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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see http://ntp.niehs.nih.gov/ntp/htdocs/levels/09-3566%20NTP-ITOX-R1.pdf). 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 Nitrofurazone
in Female B6C3F1 Mice
NTP Report Number IMM90011
semicarbozone] is a synthetic furan derivative active against
a broad spectrum of bacteria. It is an antimicrobial compound
administered both topically and systemically to humans and animals.
Nitrofurazone was nominated to the NTP for toxicological evaluation and it was recommended for immunotoxicological evaluation by the chemical manager. The purpose of these studies was to determine the effects of nitrofurazone on the immune system.
Female B6C3F1 mice were administered nitrofurazone at doses of 40, 60 or 80 mg/kg daily for 14 consecutive days. Nitrofurazone was administered by gavage as a solution in corn oil. Cyclophosphamide was used as a positive control.
The baseline toxicology data are summarized in Table ES-1. Nitrofurazone produced a dose-dependent increase (16%) in liver weight, while no changes occurred in body, spleen or thymus weights. Hematological parameters were not affected, with the exception of the reticulocyte count which was increased (27%) in a dose-dependent manner. Serum chemistries were unaffected by nitrofurazone exposure.
Table ES-2 summarizes the immunology studies. Nitrofurazone produced no changes on indicators of humoral immunity, such as B cell number, proliferative ability or ability to differentiate into antibody-producing cells to a T-dependent antigen. Although some changes were observed in the proliferative capacity of T lymphocytes in one of the mitogenicity studies, no effects on the proliferation capacity were observed in the mixed leukocyte response. There were no changes in the percent or number of T cells or subsets of T cells in mice exposed to nitrofurazone. The differentiation and killing mechanisms of T cells were intact in mice treated with nitrofurazone as seen in a CTL response which did not differ from the control group.
With respect to innate immunity, natural killer cell function was unaffected by nitrofurazone exposure.
Table ES-3 summarizes the host resistance study which was conducted. The B16F10 pulmonary metastatic melanoma model was unaffected by exposure to nitrofurazone.
In summary, nitrofurazone, administered daily for 14 days, did not substantially alter any of the immunological or host resistance parameters measured.
SUMMARY TABLE FOR TOXICOLOGY
|Body Weight||No Effect|
|Gross Pathology||No Effect|
|Increased||16%||80 mg/kg||Dose Dependent|
|60 mg/kg||Dose Dependent|
|Decreased Cell Numbers Observed At Low Dose Levels Only|
|80 mg/kg||Dose Dependent|
SUMMARY TABLE FOR IMMUNOLOGY
|T Cells||No Effect|
|B Cells||No Effect|
|IgM AFC to sRBC
- Con A
|Decreased||50%||60 mg/kg||Increased Response at Low Dose; Decreased Response at Middle Dose|
|Increased||53%||40 mg/kg||Increased Response at Low Dose; Decreased Response at Middle and High Doses|
|F(ab')2 + BSF-1||No Effect|
|(5 mg/ml + 200 Units/ml)||No Effect|
|NK Cell Activity||No Effect|
SUMMARY TABLE FOR HOST RESISTANCE
|B16F10 Melanoma||No Effect|