Clobetasol propionate at concentrations up to % did not increase the rate of formation of ultra violet light-induced skin tumors when topically applied to hairless mice 5 days per week for a period of 40 weeks.
Clobetasol propionate was negative in the in vitro mammalian chromosomal aberration test and in the in vivo mammalian erythrocyte micronucleus test
The effect of subcutaneously administered clobetasol propionate on fertility and general reproductive toxicity was studied in rats at doses of 0, , 25, and 50 μg/kg/day. Males were treated beginning 70 days before mating and females beginning 15 days before mating through day 7 of gestation. A dosage level of less than μg/kg/day clobetasol propionate was considered to be the no-observed-effect-level (NOEL) for paternal and maternal general toxicity based on decreased weight gain and for male reproductive toxicity based on increased weights of the seminal vesicles with fluid. The female reproductive NOEL was μg/kg/day (ratio of animal dose to proposed human dose of on a mg/m 2 /day basis) based on reduction in the numbers of estrous cycles during the pre-cohabitation period and an increase in the number of nonviable embryos at higher doses.
Azelastine hydrochloride displayed no sensitising potential in the guinea pig. Azelastine demonstrated no genotoxic potential in a battery of in vitro and in vivo tests, nor any carcinogenic potential in rats or mice. In male and female rats, azelastine at oral doses greater than 3 mg/kg/day caused a dose-related decrease in the fertility index; no substance-related alterations were found in the reproductive organs of males or females during chronic toxicity studies, however, embryotoxic and teratogenic effects in rats, mice and rabbits occurred only at maternal toxic doses (for example, skeletal malformations were observed in rats and mice at doses of mg/kg/day).
Mild nasopharyngeal irritation following the use of beclomethasone aqueous nasal spray has been reported in up to 24% of patients treated, including occasional sneezing attacks (about 4%) occurring immediately following use of the spray. In patients experiencing these symptoms, none had to discontinue treatment. The incidence of transient irritation and sneezing was approximately the same in the group of patients who received placebo in these studies, implying that these complaints may be related to vehicle components of the formulation.