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Administrative data

Description of key information

NOAEL (oral) = 500 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
500 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
This GLP study was performed according to OECD, EU and EPA guidelines.

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

- Repeated dose toxicity, oral:

4-phenylbutan-2-one is deemed to not show a classifiable specific target organ toxicity. One reliable study conducted according to OECD TG 407 and 408, EU Method B.7, EPA OPPTS 870.6050 and GLP in rats (Damme 2012) using 90-day oral (gavage) dose levels of 0, 55, 165, 250 and 500 mg/kg bw/day 4-phenylbutan-2-one. The minimal to moderate tubular degeneration/regeneration in the outer and inner cortex of male rats at 250 and 500 mg/kg bw/day was considered as specific effect in male rat which is no relevant to humans. Because the increased liver weight, centrilobular hepatocellular hypertrophy and hypertrophy in the thyroid gland were seen as adaptive process they were not interpreted as adverse effects. Therefore no adverse effects were seen in the study and therefore the NOAEL is 500 mg/kg bw/day. It is concluded that 4-phenylbutan-2-one does not need to be classified according to CLP Regulation.

In the supporting study conducted according to OECD TG 422 and GLP principles (Thorsrud 2003), the read across substance acetophenone was administered to rats via oral (gavage) at dose levels of 0, 75, 225 and 750 mg/kg bw/day. Due to systemic and neurologic effects observed at 750 mg/kg bw/day acetophenone dose (925 mg/kg bw/day 4-phenylbutan-2-one), the NOAEL was established at 225 mg/kg bw/day acetophenone (278 mg/kg bw/day 4-phenylbutan-2-one).

In the supporting subchronic oral (feeding) study (17-week) conducted in rats according to scientific principles (Hagan at al 1967), at dose levels of 0, 1000, 2500 and 100000 ppm of acetophenone, the NOEL was 100000 ppm. Assuming 400 g rat body weight and 30 mg food consumption per day, 100000 ppm corresponds to 750 mg/kg bw/day dose. In this feeding study, 31 % loss of acetophenone from laboratory animal diet during a 7-day period should be considered. Therefore the NOEL should be reduced to 518 mg/kg bw/day acetophenone (equivalent to 639 mg/kg bw/day 4-phenylbutan-2-one).

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

Only one reliable study is available.

Justification for classification or non-classification

- Repeated dose toxicity, oral:

Based on the above stated assessment of the specific target organ toxicity potential after repeated oral exposure of 4-phenylbutan-2-one, the compound does not need to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) or according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.

-Repeated dose toxicity, dermal:

Based on the oral data and skin/eye irritation data, the expert opinion is that classification according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) or according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU is not necessary.

 

-Repeated dose toxicity, inhalation:

Based on the oral data and skin/eye irritation data, the expert opinion is that classification according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) or according to CLP (Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU is not necessary.