RESUMO
1,2-Dichloropropane (1,2-DCP), a solvent, which is the main component of the cleaner used in the offset printing companies in Japan, is suspected to be the causative agent of bile duct cancer, which has been recently reported at high incidence in those offset printing workplaces. While there are some reports about the acute toxicity of 1,2-DCP, no information about its metabolism related to toxicity in animals is available. As part of our efforts toward clarifying the role of 1,2-DCP in the development of cancer, we studied the metabolic pathways and the hepatotoxic effect of 1,2-DCP in mice with or without cytochrome P450 2E1 (CYP2E1) activity. In an in vitro reaction system containing liver homogenate, 1,2-DCP was only metabolized by liver tissue of wild-type mice but not by that of cyp2e1-null mice. Furthermore, the kinetics of the solvent in mice revealed a great difference between the two genotypes; 1,2-DCP administration resulted in dose-dependent hepatic damage, as shown biochemically and pathologically, but this effect was only observed in wild-type mice. The nuclear factor κB p52 pathway was involved in the liver response to 1,2-DCP. Our results clearly indicate that the oxidative metabolism of 1,2-DCP in mice is exclusively catalyzed by CYP2E1, and this step is indispensable for the manifestation of the hepatotoxic effect of the solvent.
Assuntos
Carcinógenos Ambientais/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Citocromo P-450 CYP2E1/metabolismo , Fígado/metabolismo , Propano/análogos & derivados , Solventes/metabolismo , Ativação Metabólica , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Animais não Endogâmicos , Carcinógenos Ambientais/administração & dosagem , Carcinógenos Ambientais/análise , Carcinógenos Ambientais/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocromo P-450 CYP2E1/genética , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Inseticidas/administração & dosagem , Inseticidas/sangue , Inseticidas/metabolismo , Inseticidas/toxicidade , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Knockout , Subunidade p52 de NF-kappa B/metabolismo , Oxirredução , Propano/administração & dosagem , Propano/sangue , Propano/metabolismo , Propano/toxicidade , Solventes/administração & dosagem , Solventes/análise , Solventes/toxicidade , ToxicocinéticaRESUMO
COVID-19 is around the world. We attempt to apply three-step method in ISO/IEC Guide 51: 2014 to COVID-19 infection control in the workplace. The results show that the COVID-19 infection control measures include the eradication of the virus, the destruction of infectivity, the detoxification and weakening and the elimination of opportunities for infection as "Inherently Safe Design Measures", the avoidance of contact as "Safeguarding and Complementary Protective Measures" and the reduction of contact and the avoidance of seriousness as "Information for Use". Among these specific measures, the New Normal, especially in the manufacturing industries, would be "telecommuting" and "unmanned workplaces", which are part of the elimination of opportunities for infection, and "changes in flow lines" and "changes in airflow", which are part of the avoidance of contact. Where "telecommuting" and "unmanned workplaces" are feasible, they should be implemented as much as possible, and where they are not, attempts should be made to minimize human-to-human contact by "changes in flow lines". In addition, in the area of "changes in airflow", there are high expectations for future research on how to establish a ventilation design for COVID-19, in which but also the source would be workers themselves, not only combustible gases and toxic gases.
Assuntos
COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Infecções/organização & administração , Saúde Ocupacional/normas , Local de Trabalho/organização & administração , Saúde Global , Humanos , Controle de Infecções/normas , Instalações Industriais e de Manufatura/normas , SARS-CoV-2 , Teletrabalho , Ventilação/normas , Local de Trabalho/normasRESUMO
[This corrects the article DOI: 10.1186/s41021-020-0146-3.].
RESUMO
BACKGOUND: A variety of in vivo and in vitro studies to assess the genotoxicity of titanium dioxide nanoparticles (TiO2 NPs) have been reported, but the results are inconsistent. Recently, we reported that TiO2 NPs exhibit no genotoxic effects in the liver and erythrocytes during a relatively brief period following intravenous injection into mice. However, there is no information about long-term genotoxicity due to TiO2 NP accumulation in tissues. In this study, we investigated the long-term mutagenic effects of TiO2 NPs and the localization of residual TiO2 NPs in mouse liver after multiple intravenous injections. RESULTS: Male gpt delta C57BL/6 J mice were administered with various doses of TiO2 NPs weekly for 4 consecutive weeks. The long-term mutagenic effects on the liver were analyzed using gpt and Spi- mutation assays 90 days after the final injection. We also quantified the amount of titanium in the liver using inductively coupled plasma mass spectrometry and observed the localization of TiO2 NPs in the liver using transmission electron microscopy. Although TiO2 NPs were found in the liver cells, the gpt and Spi- mutation frequencies in the liver were not significantly increased by the TiO2 NP administration. CONCLUSIONS: These results clearly show that TiO2 NPs have no mutagenic effects on the liver, even though the particles remain in the liver long-term.
RESUMO
The goal of our study was to determine if toluene affected the synthesis and secretion of testosterone in fetal rats. Dams were exposed to atmospheres that contained 0.09 ppm, 0.9 ppm or 9 ppm of toluene for 90 min/day from gestational days (GDs) 14.5 to 18.5 via nasal inhalation. Fetal plasma testosterone concentrations determined by enzyme immunoassay were significantly reduced on GD 18.5 after exposure to 0.9 and 9 ppm, but not to 0.09 ppm, of toluene in male, but not in female, fetuses. We measured, using real-time PCR methods, mRNA levels in fetal testes for several steroidogenic enzymes involved in testosterone synthesis and insulin-like 3 (Insl3), a maker of Leydig cell differentiation. The mRNA levels of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) were significantly reduced after exposure to 0.9-ppm toluene. However, the mRNA levels of cytochrome P450 cholesterol side-chain cleavage, cytochrome P450 17alpha-hydroxylase/c17-20 lyase, 17beta-hydroxysteroid dehydrogenase, and Insl3 were not significantly altered by exposure to 0.9-ppm toluene. In addition, immunohistochemical analysis showed reduced 3beta-HSD-immunoreactive areas in the interstitial region of fetal testes after exposure to 0.9 and 9 ppm, but not 0.09 ppm, toluene. These findings indicate that toluene reduced the synthesis and secretion of testosterone in fetal testes from rats possibly as a consequence of reduced 3beta-HSD expression.
Assuntos
Poluentes Atmosféricos/toxicidade , Sangue Fetal/química , Exposição por Inalação/efeitos adversos , Exposição Materna/efeitos adversos , Testosterona/sangue , Tolueno/toxicidade , Poluentes Atmosféricos/farmacocinética , Animais , Ensaio de Imunoadsorção Enzimática , Feminino , Masculino , Troca Materno-Fetal , Reação em Cadeia da Polimerase , Gravidez , Ratos , Ratos Long-Evans , Testículo/efeitos dos fármacos , Testículo/embriologia , Testículo/metabolismo , Testosterona/biossíntese , Tolueno/farmacocinéticaRESUMO
Most of the volatile organic compounds used in industrial and household products are reported to be toxic. While the effects of toxic chemicals on pulmonary and other systemic functions have been studied substantially, little is known about their effects on higher brain functions, particularly on the events in learning performance. From the particular perspective of environmental health, it is necessary to examine the toxic effects of environmental chemicals on higher brain functions. The aim of the present study is to establish a mouse model for simultaneous assessment of the effect of toluene (150 mg/kg, i.p.) on extracellular glutamate level in the hippocampus, using in vivo microdialysis and learning performance with a procedure of schedule-controlled operant behavior (SCOB). Different patterns of hippocampal glutamate level were observed in control and toluene-treated mice during learning performance. During learning performance in an operant chamber, control mice showed a saturated and persistent increased glutamate level with good learning performance, while toluene-treated mice showed a decreased glutamate level with poor learning performance. This is the first time to establish a new method to assess the effect of environmental chemical exposure on the brain neurotransmitter level during learning performance in an animal model.
Assuntos
Aprendizagem/efeitos dos fármacos , Modelos Animais , Neurotransmissores/análise , Tolueno/toxicidade , Animais , Condicionamento Operante/efeitos dos fármacos , Glutamatos/análise , Hipocampo/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicrodiáliseRESUMO
Currently, protocols for the dispersal of titanium dioxide (TiO2) nanoparticles are not standardized and often yield non-uniform particles and/or insufficient dispersal in liquid medium. Our study aimed to improve dispersal so that TiO2 nanoparticles are of uniform size, making nanotoxicity testing more reliable. Various combinations of vehicles, sonication durations, and sonication volumes were assessed for optimizing preparations of TiO2 nanoparticles. We tested each of five vehicles: ultrapure water (UPW), 0.2% disodium hydrogen phosphate (DSP), Dulbecco's phosphate-buffered saline (PBS), 0.9% saline (S), or S containing 0.05% Tween 80 (ST). We also assessed two sonication durations and three sonication volumes. Each suspension underwent ultrasonication and centrifugation; the supernatants were then analyzed. Particle size was measured by dynamic light scattering. P25 nanoparticles (~100 nm; the type of TiO2 nanoparticles used in our study) in UPW and 0.2% DSP were effectively dispersed; however, those in PBS, S, or ST were not. Relevant duration time and volume for sonication were examined with 0.2% DSP. A sonication time of 30 min and volume of 10 mL for each vial were determined to be optimal sonication conditions as determined with our dispersal assay. Under these optimal conditions, P25 nanoparticles sonicated/centrifuged in UPW or 0.2% DSP remained dispersed and exhibited long-term stability (90 days). We thus have developed a reliable procedure for preparing TiO2 nanoparticles in liquid-phase dispersions for toxicity testing.
Assuntos
Nanopartículas Metálicas/toxicidade , Titânio/toxicidade , Testes de Toxicidade/métodos , Centrifugação , Estabilidade de Medicamentos , Tamanho da Partícula , Fosfatos , Solução Salina , Sonicação , ÁguaRESUMO
In the sexually dimorphic nucleus of the preoptic area (SDN-POA) of postnatal rats, apoptotic cells are detected more frequently in females than males. This sex difference is under the influence of aromatized androgen. We have reported that there are sex differences in the levels of Bcl-2 (female
Assuntos
Estradiol/análogos & derivados , Área Pré-Óptica/citologia , Área Pré-Óptica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Caracteres Sexuais , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Estradiol/metabolismo , Estradiol/farmacologia , Feminino , Masculino , Gravidez , Área Pré-Óptica/crescimento & desenvolvimento , Ratos , Ratos Long-Evans , Regulação para Cima/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismoRESUMO
Smell of very low dose of chemical might evoke subjective physical symptoms in human by some process of learning named the aversion conditioning. But few scientific evidences of the hypothesis have been reported so far. Validity of conditioned odor aversion (COA) using low-doses of organic solvent as odor conditioned stimulus (CS) was examined. In conditioning phase, water-deprived male Sprague-Dawley rats were presented low, medium or high dose solution for 30 min followed by 0.3 M Lithium Chloride (LiCl) solution or saline injection. The xylene solution and drink water were simultaneously provided on the next day as two-bottle test. Consumption of medium dose of xylene solution was significantly decreased in LiCl injection group as compared with saline group. There was no difference between LiCl and saline injected animals in low group. Animals in high dose did not access to xylene even on the conditioning. These results indicate that animals showed high sensitivity for discrimination against concentration of xylene and that the medium dose of xylene functioned as the CS. We concluded that the COA used in the present study may be one of useful procedures to investigate olfaction of animal.
Assuntos
Olfato/fisiologia , Paladar/fisiologia , Xilenos , Animais , Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico/fisiologia , Cloreto de Lítio/administração & dosagem , Masculino , Ratos Sprague-DawleyRESUMO
Volatile organic compounds are the main substances causing multiple chemical sensitivity reactions in human. Our laboratory has previously showed that the exposure of low-level formaldehyde causes immunogenic and neurogenic inflammatory responses in mice. The aim of the present study was to investigate the effect of long-term, low-level toluene exposure on airway inflammatory responses in mice lung. We exposed female C3H mice to filtered air (0ppm) or 50ppm of toluene for 6h/day on 5days/week for 6 or 12 weeks in the whole body exposure chamber. One day following the last toluene exposure, we collected bronchoalveolar lavage fluid from each mouse and examined cellular infiltration and production of cytokines, chemokines, neurotrophins and substance P by using ELISA method. We found that the number of total cells and macrophages increased significantly in both 6 and 12-week-exposed mice. In addition, the production of interferon-gamma and substance P were decreased significantly and nerve growth factor was not affected in both 6 and 12-week-exposed mice. In contrast, neurotrophin-3 production in bronchoalveolar lavage fluid was significantly increased only in 12-week-exposed mice. Our findings suggest that long-term (12-week) exposure of mice to low-level toluene modulates airway inflammatory response via neurological signaling.
Assuntos
Inflamação/induzido quimicamente , Inflamação/patologia , Tolueno/toxicidade , Administração por Inalação , Animais , Brônquios/patologia , Líquido da Lavagem Broncoalveolar/citologia , Quimiocinas/análise , Quimiocinas/biossíntese , Citocinas/análise , Citocinas/biossíntese , Feminino , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C3H , Fatores de Crescimento Neural/análise , Fatores de Crescimento Neural/biossíntese , Fatores de Crescimento Neural/fisiologia , Neurotrofina 3/biossíntese , Pneumonia/induzido quimicamente , Pneumonia/patologia , Solventes/toxicidade , Substância P/análise , Substância P/biossínteseRESUMO
Titanium dioxide (TiO2) nanoparticles are increasingly manufactured in large amounts for use in industrial applications such as cosmetics, pigments, foods, and as photo-catalysts. Many in vitro studies have examined the genotoxicity of TiO2 nanomaterials; some of these studies suggest that TiO2 nanoparticles (NPs) are genotoxic. Several in vivo studies have also been reported recently, but the results are inconsistent. In this study, we investigated, using several genotoxicity endpoints, the effects of dispersed TiO2 suspensions following multiple intravenous injections in mice. Male gpt Delta C57BL/6J mice were administered TiO2 NPs at doses of 2, 10 or 50mg/kg body weight per week for 4 consecutive weeks. Genotoxic effects were then analyzed by the Pig-a gene mutation assay and the micronucleus assay on peripheral blood, and by the alkaline comet, gpt mutation, and Spi(-) mutation assays on the liver. We also assessed the localization of TiO2 NPs in the liver, by transmission electron microscopy. Administration of TiO2 NPs did not significantly increase any of the following endpoints: frequency of Pig-a mutants (erythrocytes); frequency of micronuclei (reticulocytes); level of DNA damage (liver); frequencies of gpt and Spi(-) mutants (liver). Most TiO2 NPs in the liver were found in the sinuses and inside Kupffer cells, although some were occasionally observed in liver parenchymal cells. These results indicate that TiO2 NPs do not have genotoxic effects on mouse liver or bone marrow.
Assuntos
Dano ao DNA/genética , DNA/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Testes para Micronúcleos , Titânio/toxicidade , Animais , Dano ao DNA/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos TransgênicosRESUMO
A behavioral-history procedure was used to study the function of terminal-link stimuli as conditioned reinforcers in multiple concurrent-chain schedules of reinforcement. First, three pigeons were exposed to multiple concurrent-chain schedules in which the two multiple-schedule components were correlated with a blue and a white stimulus, respectively. In each component the initial links were equal independent variable-interval (VI) 15 s schedules. A fixed-interval (FI) 10 s schedule operated on the red key in one terminal link while extinction operated on the green key in the alternative terminal link. When large preferences for the red stimulus had been established, two tests were conducted. In the terminal-link test, under new initial-link stimuli--purple and brown--an FI 10 s schedule operated for both the red and green terminal-link stimuli. In the subsequent initial-link test, the blue and white initial-link stimuli were reintroduced, and, as in the terminal-link test, FI 10s operated for both the red and the green terminal-link stimuli. In the terminal-link test, the three pigeons showed no preference for the terminal links with the red stimulus, but showed clear and consistent preferences for the red stimulus when blue and white stimuli were reintroduced as initial-link stimuli in the initial-link test. This suggests that there are multiple sources of control over initial-link response allocation in concurrent-chains, including control by both terminal- and initial-link stimuli.
Assuntos
Comportamento Animal , Reforço Psicológico , Animais , Columbidae , Condicionamento Psicológico , Aprendizagem por Discriminação , Esquema de ReforçoRESUMO
To examine the validity of a newly established "three-odor detection (TOD)" procedure using one of volatile organic compounds (VOCs), limonene, food-restricted male mice were used. Five animals each were assigned to either TOD or single-odor detection (SOD). TOD was composed of two trainings and one test (TEST) session. Mice were trained to discriminate an odor of coffee from no odor and odors of coffee and cheese from no odor in trainings 1 and 2, respectively. In TEST, mice were required to discriminate odors of coffee, cheese, and limonene from no odor. In SOD, mice were required to discriminate an odor of limonene from no odor. Each training or test was conducted once a day until animals achieved a learning criterion (75% correct response rate for 2 consecutive days), or until a maximum number of sessions (20 sessions) was completed. The number of sessions for reaching the learning criterion of animals in TEST (8.2 ± 0.8) was smaller than that of animals in SOD (19.2 ± 0.8). Results indicated that mice in TOD detected low levels of VOCs more rapidly than animals in SOD. I concluded that TOD is a useful procedure for detecting low levels of VOCs.
Assuntos
Comportamento Animal/fisiologia , Condicionamento Operante/fisiologia , Cicloexenos , Aprendizagem por Discriminação/fisiologia , Discriminação Psicológica/fisiologia , Odorantes , Reforço Psicológico , Olfato/fisiologia , Terpenos , Compostos Orgânicos Voláteis , Animais , Limoneno , Masculino , Camundongos Endogâmicos C3HRESUMO
Pregnant Sprague-Dawley rats received a single oral dose of 0, 20, 60, or 180 ng/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin on day 8 of gestation. Each litter contributed a single male-female pair trained to press a lever to obtain food pellets under two operant behavior procedures. Initially, each lever press was reinforced. The fixed-ratio (FR) requirement was then increased every four sessions from the initial setting of 1 to values between 6 and 71. We then studied responses for 30 days under a multiple schedule combining FR 11 and another schedule requiring a pause of at least 10 sec between responses (DRL 10-sec). TCDD evoked a sexually dimorphic response pattern. Generally, TCDD-exposed males responded at lower rates than control males. In contrast, exposed females responded at higher rates than controls. Each response measure from the mult-FR DRL schedule yielded a male-female difference score. We used the differences in response rate to calculate benchmark doses based on the relative displacement from modeled zero-dose performance of the effective dose at 1% (ED(01)) and 10% (ED(10)), as determined by a second-order polynomial fit to the dose-effect function. For the male-female difference in FR rate of responding, the mean ED(10) was 2.77 ng/kg with a 95% lower bound of 1.81 ng/kg. The corresponding ED(01) was 0.27 ng/kg with a 95% lower bound of 0.18 ng/kg. For the male-female difference in DRL rate, the mean ED(10) was 2.97 ng/kg with a 95% lower bound of 2.02 ng/kg. The corresponding ED(01) was 0.30 ng/kg with a 95% lower bound of 0.20 ng/kg. These values fall close to, but below, current estimates of human body burdens of 13 ng/kg, based on TCDD toxic equivalents.
Assuntos
Condicionamento Operante , Dioxinas/efeitos adversos , Poluentes Ambientais/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Caracteres Sexuais , Administração Oral , Animais , Carga Corporal (Radioterapia) , Relação Dose-Resposta a Droga , Feminino , Masculino , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
The present study proposes a novel experimental approach to examine the effect of previous schedule history on subsequent responses. College students used a three-button device to indicate their choice of response. We performed two experiments. Each experiment consisted of three phases. In experiment I, fixed-ratio 10 (FR 10) reinforcement schedule was employed in phases 1 and 3. Phase 2 employed "Rotary-FR 10" schedule: after obtaining a point produced by pressing one of three specified buttons in a triangular array 10 times, the effective button changed to another in a clockwise direction. Optimal response pattern for Rotary-FR 10 was analyzed. Two types of behavior, referred to as "consecutive" and "scatter" were observed in phase 1. The mean number of optimal responses in consecutive type was significantly higher than scatter type in phases 2 and 3. In experiment II, two schedules were used in phase 1, and the same protocol used in experiment I was followed. We found that the reinforcement schedule used in phase 1 affected acquisition of the optimal response in phase 2. These results suggest that the earlier behavioral tendencies play an important role in determining subsequent behavior and that such behavioral tendency can be modified by specifically designed protocols.
Assuntos
Comportamento de Escolha , Esquema de Reforço , Feminino , Humanos , Masculino , EstudantesRESUMO
The role of thyroid hormones in gonad development remains incompletely understood. We examined the dose-related effects of perinatal hypothyroidism induced by a reversible goitrogen, 6-propyl-2-thiouracil (PTU), on reproductive development in male rat offspring. Timed-pregnant Sprague-Dawley rats were orally administered PTU (0, 0.5, 1.0, or 2.0 mg/kg/day) by gavage from gestational day 15 through postnatal day 20. We observed a significant dose-dependent decrease in body weight in offspring with PTU exposure up to 13 weeks of age, but body weight became comparable among groups by 26 weeks of age. Testicular weight tended to be lower up to 7 weeks but was higher after 13 weeks of age. Epididymis weight was not different among the groups at any age. Plasma concentrations of thyroxine and triiodothyronine in the PTU groups were significantly lower at 3 weeks of age but recovered to normal levels by 26 weeks of age. No dose-related trend in plasma testosterone concentrations was found. Seminiferous tubules were larger at 13 and 26 weeks of age with PTU exposure. The number of Sertoli cells was significantly higher from 3 through 26 weeks of age. The number of Leydig cells was significantly lower up to 7 weeks of age but was comparable among groups from 13 weeks of age onwards. Thus, transient gestational and lactational thyroid hormone suppression induced small testes in early life but led to paradoxical dose-dependent testicular enlargement in adults as indicated partly by larger seminiferous tubules with numerous Sertoli cells in male rat offspring.
Assuntos
Animais Recém-Nascidos/crescimento & desenvolvimento , Antitireóideos/farmacologia , Hipotireoidismo/fisiopatologia , Propiltiouracila/farmacologia , Testículo/crescimento & desenvolvimento , Administração Oral , Animais , Antitireóideos/administração & dosagem , Antitireóideos/farmacocinética , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Idade Gestacional , Hipotireoidismo/induzido quimicamente , Células Intersticiais do Testículo , Masculino , Troca Materno-Fetal , Gravidez , Propiltiouracila/administração & dosagem , Propiltiouracila/farmacocinética , Ratos Sprague-Dawley , Túbulos Seminíferos/crescimento & desenvolvimento , Células de Sertoli , Testículo/citologiaRESUMO
The potential for health effects on humans with exposure to bisphenol A (BPA) has raised concerns, and the adverse effects of low-dose exposure to BPA on reproduction have been controversial. The purpose of the present study was to investigate the effects of low-dose exposure to BPA on reproductive development in F(1) rat offspring. Pregnant female Sprague-Dawley rats (F(0)) were fed a diet containing low doses of BPA (0, 0.33, 3.3, or 33 ppm) from gestational day (GD) 6 through postnatal day (PND) 21. The weanlings (F(1)) from all dose groups were fed a normal diet ad libitum after weaning and then were subjected to necropsy at 5 weeks or 3 months of age. No BPA-related changes were observed in body weight or weight of any of the major reproductive organs in F(1) males and females. Epididymis weight was significantly lower only in 3-month-old F(1) males exposed to 33 ppm BPA. Anogenital distance (AGD), the ratio of AGD to the cube root of body weight, and relative ovary weight were significantly lower in 5-week-old F(1) females exposed to 3.3 and 33 ppm BPA, but significant differences were not observed in 3-month-old females. There were no BPA-related effects on cauda epididymal sperm motility in 3-month-old F(1) males. Plasma reproductive steroid hormone concentrations were not altered among groups in either sex. These outcomes indicate that low-dose exposure to BPA in the diet does not adversely affect reproductive development in F(1) rat offspring.
Assuntos
Genitália/efeitos dos fármacos , Genitália/crescimento & desenvolvimento , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/patologia , Reprodução/efeitos dos fármacos , Animais , Compostos Benzidrílicos , Peso Corporal/efeitos dos fármacos , Dieta , Relação Dose-Resposta a Droga , Feminino , Hormônios/análise , Hormônios/metabolismo , Lactação , Masculino , Tamanho do Órgão , Gravidez , Ratos , Ratos Sprague-Dawley , Motilidade dos Espermatozoides/efeitos dos fármacos , DesmameRESUMO
OBJECTIVES: We studied and compared the possible effects of in utero and lactational exposure to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) or 3, 3', 4, 4', 5-pentachlorobiphenyl (PCB126) on learning behavior in offspring. METHODS: Pregnant Long-Evans Hooded rats were administered either TCDD (50, 200, or 800 ng/kg) or PCB126 (500, 2,000 or 8,000 ng/kg) on gestational day 15. A procedure of schedule-controlled operant behavior was applied to examine learning behavior in the male and female offspring at 11 weeks of age for 30 days. Three indices, namely, response rates in a fixed ratio (FR) and in a differential reinforcement of low rates (DRL), and reward rate in the DRL component in multiple FR 20 DRL 20 s (mult-FR 20 DRL 20-s) test sessions, were used for the evaluation of learning behavior. RESULTS: Toxic effects on learning behavior in male and female pups following in utero and lactational exposure to TCDD or PCB126 were observed mainly in the FR learning component. However, no linear dose-dependent effects of either of the two compounds were observed for the above three indices. The response rates of animals in the low-dose TCDD and PCB126 groups decreased and those in medium-dose TCDD and PCB126 groups appeared to induce hyperactive behavior. The high dose of PCB126 appeared to have a distinct toxicity from that of TCDD in terms of the acquisition of learning behavior. CONCLUSIONS: Toxicities of PCB126 and TCDD in learning behavior might be similar to each other and the current toxic equivalency factor (TEF) of 0.1 for PCB126 can be considered to be appropriate for this endpoint.
RESUMO
Thimerosal, which releases the ethyl mercury radical as the active species, has been used as a preservative in many currently marketed vaccines throughout the world. Because of concerns that its toxicity could be similar to that of methyl mercury, it is no longer incorporated in many vaccines in the United States. There are reasons to believe, however, that the disposition and toxicity of ethyl mercury compounds, including thimerosal, may differ substantially from those of the methyl form. The current study sought to compare, in neonatal mice, the tissue concentrations, disposition and metabolism of thimerosal with that of methyl mercury. ICR mice were given single intramuscular injections of thimerosal or methyl mercury (1.4 mg Hg kg(-1)) on postnatal day 10 (PND 10). Tissue samples were collected daily on PND 11-14. Most analysed tissues demonstrated different patterns of tissue distribution and a different rate of mercury decomposition. The mean organic mercury in the brain and kidneys was significantly lower in mice treated with thimerosal than in the methyl mercury-treated group. In the brain, thimerosal-exposed mice showed a steady decrease of organic mercury levels following the initial peak, whereas in the methyl mercury-exposed mice, concentrations peaked on day 2 after exposure. In the kidneys, thimerosal-exposed mice retained significantly higher inorganic mercury levels than methyl mercury-treated mice. In the liver both organic and inorganic mercury concentrations were significantly higher in thimerosal-exposed mice than in the methyl mercury group. Ethyl mercury was incorporated into growing hair in a similar manner to methyl mercury. The data showing significant kinetic differences in tissue distribution and metabolism of mercury species challenge the assumption that ethyl mercury is toxicologically identical to methyl mercury.
Assuntos
Compostos de Metilmercúrio/farmacocinética , Timerosal/farmacocinética , Animais , Animais Recém-Nascidos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Distribuição TecidualRESUMO
Sex-specific patterns of cerebral cortical lateralization have been documented consistently in both the human and animal brain. Male rats tend to exhibit pronounced right hemisphere dominance compared with females, while females typically exhibit more diffuse lateralization patterns and greater left hemisphere bias compared with males. Prenatal TCDD (2,3,7,8 tetrachlorodibenzo-p-dioxin) exposure produces demasculinization of male offspring sexual behavior, suggesting interference with sexual differentiation of the brain. In previous studies, a reversal of cortical thickness patterns in rats was shown after prenatal TCDD exposure on gestational day 8 (GD 8). The current study, based on the same brain sections, attempted to define changes in the number of cortical cells and cell size distributions in brains of offspring from TCDD-treated dams. Pregnant females were given a single oral dose of 0 or 180 ng kg(-1) TCDD on GD 8. Cell counts and sizes were determined in 3-month-old offspring. Areas 17 and 18a at bregma -3.8 were analysed using digitized, enhanced images of brain sections produced by a photomicroscope fitted with a high-resolution digital camera. Prenatal TCDD exposure altered the relative proportions of smaller and larger cell sizes in male, but not in female offspring. Both exposed males and females, however, exhibited a significant reversal of hemispheric dominance based on cell number. These findings demonstrate that prenatal exposure to TCDD alters the normal patterns of cortical cell asymmetry in a manner consistent with our previous data on thickness patterns.