Review of the toxicology of beclomethasone dipropionate

Abstract

This paper reviews the published toxicity of beclomethasone dipropionate (BDP). BDP is a synthetic glucocorticosteroid which has a powerful local anti-inflammatory effect but little systemic action. It has been developed for both dermatological and inhaled applications. LD50 values and other acute studies indicated low toxicity. Findings published for repeat dose and reproductive toxicity studies embraced the known range of metabolic and physiological effects of glucocorticoids. For repeat dose studies, these included reduction in body weight gains, cushingoid syndrome in dogs, reductions in the numbers of lymphocytes and the weights of the tissues connected with the immune system, and hepatic glycogen deposition and fatty liver changes. In reproductive studies, there was an increase in the prevalence of cleft palate in mice and rabbits and in the number of dead foetuses, and ossification was retarded. Despite the route of administration, there was a general similarity of effects within and between species. All observations were characteristic of synthetic glucocorticoids and related to the intrinsic effects of these drugs.

Hyalinization of the Pyloric Stomach in CD-1 Mice Following Oral (Dietary) Administration of the Corticosteroid Agonists Mometasone Furoate, Budesonide, and Flunisolide

“…Other findings in this study, each reported to be a consequence of corticosteroid administration, included transient body weight loss and/or reduced body weight gain (De Vos et al 1995; Libretto 1995) and increases in plasma total protein concentrations reflecting increased protein synthesis (Libretto 1995; Schäcke, Wolf-Dietrich, and Asadullah 2002).…”

“…Hyaline change/hyalinization, from the Greek hualinos (glass), is a descriptive term used to denote a glassy, amorphous eosinophilic tissue appearance with hematoxylin and eosin (H&E) staining. This tinctorial change may be produced by a variety of alterations and does not represent a particular pattern of accumulation (Kumar 2005). Hyalinization is therefore seen in association with various conditions, including amyloidosis (Abbas 2005), hypertension (Hall and Gomez-Sanchez 1986), and scar formation (Ungar, Laufer, and Diengott 1956).…”

Species-specific developmental toxicity in rats and rabbits: Generation of a reference compound list for development of alternative testing approaches

“…potential target sensitivity differences. In contrast, rat and rabbit did not show any differential sensitivity to COX-inhibitors, tyrosine kinase inhibitors or glucocorticoid agonists, even though it is been previously reported that rabbits are particularly sensitive to the teratogenic property of glucocorticoids leading to high incidences of cleft palate [45]. This information on overall species differences for groups of compounds could be useful to predict the relative responses of these species to previously untested compounds in such groups.…”

Scientific Rationale for the Use of Alpha-Adrenergic Agonists and Glucocorticoids in the Therapy of Pediatric Stridor

“…GCs use predisposes to many systemic side effects including hyperglycemia, decreased bone density, altered hypothalamic-pituitary-adrenal axis, and abnormal immune responses [122]. Specific to the pediatric population is the potential decreased rate of growth [123] associated with the prolonged use of systemic GCs and high-doses of inhaled GCs [124].…”