In vitro exposure to the next-generation plasticizer diisononyl cyclohexane-1,2-dicarboxylate (DINCH): cytotoxicity and genotoxicity assessment in human cells

Detalhes bibliográficos
Autor(a) principal: Vasconcelos, Ana Luísa
Data de Publicação: 2019
Outros Autores: Silva, Maria João, Louro, Henriqueta
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/6525
Resumo: Plasticizers are currently present in many consumer products, particularly food packaging, children's toys, and medical devices. There are concerns regarding potential leaching to environment or food, thus increasing the risk of human exposure by inhalation, ingestion and/or dermal absorption potentially leading to adverse health consequences. Hexamoll diisononyl cyclohexane-1,2-dicarboxylate (Hexamoll® DINCH®), a non-phthalate plasticizer, has been used as a safer alternative to hazardous phthalates. In contrast to phthalates, evidence indicates that DINCH did not produce endocrine disruption, reproductive dysfunctions, genotoxicity or mutagenicity. However, there are limited data available regarding safety assessment, especially with respect to genotoxicity in human cells. The aim of this study was to assess DINCH cytotoxic and genotoxic effects in human liver and kidney cell lines following several exposure periods. For this purpose, the MTT cell viability, micronucleus, conventional and formamidopyrimidine DNA glycosylase (FPG)-modified comet assays were employed to detect cell death and genotoxicity, respectively. Data demonstrated that DINCH induced cytotoxicity in kidney cells exposed for 48hr, but not in liver cells. No marked chromosomal damage was noted after short-term or longer following treatment of both cell lines. However, DINCH produced oxidative DNA damage in liver cells exposed for 3 h, which decreased after a more prolonged incubation period. The occurrence of oxidative lesions, even transiently, indicates that mutation fixation may occur leading to adverse effects in liver. Therefore, these findings suggest that DINCH may be hazardous to humans and that further investigation is necessary to warrant its safety.
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spelling In vitro exposure to the next-generation plasticizer diisononyl cyclohexane-1,2-dicarboxylate (DINCH): cytotoxicity and genotoxicity assessment in human cellsPlasticizersGenotoxicityHexamoll DINCHComet AssayMicronucleus AssayMetabolic ActivationCytotoxicityGenotoxicidade AmbientalPlasticizers are currently present in many consumer products, particularly food packaging, children's toys, and medical devices. There are concerns regarding potential leaching to environment or food, thus increasing the risk of human exposure by inhalation, ingestion and/or dermal absorption potentially leading to adverse health consequences. Hexamoll diisononyl cyclohexane-1,2-dicarboxylate (Hexamoll® DINCH®), a non-phthalate plasticizer, has been used as a safer alternative to hazardous phthalates. In contrast to phthalates, evidence indicates that DINCH did not produce endocrine disruption, reproductive dysfunctions, genotoxicity or mutagenicity. However, there are limited data available regarding safety assessment, especially with respect to genotoxicity in human cells. The aim of this study was to assess DINCH cytotoxic and genotoxic effects in human liver and kidney cell lines following several exposure periods. For this purpose, the MTT cell viability, micronucleus, conventional and formamidopyrimidine DNA glycosylase (FPG)-modified comet assays were employed to detect cell death and genotoxicity, respectively. Data demonstrated that DINCH induced cytotoxicity in kidney cells exposed for 48hr, but not in liver cells. No marked chromosomal damage was noted after short-term or longer following treatment of both cell lines. However, DINCH produced oxidative DNA damage in liver cells exposed for 3 h, which decreased after a more prolonged incubation period. The occurrence of oxidative lesions, even transiently, indicates that mutation fixation may occur leading to adverse effects in liver. Therefore, these findings suggest that DINCH may be hazardous to humans and that further investigation is necessary to warrant its safety.This work was partially financed by national funds through the FCT - Foundation for Science and Technology, I.P., under the project PTDC/SAU-PUB/29481/2017 and by UID/BIM/00009/2013.Taylor & FrancisRepositório Científico do Instituto Nacional de SaúdeVasconcelos, Ana LuísaSilva, Maria JoãoLouro, Henriqueta2020-04-27T07:17:35Z2019-06-262019-06-26T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6525engJ Toxicol Environ Health A. 2019;82(9):526-536. doi: 10.1080/15287394.2019.1634376. Epub 2019 Jun 261528-739410.1080/15287394.2019.1634376info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:41:26Zoai:repositorio.insa.pt:10400.18/6525Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:41:07.307441Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv In vitro exposure to the next-generation plasticizer diisononyl cyclohexane-1,2-dicarboxylate (DINCH): cytotoxicity and genotoxicity assessment in human cells
title In vitro exposure to the next-generation plasticizer diisononyl cyclohexane-1,2-dicarboxylate (DINCH): cytotoxicity and genotoxicity assessment in human cells
spellingShingle In vitro exposure to the next-generation plasticizer diisononyl cyclohexane-1,2-dicarboxylate (DINCH): cytotoxicity and genotoxicity assessment in human cells
Vasconcelos, Ana Luísa
Plasticizers
Genotoxicity
Hexamoll DINCH
Comet Assay
Micronucleus Assay
Metabolic Activation
Cytotoxicity
Genotoxicidade Ambiental
title_short In vitro exposure to the next-generation plasticizer diisononyl cyclohexane-1,2-dicarboxylate (DINCH): cytotoxicity and genotoxicity assessment in human cells
title_full In vitro exposure to the next-generation plasticizer diisononyl cyclohexane-1,2-dicarboxylate (DINCH): cytotoxicity and genotoxicity assessment in human cells
title_fullStr In vitro exposure to the next-generation plasticizer diisononyl cyclohexane-1,2-dicarboxylate (DINCH): cytotoxicity and genotoxicity assessment in human cells
title_full_unstemmed In vitro exposure to the next-generation plasticizer diisononyl cyclohexane-1,2-dicarboxylate (DINCH): cytotoxicity and genotoxicity assessment in human cells
title_sort In vitro exposure to the next-generation plasticizer diisononyl cyclohexane-1,2-dicarboxylate (DINCH): cytotoxicity and genotoxicity assessment in human cells
author Vasconcelos, Ana Luísa
author_facet Vasconcelos, Ana Luísa
Silva, Maria João
Louro, Henriqueta
author_role author
author2 Silva, Maria João
Louro, Henriqueta
author2_role author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Vasconcelos, Ana Luísa
Silva, Maria João
Louro, Henriqueta
dc.subject.por.fl_str_mv Plasticizers
Genotoxicity
Hexamoll DINCH
Comet Assay
Micronucleus Assay
Metabolic Activation
Cytotoxicity
Genotoxicidade Ambiental
topic Plasticizers
Genotoxicity
Hexamoll DINCH
Comet Assay
Micronucleus Assay
Metabolic Activation
Cytotoxicity
Genotoxicidade Ambiental
description Plasticizers are currently present in many consumer products, particularly food packaging, children's toys, and medical devices. There are concerns regarding potential leaching to environment or food, thus increasing the risk of human exposure by inhalation, ingestion and/or dermal absorption potentially leading to adverse health consequences. Hexamoll diisononyl cyclohexane-1,2-dicarboxylate (Hexamoll® DINCH®), a non-phthalate plasticizer, has been used as a safer alternative to hazardous phthalates. In contrast to phthalates, evidence indicates that DINCH did not produce endocrine disruption, reproductive dysfunctions, genotoxicity or mutagenicity. However, there are limited data available regarding safety assessment, especially with respect to genotoxicity in human cells. The aim of this study was to assess DINCH cytotoxic and genotoxic effects in human liver and kidney cell lines following several exposure periods. For this purpose, the MTT cell viability, micronucleus, conventional and formamidopyrimidine DNA glycosylase (FPG)-modified comet assays were employed to detect cell death and genotoxicity, respectively. Data demonstrated that DINCH induced cytotoxicity in kidney cells exposed for 48hr, but not in liver cells. No marked chromosomal damage was noted after short-term or longer following treatment of both cell lines. However, DINCH produced oxidative DNA damage in liver cells exposed for 3 h, which decreased after a more prolonged incubation period. The occurrence of oxidative lesions, even transiently, indicates that mutation fixation may occur leading to adverse effects in liver. Therefore, these findings suggest that DINCH may be hazardous to humans and that further investigation is necessary to warrant its safety.
publishDate 2019
dc.date.none.fl_str_mv 2019-06-26
2019-06-26T00:00:00Z
2020-04-27T07:17:35Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/6525
url http://hdl.handle.net/10400.18/6525
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv J Toxicol Environ Health A. 2019;82(9):526-536. doi: 10.1080/15287394.2019.1634376. Epub 2019 Jun 26
1528-7394
10.1080/15287394.2019.1634376
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
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dc.publisher.none.fl_str_mv Taylor & Francis
publisher.none.fl_str_mv Taylor & Francis
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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