Relation of tributyltin and triphenyltin equilibrium sorption and kinetic accumulation in carp and Ceratophyllum demersum.

Comparatively limited knowledge is known about the accumulation processes of tributyltin (TBT) and triphenyltin (TPT) in fish and aquatic plant in the freshwater environment, which has hindered a full understanding of their bioaccumulation potential and ecological risks. In the present study, sorption of TBT and TPT on dead biota of both carp and C. demersum from water via the batch equilibrium technique as well as uptake of them on live biota of both carp and C. demersum from water at a static and a dynamic kinetics tests were investigated, respectively. Both TBT and TPT exhibit a high affinity in carps and C. demersum. And C. demersum has a faster metabolism either for TBT or TPT than carp. The apparent uptake values (Cbio = 1904-8831 µg/kg) or bioconcentration factor (BCF = 3333-44000 L/kg) were one or two orders of magnitude higher than that of estimated by a simple sorption (405-472 µg/kg) or lipid model (74.5-149.6 µg/kg) for carp, indicating the uptake of TBT and TPT did not only depend on lipids but also oxygen ligands or macromolecules such as amino acids and proteins of the living organism. In contrast, the apparent Cbio values (149.1-926.4 µg/kg) of both TBT and TPT were lower than that of estimated by sorption model (1341-1902 µg/kg) for C. demersum, which were due to the rapid metabolic rate of them, especially for TBT. But no relation was observed between TBT and TPT concentrations and lipid contents in C. demersum.

Occurrence and trophic magnification profile of triphenyltin compounds in marine mammals and their corresponding food webs.

The occurrence of triphenyltin (TPT) compounds, a highly toxic antifouling biocide, has been documented in marine environments and organisms all over the world. While some studies showed that marine mammals can be used as sentinel organisms to evaluate the pollution status of emerging contaminants in the environment because of their long lifespans and high trophic levels, information regarding the contamination status of TPT in marine mammal species has been limited over the past decade. More importantly, the primary bioaccumulation pathway of TPT in these long-lived apex predators and the corresponding marine food web is still uncertain. Therefore, this study aimed to evaluate the contamination statuses of TPT in two marine mammal species, namely the finless porpoise and the Indo-Pacific humpback dolphin, and assess the trophic magnification potential of TPT along the food webs of these two species, using stable isotope analysis, and chemical analysis with gas chromatography-mass spectrometry. The results showed that TPT is the predominant residue in majority of the analyzed individuals of two marine mammals, with concentrations ranging from 426.2 to 3476.6 ng/g wet weight in their muscle tissues. Our results also demonstrated an exponential increase in the concentration of TPT along the marine food web, indicating that trophic magnification occurs in the respective food webs of the two marine mammals. The range of trophic magnification factors of TPT in the food webs of finless porpoise and Indo-Pacific humpback dolphin was 2.51-3.47 and 2.45-3.39, respectively. These results suggest that high trophic organisms may be more vulnerable to the exposure of TPT-contaminated environments due to the high trophic magnification potential, and thus ecological risk of these compounds ought to be assessed with the consideration of their bioaccumulation potentials in these marine mammals.

Combined effect of polystyrene plastics and triphenyltin chloride on the green algae Chlorella pyrenoidosa.

The combined effect of polystyrene (PS) particles and triphenyltin chloride (TPTCl) to the green algae Chlorella pyrenoidosa was studied. The 96 h IC50 of TPTCl to the green algae C. pyrenoidosa was 30.64 µg/L. The toxicity of PS particles to C. pyrenoidosa was size-dependent, with the 96 h IC50 at 9.10 mg/L for 0.55 µm PS but no toxicity observed for 5.0 µm PS. The exposure to 0.55 µm PS led to damage on structure of algal cells, which could in turn cause inhibition on photosynthesis and population growth of the green algae. TPTCl concentrations in test medium were lowered by 15-19% at presence of 0.55 µm PS particles, indicating a reduced bioavailability of TPTCl. In spite of this reduced bioavailability, the presence of PS increased the toxicity of TPTCl, which might be attributed to facilitated uptake of TPTCl by the green algae after the damage of cell structure. The overall results of the present study provided important information on the effect of PS on the bioavailability and toxicity of TPTCl to phytoplankton species.

Frontiers in endocrine disruption: Impacts of organotin on the hypothalamus-pituitary-thyroid axis.

Endocrine disruptors (EDs), chemical substances widely used in industry and ubiquitously distributed in the environment, are able to interfere with the synthesis, release, transport, metabolism, receptor binding, action, or elimination of endogenous hormones. EDs affect homeostasis mainly by acting on nuclear and nonnuclear steroid receptors but also on serotonin, dopamine, norepinephrine and orphan receptors in addition to thyroid hormone receptors. Tributyltin (TBT), an ED widely used as a pesticide and biocide in antifouling paints, has well-documented actions that include inhibiting aromatase and affecting the nuclear receptors PPARγ and RXR. TBT exposure in humans and experimental models has been shown to mainly affect reproductive function and adipocyte differentiation. Since thyroid hormones play a fundamental role in regulating the basal metabolic rate and energy homeostasis, it is crucial to clarify the effects of TBT on the hypothalamus-pituitary-thyroid axis. Therefore, we review herein the main effects of TBT on important metabolic pathways, with emphasis on disruption of the thyroid axis that could contribute to the development of endocrine and metabolic disorders, such as insulin resistance and obesity.

Effect of dibutyltin on placental and fetal toxicity in rat.

In order to elucidate the effect of chorioallantoic and yolk sac placenta on the embryonic/fetal toxicity in dibutyltin dichloride (DBTCl)-exposed rats, we examined the histopathological changes and the tissue distribution of dibutyltin in the placentas and embryos. DBTCl was orally administered to the groups at doses of 0 mg/kg during gestation days (GD)s 7-9 (control group) and 20 mg/kg during GDs 7-9 (GD7-9 treated group), and GDs 10-12 (GD10-12 treated group). The total fetal mortality was increased, and malformations characterized by craniofacial dysmorphism were detected in the GD7-9 treated group. The embryonic/fetal weight and placental weight showed a decrease in both DBTCl-treated groups. Histologically, some embryos on GD 9.5 in the GD7-9 treated group underwent apoptosis without any changes of yolk sac. In the laser ablation-inductively coupled plasma-mass spectrometry analysis (LA-ICP-MS), tin was detected in the embryo, allantois, yolk sac, ectoplacental cone and decidual mass surrounding the conceptus on GD 9.5 in the GD7-9 treated group. Thus, it is considered that the embryo in this period is specifically sensitive to DBTCl-induced apoptosis, compared with other parts. The chorioallantoic placentas in both DBTCl-treated groups showed the developmental delay and hypoplasia in the fetal parts of placenta, resulting from apoptosis and mitotic inhibition. Thus, it was speculated that the DBTCl-induced malformations and fetal resorption resulted from the apoptosis in the embryo caused by the direct effect of DBTCl. The DBTCl-induced lesions in the chorioallantoic placenta were a non-specific transient developmental retardation in the fetal parts of placenta, leading to intrauterine growth retardation.

Organotins in fish muscle and liver from the Polish coast of the Baltic Sea: Is the total ban successful?

Muscle and liver tissues of nine fish species were analyzed to assess butyltin and phenyltin contamination. The samples were collected from three basins located in the Southern Baltic Sea coastal zone that each represent different potential for organotin pollution. Maximum total concentrations of butyltin compounds (BTs) in the fish muscles and livers were 715 and 1132ng Sn g(-1) d.w., respectively, whereas triphenyltin (TPhT) was not detected. In the muscle samples, the predominant compound in the sum of butyltins was tributyltin (TBT), while in the liver samples, tributyltin degradation products were found in the majority. The results demonstrate that 6-7years after the implementation of the total ban on harmful organotin use in antifouling paints, butyltins remain present in fishes from the Polish coast of the Baltic Sea. According to the HELCOM recommendation, eight samples exceeded the good environmental status boundary for tributyltin in seafood.

In vitro and in vivo biological characterization of the anti-proliferative potential of a cyclic trinuclear organotin(iv) complex.

Identification of novel molecules that can selectively inhibit the growth of tumor cells, avoid causing side effects to patients and/or intrinsic or acquired resistance, usually associated with common chemotherapeutic agents, is of utmost importance. Organometallic compounds have gained importance in oncologic chemotherapy, such as organotin(iv) complexes. In this study, we assessed the anti-tumor activity of the cyclic trinuclear organotin(iv) complex with an aromatic oximehydroxamic acid group [nBu2Sn(L)]3(H2L = N,2-dihydroxy-5-[N-hydroxyethanimidoyl]benzamide) - MG85 - and provided further characterization of its biological targets. We have previously shown the high anti-proliferative activity of this complex against human colorectal and hepatocellular carcinoma cell lines and lower cytotoxicity in neonatal non-tumor fibroblasts. MG85 induces tumor cell apoptosis and down-regulation of proteins related to tubulin dynamics (TCTP and COF1). Further characterization included the: (i) evaluation of interference in the cell cycle progression, including the expression of critical genes; (ii) affinity to DNA and the corresponding mode of binding; (iii) genotoxic potential in cells with deficient DNA repair pathways; and (iv) in vivo tumor reduction efficiency using mouse colorectal carcinoma xenografts.

Accumulation of organotins in seafood leads to reproductive tract abnormalities in female rats.

Organotins (OTs) are environmental contaminants used as biocides in antifouling paints that have been shown to be endocrine disrupters. However, studies evaluating the effects of OTs accumulated in seafood (LNI) on reproductive health are particularly sparse. This study demonstrates that LNI leads to impairment in the reproductive tract of female rats, as the estrous cycle development, as well as for ovary and uterus morphology. Rats were treated with LNI, and their reproductive morphophysiology was assessed. Morphophysiological abnormalities, such as irregular estrous cycles, abnormal ovarian follicular development and ovarian collagen deposition, were observed in LNI rats. An increase in luminal epithelia and ERα expression was observed in the LNI uteri. Together, these data provide in vivo evidence that LNI are toxic for reproductive morphophysiology, which may be associated with risks to reproductive function.

Resistance to oxidative damage but not immunosuppression by organic tin compounds in natural populations of Daubenton's bats (Myotis daubentonii).

The acute toxicity of organic tin compounds (OTCs) has been studied in detail. However, due to their complex nature, very little is known about species-specific methods of accumulation and consequences for food-webs. Chironomids, on which e.g. Daubenton's bats feed, may act as vectors for the transport of organic tin compounds from aquatic to terrestrial ecosystems. Bats are prone to environmental toxins because of their longevity and their ecological role as top predators. Organic tin compounds are associated with increased formation of reactive oxygen species and associated oxidative damage as well as suppression of immune function. The present paper investigates whether the OTC, tributyltin (TBT) and its metabolite, dibutyltin (DBT), accumulate in natural populations of Daubenton's bats and whether TBT-associated effects are seen in general body condition, redox balance, redox enzyme activities, associated oxidative damage of red blood cells and complement function. We discovered the concentration of bat fur DBT correlated with local marine sediment TBT concentrations. However, we did not find a correlation between the explanatory factors, bat fur DBT and marine sediment TBT concentrations, and several physiological and physical response variables apart from complement activity. Higher DBT concentrations resulted in weaker complement activity and thus a weaker immune response. Although the observed physiological effects in the present study were not strongly correlated to butyltin concentrations in fur or sediment, the result is unique for natural populations so far and raises interesting questions for future ecotoxicological studies.

Inhibition of cytochrome P450 3A in rat liver by the Diorganotin (IV) compound di-n-Butyl-di-(4-chlorobenzo-hydroxamato)tin (IV) and Its Probable Mechanism.

The specific aims of this study were to evaluate the inhibition effect on CYP3A of di-n-butyl-di-(4-chlorobenzohydroxamato)tin (IV) (DBDCT), a tin-based complex with high antitumor activity, and the probable mechanism(s) of this action. Adult male SD rats were treated separately with natural saline (NS), lipopolysaccharide (LPS, 5 mg/kg), DBDCT (1.25, 2.5 and 5.0 mg/kg) intraperitoneally for 2 days after induction of CYP3A with dexamethasone (DEX, 100 mg/kg) for 4 days. Western blot analysis and fluorescent quantitation PCR (FQ-PCR) were conducted to determine the changes in expression of CYP3A, PXR, CAR and RXR. The biological accumulation of DBDCT and total Sn were determined by high-performance liquid chromatography (HPLC) and atomic fluorescence spectrometry (AFS). CYP450 content and CYP3A activities were significantly inhibited (p < 0.05) in DBDCT-treated rats compared with the control group, as was the expression of CYP3A (p < 0.05) at both protein and mRNA levels. In DBDCT-treated groups, the expression of PXR protein and mRNA increased, while the expression of CAR decreased. The biological accumulation of DBDCT and Sn in rat livers treated with DBDCT was high. The accumulation of DBDCT and Sn due to the inhibition of CYP3A may be involved in the mechanism of toxicity of DBDCT in rat liver.

Toxicity and uptake of TRI- and dibutyltin in Daphnia magna in the absence and presence of nano-charcoal.

Butyltins (BTs), such as tributyltin (TBT) and dibutyltin (DBT), are toxic to aquatic organisms, but the presence of the strong adsorbent, black carbon (BC), can markedly influence BT toxicity and uptake in organisms. In the present study, the acute toxicity and uptake of TBT and DBT in the crustacean, Daphnia magna, were investigated with and without addition of nano-charcoal at different pHs and water hardnesses. The results showed that the toxicity of TBT and DBT increased by lowering the pH from 8 to 6. This reflects a relatively higher toxicity of cationic BT species than of the neutral species. At pH 6, by enhancing the water hardness of the media from 0.6 to 2.5 mM, the toxicity of TBT and DBT consistently decreased due to competitive binding of bivalent cations (Mg²âº, Ca²âº) to biotic ligands of D. magna. Furthermore, the toxicity of TBT to D. magna significantly decreased in the presence of nano-charcoal compared with experiments without nano-charcoal at pH 6 and 8, while no significant decrease in toxicity of DBT was observed in the presence of nano-charcoal. This can be attributed to the insignificant decrease of free DBT concentration in the presence of nano-charcoal compared with that for TBT. Conversely, it was observed that more TBT and DBT were taken up in D. magna in the presence of nano-charcoal due to the uptake of TBT or DBT associated with nano-charcoal by Daphnia in gut systems, as seen by light microscopy. This indicated that only free nonadsorbed BTs were toxic to D. magna, at least during short periods of exposure.

[Occurrence and distribution of organotin compounds in Thais clavigera from Xiamen coast].

Occurrence and distribution of 6 organotin compounds including butyltin and phenyltin species were detected in Thais clavigera which were collected from 9 coastal areas sites around Xiamen Coast, by pentylized derivatization, GC-FPD. Results indicated that all Thais clavigera samples were contaminated with organotin compounds. The concentrations in Thais clavigera soft bodies varied from 0.3 to 70.6 ng x g(-1) with a mean value of 28.8 ng x g(-1) for butyltin compounds, and from nd to 18.8 ng x g(-1) with a mean value of 7.9 ng x g(-1) for phenyltin compounds, respectively. MBT and TPhT were high levels in butyltin compounds and phentyltin compounds, respectively. In addition, butyltin compounds were the dominant contaminates in all samples with high percentage from 74.3% to 96.8%. There was a significant correlation between TBT and TPhT (R2=0.7109, p<0.01). This result showed that both TBT and TPhT came from antifouling paints for ships or for mariculture nets. Compared with those data reported from the other regions around southeast coast of China, present study reveals that contaminated level of organotin compounds in Thais clavigera are relatively lower in Xiamen Coast. But it is higher than those in 2002.

Decade-long monitoring reveals a transient distortion of baseline butyltin bioaccumulation pattern in gastropods.

Worldwide measures to restrict tributyltin (TBT) in antifouling paints have been legislated for decades, and were upgraded to a total ban on September 2008. With a view to test the response of coastal biota to changing pollution, since 1996 we have determined the concentration of TBT and derivatives di- and mono-butyltin (DBT and MBT) in NW Spain populations of two gastropods of contrasting biology, the rock-snail Nucella lapillus (n=18) and the mud-snail Nassarius reticulatus (n=24). TBT pollution in the study area has decreased consistently and considerably over time. In addition, the baseline butyltin (BT) bioaccumulation patterns showed a marked but transient distortion. These field observations are consistent with BT desorption from sediments, a natural phenomenon that is now to be expected in developing countries recently subject to the global TBT ban.

Distribution of butyltins (TBT, DBT, MBT) in sediments of Gulf of Cádiz (Spain) and its bioaccumulation in the clam Ruditapes philippinarum.

Surface sediment samples were analyzed for organotins namely tributyltin (TBT), dibutyltin and monobutyltin from six areas located in the Gulf of Cádiz (14 stations), Spain. The total butyltin ranged between undetected and 1,580 ng Sn g(-1). TBT generally prevailed in most of the samples, suggesting fresh inputs of butyltin compounds and/or less degradation of TBT. The observed levels of butyltins at several sites are much higher than that required to induce toxic effect on marine organisms, suggesting that these sediments are polluted with butyltin compounds. The clam Ruditapes philippinarum was used for studying bioaccumulation of butyltins by exposing them to contaminated sediments from the Gulf of Cádiz over a period of 28 days under laboratory conditions. Biota-sediment accumulation factor (BSAF) ranged from 0.44 to 3.99.

Imposex and butyltin body burden in Nassarius nitidus (Jeffreys, 1867), in coastal waters within the Basque Country (northern Spain).

Levels of imposex (superimposition of male characters, upon females) and the presence of sterile females are assessed in the gastropod Nassarius nitidus (Jeffreys, 1867), at 22 locations in the Basque Country (northern Spain). At 18 of these localities, butyltin bioaccumulation (tributyltin (TBT); dibutyltin; monobutyltin) was analysed using isotope dilution and GC-ICP-MS. Higher imposex levels and TBT body burden were found in confined harbours, with a large vessel traffic or the presence of a fishing fleet or a shipyard. For the first time, four apparently sequential types of aborted capsules are described in this species. Another novelty is the interspecific comparison between imposex intensities in sympatrically living populations of N. nitidus and N. reticulatus. This showed that sensitivity to TBT pollution of both species is relatively similar (in terms of Relative Penis Length Index). Since N. nitidus has a restricted habitat distribution due to its low presence in wave-exposed habitats, its complementary use with other species is recommended for its use in TBT monitoring programmes.

Determination and pharmacokinetics of a new diorganotin(IV) complex dibutyldi(4-chlorobenzohydroxamato)tin(IV) in rat plasma by a high performance liquid chromatographic method.

Dibutyldi(4-chlorobenzohydroxamato)tin(IV) is a new diorganotin(IV) arylhydroxamate complex with 4-chloro-benzohydroxamic acid as ligand which shows high in vivo and in vitro antitumor activity. A high performance liquid chromatographic (HPLC) method using a Diamonsil ODS column was first validated in the pharmacokinetic studies in rat plasma. The plasma was deproteinized with methanol that contained acetanilide as the internal standard. The mobile phase was a mixture of methanol and 0.5% trifluoroacetic acid (TFA) in water (30:70) (pH 3.0). The detection wavelength was set at 238 nm. A linear curve over the concentration range 0.1-25 microg/ml (r = 0.9992) was obtained. The method was used to determine the concentration-time profiles for dibutyldi(4-chlorobenzohydroxamato)tin(IV) in the plasma after a single intravenous dose of 2, 5, and 12 mg/kg to rats. The pharmacokinetics parameter calculations and modeling were carried out using the 3p97 pharmacokinetics software. A nonlinear pharmacokinetics was found in rats at doses from 2 to 12 mg/kg. The results showed that the concentration-time curves of dibutyldi(4-chlorobenzohydroxamato)-tin(IV) in rat plasma could be fitted to two-compartment model.

Characterization of the planktonic shrimp, Acetes intermedius, as a potential biomonitor for butyltin.

Acute toxic responses as well as uptake and depuration rates for tributyltin (TBT) and dibutyltin (DBT) were examined in the small planktonic shrimp, Acetes intermedius. The 72-h LC(50) values of TBT and DBT for the shrimp were found to be 18.6 and 82.6 microg L(-1) as tin. The uptake rate constants of TBT and DBT in the shrimp were 0.0006 and 0.0002 L g(-1) h(-1), and the corresponding depuration rate constants were 0.0303 and 0.0106 h(-1), respectively. It appears that real-time ambient TBT pollution status can be more closely reflected in this species. The shrimp may serve as a biomonitor to indicate short-term fluctuations in ambient TBT pollution. A field survey was also conducted to distinguish contrasts in butyltin accumulation under different ambient conditions. These observations provide valuable information for the evaluation of TBT pollution status in the environment using A. intermedius as a biomonitor.

Concentration and persistence of tin in rat brain and blood following dibutyltin exposure during development.

Dibutyltin (DBT), a widely used plastic stabilizer, has been detected in the environment as well as human tissues. Although teratological and developmental effects are well documented, there are no published reports of DBT effects on the developing nervous system. As part of a developmental neurotoxicity study of DBT, tissue samples were periodically collected to determine the distribution of total tin (Sn) in brain and whole blood. Pregnant Sprague-Dawley rats were exposed to 0, 10, or 25 ppm DBT in drinking water from gestational day (GD) 6 to weaning at postnatal day (PND) 21. Beginning on PND 3, half of the litters were directly dosed every 2 to 3 d via oral gavage with 0, 1, or 2.5 mg/kg DBT such that the dose level matched the water concentration (for example, litters with 25 ppm DBT in the water received 2.5 mg/kg). For Sn analysis, brain and blood samples were collected from culled pups on PND2 (males and females pooled), from pups (males and females separately) as well as dams at weaning (PND21), and from adult offspring (males and females) at PND93. Total Sn was quantified using inductively coupled plasma-mass spectroscopy (ICP-MS). At all ages, brain Sn levels were higher than blood. At culling, in the directly dosed pups at weaning, and in dams at weaning, Sn levels in both tissues were linearly related to dose. Weanling pups without direct dosing showed lower levels than either culled pups or dams, indicating that lactational exposure was minimal or negligible even while maternal exposure is ongoing. In the adults, Sn levels persisted in brains of directly dosed rats, and the high-dose females had higher levels than did high-dose males. No Sn was detected in adult blood. Thus, during maternal exposure to DBT in drinking water, Sn is placentally transferred to the offspring, but lactational transfer is minimal, if any. Furthermore, Sn is concentrated in brain compared to blood, and its elimination is protracted, on the order of days to months after exposure ends.

Organotin speciation and tissue distribution in rat dams, fetuses, and neonates following oral administration of tributyltin chloride.

Tributyltin (TBT) is a biocide that contaminates human foodstuffs, especially shellfish. TBT is an endocrine disrupter, producing imposex in several marine gastropods. Previous studies showed that oral dosing of rat dams with TBT chloride leads to abnormal fetal and postnatal development. In this study, the tissue distribution and speciation of organotins in tissues were examined in dams, fetuses, and neonates following dosing of rat dams commencing on gestational day (GD) 8 by oral gavage with TBT in olive oil at 0, 0.25, 2.5, or 10 mg/kg body weight (BW)/d. Dams' body weights were significantly reduced by the 10-mg/kg BW/d TBT treatment. At GD20, there were no significant effects of any TBT treatment on pup weights, litter size, sex ratio, or tissue weights. However, at postnatal day (PND) 6 and 12, neonatal pup weights were reduced by the 10-mg/kg BW/d TBT treatment but tissue weights were unaffected, except for the liver weight of female pups, which was reduced by the 10-mg/kg BW/d TBT treatment. Tissues harvested on GD20 and PND6 and PND12 were extracted for determination of organotins by gas chromatography-atomic emission detection (GC-AED). In most tissues, TBT and its metabolite dibutyltin (DBT) were evident but monobutyltin (MBT) was rarely measured above the detection limit. The livers and brains of fetuses contained TBT and DBT at levels that were approximately 50% of the equivalent tissues in the dams. Furthermore, these tissues appeared to preferentially absorb/retain organotins, since the concentrations were greater than were found for the total loading in whole pups. The placenta also contained relatively large quantities of TBT and DBT. Postnatally, the TBT levels in pups decreased markedly, a probable consequence of the extremely low levels of organotins in rat milk. However, DBT levels in pups livers and brains were maintained, probably due to metabolism of TBT to DBT. Similarly, while dams' spleens contained significant quantities of organotins, the pups' spleens contained smaller quantities, and these decreased rapidly between PND6 and PND12. These results show that organotins cross the placenta and accumulate in fetal tissues but that during lactation, the pups would receive minimal organotins through the milk and during this period, the levels of TBT in pups' tissues decreases rapidly. Consequently, fetuses would be at greater risk of the adverse effects of TBT, but due to the lack of transfer through milk, the risk would be reduced during the lactational period.

Methylation of dimethyltin in mice and rats.

Organotins are widely used as stabilizers of polyvinyl chloride and as catalysts or biocides. It is well known that dimethyltin (DMT) is less neurotoxic than trimethyltin (TMT). A Korean worker who was exposed to DMT compounds showed neurological symptoms similar to those of TMT encephalopathy, in association with high levels of both DMT and TMT in the urine and blood. The case suggested the possibility of the methylation of DMT in humans. Here, we investigated whether TMT is detected in the urine of mice and rats exposed only to DMT dichloride (DMTC). Three Slc:ICR mice and three Slc:Wistar rats were placed in individual metabolic cages, and one day later, they were injected intraperitoneally with DMTC (10 mg/kg body weight (wt); 5.4 mgSn/kg body wt; 45.5 micromol/kg body wt) over 4 consecutive days. Twenty-four hour urine samples were collected every evening for 11 consecutive days starting at baseline (before treatment). Speciation analyses of methyltin compounds in urine were performed using a combination of high performance liquid chromatograph-inductively coupled plasma mass spectrometry. High concentrations of DMT and time-dependent increase in TMT concentrations were found in both mice and rats during the 4-day treatment, and their concentrations decreased gradually after the cessation of treatment. The chemical compound of the detected peak was confirmed to be TMT by liquid chromatography-tandem mass spectrometry. Neither DMT nor TMT was detected in the samples collected at baseline. Our results indicate urinary excretion of TMT in mice and rats injected with DMTC, confirming the production of TMT in vivo, probably through methylation of DMT.