Mono- and disubstituted methyltin, butyltin, and octyltin compounds

Abstract

This CICAD1 on mono- and disubstituted methyltin, butyltin, and octyltin compounds was prepared by the United Kingdom's Centre for Ecology & Hydrology and by Risk & Policy Analysts Limited of the United Kingdom and was based on an assessment report of the risks to health and the environment associated with the use of organotin compounds (excluding use as a biocide in antifouling paints) submitted to the European Commission (Enterprise Directorate-General). To address literature not included in this source report, a comprehensive literature search of several online databases was conducted in April 2005. Information on the source document and its peer review is presented in Appendix 2. Information on the peer review of this CICAD is presented in Appendix 3. This CICAD was approved as an international assessment at a meeting of the Final Review Board, held in Nagpur, India, on 31 October - 3 November 2005. Participants at the Final Review Board meeting are presented in Appendix 4. The IPCS International Chemical Safety Cards for dibutyltin oxide and dibutyltin dilaurate are reproduced in this CICAD IPCS, 1999c, 2005). Previous CICADs have reviewed triphenyltin compounds and tributyltin oxide (IPCS, 1999a,b). Organotin compounds are characterized by a tincarbon bond and have the general formula RxSn(L)(4-x), where R is an organic alkyl or aryl group and L is an organic (or sometimes inorganic) ligand. The organotin moiety is significant toxicologically. The anionic ligand influences physicochemical properties but generally has little or no effect on the toxicology. Because of the influence of the ligand, physicochemical properties and environmental fate modelling derived from them are often uncertain for the organotins. Water solubility across the group is low; however, hydrolysis of the reactive ligands and/or ligand exchange in the environment or tissues of organisms could lead to the formation of species that are more soluble, casting doubt on the relevance of some of the modelled data. Methyltins are less likely than the butyl- and octyltins to partition to sediments, soils, and organic carbon. Modelled data for Koc suggest much lower capacity for binding to organic carbon than do measured values, often by several orders of magnitude. Measured data have been used in preference to model environmental fate of the compounds. The compounds also bind strongly to clay minerals, montmorillonite in particular. The organotins have a wide range of uses, which are largely specific for the different organotins. Thus, mono- and disubstituted organotin compounds are not suitable as biocides, and trisubstituted organotin compounds are not suitable as PVC stabilizers. The mono- and disubstituted organotins considered here are used as stabilizers in PVC or as catalysts for the production of electrodeposited coatings (mainly in motor vehicle primers), silicone rubbers, esterification and powder coatings, and polyurethanes, as well as for coating glass. Standard tests using the organotin compounds show ready biodegradation. However, there is some doubt as to whether this reflects full degradation or dissociation of the ligand. For the purposes of fate modelling and risk assessment, the compounds have been assumed to be "inherently" biodegradable, giving a default half-life of 150 days. Measured half-lives in soils for dialkyltins are around 120-150 days in laboratory tests. Methyltins and butyltins in forest soils showed half-lives ranging from 6 months to 15 years. There are few measured concentrations of organotins in the environment. Measured values for butyltins (where widespread use of tributyltin has led to levels in the environment of dibutyltin as a breakdown product not related to the manufacture or use of dibutyltin as a stabilizer or catalyst) and methyltins (which are produced in the environment by bacterial action) are not reliable indicators of current industrial use of the substances. Despite quite substantial monitoring effort, octyltins have never been measured in the wider environment. Data are available on measured octyltin concentrations in wastewater treatment plants, to a maximum of 715 and 560 μg/kg dry weight for monooctyltin trichloride and dioctyltin dichloride, respectively, in sludge and 0.12 and 0.008 μg/l for monooctyltin trichloride and dioctyltin, respectively, in effluent. Maximum concentrations of mono- and dibutyltins in water and sediment are 76 and 810 ng/l and 3360 and 8510 μg/kg dry weight, respectively, both expressed as tin. Similar maxima for mono- and dimethyltins are 1200 and 400 ng/l and 170 and 0.27 μg/ kg dry weight, respectively, both expressed as tin. Two studies have looked at leaching of PVC additives from landfill sites; both showed some organotins in leachate, at concentrations up to 2 μg/l as tin. PECs have been calculated for various scenarios (production, formulation, and use) as a means to conduct a risk assessment. Organotins have been detected in a wide range of consumer products; these measured values have been used to calculate worst-case exposure of human consumers (adults and children). There are very limited data on the kinetics and metabolism of organotins in laboratory mammals. A widespread distribution of organotins throughout body tissues has been observed. Transplacental transfer seems to occur, whereas transfer across the blood-brain barrier is limited, since brain levels are usually low. The only compound for which data are available on metabolites is dibutyltin, which has butyl(3-hydroxybutyl)tin as its major metabolite. Limited information suggests quite rapid metabolism and elimination, with half-lives of several days. Much of an oral dose of dioctyltin was eliminated in the faeces, with the remainder in urine. The organotins covered in this assessment have low acute toxicity to laboratory mammals, with most studies indicating LD50s above 100 mg/kg body weight, and many above 1000 mg/kg body weight; this may reflect low absorption from the gut. Studies on irritation are highly variable, with reports ranging from non-irritating to severely irritating for the same compound. The compounds should be regarded as irritating to skin and eyes. Similar variation occurs in sensitization tests, and the database should be regarded as inadequate to draw firm conclusions; however, a number of organotin compounds have shown strong sensitization in some tests, and it would be precautionary to regard the group as sensitizing. Short- to medium-term exposures have shown neurotoxicity, developmental toxicity, immunotoxicity, and endocrine disruption to be relevant end-points, although the degree of each of these toxic end-points differs across the group as a whole. Neurotoxicity is the major end-point for the methyltins, with a NOAEL of approximately 0.6 mg/kg body weight based on neuropathology for dimethyltin; limited data for monomethyltin preclude the derivation of a NOAEL. No neurotoxicity was found with dibutyltin or mono- and dioctyltins; no information is available for monobutyltin. Developmental toxicity is shown by the disubstituted methyl-, butyl-, and octyltins, but not by the corresponding monosubstituted compounds. The major reported effect is teratogenicity, with effects on fetuses shown at doses close to maternally toxic ones in most cases. NOAELs for dimethyltin, dibutyltin, and dioctyltin are 10 (10), 2.5 (1.0), and 45 (30) mg/kg body weight per day for teratogenicity (maternal toxicity NOAELs in parentheses). Immunotoxicity, consistently effects on thymus weight but also measures of functional immunotoxicity, is demonstrated for dibutyltin and mono- and dioctylins. A NOAEL could not be determined for dibutyltin, but the lowest dose reported as causing effects was 2.5 mg/kg body weight per day (as dibutyltin dichloride). NOAELs for mono- and dioctyltin have been determined to be 0.87 and 0.23 mg/kg body weight per day, respectively, although the value for monooctyltin is an estimate, because the study was performed using a mixture. Other information suggests that dioctyltin is the more immunotoxic of the two compounds. Tributyltin is well established as an aromatase inhibitor, and dibutyltin appears to have some potency also (exact characterization of the endocrine disrupting capacity of dibutyltin alone is difficult because of the presence of tributyltin as an impurity). Monobutyltin and mono- and dioctyltins have no aromatase inhibiting capacity in in vitro tests. No data are available for this end-point for the methyltins. The vast majority of in vivo tests show no genotoxicity of mono- and dialkyltins. Results from in vitro tests are variable, with little indication of DNA reactivity. There are, however, indications of clastogenicity and effects on spindle formation in mitosis in vitro. Brief summaries were available for unpublished long-term studies for some of the organotins under consideration. These showed no carcinogenicity for mixtures of mono- and dimethyltins in rats and mono- or dioctyltins in rats or dogs except for a single study on a mixture of mono- and dioctyltin chlorides. This showed significantly increased frequency of thymic lymphomas in female rats only at the 150 mg/kg diet dose. Significant increases were seen in the incidence of generalized malignant lymphomas in males of the 50 and 150 mg/kg groups, but only in females at the highest dose. Very few data are available on the effects of organotins in humans. Of the reported unintentional occupational exposures, none has an estimate of exposure concentration. Exposure was largely via the inhalation route, with some possibility of dermal exposure. Neurological effects were the most commonly reported, and these can persist for long periods. Reliable lifetime TDI values cannot be derived, since long-term studies at the appropriate doses and in the appropriate species are not available...