| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Ten male and ten female mice/dose were offered food containing each of the following concentrations of SKW 20010 (/forchlorfenuron/ 100% purity): 0, 900, 1800, 3500 or 7000 ppm. Food containing the test article was offered ad libitum for 90 days. Mean consumption of test compound at the 5 dosage levels in ascending order was males/females 162/206, 332/411, 609/788 and 1288/1683 mg/kg/day. There was no mortality and clinical signs were limited to a higher incidence of scabbing and reddening of the ears of treated maleshowever, there was no dose-response for this clinical sign and it was not observed in females. Only animals fed 7000 ppm had mean body weights which were lower than controls. This was true for both males and females, starting at 3 weeks. However, only in the case of males during the ninth week was the difference statistically significant. Food consumption was significantly lower for animals fed the highest dose, for a total of 4 weeks in the case of males and for one week in the case of females. At 3500 ppm both sexes suffered a single week with significantly lower food consumption. Tests in clinical pathology at 90 days revealed no convincing compound-related effects. Platelets were elevated for all males fed the test compound, but these increases were not statistically significant, showed no dose-response, and were absent from treated females. A similar pattern was noted for elevated urea nitrogen in treated males with one difference: the increase at 900 ppm was statistically significant. Bilirubin was elevated for both males and females at 7000 and 3500 ppmhowever, only the increases at 7000 ppm for females and 3500 ppm for males were statistically significant. At necropsy, 4 males and 4 females were noted as having gray lacrimal glands, compared to none in controls. However, there was no dose-response for this endpoint. Free organ weights were not significantly different for treated versus control animals. In contrast, when organ weights were normalized to final bodyweights, significant increases in liver weights were identified in males at 3500 and 7000 ppm and in females at 7000 ppm. Normalized liver weights were also elevated in males at the two lower doses (though not significantly), perhaps suggesting a dose-response. However, since free liver weights were not significantly different from controls and microscopic examination of stained liver sections were negative, it is doubtful that the test compound caused liver enlargement. Lastly, the normalized kidney weights of females fed the highest dose were significantly elevated compared to controls, and microscopic examination of that organ revealed an increased incidence of infiltration of lymphocytes into the interstitium and pelvis (true for both males and females). However, since these infiltration events were almost always graded as minimal, and free kidney weights were not significantly elevated compared to controls, the case for a compound-related effect on the kidneys is weak./LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Four male and four female Beagle dogs/dose were offered feed containing each of the following concentrations of CN-11-3183 (/forchlorfenuron/ 99.9% purity): 0, 50, 500, 5000 ppm. The food was offered for 2 hours/day for 90 consecutive days. Samples of feed from weeks 1, 2, 3, 4, 8 and 12 were analyzed chemically to ensure that proper dosage levels were maintained. Calculated mean test compound consumption for the four dosage levels, in ascending concentration, were 0, 1.8, 18.0 and 176 mg/kg/day. No animals died during the study. Abnormal in-life clinical signs were never detected in more than one animal per dosage level and were short in durationtherefore, they were not considered to be compound-related. Mean body weights of treated animals were not significantly different from controls. Tests in hematology, serum chemistry and urinalysis detected few statistically significant differences between treated animals and controls. MCH was significantly lower at 90 days for females fed 5000 ppmhowever, lack of any effect in males or in other red cell parameters suggested that the test compound was not the cause. The alterations in SGOT activity, while significant, fit no pattern consistent with any dose-response. Only cholesterol levels in both males and females were consistently higher than controls at 5000 ppm, at both 45 and 90 days (although the increases at 90 days were not statistically significant). Pathological exams identified two alterations which each occurred in treated animals but not in controls: nodules in the duodenum and a dark blue or enlarged spleen. However, there was no dose response for either abnormality and microscopic examination of the tissues did not support a compound-related etiology. Lastly, whether organ weights were normalized to final body weight or brain weight, there were no significant effects in treated animals. ... NOEL (M/F) 500 ppm (based on elevated serum cholesterol levels at 45 and 90 days for animals fed 5000 ppm, with only the 45 day levels being significantly above controls)./LABORATORY ANIMALS: Subchronic or Prechronic Exposure/Two male and two female Beagle dogs/dose were offered feed containing each of the following concentrations of SKW 20010 (/forchlorfenuron/ purity: 99.4%): 0, 7500, 10000 ppm. The food was offered for one hour/day for 91 consecutive days. Samples of feed taken at weeks 0, 1, 6 and 13 were analyzed chemically to ensure that proper dosage levels were maintained. Consumption of test article for the 7500 and 10000 ppm dosage levels was 173 and 212 mg/kg/day for males and 208 and 232 mg/kg/day for females (means of the 13 weeks). There was no animal mortality. The only compound-related abnormal clinical sign was decreased defecation in all animals fed 10000 ppm and in one male fed 7500 ppm. Both males and females lost weight for the first 3 weeks at the highest dose (mean body weights)the 2 males gained weight thereafter while the females remained essentially constant. At the 7500 ppm level the males' weights remained fairly constant, while the females gained weight (about 33% of the control group's weight gain) after a 2 week lag. Decreased food consumption probably accounted for some of these effects, since it was sporadically lower for both males and females in both dosage groups. Hematology tests detected elevated white cells in males at 7500 and 10000 ppm which was primarily due to an increase in segmented neutrophils. Males also showed elevated reticulocytes for the higher dose. Females exhibited decreased red cells and decreased hematocrit at the higher dose. Although platelet counts were elevated in treated males and females, the changes were not considered compound-related since the values fell within the ranges of historical controls. Leukocyte counts and serum chemistry did not reveal any changes in treated animals which were outside the range of historical controls except for elevated cholesterol in females at 7500 and 10000 ppm (males were also elevated but within historical controls) and elevated total protein in females at 10000 ppm (only the change in protein was statistically significant). The gross pathological exam detected no abnormalities common to the 2 animals in each dosage group. Microscopic examination of fixed tissue was also negative. Lastly, mean liver weights normalized to final body weights were elevated for both sexes at both doseshowever, free liver weights were not elevated, indicating that the increase in normalized liver weight was due to decreased animal body weight. The absence of histopathologic lesions in the liver supported this conclusion./LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ One male and one female Beagle dog/dose were offered feed containing each of the following concentrations of CN-11-3183 (/forchlorfenuron/ purity: 98.9%): 0, 150, 500, 2500, 7500 ppm. Food containing the test article was offered for 2 hours/day for 10 days, followed by a 5 day interval when feed without test article was mistakenly used, followed again by a 42 day interval of daily compound presentation in the feed. Weekly samples of feed were analyzed chemically to ensure that proper dosage levels were maintained. No animals died during the study and there were no abnormal clinical signs. Similarly, necropsy at study termination revealed no abnormalities common to the different dosage levels. Despite the use of only one male and one female per dose, the data suggest that the subject product did affect body weights and food intake. The male fed 7500 ppm exhibited decreased weight gain relative to the control, not exceeding its starting weight until week 5. Females were more sensitiveanimals fed 2500 or 7500 ppm suffered both an early growth delay and a late weight loss. Smaller but similar effects may have been seen in the females fed the two lower doses. Food intake on a grams/animal/day basis was reduced for males at 7500 pm and for females at 7500 and 2500 ppm. When food consumption was normalized to animal weight (grams/kg/day), the compound's effect was only evident at the highest dose of 7500 ppm, again for both sexes.For more Non-Human Toxicity Excerpts (Complete) data for Forchlorfenuron (19 total), please visit the HSDB record page. |
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