Effects of dietary tin on tin and calcium metabolism of adult males
ABSTRACT
The effects of dietary tin on tin and calcium metabolism were determined in eight adult males. Subjects were fed mixed diets containing 0.11 mg tin daily (control diet) and 49.67 mg tin daily (test diet) for 20 days each in a cross-over design. The level of tin in the control diet was typical of the level of tin found in diets that contained only fresh and frozen foods; the level of tin in the test diet was typical of the amount of tin in diets that contained several servings of certain canned foods. Subjects apparently absorbed 3 and 50% of their dietary tin intake when fed the test and control diets, respectively. Subjects lost significantly more tin in their urine, but retained significantly more tin when fed the test diet rather than the control diet. The fecal and urinary losses and serum levels of calcium were not affected by the dietary treatments.
References (28)
- BenoyCJ et al.
The toxicity of tin in canned fruit juices and solid foods.
Food Cosmet Toxicol
(1971) - GregerJL et al.
Effect of dietary tin on zinc, copper and iron utilization by rats.
Food Cosmet Toxicol
(1981) - HilesRA
Absorption, distribution and excretion of inorganic tin in rats.
Toxic Appl Pharmacol
(1974) - YamaguchiM et al.
Effect of tin on calcium content in the bile of rats.
Toxic Appl Pharmacol
(1978) - YamaguchiM et al.
Decreased gastric secretion in rats treated with stannous chloride.
Toxic Appl Pharmacol
(1976) - HegstedM et al.
Urinary calcium and calcium balance in young men as affected by level of protein and phosphorous intake.
J Nutr
(1981) - PetersJH
The determination of creatinine and creatine in blood and urine with a photoelectric colorimeter.
J Biol Chem
(1942) - SchwarzK et al.
Growth effects of tin compounds in rats maintained in a trace elementcontrolled environment.
Biochem Biophys
(1970) - WarburtonS et al.
Outbreak of foodborne illness attributed to tin.
US Publ Hlth Rep
(1962) - Monier-WilliamsGW
Tin.
Fecal excretion of iron and tin by men fed stored canned foods.
Am J Clin Nutr
Abnormal trace metals in man-tin.
J Chron Dis
Dose-effect of inorganic tin on biochemical indices in rats.
Toxicology
Accumulation of calcium in kidney and decrease of calcium in serum of rats treated with tin chloride.
J Toxicol Environ Health
Cited by (26)
Tin
2021, Handbook on the Toxicology of Metals: Fifth EditionTin can be found in both inorganic and organic forms. Inorganic and organic tin compounds are widely distributed in nature. Inorganic tin occurs naturally in environmental media, whereas organic tin compounds are pollutants of anthropogenic origin. The inorganic tin compounds are not highly toxic due to their low solubility and poor absorption. However, chemical and biochemical methylation reactions may convert inorganic tin compounds into methyltin forms. Hydrophobic organotins are harmful to both prokaryotes and eukaryotes due to their solubility. Their toxicity depends on the length of alkyl chain, hydrophobicity, and other physicochemical properties. The alkyl tins are more toxic than the aryl tins, whereas the toxicity of the short-chain trimethyl and triethyl tins is the highest. The use of tin compounds in economic development can create an accumulation of toxic waste in the environment. For over 40 years, tributyltin was used as a biocide in antifouling paint. Despite the demonstrated economic benefit of organotin compounds, extensive usage resulted in the pollution of freshwater and marine ecosystems. Although organotins were banned from use, they are still of concern in the aquatic environment. Contaminated sediments release accumulated organotin compounds to the environment long after the initial deposition has ceased. The widespread agricultural applications of organotin-based biocidal agents are very hazardous to humans, plants, and animals. Endocrine disruption induced by organotin compounds predisposes to obesity and associated metabolic syndrome disorders including diabetes. Organotins exert immunotoxic, neurotoxic, hepatotoxic, and genotoxic effects. Central nervous system toxicity manifests as confusion, loss of vigilance, loss of memory, and tremors.
Some plastics can leak organotin compounds into food from packaging. Plastic waste is flooding oceans. The leaching of organotin stabilizers into the environment is a great concern, considering that more than 2 million tons of plastic enter the ocean every year. Over time, plastic degrade into small pieces called microplastics. Photochemical weathering leads to plastics’ degradation and release of chemical additives, including organotin compounds. Microplastics can be consumed by different marine biota leading to organotins transfer in an aquatic food chain. Accumulation of organotin compounds has well-documented adverse effects on the marine environment and human health. Negative environmental consequences include a decline in both the total number of species and species diversity.
This chapter summarizes the research progress on inorganic and organic tin toxicity and recent advances in the determination and mode of action of organotin compounds.
Environmental tin exposure in a nationally representative sample of U.S. adults and children: The National Health and Nutrition Examination Survey 2011–2014
2018, Environmental PollutionTin is a naturally occurring heavy metal that occurs in the environment in both inorganic and organic forms. Human exposure to tin is almost ubiquitous; however, surprisingly little is known about factors affecting environmental tin exposure in humans. This study analyzed demographic, socioeconomic and lifestyle factors associated with total urinary tin levels in adults (N = 3522) and children (N = 1641) participating in the National Health and Nutrition Examination Survey (NHANES) 2011–2014, a nationally representative health survey in the United States. Urinary tin levels, a commonly used biomarker of environmental tin exposure, were determined by inductively coupled plasma mass spectrometry (ICP-MS). Detection frequencies of tin were 87.05% in adults and 91.29% in children. Median and geometric mean levels of urinary tin in the adult population were 0.42 μg/L and 0.49 μg/L, respectively. For children, median and geometric mean levels of urinary tin were 0.60 μg/L and 0.66 μg/L, respectively. Age was identified as an important factor associated with urinary tin levels. Median tin levels in the ≥60 year age group were almost 2-fold higher than the 20–39 year age group. Tin levels in children were 2-fold higher than in adolescents. Race/ethnicity and household income were associated with tin levels in both adults and children. In addition, physical activity was inversely associated with urinary tin levels in adults. These results demonstrate that total tin exposures vary across different segments of the general U.S. population. Because the present study does not distinguish between organic and inorganic forms of tin, further studies are needed to better characterize modifiable factors associated with exposures to specific tin compounds, with the goal of reducing the overall exposure of the U.S. population.
Derivation of biomonitoring equivalent for inorganic tin for interpreting population-level urinary biomonitoring data
2016, Regulatory Toxicology and PharmacologyPopulation-level biomonitoring of tin in urine has been conducted by the U.S. National Health and Nutrition Examination Survey (NHANES) and the National Nutrition and Health Study (ENNS – Étude nationale nutrition santé) in France. The general population is predominantly exposed to inorganic tin from the consumption of canned food and beverages. The National Institute for Public Health and the Environment of the Netherlands (RIVM) has established a tolerable daily intake (TDI) for chronic exposure to inorganic tin based on a NOAEL of 20 mg/kg bw per day from a 2-year feeding study in rats. Using a urinary excretion fraction (0.25%) from a controlled human study along with a TDI value of 0.2 mg/kg bw per day, a Biomonitoring Equivalent (BE) was derived for urinary tin (26 μg/g creatinine or 20 μg/L urine). The geometric mean and the 95th percentile tin urine concentrations of the general population in U.S. (0.705 and 4.5 μg/g creatinine) and France (0.51 and 2.28 μg/g creatinine) are below the BE associated with the TDI, indicating that the population exposure to inorganic tin is below the exposure guidance value of 0.2 mg/kg bw per day. Overall, the robustness of pharmacokinetic data forming the basis of the urinary BE development is medium. The availability of internal dose and kinetic data in the animal species forming the basis of the assessment could improve the overall confidence in the present assessment.
Chelation Treatment During Acute and Chronic Metal Overexposures-Experimental and Clinical Studies
2016, Chelation Therapy in the Treatment of Metal IntoxicationMetal overexposures, ranging from nonsymptomatic, elevated body levels to life threatening acute or chronic poisonings, should in general be treated by eliminating the exposure source, by various decontamination procedures, and by supportive treatment. However, in a quite extensive number of cases, various chelation treatment schedules offer an efficient way of handling the adverse effects of overexposure to metals, either by reducing the toxicity of the metal by forming a less toxic complex, by changing the toxicodynamics of the metal thereby reducing the interaction of the metal with a vulnerable target, and/or reducing its uptake and/or enhancing its excretion.
The present chapter offers a systematic review of the present state-of-the-art for chelation treatment of metal overexposures. Such exposures can be due to occupational, environmental, dietary, or lifestyle factors, or iatrogenic procedures. The review is ordered alphabetically citing animal experimental studies and epidemiological and clinical studies for each metal, if available.
The general experience is that the metal (Lewis acid) and the chelator (Lewis base) should have high affinity for each other (high stability constant), thus soft metals should be chelated by chelators with soft ligands (eg, C-SH), and hard metals with chelators with hard ligands (eg, COOH, CRO, CR2OH). Intermediate metals prefer, for example, N-containing ligands, but can be chelated by both hard and soft bases. However, the pharmacokinetics of the chelating agent is highly important also, especially whether the chelator and the metal-chelator complex formed are hydrophilic with enhanced renal excretion as result, or lipophilic with enhanced biliary excretion and/or brain deposition as a potential result.
Some important questions are: Can the chelator be administered orally, and will it enhance or prevent systemic uptake of toxic metal remaining in the gastrointestinal tract? Is the chelator metabolically stable to allow extended treatment with appropriate time lag between doses?
According to generally accepted ethical principles in pharmacology and medicine, experimental chelating agents proven efficient in animal experiments cannot be used in humans except in special cases, where the benefit clearly outweighs the potential toxicity of the agent. Based on the experimental and clinical work, optimal chelating agents for acute poisonings with selected metals are as follows:
Deferoxamine for aluminum compounds.
Dimercaptosulfonate (DMPS) for arsenic compounds, deferoxamine for iron compounds, with deferiprone and deferasirox as potential alternative chelators.
Dimercaptosuccinic acid (DMSA) for lead compounds, DMPS for inorganic mercury compounds including mercury vapor, DMSA may be superior for organic mercury compounds.
Today new chelators are being developed as decorporating agents for all classes of metals.
Tin
2015, Handbook on the Toxicology of Metals: Fourth EditionInorganic tin compounds occur naturally in the Earth’s crust. In the environment, tin can be found in both inorganic and organic forms. Inorganic tin compounds are released from natural and anthropogenic sources. The conversion of metallic tin forms to compounds that may be more soluble increases the risk of exposure and toxicity. Organotin compounds in the environment largely originate from anthropogenic activities. However, chemical and biochemical methylation reactions convert inorganic tin compounds into methyltin form. Biomethylation of alkyltins results in the accumulation of more toxic organotin compounds.
Tin is not regarded an essential nutrient for humans. However, tin is considered an essential for the growth of rats, with a requirement for tin of between 1 and 2 mg/kg in the diet. Elemental tin, inorganic tin compounds, and long-chain alkyltins are poorly absorbed when ingested, which accounts for their relatively low toxicity. The toxicity of organotin compounds depends on the length of alkyl chain, hydrophobicity, and other physicochemical properties. Hydrophobic organotins are toxic to a wide variety of organisms owing to their high solubility in cell membranes. The alkyl tins are more toxic than the aryl tins, whereas the toxicity of short-chain alkyltin compounds such as trimethyl- and triethyltin is higher than that of long-chain compounds: toxicity increases with number of alkyl groups. The excretory routes of tin compounds may vary depending of the type of compounds and the mode of exposure.
Insoluble inorganic tin compounds are largely nontoxic. However, inhalation of tin dust results in its deposition in lungs and may cause “stannosis,” a benign pneumoconiosis. Some tin salts are irritating or can liberate toxic fumes during decomposition. Gastrointestinal absorption of soluble tin salts is only a few percent of the ingested dose. In chronic exposure, tin tends to accumulate in kidney, liver, and bones. Bones comprise a major site of deposition of tin after long-term exposure and intramuscular injection. The biological half-life of tin in bone is approximately 100 days. Exposure to high concentrations of inorganic tin may cause gastrointestinal illness, as well as liver and kidney problems. No noteworthy histopathological observations of nonneoplastic nature were reported in a long-term study.
Short-chain alkyls are easily absorbed from gastrointestinal tract. Some alkyltin compounds, particularly tributyltin and triphenyltin, have high toxicity. Chronic exposure to butyltin compounds causes imposex, a pathological condition characterized by development of male sex characteristics in female gastropods. Toxicity of organotins in humans is most frequently reported as loss of memory and seizure, as well as other symptoms including death. Short-chain alkyltin, particularly the trialkyl derivatives, and aromatic tin compounds are neurotoxic. Hydrophobic trimethyltin and triethyltin compounds readily diffuse into richly lipophilic tissues such as brain and cause encephalopathy, cerebral edema, and severe seizures. Tetraalkyltins are enzymatically converted to the trisubstituted form and exert delayed but similar neurotoxic effects. Tributyltin compounds are less toxic than trimethyl- and triethyltins. They may be strongly irritating to the skin in humans. It was reported that shipyard workers exposed to tributyltin oxide developed severe dermatitis, difficulty in breathing, and flu-like symptoms. Trisubstituted organotin derivatives are implicated in hepatotoxicity, immunodeficiency, endocrine disruption, and both reproductive anomalies and infertility in laboratory animals. Monobutyltin and dibutyltin show genotoxicity, while mono- and dimethyltin are not genotoxic. Organotin compounds penetrate the cell membrane and interrupt oxidative phosphorylation, disturb calcium homeostasis, damage mitochondria, and induce apoptosis.
Tin
2014, Handbook on the Toxicology of MetalsInorganic tin compounds occur naturally in the Earth’s crust. In the environment, tin can be found in both inorganic and organic forms. Inorganic tin compounds are released from natural and anthropogenic sources. The conversion of metallic tin forms to compounds that may be more soluble increases the risk of exposure and toxicity. Organotin compounds in the environment largely originate from anthropogenic activities. However, chemical and biochemical methylation reactions convert inorganic tin compounds into methyltin form. Biomethylation of alkyltins results in the accumulation of more toxic organotin compounds.
Tin is not regarded an essential nutrient for humans. However, tin is considered an essential for the growth of rats, with a requirement for tin of between 1 and 2 mg/kg in the diet. Elemental tin, inorganic tin compounds, and long-chain alkyltins are poorly absorbed when ingested, which accounts for their relatively low toxicity. The toxicity of organotin compounds depends on the length of alkyl chain, hydrophobicity, and other physicochemical properties. Hydrophobic organotins are toxic to a wide variety of organisms owing to their high solubility in cell membranes. The alkyl tins are more toxic than the aryl tins, whereas the toxicity of short-chain alkyltin compounds such as trimethyl- and triethyltin is higher than that of long-chain compounds: toxicity increases with number of alkyl groups. The excretory routes of tin compounds may vary depending of the type of compounds and the mode of exposure.
Insoluble inorganic tin compounds are largely nontoxic. However, inhalation of tin dust results in its deposition in lungs and may cause “stannosis,” a benign pneumoconiosis. Some tin salts are irritating or can liberate toxic fumes during decomposition. Gastrointestinal absorption of soluble tin salts is only a few percent of the ingested dose. In chronic exposure, tin tends to accumulate in kidney, liver, and bones. Bones comprise a major site of deposition of tin after long-term exposure and intramuscular injection. The biological half-life of tin in bone is approximately 100 days. Exposure to high concentrations of inorganic tin may cause gastrointestinal illness, as well as liver and kidney problems. No noteworthy histopathological observations of nonneoplastic nature were reported in a long-term study.
Short-chain alkyls are easily absorbed from gastrointestinal tract. Some alkyltin compounds, particularly tributyltin and triphenyltin, have high toxicity. Chronic exposure to butyltin compounds causes imposex, a pathological condition characterized by development of male sex characteristics in female gastropods. Toxicity of organotins in humans is most frequently reported as loss of memory and seizure, as well as other symptoms including death. Short-chain alkyltin, particularly the trialkyl derivatives, and aromatic tin compounds are neurotoxic. Hydrophobic trimethyltin and triethyltin compounds readily diffuse into richly lipophilic tissues such as brain and cause encephalopathy, cerebral edema, and severe seizures. Tetraalkyltins are enzymatically converted to the trisubstituted form and exert delayed but similar neurotoxic effects. Tributyltin compounds are less toxic than trimethyl- and triethyltins. They may be strongly irritating to the skin in humans. It was reported that shipyard workers exposed to tributyltin oxide developed severe dermatitis, difficulty in breathing, and flu-like symptoms. Trisubstituted organotin derivatives are implicated in hepatotoxicity, immunodeficiency, endocrine disruption, and both reproductive anomalies and infertility in laboratory animals. Monobutyltin and dibutyltin show genotoxicity, while mono- and dimethyltin are not genotoxic. Organotin compounds penetrate the cell membrane and interrupt oxidative phosphorylation, disturb calcium homeostasis, damage mitochondria, and induce apoptosis.