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Toxicological information

Acute Toxicity: oral

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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 OECD andf GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method

Test material

Constituent 1
Chemical structure
Reference substance name:
2'-methoxyacetoacetanilide
EC Number:
202-131-0
EC Name:
2'-methoxyacetoacetanilide
Cas Number:
92-15-9
Molecular formula:
C11H13NO3
IUPAC Name:
N-(2-methoxyphenyl)-3-oxobutanamide
Details on test material:
- Name of test material (as cited in study report): P0004 or Acetoacet-o-anisidide

Test animals

Species:
rat
Strain:
other: Crl:CD (SD) BR VAF plus
Sex:
male/female
Details on test animals or test system and environmental conditions:
weight range of 108 to 135 g; four to six weeks of age. All rats were acclimated to the experimental environment for a period of eight days prior to the start of the main study.
The rats were allocated to cages within the treatment groups. They were housed in groups of up to five rats of the same sex in metal cages with wire mesh floors.
A standard laboratory rodent diet (Biosure LAD1) and domestic quality potable water were provided ad libitum. Access to food only was prevented overnight prior to and approximately 4 hours after dosing.
The mean daily minimum and maximum temperatures of the animal room were 20 °C and 22°C respectively and the mean daily relative humidity value was 59% R.H. The rate of air exchange was maintained at apporoximately 15 air changes/hour. Lighting was controlled by means of a time switch to provide 12 hours artificial light in each 24-hour period.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Doses:
1260, 1600, 2000 mg/kg bw
No. of animals per sex per dose:
5 males
5 females
Control animals:
no
Statistics:
LD50 was calculated using the method of Finney (1971) Probit Analysis

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 637 mL/kg bw
Based on:
test mat.
95% CL:
1 423 - 1 911
Sex:
male
Dose descriptor:
LD50
Effect level:
1 638 mg/kg bw
Based on:
test mat.
95% CL:
1 350 - 2 011
Sex:
female
Dose descriptor:
LD50
Effect level:
1 635 mg/kg bw
Based on:
test mat.
95% CL:
1 326 - 2 053
Mortality:
male
1260 mg/kg bw.: 1/5
1600 mg/kg bw.: 3/5
2000 mg/kg bw.: 3/5

female
1260 mg/kg bw.: 0/5
1600 mg/kg bw.: 2/5
2000 mg/kg bw.: 5/5
Clinical signs:
Pilo-erection was observed in all rats within 10 minutes of dosing and troughout the remainder of day 1. This finding was accompanied on day 1 and/or at later intervals by: decreased respiratory rate, ptosis and pallor of extremities in all rats; abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, ataxia and collapsed state in a majority of rats.
Less commonly observed were:
increased lachrymation on day 2 only in rats dosed at 1260 and 2000 mg/kg; prostartion, preceding daeth, in rats dosed at 1600 mg/kg. Recovery, as judged by external appearance and behaviour was complete by day 3 in males dosed at 1260 mg/kg and rats dosed at 1600 mg/kg, day 4 in rats dosed at 2000 mg/kg and day 5 in female rats dosed at 1260 mg/kg bodyweight.
Body weight:
A slightly low bodyweight gain was recorded for one female rat dosed at 1260 mg/kg on day 8. All other rats that survived achieved anticipated bodyweight gains throughout the study.
Gross pathology:
Autopsy of the rats that died revealed pale kidneys, pale and patchy livers, congested lungs and congested blood vessels in the small intestine in two males and one female rat dosed at 2000 mg/kg, and a pale spleen and congested blood vessels in the large intestine in two male rats dosed at 2000 mg/kg bodyweight. No other macroscopic abnormalities were observed. Terminal autopsy findings in surviving rats were normal

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
LD50: 1635 mg/kg bw
Executive summary:

The acute median lethal oral doses (LD50) for the rat were estimated to be:

Male and female combined:       1637 mg/kg bw

Male:                                         1638 mg/kg bw

Female:                                      1635 mg/kg bw

Although Acetoacetanilide congeners are suspected to form methemoglobin no definite indications for MetHb formation were observed.