Isopropyl acetoacetate

Endpoint summary

Description of key information

The LD50 for acute oral toxicity of the test item in rats was determined to be greater than 2000 mg/kg bw (reference 7.2.1-1).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-01-13 to 1988-02-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987-02-24

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

1984-04-25

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG
- Females nulliparous and non-pregnant: not detailed
- Rationale for use of males: according to guideline followed for a limit test each 5 females and 5 males should be used
- Age at study initiation: female: ca. 7 weeks, males: ca. 8 weeks
- Weight at study initiation: female: 190 ± 2.1 g, males: 201 ± 7.7 g
- Fasting period before study: yes, ca. 16 h before study; additionally 3-4 h after application
- Housing: 5 animals per cage, Makrolon cages Typ 4 with wooden bedding
- Diet: ad libitum, rat diet Altromin 1324
- Water: ad libitum, tap water
- Acclimation period: at least 5 days
- Microbiological status when known
- Method of randomisation in assigning animals to test and control groups: accoring to schedule 931/87 and 1399/87

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): not detailed, but air condition in animal rooms
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: sesame oil (Oleum Sesami)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 %
- Amount of vehicle: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation: after 10, 30 min, 1, 2, 4, 6 h and afterwards once per day; weighing: once per week
- Necropsy of survivors performed: yes
- Examinations performed: clinical signs, body weight, macroscopic changes

Statistics:

no details provided

Preliminary study:

A preliminary study was performed with the test item at a concentration of 10 % in sesame oil. Doses of 500, 1000 and 2000 mg/kg bw were administered to each one female and male animal per dose group. They were observed for 14 days and body weight was recorded. All animals showed general signs of toxicity and difficulties with breathing. An increase of body weight was observed in all animals independent on dose group. All animals were sacrificed after observation period and no macroscopic changes were detected.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: Crouched position, retracted flanks, stalked and uncoordinated movement and uneven breathing were observed in animals of both sexes in the first hours and the first day after treatment. Starting from the second day after treatment no clinicals signs were

Gross pathology:

No macroscopic changes were detected.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral toxicity LD50 of the test item was greater than 2000 mg/kg bw in rats.

Executive summary:

The acute oral toxicity of the test item was assessed in a study according to OECD 401 in rats. Animals of both sexes, each 5, were treated with 2000 mg/kg bw by gavage. Afterwards animals were observed for 14 days. During this time no animals died and the body weight gain was not affected by treatment. The animals showed signs of toxicity such as crouched position, retracted flanks, stalked and uncoordinated movement and uneven breathing in the first hours and on the first day after treatment. From the second day after treatment onwards no clinical signs were observed. Macroscopic examination after sacrifice at the end of the observation period showed no changes. Based on the results of the study the LD50 for acute oral toxicity was determined to be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The study was conducted according to guideline and therefore is considered as reliable.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The acute oral toxicity of the test item was assessed in a study according to OECD 401 in rats. Animals of both sexes, each 5, were treated with 2000 mg/kg bw by gavage. Afterwards animals were observed for 14 days. During this time no animals died and the body weight gain was not affected by treatment. The animals showed signs of toxicity such as crouched position, retracted flanks, stalked and uncoordinated movement and uneven breathing in the first hours and on the first day after treatment. From the second day after treatment onwards no clinical signs were observed. Macroscopic examination after sacrifice at the end of the observation period showed no changes. Based on the results of the study the LD50 for acute oral toxicity was determined to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity, the test item does not require classification for acute toxicity via the oral route according to Regulation (EC) No 1272/2008 (CLP), as amended for the fifteenth time in Regulation (EU) 2020/1182.