long chain alkyl thio carbamide metal complex

Endpoint summary

Description of key information

The subacute oral NOAEL is 300 mg/kg bw/day.
The subacute dermal NOAEL is 670 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

300 mg/kg bw/day

Species:

rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

670 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

No treatment-related systemic adverse effects were seen in a GLP 28-day repeated-dose dermal toxicity study of a substance structurally and chemically similar to EC# 457-320-2. The top dose used was 1,000 mg test material/kg bw/day, and the test material comprised 67% active substance. The NOAEL for systemic effects was therefore 670 mg/kg bw/day. (The NOAEL for local dermal irritation effects was 2 mL/kg of 5% solution, or 100 mg/kg bw/day).

No treatment-related systemic adverse effects were seen in a GLP 28-day repeated-dose oral toxicity study of the same substance structurally and chemically similar to EC# 457-320-2. An increase in liver weight was seen in treated animals, but there was no associated histopathology and the study personnel did not consider it to be a toxicologically-significant effect. The NOAEL was therefore 1,000 mg/kg bw/day, the top dose used.

A reproduction/developmental toxicity screening study in which EC# 457-320-2 was orally administered to male and female rats for up to 28 (males) or 45 (females) days at doses of 100, 300 and 1000 mg/kg bw/day is also available. Adverse behaviour/CNS-related findings of intermittent tremors, repetitive movement of mouth and jaws, excessive pawing and/or licking of the cage floor and/or walls (females only, beginning on study day 13), and/or head twitch were noted in the 1000 mg/kg bw/day animals. An increase in liver weight was also seen in 1000 mg/kg bw/day females. Based on these effects, the NOAEL was concluded to be 300 mg/kg bw/day.

Overall, therefore, the subacute repeat-dose oral NOAEL for EC# 457-320-2 is concluded to be 300 mg/kg bw/day.

Repeated dose toxicity: via oral route - systemic effects (target organ) neurologic: behaviour; neurologic: central nervous system

Justification for classification or non-classification

No treatment-related systemic toxicity was seen in the 28-day dermal toxicity study of a substance structurally and chemically similar to EC# 457-320-2, and the NOAEL was concluded to be 670 mg/kg bw/day. No hazard classifications are required based on this study.

The two repeat-dose oral studies available (28-day toxicity study and a reproduction/developmental toxicity screening study) identifed no consistent identifiable treatment-related toxic effects at dose levels that might necessitate classification for Specific Target Organ Toxicity (STOT-RE). Consequently, in accordance with CLP, no hazard classifications are proposed.