Is Nickel Chloride really a Non‐Genotoxic Carcinogen?

Stannard, Leanne; Doak, Shareen H.; Doherty, Ann; Jenkins, Gareth

doi:10.1111/bcpt.12689

Cited by 24 publications

(11 citation statements)

References 36 publications

(43 reference statements)

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“…5 , 6 ), possibly linking to its shorter exposure duration (4 h). However, this also reflects some NGC trends, perhaps suggesting a ROS-centric mechanism (Stannard et al 2016 ). It was hypothesised that the mammalian target of rapamycin (mTOR) may orchestrate cell morphology alterations (Fumarola et al 2005 ; Llanos et al 2016 ; Pincus and Theriot 2007 ).…”

Section: Discussionmentioning

confidence: 61%

“…1 ) or in some other studies (Biggart and Costa 1986 ; Chakrabarti et al 2001 ). Therefore, NiCl 2 may not be a true NGC, as was previously believed, and its genotoxicity may be dependent on its exposure time (Stannard et al 2016 ). It is, therefore, apparent that different groups of carcinogens have a unique in vitro “fingerprint” or “signature” for carcinogenicity.…”

Section: Discussionmentioning

confidence: 89%

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A novel, integrated in vitro carcinogenicity test to identify genotoxic and non-genotoxic carcinogens using human lymphoblastoid cells

et al. 2017

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Human exposure to carcinogens occurs via a plethora of environmental sources, with 70–90% of cancers caused by extrinsic factors. Aberrant phenotypes induced by such carcinogenic agents may provide universal biomarkers for cancer causation. Both current in vitro genotoxicity tests and the animal-testing paradigm in human cancer risk assessment fail to accurately represent and predict whether a chemical causes human carcinogenesis. The study aimed to establish whether the integrated analysis of multiple cellular endpoints related to the Hallmarks of Cancer could advance in vitro carcinogenicity assessment. Human lymphoblastoid cells (TK6, MCL-5) were treated for either 4 or 23 h with 8 known in vivo carcinogens, with doses up to 50% Relative Population Doubling (maximum 66.6 mM). The adverse effects of carcinogens on wide-ranging aspects of cellular health were quantified using several approaches; these included chromosome damage, cell signalling, cell morphology, cell-cycle dynamics and bioenergetic perturbations. Cell morphology and gene expression alterations proved particularly sensitive for environmental carcinogen identification. Composite scores for the carcinogens’ adverse effects revealed that this approach could identify both DNA-reactive and non-DNA reactive carcinogens in vitro. The richer datasets generated proved that the holistic evaluation of integrated phenotypic alterations is valuable for effective in vitro risk assessment, while also supporting animal test replacement. Crucially, the study offers valuable insights into the mechanisms of human carcinogenesis resulting from exposure to chemicals that humans are likely to encounter in their environment. Such an understanding of cancer induction via environmental agents is essential for cancer prevention.Electronic supplementary materialThe online version of this article (10.1007/s00204-017-2102-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 89%

A novel, integrated in vitro carcinogenicity test to identify genotoxic and non-genotoxic carcinogens using human lymphoblastoid cells

et al. 2017

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“…Some systems are more prone to ROS, which may lead to positive genotoxicity results. However, some systems have relatively high antioxidant capacity that can scavenge excessively produced ROS, and therefore attenuate the damaging effects of ROS (Stannard et al., 2017).…”

Section: Assessmentmentioning

confidence: 99%

Update of the risk assessment of nickel in food and drinking water

Schrenk¹,

Bignami²,

Bodin³

et al. 2020

EFS2

101

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The European Commission asked EFSA to update its previous Opinion on nickel in food and drinking water, taking into account new occurrence data, the updated benchmark dose (BMD) Guidance and newly available scientific information. More than 47,000 analytical results on the occurrence of nickel were used for calculating chronic and acute dietary exposure. An increased incidence of postimplantation loss in rats was identified as the critical effect for the risk characterisation of chronic oral exposure and a BMDL 10 of 1.3 mg Ni/kg body weight (bw) per day was selected as the reference point for the establishment of a tolerable daily intake (TDI) of 13 lg/kg bw. Eczematous flare-up reactions in the skin elicited in nickel-sensitised humans, a condition known as systemic contact dermatitis, was identified as the critical effect for the risk characterisation of acute oral exposure. A BMDL could not be derived, and therefore, the lowest-observed-adverse-effect-level of 4.3 lg Ni/kg bw was selected as the reference point. The margin of exposure (MOE) approach was applied and an MOE of 30 or higher was considered as being indicative of a low health concern. The mean lower bound (LB)/upper bound (UB) chronic dietary exposure was below or at the level of the TDI. The 95th percentile LB/UB chronic dietary exposure was below the TDI in adolescents and in all adult age groups, but generally exceeded the TDI in toddlers and in other children, as well as in infants in some surveys. This may raise a health concern in these young age groups. The MOE values for the mean UB acute dietary exposure and for the 95th percentile UB raises a health concern for nickel-sensitised individuals. The MOE values for an acute scenario regarding consumption of a glass of water on an empty stomach do not raise a health concern.

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“…Cependant, la génotoxicité des nanoparticules d'oxide de nickel (NiO-NPs), a été prouvée chez Allium cepa (Manna et Bandyopadhyay, 2017). Chez les mammifères, la génotoxicité de Ni a été aussi discutée par Stannard et al (2017) suite à la classification de NiCl2 en tant qu'un « carcinogène non-génotoxique », sans effets directs sur l'ADN et sur le nombre et la structure des chromosomes. Sa cancérogénicité a été, plutôt, attribuée aux espèces réactives de l'oxygène (ROS) produites sous ce stress métallique.…”

Section: Discussionunclassified

Effets génotoxiques de l’irrigation à long-terme par des eaux usées traitées : cas du périmètre Cebala- Borj Touil

Souguir¹,

Hörmann²,

Hachicha³

2019

J. App. Bioscience.

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La réutilisation à long-terme des eaux usées traitées (EUT) pourrait constituer une source de contamination avec un apport cumulé en éléments toxiques. Le but de cette étude est d'évaluer l'impact génotoxique d'une telle irrigation sur les sols du périmètre irrigué Cebala-Borj Touil à travers le test de Vicia-micronoyaux. Méthodologie et résultats. Les lixiviats des sols issus de 3 parcelles recevant des EUT depuis 2 (P2), 4 (P4) et 10 (P10) ans ont servi pour l'étude génotoxique. Ces lixiviats sont basiques avec une salinité ne dépassant pas 2,23 dS m-1 dominée par des ions Cl et Na. La composition métallique a montré des teneurs plus élevées chez les sols ayant reçu des irrigations avec les EUT par rapport à celui du contrôle jamais irrigué (P0). L'étude génotoxique a révélé une activité mitotique importante chez tous les lixiviats, une induction des micronoyaux surtout chez P10, et une apparition des aberrations chromosomiques et nucléaires. Conclusion et application. Bien que l'échantillonnage se soit déroulé pendant la période pluvieuse, supposée lessiver les contaminants en profondeur, le sol de Cebala-Borj Touil semble avoir un potentiel génotoxique. Le transfert de ces contaminants vers les cultures occupées par ces sols, spécialement fourragères, nécessite une attention dans une crainte d'atteindre la chaine trophique. Le test de micronoyaux à travers une exposition indirecte (à travers les lixiviats) semble être un outil rapide et fiable dans la détection de la toxicité pouvant nuire la santé humaine. Mots clés : contaminants, eaux usées traitées, génotoxicité, lixiviats, long-terme.

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Is Nickel Chloride really a Non‐Genotoxic Carcinogen?

Cited by 24 publications

References 36 publications

A novel, integrated in vitro carcinogenicity test to identify genotoxic and non-genotoxic carcinogens using human lymphoblastoid cells

A novel, integrated in vitro carcinogenicity test to identify genotoxic and non-genotoxic carcinogens using human lymphoblastoid cells

Update of the risk assessment of nickel in food and drinking water

Effets génotoxiques de l’irrigation à long-terme par des eaux usées traitées : cas du périmètre Cebala- Borj Touil

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