New study finds chemical TMT, even at low levels, may contribute to the global kidney stone epidemic

BUFFALO, N.Y. – A study by researchers at UB and three Chinese research institutions is the first to demonstrate that low-level occupational exposure to the industrial chemical trimethyltin chloride (TMT) may be a risk factor for nephrolithiasis, or kidney stones.

The study, “Chronic low level trimethyltin exposure and the risk of developing nephrolithiasis,” was published in the most recent issue of Occupational and Environmental Medicine (June 13, Volume 70, issue 6).

TMT is a deadly neurotoxin produced as a byproduct of the plastic-stabilization process. At high levels it is implicated in a wide range of neurological disorders; acute poisoning has caused death.

The hunt is on for the cause of the silent epidemic of nephrolithiasis, an excruciating, unpredictable, treatable but potentially deadly disease whose prevalence and incidence has been increasing globally across divisions of age, sex and race. Its prevalence in the U.S. alone doubled between 1994 and 2010, and is rising among men, women and in children as young as 5. Researchers have taken aim at processed and junk foods, obesity and rising temperatures as causal agents.

“This study provides evidence that even low-level exposure to TMT in the workplace may increase the risk of developing kidney stones, a disease for which effective treatment is not universally available,” says co-author Xuefeng Ren, assistant professor in the UB departments of Social and Preventive Medicine, and Pharmacology and Toxicology.

“There is not enough information available about environmental methyltin exposure,” Ren says, “but given the widespread use of PVC pipes in public facilities, homes and workplaces, there is growing concern that methyltins leached from these materials can contaminate drinking water, food and various ecosystems.

“This study, combined with the recent epidemic of kidney disease, highlights the unique vulnerability of the kidney to environmental assault,” he says.

“We suggest that larger, more comprehensive studies be undertaken to confirm these findings, particularly in members of the general public, who may encounter low levels of TMT and other methyltin compounds through drinking water or other pathways.”

Ren says that in the U.S., the occupational exposure limits (OEL) for methyltins have not been established. The National Institute for Occupational Safety and Health’s recommended exposure limits for all organotin compounds, including methyltins, are 0.1 mg/m³ (permissible concentration-time weighted average, PC-TWA) and 0.2 mg/m³ (permissible concentration-short term exposure limit, PC-STEL). Although the 8 hour time-weighted average of TMT air level in this study was 0.013 (0.008, 0.028) mg/m³, much lower than the U.S. standards, it still produced stones. 

The study is a cross-sectional analysis of 335 workers in three plants in the manufacturing hub of Qing Yuan, a city in Guangdong, China. The study group comprised 216 workers in two plants that use methyltins as the heat stabilizer for PVC production in the manufacture of plastic window blinds. A control group of 119 workers was recruited from a factory that did not employ TMT in its manufacturing process.

Researchers employed a variety of research instruments, including air sampling, interviews, questionnaires, clinical examination that included ultrasonography, and blood and urine samples collected at the end of work shifts from both study and control groups.

They found that, relative to subjects in the control group:

• The prevalence of kidney stones determined by abdominal ultrasonography was 18.06 percent in the TMT exposure group and only 5.88 percent in the control workers (p<0.01).
• Increased TMT levels in personal air samples, blood and urine had statistically significant positive associations for the risk of kidney stones.
• The length of employment at the window blind plants also was strongly positively associated with the development of kidney stones in the TMT exposure group.
• TMT-exposed workers were more likely to have specific clinical symptoms of, or abnormal laboratory tests for, hypertension, gallstones, kidney stones, abnormal ECG, low hemoglobin count, elevated aspartate aminotransferase activity and occult blood in the urine.
• Even workers with a relatively low level of occupational TMT exposure were more likely to have kidney stones than those in the control group.

In addition to Ren, who is affiliated with the Guangdong Medical Laboratory Animal Center in Guangdong, China, UB authors are Amber M. Dubois of the Department of Pharmacology and Toxicology; Zhihong Gong and Yichen Ge of the Department of Social and Preventive Medicine (Ge also is affiliated with the Guangdong Poison Control Center); and James R. Olson of the departments of Pharmacology and Toxicology and Social and Preventive Medicine.

Chinese authors are Xiaojiang Tang of the Guangdong Medical Laboratory Animal Center and the Guangdong Poison Control Center; Nanchun Li of the Quingyuan Center for Disease Control and Prevention, Quingyan, Guangdong; Lisha Kang of the Guangdong Medical Laboratory Animal Center; Banghua Wu, Guanchao Lai, Aichu Yang, Xiaoling Ruan, Hongbin Gao and Guanghua Zhu of the Guangdong Poison Control Center; and Jinxin Zhang and Zhongning Lin of the School of Public Health, Sun Yat-Sen University, Guangshou, Guangdong.

Many researchers, including Chinese authors of this paper, are investigating the TMT pollution of China’s aquatic system.