title: Normal temperature variation in New Zealand white rabbits during restraint for preliminary pyrogen test.
abstract: The in vivo pyrogen test is the main toxicological assay used in the quality control of injectable products, especially immunobiologicals. Pharmacopoeias state that, before the main test, a preliminary test must be conducted on all animals, and must follow the same conditions as the main test. The aim of this study was to determine the normal temperature variation in New Zealand white rabbits during restraint and propose a limit value for considering an animal as suitable for testing. Results of the temperature variation in 4,689 rabbits during preliminary tests were obtained from the routine database of the Pharmacology and Toxicology Department of the National Institute of Quality Control in Health (INCQS/FIOCRUZ), Brazil. From these preliminary tests, 3,364 rabbits were considered suitable for testing according to the Brazilian Pharmacopoeia criteria (temperature variation < 0.5 °C). Results showed that about 92 per cent of the rabbits presented a normal individual temperature variation equal to or below 0.30 °C. Animals presenting a temperature variation close to the fever temperature must not be included in the main test, since they can be stressed or sick. Consequently, the temperature variation of 0.30 °C could be adopted by pharmacopoeias as a limit temperature to be considered in the preliminary test to determine which animals can be used in the main rabbit pyrogen test. Animals can be pre-tested until presenting this safe variation, in order to ensure they are healthy and minimise interference in the result.
authors: Instituto Nacional de Controle de Qualidade em Saúde, Fundação Oswaldo Cruz; Departamento de Farmacologia e Toxicologia, INCQS/FIOCRUZ, Avenida Brasil, 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil, cristiane.caldeira@incqs.fiocruz.br.
authors: C
authors: C
authors: Caldeira
authors: Instituto Nacional de Controle de Qualidade em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors: J C B R
authors: JC
authors: Freitas
authors: Instituto Nacional de Controle de Qualidade em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors: I
authors: I
authors: Gimenes
authors: Instituto Nacional de Controle de Qualidade em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors: S A
authors: SA
authors: Silva
authors: Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors: P
authors: P
authors: Cabello
authors: Instituto Nacional de Controle de Qualidade em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors: O A F
authors: OA
authors: Presgrave
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000502:physiology*; D004340:Drug Contamination; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology; D011749:Pyrogens / Q000494:pharmacology* / Q000592:standards; D011786:Quality Control; D011817:Rabbits / Q000502:physiology*; D012016:Reference Values; D012149:Restraint, Physical / Q000502:physiology
chemical_list: D011749:Pyrogens
keywords: individual temperature variation; laboratory animals; preliminary test; quality control; rabbit; rabbit pyrogen test