Hazard assessment of the veterinary pharmaceuticals monensin and nicarbazin using a soil test battery.

Veterinary pharmaceuticals are widely used as food additives in the poultry industry, and the unknown consequences of releasing these compounds into the environment are of concern. The purpose of the present study was to determine the direct impact of 2 veterinary pharmaceuticals (nicarbazin and monensin), commonly used in the poultry industry, on nontarget invertebrates and plant species. Ecotoxicological tests were used to evaluate the acute and chronic toxicity in earthworms (Eisenia andrei), collembolans (Folsomia candida), and 2 plant species (Brassica rapa and Triticum aestivum). Chemical analytical measurements were in good agreement with the nominal concentrations used, although some variability was seen. The results obtained showed no effects of nicarbazin at the highest nominal tested concentration of 1000 mg a.i./kg soil dry weight on any of the organisms, whereas exposure to monensin caused a concentration-specific response pattern. Species sensitivity to monensin decreased in the following rank order: B. rapa > T. aestivum > E. andrei > F. candida, with measured median effect concentrations (based on soil exposure) ranging between approximately 10 and 120 mg/kg. Our results emphasize the importance of using a test battery when assessing ecotoxicological effects by using different ecophysiological endpoints and species from different trophic levels. Environ Toxicol Chem 2018;37:3145-3153. © 2018 SETAC.

4,4'-Dinitrocarbanilide (DNC) concentrations in egg shells as a predictor of nicarbazin consumption and DNC dose in goose eggs.

Nicarbazin is being investigated as an infertility agent for the control of non-migratory Canada geese (Branta canadensis L) populations. Nicarbazin is presently registered for use as a coccidiostat for poultry. Geese fed sufficient quantities of nicarbazin will lay non-viable eggs. We established nicarbazin consumption by measuring the concentration of a component of the formulation, 4,4'-dinitrocarbanilide (DNC) in the egg contents (yolk, albumin) in non-viable eggs. To estimate the nicarbazin consumption of birds that laid viable eggs (eggs that hatched or contained an embryo), a high-performance liquid chromatography method was developed to measure the concentration of DNC in egg shells. A statistically significant correlation was established using linear regression between the mean concentrations of DNC in the egg shell and in the egg contents in non-viable eggs. Viable eggs were estimated to contain lower levels of DNC than non-viable eggs. DNC concentrations in both the egg contents and the egg shell increased with increases in nicarbazin dose in feed. Our method allows for the estimation of nicarbazin consumption and DNC dose in eggs under field conditions, which is important in developing an effective infertility agent for over-abundant non-migratory goose populations.

Effects of exposing broiler breeders to nicarbazin contaminated feed.

Ten-mo-old broiler feeds were fed nicarbazin (NCZ) at 0, 25, 50 and 100 ppm of their diet for 2, 4, or 6 days to simulate accidental contamination of their feed with the medicant. Reduced egg production was observed in all treatments except 25 and 50 ppm NCZ for 2 days. A consistent reduction in egg weight occurred only at the maximum treatment level of 100 ppm for 6 days. Reduction in hatchability was generally evident by Days 5 and 6 of the experiment except for the lowest treatment of 25 ppm NCZ for 2 days. Due partially to the low number of eggs set, no statistically significant reduction in hatchability was seen for the group receiving 50 ppm NCZ for 4 days, but hatchability had dropped over 17 percentage points (from 93.3 to 75.5%) by Days 5 and 6 of the experiment, and continued to drop to a low of 31% on Days 11 and 12 of the experiment. Shell pigmentation was the most sensitive characteristic measured, with significant depigmentation occurring after only 2 days of feeding 25 ppm NCZ. Generally, the severity and duration of effects were in proportion to medicant concentration and length of treatment time. Fertility was not influenced by the medicant.

Lack of effect of dietary factors on nicarbazin toxicity in broiler chicks.

Effects of dietary fat, protein, and methionine levels and the type of dietary grain in nicarbazin-containing diets on the growth response of broiler chicks were evaluated in five experiments in a factorial design. Nicarbazin at levels ranging from 100 to 200 mg/kg significantly (P less than .05) depressed weight gain and feed efficiency. Feed intake was significantly reduced only when nicarbazin was used at levels of 150 and 200 mg/kg. The latter concentration also significantly decreased water intake and water:feed ratio. Nicarbazin, at a level of 150 mg/kg, did not affect dietary metabolizable energy content or the retention of nitrogen and dry matter. A higher level of soybean oil (3.5 vs. .5 or 1.0%) did not counteract the growth-depressing effects of 100, 150, and 200 mg nicarbazin/kg. The growth-depressing effect of the highest dose also was not affected by increasing the protein level from 18.2 to 20.4%. Neither type of dietary grains (corn vs. sorghum) nor supplemental methionine level affected the toxicity of 125 mg nicarbazin/kg. Water intake and water:feed ratio were significantly increased due to elevation of dietary protein and fat levels. It was concluded that the severity of the growth-depressing effect of nicarbazin on chicks was not dependent on the levels of dietary unsaturated fat, protein, and methionine.

Anticoccidial drugs: growth and performance depressing effects in young chickens.

Monensin, lasalocid, salinomycin, nicarbazin, halofuginone, or arprinocid were fed to 1-week-old male broiler chicks at recommended levels and 1.5, 2, 2.5, and 3 times the recommended level, for 3 weeks. Pair-feeding experiments also were conducted to investigate the extent that growth depression with medicated diets could be attributed to the drop in feed consumption. At the recommended level of drugs, growth and feed conversion were not significantly affected. At elevated drug levels, performance was impaired; the adverse effects of drugs became more pronounced with increasing the concentrations in the diets. Weight gain was significantly depressed at 1.5X with arprinocid, halofuginone, and salinomycin, at 1 to 2X with monensin, at 2X with lasalocid, and at 2.5X with nicarbazin. Feed conversion, however, was adversely affected by 2X with halofuginone or 2.5X with salinomycin, nicarbazin, arprinocid, monensin, or lasalocid. The results of the pair-feeding experiments with 2 to 3 times drug levels indicated that most of the growth depression with medicated diets could be attributed to reduced feed consumption, but all drugs except arprinocid caused some additional growth depression.