N-Cyclohexyl-2-benzothiazolesulfenamide was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 25, 80, 250 and 800 mg/kg/day.
Suppressions of food consumption and body weight gain was observed in females of the 250 mg/kg group and males and females of the 800 mg/kg group. Laboratory examinations revealed increases of total protein and urinary ketone bodies and a reduced prothrombin time in males of the 250 and 800 mg/kg groups, an increase of calcium and decreases in the hematocrit value, reticulocyte count, platelet count and sodium in females of 800 mg/kg group, and a decrease in chloride in males and females of the 800 mg/kg group. Kidney relative weights were increased in males and females of the 800 mg/kg group. Histopathological examination revealed increased of deposition of hyaline droplets in the renal proximal tubular epithelium in males of the 250 and 800 mg/kg groups. Histopathological changes in the kidney tended to recover and the other changes related to the test substance disappeared after a 14-day recovery period. The NOELs are considered to be 80 mg/kg/day for both sexes.
N-Cyclohexyl-2-benzothiazolesulfenamide was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA, with or without an exogeneous metabolic activation system.
Genotoxicity of N-cyclohexyl-2-benzothiazolesulfenamide was studied by chromosomal aberration test in cultured Chinese hamster lung (CHL/IU) cells. With short-term treatment and an exogenous metabolic activation system, the compound marginally induced structural chromosomal aberrations at 0.041 mg/ml (low concentration) and polyploidy at 0.081 mg/ml (high concentration). However, trend tests showed no dose dependency for the structural chromosomal aberrations and polyploidy.
| Purity | : | 98.8% |
| Test species/strain | : | Rat/Crj:CD (SD) |
| Test method | : | Guidelines for 28-Day Repeat Dose Toxicity Testing of Chemicals (Japan) |
| Route | : | Oral (gavage) |
| Doses | : | 0 (vehicle), 25, 80, 250, 800 mg/kg/day |
| Number of animals/group | : | Males, 6 Females, 6 |
| Vehicle | : | Sesame oil |
| Administration period | : | Males and females, 28 days |
| Terminal kill | : | Days 29 or 43 |
| GLP | : | Yes |
Test results:
Urinalysis revealed an increase of ketone bodies in males of the 250 and 800 mg/kg groups.
| Purity | : | 98.8 % |
| Test species/strains | : | Salmonella typhimurium, TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA |
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Guideline No. 471 and 472 |
| Procedures | : | Pre-incubation method |
| Solvent | : | DMSO |
| Positive control | : | -S9 mix, 2-(2-Furyl)-3-(5-nitro-2-furyl) acrylamide (TA100, TA98, WP2), Sodium azide (TA1535) and 9-Aminoacridine (TA1537) +S9 mix, 2-Aminoanthracene (five strains) |
| Doses | : | -S9 mix; 0, 6.25, 12.5, 25.0, 50.0, 100, 200, 400 μg/plate (TA1537) 0, 156 - 5000 μg/plate (TA100, TA1535, TA98) 0, 313 - 5000 μg/plate (WP2)
+S9 mix; |
| S9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone |
| Plates/test | : | 3 |
| Number of replicates | : | 2 |
| GLP | : | Yes |
Test results:
Genetic effects:
Salmonella typhimurium TA100, TA1535, TA98, TA1537
| + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] |
Escherichia coli WP2 uvrA
| + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] |
| Purity | : | 98.8 % | |
| Type of cell used | : | Chinese hamster lung (CHL/IU) cells | |
| Test method | : | Guidelines for Screening Mutagenicity Testing of Chemicals (Japan) and OECD Guideline No. 473 | |
| Solvent | : | Dimethylsulfoxide | |
| Positive controls | : | -S9 mix, Mitomycin C +S9 mix, Cyclophosphamide | |
| Doses | : | -S9 mix (continuous treatment):0, 0.010, 0.020, 0.040 mg/ml -S9 mix (short-term treatment):0, 0.021, 0.041 mg/ml +S9 mix (short-term treatment):0, 0.021, 0.041, 0.081 mg/ml | |
| S-9 | : | Rat liver, induced with phenobarbital and 5,6-benzoflavone | |
| Plates/test | : | 2 | |
| GLP | : | Yes |
Test results:
With short-term treatment and an exogenous metabolic activation system, structural chromosomal aberrations (4.5%, including gap) were induced at 0.041 mg/ml (low concentration) and polyploidy (1.88%) at 0.081 mg/ml (high concentration). However, a trend test showed no dose dependency for the structural chromosomal aberrations. In a confirmation test, structural chromosomal aberrations (3.5%, including gap) were induced at 0.081 mg/ml (high concentration) and polyploidy (1.13%) at 0.041 mg/ml (mid concentration). However, a trend test showed no dose dependency for the structural chromosomal aberrations or the polyploidy.
Genotoxic effects:
| clastogenicity | polyploidy | |||||
| + | ? | - | + | ? | - | |
| Without metabolic activation: | [ ] | [ ] | [*] | [ ] | [ ] | [*] |
| With metabolic activation: | [ ] | [ ] | [*] | [ ] | [ ] | [*] |
| 1) | The tests were performed by the Research Institute for Animal Science in Biochemistry and Toxicology, 3-7-11 Hashimotodai, Sagamihara-shi, Kanagawa 229, Japan. Tel +81-427-62-2775 Fax +81-427-62-7979 |
| 2) | The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627 |