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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:
supporting study
Study period:
1958 or before
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study published in a peer-reviewed journal, according to scientific standards. Experimental details well documented, but no data on acclimatization and housing. Results: LD50 after 1,2,4 and 7 days, incl. statistical evaluation. Performed 1958, before GLP and OECD guidelines were introduced. Sufficient numbers of animals investigated, but only one sex (males). No necropsy reported for any animals that died during the study or were sacrificed thereafter.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Comparative pharmacological and toxicological evaluation of N-acetyl-p-aminophenol, salicylamide, and acetylsalicylic acid
Author:
Boxill GC, Nash CB & Wheeler AG
Year:
1958
Bibliographic source:
J. Am. Pharm. Assoc. Sci. Ed., 1958, 47, 479-487

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Principles of LD50 determination followed as described in guideline
Deviations:
yes
Remarks:
One sex only, no necropsy, no body weight development, no data on acclimatization and housing
GLP compliance:
no
Remarks:
GLP not available at study time
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
other: H L A
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 17-30 g
- Fasting period before study: 15-17 hours (study performed with and without fasting)
- Housing: no data
- Diet: ad libitum, except during 6-h observation period after application
- Water: ad libitum, except during 6-h observation period after application
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24.4 - 25.5

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 10% gum acacia suspension in water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: depending on dose (not stated)
- Amount of vehicle (if gavage): 10 - 30 ml / kg

MAXIMUM DOSE VOLUME APPLIED: 20 ml / kg

Doses:
4 doses to fasted animals, to calculate LD50, not individually stated
6 doses to non-fasted animals, to calculate LD50, not individually stated
No. of animals per sex per dose:
10 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days (for LD50 calculation), 21 days for some recovery experiments
- Frequency of observations: 6 d, 1, 2, 4, 7 d for LD50; no weighing
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Statistics:
Litchfield JT & Wilcoxon F, J. Pharmacol. Exptl. Therap. 96:99 (1949)

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
1 200 mg/kg bw
Based on:
act. ingr.
95% CL:
1 090 - 1 321
Remarks on result:
other: fasted animals, observation of mortality at 2, 4, and 7 days
Sex:
male
Dose descriptor:
LD50
Effect level:
1 210 mg/kg bw
Based on:
test mat.
95% CL:
1 077 - 1 355
Remarks on result:
other: fasted animals, observation of mortality at 1 day
Sex:
male
Dose descriptor:
LD50
Effect level:
1 500 mg/kg bw
Based on:
test mat.
95% CL:
1 340 - 1 679
Remarks on result:
other: non-fasted animals, observation of mortality at 7 days
Sex:
male
Dose descriptor:
LD50
Effect level:
1 590 mg/kg bw
Based on:
test mat.
95% CL:
1 355 - 1 867
Remarks on result:
other: non-fasted animals, observation of mortality at 1, 2, and 4 days
Sex:
male
Dose descriptor:
other: TD50 minimal neurological deficit dose
Effect level:
87 mg/kg bw
Based on:
test mat.
95% CL:
59.6 - 126.7
Remarks on result:
other: fasted animals, mean body weight 20.7 g, 24 h observation
Sex:
male
Dose descriptor:
other: TD50 minimal neurological deficit dose
Effect level:
142 mg/kg bw
Based on:
test mat.
95% CL:
107.7 - 187
Remarks on result:
other: non-fasted animals, mean body weight 20.8 g, 24 h observation
Clinical signs:
Ataxia, depression (progressing to hypnosis at higher doses). Labored respiration and cyanosis prior to death (result of respiratory failure). Either prolonged period of depression, or intermittent episodes of hyperactivity, coarse tremors, and convulsions after recovery from hypnosis. Occasionally (in some animals) bizarre motions (rapid vertical or horizontal movements of the head, rapid circular locomotion), with no recovery within 3 weeks.

Applicant's summary and conclusion

Conclusions:
Study conducted using non-preferred test species. Provided as supporting information.