N,N'-ビス(4-ニトロフェニル)尿素·4,6-ジメチル-2(1H)-ピリミドン

0.5 g/ml

Yellowish-tan solid, round to oblong, semisoft kibbles. None to slight grain odor. Density: 25-33 lbs/bushel. /OvoControl-G/

Crystals

Light yellow, fine powder

Practically insoluble in water. Complex is slowly decomposed by trituration with water, or more rapidly by dilute aqueous acids.

Slightly soluble in dimethylsulfoxide (DMSO) and dimethylformamide (DMF); insoluble in water and ethanol, however it decomposes slowly when mixed with them

Nicarbazin is a complex of two compounds, 4,4'-dinitrocarbanilide (DNC, 302.35 molecular weight) and 4,6-dimethyl-2-pyrimidinol (HDP, 124.14 molecular weight). DNC is considered the active ingredient while HDP aids in adsorption.

The dry crystals are strongly electrostatic and present some drying problems.

This chemical does not meet GHS hazard criteria for 4.4% (2 of 45) of reports.

Warning

H315 (95.6%): Causes skin irritation [Warning Skin corrosion/irritation]

P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 45 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Regulation (EC) No 1831/2003 (amended)

Nicarbazin: Does not have an individual approval but may be used under an appropriate group standard

An equimolar complex of 4,4'-dinitrocarbanilide and 2-hydroxy-4,6-dimethylprimidine; A moderate eye irritant; Oral LD50 (rat) >10,000 mg/kg; In high-dose feeding studies of dogs over 2 years, it caused liver injury in doses >240 mg/kg/day; In another animal study, the NOEL for maternal and fetal toxicity was 200 mg/kg/day; [HSDB] An irritant; [MSDSonline]

A tolerance of 4 parts per million is established for residues of nicarbazin in uncooked chicken muscle, liver, skin, and kidney.

New animal drugs for use in animal feeds. Nicarbazin. a) Specifications. Type A medicated articles containing 25 percent nicarbazin. (b) Approvals. See Nos. 000986, 060728, and 066104 in §510.600(c) of this chapter for use as in paragraph (d) of this section. (c) Related tolerances. See §556.445 of this chapter. (d) Conditons of use. It is used in chicken feed as follows: [Table#7129]

Based on the limited use pattern/exposure scenario, the submitted data are deemed adequate to support nicarbazin registration. Avoiding nontarget exposure is the primary concern with use of OvoControl-G. Reduction in egg hatchability is the primary concern if nontarget birds are exposed to nicarbazin. On the basis of label requirements, it can be reasonably assumed that exposure and resultant risk to non-target and endangered species would be low.

Safe Storage of Pesticides. Always store pesticides in their original containers, complete with labels that list ingredients, directions for use, and first aid steps in case of accidental poisoning. Never store pesticides in cabinets with or near food, animal feed, or medical supplies. Do not store pesticides in places where flooding is possible or in places where they might spill or leak into wells, drains, ground water, or surface water.

If a spill occurs, clean it up promptly. Don't wash it away. Instead, sprinkle the spill with sawdust, vermiculite, or kitty litter. Sweep it into a plastic garbage bag, and dispose of it as directed on the pesticide product label.

After Applying a Pesticide, Indoors or Outdoors. To remove pesticide residues, use a bucket to rinse tools or equipment three times, including any containers or utensils that you used when mixing the pesticide. Then pour the rinsewater into the pesticide sprayer and reuse the solution by applying it according to the pesticide product label directions. After applying any pesticide wash your hands and any other parts of your body that may have come in contact with the pesticide..To prevent tracking pesticides inside, remove or rinse your boots or shoes before entering your home. Wash any clothes that have been exposed to a lot of pesticide separately from your regular wash.

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Safe Disposal of Pesticides. The best way to dispose of small amounts of excess pesticides is to use them - apply them - according to the directions on the label. If you cannot use them, ask your neighbors whether they have a similar pest control problem and can use them. If all of the remaining pesticide cannot be properly used, check with your local solid waste management authority, environmental agency, or health department to find out whether your community has a household hazardous waste collection program or a similar program for getting rid of unwanted, leftover pesticides. These authorities can also inform you of any local requirements for pesticide waste disposal.

Safe Disposal of Pesticides. An empty pesticide container can be as hazardous as a full one because of residues left inside. Never reuse such a container. When empty, a pesticide container should be rinsed carefully three times and the rinsewater thoroughly drained back onto the sprayer or the container previously used to mix the pesticide. Use the rinsewater as a pesticide, following label directions. Replace the cap or closure securely. Dispose of the container according to label instructions. Do not puncture or burn a pressurized container like an aerosol - it could explode. Do cut or puncture other empty pesticide containers made of metal or plastic to prevent someone from reusing them. Wrap the empty container and put it in the trash after you have rinsed it.

Causes moderate eye irritation. Remove and wash contaminated clothing before reuse. Avoid contact with eyes or clothing. Wear protective eyewear. Wash thoroughly with soap and water after handling and before eating, drinking, chewing gum, or using tobacco. Wear: Long-sleeved shirt and long pants, Socks, Shoes, and gloves.

Wear the items of protective clothing the label requires: for example, non-absorbent gloves (not leather or fabric), rubber footwear (not canvas or leather), a hat, goggles, or a dust-mist filter. If no specific clothing is listed, gloves, long-sleeved shirts and long pants, and closed shoes are recommended. You can buy protective clothing and equipment at hardware stores or building supply stores.

Indoor Applications. If the label directions permit, leave all windows open and fans operating after the application is completed. If the pesticide product is only effective in an unventilated (sealed) room or house, do not stay there. Put all pets outdoors, and take yourself any your family away from treated areas for at least the length of time prescribed on the label. Apply most surface sprays only to limited areas such as cracks; don't treat entire floors, walls, or ceilings. Don't let pesticides get on any surfaces that are used for food preparation. Wash any surfaces that may have pesticide residue before placing food on them.

Outdoor Applications. Never apply pesticides outdoors on a windy day (winds higher than 10 mph). Position yourself so that a light breeze does not blow pesticide spray or dust into your face.

LC50 Anas platyrhynchos (mallard ducks) > 3680 ppm (99% Nicarbazine (both moieties)) A mortality was 80% at 5720 ppm ai, 10% at 1968 ppm nicarbazin, and 0% at the control and < or = 802 ppm ai test levels; treatment-related signs of toxicity were evident by day 2.

LC50 Northern bobwhite > 5720 ppm (99% Nicarbazine (both moieties)) Single mortalities (10%) were observed at the 1968 and 5720 ppm nicarbazin levels and may have been caused by exposure; effects were first observed between Days 5 and 6 and included wing droop, ruffled appearance, and/or foot lesions (from picking)

LC50 Salmo gairdnerii (rainbow trout) > 69 ppm (96 hr) /98.0% Nicarbazine (moiety - 4,4'-dinitrocarbanilide (DNC)/

LC50 Salmo gairdnerii (rainbow trout) > 110 ppm (96 hr) /99.4% Nicarbazine (moiety - 4,6-dimethyl-2-pyrimidinol (HDP)/

For more Ecotoxicity Values (Complete) data for NICARBAZIN (6 total), please visit the HSDB record page.

Nicarbazin concentrations in liver of chickens reared on the ground and fed diets containing this compound ranged from 0.2 to 0.4 mg/kg(1). Levels in the litter were 80 to 100 mg/kg(1). In samples from cage-reared chickens, nicarbizin was not detected from the 9th day after withdrawal(1).

/BIRDS and MAMMALS/ /Nicarbazine/ causes reproductive effects in several bird species. ... Low concentrations of nicarbazin fed in the diet will adversely impact avian reproduction (which is to be expected given its mode of action). For example, significantly reduced egg production and hatchability of fertile eggs was reported at a dietary concentration of 25 ppm when fed to chickens for only four days, and eggshell pigmentation was reduced after only two days of feeding. These effects were even more pronounced at dietary concentrations of 50 and 100 ppm. In several studies, negative impacts on egg hatchability in chickens fed 20 ppm nicarbazin in the diet for only 9 to 10 days have been reported in several studies. In another study, mortality occurred in chickens fed 1600 and 2500 ppm nicarbazin in food ration, and depressed growth and reduced egg hatchability was seen at lower concentrations.

/BIRDS and MAMMALS/ ... By the 2nd week of nicarbazin treatment, egg production was significantly reduced in birds fed 125 and 200 ppm (P<0.05). Similarly, increasing levels of nicarbazin resulted in decreasing egg weights (P<0.01) and feed intake was significantly decreased. By the 2nd week post-nicarbazin treatment, egg production, egg weight, and feed intake had returned to normal. Nicarbazin had no effect on egg shell deformation or body weight. 125 and 200 ppm reduced hatchability significantly (P<0.01) as well as producing an increased incidence of malpositions and malformations. When nicarbazin was withdrawn from the diet, hatchability returned to pretreatment values although malpositions and malformations were still in evidence. Effect of nicarbazin on production of brown-shelled eggs: dietary nicarbazin resulted in significant loss of shell color at 20 and 40 ppm, whereas 80, 125, and 200 ppm, brown eggs lost virtually all their color.

/BIRDS and MAMMALS/....Mallards were given gelatin capsules containing 0, 8.5, 17.0, or 33.75 mg of NCZ/kg of BW perorally once daily for 14 d. Fecal 4,4'-dinitrocarbanilide (DNC) and fluorescein were evaluated as potential markers of plasma and egg DNC levels. Plasma, egg, and fecal DNC levels differed among treatment groups in a dose response relationship. There were no significant effects on the numbers of eggs laid per female per day, proportion of fertile eggs, proportion of eggs hatching, or egg yolk mottling. Hatchability was 0.55 +/- 0.1 in the control group compared with 0.26 +/- 0.1 in the 33.75 mg/kg of BW group. Degeneration of the vitelline membrane was evident at all treatment levels; severity was dose-related and greater in the outer vitelline membrane than the inner vitelline membrane. No significant health effects were observed for birds treated with NCZ. The heterophil:lymphocyte ratio was elevated during the treatment and posttreatment periods in all groups, indicating birds were experiencing stress due to handling. Fecal DNC levels did not correlate well with plasma DNC levels, likely due to NCZ being administered as a bolus dose rather than being fed ad libitum. Fluorescein correlated well with plasma DNC levels during the treatment period and can therefore be used successfully as a noninvasive marker to determine the approximate amount of NCZ a bird is consuming. ...

/BIRDS and MAMMALS/ ...Using broilers not acclimated to heat stress, nicarbazin increased /heat production/ (P<0.05) (9.5 vs. 9.0 kcal/hr per MWT) and body temperature (P=0.08), reduced (P<0.05) respiration rate, and had no impact on /evaporative heat loss/ or /sensible heat loss/ (P>0.1). In contrast, the bird acclimated to heat stress exhibited similar (P>0.1) thermobalance responses irrespective of nicarbazin supplementation.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Groups of five male and five female beagle dogs were fed diets containing the phenylurea and the pyrimidone components (purity unspecified) in a ratio of 3:1 on six days per week for two years. The actual intakes were 0, 60, 180, or 600 mg/kg bw/day of the phenylurea component and 0, 20, 60, or 200 mg/kg bw/day of the pyrimidone component. Two animals of each sex per group were killed after one year. Clinical observations were made daily, and body weight, food consumption, and reflexes were determined weekly; water intake and urinary output were measured monthly. Hematological, clinical chemical, and urinary parameters were determined before treatment and in months 3, 6, 12, 18, and 24. A wide range of tissues from all dogs was examined grossly and microscopically. ...No abnormal behavior or physical signs were seen; however, one male at the intermediate dose died of unknown causes during week 44. A green-to-yellowish hue was seen in the excreta of all treated dogs. Body-weight gain, food intake, and hematological and urinary parameters were unaffected by treatment. Serum alanine aminotransferase activity was increased in several dogs at the highest dose and in one dog at each of the lower doses, but in most cases the effects were transitory. The highest values were observed at about 12 months, and elevated activity persisted in only two animals at the high dose. Organ weights and gross pathological appearance revealed no treatment-related changes. The histopathological appearance was unremarkable, apart from slight bile-duct proliferation in one dog killed after one year of treatment with the high dose. This animal had been found to have elevated serum alanine aminotransferase activity. Although the relationship between the hepatic findings and treatment was unclear, the conservative NOEL in this study is 240 mg/kg bw day.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Groups of FDRL rats were fed diets containing the phenylurea and the pyrimidone components (purity unspecified) for two years at concentrations calculated to give doses of 0, 50, 150, or 300 mg/kg bw/day of the phenylurea component and 0, 17, 50, or 100 mg/kg bw/day of the pyrimidone component. The groups consisted of 50 males and 50 females for control and the high doses and 40 males and 40 females for the low and intermediate doses. Five rats of each sex from the control and high-dose groups were killed during months 6 and 18, and 10 rats of each sex per group were killed in week 56. The animals were observed daily for behavior, physical appearance, and survival. Food consumption and the efficiency of food use were assessed weekly for the first 12 weeks and then periodically on 15 animals of each sex per group. Body weight was recorded weekly for the first 12 weeks, then biweekly until week 26 and monthly thereafter. Water intake and urinary output were measured on 10 rats of each sex per group during one week per month for the first three months. Limited hematological, clinical chemical and urinary parameters were examined on 10 rats of each sex per group at 3, 6, 9, 12, 18, and 24 months. A wide range of tissues from all rats was examined grossly and microscopically. ...No abnormal behavior was noted, and mortality was unaffected by treatment. Food and water intake and body-weight gain were similar in all groups. There were no treatment-related effects on hemoglobin, hematocrit, leukocytes, blood urea nitrogen, serum alanine aminotransferase activity, blood glucose, urinary parameters, organ weights, or gross pathological appearance. Changes in the kidney, such as calcareous material in the tubules, calcification in the renal pelvis, tubules, glomeruli, or medulla, and calculi, were more frequent in treated groups at 56 weeks, but the overall incidence was similar in all groups at the end of the study. The incidence of testicular atrophy was slightly elevated in some treated males at 104 weeks, but significance was not attained. Tumor incidences were unaffected. The NOEL was 400 mg/kg bw/day of the 3:1 mixture.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Groups of 12 male and 12 female FDRL rats were fed diets containing the phenylurea and the pyrimidone components (purity unspecified) at concentrations calculated to achieve doses of 0, 50, 150, or 300 mg/kg bw/day of the phenylurea and 0, 17, 50, or 100 mg/kg bw/day of the pyrimidone. Treatment was administered continuously during the production of 2 litters per generation for 3 successive generations. The initial groups of animals were paired 10 weeks after the start of treatment to produce the F1a litter and were paired again 7 days after weaning of the first litter to produce the F1b litter. At 4 weeks of age, 12 male and 12 female F1b offspring were mated according to the above schedule to produce the F2a and F2b litters, and the F2b offspring were used to produce the F3a and F3b litters. The animals were examined daily for survival, behavior, and appearance. Body weight and food consumption were measured weekly in adults. After birth, each litter was limited to 8 pups, which were weighed at birth and on postnatal days 4, 12, and 21. After the offspring had been weaned, the adult rats were autopsied, and the testes of F2 males in the control and high-dose groups were examined histopathologically. The liver, kidneys, heart, urinary bladder, and gonads from 5 male and 5 female F3b weaned pups from each group were also examined microscopically. ...Adult rats of each generation showed no effects on survival, body-weight gain, or food intake, and the results of gross autopsy and testicular examinations were unremarkable. The pregnancy rates and duration of gestation were unaffected. The body-weight gain of F1b pups at the high dose was slightly depressed during lactation, but a similar effect was not found in any other litter. In subsequent generations, the F2a and F3a litters at the high dose had slightly fewer pups, but the effect was not reproduced in the F2b or F3b litters. Histopathological examination of limited organs from F3b pups revealed no abnormalities attributable to treatment, and it was considered that there were no significant effects on reproduction. The NOEL was the highest dose tested, 400 mg/kg bw/day of the 3:1 mixture.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Groups of 24-25 CD/CRJ pregnant rats were given nicarbazin (equimolar complex; purity unspecified) as a suspension in 1% carboxymethyl cellulose by gavage at doses of 0, 70, 200, or 600 mg/kg bw per day on gestation days 7-17. Details of the method were not given in the report, but the tabulated results indicate that food and water intake and body weights were recorded daily on gestation days 7-21. The times of sacrifice of dams and examination of fetuses were not indicated. Fetuses were subjected to external, visceral, and skeletal examinations. Since the protocol was not provided, it is not known whether a recognized test guideline was followed or if quality assurance was undertaken, and the adequacy of the study could not be determined. Seven rats at 600 mg/kg bw per day died, mostly during the treatment period. The food intake and body-weight gain of dams at 600 mg/kg bw per day were depressed from gestation day 8. Implantations and in-utero survival were similar in all groups, while fetal body weight was lower at 600 mg/kg bw per day. The fetuses of the dams at 600 mg/kg bw per day had delayed ossification, hyperplastic and bent ribs (four fetuses), sacralization of the 6th or 7th lumbar vertebrae (two fetuses), cleft palate (two in same litter), subcutaneous edema (three in same litter), hydronephrosis (five fetuses), cryptorchismus (one fetus), and remained Merkel's diverticulum (one fetus). The NOEL for maternal and fetal toxicity was 200 mg/kg bw per day.

For more Non-Human Toxicity Excerpts (Complete) data for NICARBAZIN (6 total), please visit the HSDB record page.

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

LD50 Mouse oral approx 4,000 mg/kg /2-Hydroxy-4,6-dimethylpyrimidine (HDP)/

LD50 Rat oral > 10,000 mg/kg bw

LD50 Mouse oral > 18,000 mg/kg bw /4,4'-Dinitrocarbanilide (DNC)/

LD50 Mouse oral > 25,000 mg/kg bw

LD50 Rat dermal > 5,000 mg/kg

A tolerance of 4 parts per million is established for residues of nicarbazin in uncooked chicken muscle, liver, skin, and kidney.

New animal drugs for use in animal feeds. Nicarbazin. a) Specifications. Type A medicated articles containing 25 percent nicarbazin. (b) Approvals. See Nos. 000986, 060728, and 066104 in §510.600(c) of this chapter for use as in paragraph (d) of this section. (c) Related tolerances. See §556.445 of this chapter. (d) Conditons of use. It is used in chicken feed as follows: [Table#7129]

Based on the limited use pattern/exposure scenario, the submitted data are deemed adequate to support nicarbazin registration. Avoiding nontarget exposure is the primary concern with use of OvoControl-G. Reduction in egg hatchability is the primary concern if nontarget birds are exposed to nicarbazin. On the basis of label requirements, it can be reasonably assumed that exposure and resultant risk to non-target and endangered species would be low.

Nicarbazin interferes with the formation of the vitelline membrane, separating the egg yolk and egg white. The exact mode of action is unknown, although it is thought nicarbazin interferes with cholesterol metabolism in the formation of the membrane. Eggs from treated birds are described as mottled in appearance, reflecting a porous vitelline membrane. The effect on hatchability is a function of time and dose and the effect is reversible.

Rats received single oral doses of 1, 5, or 10 mg/kg bw nicarbazin; one animal at each dose was killed 6 or 18 hr after treatment, and the blood concentrations of the phenylurea and pyrimidone components were determined. Low concentrations of the phenylurea component were detected at 6 hr, but it was not detected at 18 hr. The pyrimidone component was found at considerably higher concentrations, which increased between 6 and 18 hr. Qualitatively similar findings were obtained in rats given oral doses of 0.1, 1, or 5 mg/kg bw per day for eight days and killed 4 or 24 hr after the last dose. The blood concentrations of the pyrimidone component were dose-related, while those of the phenylurea component showed a flat response. In the latter experiment, urine collected for 5 hr after the last dose contained dose-related concentrations of each component of nicarbazin, although the concentrations of the pyrimidone were an order of magnitude higher than those of the phenylurea component

...Nicarbazin, in the form of 4,4'-dinitrocarbanilide (DNC), was detected in 39 of the 190 eggs analysed. ... The concentrations of both the DNC and 4,6-dimethyl-2-hydroxypyrimidine (DHP) components of the drug in eggs were proportional to feed levels. The maximum feed nicarbazin concentration of 12.1 mg/kg (8.6 mg/kg DNC and 3.5 mg/kg DHP) gave rise to mean maximum whole egg concentrations of 631 micrograms/kg DNC and 51.8 micrograms/kg DHP. After withdrawal of the experimental diet, DNC was undetectable in eggs after 12 days and DHP after 3 days. Feed contaminated with nicarbazin at concentrations greater than about 2 mg/kg gave rise to egg DNC residues at concentrations greater than the Differential Action Limit (DAL) set by the UK (100 micrograms/kg). DNC was contained almost entirely in the yolk of the egg, whereas DHP was distributed between albumen and yolk in a ratio of approximately 3:1.

Used as a coccidiostat for poultry and to reduce egg hatching in resident Canadian geese; [HSDB]

Farming (Pesticides) [Category: Industry]

For nicarbazin (USEPA/OPP Pesticide Code: 85712) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Egg hatch reduction in resident Canada geese (Branta canadensis)

Therapeutic category (veterinary): coccidiostat

Nicarbazin ... first product to have truly broad-spectrum activity /for treatment of coccidiosis in chickens/

Urea, N,N'-bis(4-nitrophenyl)-, compd. with 4,6-dimethyl-2(1H)-pyrimidinone (1:1): ACTIVE

The use of OvoControl G is limited to sites in urban areas such as office parks, recreational parks, golf courses, schools, hospitals, restaurants, and commercial and industrial sites. Urban is defined as a municipality and its adjacent areas with a population of 50,000 or more. It may also be used at land airports holding FAA certifications under 14 Code of Federal Regulations 139.101 and having a wildlife hazard management plan under 14 Code of Federal Regulations 139.337.

Equimolar complex of 4,4'-dinitrocarbanilide and 2-hydroxy-4,6-dimethylprimidine