Toxicological aspects of trihalomethanes: a systematic review.

Chlorine is considered the most used chemical agent for water disinfection worldwide. However, water chlorination can lead to by-product generation which can be toxic to humans. The present study aimed to perform a systematic review on the toxicity of trihalomethanes (THMs) through bioindicators of cytotoxicity, genotoxicity, and mutagenicity. The results showed that studies on the effects of THMs on DNA are a current research concern for evaluating the toxicity of the pure compounds and real samples involving several types including water for recreational use, reused water, and drinking water. THMs deleterious effects have been assessed using several biosystems, where the Ames test along with experimental animal models were the most cited. A wide range of THM concentrations have been tested. Nevertheless, DNA damage was demonstrated, highlighting the potential human health risk. Among the studied THMs, chloroform presented a different action mechanism when compared with brominated THMs, with the former being cytotoxic while brominated THMs (bromodichloromethane, bromoform, and dibromochloromethane) were cytotoxic, genotoxic, and mutagenic. The described evidence in this research highlights the relevance of this topic as a human health issue. Nevertheless, research aimed to represent THMs current exposure conditions in a more accurate way would be needed to understand the real impact on human health.

Influence of sexual dimorphism on pulmonary inflammatory response in adult mice exposed to chloroform.

Chloroform is an organic solvent used as an intermediate in the synthesis of various fluorocarbons. Despite its widespread use in industry and agriculture, exposure to chloroform can cause illnesses such as cancer, especially in the liver and kidneys. The aim of the study was to analyze the effects of chloroform on redox imbalance and pulmonary inflammatory response in adult C57BL/6 mice. Forty animals were divided into 4 groups (N = 10): female (FCG) and male (MCG) controls, and females (FEG) and males (MEG) exposed to chloroform (7.0 ppm) 3 times/d for 20 minutes for 5 days. Total and differential cell counts, oxidative damage analysis, and protein carbonyl and antioxidant enzyme catalase (CAT) activity measurements were performed. Morphometric analyses included alveolar area (Aa) and volume density of alveolar septa (Vv) measurements. Compared to FCG and MCG, inflammatory cell influx, oxidative damage to lipids and proteins, and CAT activity were higher in FEG and MEG, respectively. Oxidative damage and enzyme CAT activity were higher in FEG than in FCG. The Aa was higher in FEG and MEG than in FCG and MCG, respectively. The Vv was lower in FEG and MEG than in FCG and MCG, respectively. This study highlights the risks of occupational chloroform exposure at low concentrations and the intensity of oxidative damage related to gender. The results validate a model of acute exposure that provides cellular and biochemical data through short-term exposure to chloroform.

Evaluation of the genotoxic potential of Austroplenckia populnea (Reiss) Lundell chloroform fraction from barkwood extract in rodent cells in vivo.

The genotoxic effect of the Austroplenckia populnea chloroform fraction from barkwood extract was tested in vivo on peripheral blood cells of Swiss mice with the comet assay (SCGE), and the clastogenic effect was investigated on peripheral blood cells of Swiss mice and bone marrow cells of Wistar rats, with the micronucleus and chromosome aberrations tests. The animals were treated by gavage with 3 concentrations of the extract: 300, 600 and 900 mg.kg-1. Peripheral blood cells of Swiss mice were collected 4 and 24 hours after the treatment to the SCGE assay and 48 and 72 hours to the micronucleus test. Bone marrow cells of Wistar rats were collected 24 hours after the treatment to the micronucleus and chromosome aberration tests. The results showed that the A. populnea chloroform fraction induced an increase in the average number of DNA damage in peripheral blood cells at the three concentrations tested, but this increase was not statistically significant. In the micronucleus and chromosome aberrations test, no significant increase was observed in the mean number of micronucleated polychromatic erythrocytes (MNPCE) of Swiss mice or MNPCE or chromosome aberrations for the rat bone marrow cells, for any of the tested doses. Our findings enable us to conclude that by the comet assay, A. populnea chloroform fraction from barkwood extract showed no genotoxic effects, and by the micronucleus and chromosome aberration tests, the extract fraction showed no clastogenic/aneugenic effects on the rodent cells tested.

Evaluation of the genotoxic potential of Austroplenckia populnea (Reiss) Lundell chloroform fraction from barkwood extract in rodent cells in vivo / Avaliação do potencial genotóxico da fração clorofórmica de cascas do caule de Austroplenckia populnea em células de roedores in vivo

The genotoxic effect of the Austroplenckia populnea chloroform fraction from barkwood extract was tested in vivo on peripheral blood cells of Swiss mice with the comet assay (SCGE), and the clastogenic effect was investigated on peripheral blood cells of Swiss mice and bone marrow cells of Wistar rats, with the micronucleus and chromosome aberrations tests. The animals were treated by gavage with 3 concentrations of the extract: 300, 600 and 900 mg.kg-1. Peripheral blood cells of Swiss mice were collected 4 and 24 hours after the treatment to the SCGE assay and 48 and 72 hours to the micronucleus test. Bone marrow cells of Wistar rats were collected 24 hours after the treatment to the micronucleus and chromosome aberration tests. The results showed that the A. populnea chloroform fraction induced an increase in the average number of DNA damage in peripheral blood cells at the three concentrations tested, but this increase was not statistically significant. In the micronucleus and chromosome aberrations test, no significant increase was observed in the mean number of micronucleated polychromatic erythrocytes (MNPCE) of Swiss mice or MNPCE or chromosome aberrations for the rat bone marrow cells, for any of the tested doses. Our findings enable us to conclude that by the comet assay, A. populnea chloroform fraction from barkwood extract showed no genotoxic effects, and by the micronucleus and chromosome aberration tests, the extract fraction showed no clastogenic/aneugenic effects on the rodent cells tested.

O possível efeito genotóxico da fração clorofórmica de cascas de caule de Austroplenckia populnea foi testado in vivo em células do sangue periférico de camundongos Suíços pelo ensaio cometa, e o seu possível efeito clastogênico foi investigado em células de sangue periférico de camundongos Suíços e células da medula óssea de ratos Wistar, respectivamente pelos testes do micronúcleo e de aberrações cromossômicas. Os animais foram tratados por via oral com três concentrações do extrato: 300, 600 e 900 mg.kg-1 de peso corpóreo. Células do sangue periférico dos camundongos foram coletadas 4 e 24 horas após o tratamento para a realização do ensaio cometa, e 48 e 72 horas para o teste do micronúcleo. Células da medula óssea dos ratos Wistar foram coletadas 24 horas após o tratamento para os testes do micronúcleo e de aberrações cromossômicas. Os resultados mostraram que a fração clorofórmica do extrato de A. populnea induziu um pequeno aumento no número médio de danos ao DNA nas células sanguíneas nas três concentrações testadas, mas tal aumento não foi estatisticamente significativo. Nos testes do micronúcleo e de aberrações cromossômicas não houve um aumento significativo no número médio de eritrócitos policromáticos micronucleados (EPM) dos camundongos, bem como nos EPM e aberrações cromossômicas nas células da medula óssea dos ratos, em nenhuma das doses testadas. Nossos resultados nos permitem concluir que, pelo ensaio cometa, a fração clorofórmica de cascas do caule de A. populnea não apresentou efeito genotóxico, e, pelos testes do micronúcleo e de aberrações cromossômicas, o extrato não mostrou efeitos clastogênicos e/ou aneugênicos nas células analisadas dos roedores.

Biocompatibility of gutta-percha solvents using in vitro mammalian test-system.

OBJECTIVES: Taking into consideration that DNA damage and cellular death play important roles during carcinogenesis, the purpose of the present study was to evaluate in vitro genotoxic or cytotoxic effects of chloroform and eucalyptol by single cell gel (comet) assay and trypan blue exclusion test, respectively. STUDY DESIGN: Chloroform and eucalyptol were exposed to Chinese hamster ovary cells in culture directly for 3 hours at 37 degrees C at final concentrations ranging from 1.25 to 10 microL/mL. The negative control group was treated with vehicle control (phosphate-buffered solution), and the positive control group was treated with methyl metasulfonate (MMS, at 1 microg/mL concentration). All data were analyzed by the Kruskal-Wallis nonparametric test followed by the Dunn test. RESULTS: The results showed that both gutta-percha solvents were cytotoxic at concentrations of 2.5, 5, and 10 microL/mL (P < .05). On the other hand, both solvents did not induce DNA breakage at 1.25 microL/mL concentration. CONCLUSIONS: These results suggest that both chloroform or eucalyptol are strong cytotoxicants, but they may not be a factor that increases the level of DNA lesions in mammalian cells.

In vitro evaluation of macrophage viability after incubation in orange oil, eucalyptol, and chloroform.

OBJECTIVE: The aim of this study was to evaluate the cytotoxicity of orange oil, eucalyptol, and chloroform in a cell culture assay by using peritoneal macrophages from Swiss mice. STUDY DESIGN: Control (Dulbecco's modified Eagle's medium [DMEM] plus 1.25% ethyl alcohol) and experimental (orange oil, eucalyptol, and chloroform) groups were studied. Solvents used were tested at 0.025% and 0.050% concentrations in DMEM plus 1.25% ethyl alcohol. RESULTS: Orange oil, eucalyptol, and chloroform were all cytotoxic in comparison to the control group (P < .001). Orange oil showed the least cytotoxicity (P < .001). No significant differences were observed regarding cell viability when comparing the eucalyptol and chloroform groups (P < .05). There were significant differences in the cytotoxicity of eucalyptol and chloroform with an increase in concentration (P < .0001). Nevertheless, this difference was not significant in the orange oil group (P < .05). CONCLUSION: Orange oil was less cytotoxic than eucalyptol and chloroform.

In vitro cytotoxic and non-genotoxic effects of gutta-percha solvents on mouse lymphoma cells by single cell gel (comet) assay.

Chloroform and eucalyptol are widely used in clinical dentistry as gutta-percha solvents. However, these compounds may represent a hazard to human health, especially by causing injury to genetic apparatus and/or inducing cellular death. In this study, the genotoxic and cytotoxic potentials associated with exposure to chloroform and eucalyptol were assessed on mouse lymphoma cells in vitro by the single cell gel (comet) assay and trypan blue exclusion test, respectively. Both gutta-percha solvents proved to be cytotoxic at the same levels in concentrations of 2.5, 5 and 10 microL/mL (p<0.05). On the other hand, neither of the solvents induced DNA breakage. Taken together, these results suggest that although both tested compounds (chloroform and eucalyptol) are strong cytotoxicants, it seems that they are not likely to increase the level of DNA damage on mammalian cells.

In vitro cytotoxic and non-genotoxic effects of gutta-percha solvents on mouse lymphoma cells by single cell gel (comet) assay

Chloroform and eucalyptol are widely used in clinical dentistry as gutta-percha solvents. However, these compounds may represent a hazard to human health, especially by causing injury to genetic apparatus and/or inducing cellular death. In this study, the genotoxic and cytotoxic potentials associated with exposure to chloroform and eucalyptol were assessed on mouse lymphoma cells in vitro by the single cell gel (comet) assay and trypan blue exclusion test, respectively. Both gutta-percha solvents proved to be cytotoxic at the same levels in concentrations of 2.5, 5 and 10 muL/mL (p<0.05). On the other hand, neither of the solvents induced DNA breakage. Taken together, these results suggest that although both tested compounds (chloroform and eucalyptol) are strong cytotoxicants, it seems that they are not likely to increase the level of DNA damage on mammalian cells.

Clorofórmio e eucaliptol são amplamente utilizados na clínica odontológica como solventes de guta-percha. Entretanto, estes compostos podem representar um perigo à saúde humana, especialmente por causar danos ao aparelho genético e/ou induzir morte celular. Neste estudo, o potencial genotóxico e citotóxico associado à exposição ao clorofórmio e eucaliptol foram avaliados em células de linfoma murino in vitro pelo teste de células individualizadas (teste do cometa) e pelo teste do azul de tripan, respectivamente. Ambos os solventes de guta-percha provaram ser citotóxicos nos mesmos níveis em concentrações de 2,5, 5 e 10 miL/mL (p<0.05). Por outro lado, nenhum dos dois solventes induziu danos ao DNA. Em conclusão, esses resultados sugerem que ambos os compostos testados (clorofórmio e eucaliptol) são potentes citotoxinas, mas não representam um fator que aumenta o nível de danos no DNA em células de mamíferos.

Residual toxicity after biodegradation: interactions among benzene, toluene, and chloroform.

A microbial enrichment originating from a pristine aquifer was found to aerobically biodegrade benzene and toluene, but not chloroform. This enrichment culture was used to study changes in pollutant toxicity as affected by biodegradative activity. Two assays for toxicity were used: (1) a 48-h acute toxicity test using the freshwater invertebrate Ceriodaphnia dubia and (2) microbial biodegradation activity as affected by the presence of mixed pollutants. At 20-ppm concentrations, toluene was significantly more toxic (99% mortality) to C. dubia than benzene (48% mortality) or chloroform (40% mortality). Also at 20-ppm concentrations, but before biodegradation, toluene was significantly more toxic (88% mortality) to C. dubia than benzene (33% mortality). After biodegradation of 98% of toluene and benzene, significant residual toxicity still remained in the bacterial supernatant: toluene-degraded supernatant caused 33% mortality in C. dubia and benzene-degraded supernatant caused 24% mortality. In the second toxicity assay, examining the effect of mixed pollutants on biodegradation activity, the presence of benzene slowed the biodegradation of toluene, but chloroform had no effect on either benzene or toluene biodegradation. Results indicate that significant toxicity remain after biodegradation and that halogenated aliphatic hydrocarbons may have little or no effect on aromatic hydrocarbon biodegradation at sites impacted by mixed pollutants.

Hepatite e insuficiência renal induzidas pela inalaçäo de substâncias cloradas ("cheirinho da loló) / Hepatitis and renal insufficiency induced by inhalation of halogenated substances (\"cheirinho da loló\")

Säo apresentados dois casos de pacientes jovens, que desenvolveram insuficiência renal aguda e icterícia por dano hepático, após a inalaçäo de "cheirinho de loló", utilizado como o objetivo de promover euforia. O uso desses preparados caseiros, à base de éter e clorofórmio ou tetracloreto de carbono, esteve, em ambos os casos, associado a uma ingestäo abusiva de bebidas alcoólicas. Uma revisäo bibliográfica é apresentada, sendo sugerido que campanhas educativas acerca dos potenciais malefícios de tais substâncias possam contribuir a uma reduçäo do seu uso

[Inhalation of organic solvents during the last third of pregnancy in Sprague-Dawley rats. Somatometric and cerebellar consequences in newborn animals]. / Inhalación de solventes orgánicos durante el último tercio del embarazo de ratas Sprague-Dawley. Consecuencias somatométricas y cerebelosas en neonatos.

Cerebellar morphogenesis as well as somatometric parameters of progenies from mothers exposed to ethyl-ether, chloroform, turpentine or thinner were registered a 24, 48 and 7 hours of age. 1. Mortality rate of 20 and 59% was observed in progenies of thinner or turpentine exposed mothers, correspondingly. 2. Delay of intrauterine growth manifested by body weight, size and cephalic diameter was evident in chloroform exposed groups (P < 0.01). 3. Cerebellar maturation delay was found in thinner or turpentine prenatally exposed litters. 4. The number of Purkinje cells was significantly reduced in ethyl-ether and chloroform exposed groups (P < 0.01). These cells were found less affected by thinner or turpentine exposure (P < 0.01).

Riscos químicos e toxicológicos de algumas substâncias utilizadas em laboratórios / Chemical and toxicological risks of some substances used in the laboratory

A segurança em laboratório se fundamenta no conhecimento das caracteristícas físico-químicas, na toxicocinética e/ou principais açöes e efeitos tóxicos das substâncias mais comumente utilizadas, como diversos solventes orgânicos, o ácido sulfúrico, a amônia e o hidróxido de sódio. É importante também, conhecer-se quais säo os riscos e os cuidados que se deve tomar no armazenamento e manuseio destes materiais e as medidas de primeiros socorros nos casos de exposiçäo excessiva.