Registration Dossier
Registration Dossier
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EC number: 208-494-1 | CAS number: 530-78-9
Endpoint summary
Administrative data
Description of key information
No internal acute toxicity studies were conducted with Flufenaminsäure.
Results of acute toxicity studies with Flufenaminsäure (Flufenamic acid) are cited in RTECS database and were found in literature (Nov 2011):
Oral (rat): LD50 = 249 mg/kg
(Archives Internationales de Pharmacodynamie et de Therapie (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- v. 221, p. 132, 1976 (AIPTAK))
Oral (rat): LD50 = 400 mg/kg (male), 410 mg/kg (female)
Oral (mouse): LD50 = 490 mg/kg (male), 500 mg/kg (female)
(Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- v.16, p. 1011, 1978 (OYYAA2))
Oral (rat): LD50 = 595 mg/kg
Oral (mouse): LD50 = 1110 mg/kg
Oral (guinea pig): LD50 = 925 mg/kg
(Pharmacology: International Journal of Experimental and Clinical Pharmacology. (S. Karger AG, Postfach CH-4009 Basel, Switzerland) V.1- 1968- v.11, p. 220, 1974 (PHMGBN))
Oral (rat): LD50 = 300 mg/kg (male)
Oral (mouse): LD50 = 590 mg/kg (male)
(Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- v.18, p. 845, 1979 (OYYAA2))
Oral (rat): LD50 = 272 mg/kg (male), 718 mg/kg (female)
Oral (mouse): LD50 = 550 mg/kg (male), 1047 mg/kg (female)
(Arzneimittel-Forschung/Drug Research, v.27(I), no. 6b, p.1333, 1977)
Oral (rat): LD50 = 395 mg/kg
Oral (mouse): LD50 = 940 mg/kg
(Journal of the Medicinal Society of Toho University, v.17(2), p. 153, 1970)
sc (rat): LD50 = 280 mg/kg (male)
sc (mouse): LD50 = 620 mg/kg (male)
(Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- v.18, p. 845, 1979 (OYYAA2))
ip (rat): LD50 = 185 mg/kg (male), 190 mg/kg (female)
ip (mouse): LD50 = 245 mg/kg (male), 255 mg/kg (female)
(Oyo Yakuri. Pharmacometrics. (Oyoy Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- v.16, p. 1011, 1978 (OYYAA2))
ip (mouse): LD50 = 150 mg/kg
(National Technical Information Service...
iv and im see discussion
Key value for chemical safety assessment
Additional information
The acute oral toxicity of Flufenamic acid was studied in rats, mice and guinea pigs.
The acute oral LD50 for rats was determined to lie in between 249 mg/kg and 718 mg/kg. No other effects than the lethal dose value were reported.
The acute oral LD50 for mice was determined to lie in between 409 mg/kg and 1110 mg/kg. Within one study behavioral effects (such as changes in the motor activity (measured in a specific assay) and ataxia) and respiratory depression were reported (Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- v.16, p. 1011, 1978 (OYYAA2)). No other effects than the lethal dose value were reported in the other studies.
The acute oral LD50 for guinea pigs was determined to be 925 mg/kg. No other effects than the lethal dose value were reported.
Administration of two consecutive single doses of Flufenamic acid spaced at an interval of 15 h to guinea pigs (dose levels: 50, 100, 200 and 400 mg/kg) and rats and mice (dose levels: 25, 50, 100 and 200 mg/kg) resulted in ulcerations of the gastrointestinal tract. Rats proved to be more vulnerable since already at 25 mg/kg 50% of the animals showed ulcers whereas in mice at 100 mg/kg 3/10 animals and at 200 mg/kg 5/10 animals and in guinea pigs at 200 mg/kg 1/6 animals and at 400 mg/kg 4/6 animals showed such effect
(Pharmacology: International Journal of Experimental and Clinical Pharmacology. (S. Karger AG, Postfach CH-4009 Basel, Switzerland) V.1- 1968- v.11, p. 220, 1974 (PHMGBN)).
The acute subcutaneous toxicity of Flufenamic acid was studied in rats and mice.
The acute subcutaneous LD50 was determined to be 280 mg/kg for rats and 620 mg/kg for mice. In both species adverse effects such as antipsychotic effects, gastrointestinal hypermotility and diarrhea as well as weight loss and decreased body weight gain were reported (Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- v.18, p. 845, 1979 (OYYAA2)).
The acute intraperitoneal toxicity of Flufenamic acid was studied in rats and mice.
The acute intraperitoneal LD50 was determined to be 185 mg/kg for male rats and 190 mg/kg for female rats. Within the study behavioral effects (such as changes in the motor activity (measured in a specific assay) and ataxia) and respiratory depression were reported (Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- v.16, p. 1011, 1978 (OYYAA2)).
The acute intraperitoneal LD50 for mice was determined to lie in between 150 mg/kg and 245 (male) or 250 mg/kg (female). Within one study behavioral effects (such as changes in the motor activity (measured in a specific assay) and ataxia) and respiratory depression were reported (Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- v.16, p. 1011, 1978 (OYYAA2)). Within the other study no other effects than the lethal dose value were reported (National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. AD691 -490)
The acute intravenous toxicity of Flufenamic acid was studied in rats and mice.
The acute intravenous LD50 was determined to be 98 mg/kg for rats (Current Medical Research and Opinion. (Clayton-Wray Pub. Ltd., 1a High St., Alton, Hants., UK) V.1- 1972- v.4, p.17, 1976 (CMROCX)) and 158 mg/kg for mice (Yakugaku Zasshi. Journal of Pharmacy. (Nippon Yakugakkai, 2 -12 -15 Shibuya, Shibuya-ku, Tokyo 150, Japan) No.1- 1881- v.89, p. 1392, 1969 (YKKZAJ)). No other effects than the lethal dose value were reported.
The acute intramuscular LD50 was determined to be 500 mg/kg for mice (Pharmaceutical Chemistry Journal (English Translation), Translation of KHFZAN. (Plenum Pub. Corp., 233 Spring St., New York, NY 10013) No.1- 1967- v.17, p. 353, 1983 (PCJOAU)). The substance is described as active as anti-cancer agent.
Additionally to the discussed LD50 values some lowest published toxic doses (TDLo) are cited in RTECS (Nov 2011):
In rats the intravenous TDLo is reported to be 250 mg/kg with observed liver changes and an effect on inflammation or a mediation of inflammation (Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958- v.67, p. 2141, 2004 (BCPCA6)).
In rats the intraperitoneal TDLo is reported to be 5 mg/kg with observed analgesia (Biorganic & Medicinal Chemistry. (Elsevier Science, The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK) V.1- 1993- v.12, p. 4169, 2004 (BMECEP)).
The oral TDLo in rats is 10 mg/kg for signs such as analgesia and 100 mg/kg for signs such as ulceration or bleeding from stomach
(Biorganic & Medicinal Chemistry. (Elsevier Science, The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK) V.1- 1993- v.12, p. 4169, 2004 (BMECEP)).
Justification for classification or non-classification
Based on the study results and based on the possible methemoglobin-forming property observed in repeated oral dose toxicity studies
Flufenamic acid has to be classified according to Directive 67/548/EEC and Regulation (EC) No. 1272/2008 (CLP) as toxic if swallowed (T, R25) and as acute oral toxic, category 3 (H301).Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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