Development of an in vitro approach to point-of-contact inhalation toxicity testing of volatile compounds, using organotypic culture and air-liquid interface exposure.

In vitro chemical risk assessment using human cells is emerging as an alternative to in vivo animal testing with reduced costs, fewer animal welfare concerns, and the possibility of greater human health relevance. In vitro inhalation toxicity testing of volatile compounds poses particular challenges. Here we report our efforts to establish a testing protocol in our own lab using the EpiAirway bronchial epithelium cell culture model and the Vitrocell 12/12 system for air-liquid interface (ALI) exposures. For purposes of method development, we used methyl iodide (MeI) as a test compound. We examined viability, cytotoxicity, and epithelial integrity responses. Dose-dependent, reproducible responses were observed with all assays. EpiAirway and BEAS-2B cytotoxicity responses to acute exposure were roughly similar, but EpiAirway was more resistant than BEAS-2B by the viability measurement, suggesting a proliferative response at low MeI concentrations. If wells were sealed to prevent evaporation, in-solution MeI concentration-response could be used to predict the response to MeI vapor within 2-fold by converting from the media- to the air-concentration at equilibrium using the blood:air partition coefficient for MeI. The long-term stability of EpiAirway cultures enabled repeated exposures over a 5-d period, which produced responses at lower concentrations than did acute exposure.

Estrogenic effects of fluorinated diiodine alkanes in MCF-7 cells, H295R cells and zebrafish embryo assays.

Fluorinated diiodine alkanes (FDIAs), important industrial intermediates in the synthesis of various perfluorinated compounds, which are distributed widely in wildlife and humans. Recent studies showed that FDIAs had in vitro estrogenic effects. However, to date, little information is available regarding the in vivo estrogenic effects of FDIAs and the mechanisms are unclear. In this study, a combination of in vitro and in vivo assays was used to investigate the estrogenic effects of FDIAs. We tested the in vitro estrogenic effects and estrogen receptor-related gene expression via MCF-7 cell assay. The hormone level of estradiol and the expression of estrogenic synthesis genes were measured in the H295R cell assay. Finally, the in vivo effects of FDIAs on development and estrogen-related gene expression were assessed in the zebrafish embryos assay. The results demonstrated that FDIAs could exhibit estrogenic activity through inducing cell proliferation (1.6-6.7-fold of the control) and estrogen receptor alpha gene expression (1.07-1.39-fold of the control), altering estradiol production (1.14-1.22-fold of the control) and the major estrogenic synthesis gene expression of CYP19 (1.22-1.31-fold of the control), disrupting the estrogen-related genes (esr1 and cyp19b) levels in zebrafish (1.52-2.99-fold and 2.95-5.00-fold of the control for esr1 and cyp19b, respectively). The current findings indicated the potential estrogenic effects of FDIAs and provided novel information for human risk assessment.

A method for quantitative risk appraisal for pesticide risk assessments.

Pesticide risk assessments are fraught with uncertainties that arise from the process of estimating exposure to and toxicity of chemicals. Regulatory agencies resolve those uncertainties in a health-protective (conservative) manner, typically acknowledging only inter- and intraspecies uncertainties quantitatively. Other uncertainties may be acknowledged qualitatively, but those safety factors (SF) are not enumerated. Quantitative risk appraisal may be used to enumerate the multiplicative SF generated by conservative assumptions regarding uncertainties. The magnitude of SF derived from decision points dealing with historically unquantified uncertainty may far exceed explicit SF used to gauge acceptable margins of exposure (MoE). Examination of the basis for some previously unenumerated SF may justify potential changes in regulatory practices and policies. Using past risk assessments of 3 pesticides (mevinphos, parathion, and methyl iodide) for which the California Department of Pesticide Regulation found unacceptable risk as examples, the previously unquantified SF ranged from 47 to 1 × 106 for scenarios involving handlers, reentry workers, and bystanders.

Evaluation of the genotoxicity and cytotoxicity of filling pastes used for pulp therapy on deciduous teeth using the micronucleus test on bone marrow from mice (Mus musculus).

Pulp therapy is the last resort for preserving deciduous teeth. However, the genotoxic and cytotoxic effects of many products used in this therapy are not well established. The aim of this study was to use the micronucleus test on bone marrow from mice to evaluate the genotoxic and cytotoxic effects of four filling pastes: zinc oxide, calcium hydroxide P.A., mineral trioxide aggregate and an iodoform paste (iodoform + camphorated + paramonochlorophenol + rifamycin + prednisolone). Male Swiss mice were divided into 4 groups of 10 animals, each exposed to one of the pastes, and were subdivided according to the dilutions tested: 1/10, 1/50, 1/500 and 1/1000 administered intraperitoneally (0.1ml/10g of weight). Cyclophosphamide was the positive control. The negative controls were dimethylsulfoxide and buffered saline solution. Five animals were killed 24h and five 48h after the treatment. The material was processed in accordance with Schmid (1976) and micronuclei were counted in 1000 polychromatic erythrocytes (PCE), under an optical microscope in a blinded test. Cytotoxicity was evaluated using the PCE/normochromatic erythrocyte (NCE) ratio in 200 erythrocytes. The micronucleus analysis results were evaluated using the conditional test for comparing proportions in situations of rare events. Analysis of variance and Tukey's test were used to evaluate the PCE/NCE ratio. There was significantly greater occurrence of micronuclei in the animals treated with iodoform paste at all the dilutions tested, at both sacrifice times. Greater occurrence of micronuclei was observed among the animals treated with zinc oxide and sacrificed 48h after the treatment, at the dilutions 1:50; 1:500 and 1:1000. Calcium hydroxide P.A. and mineral trioxide aggregate did not present any genotoxic or cytotoxic effects. The genotoxicity and cytotoxicity of zinc oxide and iodoform paste revealed here constitute an initial step towards their contraindication, but additional studies will be necessary in order to securely establish the risks involved in their use.

Rat subcutaneous tissue response to MTA Fillapex® and Portland cement.

The aim of this study was to evaluate the response of rat subcutaneous tissue to MTA Fillapex® (Angelus), an experimental root canal filling material based on Portland cement and propylene glycol (PCPG), and a zinc oxide, eugenol and iodoform (ZOEI) paste. These materials were placed in polyethylene tubes and implanted into the dorsal connective tissue of Wistar rats for 7 and 15 days. The specimens were stained with hematoxylin and eosin, and evaluated regarding inflammatory reaction parameters by optical microscopy. The intensity of inflammatory response against the sealers was analyzed by two blinded and previously calibrated examiners for all experimental periods (kappa=0.96). The histological evaluation showed that all materials caused a moderate inflammatory reaction at 7 days, which subsided with time. A greater inflammatory reaction was observed at 7 days in the tubes filled with ZOEI paste. Tubes filled with MTA Fillapex presented some giant cells, macrophages and lymphocytes after 7 days. At 15 days, the presence of fibroblasts and collagen fibers was observed indicating normal tissue healing. The tubes filled with PCPG showed similar results to those observed in MTA Fillapex. At 15 days, the inflammatory reaction was almost absent at the tissue, with several collagen fibers indicating normal tissue healing. Data were analyzed by the nonparametric Kruskal-Wallis test (α=0.05). Statistically significant difference (p<0.05) was found only between PCPG at 15 days and ZOEI at 7 days groups. No significant differences were observed among the other groups/periods (p>0.05). MTA Fillapex and Portland cement added with propylene glycol had greater tissue compatibility than the PCPG paste.

Drinking water disinfection byproduct iodoacetic acid induces tumorigenic transformation of NIH3T3 cells.

Iodoacetic acid (IAA) and iodoform (IF) are unregulated iodinated disinfection byproducts (DBPs) found in drinking water. Their presence in the drinking water of China has not been documented. Recently, the carcinogenic potential of IAA and IF has been a concern because of their mutagenicity in bacteria and genotoxicity in mammalian cells. Therefore, we measured their concentrations in Shanghai drinking water and assessed their cytotoxicity, genotoxicity, and ability to transform NIH3T3 cells to tumorigenic lines. The concentrations of IAA and IF in Shanghai drinking water varied between summer and winter with maximum winter levels of 2.18 µg/L IAA and 0.86 µg/L IF. IAA with a lethal concentration 50 (LC50) of 2.77 µM exhibited more potent cytotoxicity in NIH3T3 cells than IF (LC50 = 83.37 µM). IAA, but not IF, induced a concentration-dependent DNA damage measured by γ-H2AX staining and increased tail moment in single-cell gel electrophoresis. Neither IAA nor IF increased micronucleus frequency. Prolonged exposure of NIH3T3 cells to IAA increased the frequencies of transformed cells with anchorage-independent growth and agglutination with concanavalin A. IAA-transformed cells formed aggressive fibrosarcomas after inoculation into Balb/c nude mice. This study demonstrated that IAA has a biological activity that is consistent with a carcinogen and human exposure should be of concern.

Cytotoxicity and proliferative effects of Iodoform-containing root canal-filling material on RAW 264.7 macrophage and RKO epithelial cell lines.

OBJECTIVE: The present study investigated the effect of the Iodoform-containing root canal filling material on the viability of cultured macrophages and epithelial cells, and on cytokine secretion. DESIGN: The effect of Endoflas F.S. on the proliferation of a RAW 264.7 macrophage cell line and on a RKO epithelial cell line, and on the production of tumour necrosis factor alpha (TNFα) from macrophages was examined. Cell vitality was evaluated using a colourimetric XTT (sodium 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)-carbonyl]-2H-tetrazolium inner salt) assay. The presence of cytokines was determined by two-site enzyme-linked immunosorbent assay (ELISA). RESULTS: Direct exposure of Endoflas F.S. and its media, up to a dilution of 1/8, decreased the viability of macrophages and epithelial cells by ∼70% compared to control media (P<0.05). Media dilution from 1/16 to 1/1024 demonstrated a proliferative effect, increasing cell viability by about 60% compared to media without Iodoform-containing root canal filling material. CONCLUSIONS: Direct and indirect exposure to high concentrations of iodoform-containing root canal filling material showed a cytotoxic effect on macrophages and epithelial cells, while low concentrations induced cell proliferation.

Rat subcutaneous tissue response to MTA Fillapex® and Portland cement

The aim of this study was to evaluate the response of rat subcutaneous tissue to MTA Fillapex® (Angelus), an experimental root canal filling material based on Portland cement and propylene glycol (PCPG), and a zinc oxide, eugenol and iodoform (ZOEI) paste. These materials were placed in polyethylene tubes and implanted into the dorsal connective tissue of Wistar rats for 7 and 15 days. The specimens were stained with hematoxylin and eosin, and evaluated regarding inflammatory reaction parameters by optical microscopy. The intensity of inflammatory response against the sealers was analyzed by two blinded and previously calibrated examiners for all experimental periods (kappa=0.96). The histological evaluation showed that all materials caused a moderate inflammatory reaction at 7 days, which subsided with time. A greater inflammatory reaction was observed at 7 days in the tubes filled with ZOEI paste. Tubes filled with MTA Fillapex presented some giant cells, macrophages and lymphocytes after 7 days. At 15 days, the presence of fibroblasts and collagen fibers was observed indicating normal tissue healing. The tubes filled with PCPG showed similar results to those observed in MTA Fillapex. At 15 days, the inflammatory reaction was almost absent at the tissue, with several collagen fibers indicating normal tissue healing. Data were analyzed by the nonparametric Kruskal-Wallis test (α=0.05). Statistically significant difference (p<0.05) was found only between PCPG at 15 days and ZOEI at 7 days groups. No significant differences were observed among the other groups/periods (p>0.05). MTA Fillapex and Portland cement added with propylene glycol had greater tissue compatibility than the PCPG paste.

O objetivo deste estudo foi avaliar a resposta do tecido subcutâneo de rato ao MTA Fillapex® (Angelus), a um cimento endodôntico experimental à base de cimento Portland e propilenoglicol, e à pasta de óxido de zinco e eugenol com iodofórmio. Estes materiais foram colocados em tubos de polietileno e implantados no tecido conjuntivo do dorso de ratos Wistar, por 7 e 15 dias. Os espécimes foram corados com hematoxilina e eosina e os parâmetros de reação inflamatória foram avaliados em microscópio óptico. A intensidade da resposta inflamatória provocada pelos cimentos foi analisada em todos os períodos por dois observadores previamente calibrados (kappa 0,96) e sem conhecimento dos grupos experimentais. O exame histológico mostrou que todos os materiais provocaram reação inflamatória moderada aos 7 dias que regrediu com o tempo. A maior resposta inflamatória do tecido foi observada aos 7 dias, nos tubos preenchidos com pasta de Óxido de Zinco e Eugenol com Iodofórmio. Os tubos com MTA Fillapex apresentaram algumas células gigantes, macrófagos e linfócitos após 7 dias. Aos 15 dias, a presença de fibroblastos e fibras de colágenas foi observada, indicando processo de cicatrização do tecido. Os tubos com o cimento Portland mostraram resultados semelhantes aos observados no grupo MTA Fillapex. Aos 15 dias, a reação inflamatória apresentada foi praticamente ausente, com muitas fibras colágenas, indicando cicatrização normal do tecido. A análise estatística mostrou diferença estatisticamente significante entre o grupo de cimento Portland (15 dias) e óxido de zinco eugenol com Iodofórmio (7 dias) (p<0,05). Nos outros grupos não houve diferença estatística significante. MTA Fillapex e cimento Portland são mais biocompatíveis do que os outros cimentos testados.

The effect of prolonged oral exposure of cockerels to disinfectant (Iodosteryl(®)) on induction of oxidative stress and liver damage.

This study was designed to investigate the effect of prolonged oral exposure of cockerels to disinfectant (Iodosteryl(®)) present in drinking water and its ability to induce liver damage and oxidative stress. Thirty-two healthy birds were used for this study. They were grouped into four groups of eight per group. Group I received 10 ml/kg body weight of physiological saline. Groups II, III and IV received 1 part per million, 2 part per million and 4 part per million of Iodosteryl(®) in their drinking water for six weeks. The results revealed significant (P<0.05) increase in alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities in a dose-dependent manner in birds administered with Iodosteryl(®) when compared with control. Significant (P<0.05) increase in sodium and potassium ions was obtained from birds that received Iodosteryl(®) (4 part per million) compared with control. Also, there was significant (P<0.05) increase in total cholesterol, triglycerides, high density lipoprotein and low density lipoprotein levels in all treatment groups (1, 2 and 4 part per million) compared with control. Serum blood urea nitrogen levels increased significantly (P<0.05) in a dose-dependent manner. Biologic markers of oxidative stress (malondialdehyde and hydrogen peroxide generation) increased significantly with concomitant significant (P<0.05) decrease in serum glutathione level in a dose-dependent manner when compared with control. Histological sections revealed hepatic congestion, vacuolation and fibrosis at varying concentration of Iodosteryl(®). Overall, Iodosteryl(®) induced hepatic damage, increased oxidative stress and decreased antioxidant defense system; hence exposure of both animals and humans to prolonged iodine disinfectant is potentially harmful.

Structure-function relationships of iodinated contrast media and risk of nephrotoxicity.

Characteristics of CM have greatly changed over time. First-generation ionic CM have many-fold (5-7) greater osmolalities than plasma. Subsequently non ionic CM generations were looked for to reduce osmolality, and encompass nonionic monomers and nonionic dimers reaching osmolality as low as that of plasma (iso-osmolar CM) but paying however dear, as viscosity is considerably increased. Intrarenal microcirculation has its "Achilles" heel in the outer medulla, where the smallness of capillary lumen and the slackness of the capillary mesh render regular blood flow at high risk, mainly because it is the same area in which the only renal work needing oxygen is made and? Iodinated CM may exert their nephrotoxic effects in three different ways: by interfering with vascular hemodynamics, by interfering with intratubular fluid volume and composition, and by producing direct cytotoxic effects to glomerular and tubular cells due to iodine by-itself. Furthermore, effects of oxygen free radical can damage glomerular cells by increasing the permeability and tubular cells impairing specific function and leading to apoptosis. Although clinical nephrotoxicity has considerably improved over time, there is no evidence for an a priori superiority of a specific CM. In general, low-osmolar (2-3 times blood) and iso-osmolar (the same as blood) CM are recommended, keeping in mind that within last generation CM dimeric iso-somolar compounds reach viscosity values higher than monomeric low-osmolar compounds and hyperviscosity is a neglected mechanisms of nephrotoxicity. We suggest that CM should be classified not only by osmolality, but also by viscosity.

Bismuth iodoform paraffin paste: a review.

INTRODUCTION: This article reviews the literature pertaining to bismuth iodoform paraffin paste. OVERVIEW: Bismuth iodoform paraffin paste is used in most otolaryngology departments on a daily basis. Questions about its properties are common in postgraduate otolaryngology examinations. This article reviews bismuth iodoform paraffin paste's current and historical usage, constituents, properties, side effects, and radiographic properties, and its alternatives in otological and rhinological practice.

Cytotoxic effects of primary tooth root canal filling materials on L929 cell line.

PURPOSE: The purpose of this study was to determine the cytotoxic effects of five different primary tooth root canal filling materials on L929 permanent cell line with MTT assay. METHODS: Kri 1 paste (iodoform), Diapex (iodoform+Ca(OH)(2)), Metapaste (Ca(OH)(2) with distilled water), Dentalis (iodoform+ZOE+Ca(OH)(2)) and Kalsin (Ca(OH)(2) with glycerin) were used in this study. Tested materials were in contact for 24, 48 and 72 hours with L929 cells. At the end of the test periods, MTT test solutions were added to the plates and incubated for 3 hours at 37 degrees C. Then optic densities were read using UV visible spectrophotometer. All assays were repeated three times to ensure reproducibility. The obtained data were analyzed statistically by one-way analysis of variance and Dunnett T3 post hoc test (P<0.05). RESULTS: All tested materials were found cytotoxic on L929 cell line. It was found that Kri 1 paste group showed the highest survival rates. CONCLUSIONS: We concluded that the use of Kri 1 paste as a root canal filling material is a better option than other medications in primary teeth. Further research is necessary to determine the effect of root canal filling materials on vital tissues.

Prenatal developmental toxicity studies of inhaled methyl iodide vapor in rabbits reveal a susceptible window of exposure inducing late gestational fetotoxicity.

Methyl iodide (MeI), an intermediate used in the manufacture of some insecticides and pharmaceuticals, is under review for U.S. registration as a non-ozone-depleting alternative to methyl bromide in the pre-plant soil fumigation market. Guideline (OPPTS 870.3700) developmental toxicity studies in New Zealand White (NZW) rabbits showed dose-dependent increases in the litter proportions of late fetal deaths and postimplantation loss and/or decreased fetal body weight following inhalation exposure of pregnant rabbits to MeI during gestation days (GD) 6-28. A subsequent phased-exposure study was performed to pinpoint the critical window of gestational exposure that produced the rabbit fetotoxicity. Artificially inseminated NZW female rabbits were exposed to 20 ppm MeI vapors by whole-body inhalation (6 h/day) throughout major organogenesis and fetal development (GD 6-28), during early gestation (GD 6-14) or mid-gestation (GD 15-22) only, or during 2-day intervals late in gestation (GD 23-24, 25-26, or 27-28). No maternal or developmental toxicity was elicited from maternal exposure during GD 6-14, 15-22, or 27-28. However, MeI-related fetotoxicity, including increased litter proportions of late fetal deaths with or without corresponding decreases in fetal body weight, were observed for females exposed during GD 6-28 (p < .01), 23-24 and 25-26. Although the increase in late-stage fetal death for each of the 2-day exposures on GD 23-24 and GD 25-26 was not statistically significant, as noted for the combined total of fetal deaths during the GD 6-28 exposure, it can be deduced that the gestational window of GD 23-26 was the most susceptible window of exposure for eliciting developmental toxicity in rabbits exposed to MeI vapors.

Methyl iodide-induced fetal hypothyroidism implicated in late-stage fetal death in rabbits.

Methyl iodide (MeI) induces fetotoxicity in New Zealand White (NZW) rabbits when maternal exposure occurs during a susceptible window late in gestation (gestation days [GD] 23-26). To identify the possible mode of action, comprehensive maternal and fetal bioanalysis and thyroid structure/function assessments were conducted in MeI-exposed (25 ppm by whole-body inhalation) and unexposed time-mated NZW rabbits (10/group) during GD 21-27. Key developmental events were observed within this window in unexposed fetuses, including the appearance of colloid in the thyroid follicular lumen and the detection of serum T(3) beginning on GD 22. Fetal T(4) and T(3) levels were diminished following maternal MeI exposure compared to baseline values. Fetal TSH was significantly increased following 4 days of maternal MeI exposure. MeI-induced changes in the fetal thyroid included reduced colloid formation, epithelial follicular hypertrophy, and epithelial cytoplasmic vacuolation. Time-course investigations using 20 ppm MeI revealed highly concentrated levels of iodide in fetal versus maternal serum. Direct maternal administration of sodium iodide by intravenous infusion during GD 23-26 induced similar effects on fetal thyroid structure and function as MeI, identifying iodide as the putative agent. Elevated S-methylcysteine adduct concentrations were noted in fetal hemoglobin, indicating that some unreacted MeI may be delivered directly to the fetus. However, the weight of evidence from these studies suggests that late-stage fetal death following maternal exposure to MeI during GD 23-26 is the result of preferential accumulation of iodide in the fetal compartment causing disruption of the fetal hypothalamic-pituitary-thyroid axis at a critical time in the development of the rabbit fetal thyroid.

Two-day inhalation toxicity study of methyl iodide in the rat.

The effects of inhaled methyl iodide (MeI) on clinical pathology parameters, glutathione (GSH) tissue levels, serum thyroid hormone and inorganic iodide concentrations, S-methylcysteine hemoglobin concentrations, and liver UDP-glucuronyltransferase activity were studied in the rat. Male rats were exposed by whole-body inhalation to 0, 25, or 100 ppm MeI, 6 h/day for up to 2 days. Serum cholesterol concentrations (both high-density lipoprotein [HDL] and low-density lipoprotein [LDL] fractions) were increased and triglycerides were decreased at both exposure levels. Serum thyroid-stimulating hormone (TSH) concentrations were increased at 25 and 100 ppm, and serum triiodothyronine (T(3)) and thyroxine (T(4)) concentrations were decreased at 100 ppm. There was no change in either reverse triiodothyronine (rT(3)) or UDP-glucuronyltransferase activity at either exposure level. A dose- and time-dependent reduction in GSH levels in blood, kidney, liver, and nasal tissue was observed, with the greatest reduction in nasal tissue (olfactory and respiratory epithelium). MeI exposure also resulted in a substantial dose- and time-dependent increase in both serum inorganic iodide and red blood cell S-methylcysteine hemoglobin adducts. These results indicate that following inhalation exposure, MeI is rapidly metabolized in blood and tissue of rats, resulting in methylation products and release of inorganic iodide.

Effect of methyl iodide on deiodinase activity.

Methyl iodide (MeI) has been proposed as an alternative for methyl bromide in pre-plant soil fumigation applications that does not affect stratospheric ozone. Preliminary studies in rabbits noted fetal resorptions if the pregnant does were exposed to MeI during a critical period during gestation. In addition, abnormalities in thyroid hormone parameters were also observed in animals exposed to MeI. Since monodeiodination is the major metabolic pathway of the thyroid hormones, we examined the effect of MeI on deiodinase activity as a possible etiology for the alteration in thyroid hormone parameters and ultimate fetal demise. In vitro studies using tissue microsomes and cell culture showed that MeI has no effect on type I 5'-deiodinase (D1) or type II 5'-deiodinase (D2) at physiologically relevant concentrations. At high concentrations (>10 mM,>10,000 ppm), MeI caused a nonspecific inactivation of D1 and D2. Analysis of D1 and D2 activity in rats exposed by inhalation to increasing concentrations of MeI showed a significant decrease in enzyme activity at 100 ppm, while brain type III 5'-deiodinase (D3) was unaffected by MeI at the exposures studied. While the drop in D1 can be explained by the induction of a hypothyroid state in the exposed rats, there is no clear explanation for the fall in D2 levels. In the rabbit studies, there was a significant decrease in kidney D1 in the adult rabbits exposed to 20 ppm MeI. However, there was no effect on liver D1, brain D2, or placental D3 in the MeI-exposed rabbits. Similarly, there was no effect of MeI on fetal D1 or D2 activity. The lack of a significant direct effect of MeI on deiodinase activity and the absence of a change in placental or fetal deiodinase activity make it unlikely that alterations in deiodinase activity plays a role in the fetal resorptions in the MeI-exposed rabbits.

Evaluation of respiratory parameters in rats and rabbits exposed to methyl iodide.

Laboratory animals exposed to methyl iodide (MeI) have previously demonstrated lesions of the olfactory epithelium that were associated with local metabolism in the nasal tissues. Interactions of MeI in the nasal passage may, therefore, alter systemic toxicokinetics. The current study used unrestrained plethysmographs to determine the MeI effect on the breathing frequency and minute volume (MV) in rats and rabbits. Groups of 4 rats each were exposed to 0, 25, or 100 ppm and groups of 4 rabbits each were exposed to 0 and 20 ppm MeI for 6 h. Breathing frequency and MV were measured and recorded during the exposure. Blood samples were collected for inorganic serum iodide and the globin adduct S-methylcysteine (SMC) as biomarkers of systemic kinetics immediately following exposure. No significant reductions in breathing frequency were observed for either rats or rabbits. Significant changes in minute volume were demonstrated by both rats and rabbits; however, the changes observed in rats were not concentration dependent. The MeI-induced changes in MV resulted in significant differences in the total volume of test substance atmosphere inhaled over the 6-h period. Rats demonstrated a concentration-dependent increase in both inorganic serum iodide and SMC. Rabbits exposed to 20 ppm MeI demonstrated a significant increase of inorganic serum iodide; SMC was also increased but was not statistically significant. The results of this study are consistent with previous kinetic studies with MeI, and the data presented here can be integrated into a computational fluid dynamics physiologically based pharmacokinetic model for both rats and rabbits.

Evaluation of tissue response to MTA and Portland cement with iodoform.

OBJECTIVE: The aim of this study was to evaluate the biocompatibility of Portland cement with the addition of iodoform, compared to MTA (ProRoot). STUDY DESIGN: Eighteen Wistar albino rats were divided into 3 groups of 6 animals each. Polyethylene tubes were filled either with freshly mixed MTA or Portland cement mixed with iodoform (20% wt/wt) and implanted subcutaneously. An empty tube served as control. After 7, 30, or 60 days, the implants together with the surrounding tissues were removed in blocks. Sections were evaluated for the presence and thickness of a fibrous capsule, presence of granulation tissue, and the severity of inflammatory response. Data were submitted to nonparametric statistical analysis with individual comparisons between groups at a significance level of P < 0.05. RESULTS: There were no differences between inflammatory responses at 7 and 30 days. After 60 days from surgical removal, there was significantly more tissue reaction to the MTA and Portland cement compared to the control group. CONCLUSION: There were no significant differences regarding inflammatory responses between MTA and Portland cement with iodoform after 7, 30, or 60 days. After 60 days, the fibrous capsule around the Portland cement appeared more organized than tissue surrounding MTA implants. After 60 days, there was still a significantly increased tissue reaction to the 2 cements compared to the empty polyethylene tubes.

Acute methyl iodide exposure with delayed neuropsychiatric sequelae: report of a case.

BACKGROUND: Methyl iodide is a monohalomethane used as an analytic and organic chemistry reagent, as a methylating agent in organic chemical synthesis, and as a fumigant. In an acute exposure, methyl iodide is a pulmonary and dermal irritant. Chronic neurotoxicity has been reported in survivors of acute exposure. METHODS: A review of the 11 case reports of methyl iodide poisoning in the medical literature of the 20th century found that six of the patients experienced a chronic neurological syndrome characterized primarily by delayed psychiatric, behavioral, and cognitive sequelae. RESULTS: The case patient experienced a massive exposure to methyl iodide with resulting life-threatening burns. During convalescence, various cognitive and behavioral deficits became apparent. The results of a comprehensive evaluation at our occupational toxicology clinic, which included sequential neuropsychometric testing, are described. CONCLUSION: The findings in the case patient may advance our understanding of the mechanisms and clinical manifestations of chronic neurotoxicity after exposure to methyl iodide.