Human Health Aspects

A comprehensive report [1] compiled recently by an academic institute (Forschungszentrum für Umwelt und Gesundheit in Nürnberg, Germany by Professor Greim) concludes that organotin stabilizers are safe, both for processors and consumers.

Although the ORTEP Association summarized the information available to the best of their knowledge, for specific products reference is made to the particular safety data sheet for obtaining more detailed information and advice on safe handling.

Overall human safety evaluation
Methyl-, Octyl- and Dodecyltin stabilizers have had widespread national approvals for food-contact applications over many years. The Scientific Committee for Food (SCF) of the EU has defined specific migration limits [3] for organotin stabilizers based on the tolerable daily intake value (TDI). Although the TDI-value for dioctyltin stabilizers is most restrictive, recent evaluation of migration data [4] reconfirmed that this requirement can well be fulfilled. Therefore, the use of these organotin stabilizers in PVC for food packaging is not a risk for the consumer [1].

Exposure limit values in the workplace have been defined based on the above-mentioned toxicological data.

The MAK (Maximale Arbeitsplatz-Konzentration) Commission in Germany as well as the ACGIH (American Conference of Governmental Industrial Hygienists, Inc.) in the U.S., established 0.1 mg/m³ as tin as the 8-hour TLV (threshold limit value) while the TLV-STEL (short-term exposure level) is 0.2 mg/m³ as tin.

Therefore, organotin stabilizers can be handled safely in the working place, if the established exposure limit values are observed. Compliance with these exposure limit values is the basis for the safe handling of all organotin stabilizers during PVC-processing.
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Acute toxicity
The acute oral and dermal toxicity of most organotin stabilizers is moderate to low. Within the EU they are either classified as harmful or do not require this type of classification. Although aerosols of some mono- or diorganotins were found to be toxic, vapors of organotin stabilizers at room temperature will mostly not represent acute hazards on account of the low vapor pressure. Generally, dialkyltin chlorides show somewhat higher acute toxicity than the respective carboxylates or thioglycolates.
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Local tolerance and dermal sensitization
The irritating potential of organotin stabilizers on skin and eyes varies between the different products. Certain organotin stabilizers were found to be dermal sensitizer in the guinea pig. For specific products reference is made to the respective safety data sheets.
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Toxicokinetics and metabolism
Following oral intake mono- and dialkyltin compounds are only slightly absorbed from the gastrointestinal tract. In studies with experimental animals, the highest levels were generally found in the excretory organs, liver and kidneys. No particular affinity to other organs was noted.

Stabilizers such as di-octyltin-di(ethylmaleate) or di-octyltin-di-2-ethylhexylthioglycolate are hydrolytically cleaved in gastric juice whereby the maleate or thioglycolate moiety is exchanged for chloride. Furthermore, the available data indicate that the alkyltin moiety is subject to metabolism leading to de-alkylation and finally inorganic tin. Accordingly, organotin stabilizers do not appear to have major cumulative properties in the mammalian organism.
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Mutagenicity
The majority of the studies in vitro and in vivo do not indicate a mutagenic potential for mono- and di-alkyltin compounds, although some contradictory results were observed with dibutyltins and di-octyltins. A few positive findings were noted in investigations in vitro in the absence of metabolic activation only, which indicates that metabolism in mammals will lead to formation of inactive (i.e., harmless) metabolites.

Therefore, in accordance with the above-mentioned conclusions on the mutagenicity tests, the available results from long-term studies in rodents do not provide evidence of a tumor risk for humans at the established levels of exposure to organotin stabilizers [1].
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Tumorigenicity
Although the tumorigenicity studies with various methyltin stabilizers in rats had certain limitations in their design, no evidence of a tumorigenic potential was observed.

Further long-term feeding studies with dibutyltin diacetate in rats and mice were also hampered by deficiencies; however, the results do not provide evidence of a carcinogenic potential. A mixture of mono- and di-octyltin chlorides administered to rats in a carcinogenicity study caused an increase in primary tumors of the thymus in females in the highest dose group. These tumors were probably induced by a non-genotoxic mechanism. Such tumors are not to be expected in workers or consumers exposed to octyltins.
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Reproductive toxicity
A number of teratogenicity studies and two-generation reproductive toxicity studies were conducted with various organotin stabilizers. No evidence of adverse effects on reproduction or development was noted in studies with mixtures of mono- and dimethyltins. In teratogenicity studies with several dibutyl compounds in rats, malformations were found. A further study with dibutyltin dichloride using a larger number of rats indicated that effects on the dams occur at lower dose levels than those producing embryotoxicity. In a two-generation reproduction toxicity study and in embryotoxicity studies with an octyltin stabilizer mixture no evidence of specific adverse effects on reproduction was noted [2]. No adverse effects on embryonic development were observed in studies with a mixture of mono- and didodecyltin thioglycolates in two animal species.

Therefore, workplace standards and tolerable daily intakes set with regard to general toxic effects are considered sufficient for protection of mothers and their children.
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Safety upon repeated exposure
Following repeated oral intake, the most prominent effects of dibutyltin and dioctyltin compounds in rats were damage to the lymphatic organs (mainly thymic atrophy) and a suppression of the thymus-dependent immune system.

Species other than the rat were found to be less sensitive. No particular target organs were identified for monoalkyl-, dimethyl- and didodecyltin derivatives. These effects were taken into account when setting occupational exposure limit values and migration limits for use of organotin stabilizers in PVC for food contact.

These limits form the basis of safety measures recommended in the safety data sheets.
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