Testing Status of Agents at NTP
Executive Summary Chaconine and Solanine: Table 4
Table 4. Acute Exposure to a-Chaconine and a-Solanine
| Species, Strain, and Age | Number and Sex of Animals | Chemical Forma and Purity | Dose | Exposure/Observation Period | Results/Comments | Reference |
|---|---|---|---|---|---|---|
| 9.1.3.1 Oral Administration | ||||||
| Mice (Albino, age n.p.) | 10 M | solanine, purity n.p. | 1000 mg/kg (1 mmol/kg) | single exposure; observation period n.p. | Nontoxic. No other experimental details were given. | Nishie et al. (1971) |
| Rats (Sprague-Dawley, age n.p.) | 5 M | solanine, 'purified' | 250 mg/kg (0.29 mmol/kg) by gavage | single exposure; 24 hour observation | Treatment did not alter activities of ALT, AST, or serum cholinesterase. The authors presumed that hepatoxicity was not induced due to poor absorption of the dose in the stomach. | Dalvi (1985) |
| Hamsters (SPF Charles River/Wiga Syrian, golden, 12-15 wks-old) | 5 M | a-[3H] solanine, purity n.p. | 0.17 mg/kg (0.00020 mmol/kg) | single exposure; observation period n.p. | Caused severe damage of the duodenal wall in some animals, but the incidence ratio was n.p. | Groen et al. (1993) |
| Rats (strain and age n.p.) | n.p. | potatoes containing varying amounts of glycoalkaloids | n.p. | n.p. | Serum levels of calcium, phosphorous, magnesium, and hydroxyproline were decreased. The decrease had no relation to the solanine content of the potatoes (concentration n.p.). The authors stated that solanine appeared to exert a Vitamin D-like effect by increasing calcium absorption. | Yoon and Kirkowski (1979) |
| Rats (strain and age n.p.) | n.p. | Cara potato top homogenate | 10 or 20 mL/kg by gavage (higher dose contained 1.76 mg a-chaconine/kg and 0.66 mg a-solanine/kg (0.00207 and 0.00076 mmol/kg, respectively) | single exposure; observation period n.p. | No changes in body weight were observed. No abnormalities were observed during necropsy. | Phillips et al. (1996) |
| Hamsters (Syrian, mature) | 10 F (potato sprouts)
5 F (alkaloid extract) | potato sprouts or an extract of potato sprout alkaloids, crude | 4,170 mg/kg potato sprouts or 330 mg/kg alkaloid extract, by gavage | single exposure; 72 hour observation | a-Chaconine and a-solanine were confirmed in significant quantities in the potato sprouts and in trace amounts in the crude alkaloidal extract.
Administration of the sprout material induced 5/10 deaths within 24 hours; only one survived for the entire exposure period. Gross and microscopic lesions of the stomach and proximal small intestine were identified in all animals which died (9/10). The glandular mucosa of the stomach was thickened and hemorrhagic. The duodenum and jejunum were dilated with blood-tinged luminal contents and a red, hemorrhagic mucosa. Occasional subseral petechial hemorrhages on the cecum were observed. The one animal which survived had mild, focal areas of necrosis with hemorrhage and congestion of the gastric glandular mucosa. 3/5 hamsters administered the extract died during the 72 hour exposure period. The gross and microscopic lesions in those which died were similar to the lesions identified in those who died from administration of sprout material. The 2 surviving animals had mild congestion of the gastric glandular mucosa and epithelial necrosis. | Baker et al. (1987) |
| Hamsters (Syrian, adult) | 10 F per group | potato sprout material | 300, 400, or 500 mg/kg by gavage | single exposure; 72 hour observation | Concentrations of a-chaconine and a-solanine in the sprout material were not provided.
Acetylcholinesterase activity was significantly increased in the 300 mg/kg group. In the 400 and 500 mg/kg groups, acetylcholinesterase activity was 90 and 84% of the mean activity in the control group, respectively. The incidences of death prior to 72 hours were 1/10 at 300 mg/kg, 4/10 at 400 mg/kg, and 9/10 at 500 mg/kg. Those hamsters which died prior to 72 hours had severe gastric and proximal small intestinal necrosis. In the 400 mg/kg group, 2 of the hamsters which survived for 72 hours had valvular endocarditis and infarcts. 8/10 of the hamsters dosed with 300 mg/kg had lesions, while all of the hamsters at the 400 and 500 mg/kg levels had lesions. The authors concluded that death was not attributed to the slight acetylcholinesterase inhibition induced by the 2 higher doses of potato sprout material. Rather, death was related to severe gastrointestinal necrosis. | Baker et al. (1988) |
| Hamsters (strain and age n.p.) | n.p. | potato leaves, freeze-dried, suspended in corn oil | estimated dose: 2.65 mg/kg (0.00311 mmol/kg) a-chaconine plus 0.95 mg/kg (0.0011 mmol) a-solanine by gavage | single exposure; observation period n.p. | No effect on body weight or behavior was noted. No abnormalities were observed in any tissue, including the stomach mucosa, during necropsy. | Phillips et al. (1996) |
| Rabbits (White New Zealand, both young and adult) | 5 young and 4 adult (sex n.p.) | succulent potato plants | 100% of the diet | single exposure; 17 day observation | 3 of the young rabbits developed diarrhea 6 days after feeding, had torticollis and stretched legs, and went into a coma before death.
All young rabbits died by day 17 post-feeding. Most had turbid urine with amorphous crystals. 1 rabbit had an increased number of erythrocytes in the blood. All of the adult rabbits lost weight, became emaciated, and had symptoms similar to those of the young rabbits; leucopenia and lymphopenia were also induced. All adult rabbits died within 16 days. Treatment of both young and adult rabbits induced marked congestion in the lung, small intestines and liver. The spleen was atrophied. Hyperemia of the brain, lung, and kidneys was observed. Edema was seen in brain and lung tissues. Liver tissues had engorged sinusoids, blood vessels, and focal proliferation of mononuclear cells adjoining to blood vessels. | Somvanshi et al. (1992) |
| Sheep (strain and age n.p.) | n.p. | solanineb', purity n.p. | 225 mg/kg (0.259 mmol/kg) | single exposure; observation period n.p. | Dose was not lethal, but produced blood dyscrasias. | Konig and Stafze (1953; cited by Dalvi and Bowie, 1983) |
| Sheep (strain and age n.p.) | n.p. | 'solanineb', purity n.p. | 500 mg/kg (0.6 mmol/kg) | single exposure; observation period n.p. | The dose was lethal. | Konig (1953; cited by Maga, 1980) |
| 9.1.3.2 Intraperitoneal Injection | ||||||
| Mice (Swiss-Webster, adult) | 6-10 M | a-chaconine, >95% purity | 12-50 mg/kg (0.014-0.06 mmol/kg) | single exposure; 7 day observation | The higher doses (n.p.) produced respiratory distress and the animals died within a few hours. Animals treated with the lower doses (n.p.) died three days after exposure.
All doses caused hyperemia in the kidney. Effects were not dose-related. | Sharma et al. (1979) |
| Rats (Wistar, 9-wk-old) | F (see results/ comments for numbers) | a-chaconine, pure | 10-100 mg/kg (0.01-0.1 mmol/kg) | single exposure; 11 day observation | Doses of 50-100 mg/kg caused death: 50 mg/kg, 3/11; 75 mg/kg, 2/6; 85 mg/kg, 5/10; and 100 mg/kg, 4/4.
Observed signs of toxicity included periorbital, nasal, and oral hemorrhage. Internally, bloody ascitic fluid and pleuritic fluid were observed. | Chaube and Swinyard (1976) |
| Rats (Sprague-Dawley, age n.p.) | 3 M per group | a-chaconine, purity n.p. | 10, 30, or 60 mg/kg (0.01, 0.04, or 0.07 mmol/kg) | single exposure; 3 hour observation | All rats showed initial signs of depression and respiratory depression.
Acetylcholinesterase activity in brain homogenates was reduced dose-dependently to 79, 55, and 18% of that found in the control group. Heart acetylcholinesterase activity was reduced to 40% of the control in all treatment groups; plasma cholinesterase activity was also reduced compared to the control group. The authors concluded that a-chaconine is a fairly potent cholinesterase inhibitor. | Alozie et al. (1978; cited by JECFA, 1993) |
| Rats (Sprague-Dawley, age n.p.) | 12 M per dose | a-chaconine, purity n.p. | 3, 8, or 20 mg/kg (0.004, 0.009, or 0.02 mmol/kg) | single exposure; 3 or 12 hour observation | Treatment did not alter levels of acetylcholine, catecholamine, seratonin, or its metabolite 5-hydroxyindoleacetic acid at any dose. Norepinephrine levels decreased with increasing doses in the groups observed for 3 hours.
Symptoms observed at 8 mg/kg included sedation, respiratory impairment, and constriction of abdominal muscles. | Aldous et al. (1980) |
| 3 M ( 3 lower doses); 1 M (high dose) | - | 10, 20, 30 , or 40 mg/kg (0.01, 0.02, 0.04, or 0.05 mmol/kg) | single exposure; observed at time of exposure and 3 and 7 hours later | There was a significant increase in the proportion of low frequency activity, as observed on the EEG, following administration of 10 mg/kg.
Tachycardia was observed at the 10 and 40 mg/kg levels, while bradycardia was observed at the 20 and 30 mg/kg levels. | ||
| Rabbits (White New Zealand, age n.p.) | n.p. | a-chaconine, purity n.p. | 60 mg/kg (0.07 mmol/kg) | single exposure; observed for 2.5 hours | No significant abnormal EEG patterns were initially observed. Over time, however, high voltage delta waves, cyanosis, tachycardia, and coma were observed. The respiratory rate increased in the first hour of exposure, and then decreased steadily. Terminal signs of death began with isoelectric EEG signals followed by respiratory arrest and cardiac arrest. | Nishie et al. (1975) |
| Mice (Albino, age n.p.) | 10 M per group | solanine, purity n.p. | 5 or 10 mg/kg (0.006 or 0.01 mmol/kg) | single exposure; 5 minute observation | 10 mg/kg caused a significant reduction in spontaneous motor activity. No effect was noted at 5 mg/kg. | Nishie et al. (1971) |
| Mice (Albino, age n.p.) | 10 M per group | solanine, purity n.p. | 50 mg/kg pentobarbital sodium followed by 5, 10, or 20 mg/kg (0.006, 0.01, or 0.02 mmol/kg) solanine | single exposure; observed until time of recovery of righting reflex | Only the 20 mg/kg dose produced a significant increase in pentobarbital-induced sleeping time. | Nishie et al. (1971) |
| Mice (Swiss-Webster, adult) | 10 M per group | solanine, purity n.p. | 10-50 mg/kg (0.01-0.06 mmol/kg) | single exposure; 24 hour observation | 10 mg/kg elicited symptoms but no deaths, while 50 mg/kg caused death within 1-3 hours.
The animals were irritated for 1 minute after administration and then became drowsy and apathetic. Breathing was increased and the animals developed diarrhea, followed by hind-leg paralysis and dyspnoea. Before death, the animals experienced a deep and prolonged state of unconsciousness. | Patil et al. (1972) |
| Mice (Swiss-Webster, adult) | 6-10 M | a-solanine, >95% purity | 12-50 mg/kg (0.01-0.06 mmol/kg) | single exposure; 7 day observation= | The higher doses (actual doses n.p.) produced respiratory distress and the animals died within a few hours. Deaths of animals treated with the lower doses were distributed throughout the observation period.
a-Solanine treatment caused occasional hepatic leukocytic infiltration. Effects were not dose-related. | Sharma et al. (1979) |
| Rats (Wistar, 9-wk-old) | F (see results/ comments for numbers) | a-solanine, purity n.p. | 10-85 mg/kg (0.01-0.098 mmol/kg) | single exposure; 11 day observation | Doses of 40-85 mg/kg caused death: 40 mg/kg, 1/9; 60 mg/kg, 3/8; and 85 mg/kg, 6/6.
Signs of toxicity included periorbital, nasal, and oral hemorrhage. Internally, bloody ascitic fluid and pleuritic fluid were observed. | Chaube and Swinyard (1976) |
| Rats (Sprague-Dawley, age n.p.) | 5 M | solanine, 'purified' | 20 mg/kg (0.02 mmol/kg) | single exposure; 24 hour observation | Treatment significantly increased ALT and AST levels and decreased the activities of serum cholinesterase and microsomal enzymes, including cytochrome P-450. These results indicate the hepatotoxic nature of solanine. | Dalvi (1985) |
| Rabbits (strain and age n.p.) | 1 per dose (sex n.p.) | solanine, purity n.p. | 10, 15, 20, or 30 mg/kg (0.01, 0.017, 0.02, or 0.03 mmol/kg) | single exposure; observation period n.p. | Rabbits administered doses below 15 mg/kg did not have EEG readings different from the controls, but did experience an increase in heart rate.
Generally, the EEG changed gradually with time at doses ranging from 15-30 mg/kg. During an initial period of rapid rise in respiratory rate (1 to 1.5 hours after dosing), the EEG was slightly activated. Delta waves appeared on the EEG when the respiratory rates dropped below those of the controls (2.5 to 6 hours after dosing). Significant increases in heart rate were also induced at 20 and 30 mg/kg, but the rabbit dosed with 15 mg/kg experienced no change in heart rate. The animal administered 20 mg/kg died overnight and the animal treated with 30 mg/kg died in 6.25 hours. The heart kept beating after breathing ceased. Deep cyanosis and semiconsiousness preceded death. | Nishie et al. (1971) |
| Rabbits (New Zealand white, age n.p.) | At the low dose, 2 M and 1 F
At the high dose, 1 F | solanine, purity n.p. | 20 or 30 mg/kg (0.02 or 0.03 mmol/kg) | single exposure; observation period n.p. | No marked parasympathetic stimulation, excess secretions, or muscular twitching was observed.
Rate of respiration was increased for the first 15 to 30 minutes after injection. Breathing was difficult. Animals experienced a depressive phase caused by prostration (severe exhaustion) prior to death. Depressive phase was indicated by lack of response to stimuli, partially closed eyes, disinclination to move, and muscle weakness resembling partial paralysis of the limbs. Occasional twitching or convulsions preceded death; pupils were widely dilated. The rabbit given 30 mg/kg died within 50 minutes. At 20 mg/kg, 1 rabbit died in 145 minutes, one died in 24 hours, and a third survived and recovered completely. The authors noted that solanine was a weak to moderate inhibitor of both specific and non-specific cholinesterase when tested in serum and erythrocytes after dosing. Generally, there was less inhibition in the erythrocytes than in the plasma. | Patil et al. (1972) |
| Monkeys (Rhesus, age n.p.) | 1 F | solanine, reference standard | 20 mg/kg (0.02 mmol/kg) | 2 doses given 24 hours apart; observed 2 hours after last injection | The dose caused an increase in pulse, systolic pressure, and respiratory rate, followed by death approximately 2 hours after the last injection. Hemorrhage of the nasal and periorbital cavities was noted at necropsy, in addition to hemorrhagic congestion in the lung, liver, and spleen. Accumulation of serosanguinous pleural and peritoneal fluids and mild hepatic and splenic congestion were induced. | Swinyard and Chaube (1973) |
| Hamsters (strain and age n.p.) | n.p. | 1:1 mixture ofa-chaconine and a-solanine | 5, 10, 25, 50, or 100 mg/kg (0.006, 0.01, 0.029, 0.058, or 0.116 mmol/kg) | single exposure; 24 hour observation | No effect was observed at 5 and 10 mg/kg.
At 25, 50, and 100 mg/kg, death occurred within 24 hours. Blood was found in and around the stomach and duodenum during necropsy, which indicates that uptake is facilitated by cell membrane disruption. | Phillips et al. (1996) |
| Monkeys (rhesus, age n.p.) | 2 F | glycoalkaloids, purity n.p. | 40 mg/kg (0.05 mmol/kg) | single exposure; 48 hour observation | Both animals died 48 hours after treatment. Prior to death, pulse, systolic pressure, and respiratory rate was increased. Hemorrhage of the nasal and periorbital cavities was noted at necropsy, in addition to hemorrhagic congestion in the lung, liver, and spleen. Accumulation of serosanguinous pleural and peritoneal fluids and mild hepatic and splenic congestion were induced. | Swinyard and Chaube (1973) |
| 9.1.3.3 Intravenous Injection | ||||||
| Rabbits (White New Zealand, age n.p.) | n.p. | a-chaconine, purity n.p. | 1.0, 1.5, or 2.0 mg/kg (0.0012, 0.0018, or 0.0023 mmol/kg) | single exposure; observation period n.p. | Treatment with 1.0-1.5 mg/kg slightly decreased heart rate and blood pressure.
2.0 mg/kg produced short runs of ventricular extrasystoles and bigeminy within 1-7 minutes after injection. | Nishie et al. (1975) |
| Rabbits (strain and age n.p.) | 1 (sex n.p.) | solanine, purity n.p. | 10 mg/kg (0.01 mmol/kg) | single exposure; observation period n.p. | Death was induced within 2 minutes. Respiration and EEG signals stopped simultaneously. | Nishie et al. (1971) |
| n.p. | - | pentobarbital followed by 2 or 3 mg/kg solanine (0.002 or 0.003 mmol/kg) | - | At 2 mg/kg, solanine induced a transient increase in respiratory rate, ventricular extrasystoles, and a lowering of blood pressure.
3 mg/kg caused a 30-second cessation of respiration 2.5 min. after injection. | - | |
| Rabbits (White New Zealand, age n.p.) | n.p. | solanine, purity n.p. | 1.0, 1.5, or 2.0 mg/kg (0.0011, 0.0017, or 0.0023 mmol/kg) | single exposure; observation period n.p. | Treatment with 1.0-1.5 mg/kg slightly decreased heart rate and blood pressure.
The 2.0 mg/kg dose produced short runs of ventricular extrasystoles and bigeminy within 1-7 minutes after injection. | Nishie et al. (1975) |
| Dog (strain and age n.p.) | 1 M | solanine, purity n.p. | pentobarbital sodium followed by 5 doses of 6 mg/kg (0.007 mmol/kg) solanine administered 10 min. apart | see dose for exposure; observation period n.p. | Quick serum cholinesterase inhibition was followed by a rapid recovery. Erythrocyte cholinesterase inhibition was not observed. | Patil et al. (1972) |
| Sheep (strain and age n.p.) | n.p. | 'solanineb', purity n.p. | 17 or 50 mg/kg (0.020 or 0.06 mmol/kg) | single exposure; observation period n.p. | 17 mg/kg was poisonous and 50 mg/kg was lethal. No other experimental details were provided. | Konig (1953; cited by Maga, 1980) |
aThe chemical form is given as the original author(s) presented it.
bThe 'solanine' isolated prior to 1954 was actually a mixture of a-chaconine and a-solanine (Friedman and McDonald, 1997).
Abbreviations: ALT = alanine aminotransferease; AST = aspartate aminotransferase; ECG = electrocardiogram; EEG = electroencephalogram; F = Female; M = Male; n.p. = not provided
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