4'-methoxyacetoacetanilide

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:

1997

Report date:

1997

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:

4'-methoxyacetoacetanilide

EC Number:

226-615-6

EC Name:

4'-methoxyacetoacetanilide

Cas Number:

5437-98-9

Molecular formula:

C11H13NO3

IUPAC Name:

N-[4-(methoxyacetyl)phenyl]acetamide

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Olac Ltd, Shaw's Farm, Blackthorn, Bicester
- Age at study initiation: 5-7 weeks old
- Weight at study initiation:
-- male , mean: 192 g
-- female, mean: 156 g
- Fasting period before study: overnight prior to dosing
- Housing: in suspended polypropylene cages with stainless steel grid tops and bottoms
- Diet (e.g. ad libitum): Rat and Mouse No. 1 Maintenance Diet, supplied by Special Diets Services, 1 Stepfield, Witham, Essex, CM8 3AD, ad libitum
- Water (e.g. ad libitum): Domestic mains quality drinking water, ad libitum
- Acclimation period: for at least 5 days prior to commencement of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): maximum/minimum 20°C / 19°C
- Humidity (%): Although the mean humidity is outwith the range specified in the protocol, 55 % ± 15 %, it is considered not to have affected the outcome of the study.
- Air changes (per hr): 15-20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5%

Details on oral exposure:

VEHICLE

- Concentration in vehicle:

Dose level / Conc.
1250 / 125 mg/ml
1500 / 150 mg/ml
1750 / 175 mg/ml
2000 / 200 mg/ml

- Amount of vehicle (if gavage): 10 ml/kg bw

Doses:

1250, 1500, 1750 and 2000 mg/kg bw.

No. of animals per sex per dose:

4 groups of 5 male and 5 female rats were dosed

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
-- Body weights were recorded weekly
-- Animals were observed daily up to 14 days

- Necropsy of survivors performed: yes

- Other examinations performed:
-- clinical signs: yes
-- body weight: yes
-- organ weights: no
-- necropsy: yes

Statistics:

The intercept and slope values of the dose-response curve and hence the LD50, was estimated by applying the standard technique of maximum likelihood estimation to the probit model, as described in Finney (1971)

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

1 941 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

1 755 mg/kg bw

Based on:

test mat.

Mortality:

Dose / male / female
level

1250 / 0 of 5 / 0 of 5
1500 / 1 of 5 / 1 of 5
1750 / 1 of 5 / 1 of 5
2000 / 3 of 5 / 5 of 5

Clinical signs:

other: Clinical signs noted from Day 1 included ataxia, subdued behaviour, piloerection, prostration, tremors, hunched appearance, laboured breathing, increased salivation and a red discharge from the eyes and/or nose. Generally, the surviving animals recovered

Gross pathology:

None of the necropsy findings were considered to be related to treatment.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the median oral lethal doses (LD50s) for the test item in rats were estimated to be:
Males: 1941 mg/kg bw
Females: 1755 mg/kg bw
Males and Females: 1830 mg/kg bw

These findings meet criteria for a classification as acutely toxic according to REGULATION (EC) No 1272/2008:

Acute oral toxicity: Category 4

Executive summary:

This study investigated the acute oral toxicity potential and median oral lethal dose (LD50) of the test substance, after a single oral gavage administration to rats.

 

In the study, 4 groups of 5 male and 5 female rats were dosed with 1250, 1500, 1750 and 2000 mg/kg bw. Dosing solutions were administered via oral gavage at a dose volume of 10 ml/kg bw. The vehicle was 0.5% Carboxymethylcellulose. The animals were observed daily for reaction to treatment for up to 14 days after dosing. Following premature death or sacrifice, on Day 15, the animals were subjected to necropsy. Body weights were recorded weekly.

 

At 1250 mg/kg bw there were no premature decedents, at 1500 mg/kg bw, one male was found dead on Day 2 and 1 female was killed humanely on Day 2. At 1750 mg/kg bw, one male and 1 female were found dead on Day 2 and at 2000 mg/kg bw, one male was found dead on Day 1, and another 2 males were killed humanely, one on Day 1 and another on Day 2, all 5 females were killed humanely, three on Day 1 and two on Day 2.

 

Clinical signs noted from Day 1 included ataxia, subdued behaviour, piloerection, prostration, tremors, hunched appearance, laboured breathing, increased salivation and a red discharge from the eyes and/or nose. Generally, the surviving animals recovered by Day 4.

 

Body weight performance was considered to have been satisfactory.

 

None of the necropsy findings were considered to be related to treatment.