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Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
43 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
GLP-compliant study with Klimish 1.

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

In a GLP 13 -week repeated dose oral toxicity study conducted according to the OECD Guideline 408, CHIMEXANE HB was administered in the diet to groups of Sprague-Dawley, Rj Han: SD, rats (10/sex/dose) at the target doses of 50, 150 and 450 mg active content/kg bw/day.

CHIMEXANE HB did not induced any deaths nor clinical signs. However, some signs of nephrotoxicity were observed at 150 (7/10 females and 1/10 males) and 450 (all animals) mg active content/kg bw/day.They consisted at urinalysis of lower urine pH, differences in urine turbidity and color, and of trace levels of bilirubin and proteins in urine. At necropsy, higher relative kidney weights were noted, associated with microscopic changes (vacuolar degeneration in the tubules of the inner cortex, inflammatory mononuclear cell infiltration and/or increased tubular basophilia).

Under these test conditions, the No Observed Adverse Effect Level (NOAEL) of CHIMEXANE HB was considered to be 43 and 47 mg active content/kg bw/day for males and females, respectively (target dose-level: 50 mg active content/kg bw/day).

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

The study with the longest duration (90-days) and the lowest NOAEL was chosen (key study).

Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: kidneys

Justification for classification or non-classification

As the submission substance (i.e., the active content of Chimexane HB) has a NOAEL in the range 10 -100 mg/kg bw/day in a subchronic toxicity study, it is classified STOT-RE Category 2 according to the CLP Regulation (EC) N°1272/2008. However, as no nephrotoxicity was observed at doses <50 mg/kg bw/day, it is not classified according to the Annex VI to the Directive 67/548/EEC.