Each 1 mL serving contains: Arsenicum Iodatum D10 • Aurum Metallicum D10 • Calcarea Carbonica D10 • Calcarea Fluorica D10 • Ferula Asafoetida D10 • Phosphorus D30 • Silicea D10 • Symphytum Officinale Spag D3 • Alcohol (preservative) 20%.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
This is a homeopathic preparation. Homeopathy is a system of medicine established in the 19th century by a German physician named Samuel Hahnemann. Its basic principles are that "like treats like" and "potentiation through dilution." For example, in homeopathy, diarrhea would be treated with an extreme dilution of a substance that normally causes diarrhea when taken in high doses.
Practitioners of homeopathy believe that more dilute preparations are more potent. Many homeopathic preparations are so diluted that they contain little or no active ingredient. Therefore, most homeopathic products are not expected to have any pharmacological effects, drug interactions, or other harmful effects. Any beneficial effects are controversial and cannot be explained by current scientific methods.
Dilutions of 1 to 10 are designated by an "X." So a 1X dilution = 1:10, 3X=1:1000; 6X=1:1,000,000. Dilutions of 1 to 100 are designated by a "C." So a 1C dilution = 1:100; 3C = 1:1,000,000. Dilutions of 24X or 12C or more contain zero molecules of the original active ingredient.
Homeopathic products are permitted for sale in the US due to legislation passed in 1938 sponsored by a homeopathic physician who was also a Senator. The law still requires that the FDA allow the sale of products listed in the Homeopathic Pharmacopeia of the United States. However, homeopathic preparations are not held to the same safety and effectiveness standards as conventional medicines. For more information, see the Homeopathy monograph.
Below is general information about the effectiveness of the known ingredients contained in the product Osto. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
There is insufficient reliable information available about the effectiveness of asafoetida.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Osto. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when organic arsenic is consumed in normal food amounts. Organic forms of arsenic normally found in foods have not been linked to toxicity (7135,16309). ...when arsenic trioxide is used intravenously and appropriately under the guidance of a healthcare provider. Arsenic trioxide (Trisenox) is an FDA-approved prescription drug (15).
LIKELY UNSAFE ...when inorganic arsenic is used orally, especially when used long-term or in high doses. Taking large doses acutely, or in small doses for prolonged periods of time, can cause serious side effects. Chronic intake of 10 mcg/kg daily has been associated with symptomatic arsenicism. Acute doses of 5 mg, or sometimes less, can cause gastrointestinal symptoms. Higher doses can cause severe poisoning and death (7135,16310,16312,16313,16316,102892). Prolonged exposure to inorganic arsenic in drinking water and other sources has been linked to an increased risk of cardiovascular disease, diabetes, cancer, hypertension, and mortality (99824,99827,99829,99830,99832,99834,99835,109108,109110). Inorganic arsenic is classified as a human carcinogen (16312,16316). The maximum permissible level of arsenic in drinking water is 10 mcg/L (16316).
CHILDREN: LIKELY SAFE
when organic arsenic is consumed in food amounts.
Organic forms of arsenic found in a normal diet have not been linked to toxicity (7135,16309).
CHILDREN: LIKELY UNSAFE
when inorganic arsenic is used orally, especially when used long-term or in high doses.
Large doses acutely, or in small doses for prolonged periods of time, can cause serious side effects. Prolonged exposure to inorganic arsenic in drinking water has been linked to reduced scores on intelligence tests, developmental delays, impaired verbal comprehension, decreased memory and attention, and higher blood pressure in children (16319,99826,99828,99836,102898).
PREGNANCY AND LACTATION: LIKELY SAFE
when organic arsenic is consumed in food amounts.
Organic forms of arsenic found in a normal diet have not been linked to toxicity (7135,16309).
PREGNANCY AND LACTATION: LIKELY UNSAFE
when inorganic arsenic is taken orally, especially when used long-term or in high doses.
While exposure to inorganic arsenic in drinking water does not seem to increase the risk of neural tube defects (102897), it has been associated with an increased risk for spontaneous abortion, stillbirth, and neonatal mortality (99833). Exposure to inorganic arsenic in drinking water and other sources while pregnant has also been linked to changes in birth weight, length, and head circumference (102895), with one study showing that higher maternal blood arsenic levels are associated with 44% greater odds of delivering a small for gestational age infant and 103% greater odds of delivering a large for gestational age infant (102895,102896). Avoid arsenic supplements and water contaminated with arsenic during pregnancy or lactation.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Asafoetida has Generally Recognized As Safe status (GRAS) for use in foods in the US (4912).
POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (12).
CHILDREN: UNSAFE
when used orally in infants due to the possible risk of methemoglobinemia (4,102549).
PREGNANCY: LIKELY UNSAFE
when used orally in medicinal amounts; asafoetida might cause abortion (4).
LACTATION: UNSAFE
when used orally due to the possible risk of methemoglobinemia in infants (4).
POSSIBLY SAFE ...when used topically for less than 6 weeks on unbroken skin at a daily dose providing no more than 100 mcg of pyrrolizidine alkaloid (PA) constituents. PAs are absorbed through the skin (11990,44898,44902,92568).
POSSIBLY UNSAFE ...when used for extended durations or in high concentrations on unbroken skin. Topically, hepatotoxic pyrrolizidine alkaloids (PAs) in comfrey can be absorbed in quantities sufficient to cause toxicity with extended use for greater than 6 weeks or in quantities providing more than 100 mcg of PAs (11990,92568). ...when used topically on broken skin. PAs can be absorbed through broken skin. In countries where the PA content of comfrey is not regulated, including Australia and the United States, creams containing comfrey are required to include a warning not to use on broken skin (44950,44951).
LIKELY UNSAFE ...when used orally because of its potential for acute or chronic liver toxicity. Comfrey contains hepatotoxic pyrrolizidine alkaloids (PAs). Chronic ingestion of more than 1 mg daily for 2 weeks or more than 100 mcg daily for longer durations can cause liver disease. PAs may also be carcinogenic (11987,99068). The FDA has recommended removal of oral comfrey products from the market (11988).
PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally or topically.
In addition to hepatotoxicity and possible carcinogenicity, the pyrrolizidine alkaloids (PAs) in comfrey might be teratogenic. PAs are absorbed through the skin (11987,11988,11990).
LIKELY SAFE ...when used orally and appropriately. Fluoride is safe when used in doses below the tolerable upper intake level (UL) of 10 mg daily of elemental fluoride (7555). ...when used topically and appropriately. Fluoride is safe when used in quantities typically found in toothpastes, mouth rinses, and professionally applied fluoride dental treatments (8950,101102,101105).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Elemental fluoride is safe when used in doses below the daily tolerable upper intake level (UL) of 0.7 mg for 0-6 months of age, 0.9 mg for 7-12 months of age, 1.3 mg for 1-3 years of age, 2.2 mg for 4-8 years of age, and 10 mg for children 8 years and older (7555). Although infants and children have consumed fluoridated water with apparent safety for many years, some population research suggests that more information is needed to determine a safe level of fluoride exposure in infants and children living in regions with fluoridated water. Population research has found an association between urinary fluoride levels and diagnosis of ADHD with higher inattention scores at age 14 years, but not at age 9 years (103551). Also, there is some concern that reconstitution of infant formula with fluoridated water might result in fluoride intakes above the UL in infants under 6 months of age, which may be linked to negative cognitive effects (103529). The Canadian Dental Association recommends that when infant formulas are used as the main source of nutrition, drinking water that contains natural fluoride above recommended levels should not be used to reconstitute the formula (103545). More research is needed to determine whether these effects are due to fluoride or to confounding factors such as socioeconomic status, use of formula instead of breast-feeding, parental intelligence, choice of IQ tests used in studies, and other factors (103542,103544). ...when used topically and appropriately. Fluoride is safe in quantities typically found in toothpastes, mouth rinses, and professionally applied fluoride dental treatments (8950,9100,94406,107648).
CHILDREN: POSSIBLY UNSAFE
when used orally in high doses, long-term.
Exposure to high doses above the UL for greater than 10 years can cause skeletal fluorosis (7555). To reduce fluoride intake, toothpaste and fluoride rinses should not be routinely swallowed. Recommend limiting the use of toothpaste to a pea-sized amount for children 6 years and younger in case of accidental swallowing (9100). When infant formulas are used as the main source of nutrition, drinking water that contains natural fluoride above recommended levels should not be used to reconstitute the formula (103545).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Elemental fluoride is safe when used in doses below the tolerable upper intake level (UL) of 10 mg daily (7555). Although fluoridated water has been consumed during pregnancy with apparent safety for many years, some population research suggests that more information is needed to determine a safe level of fluoride exposure for those living in regions with fluoridated water. Some emerging population research suggests that increased fluoride intake during pregnancy, from appropriately fluoridated water or fluoridated salt, might be associated with negative cognitive effects in the infant (103543,103547). However, more information is needed to determine if these results are clinically significant at the population level, as well as whether these effects are due to fluoride or to confounding factors such as socioeconomic status, use of formula instead of breast-feeding, parental intelligence, choice of IQ tests used in studies, and other factors (103542,103544,103546,103547,103548,103549,103550). ...when used topically and appropriately. Fluoride is safe in quantities typically found in toothpastes, mouth rinses, and professionally applied fluoride dental treatments (8950).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally at doses above the tolerable upper intake level (UL) of 10 mg daily of elemental fluoride for prolonged periods.
Long-term exposure to high doses can cause skeletal fluorosis, but pregnancy or lactation doesn't seem to affect susceptibility to skeletal fluorosis (7555).
LIKELY SAFE ...when used orally and appropriately short-term (15). ...when sodium phosphate is used rectally and appropriately, no more than once every 24 hours, short-term (104471). Long-term use or high doses used orally or rectally require monitoring of serum electrolytes (2494,2495,2496,2497,2498,3092,112922). ...when used intravenously. Potassium phosphate is an FDA-approved prescription drug (15).
POSSIBLY UNSAFE ...when phosphate (expressed as phosphorus) intake exceeds the tolerable upper intake level (UL) of 4 grams daily for adults under 70 years and 3 grams daily for adults older than 70. Hyperphosphatemia, resulting in electrolyte disturbances, alterations in calcium homeostasis, and calcification of nonskeletal tissues, may occur (7555). ...when used rectally more frequently than once every 24 hours, in excessive doses, with longer retention enema time, or in older patients with comorbidity or renal impairment (112922). The US Food and Drug Administration (FDA) warns that this may increase the risk of hyperphosphatemia, dehydration, and electrolyte imbalances leading to kidney and heart damage (104471).
CHILDREN: LIKELY SAFE
when used orally and appropriately at recommended dietary allowances (RDAs).
The daily RDAs are: children 1-3 years, 460 mg; children 4-8 years, 500 mg; males and females 9-18 years, 1250 mg (7555). ...when sodium phosphate is used rectally and appropriately, no more than once every 24 hours, short-term in children 2 years and older (104471). ...when used intravenously. Intravenous potassium phosphate is an FDA-approved prescription drug (15).
CHILDREN: POSSIBLY UNSAFE
when phosphate (expressed as phosphorus) intake exceeds the tolerable upper intake level (UL) of 3 grams daily for children 1-8 years of age and 4 grams daily for children 9 years and older.
Hyperphosphatemia, resulting in electrolyte disturbances, alterations in calcium homeostasis, and calcification of nonskeletal tissues, may occur (7555). ...when sodium phosphate is used rectally more frequently than once every 24 hours, or in children under 2 years of age or with Hirchsprung disease (112922). The US Food and Drug Administration (FDA) warns that these uses may increase the risk of hyperphosphatemia, dehydration, and electrolyte imbalances leading to kidney and heart damage (104471).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately at the recommended dietary allowance (RDA) of 1250 mg daily for individuals 14-18 years of age and 700 mg daily for those over 18 years of age (7555).
...when sodium phosphate is used rectally and appropriately short-term (15). ...when used intravenously. Intravenous potassium phosphate is an FDA-approved prescription drug (15).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when phosphate (expressed as phosphorus) intake exceeds the tolerable upper intake level (UL).
Hyperphosphatemia, resulting in electrolyte disturbances, alterations in calcium homeostasis, and calcification of nonskeletal tissues, may occur. The UL during pregnancy is 3.5 grams daily. During lactation, the UL is 4 grams daily (7555).
Below is general information about the interactions of the known ingredients contained in the product Osto. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Arsenic trioxide can prolong the QT interval.
Details
Up to 40% of patients treated with prescription arsenic trioxide have a prolonged QT interval on their electrocardiogram (ECG) (15). Theoretically, non-prescription arsenic could have an additive effect when combined with drugs that prolong the QT interval.
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Theoretically, asafoetida might increase the risk of bleeding when used concomitantly with anticoagulant/antiplatelet drugs (4). Some anticoagulant/antiplatelet drugs include aspirin, clopidogrel (Plavix), diclofenac (Voltaren, Cataflam, others), ibuprofen (Advil, Motrin, others), naproxen (Anaprox, Naprosyn, others), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, warfarin (Coumadin), and others.
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Evidence from animal research suggests that asafoetida has hypotensive effects (4,32480). Theoretically, concomitant use may increase therapeutic effects of antihypertensive therapy due to hypotensive activity of asafoetida. Some antihypertensive drugs include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), Amlodipine (Norvasc), hydrochlorothiazide (HydroDiuril), furosemide (Lasix), and many others.
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Theoretically, CYP3A4 inducers might increase the risk of adverse effects from the pyrrolizidine alkaloid constituents in comfrey.
Details
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Theoretically, comfrey might have additive adverse effects on the liver when used with hepatotoxic drugs.
Details
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Theoretically, taking phosphate salts with bisphosphonates might increase the risk of hypocalcemia.
Details
Combining bisphosphonates and phosphate can cause hypocalcemia. In one report, hypocalcemic tetany developed in a patient taking alendronate (Fosamax) who received a large dose of phosphate salts as a pre-operative laxative (14589).
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Taking erdafitinib with phosphate salts increases the risk of hyperphosphatemia.
Details
Erdafitinib increases phosphate levels. It is recommended that patients taking erdafitinib restrict phosphate intake to no more than 600-800 mg daily (104470).
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Taking futibatinib with phosphate salts increases the risk of hyperphosphatemia.
Details
Futibatinib can cause hyperphosphatemia, as reported in 88% of patients in clinical studies. In addition, 77% of patients in clinical studies required use of a phosphate binder to manage hyperphosphatemia. Phosphate salts should generally be avoided by people taking this medication (112912).
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Below is general information about the adverse effects of the known ingredients contained in the product Osto. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally, organic forms of arsenic found in the diet are well tolerated, with no clear links to adverse effects.
However, high doses or chronic intake of inorganic arsenic is associated with potentially serious adverse effects.
Serious Adverse Effects (Rare):
Orally: With the acute ingestion of inorganic arsenic, anemia, arrhythmias, bruising, gastrointestinal irritation or damage, hepatotoxicity, and peripheral neuropathy.
With chronic intake of inorganic arsenic, arsenicism can occur, including anorexia, cancer, skin hyperpigmentation and hyperkeratosis, and toxicity of the cardiovascular and neurological systems.
Cardiovascular
...Orally, doses of inorganic arsenic 1 mg/kg daily can cause hematopoietic depression including anemia, arrhythmias, and blood vessel damage leading to bruising (7135,16309,16312).
Acute ingestion of inorganic arsenic 10 mg/kg daily or more causes vasodilation and myocardial depression leading to myocardial injury, shock, and circulatory failure (17,7135,16313,16316,102892). Chronic intake of 10 mcg/kg daily of inorganic arsenic produces arsenicism, characterized in part by cardiomyopathy and arrhythmias (17,7135,16309,16310,16316). Prolonged exposure to inorganic arsenic in drinking water at levels greater than or equal to 20 mcg/L has been linked, in a dose-dependent manner, to a 9% to 43% greater risk of cardiovascular disease, 11% to 55% greater risk of coronary heart disease, and 16% to 90% greater risk of cardiovascular-related death (99827). Also, each interquartile increase in urinary inorganic arsenic levels is associated with an increased risk of both cardiovascular and all-cause mortality in a specific area of the US (109110). A metabolite of arsenic, monomethylarsonic acid, has also been positively linked to stroke risk (99831). Increased exposure to inorganic arsenic has also been linked to the development of left ventricular hypertrophy (99835). The cardiovascular adverse effects of inorganic arsenic appear to be more profound in males with hypertension (99829).
The association between arsenic exposure and hypertension has also been investigated. A meta-analysis of observational research has found that the odds of having hypertension and risk of hypertension were increased by 14% and 30%, respectively, in those with the highest arsenic exposure when compared with the lowest. Exposure was determined based on intake of rice and rice products, as well as exposure in water, or levels in urine, hair, or toenails (109108). Additionally, increased exposure to inorganic arsenic in drinking water has been linked to higher blood pressure in children (102898).
Dermatologic ...Orally, chronic intake of 10 mcg/kg daily of inorganic arsenic produces arsenicism, characterized in part by skin hyperpigmentation, hyperkeratosis, alopecia, and occlusive peripheral vascular disease leading to gangrene (17,7135,16309,16310,16316,102894). In one case, chronic intake of inorganic arsenic 30 ng daily has reportedly caused eczema of the hands, arms, and legs (102893).
Endocrine ...Orally, prolonged exposure to inorganic arsenic in drinking water has been associated with a 23% to 75% increase in the risk for diabetes (99830,99834). For every 100 mcg/L increase in inorganic arsenic levels in drinking water, the associated risk for diabetes increases by 13% (99834). A small meta-analysis has found that overall exposure to arsenic, including organic and inorganic arsenic, is associated with an increased risk of developing gestational diabetes (106539).
Gastrointestinal ...Orally, acute ingestion of inorganic arsenic 5 mg, or sometimes less, can cause vomiting, diarrhea, stomach cramps, and flatulence (16316,102893). These effects usually resolve in about 12 hours without treatment (16316). Doses of inorganic arsenic 1 mg/kg daily can cause gastrointestinal irritation (7135,16309,16312). Acute ingestion of inorganic arsenic 10 mg/kg daily or more causes severe gastrointestinal symptoms including bloody rice-water diarrhea (17,7135,16313,16316,102892). Chronic intake of 10 mcg/kg daily of inorganic arsenic produces arsenicism, characterized in part by anorexia and gastrointestinal disturbances (17,7135,16309,16310,16316).
Genitourinary ...Orally, chronic intake of inorganic arsenic 30 ng daily has reportedly caused irregular menstruation (102893). A long-term observational study in adults has found that exposure to inorganic arsenic from consumption of contaminated milk powder during infancy is associated with increased mortality from genitourinary diseases (106541).
Hematologic ...Orally, chronic intake of 10 mcg/kg daily of inorganic arsenic produces arsenicism, characterized in part by anemia, leukopenia, and occlusive peripheral vascular disease (17,7135,16309,16310,16316).
Hepatic
...Orally, doses of inorganic arsenic 1 mg/kg daily can cause hepatotoxicity (7135,16309,16312).
The homeopathic remedy, arsenicum album, has been associated with three cases of acute liver injury. In one case, a 70-year-old male with pre-existing non-alcoholic steatohepatitis (NASH) cirrhosis died following the acute liver injury associated with use of this compound for about 12 weeks. High levels of arsenic were found in his hair and nail samples. Symptoms in the two other individuals resolved upon discontinuation of homeopathic arsenic and use of corticosteroids (109114).
Musculoskeletal ...Orally, chronic intake of inorganic arsenic 30 ng daily has reportedly caused leg cramps in one patient (102893).
Neurologic/CNS
...Orally, doses of inorganic arsenic 1 mg/kg daily can cause peripheral neuropathy and encephalopathy (7135,16309,16312).
In one case, chronic intake of inorganic arsenic 30 ng daily has reportedly caused headache, dizziness, and difficulty concentrating (102893). Acute ingestion of inorganic arsenic 10 mg/kg daily or more can cause cerebral edema, leading to encephalopathy, convulsions, coma, and death (17,7135,16313,16316). Chronic intake of 10 mcg/kg daily of inorganic arsenic produces arsenicism, characterized in part by sensory disturbances, peripheral neuropathy, encephalopathy, confusion, and memory loss (17,7135,16309,16310,16316). A long-term observational study in adults has found that exposure to inorganic arsenic from consumption of contaminated milk powder during infancy is associated with increased mortality from nervous system diseases (106541).
In children, prolonged exposure to inorganic arsenic in drinking water has been linked to reduced scores on intelligence tests, developmental delays, impaired verbal comprehension, and decreased memory and attention (16319,99826,99828,99836).
Ocular/Otic ...Orally, chronic intake of inorganic arsenic 30 ng daily has reportedly caused conjunctivitis in one patient (102893). A long-term observational study in adults has found that exposure to inorganic arsenic from consumption of contaminated milk powder during infancy is associated with increased mortality from traffic accidents. This is suggested to be related to a higher prevalence of visual field narrowing due to macular degeneration, as well as motor or sensory dysfunction, in those exposed to arsenic during infancy (106541).
Oncologic ...Inorganic arsenic is classified as a human carcinogen (16312,16316). Orally, chronic intake of 10 mcg/kg daily of inorganic arsenic produces arsenicism, which can result in cancers of the skin, lungs, liver, kidneys, and bladder (17,7135,16309,16310,16316). Chronic ingestion of lower doses of inorganic arsenic, as a contaminant in well water, has also been linked to cancers of the skin, bladder, kidneys, and lungs (7135,99824,99832,106540). More specifically, levels of inorganic arsenic greater than 200 mcg/L in drinking water have been linked to lung cancer (99824). Levels of inorganic arsenic greater than 10 mcg/L in drinking water are also dose-dependently linked to an increased risk for bladder and kidney cancers (99832). A meta-analysis of observational research has found that arsenic exposure, especially from water and soil, is associated with prostate cancer risk (109109). A long-term observational study in adults has found that exposure to inorganic arsenic from consumption of contaminated milk powder during infancy is associated with increased mortality from liver cancer (106541).
Psychiatric ...Orally, chronic intake of inorganic arsenic 30 ng daily has reportedly caused insomnia and anxiety in one patient (102893).
Pulmonary/Respiratory ...A long-term observational study in adults has found that exposure to inorganic arsenic from consumption of contaminated milk powder during infancy is associated with increased mortality from respiratory diseases (106541).
Other
...Orally, high doses of inorganic arsenic can cause death.
In one case, a 24-year-old female receiving a combination of arsenic trioxide, realgar, and mung bean flour from an illegal medical provider died within days of taking the compounded preparation. Laboratory analysis revealed the amount of arsenic consumed to be around 1.1 grams on day 1 and 0.9 grams on day 4. Researchers concluded that arsenic as the source of poisoning was clear based on the amount of arsenic ingested and the patient's clinical presentation prior to death, which included vomiting, diarrhea, reduced urine output, liver and kidney abnormalities, and myocardial injury (102892).
A long-term observational study in adults has found that exposure to inorganic arsenic from consumption of contaminated milk powder during infancy is associated with increased all-cause mortality (106541).
General ...Orally, asafoetida appears to be generally well tolerated. Large amounts of asafoetida have been reported to cause swelling of the lips, belching, flatulence, diarrhea, headache, or convulsions (18). There are reports of infantile methemoglobinemia associated with asafoetida (4,102549). Topically, asafoetida has been reported to cause genital organ swelling (18).
Dermatologic ...Orally, large amounts of asafoetida have been reported to cause swelling of the lips (18).
Gastrointestinal ...Orally, large amounts of asafoetida have been reported to cause belching, flatulence, and diarrhea (18).
Genitourinary ...Topically, genital organ swelling was reported after application of asafoetida to the abdomen (18).
Hematologic ...Orally, asafoetida has been associated with methemoglobinemia in infants (4,102549). In one case, a 3-month-old boy who was given asafoetida gum resin for colic presented with tachypnea, hypoxia, and tachycardia. The child had very high methemoglobin levels and other markers consistent with metabolic acidosis with lethal methemoglobinemia. The child was intubated and treated with 100% oxygen plus supportive measures and eventually made a full recovery (102549).
Neurologic/CNS ...Orally, asafoetida in doses of 50-100 mg has been reported to cause headache or convulsions (18).
General
...When used orally, comfrey may be unsafe.
Topically, comfrey is generally well tolerated when applied to intact skin.
Most Common Adverse Effects:
Topically: Eczema, erythema, irritation, itching, rash.
Serious Adverse Effects (Rare):
All ROAs: Ascites, cirrhosis, death, hepatic fibrosis, hepatomegaly, pulmonary hypertension, and sinusoidal obstruction syndrome. These adverse effects are likely related to the pyrrolizidine alkaloid constituents of comfrey.
Dermatologic ...Topically, comfrey-containing creams and ointments may cause skin redness, irritation, itching, rash, and eczema (44902,44912,44917,44919,92566,92570,92571).
Hepatic ...The pyrrolizidine alkaloid constituents of comfrey can cause acute sinusoidal obstruction syndrome characterized by sudden abdominal pain, vomiting, ascites, and hepatomegaly. In subacute disease, comfrey can cause ascites, hepatomegaly, abdominal pain, diarrhea, vomiting, and abdominal swelling. Chronic toxicity appears as asthenia and progressive ascites. Hepatic fibrosis and inflammation may resolve, but hepatic failure is common with more severe disease. This may occur as late as 2 years after the initial ingestion. Other signs and symptoms of pyrrolizidine toxicity include bile duct proliferation, fatty changes of the liver, fibrosis, cirrhosis, and vascular lesions (11988). The mortality associated with comfrey toxicity is 50%. However, specific toxic levels seem to vary among individuals (11990).
Pulmonary/Respiratory ...The pyrrolizidine alkaloid constituents of comfrey can damage the lungs, resulting in pulmonary hypertension (11987,11988,11990). A case report involving a 66-year-old female with known arterial hypertension, mild kidney insufficiency, and type 2 diabetes described severe partial respiratory insufficiency and pulmonary hypertension. The patient admitted to using a number of alternative therapies daily, including comfrey (44911).
Other ...Comfrey contains toxic pyrrolizidine alkaloids, which are carcinogenic and mutagenic (12841,12842).
General
...Orally, fluoride seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal symptoms.
Topically: Stained teeth.
Serious Adverse Effects (Rare):
Orally: Allergic reactions, including atopic dermatitis, exfoliative dermatitis, gastrointestinal allergic reactions, inflamed lips, respiratory allergic reactions, stomatitis, and urticaria.
Cardiovascular ...A meta-analysis shows that exposure to drinking water high in fluoride is associated with increases in both systolic and diastolic blood pressure, and possibly an increased risk of developing hypertension, when compared with exposure to drinking water with low to normal levels. High levels of fluoride were defined as 1.02-4.06 mg/L and low to normal levels were defined as 0.18-0.84 mg/L (107650).
Gastrointestinal
...Orally, fluoride can cause gastrointestinal symptoms (94405).
Enteric-coated and sustained-release dosage forms of sodium phosphate and sodium monofluorophosphate may cause fewer adverse effects than plain sodium fluoride (9127,9129). Adverse effects appear to be dose related. Sodium fluoride at high daily doses of 40-65 mg can cause nausea, vomiting, and GI bleeding (15,9127).
Fluoride can cause enamel fluorosis, a condition in which the ingestion of excessive amounts of fluoride during the development of permanent teeth may cause discoloration and pitting. This is a cosmetic effect only; tooth enamel may be stronger and more resistant to caries with enamel fluorosis (7555). Topically, use of stannous fluoride in toothpaste has caused staining of the teeth (94409).
Immunologic ...Exposure to fluoride can cause allergic reactions including urticaria, exfoliative dermatitis, atopic dermatitis, stomatitis, and gastrointestinal allergic reactions. Respiratory allergic reactions occur rarely (15,94408). A case of dermatitis around the mouth was thought to be related to the high fluoride levels in a specific toothpaste (NeutraFluor 5000 Plus) (94408). In another case report, lip inflammation occurred in reaction to the amine fluoride in a toothpaste product (94404). Lip inflammation and urticaria were also reported in reaction to a specific brand of toothpaste (Crest Pro-Health). However, it is not clear if this reaction occurred in response to the fluoride or tin component of stannous fluoride (94403).
Musculoskeletal ...Orally, sodium fluoride 40-65 mg daily can cause lower extremity pain and stress fractures (15,9127,94405). Fluoride at high doses for prolonged periods, over 10 mg daily for 10 or more years, can cause skeletal fluorosis. Skeletal fluorosis initially presents as joint stiffness and pain, followed by crippling, osteosclerosis, muscle wasting, and neurological defects due to hyper calcification of the vertebra. Crippling skeletal fluorosis is extremely rare in the US (7555).
Neurologic/CNS
...Exposure to high levels of natural fluoride during neurodevelopment in childhood is associated with a decreased IQ score.
This relationship has been shown in numerous population studies comparing areas with water containing high levels of natural fluoride (e.g. up to 11.5 mg/L) with the standard concentrations (0.7-1.2 mg/L) normally found in fluoridated water (94401,103544). The Canadian Dental Association recommends that when infant formulas are used as the main source of nutrition, drinking water that contains natural fluoride above recommended levels should not be used to reconstitute the formula (103545).
There is some concern that levels of fluoride found in optimally fluoridated water sources might also impact neurodevelopment during infancy or childhood. For example, population research in Canada has found a relationship between urinary fluoride levels and diagnosis of ADHD with higher inattention scores at age 14 years, but not at age 9 years. At 14 years, the predicted odds of an ADHD diagnosis was 2.8 times greater than the odds for youth in non-fluoridated regions (103551). In addition, in infants under 6 months of age using formula as the main source of energy, there is some concern that reconstitution of formula with fluoridated water might result in fluoride intakes above the tolerable upper intake level (UL). One observational study in Canada found that for each 0.5-gram increase in fluoride from reconstituted formula, there is an 8.8-point decrement in performance IQ, which measures non-verbal reasoning and visual-motor coordination, at 3-4 years of age. However, there was no association with global intellectual functioning or verbal reasoning (103529).
There is also some concern that levels of fluoride found in optimally fluoridated water sources might impact fetal neurodevelopment. Emerging population research found that increased fluoride intake during pregnancy, from appropriately fluoridated water or fluoridated salt, might be associated with negative cognitive effects. One observational study in Canada found that for each 1 mg/L increase in maternal urinary fluoride, there is a 3.7-point decrement in IQ in children aged 3-4 years, with a greater reduction in non-verbal abilities than verbal abilities. A sub-analysis revealed a decrement of 4.5 points in males, with no decrement in females (103543,103547). Another study found that increased exposure to fluoride during pregnancy is associated with symptoms of inattention in the offspring at age 6-12 years (103550).
The findings of these studies are interesting and support further research. More information is needed to know if these results are clinically significant at the population level (103548,103549,103550). In addition, although effort was made to take confounding factors into consideration, more information is needed to determine whether these neurological effects are related to fluoride exposure during pregnancy or to other factors such as socioeconomic status, use of formula instead of breast-feeding, parental intelligence, choice of IQ tests used in studies, and others. Also, the actual intake of fluoride was not known in most cases (94401,103542,103544,103546,103547,103548,103549,103550).
Other ...Population research in adolescents has found that having plasma fluoride levels of at least 0. 32 micromol/L or consuming water with fluoride levels of at least 0.73 mg/L increases the odds of hyperuricemia by approximately 1.8-fold when compared with the lowest quartiles. In addition, serum uric acid levels are increased by 0.212 mg/dL for each icromole/L increase in plasma fluoride levels (107645).
General
...Orally, intravenously, and rectally, phosphate salts are generally well tolerated when used appropriately and/or as prescribed.
Most Common Adverse Effects:
Orally: Abdominal pain, anal irritation, bloating, diarrhea, headache, gastrointestinal irritation, hyperphosphatemia, hypocalcemia, malaise, nausea, sleep disturbance, and vomiting.
Rectally: Hyperphosphatemia and hypocalcemia.
Serious Adverse Effects (Rare):
Orally: Extraskeletal calcification.
Cardiovascular ...Orally, a case of allergic acute coronary syndrome e., Kounis syndrome) is reported in a 43-year-old female after ingesting a specific sodium phosphate laxative product (Travad oral). She presented with maculopapular rash that progressed to anaphylaxis and a non-ST elevation acute coronary syndrome. The patient recovered after hospitalization for 3 days with medical management (112894).
Gastrointestinal ...Orally, phosphate salts can cause gastrointestinal irritation, nausea, abdominal pain, bloating, anal irritation, and vomiting (15,2494,2495,2496,2497,93846,93848,93850,93851,93853,107008). Sodium and potassium phosphates can cause diarrhea (15). Aluminum phosphate can cause constipation (15). A large comparative study shows that, when taken orally as a bowel preparation for colonoscopy, sodium phosphate is associated with gastric mucosal lesions in about 4% of patients (93868).
Neurologic/CNS ...Orally, phosphate salts can commonly cause malaise (93846). Headaches and sleep disturbance may also occur (93848,93851).
Renal ...Orally, use of sodium phosphate for bowel cleansing has been associated with an increased risk of acute kidney injury in some patients (93863). However, a pooled analysis of clinical research suggests that results are not consistent for all patients (93864). Some evidence suggests that female gender, probably due to lower body weight, iron-deficiency anemia, dehydration, and chronic kidney disease are all associated with an increased risk of sodium phosphate-induced kidney dysfunction (93865).
Other
...Orally, phosphate salts can cause fluid and electrolyte disturbances including hyperphosphatemia and hypocalcemia, and extraskeletal calcification.
Potassium phosphates can cause hyperkalemia. Sodium phosphates can cause hypernatremia and hypokalemia (15,2494,2495,2496,2497,107008).
Rectally, phosphate salts can cause fluid and electrolyte disturbances including hyperphosphatemia and hypocalcemia (15,112922).
Deaths related to intake of oral or rectal phosphate salts are rare and most have occurred in infants and are related to overdose (93866). However, death has also been reported in elderly patients using sodium phosphate enemas, mainly at standard doses of 250 mL (93867).