Indometacin

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Data source

Reference

Reference 1

Reference Type:

publication

Title:

A compilation of LD50 values in newborn and adult animals

Author:

Goldenthal, EI

Year:

1971

Bibliographic source:

Toxicology and Applied Pharmacology, 18: 185-207

Reference 2

Reference Type:

publication

Title:

Some peculiarities observed in the course of the acute toxicity of indomethacin

Author:

Tanev, G

Year:

1974

Bibliographic source:

Trudove na Nauchnoizsledovatelskiya Khimikofarmatsevtichen Institut, Vol. 9: 275-282

Reference 3

Reference Type:

publication

Title:

Gastrointestinal effects and acute toxicity of suprofen

Author:

Niemegeers CJE et al.

Year:

1975

Bibliographic source:

Drug Research, 25: 1537 - 1542

Reference 4

Reference Type:

publication

Title:

Indomethacin: Lack of effect on lethality of endotoxin in rats

Author:

Reichgott, MJ et al.

Year:

1975

Bibliographic source:

Circulatory Shock, Vol. 2: 215-219

Reference 5

Reference Type:

publication

Title:

Unnamed

Year:

1981

Reference 6

Reference Type:

review article or handbook

Title:

Clinical Toxicology of Commercial Products, 5th Edition

Author:

Gosselin, RE , RP Smith, HC Hodge (Editors)

Year:

1984

Bibliographic source:

Williams & Wilkins, Baltimore, USA, page II-402

Reference 7

Reference Type:

publication

Title:

A national validation study of the acute toxic class method - an alternative to the LD50 test

Author:

Schlede, U et al.

Year:

1992

Bibliographic source:

Archives of Toxicology, 66: 455-470

Reference 8

Reference Type:

publication

Title:

The effects of suprofen in rats with Mycobacterium butyricum-induced arthritis

Author:

Awouters, F et al.

Year:

1975

Bibliographic source:

Arzneimittelforschung, 25 (10): 1526 - 1537

Materials and methods

Principles of method if other than guideline:

(single) dosing of male and female rodents (mice, rats)

GLP compliance:

not specified

Test type:

other: acute toxicity, different species, different dose routes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Indometacin

EC Number:

200-186-5

EC Name:

Indometacin

Cas Number:

53-86-1

Molecular formula:

C19H16ClNO4

IUPAC Name:

2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid

Administration / exposure

Control animals:

not specified

Results and discussion

Any other information on results incl. tables

Species (Strain)	Route of Administration (Vehicle)	Gender	LD50 (mg/kg bw)	Remarks	Reference
Rat (Sprague Dawley)	Oral (n.s.)	n.s.	12 (10-14)		Goldenthal (1971)
Rat	Oral	n.s.	3300	Pathogenetic mechanism for acute death: central origin	Tanev (1974)
Rat	Oral (diet)	n.s.	2.42 (1.75 – 3.36) Calculated value from 14-day feeding study	Indomethacin was used as comparator in a desease model (experimentally induced arthritis) and given in the feed (approximate daily doses of 0.04, 8.08, 0.16, 0.31, 0.63, 1.25, 2.5 and 5 mg/kg). 3 animals with adjuvant arthritis per dose group, treatment for 14 days	Awouters et al. (1975)
Rat	Oral (n.s..)	n.s.	19		Niemegeers et al. (1975)
Rat (Sprague Dawley)	Oral (12% alcohol 0.6 M phosphate buffer pH8; final concentration 1.5 mg/mL)	M	> 10 mg/kg bw: (no mortality at 10 mg/kg)	Post administration observation period: 24 hours	Reichgott et al. (1975)
Rat (Sprague Dawley)	Oral	M       F	51.0 (38.7 – 67.8)       51.0 (38.7 – 67.8)	Death within 2 to 6 days; clinical signs: decreased spontaneous movement, diarrhea, emaciation;: at necropsy: atrophy of thymus, gastrointestinal ulcers, ascites, perforation peritonitis, intestinal adhesion, swelling of adrenal and mesenterial lymph nodes	Okubo, M. et al (1981)
Rat/guinea pig	Oral (n.s.)	n.s.	12 (in rats) to 540 (guinea pigs)	Toxic signs: decreased activity, moderate decrease in respiratory rate (all species except dogs), ulceration of gastrointestinal tract; in dogs blanching of gums, diarrhea, emesis, occult blood in feces. Humans after overdose (either 775 or 1550 mg): lethargic, stuporous, mildly confused, vital signs normal, complete recovery after 24 hours; gastrointestinal ulceration and hemorrhage are possible consequences but have not been describe in man	Gosselin et al. (1984)
Rat (Wistar)	Oral (n.s.)	M + F	> 25 and < 200   (2 laboratories)   ≤ 25   (4 laboratories)	Validation study for Acute toxic class method, observation for at least 14 days after admin. (in 6 laboratories) Toxicity signs (seen in at least 2 of 6 laboratories): apathy, tremor, respiratory dyspnoe, cyanosis, hunched posture, diarrhoea; at necropsy: discoloration and congestion of liver, lung, kidneys and adrenals, edema of the lung, fibrinopurulent peritonitis, bloody imbibition of gastro-intestinal tract, partly with ulcers, ascites, hydrothorax	Schlede et al. (1992)
n.s. : not specified; M: male; F: female