Absorption, Distribution and Excretion
After carp were given (14)C-2-mercaptobenzothiazole and fasted, the intestinal radioactivity was 45% of the dose after 1 hour, the bile radioactivity was 9%, and the radioactivity in other tissues was less than 0.05% of the dose after 72 hours. After carp were given (14)C-2-mercaptobenzothiazole and fed, the bile radioactivity was less than 0.3% after 72 hours, and the radioactivity in other tissues was negligible. Approximately 100% of the dose was excreted into the water. Four male carp and four female rats were exposed to the skin (locally) for 96 hours at doses of 0.0361 and 0.0336 mg/kg, respectively. The results showed that more radioactive test material was removed from the skin of guinea pigs than from the skin of rats. After 96 hours, male and female rats absorbed 16.1% and 17.5% of the dose, respectively. Following topical application of the test substance to male and female rats, 11.9% and 13.4% of the dose were excreted in urine, and 0.980% and 0.641% of the dose were excreted in feces, respectively. In four female guinea pigs, after exposure to the skin (topical) at 96 hours, at doses of 0.0361 and 0.0336 mg/kg, more radioactive test substance was removed by washing the skin of guinea pigs than by washing the skin of rats. After 96 hours, 38.4% of the dose was absorbed. In female guinea pigs, 33.3% of the dose was excreted in urine and 0.389% in feces after topical application of the test substance.
/In/4 male and 4 female rats/Oral (oral) administration, 96 hours/Dose/0.592, 55.5 mg/kg/Results/In high-dose test animals exposed to ¹⁴C-MBT and ¹⁴C-MBTS (2-mercaptobenzothiazole and 2-mercaptobenzothiazole disulfide, respectively), 72.1% to 106% of the administered dose was excreted in urine and 4.03% to 10.3% in feces within 96 hours. A small amount (0.423% to 2.04%) of the dose remained bound to erythrocytes. Drug retention in whole blood and plasma was higher in the low-dose group than in the high-dose group.
For more complete data on absorption, distribution, and excretion of 2-mercaptobenzothiazoles (6 in total), please visit the HSDB record page.

---

Metabolism/Metabolites
The absorption, tissue distribution, and excretion of (14)C-labeled 2-mercaptobenzothiazole in carp were investigated. The radioactive chemical in bile was identified as benzothiazole-2-mercaptoglucuronide.
Cysteine conjugate β-lyases are present in the liver, kidneys, and gut microbiota of mammals and have recently been used to selectively deliver 6-mercaptopurine to the kidneys. In this study, S-(2-benzothiazole)-L-cysteine was used to assess the activity of cysteine conjugate β-lyases in vivo. 2-Mercaptobenzothiazole and 2-mercaptobenzothiazole S-glucuronide are the major metabolites of S-(2-benzothiazole)-L-cysteine in rat liver, kidneys, plasma, and urine. The total concentrations of metabolites in the liver, kidneys, or plasma were similar at 30 minutes and higher than at 3 hours; the metabolites were mainly in the form of glucuronide. At 8 and 24 hours, the excretion of metabolites in urine was approximately 93% and 99% of that at 40 hours, respectively. Pretreatment with aminooxyacetic acid did not alter the concentrations of metabolites in the kidneys, liver, plasma, or urine of rats. Within 24 hours, the proportion of S-(2-benzothiazolyl)-L-cysteine excreted as metabolites was independent of the dose of S-(2-benzothiazolyl)-L-cysteine (100–400 μmol/kg), age (5–12 weeks), or sex of the rat. The in vitro metabolic rate of S-(2-benzothiazolyl)-L-cysteine by cysteine conjugate β-lyase in guinea pig liver and kidney was lower than that in rats, but after 24 hours, the proportion of S-(2-benzothiazolyl)-L-cysteine metabolites recovered in guinea pig urine was close to 60%, almost twice the amount recovered in the urine of rats, mice, or hamsters. The total amount of metabolites in the urine of mice and hamsters was similar, but the proportion of glucuronide metabolites in hamster urine was higher than that in mouse urine. This study investigated the metabolic fate of the sulfur atom in the sulfhydryl group of the 2-thiobenzothiazole metabolite using L-cysteine and 2-thiobenzothiazole metabolites labeled with 14C and 35S in a series of rat experiments. Male Wistar rats were orally administered 35S-labeled 2-mercaptobenzothiazole. Glutathione conjugates of 2-mercaptobenzothiazole in bile metabolites were determined in vitro in rat liver. The retention rate of 35S in 2-mercaptobenzothiazole exceeded 90%. Renal cysteine conjugate β-lyase catalyzes the bioactivation of nephrotoxic cysteine S-conjugates. Cysteine conjugate β-lyase activity is present in the renal cytoplasm and mitochondrial components. Although cytoplasmic cysteine conjugate β-lyase is identical to glutamine transaminase K, mitochondrial cysteine conjugate β-lyase has not yet been identified. Since cysteine conjugate β-lyase is a pyridoxal phosphate-dependent enzyme, it may generate pyridoxamine phosphate during the metabolism of cysteine S-conjugates. This study investigated the effects of α-keto acids (which can convert the enzyme's pyridoxamine phosphate form to pyridoxal phosphate form) on cysteine S-conjugate metabolism and cytotoxicity; pyridoxamine phosphatase showed no catalytic activity in the β-elimination reaction but did exhibit catalytic activity in the transamination reaction. Both α-keto-γ-methanethiol butyrate and α-ketobutyrate enhanced the metabolism of S-(2-benzothiazolyl)-L-cysteine to 2-mercaptobenzothiazole in rat kidney cytoplasm or mitochondria. Both α-keto-γ-methanethiol butyrate and phenylpyruvate enhanced the cytotoxicity of S-(1,2-dichlorovinyl)-L-cysteine to isolated rat proximal tubular cells and the inhibitory effect of S-(1,2-dichlorovinyl)-L-cysteine on mitochondrial respiration. These results are consistent with the formation of pyridoxamine phosphate during the metabolism of cysteine S-conjugates in the renal cytoplasm or mitochondria. Mitochondrial cysteine conjugate β-lyases have previously been localized to the outer membrane. To investigate the presence of cysteine conjugate β-lyase activity in mitochondrial plastids in the form of pyridoxamine phosphate, we investigated the effects of α-keto-γ-methanethiol butyrate on the metabolism of S-(2-benzothiazolyl)-L-cysteine to 2-mercaptobenzothiazole and the S-(1,2-dichlorovinyl)-L-cysteine-induced state 3 mitochondrial respiration inhibition. The results showed that most of the mitochondrial cysteine conjugate β-lyase activity was located in the outer membrane, and the specific activity of outer membrane cysteine conjugate β-lyase was higher than that of mitochondrial plasmid cysteine conjugate β-lyase. α-Keto-γ-methanethiol butyrate produced equivalent stimulatory effects on cysteine conjugate β-lyase activity in intact mitochondria, the outer mitochondrial membrane, and the mitochondrial plasmid, and enhanced the S-(1,2-dichlorovinyl)-L-cysteine-induced respiratory inhibition in intact mitochondria, but had no such effect on the mitochondrial plasmid. These results further confirm the central role of cysteine conjugate β-lyase in the bioactivation of nephrotoxic cysteine S-conjugates.

Toxicity Summary
Identification and Uses: Mercaptobenzothiazole (MBT) is a pale yellow powder. It is not currently registered for use in the United States, but approved pesticide uses may change periodically, so it is essential to consult federal, state, and local authorities for currently approved uses. MBT is an antioxidant and stabilizer added to polyether polymers to improve their air aging and ozone resistance. MBT and its derivatives have been used to protect copper and copper alloys from corrosion. MBT can be used as an indicator for the photometric determination of gold, cadmium, copper, lead, and palladium. It is also used in veterinary medicine. Human Exposure and Toxicity: MBT can cause contact sensitization, such as from contact with products like rubber condoms and rubber earplugs. One case of occupational anaphylactic contact dermatitis and anaphylactic shock caused by rubber latex has been reported. Occupational exposure to MBT in hospital nurses and other healthcare workers may lead to hand dermatitis. Epidemiological studies indicate an increased risk of death from bladder cancer in workers with occupational exposure to MBT. Animal Studies: Mice experienced seizures after acute exposure to MBT. No teratogenic effects were observed in rat fetuses after intraperitoneal injection of 200 mg/kg MBT during days 1-15 of gestation. In a 2-year NTP gavage study, increased incidence of monocytic leukemia, pancreatic acinar cell adenoma, adrenal pheochromocytoma, and prepuce gland adenoma or carcinoma (combined) was observed in male rats, indicating that MBT possesses some carcinogenic activity. Increased incidence of adrenal pheochromocytoma and pituitary adenoma was also observed in female rats, further suggesting that MBT has some carcinogenic activity. No carcinogenic activity was found in male mice after administration of 375 or 750 mg/kg MBT. Evidence of carcinogenic activity in female mice is unclear, but an increased incidence of hepatocellular adenoma or carcinoma (both combined) was observed. MBT was not mutagenic to Salmonella Typhimurium strains TA98, TA100, TA1535, or TA1537, regardless of metabolic activation. In the presence of rat liver S9 cells, MBT increased chromosomal aberrations and sister chromatid exchange frequencies in Chinese hamster ovarian cells, as well as the mutation frequency at the TK locus in mouse L5178Y lymphoma cells. Ecotoxicity studies: MBT is virtually non-toxic to acute oral ingestion in birds and only slightly toxic to dietary intake. MBT is highly toxic to freshwater fish and moderately toxic to aquatic invertebrates.

---

Toxicity Data
LC50 (Rats)> 1,270 mg/m3

---

Interactions
Adjuvants are components in a formulation used to enhance the pharmacological or toxic effects of the active ingredient. ...Examples of adjuvants used in toxicological formulations include...Enhancing the bactericidal activity of dithiocarbamates with mercaptobenzothiazole.
Non-human toxicity values

LD50 Mice (Slc:ddY) Male Oral LD50 1558 (mg/kg) / 5% Gum Arabic Solution Suspension /
LD50 Mice (Slc:ddY) Male Oral LD50 3148 (mg/kg) / Olive Oil Suspension /
LD50 Rats / No Administration Route / 3800 mg/kg Body Weight
LD50 Rats / No Administration Route / 2830 mg/kg Body Weight
For more complete non-human toxicity data for 2-mercaptobenzothiazole (out of 10), please visit the HSDB records page.

According to California labor law and the International Agency for Research on Cancer (IARC) of the World Health Organization, 2-mercaptobenzothiazole is carcinogenic. 2-Mercaptobenzothiazole is a pale yellow to brownish-yellow crystalline powder with an unpleasant odor. (NTP, 1992) 1,3-Benzothiazole-2-thiol refers to 1,3-benzothiazole with a thiol group substituted at the 2-position. It is both a carcinogen and a metabolite. It belongs to the benzothiazole class of compounds and is also an aryl thiol. 2-Mercaptobenzothiazole is a standardized chemical allergen. The physiological effects of 2-mercaptobenzothiazole are achieved through increased histamine release and cell-mediated immunity. The effects of 2-mercaptobenzothiazole in cattle (Bos taurus) have been reported, and relevant data are available.

---

Therapeutic Use
Antifungal Agents
(Veterinary): Ointments and lotions at a concentration of 1-2% can be used to treat various skin diseases in dogs and cow teats.

C7H5NS2

167.24

166.986

149-30-4

149-30-4 (free);2492-26-4 (Na);

697993

White to yellow solid powder

1.5±0.1 g/cm3

305.0±25.0 °C at 760 mmHg

177-181 °C(lit.)

243 ºC (dec.)

0.0±0.6 mmHg at 25°C

1.784

2.38

1

2

0

10

158

0

YXIWHUQXZSMYRE-UHFFFAOYSA-N

InChI=1S/C7H5NS2/c9-7-8-5-3-1-2-4-6(5)10-7/h1-4H,(H,8,9)

3H-1,3-benzothiazole-2-thione

Captax; Dermacid; Mercaptobenzothiazole

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~597.91 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (14.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (14.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)