Acute toxicity tests of mofezolac (N-22) in mice and rats.

Satoh K1, Yamamoto N, Kuwasaki E, Ichiki T, Sone H, Kodama R, Kuwata M, Yamashita K.

Abstract

Mofezolac (N-22) is a newly developed analgesic and anti-inflammatory agent. The acute toxicities of N-22 were investigated in ICR mice and Wistar rats in oral (p.o.), intraperitoneal (i.p.) and subcutaneous (s.c.) routes. LD50 values of N-22 in mice were 1528 mg/kg (p.o.), 275 mg/kg (i.p.) and 612 mg/kg (s.c.) for males, and 1740 mg/kg (p.o.), 321 mg/kg (i.p.) and 545 mg/kg (s.c.) for females. Those in rats were 920 mg/kg (p.o.), 378 mg/kg (i.p.) and 572 mg/kg (s.c.) for males, and 887 mg/kg (p.o.), 342 mg/kg (i.p.) and 510 mg/kg (s.c.) for females. The sex difference was not clearly observed in mice and rats, but the species difference was observed in p.o. routes. As an initial toxic sign, the hypoactivity was observed in mice and rats of all routes, subsequently, paleness of skin, anemic conjunctiva, emaciation, stupor and/or coma were observed in mice and rats of p.o. and i.p. routes. In rats of those routes, tonic and/or asphyxial convulsion and dyspnea were also observed. In pathological examination of mice and rats, gastrointestinal disorders were observed in p.o. and i.p. routes, and changes of subcutaneous tissue at the injection site were observed in s.c. route.

http://www.ncbi.nlm.nih.gov/pubmed/2231785

The most commonly used technique at this point is the up-and down process.  That requires fewer animals than developing the standard dose response curve.  The up-down will only provide an estimate of LD50 not any information about slope of the curve near the midpoint.  There are lots of examples and founadational literature from OECD, and USEPA.  You can also review our publication: Age dependent acute oral toxicity of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and two anaerobic N-nitroso metabolites in deer mice (Peromyscus maniculatus) Jordan N Smith · Jun Liu · Marina A Espino · George P Cobb.  Chemosphere 06/2007; 67(11):2267-73. DOI:10.1016/j.chemosphere.2006.12.005

Acute toxicity studies, as defined in this book, are those which evaluate the

short-term (less than 30 days) adverse biological effects of a single exposure

(or a small number of exposures over a week or less) to a material or physical

agent. Generally, such exposures occur at such large amounts or high concentrations that long-term repeated exposures would not occur at similar levels.

These exposures, for materials other than cosmetics, medical devices, and

pharmaceuticals, are most frequently the result of accidents. Such exposures

could be the result of misuse of a consumer product, leaking containers,

industrial accidents, transportation mishaps (truck accidents or leaks, train

derailments, etc.), curious children or mislabeled containers, agricultural accidents,

product tampering, or intentional suicide attempts. Cosmetics, medical

devices, and pharmaceuticals exposures are both intentional and accidental,

but concerns about their short-term effects are characteristically associated

with larger exposures or doses.

Consult the oecd, usepa, or EU for up/down processes or try our publication:  Age dependent acute oral toxicity of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and two anaerobic N-nitroso metabolites in deer mice (Peromyscus maniculatus)

Jordan N Smith · Jun Liu · Marina A Espino · George P Cobb ·

Chemosphere 06/2007; 67(11):2267-73. DOI:10.1016/j.chemosphere.2006.12.005

Consulting international guidelines is a great way to start. However to develop your specific protocol take in consideration the following: What is the aim of the study?. Which is the compound to be tested?. Are there other toxicological studies using the same chemical or combination of chemicals?. For the particular compound which would be the best way for oral administration?, gavage?, mixed with food?, etc; Which acute toxicological parameters are you focusing on e.g. toxicokinetics, tissue distribution of compound, histopathology effects?. Which acute toxicity parameters are already known?., how many other investigators are involved in the study?. . Get a detail study protocol before starting. Good planning avoids headaches.

Lork 1983 method is favorite to me

A part of material and method describe Lork 1983 method