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Abstract for IMM90011

Immunotoxicity of Nitrofurazone in Female B6C3F1 Mice

CASRN: 59-87-0
Chemical Formula: C6H6N4O4
Molecular Weight: 198.1374

Abstract

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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009.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

Nitrofurazone [5-nitro-2-furaldehyde 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.

Studies

Table ES-1
Summary Table for Toxicology Studies
NFZ-14-1-PO
Parameter Results Maximum Effect Dose Comments
Body Weight No Effect      
Gross Pathology No Effect      
Histopathology Not Done      
Organ Weights

Liver

Increased 16% 80 mg/kg Dose Dependent

Spleen

No Effect      

Lungs

Increased
30%
60 mg/kg Dose Dependent

Thymus

No Effect      

Kidney

No Effect      

Brain

No Effect      
Hematology

RBCs

Decreased Cell Numbers Observed At Low Dose Levels Only

Hemaglobin

No Effect      

Hematocrit

No Effect      

MCV

No Effect      

Leukocytes

No Effect      

Leukocyte Diff

     

Lymphocytes

No Effect      

Neutrophils

No Effect      

Polys

No Effect      

Monocytes

No Effect      

Reticulocytes

Increased
27%
80 mg/kg Dose Dependent
Serum Chemistries

SGPT

No Effect      

Albumin

No Effect      

BUN

No Effect      

Glucose

No Effect      

Total Protein

No Effect      
Table ES-2
Summary Table for Immunology Studies
NFZ-14-1-PO
Parameter Results Maximum Effect Dose Comment
T Cells No Effect      
B Cells No Effect      
L3T4 No Effect      
LYT2 No Effect      
IgM AFC to sRBC
    (T-dependent)
No Effect      
Mitogens

- Con A

Decreased 50% 60 mg/kg Increased Response at Low Dose; Decreased Response at Middle Dose

- PHA

Increased 53% 40 mg/kg Increased Response at Low Dose; Decreased Response at Middle and High Doses

- LPS

No Effect      

- Medium

No Effect      
F(ab')2 + BSF-1 No Effect      
(5 mg/ml + 200 Units/ml) No Effect      
MLR No Effect      
CTL No Effect      
NK Cell Activity No Effect      

Table ES-3
Summary Table for Host Resistance Study
NFZ-14-1-PO
Parameter Results Maximum Effect Dose Comment
B16F10 Melanoma No Effect