2H-Benzimidazole-2-thione, 1,3-dihydro-ar-methyl-, sodium salt (1:1)

Endpoint summary

Description of key information

MB2 (2-mercaptomethylbenzimidazole, CAS n° 53988 -10 -6):
Male and female rats were treated orally by gavage with 2-mercaptomethylbenzimidazole at doses of 0 (corn oil), 4, 20 and 100 mg/kg bw  for 28 consecutive days. Clinical signs, body weight, food consumption, organ weights, clinical biochemistry and hematological parameters were recorded and a histopathological examination was conducted.
ZMB2 (1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione, zinc salt, CAS n° 61617 -00 -3):
In a combined repeated-dose reproductive/developmental toxicity study,  2-mercaptomethylbenzimidazole, zinc salt was administered orally in the diet to rats (10/sex/dose) at 1000, 2750 or 7500 ppm (ca. 50, 138 or 375 mg/kg bw/d). These dose levels were reduced to 900, 2500 or 6750 ppm (ca. 45, 125 or 338 mg/kg bw/d) on day 29. On study day 33 the high dose level was further reduced to 5500 ppm (ca. 275 mg/kg bw/d). Signs of systemic toxicity, body weight, food consumption, blood chemistry and hematological parameters, organ weights and histopathological examinations were recorded.
No repeated dose studies for inhalation and dermal toxicity are available

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

4 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The materials/methods and results are described in detail und are sufficient for evaluation

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

MB2 (2-mercaptomethylbenzimidazole, CAS n° 53988 -10 -6):

In the 28 day repeated dose study the relative organ weights of lung, liver, kidney, and serum cholesterol and phospholipid significantly increased in male rats treated with MMBIs at doses of 20 and 100 mg/kg bw/d. Male rats administered 100 mg/kg bw/d exhibited a 1.8 fold increase in thyroid weight associated with histopathological changes but not altered serum thyroid hormone levels. Haematology and urine analysis were uneffected. Female rats administered 100 mg/kg bw/d MMBIs exhibited significant increases of liver and kidney but not thyroid weights and serum cholesterol levels.

Reproductive organs of the rats were examined histopathologically. No adverse effects were reported from these organs. Based on these results there are no indications for specific adverse effects on the reproductive organs up to 100 mg/kg bw/day.

The no-observed-effect levels for male and female rats were found to be 4 and 20 mg/kg bw/d, respectively.

ZMB2 (1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione, zinc salt, CAS n° 61617 -00 -3):

The administration of the substance to male and female rats at dose levels up to 7500 ppm (adjusted to 6750 ppm and then to 5500 ppm), for a period of up to 47 days, resulted in treatment-related toxic effects upon adults. A No Observed Adverse Effect Level (NOAEL) was not established.

The lowest-observed-adverse-level LOAEL (systemic) was 45 -50 mg/kg bw/day (based on decreased body weight gain).

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The most reliable study for the determinatin of a NOAEL was used as key study and for classification

Justification for classification or non-classification

The no-observed-effect level (NOEL) of MMBls, under the conditions of the present subacutce toxicity study, was evaluated to be 4 mg/kg, based on the significant increases of relative liver and kidney weights and serum levels of T-CHO (total cholesterol) at doses of 20 mg/kg and above for male rats, and the NOEL for female rats was 20 mg/kg.

MB2 (2-mercaptomethylbenzimidazole, CAS n° 53988 -10 -6):

In the low dose level of the 28 day study effects were obvious, but these effects are regarded as adaptive effects and not as severe effects.At the termination of the 2-wk recovery period, changes in the absolute organ weights were no longer apparent.

ZMB2 (1,3-dihydro-4(or 5)-methyl-2H-benzimidazole-2-thione, zinc salt, CAS n° 61617 -00 -3):

In the combined repeated-dose reproductive/developmental toxicity study, the administration of the substance to male and female rats

at dose levels up to 7500 ppm (adjusted to 6750 ppm and then to 5500 ppm ), for a period of up to 47 days, resulted in treatment-related toxic effects upon adults. A No Observed Adverse Effect Level (NOAEL) was not established.

The lowest-observed-adverse-level LOAEL (systemic) was 45 -50 mg/kg bw/day (based on decreased body weight gain).

Therefore based on the result of the oral 28 d repeated dose study (increased organ weights) and the combined repeat-dose reproductive/ developmental toxicity study which has similar results as the 28 d repeat dose study a classification as Xn; R48/22 (GHS: STOT Rep. 2; H373) is justified.