ATSDR 2005 — Toxicological Profile for Tin and Tin Compounds
Summary
This is the U.S. Agency for Toxic Substances and Disease Registry’s comprehensive 2005 toxicological profile for tin and tin compounds, prepared under the CERCLA / SARA mandate. The profile is the single most authoritative public-domain reference for tin toxicology and explicitly maintains the species distinction between inorganic tin compounds (stannous and stannic ions, principally encountered through food contact with tinplated cans) and organotin compounds (mono-, di-, and tri-butyltin and triphenyltin, principally encountered through seafood from coastal waters and through plastics, PVC pipes, and historic biocide use). The two classes have toxicological profiles that differ by approximately three orders of magnitude in derived MRLs.
Minimal Risk Levels (MRLs)
ATSDR derived four oral MRLs for tin compounds, each grounded in an identified NOAEL or LOAEL and an uncertainty-factor justification.
| Species | Duration | MRL (mg/kg/day) | Basis |
|---|---|---|---|
| Inorganic tin (stannous chloride) | Intermediate (15-364 days) | 0.3 | NOAEL 32 mg/kg/day, uncertainty factor 100 |
| Dibutyltin chloride | Intermediate | 0.005 | LOAEL 5 mg/kg/day, immune system endpoint |
| Tributyltin oxide | Intermediate | 0.0003 | NOAEL, immune system endpoint |
| Tributyltin oxide | Chronic (≥365 days) | 0.0003 | NOAEL, immune system endpoint |
The thousand-fold gap between the inorganic-tin MRL and the tributyltin oxide MRL is the central toxicological fact about tin and is what makes the species distinction non-substitutable.
Inorganic tin in food
Inorganic tin enters the diet primarily through canned food, where acidic contents react with the tinplate lining and dissolve elemental tin into the food. Food from lacquered tin-lined cans contains less than 25 ppm tin because the lacquer prevents the food-tin reaction; food from unlacquered tin-lined cans can reach 100 ppm. More than 90 percent of food cans now use lacquered linings; unlacquered tinplate is retained mostly for light-colored fruit and fruit juice where elemental tin helps maintain product color. Tin concentrations in foods not packaged in metal cans are generally below 2 ppm (vegetables, fruits, nuts, dairy, meat, fish, poultry, eggs). Pastas and breads range from less than 0.003 to 0.03 ppm. Tin levels in opened cans increase over storage time as oxygen accelerates the dissolution.
Selected tin levels in foods reported from Biego et al. 1999 (ATSDR Tables 6-2 and 6-3): canned vegetables means 24-156 mg/kg by category; meats around 0.6-2.9 mg/kg; fishes 6.0 mg/kg; pasta and breads at or below 0.003 mg/kg; mineral waters at or below 0.003 mg/kg; canned alcoholic beverages around 4.5 mg/kg. The canned-vegetable to non-canned-staple ratio is approximately three orders of magnitude.
Organotins in food
The dominant dietary route for organotins is seafood, especially from coastal waters and harbor environments where tributyltin antifouling paints on ship hulls deposited TBT into sediments. ATSDR Table 6-4 reports tributyltin levels in food from multiple geographic surveys; central tendencies in fish are typically nanograms-per-gram wet weight, with crustaceans and bivalves often higher. Organotins also enter food through PVC food-contact plastics (where alkyltins serve as heat stabilizers), polyurethane catalysts, silicone-coated parchment paper, and historic uses as wood preservatives, biocides, and rodent repellants.
In tissue surveys, organotin distribution differs sharply from inorganic tin. Inorganic tin is poorly absorbed (more than 90 percent of an ingested dose is excreted in feces; bone is the primary tissue depot for the small absorbed fraction); organotins, being lipophilic, are absorbed and distribute to liver, kidney, and brain. ATSDR-summarized human-tissue surveys report monobutyltin, dibutyltin, and tributyltin in blood and liver of populations from Michigan, Poland, Denmark, and Japan, with total-butyltin liver concentrations on the order of low tens of nanograms per gram wet weight.
Toxic mechanisms
Inorganic tin’s principal toxic effect after ingestion is local irritation of the gastrointestinal mucous membrane producing acute nausea, vomiting, and diarrhea. The threshold for symptomatic effects in humans is on the order of 1,000 to 1,400 ppm tin in canned fruit juices in single-dose challenges. Systemic absorption is limited; reported chronic effects from prolonged inorganic tin exposure include anemia and liver and kidney effects in animal studies at substantially higher dose-times-duration loadings.
Organotin mechanisms are species-dependent. Tributyltin and dibutyltin are immune toxicants; the rodent thymus is the most-sensitive organ in repeat-dose studies, supporting the immune-system-endpoint MRLs. Triethyltin and trimethyltin are central nervous system toxicants. Some organotins are reproductive toxicants (reduced fertility and stillbirth in rodents), and a few are tumorigenic in animal studies. Organotins generally do not penetrate intact human skin in significant amounts, but skin and eye irritation have been reported after acute high-dose contact. The immune-system endpoint, which is the basis of the most stringent organotin MRLs, supports the wiki position that organotins must be assessed separately from inorganic tin in any food-safety analysis.
Provenance Notes
Profile authored by C. Harper, F. Llados, G. Diamond, and L. L. Chappell with peer review by Michael Aschner (Wake Forest), Olen Brown (Missouri), and Bruce Jarnot (American Petroleum Institute). The 2005 final profile supersedes the 2003 draft. ATSDR profiles are prepared under SARA 1986 / CERCLA mandate; tin and organotin compounds have been found at 214 and 8, respectively, of the 1,662 NPL hazardous-waste sites covered by the program at time of writing. Local PDF supplied via raw/Digest; access_url points to the NCBI Bookshelf canonical record.