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Regulation of the Synthetic Estrogen 17Α-Ethinylestradiol in Water Bodies in Europe, the United States, and Brazil

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Regulation of the Synthetic Estrogen 17Α-Ethinylestradiol in Water Bodies in Europe, the United States, and Brazil REVISÃO REVIEW 1 Regulamentação do estrogênio sintético 17α-etinilestradiol em matrizes aquáticas na Europa, Estados Unidos e Brasil Regulation of the synthetic estrogen 17α-ethinylestradiol in water bodies in Europe, the United States, and Brazil Regulación del estrógeno sintético Danieli Lima da Cunha 1,2 Samuel Muylaert Camargo da Silva 2 17α-etinilestradiol en matrices acuáticas Daniele Maia Bila 3 en Europa, Estados Unidos y Brasil Jaime Lopes da Mota Oliveira 1 Paula de Novaes Sarcinelli 1 Ariane Leites Larentis 1 Resumo O estrogênio sintético 17α-etinilestradiol, principal componente utilizado 1 Fundação Oswaldo Cruz, Correspondência Rio de Janeiro, Brasil. D. L. Cunha em formulações de contraceptivos orais, tem sido apontado como um dos 2 Universidade Federal Rua General Andrade Neves principais compostos responsáveis por provocar efeitos adversos no sis- Fluminense, Niterói, Brasil. 2, apto. 202, Niterói, RJ 3 Universidade do Estado do 24210-000, Brasil. tema endócrino de várias espécies. O objetivo deste estudo foi analisar o Rio de Janeiro, Rio de Janeiro, [email protected] estado da arte dos dispositivos legais e normativos referentes ao controle Brasil. desse estrogênio sintético nas águas da Europa e dos Estados Unidos, e tra- çar um paralelo com a realidade brasileira. No geral, os países têm busca- do ampliar a regulamentação e monitoramento de alguns micropoluentes emergentes que antes não eram objeto de atenção por parte dos disposi- tivos legais. A Europa está mais avançada no que tange à qualidade dos corpos hídricos, enquanto que nos Estados Unidos esta substância é alvo de regulamentação apenas para a água destinada ao consumo humano. No Brasil, ainda não há nenhum dispositivo legal ou normativo que aborde esse estrogênio, o que pode ser associado a uma baixa maturidade do siste- ma brasileiro quanto ao controle de poluentes hídricos. Disruptores Endócrinos; Etinilestradiol; Critérios de Qualidade da Água http://dx.doi.org/10.1590/0102-311X00056715 Cad. Saúde Pública, Rio de Janeiro, 32(3):e00056715, mar, 2016 2 Cunha DL et al. Introdução encontradas apenas em fêmeas 11,12,13,14. Para esses ovíparos, uma das principais funções dos Nas últimas décadas, um dos temas de grande estrogênios é a produção desses marcadores du- relevância na área ambiental é a questão dos mi- rante a ovogênese 15,16,17. Logo, os micropoluen- cropoluentes emergentes, compostos orgânicos tes estrogênicos podem aumentar a expressão e inorgânicos que mesmo em baixas concentra- dessas proteínas sexuais. ções (da ordem de μg.L-1 e ng.L-1) apresentam ris- Com relação aos seres humanos, ainda não co potencial para a saúde humana e para o meio existem estudos que comprovem os efeitos do ambiente, englobando uma grande diversidade 17α-etinilestradiol sobre a saúde humana pe- de compostos químicos naturais ou sintéticos, las exposições ambientais 18,19, o que em parte nos quais se incluem fármacos, produtos de higie- pode ser atribuído à acentuada dificuldade em ne pessoal, hormônios, surfactantes, retardado- demonstrar relação de causalidade quando se res de chama, agrotóxicos e nanopartículas 1,2,3. aborda o processo de desregulação endócrina 20. Dentre esses micropoluentes chama atenção um Dessa forma, tratando-se de um desregulador grupo, conhecido como desreguladores endó- endócrino, que tem a capacidade de promover crinos, que inclui substâncias exógenas que têm profundas alterações fisiológicas com apenas a capacidade de alterar as funções do sistema uma dose “gatilho”, é possível formular a hipó- endócrino, provocando assim efeitos adversos à tese de que uma vez presente na água ingerida saúde humana e de outros animais 3,4,5,6. pelo homem, mesmo em baixas concentrações, Dos vários micropoluentes classificados este hormônio pode desencadear efeitos adver- como desreguladores endócrinos, o estrogênio sos sobre alguns indivíduos. sintético 17α-etinilestradiol, principal compo- Basicamente, a introdução do 17α-etinilestra- nente estrogênico utilizado em formulações de diol no meio hídrico se dá por duas principais contraceptivos orais e um dos medicamentos vias: pela excreção e pelo descarte. Uma vez mais consumido no mundo, tem gerado grande consumido, esse estrogênio é excretado por preocupação no meio acadêmico, uma vez que meio da urina e fezes, na sua forma conjugada tem sido apontado como o principal composto (sulfatos e glicuronídeos) 21,22. Esses, são lança- responsável por provocar alterações endócrinas dos nos esgotos, que posteriormente vão para nos organismos aquáticos. ambientes aquáticos in natura ou na forma de Como consequência dessa desestabilização efluentes tratados em estações de tratamento de do sistema endócrino, podem ser observadas esgotos 23,24,25. Vale destacar que as tecnologias alterações bioquímicas e histopatológicas (fíga- convencionais de tratamento de esgotos apre- do, gônadas e rins), modificações no processo sentam limitações na remoção desse estrogê- reprodutivo e no desenvolvimento, mudanças nio 26,27,28,29,30,31. Tal situação é agravada já que comportamentais, entre outras. A Tabela 1 apre- o 17α-etinilestradiol apresenta-se como o mais senta uma compilação de estudos dos últimos persistente dos estrogénios, com um tempo de 15 anos que abordaram os efeitos decorrentes meia-vida em água de aproximadamente 17 dias da exposição ao 17α-etinilestradiol em várias es- e uma baixa taxa de fotodegradação 32,33. pécies em diferentes fases da vida. Dentre tais Uma vez que a poluição das águas representa efeitos adversos, o mais alarmante é o processo uma ameaça aos ambientes aquáticos, com di- de feminização – desenvolvimento de caracte- versos efeitos negativos às espécies que habitam rísticas sexuais femininas, incluindo anatomia os corpos hídricos ou que ingerem a água pro- reprodutiva feminina 7. Tal processo acaba por veniente dos mesmos (inclui-se o ser humano), comprometer o ciclo reprodutivo da população uma série de dispositivos legais e normativos afetada, podendo desencadear desequilíbrio ao tem sido criada em alguns países para estabele- ecossistema no qual esta se insere. cer limites às concentrações desses poluentes em Os peixes, por sua inerente importância eco- matrizes aquáticas. lógica e econômica, estão entre os organismos Para se discutir a legislação referente ao mais investigados. Esses organismos atuam co- 17α-etinilestradiol, é pertinente apresentar que mo importantes indicadores de potenciais efei- há dois tipos de normas que se aplicam ao tema tos de desregulação endócrina, principalmente água, a saber: aquelas que têm como foco os cri- aqueles ligados à fisiologia reprodutiva, pois seu térios de qualidade da água recomendados para sistema reprodutivo é regulado por estrogênios a proteção da vida aquática, e outras que visam à similares aos dos mamíferos 8,9,10. proteção da saúde dos seres humanos que inge- Os efeitos em peixes, anfíbios e pássaros têm rem a mesma. Nesse contexto, o presente estudo sido também avaliados pela presença de biomar- objetiva analisar o estado da arte dos dispositivos cadores, como a vitelogenina (VTG) e a proteí- legais e normativos referentes ao controle do es- na da zona radiata (ZRP), ambas normalmente trogênio sintético 17α-etinilestradiol nas águas Cad. Saúde Pública, Rio de Janeiro, 32(3):e00056715, mar, 2016 REGULAMENTAÇÃO DO ESTROGÊNIO 17α-ETINILESTRADIOL EM MATRIZES AQUÁTICAS 3 Tabela 1 Efeitos adversos provocados pelo 17α-etinilestradiol em diferentes espécies. Espécie/Fase da vida do organismo no início do teste Efeitos observados Peixes Danio rerio Embriões Alteração no comportamento de acasalamento 57; Indução da síntese de vitelogenina em machos; Anomalias e mortalidade de mebriões 58 Machos e fêmeas adultos Alterações histopatológicas nas fêmeas 59 Adultos machos Indução da síntese de vitelogenina e alterações no comportamento 60 Diferentes estágios Indução da síntese de viteloginina; Atraso e redução da desova; Redução das taxas de fertilização 61 Oryzias latipes Embriões Redução significativa na taxa de fertilização 62 Adultos machos Indução da síntese de vitelogenina e feminização 63 Um dia após o nascimento Mudança significativa na proporção de sexos (mais fêmeas) e hermafroditismo 64 Oryzias melastigma Machos e fêmeas adultos Alteração no comportamento de acasalamento e inibição da desova 65 Pimephales promelas Embriões Diminuição do tamanho do corpo e indução da síntese de vitelogenina 8; Diminuição da fertilização dos ovos e feminização 66; Indução da síntese de vitelogenina; feminização; Inibição significativa da espermatogênese 67 Adultos machos Alterações no comportamento reprodutivo, redução dos níveis hormonais e das características sexuais secundárias 68 Betta splendens Machos e fêmeas jovens e adultos Alteração no comportamento de acasalamento 69 Pomatoschistus minutus Adultos machos Indução da síntese de vitelogenina e da proteína da zona radiada 11 Gasterosteus aculeatus Adultos machos Alteração no comportamento de acasalamento 63 Gobiocypris rarus Machos e fêmeas adultos Indução da síntese de vitelogenina em ambos os sexos, alterações no fígado e nos rins, e feminização 70 Anfíbios Xenopus laevis Adultos machos Indução da síntese de vitelogenina e alterações hepáticas 71; Alteração no comportamento de acasalamento 72; Alterações significativas do comportamento 73 Hyalella azteca 4 a 6 semanas a partir da gametogênese Redução do crescimento nos machos 61 Gammarus pulex Diferentes estágios Aumento significativo do tamanho médio populacional; mudança na razão sexual dos adultos (2:1 em favor das fêmeas) 74 Crustáceos
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