4-(4-methoxyphenyl)butan-2-one

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31.05.- 21.06.2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17th December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Principles of method if other than guideline:

Frambinon methyl ether

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-(4-methoxyphenyl)butan-2-one

EC Number:

203-184-2

EC Name:

4-(4-methoxyphenyl)butan-2-one

Cas Number:

104-20-1

Molecular formula:

C11H14O2

IUPAC Name:

4-(4-methoxyphenyl)butan-2-one

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females
- Age at study initiation: 7 weeks old
- Weight at study initiation: 170.9−181.5 g
- Fasting period before study: animals were fasted overnight, approximately 16 hours
- Housing: Stainless wire mesh cage (260W×350D×210H mm)
- Diet: ad libitum, pelleted rodent chow (Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C)
- Water: ad libitum, public tap water
- Acclimation period: 4 days after 3 days of quarantine (including health examiniation)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.4−23.3
- Humidity (%): 43.1−59.7
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark, 150-300 Lux

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 400 mg/mL
- Lot/batch no. (if required): MKBV2080V

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: due to the low expected toxicity of the test substance a starting dose of 2000 mg/kg was selected.

Doses:

2000 mg/kg

No. of animals per sex per dose:

Step 1: 3
Step 2: 3

Control animals:

no

Details on study design:

- Duration of observation period following administration:14 days
- Frequency of observations: all animals were observed for mortality, general condition and clinical signs 30 minutes after dosing and at 1, 2, 4 and 6 hours after dosing on Day 0 and once daily thereafter for 14 days (Day 1−Day 14)
- Necropsy of survivors performed: yes
- Other examinations performed: since no gross findings were observed at necropsy, histopathological examinations were not performed.

Statistics:

Statistical analysis was not performed. Mean scores and values are determined.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality

Clinical signs:

Abnormal gait was observed in three to four animals from 0.5 to 6 hours after dosing at 2000 mg/kg. A decrease of fecal volume was observed in five animals on Day 1, and it disappeared on Day 2. Therefore, the clinical signs were considered to be test substance-related effects.

Body weight:

A tendency for suppression of body weight gain was observed in three animals at 2000 mg/kg on Day 1. Then, normal body weight gain was observed in these animals from Day 3. Therefore, these changes were considered to be test substance-related effects.

Gross pathology:

No abnormal morphological findings were observed in any animal at 2000 mg/kg.

Any other information on results incl. tables

Individual Body Weights

Step/ Dose (mg/kg) Animal ID   Days after dosing   Gain (g)   0 1 3 7 14 0 ~ 14 Step 1 2000 2101 186.3 195.7 206.2 224.6 248.6 62.3 2102 182.3 193.9 206.1 222.9 247.6 65.3 2103 183.7 201.3 215.3 231.2 247.4 63.7 Mean 184.1 197.0 209.2 226.2 247.9 63.8 S.D. 2.0 3.9 5.3 4.4 0.6 1.5 N 3 3 3 3 3 3 Step 2 2000 2201 193.3 211.1 229.2 235.7 250.5 57.2 2202 185.9 195.4 214.6 220.7 227.8 41.9 2203 190.5 197.5 218.7 233.3 252.1 61.6 Mean 189.9 201.3 220.8 229.9 243.5 53.6 S.D. 3.7 8.5 7.5 8.1 13.6 10.3 n 3 3 3 3 3 3

 

Applicant's summary and conclusion

Conclusions:

Based on the result, the acute oral LD50 (rat) for the test item was determined to be >= 5000 mg/kg (cut-off).

Executive summary:

The purpose of this study was to assess the potential toxicity of the test item following a single oral dose administration to female Sprague-Dawley rats and to classify the test substance under the category of GHS classification. The study was performed according to OECD guideline 423 and under GLP.

Two dose groups of three females each were utilized as follows:

Groups 1 and 2 (Steps 1 and 2): 2000 mg/kg of the test substance

Steps 1−2: A dose of 2000 mg/kg was administered and then, there was no mortality (Step 1). A second dose of 2000 mg/kg was administered (Step 2).

All animals were monitored for clinical signs and body weight changes during the 14-day observation period after administration.
They were subjected to a gross necropsy at the end of the observation period.

There were no deaths of animals at 2000 mg/kg. Abnormal gait was observed in animals on the day of dosing at 2000 mg/kg. A decrease of fecal volume was observed in animals on Day 1, and it disappeared on Day 2. A tendency for suppression of body weight gain was observed in three animals at 2000 mg/kg on Day 1. Then, normal body weight gain was observed in these animals from Day 3. No test substance-related effects were observed in necropsy findings in any animal at 2000 mg/kg.

Based on the result of the acute oral toxicity study in Sprague-Dawley rats, the test substance was classified as Category 5 or Unclassified according to the GHS classification and the median lethal dose derived was: LD50 cut off ≥ 5,000 mg/kg b.w.