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Acute Toxicity: oral

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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
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

Constituent 1
Chemical structure
Reference substance name:
3-methoxyacetophenone
EC Number:
209-573-3
EC Name:
3-methoxyacetophenone
Cas Number:
586-37-8
Molecular formula:
C9H10O2
IUPAC Name:
3-methoxyacetophenone
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 The feed was withdrawn the evening before the administration of the test substance and was offered again about 3 hours afterwards.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:
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 signs of reduced well-being (unspecific alterations, like sedation, apathy, piloerection, hunched posture or closed eyes), in single or multiple occurrence. All other animals were normal at any observation term.
Body weight:
All surviving animals gained weight in both weeks after administration.
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.