An immunotoxicity screening study on salmeterol in rats.
Salmeterol, a long-acting beta 2-adrenoreceptor agonist without known immunotoxicity, was studied in a 28-day repeated dose toxicity test in Wistar rats. Several immunotoxicity screening parameters were incorporated in the study protocol to investigate the immunotoxic potential of the compound. Male rats were orally treated with 0, 0.2, 2 and 20 mg salmeterol/kg body weight/day. At the 20 mg/kg/day dose level, intubation errors occurred because the animals tried to resist intubation. Some of these animals died intercurrently. Therefore, the magnitude of the dose was lowered to 10 mg/kg/day at day 9 of treatment. Body weight and bone marrow cellularity were not affected. Hematological parameters were not altered either, except for platelet counts, that were decreased at all dose levels. Also liver weights were decreased at all dose levels tested. Absolute thymic weights were decreased at the 2 and 20/10 mg/kg/day dose levels. No treatment-related (histo)pathological lesions were seen in the (non)lymphoid organs. Serum IgM levels were increased at the 0.2, and IgG at the 2 and 20/10 mg/kg/day dose levels, respectively. B cell numbers in the spleen were decreased at all dose levels tested. The data indicate that the test battery applied to salmeterol is able to detect low immunotoxic potential. Further research is needed to elucidate whether salmeterol interferes with immune responses in rats upon antigenic challenge.
de Waal
E J
EJ
National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
de Jong
W H
WH
van der Vliet
H
H
Verlaan
B
B
van Loveren
H
H
D000318:Adrenergic beta-Agonists / Q000633:toxicity*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D007136:Immunoglobulins / Q000097:blood; D016131:Lymphocyte Subsets / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects / Q000276:immunology; D009928:Organ Specificity / Q000187:drug effects / Q000276:immunology; D010976:Platelet Count / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000068299:Salmeterol Xinafoate; D013154:Spleen / Q000166:cytology
D000318:Adrenergic beta-Agonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007136:Immunoglobulins; D000068299:Salmeterol Xinafoate; D000420:Albuterol