Pentane-2,4-dione

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Adopted according to OECD SIDS (publicly available peer reviewed source). Original document not available.

Data source

Reference

Reference 1

Reference Type:

secondary source

Title:

Unnamed

Year:

2001

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1979

Materials and methods

Principles of method if other than guideline:

First experiment: 5 Rats per dose group were dosed with 0, 100, 500, or 1000 mg/kg bw of 2,4-pentanedione by gavage once a day. The doses were administered 1 to 11 times over a 1-15 day period. Controls received distilled water. In the 100 mg/kg bw dose group a 11th (lethal) dose of 1000 mg/kg bw was given.
Second experiment: An additional group of 5 male rats received 100 mg/kg bw of 2,4-pentanedione ten times over a 14 d period. 5 male control animals received 100 mg/kg bw of distilled water.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Details on test material:

Purity: ca. 100%

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

1-15 days

Frequency of treatment:

1-11 applications

Doses / concentrations

Remarks:

Doses / Concentrations:
100, 500, 1000 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

5 rats per dose

Control animals:

yes, concurrent vehicle

Results and discussion

Results of examinations

Details on results:

First experiment:
1000 mg/kg bw: rapid onset of dyspnea and depression followed by prostration and death of all rats within 1 h after first dosing; no 2,4-pentanedione related changes at autopsy.
500 mg/kg bw: like high dose rats except that tremors and ataxia were observed; 3/5 rats died and 2/5 were sacrificed due to poor condition after 4 applications. Autopsy: 2/5 rats with poor haircoats, 1/5 distended bladder, congested lungs, clouding of cornea; histopathology: thymic necrosis (4/5), hepatocytes swelling and hepatic congestion (3/5), nephrosis (1/5), lymphadenitis in inesenteric lymph nodes (2/5), inflammation of the heart (3/5).
100 mg/kg bw: slight depression after applications (persisted 24 h in one rat which developed head tilt to the left side). All rats died after the final application of 1000 mg/kg or were sacrificed in moribund state. Histopathologically no 2,4-pentanedione related changes.

Second experiment: no differences between the 100 mg/kg dose group and the control group with regard to clinical signs, weight gain, hematology, clinical chemistry, organ weights, gross pathology and histopathology.

Effect levels

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: No mortality occurred and no clinical signs were observed.

Target system / organ toxicity

Critical effects observed:

not specified