nivalenol and Body-Weight

Nivalenol (NIV) is considered to be an important trichothecene mycotoxin produced by Fusarium species because of its frequent contamination in wheat and barley worldwide. The present study examined the subchronic toxicity of NIV in male and female F344 rats fed diets containing 0, 6.25, 25 and 100 mg kg(-1) of the toxin for 90 days. During the experimental period there was a decrease in the white blood cell count at 100 mg kg(-1) in males and at > or =6.25 mg kg(-1) in females. Histopathologically, treatment-related changes were observed in the haematopoietic and immune systems in both sexes and in the female reproductive system at 100 mg kg(-1). Flow cytometric analysis of splenic cells revealed an elevation in the ratio of helper/cytotoxic T-lymphocytes at 100 mg kg(-1). In summary, NIV targets the female reproductive system as well as haematopoietic and immune systems in rats fed NIV for 90 days. Based on a significant decrease in white blood cells in female rats relative to controls, the lowest observable effect level was calculated as 0.4 mg kg(-1) body weight day(-1).

Topics: Animals; Body Weight; Dose-Response Relationship, Drug; Eating; Female; Genitalia, Female; Hematopoietic System; Immune System; Leukocyte Count; Lymphocyte Subsets; Male; Mycotoxins; Rats; Rats, Inbred F344; Trichothecenes

A subchronic toxicity study of nivalenol (NIV), a trichothecene mycotoxin, was conducted in male and female F344 rats fed diet containing 0, 6.25, 25 or 100 ppm concentration for 90 days. Decrease of body weight and loose stools were observed at 100 ppm in both sexes from the start of the experiment, and body weight reduction was also observed at 25 ppm in males from week 6. At necropsy, many organs demonstrated reduced absolute weights at 100 ppm in both sexes, mostly due to the reduction in the body growth, with reduction of relative thymus weight also being evident in females. Hematologically, decrease of the white blood cell count was found at 100 ppm in males and from 6.25 ppm in females. In addition, decreased platelet counts in both sexes, red blood cell counts in males, and the hemoglobin concentration in females were detected at 100 ppm. Histopathologically, treatment-related changes were predominantly observed in the hematopoietic and immune organs and the anterior pituitary in both sexes and female reproductive organs at 100 ppm, such as thymic atrophy, hypocellularity in the bone marrow, diffuse hypertrophy of basophilic cells with increase of castration cells in the anterior pituitary, and increase of ovarian atretic follicles. Based on the hematological data, the no-observed-adverse-effect level of NIV was determined to be less than 6.25 ppm (0.4 mg/kg body weight/day for both males and females).

Topics: Animals; Blood Cell Count; Blood Chemical Analysis; Body Weight; Eating; Female; Leukocyte Count; Male; Mycotoxins; No-Observed-Adverse-Effect Level; Rats; Rats, Inbred F344; Sex Characteristics; Trichothecenes

Young pigs were fed diets to which 0, 2.5, or 5 mg/kg of purified nivalenol (NIV) had been added. The exposure continued for 3 weeks without any signs of feed refusal, vomiting, or change in clinical appearance, and there were no changes in body or organ weights due to the exposure. However, the concluding macroscopic examination revealed gastrointestinal erosions and signs of nephropathy in most of the exposed pigs. There were no differences in total or differential blood leukocyte counts between control and exposed pigs in blood samples collected after 0, 1, or 3 weeks, nor in the number of thymocytes at the end of the trial. Spleen cell numbers showed a dose-dependent decrease after 3 weeks of exposure that was statistically different from controls in pigs exposed to 5 mg NIV/kg. Flow cytometric analysis of lymphocytes revealed decreased numbers of both the CD4+ and the CD8+ subpopulations in the spleen at this point in time, reflecting the lower numbers of splenocytes; but no proportional changes were seen. In blood, exposure to NIV caused a transient decrease in the proportion of CD4+ cells after 1 week of exposure. Analysis of IgG and IgA in plasma showed a time-dependent tendency of increasing plasma concentrations of IgA and decreasing concentrations of IgG in the 2.5 mg/kg group, but differences in Ig levels between experimental groups and controls were not observed at any time. No differences were seen in the mitogen-induced proliferation by lymphocytes from blood, spleen, or thymus. In conclusion, exposure of young pigs to NIV in the diet caused pathological alterations in the kidneys and gastrointestinal tract and reduced the number of splenocytes. The results also indicated that exposure to NIV caused a time-dependent increase in IgA production in the 2.5 mg/kg group.

Topics: Animal Feed; Animals; Body Weight; Diet; Digestive System; Immunity, Cellular; Immunoglobulin A; Immunoglobulin G; Kidney; Lymphocyte Subsets; Mycotoxins; Organ Size; Spleen; Swine; Thymus Gland; Trichothecenes

In two feeding trials the effect of nivalenol (NIV) on male broiler chickens was studied. A commercial starter diet was provided for ad libitum consumption throughout the whole experiment. The NIV was added to the feed when the birds were 7 d old. Growth and feed consumption were thereafter registered every 5th d during 20 d. In the first trial birds were offered feed containing 0, .5, 2.5, or 5 ppm NIV. The only variable that significantly differed from the control was the concentration of uric acid in plasma, which was increased by 94 and 66%, respectively, in treatment groups 2.5 and 5 ppm. In the second trial, NIV-concentrations of 0, 3, 6, and 12 ppm were used. The weight gain for the 20-d period was decreased by 11% with 6 and 12 ppm. During this period these birds showed a decrease of about 6% in feed consumption and feed conversion efficiency. Gizzard erosions were found in 33% of the birds fed 12 ppm NIV and in 8% of those fed 3 or 6 ppm. No such erosions were found in the control birds. Relatively, the liver weights in the 12 ppm group were reduced more than total body weights. No effects on relative organ weights were found when bursa, spleen, and gizzard were compared to control. In the blood, no change compared to control was found in hematocrit or in the plasma concentration of glucose, calcium, cholesterol, triglycerides, and uric acid, or in the plasma activity of aspartate amino transferase, alanine amino transferase, or gamma glutamyl transpeptidase.

Topics: Animals; Body Weight; Chickens; Eating; Food Contamination; Gizzard, Avian; Male; Mycotoxins; Organ Size; Stomach Diseases; Trichothecenes; Uric Acid

Effects of nivalenol (NIV), a trichothecene mycotoxin, on hepatic drug-metabolizing activity and aflatoxin B1 (AFB1) metabolism were investigated in male rats. In rats fed the diets containing 6-12 ppm NIV for 2 or 4 wk, decreases in initial feed uptake, terminal weight gain and organ weights were evident. An increase in cytochrome P-450 activity was observed in the hepatic microsomes, and Western blot analysis revealed a transient increase in P4502B1/2, together with a slight induction of P4501A2. The activity of cytosolic glutathione S-transferase (GST) enzymes was also enhanced in the rats, and Western blot analysis demonstrated an elevation of GST 1-2. The formation of aflatoxin B1-DNA adducts (AFB1-DNA) was increased in experiments using hepatic microsomal preparations from rats fed the NIV diet, whereas supplementation with cytosol prepared from NIV-treated rats reduced the microsomal potential for adduct formation. In in vivo experiments, the AFB1-DNA concentration in NIV-treated rats was lower than that in the controls. These results suggest that activities of cytochrome P-450 and GST enzymes were increased in rats fed NIV for several weeks. Alteration of these phase I and phase 2 enzyme levels resulted in the modulation of AFB1 adduction to DNA in vitro and in vivo.

Topics: Administration, Oral; Aflatoxin B1; Animals; Blotting, Western; Body Weight; Cytochrome P-450 Enzyme System; DNA; Glutathione Transferase; Male; Microsomes, Liver; Organ Size; Rats; Rats, Sprague-Dawley; Trichothecenes

In an attempt to ascertain precisely the toxic effects of nivalenol (NIV), we conducted the determination of LD50 values, and interim kills during the carcinogenic study in mice. LD50 values (mg/kg) of NIV in 6-week-old male ddY mice were determined as 38.9 (po), 7.4 (ip), 7.2 (sc), and 7.3 (iv). Seven-week-old female C57BL/6CrSlc SPF mice were fed diets containing 0, 6, 12, and 30 ppm (mg/kg) NIV over 1 year, and were assessed for effects on body weight gain, feed efficiency, terminal organ weights, hematology, and histopathology. The rates of body weight gain and feed efficiency showed a good dose-dependent correlation in all experimental periods. Gross and histopathological evaluation of the liver, thymus, spleen, kidneys, stomach, adrenal glands, pituitary gland, ovaries, sternum, bone marrow, lymph node, brain, and small intestines with or without Peyer's patch portion from control and all NIV-exposed mice revealed that these tissues were normal in appearance and in histopathological structure. Also, no changes were observed in the ultrastructural studies on the bone marrow. Dietary NIV did, however, cause dose-dependent decreases of absolute organ weights (mg) and increases of relative organ weights (mg/g body weight) in the terminal organ weights recorded. A significant leukopenia was observed in the 30 ppm group at 6 months and in all NIV-treated groups at 1 year. No marked changes were observed in the other hematological parameters. These results indicated that 6 ppm or more of dietary NIV for 1 year showed a characteristic toxic effect of trichothecene mycotoxins in mice.

Topics: Animals; Blood Cell Count; Body Weight; Diet; Eating; Female; Lethal Dose 50; Male; Mice; Mice, Inbred C57BL; Organ Size; Sesquiterpenes; Time Factors; Trichothecenes

In order to investigate the toxic effects of nivalenol, one of the trichothecene mycotoxins, we performed a short-term feeding trial for 24 days using feed supplemented with rice artificially molded with nivalenol producing fungus, Fusarium nivale Fn 2B, in female C57BL/6CrSlc SPF mice. A significant erythropenia and slight leukopenia were observed in the 30 ppm group, but no marked changes were observed in other hematological parameters, feed consumption, body weight gain, or weights of the liver, spleen, and thymus. Ultrastructural studies also revealed polyribosomal breakdowns of the bone marrow cells in the 30 ppm group.

Topics: Animals; Body Weight; Bone Marrow; Eating; Female; Mice; Mice, Inbred C57BL; Organ Size; Sesquiterpenes; Trichothecenes