National Toxicology Program

National Toxicology Program

Abstract for IMM97009 - Clarithromycin (CASRN 81103-11-9)

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program (NTP). The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.

The Immunotoxicity of Clarithromycin
(CAS No. 81103-11-9)

in Female BALB/c Mice
NTP Report Number IMM97009


Clarithromycin (CLA) has been nominated for testing in the immunotoxicology program in part due to its indications for use in the treatment of secondary infections associated with AIDS. CLA is a new macrolide antibiotic with improved acid stability and pharmacokinetic properties which induces less gastrointestinal irritation and has a wider spectrum of antimicrobial activity than erythromycin. Clinical trails have shown CLA to be promising in the treatment of disseminated Mycobacterium avium-intracellular complex in patients with AIDS.

The objective of this study was to determine the sensitizing potential of CLA when applied dermally to female BALB/c mice. Measurement of the contact hypersensitivity response was accomplished by the mouse ear swelling test (MEST) and the local lymph node assay (LLNA). Concentrations to be used in the contact hypersensitivity assays were determined by the irritancy study. The doses of CLA tested were 0.2, 1.0 and 2.0% in acetone for sensitization, and 4.0% for challenge in the MEST and 1.0, 2.0 and 4.0% for sensitization in the LLNA. DNFB (2,4-dinitrofluorobenzene, Sigma Chemical Co.) was used as the positive control for sensitization in the MEST and LLNA at a concentration of 0.20% and at the same concentration for the challenge in the MEST.

The MIC of CLA was determined to be 4.0%. Clarithromycin did not show sensitizing potential in either the MEST or the LLNA in these studies. The positive control, DNFB, showed statistically significant in both the MEST (p < 0.05) and the LLNA (p < 0.01).


Type of Response Method Used Dose Response
(p < 0.05)
Positive Response
(p < 0.05)
Irritation Ear Swelling Yes 4.0%
MEST 24 hrs No No
  MEST 48 hrs No No
  LLNA No No
Abbreviations: LLNA = Local Lymph Node Assay; MEST = Mouse Ear Swelling Test

The studies were conducted at the Medical College of Virginia Immunotoxicology Laboratory. The in-life phase of the studies was conducted between 23 June 1997 and 7 August 1997. The animals were housed in the animal facility of the Strauss Research Laboratory. To the best of our knowledge, no significant deviations from Good Laboratory Practices occurred that affected the quality of the data or the ability to interpret the data with respect to the sensitizing potential of the Clarithromycin.

Report Date: September 1997

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