N-(2-methoxy-5-methylphenyl)acetamide

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: well performed GLP and OECD guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-(2-methoxy-5-methylphenyl)acetamide

EC Number:

230-157-2

EC Name:

N-(2-methoxy-5-methylphenyl)acetamide

Cas Number:

6962-44-3

Molecular formula:

C10H13NO2

IUPAC Name:

N-(2-methoxy-5-methylphenyl)acetamide

Details on test material:

- Name of test material (as cited in study report): Acetkresidin 34 TTRS, (N-(2-methoxy-5-methylphenyl)acetamide)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, breeding colony
- Age at study initiation: males approx. 7 weeks; females: approx. 8 weeks
- Weight at study initiation: males, mean: 176 g; females, mean: 179 g
- Fasting period before study: 16 hours
- Housing: fully air conditioned rooms in Makrolone cages on soft wood granulate in groups of 5 animals
- Diet: Altromin 1324 rat diet, ad libitum
- Water: tap water in plastic bottles, ad libitum
- Acclimation period: not necessary, breeding at identical conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-3
- Humidity (%): 55 +/-20
- Photoperiod: 12hrs dark / 12 hrs light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 16, 20, 25, or 31.5% (w/v)
- Justification for choice of vehicle: Stability and homogeneity of the test substance was determined and guaranteed for 4 h
- Purity: Oleum sesame Ph Eur. III

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

Doses:

males: 1600, 2000, 2500, 3150 mg/kg bw
females: 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: twice a day
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes

Statistics:

The LD50, the 95% limits of confidence and the equation of the probit-line were established on the basis of the lethality rates by probit analysis. (method of Fieller and Sidak)

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

2 240 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: limit test

Mortality:

Dose (mg/kg bw)/ male / female
1600 / 1 of 5 / not tested
2000 / 3 of 5 / 1 of 5
2500 / 2 of 5 / not tested
3150 / 4 of 5 / not tested

Clinical signs:

other: Squatting posture, sunken flanks, decreased spontaneous activity, bristling coat, stilted, uncoordinated or ataxic gait, forward crawling, irregular respiration, decreased and increased respiratory rate as well as panting, narrow palpebral fissures, clear

Gross pathology:

Macroscopic examination of the animals foud dead: liver discoloured light, lung discoloured red, stomach filled with test substance, intestinal tract filled with reddish-black mass or yellowish mucous mass, urinary bladder filled with orange liquid.

The animals killed at the end of the observation period showed no macroscopically visible changes.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

LD50 male: 2240 mg/kg bw
LD50 female: >2000 mg/kg bw

Executive summary:

Acute oral toxicity of Acetkresidin 34 TTRS was tested in Wistar rats according to OECD 401. Following this protocol the following median lethal dose values (LD50) were determined:

Male animals: 2240 mg/kg bw

The female animals did not show a higher sensitivity to the test substance.

Lethality occurred up to day 3 of the study.

Beside unspecific symptoms the animals showed impairments of motility, respiration and reflexes. Additionally clear, colourless or blood coloured lacrimation, narrowed palpebral fissures, blood-encrusted lid margins, prone or lateral position, reduced body surface temperature, stupor and narcosis were observed. Furthermore the bedding was discoloured orange. On day 7 of the study the surviving animals were free of symptoms.

Development of body weight was not impaired.

The animals found dead showed discolourations of lung and liver, test compound in the stomach, reddish-black or yellowish mucous mass in the intestinal tract and orange coloured liquid in the urinary bladder.

The animals killed at the end of the observation period were free of macroscopically visible changes.