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EXTOXNET PIP-NICOSULFURON
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<br /> weights in males (49, 50, 51).
<br /> • Reproductive Effects: In a multigeneration reproduction study, rats were fed doses of 0, 12.5, 287, and 1,269
<br /> mg/kg body weight/day. The NOEL for systemic toxicity is 287 mg/kg/day with a lowest-observable-effect level
<br /> (LOEL) of 1,269 mg/kg/day, based on FI (first mating) females with a lower body weight gain during the final
<br /> week of gestation and a similar pattern in the FO females during the same gestational period, and in pup weights at
<br /> postpartum day 14 through 21 in the F2a high dose group. The reproductive NOEL is 287 mg/kg/day with a LOEL
<br /> of 1269 mg/kg/day based on minimal reduction in litter size at birth(49, 50, 51).
<br /> • Teratogenic Effects: A rat teratology study using doses of 0, 186, 930, 2325, and 5581 mg/kg/day showed no a
<br /> developmental or maternal effects up to 5581 mg/kg/day,the highest dose tested. The maternal and developmental
<br /> LOEL is greater than 5581 mg/kg/day. No treatment-related effects were noted on maternal or developmental
<br /> toxicity up to and including 5581 mg/kg/day, the highest dose tested (50). A rabbit teratology study using doses of
<br /> 0, 93, 465, 930, and 1860 mg/kg/day of Accent yielded a maternal NOEL of 93 mg/kg/day and LOEL of 465
<br /> mg/kg/day based upon maternal toxicity occurring at 465 mg/kg/day; an increase in clinical signs, gross
<br /> pathological observations, abortions,postimplantation loss and a decrease in body weight gain during the dosing
<br /> period. The developmental NOEL of 465 mg/kg/day and LOEL of 930 mg/kg/day is based upon developmental
<br /> toxicity occurring at 930 mg/kg/day; reduced mean fetal body weight and the apparent increase in postimplantation
<br /> loss at 465 mg/kg/day and above (50).
<br /> • Mutagenic Effects: No mutagenic activity was observed when tested in four strains of Salmonella typhimurium. In
<br /> vitro chromosomal aberration test in cultured human lymphocytes indicated negative responses at the
<br /> concentrations from 40 to 470 ug/ml. Nicosulfuron assayed with or without metabolic activation in vitro in Chinese
<br /> Hamster Ovary cells was nonmutagenic at the concentrations from 4 to 465 ug/ml and a micronucleus assay in
<br /> mouse bone marrow cells was negative at dose levels from 500 to 5,000 mg/kg. A DNA synthesis study in rat
<br /> hepatocytes(liver cells) did not cause any DNA damage in the cells at concentrations from 0.04 to 470 ug/ml (46,
<br /> 49, 50).
<br /> • Carcinogenic Effects: A 2-year chronic toxicity/oncogenicity study with male and female rats fed dosages of 0,
<br /> 1.9/2.6, 58.1/77.1, 289/382, and 786/1,098 mg/kg body weight/day showed no effects up to 786 mg/kg/day in maleE
<br /> and 1,098 mg/kg/day in females, the highest dose tested. The systemic LOEL is greater than 786 mg/kg/day and
<br /> 1,098 mg/kg/day for male and female rats, respectively(49, 50). In an 18-month oncogenicity study, male and
<br /> female mice administered dosages of 0, 3.3/4.4, 32.7/44.8, 327/438, and 993/1312 mg/kg body weight/day resulted
<br /> in no effects up to 993 and 1312 mg/kg/day, the highest dose tested for male and female mice,respectively(49, 50).
<br /> • Organ Toxicity: No information was found.
<br /> • Fate in Humans and Animals: Five groups of rats, 5 males and 5 females, were dosed in various sequences with
<br /> either 10 mg/kg or 1,000 mg/kg of[pyridinyl-14C]-DPX-V9360 or [pyrimidinyl-14C]DPX-V9360 either orally or
<br /> intravenously. Both males and females excreted essentially all of the radionuclide in the feces and urine.
<br /> Elimination of 14C-CO2was not observed. No organ or tissue showed total 14C-radioactivity>0.01%of the
<br /> administered dose. The major radioactivity was recovered as the parent which ranged from 85 to 97%. Two
<br /> metabolites,pyridine sulfonamide and 5-hydroxy pyrimidine amine, were identified. The presence of pyridine acid
<br /> sulfonamide was also suggested, but not positively identified. Several undefined metabolites makeup <10%total
<br /> recovered radioactivity(TRR). Based on the metabolites identified,the major pathway in the rat is cleavage of the
<br /> parent DPX-V9360, to yield pyridine sulfonamide and pyrimidine amine; 5-OH pyrimidine amine could be formed
<br /> either before or after the cleavage (50).
<br /> ECOLOGICAL EFFECTS
<br /> • Effects on Birds: Nicosulfuron is slightly toxic to birds on an acute and dietary basis. The oral LD50 for bobwhite
<br /> quail was>2,250 mg/kg. The dietary LC50s for mallard ducks and bobwhite quail were>5,620 ppm(46, 37, 50,
<br /> 51).
<br /> • Effects on Aquatic Organisms: Nicosulfiuon is practically non-toxic to freshwater fish and invertebrates. The 96
<br /> hour LC50 for bluegill and rainbow trout is>1,000 mg/L. The 48 hour EC50 for Daphnia magna is>1,000 mg/L (1,
<br /> 37, 50).
<br /> • Effects on Other Animals (Nontarget species): Nicosulfuron has an acute contact toxicity LD50>20 ug/bee and
<br /> littp://extoxnet.orst.edu/pips/riicosulf.htin 7/1/2006
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