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.

Chronic trimethyltin chloride exposure and the development of kidney stones in rats.

We recently reported that occupational exposure to trimethyltin (TMT) is a risk factor for developing kidney stones. To further examine the association between TMT exposure and the formation of kidney stones, we conducted a 180-day animal study and exposed the randomly grouped Sprague-Dawley (SD) rats to TMT in the drinking water at doses of 0, 8.2, 32.8 and 131.3 µg kg(-1) day(-1). Transient behavioral changes were observed in the high-dose group during the first 2 weeks of exposure. TMT exposure led to a significant dose-dependent inhibition of renal H(+)/K(+)-ATPase and an increase in urinary pH. In comparison to no kidney stones being identified in the control and the lowest dose group, 1 rat in the 32.8 µg kg(-1) day(-1) dose group and 3 out of 9 rats in the 131.3 µg kg(-1) day(-1) dose group were found to have stones in the kidney/urinary tract. Pathological analysis showed that more wide spread calcium disposition was observed in kidneys of rats with TMT exposure compared with the rats in the control group. However, X-ray diffraction (XRD) analysis found that the kidney stones were mainly composed of struvite with the formula: NH4MgPO4 6H2O, while calcium-containing components were also detected. Together, this study further demonstrates through animal studies that chronic exposure to a relatively low level of TMT induces nephrotoxicity and increases the risk for developing kidney stones.

Chronic low level trimethyltin exposure and the risk of developing nephrolithiasis.

OBJECTIVES: Nephrolithiasis (kidney stones) is a common disease with the prevalence that is increasing globally. We previously found that trimethyltin (TMT), a by-product of plastic stabilisers, can inhibit the H(+)/K(+) ATPase activity in renal intercalated cells and alter urinary pH, which is a known risk factor for nephrolithiasis. In this study, we conducted a cross-sectional analysis to evaluate the impact of chronic low level occupational TMT exposure on nephrolithiasis. METHODS: This study included 216 healthy workers with TMT exposure and 119 workers as controls with no TMT exposure. All study participants were administered a questionnaire and underwent a routine clinical examination including an ultrasonographic screening for kidney stones. Exposures were assessed by measuring TMT concentrations in personal air samples, blood and urine. Logistic regression analysis was used to estimate the ORs and 95% CIs for the risk of kidney stones. RESULTS: TMT exposed workers had a higher prevalence of kidney stones (18.06%) in comparison with control workers (5.88%). High TMT concentrations in personal air samples, blood and urines were positively associated with increased prevalence of kidney stones in workers exposed to TMT compared with controls workers (p-trend values=0.005, 0.008 and 0.002, respectively). The length of employment in plants with elevated TMT levels (duration of the exposure) was significantly associated with the increased prevalence of kidney stones (p trend=0.001). The ORs were 2.66 for <3 years, 3.73 for 3-<10 years and 7.89 for 10+ years of employment compared with control workers. CONCLUSIONS: To our knowledge, this is the first report to demonstrate that occupational exposure to TMT is a potential risk factor for nephrolithiasis.

[Determination of trimethyltin chloride in urine by headspace-gas chromatography].

OBJECTIVE: To establish a detection method for trimethyltin chloride in urine by the Head space-GC. METHOD: After derivatizing trimethyltin chloride, the urines was separated by the head space-gc, and then the trimethyltin chloride detected qualitatively and quantificationally. RESULTS: In the concentration range of 0.02 ∼ 0.40 mg/L urinary trimethyltin chloride, showed a quadratic, r = 0.9992, detection limit was 0.005 mg/L, the relative standard deviation was 1.9% ∼ 2.5%, recovery was 92.0% to 100%, the urine samples can be saved at least 90 days in -18°C refrigerator. CONCLUSION: The instrument, reagents involved in the detection require low, the operations to processing samples are simple, high sensitivity, less interference, good reproducibility, and suitable for quantitative and qualitative analysis, convenient to promotion.

Development of an analytical method to confirm toxic trimethylated tin in human urine.

Dimethyltin dichloride (DMTC) is widely used as a heat stabilizer in manufacturing the polyvinyl chloride. We previously reported a case of acute DMTC poisoning with neurological manifestations very similar to trimethylated tin (TMT) encephalopathy, based on results of speciation analysis of methylated tins in the patient's urine with use of a combination of high performance liquid chromatography and inductively coupled plasma-mass spectrometry (HPLC-ICP-MS), which yielded peaks corresponding to DMT and TMT. In this study, we developed an analytical method to confirm TMT in urine using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and found TMT molecular ion in the patient's urine.

[Biological monitoring of workers exposed to trimethyltin chloride].

OBJECTIVE: To investigate suitable biomarkers for workers exposure to trimethyltin chloride (TMT-cl). METHODS: Urinary samples of 44 male workers from five TMT-cl occupational poisoning incidents were collected. Methyltin mercaptide stabilizers and waste plastics used in the incidents were also collected. The levels of TMT-cl in all the samples were determined by gas chromatography. The concentration of blood potassium for each poisonings was determined compared to control group (50 male workers of a food company), and the correlation between blood potassium and urinary TMT-cl were also determined. RESULTS: TMT-cl was detected in urine of all the poisonings. The results were (0.869 +/- 0.392) microg/L (severe poisoning), (0.963 +/- 0.482) microg/L (moderate poisoning), (0.716 +/- 0.384) microg/L (mild poisoning) respectively and the difference was statistically significant (P < 0.01). But the severity of the clinical status did not seem to be closely correlated to the level of urinary TMT-cl (F = 1.88, P > 0.05). In the severe poisonings, there were no differences in urinary TMT-cl on day 4 after poisoning from day 1 (P > 0.05). In contrast, urinary TMT-cl was decreased significantly on day 4 than on day 1 in mild and moderate poisonings (P < 0.01). On day 21, levels of urinary TMT-cl of all the poisonings were higher than those of the workers exposed to TMT-cl who had no clinical status (P < 0.01). Blood potassium levels of exposed group was 77.3% which was significantly lower than normal value (P < 0.01). The concentration of blood potassium was lower than normal value (3.5 mmol/L) and was correlated with the severity of the clinical status (F = 4.45, P < 0.05). Level of urinary TMT-cl of exposed group was negatively correlated with blood potassium (r = -0.4456, P < 0.01). CONCLUSION: Level of urinary TMT-cl can be used as exposure biomarker of TMT-cl poisoning. Blood potassium is an early biomarker of effect for TMT-cl poisoning so as to find poisoning population early.

Trimethyltin poisoning: report of a case with postmortem examination.

A 48-year old woman died six days after intake of an unknown amount of trimethyltin (TMT). Early clinical features were tinnitus, lightheadedness, aggression and episodes of unresponsiveness. She gradually developed coma and died of multiorgan failure. The main pathologic findings were confined to the nervous system which revealed generalized chromatolysis of the neurons in the brain, spinal cord and spinal ganglia. Recent neuronal necrosis, which probably was caused by toxic effect of TMT, was present in the fascia dentata of the hippocampus and in the spinal ganglia. Recent necrosis was also present in the pyramidal cell layer of the hippocampus, cerebral cortex, basal ganglia and Purkinje cell layer of the cerebellum, but some of these changes could have been caused by an anoxic episode shortly before death. Electron microscopy revealed marked accumulation of lysosomal dense bodies and disorganization of the granular endoplasmic reticulum in the neurons. The findings were similar to those described in experimental TMT intoxications. Cytoplasmic zebra bodies, which were described in a previous human case of TMT intoxication, were not observed in the present case.