Investigation of occupational risk factors for the development of non-Hodgkin's lymphoma in adults: A hospital-based case-control study.

Non-Hodgkin's Lymphoma (NHL) is a malignancy of the lymphoid lineage of the hematopoietic system has worldwide, especially in developed countries. Better diagnostic and recording techniques, longer life expectancy, and greater exposure to risk factors are hypotheses for this growing incidence curve. Occupational exposures to chemical, biological, and physical agents have also been associated with NHL development, but the results are still controversial. We have investigated the occupational and lifestyle case-control study design with 214 adult patients and 452 population controls. Socio-demographic, clinical, and occupational exposure data were obtained through individual interviews with a standardized questionnaire. Clinical, laboratory, and histopathological data were obtained through medical records. Risk of NHL (any subtype), B-cell lymphoma, DLBCL, Follicular lymphoma and T-cell lymphoma was elevated among the those who had ever been exposed to any solvents, hydrocarbon solvents, pesticides, meat and meat products, and sunlight and tended to increase by years of exposure. A significant upward trend with years of exposure was detected for any solvents and hydrocarbon solvents (NHL (any subtype) p-value for trend<0.001), B-cell lymphoma (p-value for trend<0.001), and T-cell lymphoma (p-value for trend<0.023), pesticides (NHL (any subtype), p for trend<0.001) and T-cell lymphoma (p for trend<0.002), meat and meat products (NHL (any subtype) (p for trend<0.001) and DLBCL (p for trend<0.001), and sunlight (B-cell lymphoma (p for trend<0.001). The results of this study agree line with other international studies, can be extrapolated to other countries that have the same socio-demographic and occupational characteristics as Brazil and support strategies for surveillance and control of work-related cancer.

Hematological Changes in Gas Station Workers.

(1) Background: Benzene, toluene, and xylene isomers (BTX) are present in gasoline. Exposure to benzene may lead to the appearance of a series of signs, symptoms, and complications, which are characterized by benzene poisoning, which is an occupational disease. This study evaluated the presence of signs and symptoms related to occupational exposure and whether occupational exposure to BTX is associated with the development of hematological changes. (2) Material and Methods: This cross-sectional epidemiological study included 542 participants, in which 324 were gas station workers (GSWs) and 218 were office workers (OWs) with no occupational exposure to benzene. To characterize the type of exposure (exposed and not exposed), trans,trans-Muconic acid (tt-MA), Hippuric acid (HA), and Methylhippuric acid (MHA) were used as exposure biomarkers. The tt-MA analysis revealed that the GSWs had 0.29 mg/g of urinary creatinine and the OWs had 0.13 mg/g of urinary creatinine. For HA, the GSWs presented 0.49 g/g of creatinine while the OWs presented 0.07. MHA analysis revealed that the GSWs had 1.57 g/g creatinine and the OWs had 0.01 g/g creatinine. Occupation habits and clinical symptoms were collected by questionnaire and blood samples were analyzed for hematological parameters. The persistence of hematological changes was evaluated with three serial blood collections every 15 days followed by laboratory hematological analysis. A descriptive analysis by the Chi-square test method was performed to evaluate the association between occupational exposure to fuels and the occurrence of changes in hematological parameters. (3) Results: In the GSWs, the most described signs and symptoms were somnolence (45.1%), headache (38.3%), dizziness (27.5%), tingling (25.4%), and involuntary movement (25%). Twenty GSWs that presented hematological alterations performed serial collections fifteen days apart. In addition, these workers presented total leukocyte counts above the upper limit and lymphocyte counts close to the lower limit. Leukocytosis and lymphopenia are hematological alterations present in chronic benzene poisoning. (4) Conclusions: The results found an initial change in different hematological parameters routinely used in clinics to evaluate health conditions. These findings reveal the importance of valuing clinical changes, even in the absence of disease, during the health monitoring of gas station workers and other groups that share the same space.

Brazilian workers occupationally exposed to different toxic agents: A systematic review on DNA damage.

The evaluation of genotoxicity in workers exposed to different toxic agents is very important, especially considering the association between these exposures in a chronic context and DNA damage. Assessing biomarkers of exposure and, when possible, early biomarkers of effect, contributes to elucidating the potential toxic mechanisms involved in genotoxicity and its contribution to chronic non-communicable diseases. In Brazil, the biggest country in South America, workers are exposed to hazardous physical and chemical agents. Considering that these exposures occur, in most cases, throughout the worker's whole life, this is an important public health concern in Brazil. Therefore, this systematic review aims to analyze occupational exposure to chemical and physical agents and the association with DNA damage in studies carried out in Brazil from 1980 to 2021. A systematic and comprehensive literature search was performed in different databases based on occupational exposure to chemical and physical agents and DNA damage. Only full articles on studies that investigated experimental evidence on occupational exposure in Brazil and assessed DNA damage were included, amounting to 89 articles. Five main occupational exposure groups were identified: pesticides (36%), organic solvents (20%), dust and particles (16%), metals (11%), and ionizing radiation (6%). Another group called "others" included studies (11%) that did not fall into these main groups. It was found that comet assay and micronucleus tests are the most adopted methods to detect DNA damage. Occupational exposures were most associated with DNA damage. However, further improvements in study design would be needed to better characterize the association between biomonitoring and DNA damage, particularly to account for confounding factors.

Toxicologia crítica aplicada aos agrotóxicos - perspectivas em defesa da vida / Critical toxicology applied to pesticides - perspectives in the defense for life

RESUMO A toxicologia é aplicada aos processos regulatórios tendo como base central a linearidade das relações entre a dose e o efeito e a possibilidade de estabelecer condições de exposição seguras. Isso ocorre apesar das limitações apontadas pela literatura cientifica. A concepção, a definição das metodologias e a condução da avaliação de risco dos agrotóxicos acabam por atender aos interesses econômicos e à definição de cenários de segurança distantes da realidade. As limitações metodológicas dos estudos exigidos para fins de registro de um agrotóxico envolvem: a desconsideração das interações entre as misturas utilizadas; a não previsão de curvas dose-resposta não lineares (horméticas); a compartimentalização dos desfechos analisados; a exposição nos períodos críticos do desenvolvimento; e a desconsideração do contexto, das diversidades individuais, coletivas e dos territórios expostos aos agrotóxicos, entre outros aspectos discutido nesse ensaio. A toxicologia crítica propõe que a avaliação toxicológica parta da integralidade do problema no contexto apresentando propostas que podem ser adotadas nos processos de regulação de agrotóxicos e outras substâncias potencialmente perigosas.

ABSTRACT Toxicology is applied to regulatory processes based on the linear basis of the relationship between dose and effect and the possibility of establishing safe exposure conditions. This occurs despite the limitations pointed out by the scientific literature. The conception, definition of methodologies, and the conduct of risk assessment of pesticides ends up meeting economic interests and the definition of security scenarios that are far from reality. The methodological limitations of the studies required for the purpose of registering a pesticide involve: disregarding the interactions between the mixtures used; the failure to predict non-linear dose-response curves (hormetical); compartmentalization of the analyzed outcomes; exposure in critical periods of development; and disregarding of the context, individual and collective diversity and the territories exposed to pesticides, among other aspects discussed in this essay. Critical toxicology proposes that the toxicological assessment should start from the integrality of the problem in the context, presenting proposals that can be adopted in the regulation processes of pesticides and other potentially dangerous substances.

Exposição a agrotóxicos e desenvolvimento de câncer no contexto da saúde coletiva: o papel da agroecologia como suporte às políticas públicas de prevenção do câncer / Exposure to pesticides and cancer development in the context of public health: the role of agroecology as a support for public cancer prevention policies

RESUMO Atualmente, a agricultura brasileira é caracterizada pelo crescente consumo de agrotóxicos e fertilizantes químicos, inserindo-se no modelo de produção baseado nos fundamentos do agronegócio. As novas técnicas de cultivo baseadas no agronegócio resultaram na expansão das monoculturas sobre os ecossistemas naturais, com o consequente desmatamento, desequilíbrio e perda da biodiversidade; e o aumento da contaminação do solo, da água e do ar pelos agrotóxicos. No que tange à saúde humana, a literatura científica tem demonstrado que a contaminação química decorrente do uso de agrotóxicos na agricultura implica adoecimento dos trabalhadores rurais expostos ocupacionalmente aos agrotóxicos, dos moradores da área rural, além de consumidores de alimentos contendo resíduos de agrotóxicos. Entre os efeitos sobre a saúde humana associados à exposição a agrotóxicos, os mais preocupantes são as intoxicações crônicas, caracterizadas por infertilidade, abortos, malformações congênitas, neurotoxicidade, desregulação hormonal, imunotoxicidade, genotoxicidade e câncer. Sendo assim, neste ensaio, apresenta-se uma revisão narrativa com dados presentes na literatura científica nacional e internacional referentes à associação entre a exposição a agrotóxicos e o desenvolvimento de câncer no contexto da saúde coletiva e o papel da alimentação saudável e da agroecologia como suporte às políticas públicas de prevenção do câncer.

ABSTRACT Currently, Brazilian agriculture is characterized by the growing consumption of pesticides and chemical fertilizers, forming part of the production model based on the fundamentals of agribusiness. The new farming techniques based on agribusiness resulted in the expansion of monocultures over natural ecosystems, with the consequent deforestation, imbalance, and loss of biodiversity; and the increased contamination of soil, water, and air by pesticides. With regard to human health, the scientific literature has shown that chemical contamination resulting from the use of pesticides in agriculture implies the illness of rural workers occupationally exposed to pesticides, of rural residents, in addition to consumers of food containing pesticide residues. Among the effects on human health associated with exposure to pesticides, the most worrying are chronic intoxications, characterized by infertility, abortions, congenital malformations, neurotoxicity, hormonal dysregulation, immunotoxicity, genotoxicity, and cancer. Therefore, in this essay, we will present a narrative review with data from national and international scientific literature regarding the association between exposure to pesticides and the development of cancer in the context of public health and the role of healthy eating and agroecology as a support for public cancer prevention policies.

Risks related to the domestic laundering of filling station attendant uniforms: advances and uncertainties.

Gasoline is the most common transportation fuel in Brazil, with up to 1% of benzene. Benzene is a health-damaging organic solvent that is extensively used worldwide, being classified as a human carcinogen by the International Agency for Research on Cancer (Group 1). Many workers at filling stations are exposed to benzene, present in gasoline. The main routes of exposure and absorption of benzene are inhalation, oral, and dermal routes. The penetration and maintenance of benzene and other chemicals on personal protective equipment and clothing of workers who manipulate these solvents may increase their levels of exposure and offer risks to their family members, since contaminated clothing is laundered at their homes, which goes against legislative framework (Annex 2, Regulatory Standard No. 9). This way, the objective of this work was to discuss the importance of periodic changes and cleaning of filling station attendant uniforms performed by employers as preventive measures against the deterioration of the health of workers and their family members. We performed a narrative review; no systematic criteria were used in the search for national and international studies. After critical reading, we observed a lack of consistent data on this theme. Laundering of uniforms worn by filling station attendants should take place outside the domestic environment in order to protect the health of workers and their family members and avoid possible cross-contamination.

Evaluation of Exposure to Toluene and Xylene in Gasoline Station Workers.

The main volatile organic compounds found at gasoline stations are benzene, toluene, ethylbenzene, and xylene isomers (BTEX). They cause several harmful effects on human health. Regulatory Norm 7 (1978) provides that, in Brazil, biological monitoring of toluene and xylene is carried out by measuring the urinary metabolites hippuric acid (HA) and methylhippuric acid (MHA), respectively. The objective of this study was to assess the exposure to toluene and xylene and to identify related signs and symptoms in gasoline station workers. A cross-sectional epidemiological study was conducted with workers occupationally exposed to fuels. These gasoline station workers were divided into two groups: 94 workers exposed mainly by inhalation (convenience store workers (CSWs)) and 181 workers exposed by inhalation and dermal route (filling station attendants (FSAs)). A comparison group was formed by 119 workers not occupationally exposed to fuels (office workers (OWs)). Workers exposed to fuels had higher average levels of these exposure biomarkers (HA and MHA), which were also higher in convenience store workers than in filling station attendants. In addition, individuals exposed to the solvents present in gasoline had altered mood/depression, cramps, dizziness, drowsiness, headaches, irritability/nervousness, weakness, weight loss, and other symptoms more frequently and had higher urinary levels of HA and MHA compared to the comparison group. Gasoline station workers showed high levels of HA and MHA, reflecting high occupational exposure to the solvents toluene and xylene present in gasoline, demonstrating that changes in the current legislation and in the work environment are necessary to ensure better health protection for these workers.

International regulatory situation of pesticides authorized for use in Brazil: potential for damage to health and environmental impacts. / Situação regulatória internacional de agrotóxicos com uso autorizado no Brasil: potencial de danos sobre a saúde e impactos ambientais.

The Brazilian legislation does not provide for a periodic review of the registration of pesticides and, even nowadays, products banned in other countries are still used. Based on the pesticide active substances registered in the country, the present study investigated the international regulatory situation in the following member countries: Organization for Economic Co-operation and Development (OECD), European Community, and the BRICS (Brazil, Russia, India, China, and South Africa). Moreover, we sought to relate the main chronic effects to human health and the environment of the most commercialized pesticide active substances in Brazil in lists of classification of carcinogenic potential (US Environmental Protection Agency - USEPA and International Agency for Research on Cancer - IARC), endocrine disruption, and candidates for substitution, both from the European Community. A total of 399 pesticide active substances registered in Brazil for agricultural use were identified, excluding microbiological and biological control agents. Of these, the percentage of unauthorized pesticide active substances according to countries is as follows: 85.7% in Iceland; 84.7% in Norway; 54.5% in Switzerland; 52.6% in India; 45.6% in Turkey; 44.4% in Israel; 43.4% in New Zealand; 42.4% in Japan; 41.5% in the European Community; 39.6% in Canada; 38.6% in China; 35.8% in Chile; 31.6% in Mexico; 28.6% in Australia; and 25.6% in the United States. 120 pesticide active substances were related to damage to health and the environment. Considering the pesticide active substances for which commercialization data are available in the country, 67.2% of this volume is associated with at least one serious chronic damage assessed in this study. The results of the present study indicate the need for promoting transparency of international databases, regarding the motivations of the respective regulatory decisions and the Brazilian regulatory bodies to reevaluate the registration of obsolete products and to strengthen public policies related to the reduction of the use of pesticides.

A legislação brasileira não prevê revisão periódica do registro dos agrotóxicos e, ainda hoje, são utilizados produtos proibidos em outros países. Partindo dos ingredientes ativos de agrotóxicos registrados no país, o presente estudo investigou a situação regulatória internacional nos países-membros da Organização para a Cooperação e Desenvolvimento Econômico (OCDE), da Comunidade Europeia e BRICS. Também se buscou relacionar os principais efeitos crônicos à saúde humana e ao meio ambiente dos ingredientes ativos de agrotóxicos mais comercializados no Brasil, em listas de classificação de potencial cancerígeno (Agência de Proteção Ambiental dos Estados Unidos - USEPA e Agência Internacional de Pesquisa em Câncer - IARC), desregulação endócrina e candidatos para substituição (estes dois últimos da Comunidade Europeia). Foram identificados 399 ingredientes ativos de agrotóxicos registrados no Brasil para uso agrícola, excluindo-se os microbiológicos e agentes biológicos de controle. Destes, não têm autorização 85,7% na Islândia, 84,7% na Noruega, 54,5% na Suíça, 52,6% na Índia, 45,6% na Turquia, 44,4% em Israel, 43,4% na Nova Zelândia, 42,4% no Japão, 41,5% na Comunidade Europeia, 39,6% no Canadá, 38,6% na China, 35,8% no Chile, 31,6% no México, 28,6% na Austrália e 25,6% nos Estados Unidos. Foram relacionados a danos à saúde e ao ambiente 120 ingredientes ativos de agrotóxicos. Considerando os ingredientes ativos de agrotóxicos para os quais estão disponíveis dados de comercialização no país, 67,2% deste volume está associado a pelo menos um dano crônico grave avaliado neste estudo. Os resultados do presente estudo indicam a necessidade de promover a transparência das bases de dados internacionais, no que tange às motivações para as respectivas decisões regulatórias e os órgãos reguladores brasileiros reavaliarem o registro de produtos obsoletos, fortalecendo políticas públicas relacionadas à redução do uso de agrotóxicos.

La legislación brasileña no prevé una revisión periódica del registro de los pesticidas e incluso hoy se utilizan productos prohibidos en otros países. Partiendo de los ingredientes activos de pesticidas registrados en el país, el presente estudio investigó la situación regulatoria internacional en los siguientes países-miembros: Organización para la Cooperación y Desarrollo Económico (OCDE), Comunidad Europea, y BRICS. También se buscó relacionar los principales efectos crónicos para la salud humana y en el medio ambiente de los ingredientes activos de pesticidas más comercializados en Brasil en listas de clasificación con potencial cancerígeno (Agencia de Protección Ambiental de Estados Unidos - USEPA e Agencia Internacional de Investigación sobre el Cáncer - IARC), desregulación endocrina y candidatos para sustitución, ambos de la Comunidad Europea. Se identificaron 399 ingredientes activos de pesticidas registrados en Brasil para uso agrícola, excluyéndose los microbiológicos y agentes biológicos de control. De estos, no tienen autorización en Islandia 85,7%, Noruega 84,7%, Suiza 54,5%, India 52,6%, Turquía 45,6%, Israel 44,4%, Nueva Zelanda 43,4%, Japón 42,4%, Comunidad Europea 41,5%, Canadá 39,6%, China 38,6%, Chile 35,8%, México 31,6%, Australia 28,6% y Estados Unidos 25,6%. 120 ingredientes activos de pesticidas estuvieron relacionados con daños en la salud y medioambiente. Considerando los ingredientes activos de pesticidas para los cuales están disponibles datos de comercialización en el país, un 67,2% de este volumen está asociado a por lo menos una enfermedad crónica grave evaluada en ese estudio. Los resultados del presente estudio indican la necesidad de promover la transparencia de las bases de datos internacionales, en lo que respecta a las motivaciones de las respectivas decisiones regulatorias, con el fin de que los órganos reguladores brasileños reevalúen el registro de productos obsoletos, así como para fortalecer políticas públicas relacionadas con la reducción del uso de pesticidas.

Gasoline-station workers in Brazil: Benzene exposure; Genotoxic and immunotoxic effects.

Chronic exposure to benzene is a risk factor for hematological malignancies. Gasoline-station workers are exposed to benzene in gasoline, via both inhalation and dermal contact (attendants and managers) or inhalation (workers in the on-site convenience stores and offices). We have studied the exposure of these workers to benzene and the resulting genotoxic and immunotoxic effects. Levels of urinary trans, trans-muconic acid were higher among gasoline-station workers than among office workers with no known exposure to benzene (comparison group). Among the exposed workers, we observed statistically significant biological effects, including elevated DNA damage (comet assay); higher frequencies of micronuclei and nuclear buds (CBMN assay); lower levels of T-helper lymphocytes and naive Th lymphocytes; lower CD4 / CD8 ratio; and higher levels of NK cells and memory Th lymphocytes. Both groups of exposed workers (inhalation and inhalation + dermal routes) showed similar genotoxic and immunotoxic effects.

Situação regulatória internacional de agrotóxicos com uso autorizado no Brasil: potencial de danos sobre a saúde e impactos ambientais / Situación regulatoria internacional de pesticidas con uso autorizado en Brasil: potencial de daños sobre la salud e impactos ambientales / International regulatory situation of pesticides authorized for use in Brazil: potential for damage to health and environmental impacts

A legislação brasileira não prevê revisão periódica do registro dos agrotóxicos e, ainda hoje, são utilizados produtos proibidos em outros países. Partindo dos ingredientes ativos de agrotóxicos registrados no país, o presente estudo investigou a situação regulatória internacional nos países-membros da Organização para a Cooperação e Desenvolvimento Econômico (OCDE), da Comunidade Europeia e BRICS. Também se buscou relacionar os principais efeitos crônicos à saúde humana e ao meio ambiente dos ingredientes ativos de agrotóxicos mais comercializados no Brasil, em listas de classificação de potencial cancerígeno (Agência de Proteção Ambiental dos Estados Unidos - USEPA e Agência Internacional de Pesquisa em Câncer - IARC), desregulação endócrina e candidatos para substituição (estes dois últimos da Comunidade Europeia). Foram identificados 399 ingredientes ativos de agrotóxicos registrados no Brasil para uso agrícola, excluindo-se os microbiológicos e agentes biológicos de controle. Destes, não têm autorização 85,7% na Islândia, 84,7% na Noruega, 54,5% na Suíça, 52,6% na Índia, 45,6% na Turquia, 44,4% em Israel, 43,4% na Nova Zelândia, 42,4% no Japão, 41,5% na Comunidade Europeia, 39,6% no Canadá, 38,6% na China, 35,8% no Chile, 31,6% no México, 28,6% na Austrália e 25,6% nos Estados Unidos. Foram relacionados a danos à saúde e ao ambiente 120 ingredientes ativos de agrotóxicos. Considerando os ingredientes ativos de agrotóxicos para os quais estão disponíveis dados de comercialização no país, 67,2% deste volume está associado a pelo menos um dano crônico grave avaliado neste estudo. Os resultados do presente estudo indicam a necessidade de promover a transparência das bases de dados internacionais, no que tange às motivações para as respectivas decisões regulatórias e os órgãos reguladores brasileiros reavaliarem o registro de produtos obsoletos, fortalecendo políticas públicas relacionadas à redução do uso de agrotóxicos.

La legislación brasileña no prevé una revisión periódica del registro de los pesticidas e incluso hoy se utilizan productos prohibidos en otros países. Partiendo de los ingredientes activos de pesticidas registrados en el país, el presente estudio investigó la situación regulatoria internacional en los siguientes países-miembros: Organización para la Cooperación y Desarrollo Económico (OCDE), Comunidad Europea, y BRICS. También se buscó relacionar los principales efectos crónicos para la salud humana y en el medio ambiente de los ingredientes activos de pesticidas más comercializados en Brasil en listas de clasificación con potencial cancerígeno (Agencia de Protección Ambiental de Estados Unidos - USEPA e Agencia Internacional de Investigación sobre el Cáncer - IARC), desregulación endocrina y candidatos para sustitución, ambos de la Comunidad Europea. Se identificaron 399 ingredientes activos de pesticidas registrados en Brasil para uso agrícola, excluyéndose los microbiológicos y agentes biológicos de control. De estos, no tienen autorización en Islandia 85,7%, Noruega 84,7%, Suiza 54,5%, India 52,6%, Turquía 45,6%, Israel 44,4%, Nueva Zelanda 43,4%, Japón 42,4%, Comunidad Europea 41,5%, Canadá 39,6%, China 38,6%, Chile 35,8%, México 31,6%, Australia 28,6% y Estados Unidos 25,6%. 120 ingredientes activos de pesticidas estuvieron relacionados con daños en la salud y medioambiente. Considerando los ingredientes activos de pesticidas para los cuales están disponibles datos de comercialización en el país, un 67,2% de este volumen está asociado a por lo menos una enfermedad crónica grave evaluada en ese estudio. Los resultados del presente estudio indican la necesidad de promover la transparencia de las bases de datos internacionales, en lo que respecta a las motivaciones de las respectivas decisiones regulatorias, con el fin de que los órganos reguladores brasileños reevalúen el registro de productos obsoletos, así como para fortalecer políticas públicas relacionadas con la reducción del uso de pesticidas.

The Brazilian legislation does not provide for a periodic review of the registration of pesticides and, even nowadays, products banned in other countries are still used. Based on the pesticide active substances registered in the country, the present study investigated the international regulatory situation in the following member countries: Organization for Economic Co-operation and Development (OECD), European Community, and the BRICS (Brazil, Russia, India, China, and South Africa). Moreover, we sought to relate the main chronic effects to human health and the environment of the most commercialized pesticide active substances in Brazil in lists of classification of carcinogenic potential (US Environmental Protection Agency - USEPA and International Agency for Research on Cancer - IARC), endocrine disruption, and candidates for substitution, both from the European Community. A total of 399 pesticide active substances registered in Brazil for agricultural use were identified, excluding microbiological and biological control agents. Of these, the percentage of unauthorized pesticide active substances according to countries is as follows: 85.7% in Iceland; 84.7% in Norway; 54.5% in Switzerland; 52.6% in India; 45.6% in Turkey; 44.4% in Israel; 43.4% in New Zealand; 42.4% in Japan; 41.5% in the European Community; 39.6% in Canada; 38.6% in China; 35.8% in Chile; 31.6% in Mexico; 28.6% in Australia; and 25.6% in the United States. 120 pesticide active substances were related to damage to health and the environment. Considering the pesticide active substances for which commercialization data are available in the country, 67.2% of this volume is associated with at least one serious chronic damage assessed in this study. The results of the present study indicate the need for promoting transparency of international databases, regarding the motivations of the respective regulatory decisions and the Brazilian regulatory bodies to reevaluate the registration of obsolete products and to strengthen public policies related to the reduction of the use of pesticides.

Occurrence of green tobacco sickness and associated factors in farmers residing in Dom Feliciano Municipality, Rio Grande do Sul State, Southern Region of Brazil.

This study aimed to evaluate the occurrence of the green tobacco sickness (GTS) and its associated factors in tobacco familiar farmers residing in Dom Feliciano, Rio Grande do Sul State, Brazil. A cross-sectional study was conducted evaluating the sickness in 354 small tobacco farmers, between October 2011 and March 2012. The urinary concentration of cotinine, a biomarker of exposure to nicotine, was determined during the tobacco harvest period. Subjects presenting cotinine urinary levels ≥ 50ng/mL, that had contact with tobacco leaves up to 48 hours before the sample collection and reported at least one disease symptom were deemed as cases. A non-conditional logistic analysis was performed to evaluate the association between GTS and the population characteristics. A total of 122 (34.5%) cases were identified, with 39% of them being smokers and 61% being males. The median cotinine urinary concentrations were 75.6ng/mL (74.1ng/mg of creatinine) for non-cases and 755.8ng/mL (632.1ng/mg of creatinine) for the cases (p-value ≤ 0.01). The multivariate analysis showed a positive association between GTS and sunlight exposure time, exposure to pesticides, worse health status, and inverse association with wood cultivation. This study presented a high GTS prevalence and suggest that the use of urinary cotinine is a significant biomarker to determine GTS cases, influencing in the distribution by sex. Once the tobacco production involves health hazards, is important to implement measures to prevent the harm caused to tobacco farmers, as set in articles 17 and 18 of the World Health Organization Framework Convention on Tobacco Control.

Analysis of Benzene Exposure in Gas Station Workers Using Trans,Trans-Muconic Acid.

In Brazil, gas station workers are occupationally exposed to the benzene present in gasoline. Brazilian law indicates the use of trans,trans-muconic acid(t,t-MA) as a biomarker of benzene exposure. The aim of this study was to evaluate the level of exposure to benzene in gas station workers, through the quantification of t,t-MA present in urine. A total number of 269 gas station workers divided into 179 filling station attendants exposed by inhalation and dermal route and 90 convenience store workers exposed only by inhalation were included. A control group was formed by 100 office workers, without occupational exposure to benzene. The urinary levels of t,t-MA were evaluated by HPLC with a UV detector. Gas station workers showed higher mean values of t,t-MA (0.204 mg/g creatinine; 95% CI 0.170-0.237) than office workers (0.126 mg/g creatinine; 95% CI 0.0817-0.1693). T,t-MA levels were higher in convenience store workers exposed to gasoline only by inhalation (0.221 mg/g creatinine; 95% CI 0.160-0.282), than in those exposed to gasoline by inhalation and dermal route-filling station attendants (0.195 mg/g creatinine; 95% CI 0.155-0.235). Gas station workers with a higher level of t,t-MA had epistaxis. T,t-MA values were higher in the Downtown (0.15 mg/g creatinine) region's workers than in the more affluent South Zone region's workers (0.07 mg/g creatinine). Smoking habits influenced the urinary t,t-MA values, while the frequency of consumption of industrialized and frozen foods showed no influence.

Occurrence of green tobacco sickness and associated factors in farmers residing in Dom Feliciano Municipality, Rio Grande do Sul State, Southern Region of Brazil / Ocorrência da doença da folha verde do tabaco e fatores associados entre fumicultores no Município de Dom Feliciano, Rio Grande do Sul, Região Sul do Brasil / Ocurrencia de la enfermedad del tabaco verde y factores asociados en agricultores que residen en el Municipio de Dom Feliciano, Estado de Rio Grande do Sul, Región Sur de Brasil

Abstract: This study aimed to evaluate the occurrence of the green tobacco sickness (GTS) and its associated factors in tobacco familiar farmers residing in Dom Feliciano, Rio Grande do Sul State, Brazil. A cross-sectional study was conducted evaluating the sickness in 354 small tobacco farmers, between October 2011 and March 2012. The urinary concentration of cotinine, a biomarker of exposure to nicotine, was determined during the tobacco harvest period. Subjects presenting cotinine urinary levels ≥ 50ng/mL, that had contact with tobacco leaves up to 48 hours before the sample collection and reported at least one disease symptom were deemed as cases. A non-conditional logistic analysis was performed to evaluate the association between GTS and the population characteristics. A total of 122 (34.5%) cases were identified, with 39% of them being smokers and 61% being males. The median cotinine urinary concentrations were 75.6ng/mL (74.1ng/mg of creatinine) for non-cases and 755.8ng/mL (632.1ng/mg of creatinine) for the cases (p-value ≤ 0.01). The multivariate analysis showed a positive association between GTS and sunlight exposure time, exposure to pesticides, worse health status, and inverse association with wood cultivation. This study presented a high GTS prevalence and suggest that the use of urinary cotinine is a significant biomarker to determine GTS cases, influencing in the distribution by sex. Once the tobacco production involves health hazards, is important to implement measures to prevent the harm caused to tobacco farmers, as set in articles 17 and 18 of the World Health Organization Framework Convention on Tobacco Control.

Resumo: O estudo teve como objetivo avaliar a ocorrência de doença da folha verde (DFV) e fatores associados entre fumicultores familiares no Município de Dom Feliciano, Estado do Rio Grande do Sul, Brasil. Foi realizado um estudo transversal sobre DFV em 354 pequenos produtores de tabaco, entre outubro de 2011 e março de 2012. Foi medida a concentração urinária da cotinina, um biomarcador da exposição à nicotina, durante a temporada de colheita do tabaco. Os casos de DFV foram definidos como indivíduos com níveis urinários de cotinina ≥ 50ng/mL, que tiveram contato com folhas de tabaco em até 48 horas antes da coleta da amostra sanguínea e que relatavam pelo menos um sintoma da doença. Foi realizada uma análise logística não condicional para avaliar a associação entre DFV e as características da população. Foram identificados um total de 122 (34,5%) casos da doença, entre os quais 39% eram fumantes e 61% eram do sexo masculino. As concentrações urinárias medianas de cotinina foram 75,6ng/mL (74,1ng/mg de creatinina) para não-casos e 755,8ng/mL (632,1ng/mg de creatinina) para os casos (valor de p ≤ 0,01). A análise multivariada mostrou uma associação positiva entre DFV e tempo de exposição à luz solar, exposição a pesticidas e pior estado de saúde geral, e uma associação inversa com cultivo de lenha. O estudo identificou alta prevalência de DFV e sugere o uso da cotinina como biomarcador significativo para identificar os casos de DFV, influenciando a distribuição por sexo. Uma vez que a fumicultura envolve danos à saúde, é importante implementar medidas para prevenir os impactos para os fumicultores, de acordo com os artigos 17 e 18 da Convenção-Quadro para o Controle do Tabaco da Organização Mundial da Saúde.

Resumen: Este estudio visó evaluar la ocurrencia de la enfermedad del tabaco verde (GTS por sus siglas en inglés) y sus factores asociados en pequeños agricultores de tabaco, que residen en Dom Feliciano, Rio Grande do Sul, Brasil. Se realizó un estudio transversal, evaluando la enfermedad del tabaco verde, en 354 pequeños agricultores de tabaco, entre octubre de 2011 y marzo 2012. La concentración urinaria de cotinina, un biomarcador de la exposición a la nicotina, se determinó durante el periodo de cosecha del tabaco. Los individuos que presentan niveles de cotinina urinarios ≥ 50ng/mL, que tuvieron contacto con hojas de tabaco hasta 48 horas antes de la recogida de la muestra, e informaron de al menos un síntoma de la enfermedad, fueron considerados casos. Se realizó un análisis logístico no condicional para evaluar la asociación entre GTS y las características de la población. Se identificaron un total de 122 (34,5%) casos, siendo un 39% de ellos fumadores y un 61% hombres. Las concentraciones medias de cotinina urinaria fueron 75,6ng/mL (74,1ng/mg de creatinina) para los no casos y 755,8ng/mL (632,1ng/mg de creatinina) para los casos (valor de p ≤ 0,01). El análisis multivariado mostró una asociación positiva entre el GTS y las horas de exposición a la luz solar, exposición a los pesticidas, un estatus peor de salud, y la asociación inversa con la cultura maderera. Este estudio presentó una alta prevalencia de GTS y sugiere que el uso de la cotinina urinaria es un biomarcador significativo para identificar casos de GTS, influenciando en la distribución por sexo. Debido a que la producción de tabaco implica perjuicios para la salud, es importante implementar medidas para prevenirlos en los agricultores del tabaco, como está estipulado en los artículos 17 y 18 del Convenio Marco para el Control del Tabaco de la Organización Mundial de la Salud.

Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis.

In this study, we investigated the expression and activity of liver cytochrome P450s (CYPs) and praziquantel (PZQ) kinetics in mice infected with Schistosoma mansoni. Swiss Webster (SW) mice of both genders were infected (100 cercariae) on postnatal day 10 and killed on post-infection days (PIDs) 30 or 55. Non-infected mice of the same age and sex served as controls. Regardless of mouse sex, infection depressed the activities of CYP1A [ethoxy/methoxy-resorufin-O-dealkylases (EROD/MROD)], 2B9/10 [pentoxy/benzyloxy-resorufin-O-dealkylases (PROD, BROD)], 2E1 [p-nitrophenol-hydroxylase (PNPH)] and 3A11 [erythromycin N-demethylase (END)] on PID 55 but not on PID 30. On PID 55, infection decreased liver CYP mRNA levels (real-time reverse transcription-polymerase chain reaction). On PID 30, whereas mRNA levels remained unaltered in males, they were depressed in females. Plasma PZQ (200 and 400 mg/kg body weight intraperitoneally) levels were measured (high-performance liquid chromatography) at different post-treatment intervals. In males and females, infection delayed the PZQ clearance on PID 55, but not on PID 30. Therefore, it can be concluded that schistosomiasis down-modulated CYP expression and activity and delayed PZQ clearance on PID 55, when a great number of parasite eggs were lodged in the liver. On PID 30, when egg-laying was initiated by the worms, no change of CYP expression and activity was found, except for a depression of CYP1A2 and 3A11 mRNAs in female mice.

Modulation of expression and activity of cytochrome P450s and alteration of praziquantel kinetics during murine schistosomiasis

In this study, we investigated the expression and activity of liver cytochrome P450s (CYPs) and praziquantel (PZQ) kinetics in mice infected with Schistosoma mansoni. Swiss Webster (SW) mice of both genders were infected (100 cercariae) on postnatal day 10 and killed on post-infection days (PIDs) 30 or 55. Non-infected mice of the same age and sex served as controls. Regardless of mouse sex, infection depressed the activities of CYP1A [ethoxy/methoxy-resorufin-O-dealkylases (EROD/MROD)], 2B9/10 [pentoxy/benzyloxy-resorufin-O-dealkylases (PROD, BROD)], 2E1 [p-nitrophenol-hydroxylase (PNPH)] and 3A11 [erythromycin N-demethylase (END)] on PID 55 but not on PID 30. On PID 55, infection decreased liver CYP mRNA levels (real-time reverse transcription-polymerase chain reaction). On PID 30, whereas mRNA levels remained unaltered in males, they were depressed in females. Plasma PZQ (200 and 400 mg/kg body weight intraperitoneally) levels were measured (high-performance liquid chromatography) at different post-treatment intervals. In males and females, infection delayed the PZQ clearance on PID 55, but not on PID 30. Therefore, it can be concluded that schistosomiasis down-modulated CYP expression and activity and delayed PZQ clearance on PID 55, when a great number of parasite eggs were lodged in the liver. On PID 30, when egg-laying was initiated by the worms, no change of CYP expression and activity was found, except for a depression of CYP1A2 and 3A11 mRNAs in female mice.

Postnatal development and fertility of offspring from mice exposed to triphenyltin (fentin) hydroxide during pregnancy and lactation.

Fentin or triphenylthin (TPT) is an organotin compound (OTC) widely used as an agricultural fungicide and miticide. It is well known that TPT exerts adverse effects on the reproductive and immune systems and may disrupt the endocrine system, raising concerns regarding the risks posed by exposure to this metal on environmental and human health. In this study the effects of maternal exposure to TPT at doses of control (0), 1.875, 3.75, or 7.5 mg/kg body weight/d, po, were examined during gestation and lactation on offspring growth, organ weights, and fertility. Except for a significant liver enlargement at the highest dose, TPT produced no maternal toxicity. Increased neonatal mortality (death of 3 entire litters from a total of 18 treated litters) was noted at 7.5 mg/kg. Pup body weight at birth was significantly reduced at all dose levels, but no marked weight loss was found on postnatal day (PND) 5 and thereafter. Offspring maturation (ear unfolding, incisor eruption, vagina opening, and testes descent) and fertility in adulthood were not significantly affected by maternal exposure to TPT. In conclusion, data provided by this study indicate that maternal treatment with TPT during pregnancy and lactation delayed prenatal growth but did not impair postnatal development and fertility in exposed offspring in adulthood.

Postnatal development and resistance to Plasmodium yoelii infection of mice prenatally exposed to triphenyltin hydroxide.

In this study, we evaluated the effects of prenatal exposure to triphenyltin hydroxide (TPTH) on the postnatal development of Swiss Webster mice. Females were treated by gavage (0, 7.5 15 and 30 mg TPTH/kg/day) on days 6-17 of gestation. After birth, the progeny was examined for deaths, body weight gain and appearance of developmental landmarks. On postnatal day 50, one male and one female of each litter were inoculated with Plasmodium yoelii and the time-course of infection was monitored. TPTH was embryolethal at doses > or =15 mg/kg/day. Body weight at birth was decreased, but no alteration of pup body weight was observed after postnatal day 5. Except for an advancement of incisor eruption in the group treated with 15 mg/kg/day, no alteration of somatic development was noted. A shorter latency to peak parasitemia and a reduced malaria-induced spleen enlargement were observed in mice prenatally exposed to TPTH. In conclusion, prenatal exposure to TPTH at doses > or =15 mg/kg enhanced neonatal lethality, reduced pup birth weight and interfered with the response to infection with P. yoelii in adulthood.

Developmental toxicity of triphenyltin hydroxide in mice.

Triphenyltin-hydroxide (TPTH) is used as agricultural fungicide in Brazil and elsewhere. This study was undertaken to evaluate the developmental toxicity of TPTH in mice. Swiss Webster mice were treated by gavage with TPTH (0, 3.75, 7.5, 15 and 30 mg/kg bw/day) on gestation days (GD) 6-17. Caesarean sections were performed on GD 18, and implantations, resorptions and live and dead fetuses were counted. Half of each litter was fixed and examined for visceral anomalies while the remaining fetuses were cleared and stained with Alizarin Red S for skeleton evaluation. A reduced pregnancy weight gain (after subtraction of uterine weights), smaller thymus, spleen and liver, and deaths indicated that doses > or = 7.5mg/kg body wt/day were toxic to mothers. At the two highest doses, TPTH enhanced embryolethality and reduced fetal body weight. The incidence of cleft palate (not seen in controls) was augmented (36.8%) at the highest dose of TPTH, while palatine bone defects were increased at the lowest dose (3.75 mg/kg bw/day). Soft-tissue anomalies, such as misshapened thymus, and malpositioned testes and uteri, were more frequent at doses of TPTH > or = 7.5 mg/kg bw/day. TPTH also caused a dose-related increase of fetal skeleton variations (e.g. poorly ossified skull bones) and malformations (misshapened Axis and skull bones). In conclusion, TPTH was toxic to the embryos (NOAEL <3.75 mg/kg bw/day) at doses that were not overtly toxic to their mothers.

Avaliação da toxicidade pré-natal do trifenil hidróxido de estanho (TPTH) em camundongos / Evaluation of the prenatal toxicology of the terphenil tin hidroxides (TPTH) in mice

O grupo de compostos organoestanhosos inclui uma variedade de químicos amplamente empregados na agricultura e na indústria em geral. Os triorganoestanhosos são biologicamente mais ativos e são largamente usados como biocidas. Compostos trifenil de estanho em adição com compostos tributil de estnho são usados como algicidas, moluscicidas e como preservativo da madeira. O objetivo deste estudo foi avaliar o potencial embriofeto-tóxico do trifenil hidróxido de estanho (TPTH) em camundongos. Camundongos Swiss Webster (FIOCRUZ) foram acasalados, sendo considerado dia ´0` de gravidez as 24 horas que se seguiram à confirmação do cruzamento pela presença do plug vaginal. As fêmeas grávidas foram tratadas com doses de 0; 3,75; 7,5; 15 e 30 mg TPTH/kg de peso corpóreo/dia por entubação gástrica nos dias 6-17 de gravidez. O grupo controle recebeu apenas o veículo (óleo de milho). No dia 18, as fêmeas foram submetidas à cesariana sendo registrado o número de fetos vivos, mortos e reabsorções. Os fetos foram pesados, sendo ½ de cada ninhada fixada em Bouin para análise de vísceras e a ½ restante diafanizada e corada (alizarina red S) para avaliação de esqueleto. Morreram 01 mãe tratada com 3,75 mg/kg, 01 com 15mg/kg e 02 com 30mg/kg. Drástica redução de peso materno foi notada a partir de 15mg/kg, mas a análise do ganho de peso durante todo o período de gravidez (dia 0-18), descontado o peso do útero, indicou que o TPTH causou consistentemente toxicidade materna a partir de 7,5mg/kg. Um aumento de reabsorções foi notado nas doses de 15 e 30mg TPTH/kg. Não houve alteração do número de sítios de implantação. A partir de 15mg/kg, o TPTH causou evidente redução do peso corpóreo fetal. Sinais de malformações viscerais, tais como alterações de timo, testículos e útero, foram evidentes a partir de 7,5mg/kg. Sinais de retardo de ossificação (pobremente calcificado, osso não calcificado e esponjoso) e uma alta incidência de malformações de esqueleto foram observadas a partir da dose de 3,75 mg TPTH/kg. Estes achados indicam que o TPTH foi tóxico para a mãe a partir da dose de 7,5mg/kg e embriofeto-tóxico a partir da dose 3,75 mg TPTH/kg; apontando para uma certa seletividade dos efeitos adversos sobre o desenvolvimento embriofetal.