Dibutyltin dilaurate is a pale yellow, transparent, oily liquid at room temperature. As a highly effective organotin catalyst, it is commonly used in polyurethane synthesis, as a heat stabiliser for PVC plastics, a curing accelerator for silicone rubber and a drying agent for coatings; it accelerates ester exchange and addition polymerisation reactions. This substance is toxic to living organisms; prolonged exposure may cause damage to the liver and kidneys, and may irritate the skin and respiratory tract. It must not come into direct contact with food.

A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity

Organic tin is a metal organic compound that has important industrial application potential, by serving as a polyvinyl chloride stabilizer, and as antifouling coatings in pesticides and fungicides. The primary role of tin is as a polyvinyl chloride stabilizer which accounts for 70% of the output of total organic tin compounds. Since tributyltin can induce sexual aberration in marine life, organic tin as a pollutant has received increasing attention.  Dibutyltin dilaurate is an organic tin compound, with a lower toxicity than tributyltin. DBTD mainly serves as a promoting agent in the rubber industry, as a polyethylene plastic stabilizer, and as a catalyst for aldol condensation and esterification. Dibutyltin dilaurate also plays a crucial role in marine antifouling coatings, wood preservative protection, fluorescent dyes, photochemical reactions, and ceramic and polymer modifications. Organic tin compounds can affect nervous system development and function because of their neurotoxicity. Although people are exposed to dibutyltin dilaurate through daily life and work exposure, its cerebral neurotoxicity is seldom reported. DBTD can damage the phosphatidylinositol signaling system in rat brains and decrease the levels of diacylglycerol and inositol phosphates in the cerebral cortex. High-dose (40 mg/kg) dibutyltin dilaurate increased the contents of cerebral polyamine and spermine levels in the pons, hypothalamus and frontal cortex, which led to synaptic dysfunction and aggravated poisoning symptoms.[1]

Glial cells that had adhered to the capillary walls began to swell in the protrusions, with apparent cavitations. In addition, large amounts of dark neuron cells were visible. These ultrastructure changes in the cerebral cortex suggested that even low-dose dibutyltin dilaurate can damage glial cells, cross through blood-brain barrier, and lead to slight changes in neurons. High-dose dibutyltin dilaurate induced the apparent cavitation of cerebral cortex neuropil. High-dose dibutyltin dilaurate also caused neuronal nuclei deformation and swelling of mitochondria, reduced the number of cell organelles, and showed apoptotic-like changes, which contributed to the pro-apoptotic effect of nitric oxide and lipid peroxidation damage. Tributyltin can cause neurodegenerative changes, and its molecular mechanism depends on the generation of reactive oxygen species. This is consistent with our experimental findings, and all above changes indicate that increased doses cause more apparent ultrastructural changes in the cerebral cortex, and aggravate neuronal and glial cell damage. We speculate that dibutyltin dilaurate can pass through the blood-brain barrier, induce the apoptosis of glial cells and neurons, damage the rat nervous system, and is neurotoxic.

Dibutyltin Compounds Effects on PPARγ/RXRα Activity

Based on studies of dibutyltin dichloride, ECHA classifies the different types of dibutyltins as toxic for reproduction (European Chemicals Agency [ECHA], 2016). In 2014, the TIB Chemicals company filed a proposal with ECHA to revise this classification for dibutyltin dilaurate, arguing that the studies on which it is based are old and probably had contamination by tributyltin chloride (TIB Chemicals AG, 2014). Regarding adipogenesis, a 2011 study in BMS2 murine multipotent stromal cells showed that dibutyltin dichloride induced adipocyte differentiation, albeit with less efficacy than tributyltin chloride (Yanik et al., 2011), yet the adipogenic mechanism underlying it was not investigated. Furthermore, the adipogenic effects of other dibutyltin compounds such as dibutyltin diacetate, dibutyltin dilaurate, and dibutyltin maleate were not previously evaluated. PPARγ activation is also linked to anti-inflammatory effects (Lehrke and Lazar, 2005). Aiming to further understand the actions of dibutyltins, we investigated the effects of four of these compounds – dibutyltin diacetate, dibutyltin dichloride, dibutyltin dilaurate, and dibutyltin maleate – on the transcriptional activity of PPARγ and RXRα, adipogenesis in 3T3-L1 preadipocytes and the expression of inflammatory response-related genes in 3T3-L1 adipocytes and RAW 264.7 macrophages.[2]

These findings indicate that the organotins dibutyltin diacetate, dibutyltin dichloride, dibutyltin dilaurate, and dibutyltin maleate are partial PPARγ agonists and that dibutyltin dichloride and dibutyltin dilaurate are also partial RXRα agonists. To our knowledge, these effects had not been addressed before. Moreover, tributyltin chloride and dibutyltin compounds repressed inflammatory response genes and induced adipogenesis. Although the translation of cell-based results assays into in vivo effects is not entirely known, the current findings open new avenues to understand how organotin compounds may affect the human health. Nevertheless, further studies are necessary to address their effects in different periods of life and to elucidate the complex actions of organostannic compounds in whole-body context.

References

[1]Jin M, Song P, Li N, Li X, Chen J. A plastic stabilizer dibutyltin dilaurate induces subchronic neurotoxicity in rats. Neural Regen Res. 2012 Oct 5;7(28):2213-20. doi: 10.3969/j.issn.1673-5374.2012.028.007. PMID: 25538742; PMCID: PMC4268721.

[2]Milton FA, Lacerda MG, Sinoti SBP, Mesquita PG, Prakasan D, Coelho MS, de Lima CL, Martini AG, Pazzine GT, Borin MF, Amato AA, Neves FAR. Dibutyltin Compounds Effects on PPARγ/RXRα Activity, Adipogenesis, and Inflammation in Mammalians Cells. Front Pharmacol. 2017 Aug 2;8:507. doi: 10.3389/fphar.2017.00507. PMID: 28824431; PMCID: PMC5539189.