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Carcinogenesis, Mutagenesis, Impairment of Fertility In a two-year study in Sprague-Dawley rats, budesonide caused a statisti-cally significant increase in the incidence of gliomas in the male rats receiving an oral dose of 50 mcg/ kg (approximately twice the maximum recommended daily intranasal dose in adults and children on a mcg/ m 2 basis). No tumorigenicity was seen in male and female rats at respective oral doses up to 25 and 50 mcg/ kg (approximately equal to and two times the maximum recommended daily intranasal dose in adults and children on a mcg/ m 2 basis, respectively). In two additional two-year studies in male Fischer and Sprague-Dawley rats, budesonide caused no gliomas at an oral dose of 50 mcg/ kg (approximately twice the maximum recom-mended daily intranasal dose in adults and children on a mcg/ m 2 basis). Text Continues Below
However, in male Sprague-Dawley rats, budesonide caused a statistically significant increase in the incidence of hepatocellular tumors at an oral dose of 50 mcg/ kg (approximately twice the maximum recommended daily intranasal dose in adults and children on a mcg/ m 2 basis). The concurrent reference corticosteroids (prednisolone and triamcinolone acetonide) in these two studies showed similar findings. In a 91-week study in mice, budesonide caused no treatment-related carcinogenicity at oral doses up to 200 mcg/ kg (approximately 3 times the maximum recommended daily intranasal dose in adults and children on a mcg/ m 2 basis). Budesonide was not mutagenic or clastogenic in six different test systems: Ames, Salmonella/ microsome plate test, mouse micronucleus test, mouse lymphoma test, chromosome aberration test in human lymphocytes, sex-linked recessive lethal test in Drosophila melanogaster, and DNA repair analysis in rat hematocyte culture.
In rats, budesonide caused a decrease in prenatal viability and viability of the pups at birth and during lactation, along with a decrease in maternal body-weight gain, at subcutaneous doses of 20 mcg/ kg and above (less than the maximum recommended daily intranasal dose in adults on a mcg/ m 2 basis). No such effects were noted at 5 mcg/ kg (less than the maximum recommended daily intranasal dose in adults on a mcg/ m 2
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