4-isobutyl-2-methylbenzaldehyde

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-isobutyl-2-methylbenzaldehyde

Cas Number:

73206-60-7

Molecular formula:

C12H16O

IUPAC Name:

4-isobutyl-2-methylbenzaldehyde

Details on test material:

- Name of test material (as cited in study report): IBTAL
- Lot No.: 5N24
- Purity: 98.8%
- Description: Colorless and transparence liquid
- Storage conditions: Stored at room temperature (actual temperature: 18.5°C to 20.6°C; permissible range: 1°C to 30°C) in a tight container (filled with nitrogen)
- Expiration date: March 31, 2015

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc. (Hino Breeding Center)
- Age at study initiation: 9 weeks
- Weight at study initiation: Experiment 1: 190.5 to 202.3 g, Experiment 2: 181.5 to 201.5 g, Experiment 3: 205.1 to 208.3 g, Experiment 4: 206.2 to 209.8 g
- Fasting period before study: the day before administration (about 18.5 to 19.5 hours before dosing) to about 3 hours after dosing.
- Housing: four animals per cage during the quarantine and acclimatization periods, three animals per cage after the grouping, two animals per cage for the remaining animals; in stainless-steel cages on polymethylpentene floors (W × D × H: 220 × 380 × 195 mm); autoclave-sterilized wood chip bedding (White Flake, Charles River Laboratories Japan, Inc.); autoclave-sterilized nest materials (Paper Clean, Japan SLC, Inc.) were used for improvement of animal welfare and exchanged concurrently with the cage exchange.
- Diet: Autoclave-sterilized pellet diet (CRF-1, Oriental Yeast Co., Ltd.), ad libitum
- Water: Well water admixed with sodium hypochlorite (free residual chlorine concentration: about 2 ppm), ad libitum
- Acclimation period: 7 days for experiments 1 and 3, 11 days for experiment 2 and 14 days for experiment 4.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 24
- Humidity (%): 45.7 – 63.8
- Air changes (per hr): 10 - 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Lot/batch no. (if required): V3T2547, NACALAI TESQUE, INC.)

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Structurally similar analogs to the test substance were categorized as Category 4 or Unclassified of the Globally Harmonized System of Classification and Labelling of Chemicals (GHS). Therefore, the dose level for the experiment 1 was set at 300 mg/kg. The dose levels for the experiments 2 to 4 were respectively set at 300, 2000 and 2000 mg/kg.

Doses:

- Experiment 1 and 2: 300 mg/kg
- Experiment 3 and 4: 2000 mg/kg

No. of animals per sex per dose:

3 per experiment

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed before dosing and 30 minutes, 1, 3 and 5 hours after dosing on the day of administration, and thereafter, once daily for 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight (All animals were measured before dosing on Day 1 and on Days 2, 4, 8 and 15. In addition, the body weight gain between each day of measurement was calculated.)

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

2 500 mg/kg bw

Based on:

test mat.

Mortality:

- No deaths occurred in experiment 1, 2 or 3.
- In experiment 4, 1 animal died on Day 2.

Clinical signs:

- No abnormality was observed in any animal of experiment 1 or 2.
- In the experiment 3, 1 animal showed decrease in locomotor activity (grade: moderate), prone position and bradypnea on Day 2. These findings were not observed on Day 3 and thereafter.
- The animal that died showed abnormalities on Day 1 as follows: decrease in locomotor activity (grade: slight) and bradypnea at 3 hours after dosing and decrease in locomotor activity (grade: moderate), prone position and bradypnea at 5 hours after dosing. In another animal, the following findings were observed: decrease in locomotor activity (grade: slight) at 3 hours after dosing, decrease in locomotor activity (grade: slight) and bradypnea at 5 hours after dosing, and decrease in locomotor activity (grade: slight) on Day 2. No abnormality was observed in the animal on Day 3 and thereafter.

Body weight:

- A normal body weight increase was noted in all animals of experiments 1 and 2.
- In experiments 3 and 4, a decreased body weight or a suppressed body weight gain was noted in all animals between Day 1 and 2. On Day 4 and thereafter, no abnormality was noted in the body weight gain of any animals.

Gross pathology:

No abnormality was observed in any animal.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 was estimated to be 2500 mg/kg bw in females.

Executive summary:

In a GLP compliant acute oral toxicity study, in accordance with OECD Guideline 423 (acute toxic class method), female Crl: CD(SD) rats were exposed to the test substance via oral gavage. The dose levels were respectively set at 300, 300, 2000 and 2000 mg/kg for experiments 1 to 4. Three females were used in each experiment. After an observation period of 14 days animals were necropsied. No death occurred and no abnormality was noted in the clinical observation, body weight or necropsy in any animal of the experiment 1 or 2. One animal died in experiment 4 and abnormalities were noted in the experiments 3 and 4 as follows. In the clinical observation, decrease in locomotor activity, prone position or bradypnea was observed in 1 animal in the experiment 3 and 2 animals in the experiment 4 on Day 1 or 2. In the body weight, a decreased body weight or a suppressed body weight gain was noted in all animals between Day 1 and 2. On Day 3 and thereafter, no abnormality was noted in the clinical observation or body weight. All animals including the dead animal showed no finding in the necropsy. The LD50 was estimated to be 2500 mg/kg.