National Toxicology Program

Selected toxicity information from HSDB, one of the National Library of Medicine's databases. ¹

Names (NTP)

• Rotenone
• (2R-(2-ALPHA,6AALPHA,12AALPHA))-1,2,12,12A-TETRAHYDRO-8,9-DIMETHOXY-2-(1-METHYLETHENYL)-(1)BENZOPYRANO(3,4-B)FURO(2,3-H)(1)BENZOPYRAN-6(6AH)-ONE (9CI)
• ROTENONE (TRANSGENIC MODEL EVALUATION)
• (2R-(2-ALPHA,6AALPHA,12AALPHA))-1,2,12,12A-TETRAHYDRO-8,9-DIMETHOXY-2-(1-METHYLETHENYL)-(1)BENZOPYRANO(3,4-B)FURO(2,3-H)(1)BENZOPYRAN-6(6AH)-ONE (9CI)
• Transgenic model evaluation (Rotenone)

Human Toxicity Excerpts

• Local effects incl conjunctivitis, dermatitis, pharyngitis, and rhinitis. Oral ingestion of rotenone produces GI irritation, nausea, and vomiting. Inhalation of the dust is more hazardous; it can cause resp stimulation followed by depression and convulsions. [Hardman, J.G., L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.G. Goodman (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill, 1996., p. 1687]**PEER REVIEWED**
  
• No unscheduled DNA synthesis (UDS) was observed in human fibroblast cultures (VA4) in the presence or absence of a rat S9 liver enzyme activation system when rotenone was tested at 1, 10, and 1000 mM concn. [National Research Council. Drinking Water & Health. Volume 5. Washington, D.C.: National Academy Press, 1983., p. 67]**PEER REVIEWED**
  
• CHRONIC POISONING MAY PRODUCE FATTY CHANGES IN LIVER, KIDNEY. [Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1423]**PEER REVIEWED**
  
• MORE TOXIC WHEN INHALED THAN WHEN INGESTED. [Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1423]**PEER REVIEWED**
  
• ROTENONE IS RELATIVELY FREE OF HAZARDS IN NORMAL USE, BECAUSE OF 1) THE LOW PERCENTAGE (1 TO 5%) COMMONLY USED IN FORMULATIONS; 2) THE UNSTABLE NATURE OF ROTENONE ... 3) ITS IRRITANT ACTIONS WHEN INGESTED ... 4) ITS LOW SOLUBILITY IN WATER. NO HUMAN FATALITIES HAVE BEEN REPORTED. ... ALTHOUGH THE MEAN LETHAL DOSE BY MOUTH VARIES WIDELY AMONG COMMON SPECIES OF LAB MAMMALS, A REASONABLE ESTIMATE FOR MAN IS 0.3 TO 0.5 G/KG. ... BECAUSE OF POOR /GI/ ABSORPTION, COARSE PARTICLES OF SOLID ROTENONE ARE MUCH LESS TOXIC THAN FINE POWDERS. FATS AND OILS PROMOTE ABSORPTION AND SO ENHANCE TOXICITY. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-366]**PEER REVIEWED**
  
• In massive overdose, principal effects include protracted vomiting, respiratory depression, and hypoglycemia and its symptoms. [Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 1086]**PEER REVIEWED**
  
• When derris powder was applied to the armpits of four persons twice daily for 30 days, one developed a mild rash at the site of application; the rash disappeared within 24 hr. The others experienced no inconvenience, except that one person noted a very mild smarting. When applied to the forearms as a 10% ointment in anhydrous lanolin, no local irritation or anesthesia was observed. About 10 min after derris or a water extract of it was taken into the mouth of volunteers, all experienced a sensation of numbness, as well as a metallic taste; these effects lasted 3 or 4 hr ... . [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 602]**PEER REVIEWED**
  
• A previously healthy 3.5-yr old girl died after drinking about 10 mL of an insecticidal preparation of rotenone ... Symptoms were initial vomiting and drowsiness leading rapidly to coma, depressed respiration, and apnea. Despite artificial ventilation begun within 2-2.5 hr of ingestion, the girl died at 8-8.5 hr. Postmortem showed anoxic damage in the cerebrum, lungs, and heart and serohemorrhagic pleural effusion. There was also evidence of an acute renal tubular necrosis, but the authors suggested that this could have been due to various etherial oils present in the insecticide. HPLC analysis of postmortem tissues showed rotenone concentration of 6 x 10-6 to 1 x 10-5 mol/kg and the estimated oral dose was 40 mg/kg. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 602]**PEER REVIEWED**
  
• Ingestion of rotenone was a common means of suicide by native of New Ireland ... When such persons were brought to medical attention while still alive, they were found to be in a state of collapse with feeble pulse and dilated pupils. Some, especially those suspected of having taken a very small dose, recovered following gastric lavage and stimulants. The only finding in numerous autopsies was that of acute congestive heart failure. The root was not generally found in the stomach, as vomiting before death was the rule. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 602]**PEER REVIEWED**
  
• ... mentioned the primitive industrial conditions for processing rotenone-bearing plants in the Amazon valley. Physicians observed some cases of severe irritation of the throat with partial destruction of the soft palate as well as of the anterior pillars and, very frequently, an irritation of the conjunctiva followed by ulcerative keratitis. Inflammation of the skin was notable in skin folds or where perspiration led to accumulation of the powder. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 603]**PEER REVIEWED**
  
• All workers in Lyon who encountered the fine powder developed in 2 or 3 days a violent dermatitis of the genital region. It was characterized by a red-violet color, slight edema, and some itching. In 24 hr, if exposure was topped, the irritated skin underwent desquamation in plaques of different sizes. If contact persisted, the dermatitis became worse; itching, erythema, and the leatherlike texture increased. The skin became covered with large, flat, excoriated, oozing papules in patches 0.5 cm in diameter. The dermatitis recurred with each new exposure. Workers also experienced ulcerative rhinitis and temporary but complete loss of the sense of smell. In some instances there was irritation of the lips and tongue. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 603]**PEER REVIEWED**
  
• Derris powder or ointment produces only a mild rash or no irritation of human ... skin. ... No anesthetic effect, such as is seen in the human mouth following application of either rotenone or derris, can be observed in the eye. Complete recovery can be expected in several days ... . [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  

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Non-Human Toxicity Excerpts

• RESP DEPRESSION & FALL IN ARTERIAL BLOOD PRESSURE IN RABBITS /IS/ PRODUCED BY IV ROTENONE ... . [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-367]**PEER REVIEWED**
  
• GIVEN IV TO TEST ANIMALS, IT PRODUCES VOMITING, INCOORDINATION, MUSCLE TREMORS, CLONIC CONVULSIONS & RESP FAILURE. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-366]**PEER REVIEWED**
  
• HIGHLY TOXIC TO FISH (LETHAL LESS THAN 50 PPB). [Spencer, E. Y. Guide to the Chemicals Used in Crop Protection. 7th ed. Publication 1093. Research Institute, Agriculture Canada, Ottawa, Canada: Information Canada, 1982., p. 506]**PEER REVIEWED**
  
• 60 MG/KG WILL KILL GUINEA PIGS. ... POISONING RESULTS IN RESP STIMULATION & CONVULSIONS, RESP DEPRESSION, COMA & RESP FAILURE. CHRONIC POISONING OF ANIMALS FED DIET CONTAINING 75 PPM OF DERRIS ROOT CAUSES CENTRAL LOBULAR HEPATIC NECROSIS. [Thienes, C., and T.J. Haley. Clinical Toxicology. 5th ed. Philadelphia: Lea and Febiger, 1972., p. 30]**PEER REVIEWED**
  
• SIGNS OF INTOXICATION: ATAXIA, NUTATION/ACT OF NODDING ESPECIALLY INVOLUNTARY NODDING/, DYSPNEA, POLYURIA, FEATHERS FLUFFED OR HELD TIGHTLY TO BODY, WING DROP, NECK PULLED IN, IMMOBILITY. REGURGITATION OCCURRED @ LEVELS ABOVE 1500 MG/KG. SIGNS WERE OBSERVED LESS THAN AN HOUR AFTER SINGLE ORAL ADMIN, AND MORTALITIES OCCURRED UP TO 5 DAYS AFTER TREATMENT. REMISSION TOOK UP TO 1 WK. /MALLARDS &/OR PHEASANTS/ [U.S. Department of the Interior, Fish and Wildlife Service. Handbook of Toxicity of Pesticides to Wildlife. Resource Publication 153. Washington, DC: U.S. Government Printing Office, 1984., p. 69]**PEER REVIEWED**
  
• ROTENONE WAS ADMIN BY INJECTION TO WISTAR RATS FOR 2-3 MO AT DOSES OF 0.1 TO 0.2 MG/RAT/DAY, 5 DAYS/WK. EARLY MAMMARY TUMORS APPEARED 6 MO AFTER THE END OF TREATMENT AND THE NUMBER OF TUMORS INCR UP TO 24 MO. [MERCHAN J ET AL; REV ESP ONCOL 25 (1): 107-20 (1978)]**PEER REVIEWED**
  
• Short term admin of rotenone in sunflower oil, injected ip in doses of 0.1 mg/kg/day for 5 days into female rats, produced a marked elevation in serum growth hormone concn and a decr in serum prolactin. These alterations & transient elevations in concn of estrogens, progesterone, and corticosterone suggested that rotenone was stimulating the hypophysis and that the physiopathogeny of rotenone-induced mammary tumors is indirect and hormonal. [National Research Council. Drinking Water & Health. Volume 5. Washington, D.C.: National Academy Press, 1983., p. 65]**PEER REVIEWED**
  
• The colony forming ability of continuously cultivated bovine cells (T4) derived from normal ovarian tissue was reduced to 50% in the presence of 3.5X10-7 M concn of rotenone. Alkali-labile single strand DNA breakage was observed when mouse L1210 leukemia cells were exposed to 1X10-7 M rotenone. ... No sister chromatid exchanges /were observed/ in Chinese hamster ovary cells in the presence or absence of a rat liver S9 metabolic activation system. The max dose level used was the dose that reduced the proportion of dividing cells to 50%. Rotenone added to Chinese hamster cells in vitro incr the mitotic index, and mitotic cells contained monopolar spindles with chromosomes grouped around centriole pairs near the cell center. The cmpd was also found to arrest mitosis in cultured mammalian cells by inhibition of the spindle microtubule assembly. [National Research Council. Drinking Water & Health. Volume 5. Washington, D.C.: National Academy Press, 1983., p. 67]**PEER REVIEWED**
  
• ... Histological exams were conducted on 30 tissue/organ samples from approx 30 ... /Syrian golden hamsters/ of each sex and exptl group that had received /98%/ rotenone at doses of 0, 125, 250, 500, or 1000 ppm in the diet for as long as 18 mo. There was no evidence /of carcinogenicity/ ... in Sprague Dawley rat study, rotenone in corn oil was admin daily by ip injection to 25 animals of each sex at doses of 0, 1.7, or 3.0 mg/kg body wt for 42 days. Fifteen animals of each sex were used as vehicle controls. The animals were observed for an addnl 18 mo... In the Wistar rat study, rotenone in corn oil was admin by gavage to 25 animals of each sex at doses of 0, 1.7, or 3.0 mg/kg body wt for 42 days. Fifteen animals of each sex were used as vehicle controls. The Wistar rats were observed for an addnl 12 mo... There was no evidence /of carcinogenicity in either study/. [National Research Council. Drinking Water & Health. Volume 5. Washington, D.C.: National Academy Press, 1983., p. 68]**PEER REVIEWED**
  
• A 90% mortality of the 4th instar larvae of Aedes aegypti occurred after exposure for 24 hr to 1 day-aged rotenone (4 ppm) extracted from Derris elliptica roots. The mortality percentage was dose-dependent and decreased by aging rotenone extracts. The toxicity of rotenone to mosquitoes was completely lost within 14-15 days after extraction. The content of rotenone in roots was higher (2.27%) in winter than in summer (1.6%). [Ameen M et al; J Bangladesh Acad Sci 7 (1-2): 39-47 (1983)]**PEER REVIEWED**
  
• Technical grades of rotenone at 0, 2.5, 5 or 10 mg/kg doses, suspended in corn oil, were administered orally in single doses on days 6-15 of pregnancy to Wistar rats. The dams were killed on the last day of pregnancy and all fetuses were evaluated following routine teratologic methods. Rotenone was associated with an increased number of non-pregnant rats and resorptions at 10 mg/kg dose; reductions in maternal body wt gain, fetal wt and skeletal ossification; and increased incidence of extra ribs at 5-10 mg/kg; no significant effects were noted at 2.5 mg/kg. [Khera KR et al; Teratology 23 (2): 45A-6A (1981)]**PEER REVIEWED**
  
• Applications of 2 or 5 ul/l concn of synergized rotenone (2.5%) in the Pro-Noxfish formulation to 2 shallow, 0.05 hectare ponds caused a temporary reduction in both total number and diversity of benthic invertebrates, a total mortality of caged Asiatic clams (Corbicula manilensis) in both ponds, and a partial mortality of a resident population of larval leopard frogs (Rana pipiens) in the 5 ul/l treatment. At day 7 after treatment, benthic organisms were reduced 67% by the 2 ul/l concn and 96% by the 5 ul/l application. The diversity index declined sharply in both ponds between days 3 and 7 after treatment, the lowest values being recorded on day 7 and day 37 in the 2 and 5 ul/l treatments, respectively. The equitability index declined from day 3 to day 37 in both ponds. By day 69, however, total numbers of benthic organisms had more than doubled over those originally present in the 2 ul/l treatment, had more than tripled in the 5 ul/l treatment, and were virtually unchanged in the control pond. Pretreatment zooplankton populations were low; no significant deleterious effects from the treatments were observed. [Burress RM; Invest Fish Control 90-91 (Paper no 2): 1-7 (1982)]**PEER REVIEWED**
  
• Rotenone was tested for mutagenicity in the Salmonella/microsome preincubation assay using a protocol approved by the National Toxicology Program. Rotenone was tested over a wide range of doses (0, 100, 333, 1000, 3333, and 10,000 ug/plate) in four Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) in the presence and absence of Aroclor-induced rat or hamster liver S9. Rotenone was negative in these tests and the highest ineffective dose level tested (not causing the formation of a precipitate) in any Salmonella tester strain was 333 ug/plate. [Zeiger E et al; Environ Mutagen 9: 1-110 (1987)]**PEER REVIEWED**
  
• Rotenone was not mutagenic when tested according to a preincubation protocol with Salmonella typhimurium strains TA100, TA1535, TA1537, and TA98 with or without metabolic activation by rat or hamster liver S9. Rotenone induced forward mutations in the mouse L5178K/TK + or - lymphoma assay without activation; it was not tested in the presence of S9. Results of tests with rotenone in Chinese hamster oveary cells were negative for induction of sister chromatid exchanges in the absence of exogenous metabolic activation (at concentrations at which the chemical was very toxic), equivocal for sister chromatid exchanges in the presence of rat liver S9 (due to a nonrepeatable positive response when tests were conducted up to toxic concentrations), and negative for chromosomal aberratons in both the presence and absence of metabolic activation. [DHHS/NTP; Toxicology and Carcinogenesis Studies of Rotenone in F344/N Rats and B6C3F1 Mice (Feed Studies) p.4 (1988) Technical Rpt Series No. 320 NIH Pub No. 88-2576]**PEER REVIEWED**
  
• It is about one half as toxic as pyrethrum. Rotenone dust affects the nervous system and causes convulsions in animals. Animals repeatedly fed derris powder (the botanical source containing 9.6% rotenone) at levels from 312 to 4,000 ppm developed focal liver necrosis and mild kidney damage. Of 40 female rats given daily intraperitoneal injections of rotenone in sunflower oil of 1.7 mg/kg for 42 days, more than 60% developed mammary tumors 6-11 months after the end of treatment; most of the tumors were mammary adenomas and one was a differentiated adenocarcinoma; none of the control animals had tumors when examined 19 months after treatment. [Zenz, C., O.B. Dickerson, E.P. Horvath. Occupational Medicine. 3rd ed. St. Louis, MO., 1994, p. 641]**PEER REVIEWED**
  
• Early chick embryo explants /were exposed/ for 15 minutes to 1 ug/ml and observed after explantation various degrees of growth inhibition and neural tube defect. [Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986., p. 504]**PEER REVIEWED**
  
• Rats /were gavaged/ on days 6 through 15 with 2.5, 5 or 10 mg per kg. Maternal and fetal weights were reduced at 5 and 10 mg. Minor skeletal defects were found in the 5 mg group and resorptions were 46% in the 10 mg group. [Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986., p. 504]**PEER REVIEWED**
  
• Rotenone is nonphytotoxic, moderately toxic to most animals, and very toxic to swine, but produces no harmful residues on vegetable crops. [Farm Chemicals Handbook 1997. Willoughby, OH: Meister Publishing Co., 1997., p. C323]**PEER REVIEWED**
  
• Signs of serious poisoning in animals include initial respiratory stimulation followed by respiratory depression, incoordination, clonic or tonic convulsions, muscle tremors, and death from respiratory failure ... The heart continues to beat and the blood pressure is maintained for a relatively long time after respiration has stopped. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• Dogs fed rotenone at the rate of 5 mg/kg/day for a month appeared well but showed fatty changes of the liver and kidneys. A dosage of 10 mg/kg/day killed 3/5 dogs, and one that was killed showed severe toxic injury of the liver, with possibly 1/3 of the bulk occupied by fat. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 601]**PEER REVIEWED**
  
• Dietary levels of 75 and 150 ppm of rotenone were tolerated by pregnant guinea pigs but injured the young, which were either born dead or failed to thrive after birth, suggesting that rotenone or a toxic metabolite is excreted in the milk ... . [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 601]**PEER REVIEWED**
  
• ... daily oral admin of rotenone to female rats at 5 mg/kg on days 6-15 of pregnancy resulted in reduced maternal weight gain and that 10 mg/kg/day killed 60% of the dams. ... the high dose increased the number of resorptions, but without producing significant fetal abnormalities. Some skeletal malformations such as extra ribs were seen at 5 mg/kg/day although this dose rate did not increase resorptions. Dosing at 2.5 mg/kg/day had no effects. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 601]**PEER REVIEWED**
  
• There is some disagreement in the literature regarding the carcinogenic potential of rotenone ... rotenone may cause tumors only in vitamin-deficient animals. Rotenone suppresses weight gain at or above 50 ppm in the diet of rats ... or hamsters ... and so suppression of cell division may limit carcinogenic potential ... increased serum growth hormone, progesterone, and estrogen levels may be involved in rotenone carcinogenesis and showed a parallel between tumor incidence and low-level rotenone-induced obesity in rats. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 601]**PEER REVIEWED**
  
• Rotenone is a potential spindle poison. At concn ranging from 1 x 10-7 to 1 x 10-5 M, the compound causes an increase in the mitotic index of cultured hamster cells within 15 min. The index reaches a peak, the height of which is proportional to the concn of the compound. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 602]**PEER REVIEWED**
  
• ... Under the conditions of these 2 year feed studies ... there was no evidence of carcinogenic activity for male or female B6C3F1 mice fed diets containing 600 or 1200 ppm rotenone for 2 years. The decreased incidence of liver neoplasms in male mice may have been related to the administration of rotenone. [DHHS/NTP; Toxicology and Carcinogenesis Studies of Rotenone in F344/N Rats and B6C3F1 Mice (Feed Studies) p. 3 (1988) Technical Report Series No. 320 NIH Pub No. 88-2576]**PEER REVIEWED**
  
• ... Under the conditions of these 2 year feed studies, there was equivocal evidence of carcinogenic activity of rotenone for male F344/N rats, as indicated by an increased incidence of parathyroid gland adenomas (uncommon tumors). There was no evidence of carcinogenic activity in female F344/N rats fed diets containing 38 or 75 ppm rotenone. [DHHS/NTP; Toxicology and Carcinogenesis Studies of Rotenone in F344/N Rats and B6C3F1 Mice (Feed Studies) p.3 (1988) Technical Rpt Series No. 320 NIH Pub No. 88-2576]**PEER REVIEWED**
  
• Rotenone ... reduced the background incidence of hepatocellular carcinoma in male B6C3Fl mice. In the present studies, rotenone reduced the basal hepatic labeling index of male B6C3Fl mice in a dose dependent fashion and inhibited hepatocellular proliferation, but not peroxisome proliferation, induced by the peroxisome proliferator Wy-14,643. These results indicate that reduction of hepatic tumors by rotenone may have been due to decr liver cell replication, that peroxisome proliferation can be induced in the absence of hepatocellular proliferation and suggest rotenone as a potential tool in studies of relationships cell proliferation, peroxisomal proliferation and hepatocarcinogenesis. [Cunningham ML, et al; Cancer Lett 95 (1-2): 93-7 (1995)]**PEER REVIEWED**
  

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Human Toxicity Values

• Lethal dose Human 0.3-0.5 g/kg (est) [Zenz, C., O.B. Dickerson, E.P. Horvath. Occupational Medicine. 3rd ed. St. Louis, MO., 1994, p. 641]**PEER REVIEWED**
  

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Non-Human Toxicity Values

• LD50 Rat oral 132-1500 mg/kg [American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986., p. 515]**PEER REVIEWED**
  
• LD50 White mouse oral 350 mg/kg [Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994., p. 906]**PEER REVIEWED**
  
• LD50 Mouse ip 2.8 mg/kg [Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1423]**PEER REVIEWED**
  
• LD50 Rat oral 132 mg/kg [Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1423]**PEER REVIEWED**
  
• Iv LD50 rat = 6 mg/kg [Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1423]**PEER REVIEWED**
  
• Oral LD50 Rat oral 64 mg/kg /Calculated from original mortality fractions/ [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• LD50 Rat oral 25 mg/kg /Calculated from original mortality fractions; oil solution/ [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• LD50 Rat oral 60 mg/kg [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• LD50 rat ip 2.2 mg/kg /Calculated from original mortality fractions/ [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• LD50 Rat ip 1.6 mg/kg [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• LD50 Rat iv 0.2-0.3 mg/kg [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• LD50 Mouse ip 5.4 mg/kg /Calculated from original mortality fractions/ [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• LD50 Guinea pig oral 13 mg/kg /Calculated from original mortality fractions; oil solution/ [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• LD50 Guinea pig oral 130 mg/kg /Calculated from original mortality fractions/ [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• LD50 Guinea pig oral 75 mg/kg /Oil solution; minimal lethal dose/ [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• LD50 Guinea pig ip 13 mg/kg /Calculated from original mortality fractions/ [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• LD50 Guinea pig ip 2 mg/kg /Minimal lethal dose/ [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• LD50 Rabbit oral 1,500 mg/kg /Minimal lethal dose/ [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• LD50 Rabbit dermal 100-200 mg/kg [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• LD50 Rabbit iv 0.35-0.65 mg/kg /Minimal lethal dose/ [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  
• LD50 Cat iv 0.65 mg/kg /Oil solution/ [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 600]**PEER REVIEWED**
  

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Absorption, Distribution and Excretion

• EXHALATION OF (14)CO2 WITHIN 50 HR AFTER ORAL OR IP DOSING OF 5'BETA-[3-METHOXY-(14)C]ROTENONE TO MICE & RATS RESPECTIVELY WAS 27 & 12.5%. /5'BETA-[3-METHOXY-(14)C]ROTENONE/[The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 410]**PEER REVIEWED**
  
• GI ABSORPTION IS PRESUMABLY SLOW & INCOMPLETE. ... FATS & OILS PROMOTE ABSORPTION. [Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. III-366]**PEER REVIEWED**
  
• One mechanism of detoxication of natural rotenone ... or one of its metabolites was found to be 3-O-demethylation, as indicated by recovery of 27 and 13% of the admin radiocarbon as 14C-labeled carbon dioxide within 50 hr after admin to mice and rats, respectively. Within the same period, the animals excreted 7-17% of the radioactivity in their urine ... In another study, 19.5 and 20.0% of the dose were recovered in the urine of mice and rats, respectively, within 24 hr after oral admin ... . [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 601]**PEER REVIEWED**
  

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Metabolism/Metabolites

• 5'BETA-(3-METHOXY-14C)ROTENONE UNDERWENT EXTENSIVE DEMETHYLATION IN RODENTS. /5' BETA-(3-METHOXY-14C)ROTENONE/ [The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 410]**PEER REVIEWED**
  
• BIOTRANSFORMATION...IN RATS LEADS TO HYDROXYLATION OF POSITION 12A AT B/C RING JUNCTION TO GIVE ROTENOLONES...TO OXIDATION OF ISOPROPENYL SIDE-CHAIN TO AFFORD 6',7'-DIHYDRO-6',7'-DIHYDROXY-ROTENONE & 8'-HYDROXYROTENONE, & TO FORMATION OF UNIDENTIFIED WATER-SOL METABOLITES. [The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 1: A Review of the Literature Published Between 1960 and 1969. London: The Chemical Society, 1970., p. 301]**PEER REVIEWED**
  
• MICROSOME FRACTIONS FROM HOUSEFLY ABDOMENS, MOUSE LIVERS, & RAT LIVERS WERE USED TO STUDY ROTENONE DEGRADATION. METABOLITES SO PRODUCED WERE... /ROTENOLONE I & II, 8'-HYDROXYROTENONE, 8'-HYDROXYROTENOLONE I & II, 6',7'-DIHYDRO-6',7'-DIHYDROXYROTENONE, 6',7'-DIHYDRO-6',7'-DIHYDROXYROTENOLONE I & II/ [Menzie, C.M. Metabolism of Pesticides. U.S. Department of the Interior, Bureau of Sport Fisheries and Wildlife, Publication 127. Washington, DC: U.S. Government Printing Office, 1969., p. 283]**PEER REVIEWED**
  
• In rat liver and in insects, the furan ring is enzymatically opened and cleaved, leaving behind a methoxy group. The principal metabolite is rotenonone. An alcohol has been found as a further metabolite, this being formed via oxidation of a methyl group of the isopropenyl residue. [Tomlin, C.D.S. (ed.). The Pesticide Manual - World Compendium. 10th ed. Surrey, UK: The British Crop Protection Council, 1994., p. 906]**PEER REVIEWED**
  
• Rotenone is metabolized rather efficiently by the liver. In order to produce the same clinical effect, the compound must be injected into a mesenteric vein at about 10 times the dose required for injection into a femoral vein ... . [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 601]**PEER REVIEWED**
  
• Rat and mouse liver enzymes and intact mice hydroxylate rotenone at carbons 7 and 24. In vitro, the change is produced by microsomes in the presence of nicotinamide-adenine dinucleotide phosphate. The products include rotenolone I, rotenolone II, 8'-hydroxyrotenone, 6',7'-dihydro-'6',7'-dihydroxyrotenone, two rotenolones of each of the latter compounds, and uncharacterized polar materials. [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 601]**PEER REVIEWED**
  
• One mechanism of detoxication of natural rotenone ... or one of its metabolites was found to be 3-O-demethylation ... [Hayes, W.J., Jr., E.R. Laws, Jr., (eds.). Handbook of Pesticide Toxicology. Volume 2. Classes of Pesticides. New York, NY: Academic Press, Inc., 1991., p. 601]**PEER REVIEWED**
  

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TSCA Test Submissions

• None found

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Footnotes

¹ Source: the National Library of Medicine's Hazardous Substance Database, 10/28/2007.