of expo- France, Germany, Japan, the Russian Federation, sure (HSDB, 2015). and Turkey (GuideChem, 2015). 1.4.1 Natural occurrence 1.2.2 Use 2-Mercaptobenzothiazole is not known to occur in nature. 2-Mercaptobenzothiazole is principally used as a reactant in the manufacture of rubber prod- 1.4.2 Environmental occurrence ucts, but is also used as a corrosion inhibitor in oils, greases and cooling fluids. It is added (a) Air to polyether polymers as a stabilizer to resist Urban particulate matter was sampled in a damage by air and ozone, and is a component street in Stockholm, Sweden, using a device made approved in the USA in some skin medications in-house; average concentrations of 2-mercapto- for dogs (HSDB, 2015). benzothiazole were 64 pg/m3 in airborne partic- 2-Mercaptobenzothiazole is also used as an ulate matter, and 591 pg/m3 in total suspended intermediate in the production of pesticides particulate matter, and were thought to derive such as 2-(thiocyanomethylthio)benzothiazole from tyre wear (Avagyan et al., 2014). 74 Table 1.1 Selected methods of analysis for 2-mercaptobenzothiazole Sample matrix Sample preparation Assay method Limit of Reference detection Air Workplace air Collection on quartz fibre filters; stabilization by covering with double-distilled water; CE/DAD 0.2 mg/m3 a Breuer et al. desorption using an ultrasonic bath; filtration of the sample (2002) Sampling recommendation: 2 h at 1 L/min (120 L) Water Municipal and Extraction using methylene chloride at pH 6–8; drying and concentrating the sample; HPLC/UV 1.7 µg/L EPA (1993) industrial wastewater change solvent to methanol; if necessary: silica gel column clean-up Treated and raw Direct injection of the (diluted) effluent samples HPLC/ESI- 0.2 µg/L Reemtsma wastewater MS/MS (2000) Treated wastewater SPE using a co-polymeric sorbent (divinylbenzene, N-vinylpyrrolidone); elution with HPLC/ESI- 0.05 µg/L Kloepfer et al. and raw municipal methanol/acetone; addition of the internal standard; concentration of the eluent MS 0.12 µg/L (2004a) wastewater Cooling water (spiked) Direct analysis of the undiluted samples at pH 8 (buffered) SWV 0.8 mg/L Parham et al. (2008) Cooling water (spiked) SPE using a cartridge loaded with copper oxide nanoparticles at pH 5–8; washing the HPLC/UV 1.9 µg/L Parham & sorbent with 0.5 M sodium thiosulfate; desorption of the cartridge using methanol Khoshnam (2013) Cooling water and Addition of gold nanoparticle solution and citrate buffer (pH 6) RRS, SFP 1.0 µg/L Parham et al. drinking-water (spiked) (2015) Food Dietary products Milk, yoghurt, infant formula: addition of an internal standard; protein precipitation HPLC/APCI- 8–43 µg/kgb Barnes et al. by the addition of acetonitrile; sample filtration MS (2003) All other foodstuffs: addition of an internal standard, acetic acid and acetonitrile; sonication of the sample followed by centrifugation and filtering Products Coolant formulations Direct analysis of the undiluted samples HPLC/UV 0.02% Schmitt & 2-Mercaptobenzothiazole Muzher (1981) Injectable solutions Mixing with 1 M hydrochloric acid; extraction with chloroform; evaporation to HPLC/UV NA Reepmeyer & dryness and reconstitution in acetonitrile Juhl (1983) Protective gloves Extraction using acetone; evaporation to dryness and reconstitution in acetonitrile; HPLC/DAD 1 mg/L Bergendorff filtration of the sample et al. (2006) 75 76 IARC MONOGRAPHSIARC 115 – Table 1.1 (continued) Sample matrix Sample preparation Assay method Limit of Reference detection Urine Experimental animals Acidic hydrolysis using 5 M sulfuric acid; incubation at room temperature; SPE using GC/MS 20 µg/L Manninen et al. C18 cartridges; elution with ethyl acetate; evaporation to dryness and reconstitution in (1996) ethanol Exposed workers and Homogenization and addition of ammonium acetate buffer (pH 6.5), deuterated HPLC/ESI- 0.4 µg/L Gries et al. non-exposed controls internal standard (MBT-d4) and β-glucuronidase/arylsulfatase; homogenization of the MS/MS (2015) samples, incubation overnight at 37 °C and centrifugation a The analysis is considered to be semi-quantitative. The coefficient of variation of the calibration is 1.8%, therefore the analytical procedure itself is precise; however, due to the instability of 2-mercaptobenzothiazole on the filter, large overall variation can occur (up to 16% depending on the concentration) b Depending on the food APCI, atmospheric pressure chemical ionization; CE, capillary electrophoresis; DAD, diode array detection; ESI, electrospray ionization; GC, gas chromatography; HPLC, high- performance liquid chromatography; MBT, 2-mercaptobenzothiazole; MS, mass spectrometry; MS/MS, tandem mass spectrometry; NA, not available; RRS, resonance Raleigh scattering; SFP, spectrofluorophotometry; SPE, solid-phase extraction; SWV, square wave voltammetry; UV, ultraviolet detection 2-Mercaptobenzothiazole (b) Water Leaching of 2-mercaptobenzothiazole into Effluent from a waste dump was analysed for drug preparations of several constituents of 2-mercaptobenzothiazole by liquid chromato- elastomeric closures was assessed. In syringe graphy in a study aimed at developing analytical cartridges, concentrations of 2-mercaptobenzo- methods; the concentration of 2-mercaptobenzo- thiazole ranged from 8.3 to 13.8 µg/mL (Airaudo thiazole was estimated at 30 μg/L in the sample et al., 1990). tested (Cox, 1976). An investigation of instability of a therapeutic A study of municipal wastewater in Germany protein for infusion revealed that 2-mercapto- found 2-mercaptobenzothiazole at a concentra- benzothiazole and its zinc salt leached from tion of up to 0.19 μg/L (Kloepfer et al., 2004b). In the stopper used for the infusion bags (100 mL) a comprehensive survey of wastewater from 4000 (Chang et al., 2010). industrial and publicly owned treatment works (ii) Consumer products sponsored by the Effluent Guidelines Division A survey of 19 rubber gloves found that two of the EPA, 2-mercaptobenzothiazole was iden- contained 2-mercaptobenzothiazole (5–8 μg/g) tified in one discharge each from a rubber-pro- (Bergendorff et al., 2006). cessing and pesticide-manufacturing industry at In 2001, a retail market survey of 19 samples a concentration of 1.27 ppm [8.67 μg/L] and 0.86 of baby bottle teats and soothers was performed ppm [5.87 μg/L], respectively (Shackelford et al., in the Netherlands.