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Administrative data

Description of key information

The results from an oral 28-day subacute repeated dose toxicity study showed that AC-6000 exerted effects on the liver. The NOAEL of AC-6000 in rats under the present study conditions was estimated to be 40 mg/kg bw/day due to increased relative liver weights and enlargement of the liver in males and females and centrilobular hypertrophy of the hepatocytes and increased relative kidney weights in males of the 200 mg/kg bw/day groups.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
40 mg/kg bw/day
Study duration:
subacute
Species:
rat

Mode of Action Analysis / Human Relevance Framework

Additional information

In a 28-day repeated oral dose toxicity GLP study according to OECD guideline 407 and EU method B.7, groups of five male and five female Crl: CD(SD) rats were dosed with AC-6000 (Hita Laboratory, 2007). The high dose was set at 200 mg/kg bw/day, and altogether 3 doses including 40 and 8 mg/kg bw/day were employed. Recovery groups were also set for the 200 mg/kg bw/day and vehicle control groups.

No death occurred in the dosing and recovery periods. In organ weights, relative liver weights were increased in males and females of the 200 mg/kg bw/day groups. In necropsy, enlargement of the liver was observed in males and females of the 200 mg/kg bw/day groups. In males of the 200 mg/kg bw/day group increased relative kidney weights were observed. In histopathological examinations, centrilobular hypertrophy of the hepatocytes was observed in males of the 200 mg/kg bw/day group. No abnormalities were noted in clinical signs, FOB, body weights, food consumption, hematology, blood chemistry and urinalysis.

In the recovery groups, mottled teeth were observed in males of the 200 mg/kg bw/day group. No abnormalities were noted in FOB, body weights, food consumption, hematology, blood chemistry, urinalysis and histopathology.

In conclusion, the effects of AC-6000 were observed in the liver and kidneys. Even though these effects are reversible, the NOAEL was considered to be 40 mg/kg bw/day due to increased relative liver weights and enlargement of the liver in males and females and centrilobular hypertrophy of the hepatocytes and increased relative kidney weights in males of the 200 mg/kg bw/day groups.


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

Justification for classification or non-classification

Based on the results of the subacute oral repeated dose toxicity study, classification according to EU Directive 67/584/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 is not needed.