Recommendations from a global cross-company data sharing initiative on the incorporation of recovery phase animals in safety assessment studies to support first-in-human clinical trials.

An international expert group which includes 30 organisations (pharmaceutical companies, contract research organisations, academic institutions and regulatory bodies) has shared data on the use of recovery animals in the assessment of pharmaceutical safety for early development. These data have been used as an evidence-base to make recommendations on the inclusion of recovery animals in toxicology studies to achieve scientific objectives, while reducing animal use. Recovery animals are used in pharmaceutical development to provide information on the potential for a toxic effect to translate into long-term human risk.

Biological fate of [14C]-1-nitropyrene in rats following intragastric administration.

1-Nitropyrene (1-NP), a weak carcinogen associated with diesel exhaust particles, has previously been detected in workplace atmospheres with in-use diesel engines and in the general environment. In order to gain insight in its biological fate, a single dose of [14C]-1-NP (27.6 microCi, 750 mg/kg body weight, b.

Sensitive and selective detection of urinary 1-nitropyrene metabolites following administration of a single intragastric dose of diesel exhaust particles (SRM 2975) to rats.

1-Nitropyrene (1-NP) has been proposed as a marker for exposure to diesel exhaust particles (DEP). Since the extent of the actual intake of 1-NP adsorbed on DEP will be relatively low, sensitive and selective methods are needed regarding human exposure assessment. Two analytical methods are presented for the assessment of 1-NP metabolites in urine of male Sprague-Dawley rats administered a single intragastric dose of native DEP (SRM 2975, 20 mg, 35.

Determination of hemoglobin adducts following oral administration of 1-nitropyrene to rats using gas chromatography-tandem mass spectrometry.

1-Nitropyrene (1-NP) has successfully been used as a marker for environmental monitoring of exposure to diesel exhaust. This study presents a sensitive and selective method for detection of Hb adducts after oral administration of a single dose 1-NP to rats, by measuring 1-aminopyrene (1-AP) after in vitro hydrolysis of the adducts. Released 1-AP was extracted with hexane and derivatized with heptafluorobutyric acid anhydride prior to GC-MS-MS analysis.