3-methoxyacetophenone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From February 6th to February 27th, 2007.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-methoxyacetophenone

EC Number:

209-573-3

EC Name:

3-methoxyacetophenone

Cas Number:

586-37-8

Molecular formula:

C9H10O2

IUPAC Name:

1-(3-methoxyphenyl)ethan-1-one

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: BASF SE, Lot A0159430
- Expiration date of the lot/batch: not specified

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient temperature, under N2, protected from light and air.
- Stability under test conditions: stable.
- Solubility and stability of the test substance in the solvent/vehicle: the test item was soluble in corn oil.

Test animals

Species:

rat

Strain:

other: Crl:(WI)BR

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, D-97633 Sulzfeld.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Approximately 8 weeks at the time of the test substance administration.
- Weight at study initiation: group 1 mean 185.0g (SD = 12.3), group 2 mean 191.0g (SD =5.3), group 3 mean 188.3 (SD = 1.1)
- Fasting period before study: yes. The feed was withdrawn the evening before the administration of the test substance and was offered again about 3 hours afterwards.
- Housing: Single caging in Makrolon cages type III (39 cm x 23 cm bottom area, 18 cm height). Wire mesh lids. Sanitation of cages once a week. Bedding of aspen wood chips (1 change per week).
- Diet (e.g. ad libitum): Altromin 1324 forte, gamma irradiated with 25 kGy 60Co, ad libitum (Producer: Altromin GmbH, D-32791 Lage).
- Water (e.g. ad libitum): Tap water from an automatic watering system, ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average of 21.9 °C (continuous control and recording).
- Humidity (%): Average of 51.6 % (continuous control and recording).
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 h dark / 12 h light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): for the high dose group (2000 mg/kg bw), the test item was administered undiluted; for group 2 and 3 (300 mg/kg bw), the dose administered to the animals was 5 mL/kg bw.
- Justification for choice of vehicle: the test item was not soluble in water, but was soluble in corn oil.

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: starting dose of 2000 mg/kg bw indicated by the sponsor.

Doses:

step 1: 2000 mg/kg bw, step 2: 300 mg/kg bw, step 3: 300 mg/kg bw.

No. of animals per sex per dose:

3 animals per group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights: before administration, surviving animals 7 and 14 days after the administration (p.a.); clinical observations: at least once per day; Necropsy: Surviving animals were sacrificed and necropsied 14 days p.a. Deceased animals were necropsied as soon as possible.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 300 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

In the first group (2000 mg/kg bw dose), all animals died on the day of test item administration. In the second and third groups (300 mg/kg bw dose), all animals survived until the scheduled termination of the study.

Clinical signs:

other: All animals dosed with 2000 mg/kg body weight, were affected with central nervous effects: Unconsciousness. The finding had an onset shortly after the administration and lasted until death. As for the animals dosed with 300 mg/kg bw, 1/6 animals showed si

Gross pathology:

Abnormal findings were present only in deceased animals, treated with 2000 mg/kg bw: Gastric ulcers or erosion, blood within the intestinal lumen and a systolic heart arrest.
Cardial/circulatory failure may have been the cause of death. All other animals did not show any abnormal findings.

Any other information on results incl. tables

Table 1. Summary of results.

Dose (mg/kg)	Step No.	No. of animals			Prominent findings
		Exposed	Affected	deceased	in life	post mortem
2000	1	3	3	3	unconsciousness	systolic heart arrest; glandular stomach, mucosa, ulcera or erosion; small intestine, blood in the lumen
300	2	3	1	0	signs of reduced well-being	none
300	3	3	0	0	none	none

Table 2: Time of death

Dose (mg/kg)	Step No.	Animal Nos.	Time of death (p.a.)
2000	1	171 172 173	4.75 h 1 h 2.25 h
300	2	161 - 163	animals survived
300	3	164 - 166	animals survived

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

EU criteria

Conclusions:

The test item has an acute oral LD50 > 300 - 2000 mg/kg bw in rats, under test conditions.

Executive summary:

The potential acute toxicity of the test item was studied according to OECD 423, under GLP conditions. The test was performed by stepwise dosing to groups of 3 females each, at test item concentrations of 2000 mg/kg bw (step 1) and 300 mg/kg bw (steps 2, 3). All animals dosed with 2000 mg/kg bw were unconscious and died the day of administration. Upon necrosis, they showed systolic heart arrest; glandular stomach, mucosa, ulcera or erosion; small intestine, and blood in the lumen. All animals dosed with 300 mg/kg bw survived until the end of the test, and no abnormal conditions upon necrosis. Based on the test results, the test item has an acute oral LD50 > 300 - 2000 mg/kg bw in rats.