Registration Dossier

Administrative data

Description of key information

Intramuscular (rabbit, non-GLP, dose: 5 mg/kg): LD50 >5 mg/animal
(Schering AG, Report dated 1969-06-04)
Additionally, results of acute toxicity studies with hydrocortisone-21-acetate are cited in RTECS database (Feb 2010):
Subcutaneous, (rat); LDLo: 250 mg/kg
(Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- v. 27, p. 2102, 1977 (ARZNAD))
Intraperitoneal, (mouse); LD50: 2300 mg/kg
(Compilation of LD50 Values of New Drugs. (J.R. MacDougal, Dept. of National Health and Welfare, Food and Drug Divisions, 35 John St., Ottawa, Ont., Canada) (CLDND*))
Subcutaneous, (mouse); LD50: 45050 ug/kg
(National Cancer Institute Screening Program Data Summary, Developmental Therapeutics Program. (Bethesda, MD 20205) JAN1986 (NCISP*))
Oral, (mouse); LD50: 3267 mg/kg
(Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown v. (2), p. 42, 2002 (TOVEFN))
Oral, (rat); LD50: 5000 mg/kg
(Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown v. (2), p. 42, 2002 (TOVEFN))
Dermal, (rat); TDLo: 5 mg/kg
(Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown v. (2), p. 42, 2002 (TOVEFN))
Inhalation, (rat); TCLo: 0.62 mg/m3/4H
(Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown v. (2), p. 42, 2002 (TOVEFN))

Key value for chemical safety assessment

Additional information

Single intramuscular application of 5 mg ZK 5192 to 6 male rabbits did not results in any treatment-related findings: LD50 >5 mg/animal [Schering AG, Report dated 1969-06-04]

Additionally, results of acute toxicity studies with hydrocortisone-21-acetate are cited in RTECS database (Feb 2010):

Single subcutaneous application to rats results in LDLo: 250 mg/kg [Arzneimittel-Forschung. Drug Research. [Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- v. 27, p. 2102, 1977 (ARZNAD)]

Single intraperitoneal administration to mice results in LD50: 2300 mg/kg [Compilation of LD50 Values of New Drugs. (J.R. MacDougal, Dept. of National Health and Welfare, Food and Drug Divisions, 35 John St., Ottawa, Ont., Canada) (CLDND*)]

Acute subcutaneous toxicity study in mice results in LD50: 45050 ug/kg [National Cancer Institute Screening Program Data Summary, Developmental Therapeutics Program. (Bethesda, MD 20205) JAN1986 (NCISP*)]

Single oral application of hydrocortisone-21-acetate leads to somnolence (general depressed activity), reduced food intake and hemorrhage; LD50: 3267 mg/kg [Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown v. (2), p. 42, 2002 (TOVEFN)]

Oral application to rats results in somnolence (general depressed activity), changes in liver and spleen, adrenal cortex hyperplasia, hemorrhage, reduced food intake and other vascular changes; LD50: 5000 mg/kg [Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown v. (2), p. 42, 2002 (TOVEFN)]

Dermal application of hydrocortisone-21-acetate to rats leads to somnolence (general depressed activity), changes in heart, spleen and thyroid weight and other changes in liver; TDLo: 5 mg/kg [Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown v. (2), p. 42, 2002 (TOVEFN)]

Inhalation application of hydrocortisone-21-acetate to rats over 4 h results in changes in liver, decrease of urine volume and changes in serum composition (e.g. totasl protein, billirubin and cholesterol); TCLo: 0.62 mg/m3/4H [Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown v. (2), p. 42, 2002 (TOVEFN)]

Justification for classification or non-classification

Since LD50 (oral) is above 2000 mg/kg classification is not required according to 67/548/EEC and Regulation (EC) 1272/2008 (CLP).