Benzimidazole-2-thiol

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

A reliable secondary source, summaring 2-mercaptobenzimidazole properties, was used. However, the primary sources were not revisited in order to verify their contents; for this reason reliability score 2 was used. The used secondary source has been updated on 2012; therefore it covers the most updated literature on the substance.

Data source

Reference

Reference Type:

secondary source

Title:

2-Mercaptobenzimidazole

Year:

2012

Bibliographic source:

Japan Existing Chemical Data Base (JECDB)

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Guideline for the 28-Day Repeat dose toxicity test of chemicals (Japan)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Benzimidazole-2-thiol

EC Number:

209-502-6

EC Name:

Benzimidazole-2-thiol

Cas Number:

583-39-1

Molecular formula:

C7H6N2S

IUPAC Name:

1H-benzimidazole-2-thiol

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Duration of treatment / exposure:

28 days

No. of animals per sex per dose:

Males, 10 or 15 (0, 40 mg/kg)
Females, 10 or 15 (0, 40 mg/kg)

Results and discussion

Effect levels

Dose descriptor:

NOEL

Effect level:

< 1.2 mg/kg diet

Based on:

test mat.

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

One female receiving 40 mg/kg died on Day 24 of the administration. Suppression of body weight gain was found in males given 12 mg/kg from Day 18, in males given 40 mg/kg from Day 11 and in females given 40 mg/kg from Day 15 of the administration. Lower than normal body weights were continuously obtained for both sexes receiving 40 mg/kg during the recovery period. Lower food consumption was noted for males given 12 mg/kg from Week 2 and for both sexes given 40 mg/kg from Week 1. Lower food consumption values were also continuously obtained for both sexes given 40 mg/kg during the recovery period. Increased urine volume was noted in males given 40 mg/kg, and lower values for urinary specific gravity in males receiving 12 mg/kg or more. Both retuned to normal during the recovery period. On hematological examination, the following changes were found : lower values for platelet and reticulocyte counts and higher MCHC values in males given 12 mg/ kg or more and in females given 40 mg/kg, lower MCV values in males given 12 mg/kg or more, lower RBC counts in females given 12 mg/kg or more, lower values for HCT and prolonged PT in both sexes receiving 40 mg/kg, prolonged APTT in males given 40 mg/kg, and lower WBC counts in females given 40 mg/kg. After the recovery period, lower HCT values and RBC counts were also found in both sexes given 40 mg/kg and in the high dose, respectively, and lower RBC, HGB and WBC count receiving were newly found in males, both sexes and males, respectively, 40 mg/kg. On blood chemical analysis, the following changes were found : lowered values of K in both sexes given 4 mg/kg or more, lowered Ca in males given 4 mg/kg or more, lowered Cl and GOT in both sexes given 12 mg/kg or more, higher TP, BUN, CRE and T-CHO in males receiving 12 mg/kg or more and in the 40 mg/kg females, higher values for γ-GTP and ALB in both sexes given 40 mg/kg, lower values for α2-globulin, and β-globulin TG and IP in males given 12 mg/kg or more, higher values for albumin, the A/G ratio and T-Bil in males receiving 40 mg/kg, higher GLU in females given 40 mg/kg and elevated Na in females receiving 12 mg/kg or more. After the recovery period, decreased GOT and b-globulin were also found in males receiving 40 mg/kg, and increased Na was newly found in males of the same group. Enlargement of thyroids was found in both sexes receiving 4 mg/kg or more at necropsy, and also after the recovery period. Higher values for absolute and relative thyroid weights were found in males receiving 4 mg/kg or more and in females given 12 mg/ kg or more. After the recovery period, elevated values for both parameters were still found, albeit to a lesser extent, in both sexes given 40 mg/kg. On histopathological examination, both sexes receiving 1.2 mg/kg or more showed hyperplasia/hypertrophy of follicular cells in the thyroids. Animals receiving 40 mg/kg showed vacuolization of cortical cells in the adrenal glands. The histopathological changes in the thyroids and adrenal glands were still present although weaker in degree after the recovery period. Based on the above results, we conclude that 2-mercaptobenzimidazole affects the thyroids, hematopoietic functions, and hepatic functions, renal functions. NOELs of 2-mercaptobenzimidazole for 28-day repeat dose oral administration are considered to be less than 1.2 mg/kg for both sexes under the conditions of the present study.

Applicant's summary and conclusion

Conclusions:

According to Directive 67/548/EEC and to Regulation (EC) n. 1272/2008, the substance should be classified for specific target organ toxicity after repeated exposure.