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4 ACUTE AND SHORT-TERM TOXICITY OF PERMETHRIN
Pages 43-56

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From page 43...
... The allergic responses have been attributed to impurities in the pyrethrins. Most of the studies of synthetic pyrethroids involved workers applying the chemicals for fly control (Prinsen and van Sittert, 1978~.
From page 44...
... Other signs that have been reported include hyperexcitability to external stimuli, lacr~mation, occasional diarrhea, defecation, and urinary incontinence (Ishmael, 19891. Core body temperature is increased when clinical signs are severe.
From page 45...
... ACUTE AND SHORT-TERM TOXICITY 45 TABLE 4-1 Acute Toxicity of Permethrin Administered to Various Animal Species Species Sex Route LDso (mg/kg Vehicle body weight) 2,949 ~ 4,000 DMSOa 1,500 DMSO 1,000 Corn oil 500 Corn oil 430 Corn oil 470 Corn oil 1,200 Reference Rat M F F M Oral Oral M Oral Oral Oral M Oral F Oral M, F Oral M, F Oral M Dermal F Dermal M Dermal F Dermal M, F Dermal M, F Dermal M F M F Water Water Water 1,725 Water >5,176 Noneb > 4,000 None None Xylene None scc sc ipd il Parkinson, 1978 Parkinson et al., 1976 Clark, 1978 Clark, 1978 Jaggers and Parkinson, 1979 Kohda et al., 1979 Kohda et al., 1979 Braun and Killeen, 1975 Sasinovich and Panshina, 1987 Parkinson, 1978 Parkinson et al., 1976 Khoda et al., 1979 Khoda et al., 1979 Clark, 1978 Sasinovich and Panshina, 1987 Kohda et al., 1979 Kohda et al., 1979 Parkinson et al., 1976 Parkinson et al., 1976 Sasinovich and Panshina, 1987 Metker, 1978 >2,500 >2,500 > 750 2,000 Corn oil 7,800 Corn oil 6,600 Water > 3,200 Lp lp Water Inhalation None Inhalation None > 3,200 463-1,725 500 mg/m3 (6 hr/d, 5 d/wk for 13 wk)
From page 46...
... . Mouse F Oral Water ~ 4,000 Parkinson et al., 1976 M, F Oral DMSO 250-500 Clark, 1978 M Oral Corn oil 650 Kohda et al., 1979 F Oral Corn oil 540 Kohda et al., 1979 M Dermal None >2,500 Kohda et al., 1979 F Dermal None >2,500 Kohda et al., 1979 M sc Corn oil > 10,000 Kohda et al., 1979 F sc Corn oil 10,000 Kohda et al., 1979 Rabbit F Oral Water >4,000 Parkinson et al., 1976 F Dermal None > 2,000 Parkinson et al., 1976 Guinea M Oral Water > 4,000 Parkinson et al., pig 1976 Hen Oral > 1,500 Millner and Butterworth 1977 _ , aDMSO = dimethyl sulfoxide.
From page 47...
... Source: NRCC, 1986. temic signs seen when the tick-repellent formulation was applied topi catty to rabbits at 2 g/kg were weight loss and diarrhea in one animal on days 10-14 (Shapiro, l989b)
From page 48...
... Gross tissue changes were observed in female mice in the 2,000- and 10,000mg/kg groups. Histopathological examination showed regenerating tubules in the renal cortex, hypertrophy of centrilobular hepatocytes with cytoplasmic eosinophilia, that were not dose related; these changes were observed in all the treated animals (Clapp et al., 1977a)
From page 49...
... Muscle tremors were observed in all animals in the 432-mg/kg group, but doses of 216 mg/kg or less produced no toxic signs in either male or female rats. Statistically significant increases in liver-to-body-weight ratios were seen at 432 mg/kg, but compound-related histological changes were not observed in any of the tissues or organs.
From page 50...
... The activity of liver microsomal enzymes was normal 4 weeks after dosing in the permethrin-treated animals. The amount of smooth endoplasmic reticulum in rat liver cells was significantly increased as a result of permethrin dosing, but within 4 weeks after dosing, no significant histological differences were observed in the livers of treated and control animals (Bradbrook et al., 1977~.
From page 51...
... Urinalysis and hematological and clinical biochemistry values were within normal limits. Signs of hyperexcitability and tremors were observed during the study in animals given 3,000 mg/kg, and their liver weights and liver-to-bod~y-weight ratios were slightly increased.
From page 52...
... Hematological, clinical chemistry, and urinalysis values were within normal limits in all animals. There was a slight increase in the liver weight of animals receiving 2,000 mg/kg per day but no accompanying histopathological changes in the liver (Edwards et al., 1976~.
From page 53...
... No gross pathological or significant histopathological findings were seen. Hematological and clinical chemistry values were within normal limits.
From page 54...
... No significant changes were noted in rabbit body weight or organ-to-body-weight ratios at the end of the 21-day test, and no skin irritation was observed. There were no significant changes in clinical chemistry values in the treated groups and no compound-related lesions on the skin or in other tissues and organs examined (Metker et al., 1977~.
From page 55...
... was selected for risk calculations. In most studies, no effects were observed in hematological or serum chemistry values, even at exposures that produced clinical signs of toxicity.
From page 56...
... Microscopically, hepatocellular swelling occurred, which has been attributed to increased microsomal activity resulting in a proliferation of endoplasmic reticulum. No morphological changes in the liver of dogs were observed at exposures of up to 2,000 mg/kg per day (in gelatin capsules)


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