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EX OXNET PEP-ETFIEPI ION ittp://ace.orst.edu/cgi-bin/mfs/0 E/pips/cthephon.htm to 20 rats per sex per dose level at 0, 50, 100, and 200 mg/kg/day. Plasma cholinesterase and brain cholinesterase activity were found to be different from the controls at all dose levels. However, red blood cell cholinesterase activity did not differ from the controls in either sex of any dose group (315). The acute oral LD50 of 24% ethephon solution in propylene glycol for rats was reported to 4 range between 3,400 mg/kg (RTECS, 1985) to 4,229 mg/kg (Hartland Kidd, 1987) (302). The dermal LD50 for the same 24% solution for rabbits was 5,730 mg/kg. Irritation of mucous membranes in rabbits was also reported. The same study indicated that the inhalation LC50 for rats ' was greater than 5 mg/l of air(1, 242, 313). EPA reported the acute oral LD50 to be 1.6 g/kg for rats; the acute dermal LD50 for rabbits to be greater than 5 g/kg; and the primary skin irritation score for rabbits to be 6.75 (corrosive) (316). The oral LD50 for mice fed technical ethephon was 2850 mg/kg; 5,000 mg/kg for rabbits; 4,200 mg/kg for guinea pigs; and an unreported 4,200 mg/kg for mammals (313). In a dog study, ethephon was administered in the food to 4 dogs per sex per dose level at 0, 5.0, 25.0, or 187.5 mg/kg/day for 13 weeks. Plasma cholinesterase activity was depressed in both males and females at all dose levels. Red blood cell activity was depressed in the males (at all dose Ievels except 5.0 mg/kg/day at 8 weeks) and at the 25.0 and 187.5 mg/kg/day dose levels in the females. Brain cholinesterase activity was significant only in females dosed at 187.5 mg/kg/day(315). I • Chronic Toxicity: A chronic tox i c ity/oncoge ni city study using Swiss albino mice included 85 mice ' fed diets containing 0, 4.5, 45, or 150 mg/kg/day of ethephon for 78 weeks. Inhibition of plasma cholinesterase activity was significant at the 45 and 150 mg/kg/day dose levels in males and females. The No Observable Effect Level (NOEL) for plasma cholinesterase activity is 4.5 mg/kg/day for both sexes and the Lowest Effect Level (LEL) for this effect was 45 mg/kg/day for both sexes (315). There appeared to be a dose-related decrease in red blood cell cholinesterase activity in females. There was significant depression in RBC cholinesterase activity at the 45 and 150 mg/kg/day dose levels, while females in the 4.5 mg/kg/day dose groups exhibited depression in j i RBC cholinesterase activity at 52 weeks and 78 weeks, which was not considered statistically significant. Because of the apparent dose-related decrease in RBC cholinesterase activity in females E in the 4.5 mg/kg/day dose group, the NOEL for this effect in females is considered to be below 4.5 mg/kg/day, the lowest dose tested (315). RBC cholinesterase activity was nominally decreased in males at the mid- and high-dose groups. Brain cholinesterase activity was not different from control values at any dose level in males or females. In two-year feeding studies, rats receiving greater than or equal to 12,500 mg/kg diet showed no ill-effect except at top dose levels toward the end of the trial (242). The highest dose without adverse effects reported in rats was 375 mg/kg/day for 90 days (1). r • Reproductive Effects: A developmental toxicity study was conducted on New Zealand white rabbits. The doses tested were 50, 100, or 150 mg/kg. The teratogenic NOEL was greater than 50 mg/kg/day (LDT or lowest dose tested). The number of litters at termination of the study were insufficient to determine teratogenic effects at the 100 and 150 mg/kg/day levels. The embryotoxic I' NOEL was 50 mg/kg/day(LDT); an increased average number of resorptions occurred. The maternal toxic NOEL was 100 mg/kg, while the maternal LEL was 250 mg/kg (HDT or highest dose tested); decreased body weight, food consumption and increased mortality occurred at this dose level. The fetal toxic NOEL was reported to be 50 mg/kg/day. The fetotoxic LEL was 100 mg/kg/day, at which decreased fetal viability was reported (314). In another study, doses of 0, 200, 750, and 1,500 ppm of 39% ethephon were tested in a multigeneration rat reproduction study. The NOEL was reported to be greater than 1500 ppm (highest dose tested) (314). • Teratogenic Effects: The NOEL for rat teratogenic effects is 600 mg/kg/day, while in the rabbit, the NOEL was reported to be 50 mg/kg/day based on fetal resorptions at higher dose levels tested (314, 316). • Mutagenic Effects: Ethephon studies in Salmonella typhimurium indicated no mutagenic effect up to 1,000 micrograms/100 microliters, without enzyme activation (316). • Carcinogenic Effects: A carcinogenicity study was conducted in mice using 70.6-72.1% ethephon. of 4 1/26100 8:58 AM r