Levels of tin and organotin compounds in human urine samples from Iowa, United States.

Exposure to tin in the general US population is near ubiquitous, as determined using urinary tin levels measured by inductively coupled plasma mass spectrometry (ICP-MS). Urinary tin levels are associated with chronic health outcomes, such as diabetes; however, it is unclear if these associations are due to the presence of inorganic and organic forms of tin in urine. To address this knowledge gap, levels of total tin and several organotin compounds (OTCs) were measured in convenience urine samples from pregnant women and adults from Iowa, United States. Total tin and OTC levels in urine samples were quantified using ICP-MS and gas chromatography with pulsed flame photometric detection (GC-PFPD), respectively. ICP-MS detected tin in almost all urine samples from both study populations. Low levels of dibutyltin were detected in two out of fifty human urine samples. Importantly, storage of urine samples in plastic containers, but not HNO3-pretreated glass vials drastically reduced the recoveries of OTCs, in particular, tributyltin. Although their detection frequency is low, exposures to OTC should be considered when studying associations between human exposures to tin compounds and adverse health outcomes; however, urinary OTC levels measured in banked urine samples may not be suitable as biomarkers of OTC exposure.

Urinary trimethyl tin reflects blood trimethyl tin in workers recycling organotins.

AIM: Our recent case report of organotin intoxication showed higher ratio of urinary trimethyl tin (TMT) to dimethyl tin (DMT) than those of the previous cases exposed to only DMT, suggesting co-exposure to DMT and TMT occurred. The present study investigated how urinary TMT and DMT reflect blood TMT and DMT, respectively, to evaluate them as biomarkers for TMT/DMT exposure. METHODS: DMT and TMT from blood collected at different time points from three patients intoxicated with organotins were measured with HPLC-ICP/MS. Previously published data of urinary DMT and TMT were used for comparison. Regression analyses were conducted with dependent variable of blood DMT and TMT and independent variable of urinary DMT and TMT, respectively. Multiple regression analysis with dummy variables of individual was also conducted. RESULTS: Regression analysis did not show significant relation of urinary TMT to blood TMT or relation of urinary DMT to blood DMT, although the former was marginal. Multiple regression analysis showed significantly positive relation of urinary TMT to blood TMT. CONCLUSIONS: The study shows that urinary TMT reflects blood TMT. In co-exposure to TMT and DMT, urinary TMT can be an internal exposure marker of TMT, which might be not only derived from external exposure to TMT but also converted from DMT in human body.

Association between urinary tin concentration and diabetes in nationally representative sample of US adults.

BACKGROUND: Animal studies indicate that chronic exposure to certain tin compounds induces pancreatic islet cell apoptosis and glucose intolerance. However, little is known about the health effects of environmental tin exposure in humans. Therefore, we evaluated the association of tin exposure with diabetes in a nationally representative sample of US adults. METHODS: We used data from a nationally representative population (n = 3371) in the National Health and Nutrition Examination Survey 2011-14. Diabetes (n = 605) was defined as self-reported physician's diagnosis, HbA1c ≥6.5%, fasting plasma glucose ≥126 mg/dL, or 2-h plasma glucose ≥200 mg/dL. Tin concentrations in urine samples were determined by inductively coupled plasma mass spectrometry. Logistic regression with sample weights was used to estimate the odds ratios (ORs) of diabetes and 95% confidence intervals (CIs). RESULTS: Urinary tin concentrations were higher in individuals with diabetes (weighted median 0.58 µg/L) than those without diabetes (0.39 µg/L). After adjustment for urinary creatinine and other diabetes risk factors, the OR of diabetes comparing the highest with lowest quartile of urinary tin concentrations was 1.6 (95% CI 1.0-2.6; Ptrend = 0.02). CONCLUSIONS: Environmental tin exposure was positively and significantly associated with diabetes in US adults.

Environmental tin exposure in a nationally representative sample of U.S. adults and children: The National Health and Nutrition Examination Survey 2011-2014.

Tin 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.

Kinetics and tissue distribution of bismuth, tin and lead after implantation of miniature shotgun alloy pellets in rats.

INTRODUCTION: Shotgun pellets containing bismuth (Bi) as substitute for lead (Pb) are increasingly being used due to environmental concerns. Information on toxicokinetics of Bi is lacking for the assessment of humans accidentally shot by Bi-containing shotgun alloy pellets. METHODS: Male Wistar rats were exposed to miniature alloy pellets containing Bi, tin (Sn) and minor amounts of Pb by implantation in muscle tissues of the hind legs. RESULTS: The concentrations of Bi in whole blood and urine increased up to 53 weeks after implantation. The highest concentrations of Sn in whole blood were observed three weeks after implantation, then declining to background levels 53 weeks after implantation. Lead in whole blood increased up to 13 weeks of exposure, and declined for the remaining observation period. Bismuth and Sn accumulated mainly in kidney, but also in liver, testicle and brain. Analytical field emission scanning electron microscopy of post-implant pellets showed depletion of Pb towards the pellet surface. Oxygen and chlorine accumulated in Sn rich lamellas in areas next to the pellet surface. The distribution of Bi remained visually unaffected as compared to pre-implant pellets. CONCLUSION: The concentration of Bi increased during the whole observation period in blood, urine, kidney, brain, testicle and liver. The decline in the concentrations of Pb and Sn in blood and urine after reaching the peak concentration may be related to alterations in the chemical composition and element distribution of the implanted alloy pellets.

Derivation of biomonitoring equivalent for inorganic tin for interpreting population-level urinary biomonitoring data.

Population-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.

Food intake survey of kindergarten children in Korea: Part 2 increased dietary intake of tin possibly associated with canned foods.

OBJECTIVES: Dietary intake of tin (Sn) may be increased in some children in kindergartens in Korea. The present study was intended to examine this possibility and clarify the extent of the elevation. METHODS: 24-hour food duplicate and spot urine samples were collected in 2003-2004 from 108 4-6-year-old children (boys and girls combined) in 4 kindergartens (1 in Seoul and 3 in Jeju Island), as reported in a previous publication. These samples were employed in the present analyses to examine tin levels in the diet (including beverages) (Sn-D). A portion of the samples were wet-ashed, and the liquid samples were analyzed for Sn by the ICP-MS method. For statistical evaluation, χ (2) method and Smirnov's test for extreme value were used. RESULTS: Sn-D in the 108 cases distributed as extremely biased, and could be divided into two groups, i.e., those with <10 µg Sn/day (accounting for 90% of the cases), and those with >10 µg/day (for 10%). Sn-D in the former group was distributed quasi-normally with an AM (median) of 2.9 (2.5) µg/day. The maximum in the latter group was 3012 µg/day. No correlation was detected between Sn-D and Sn in urine (Sn-U). Comparison of the findings with published articles strongly suggested that the high Sn-D was due to consumption of foods (including beverages) preserved in tin-plated cans. No positive confirmation was however possible due to insufficient information on food records. CONCLUSIONS: About 10% of children surveyed had elevated Sn-D (up to 3 mg/day). It was quite possible that high Sn-D was associated with tin-canned food intake.

[Determination of stannum in urine by graphite furnace atomic absorption spectrometry].

OBJECTIVE: To establish the method of graphite furnace atomic absorption spectrometry for the measurement of stannum in urine with calcium nitrate as the matrix modifier. METHODS: Graphite tube was pretreated with calcium nitrate as the matrix modifier, the urine sample was diluted with 1% nitric acid and then direct injection was performed for these samples, and graphite furnace atomic absorption spectrometry was applied for measurement. RESULTS: The concentration of stannum in urine showed a good linear relationship within the range of 8.0~40.0 µg/L, with a correlation coefficient of 0.9981. The minimum detectable concentration was 0.72 µg/L, the degree of precision was 1.54%~6.69%, and the recovery rate was 99.23%~107.63%. CONCLUSION: This method can determine the content of stannum in urine accurately and rapidly, with a high sensitivity and a low cost.

Toxicological status of children with autism vs. neurotypical children and the association with autism severity.

This study investigates both the level of toxic metals in children with autism and the possible association of those toxic metals with autism severity. This study involved 55 children with autism ages 5-16 years compared to 44 controls with similar age and gender. The study included measurements of toxic metals in whole blood, red blood cells (RBC), and urine. The autism group had higher levels of lead in RBC (+41 %, p = 0.002) and higher urinary levels of lead (+74 %, p = 0.02), thallium (+77 %, p = 0.0001), tin (+115 %, p = 0.01), and tungsten (+44 %, p = 0.00005). However, the autism group had slightly lower levels of cadmium in whole blood (-19 %, p = 0.003). A stepwise, multiple linear regression analysis found a strong association of levels of toxic metals with variation in the degree of severity of autism for all the severity scales (adjusted R(2) of 0.38-0.47, p < 0.0003). Cadmium (whole blood) and mercury (whole blood and RBC) were the most consistently significant variables. Overall, children with autism have higher average levels of several toxic metals, and levels of several toxic metals are strongly associated with variations in the severity of autism for all three of the autism severity scales investigated.

Direct determination of tin in whole blood and urine by GF AAS.

OBJECTIVE: The aim of this work was to develop a procedure for the determination of tin in whole blood and urine by GF AAS with a minimum sample pre-treatment, using Pd/Mg as chemical modifier. DESIGN AND METHODS: The analyses of tin were conducted using an atomic absorption spectrometer with Zeeman background correction. The laboratory staff volunteered blood and urine samples for the experimental studies and application of the methodology. RESULTS: Samples were just diluted with 0.2% v/v Triton X-100, and pyrolysis and atomization temperatures of 1300 and 2200 °C were used. External calibration was performed with matrix matched calibration solutions. Limits of detection of 2.7 and 0.8 µgL(-1) were reached for blood and urine, respectively. The method was applied to the determination of Sn in blood and urine of eleven subjects not occupationally exposed, working in a laboratory of toxicology in a large Brazilian city, and the results ranged from 7.4 to 11.2 µgL(-1) and ≤0.8 to 2.2 µgL(-1), for blood and urine, respectively. Accuracy was assessed by analysis of standard reference materials for tin in blood (Contox I, lot TM144-1097, Kaulson Laboratories, USA) and urine (Seronorm, lot 0511545, Sero AS, Norway). CONCLUSIONS: Results showed good agreement between experimental and reference values according to the Student's t test at 95% of confidence.

Maternal exposure to low-level heavy metals during pregnancy and birth size.

We evaluated the effect of environmental, low-level exposure to heavy metals during pregnancy, as estimated by urine analysis, on birth size of the newborns. Spot urine samples were collected from unexposed 78 pregnant women in Tokyo during 2007 and 2008. The urinary concentrations of beryllium (Be), copper (Cu), arsenic (As), zinc (Zn), selenium (Se), molybdenum (Mo), cadmium (Cd), tin (Sn), antimony (Sb), and lead (Pb) were measured by ICP-MS. The birthweight (BW), length (BL) and head circumference (HC) of the newborns delivered to the subjects were measured and relationship with urinary metal concentration was examined. The geometric mean concentration of urinary Be, Cu, As, Zn, Se, Mo, Cd, Sn, Sb, and Pb were 0.031, 12.8, 393, 76.9, 37.6, 79.0, 0.766, 0.232, < 0.21, 0.483 microg g-creatinine(-1), respectively. The mean birth size of the newborn was close to the national average value in Japan. Stepwise multiple regression analysis using birth size as a dependent variable and urinary metal concentrations and covariates as independent variables extracted urinary Cd with a significant negative standardized partial regression coefficient (beta) for BW along with gestational age and maternal BMI. For HC, Sn was selected with a negative beta. The present study suggested that even a low-level Cd body burden of general population has slight but significant negative effect on BW.

Dietary intake of tin in Japan, and the effects on intake of canned food and beverage consumption.

The study reported herein was initiated to examine dietary tin intake (Sn-D) in Japan to elucidate the possible effects of consumption of canned food (including beverages) on Sn-D, and to compare the intake among regions and between the two sexes in reference to the current provisional tolerable weekly intake and intake in other countries. Urinary tin levels (Sn-U) were also studied. Duplicate diet samples (24 h) together with records of food intake were collected in 1999-2004 from 111 adult residents in four areas of Japan. After exclusion of incomplete samples, 95 valid samples were subjected to determination of tin by inductively coupled plasma mass spectrometry (ICP-MS) after acid digestion. Among the 95 cases, 37 women additionally provided urine samples. Distribution of Sn-D was markedly skewed. Median Sn-D was 5.6 microg day(-1) for total subjects, which was about one-tenth of the values previously reported for the Japanese population; the difference was most probably attributable to the difference in the methods of determination. Consumption of canned foods led to a substantial increase in Sn-D. Thus, the median Sn-D for canned food consumers of 35.7 microg day(-1), was eight-fold higher than the median Sn-D for non-consumers of 4.5 microg day(-1). Sn-U (as corrected for creatinine concentration) distributed log-normally with a geometric mean of 2.0 microg (g cr)(-1). No effect of canned food consumption was evident on Sn-U. When compared internationally, Sn-D for the Japanese population was substantially lower than Sn-D for populations in other industrialized countries.

The determination of metals (antimony, bismuth, lead, cadmium, mercury, palladium, platinum, tellurium, thallium, tin and tungsten) in urine samples by inductively coupled plasma-mass spectrometry.

OBJECTIVE: An analytical method has been established to determine the concentration of antimony (Sb), bismuth (Bi), lead (Pb), cadmium (Cd), mercury (Hg), Palladium (Pd), platinum (Pt), tellurium (Te), tin (Sn), thallium (Tl) and tungsten (W) in urine. The aim was to develop a method which is equally suitable for the determination of environmentally as well as occupationally caused metal excretion. METHODS: Inductively coupled plasma-mass spectroscopy (ICP-MS) was used for the determination of metals. Calibration was done using aqueous solutions and standard addition respectively. RESULTS: Urine samples of 14 persons occupationally non-exposed to metals were analysed. With the exception of Pt and Bi all the metals were found in these urine samples. The detection limits for these metals lie between 5 and 50 ng/l. CONCLUSIONS: For some metals, which are important from an occupational as well as an environmental viewpoint, ICP-MS is more sensitive than atomic absorption spectrometry (AAS). ICP-MS, moreover, is welcome as a reference method for AAS with the additional advantage of multi-element measurement.

Comparison of hepatotoxicity caused by mono-, di- and tributyltin compounds in mice.

The in vivo induction of hepatotoxicity, as evaluated by the activity of ornithine carbamyl transferase in serum, was investigated in mice administered orally with the following three butyltin compounds: tributyltin chloride (TBTC), dibutyltin dichloride (DBTC) and monobutyltin trichloride (MBTC). The minimal concentrations of TBTC and DBTC that caused hepatotoxicity at 24 h after oral administration were 180 mumol and 60 mumol/kg, respectively, while MBTC did not induce liver injury even at 7000 mumol/kg. Additionally, when the administered doses were equivalent (180 mumol/kg), a time course (3-96 h) study revealed that the hepatotoxicity of TBTC and DBTC appeared at 24 and 12 h, respectively, but that MBTC showed no hepatotoxicity even at 96 h. The amounts of Sn excreted into urine for 4 days were 1.5 fold greater with TBTC than with DBTC treatment and were lowest in MBTC group. Similarly, the total liver Sn content was 2- to 5-fold greater in the TBTC group than in the DBTC group whereas the liver Sn content in the MBTC treatment showed the lowest value throughout the 3- to 96-h period. Thus, the non-hepatotoxicity of MBTC may be due either to low absorption through the digestive tract of mice or to the low levels of Sn in liver; however, the level of Sn in liver was not associated with the induction of hepatotoxicity by TBTC and DBTC.(ABSTRACT TRUNCATED AT 250 WORDS)

Gas chromatographic determination of inorganic tin in rat urine after a single oral administration of stannous chloride and mono-, di-, and triphenyltin chloride.

A method is described for the determination of inorganic tin by gas chromatography with flame photometric detection. The inorganic tins, stannous and stannic, were extracted with hydrochloric acid and n-hexane-benzene in the presence of 0.05% tropolone, and both inorganic tins were pentylated to tetrapentyltin with a Grignard reagent prior to gas chromatography. The absolute limit of detection for tetrapentyltin was 3 pg as tin. The recovery of stannous chloride added to rat urine samples was 80.2 +/- 2.4% (mean +/- S.D., n = 8). The application of this method to the study of urinary excretion of inorganic tin and organotin compounds in rats following oral administration of tin compounds is presented. The urinary excretion of tin compounds was observed over a period of 96 h following administration of stannous chloride or phenyltin compounds. Most of the inorganic tin was excreted into urine within 24 h after administration of stannous chloride. In the experiments on organotin administration, the level of the excretion as total tin for monophenyltin reached a maximum ca. 0-24 h after administration, whereas the maxima for di- and triphenyltin were found after 24-48 h and 48-72 h, respectively. The predominant excretion product of these tin compounds found in urine was monophenyltin.

[A study on urinary tin in healthy adults: relationship between the concentration of urinary tin and life style].

The concentrations of urinary tin in healthy adults in Aichi prefecture were determined by anodic stripping voltammetry over a period of three years (1986-1988), to obtain the normal tin level in urine and to elucidate the influence of environmental alterations on health conditions in the future. In addition to the above-mentioned method, the relationship to life style, dietary habits, smoking habits and living environment were studied, and the following results were obtained. 1) The mean +/- standard deviation of urinary tin levels for males was 3.7 +/- 2.2 (micrograms/g creatinine), and 5.9 +/- 3.0 (micrograms/g creatinine) for females. The data showed logarithmic normal distributions in both sexes, and the mean concentration for females was significantly higher than that for males (P less than 0.001). The levels of urinary tin concentrations significantly increased according with age. 2) Significant correlations of urinary tin concentrations between two observations were noticed in repeated by observed subjects. 3) As to the dietary habits, fish intake increased the urinary tin concentration, but no definite association with canned-food intake was observed. 4) Smoking habits and living environment also showed a tendency to increase the urinary tin concentration, but the difference was not statistically significant.

Occupational triphenyltin acetate poisoning: a case report.

A case of triphenyltin acetate (TPTA) poisoning is described. The patient, who had been exposed mainly to cutaneous absorption, showed acute stages of an urticarial eruption, signs of hepatic injury, slight glucose intolerance, and electroencephalographic abnormalities. Concomitant with the highest concentrations of tin in plasma and the peak of tin excretion in urine, neutrophils did not show the normal increase in actin polymerisation after stimulation with a chemotactic peptide (100 nM fMLP). The peak of urinary excretion of tin occurred between the fifth and the sixth day after poisoning; subsequently, the rate of excretion became slow, suggesting biphasic kinetics with the possibility of a cumulative trend.

Dose-dependent brain tin concentration in rats given stannous chloride in drinking water.

Male Wistar rats were given either 100 mg SnCl2 X 2H2O per litre (0.44 mM), 250 mg/l (1.11 mM) or 500 mg/l (2.22 mM) in their drinking water for 1-18 weeks. Tin detected by a novel atomic absorption spectrophotometric method accumulated in the cerebrum at the highest dose level (2.22 mM) throughout the experiment. In brain, tin concentrations above the 1.11-mM dose were only found after 15 and 18 weeks. Tin did not increase in the brain at the 0.44-mM dose level. Blood tin increased promptly after one week at the highest dose (2.22 mM) without further accumulation. Blood tin at the 0.44 mM dose level did not differ from controls. Tin exposure caused a dose-dependent increase in the cerebral and muscle acetylcholinesterase activity at the two higher doses.

Methyltin intoxication in six men; toxicologic and clinical aspects.

Neurologic and psychiatric symptoms such as headache, tinnitus, defective hearing, changing desorientation and aggressiveness are initial symptoms of methyltin chloride intoxication. Some patients also developed epileptic equivalents, such as dreamy attacks and central ventilation transaminases. Laboratory findings included low levels of serum potassium, leucocytosis and elevated transaminases. The excretion rate of tin in the urine correlated with the severity of the intoxication. There was no measurable effect of plasma separation or d-penicillamine therapy on tin excretion in the urine or on the clinical picture. The long-term prognosis of severely intoxicated persons is poor. Neurohistopathologic findings confirm the animal studies by Brown et al and the severe damage and cell necrosis in the hippocampus area. To prevent such events workers need to be warned of the risk and dangers of working with organo-metallic compounds. The effectiveness of protective clothes and gas masks should be checked. In exposed workers regular testing is advised of tin concentrations in the urine.