Literature review on the genotoxicity, reproductive toxicity, and carcinogenicity of ethyl methanesulfonate

Gocke, Elmar; Bürgin, Heinrich; Müller, Lutz; Pfister, Thomas D.

doi:10.1016/j.toxlet.2009.03.016

Cited by 79 publications

(50 citation statements)

References 62 publications

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“…Examples of the latter are topoisomerase inhibitors, tubulin inhibitors, and inducers of reactive oxygen species (Parry et al 1994 In 2007, it was discovered that a manufacturing batch of the drug Viracept (nelfinavir), an human immunodeficiency virus (HIV) protease inhibitor, was contaminated with EMS at levels that exceeded permissible levels by more than 1000-fold (M€ uller & Singer 2009). EMS is an established DNAreactive mutagen, rodent carcinogen, and teratogen (reviewed in Gocke et al 2009b). In the absence of human data, EMS exposure limits were based on the generic TTCderived limit of 1.5 lg/person per day as recommended in ICH M7 (discussed above).…”

Section: Advances In Understanding Both the Implications Of Genotoxicmentioning

confidence: 99%

Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and an approach for their re-evaluation

Boobis

Brown

Cronin

et al. 2017

Critical Reviews in Toxicology

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(2017) Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and an approach for their re-evaluation, Critical Reviews in Toxicology, 47:8, 710-732, DOI: 10.1080/10408444.2017 The threshold of toxicological concern (TTC) approach is a resource-effective de minimis method for the safety assessment of chemicals, based on distributional analysis of the results of a large number of toxicological studies. It is being increasingly used to screen and prioritize substances with low exposure for which there is little or no toxicological information. The first step in the approach is the identification of substances that may be DNA-reactive mutagens, to which the lowest TTC value is applied. This TTC value was based on the analysis of the cancer potency database and involved a number of assumptions that no longer reflect the state-of-the-science and some of which were not as transparent as they could have been. Hence, review and updating of the database is proposed, using inclusion and exclusion criteria reflecting current knowledge. A strategy for the selection of appropriate substances for TTC determination, based on consideration of weight of evidence for genotoxicity and carcinogenicity is outlined. Identification of substances that are carcinogenic by a DNA-reactive mutagenic mode of action and those that clearly act by a non-genotoxic mode of action will enable the protectiveness to be determined of both the TTC for DNA-reactive mutagenicity and that applied by default to substances that may be carcinogenic but are unlikely to be DNA-reactive mutagens (i.e. for Cramer class I-III compounds). Critical to the application of the TTC approach to substances that are likely to be DNA-reactive mutagens is the reliability of the software tools used to identify such compounds. Current methods for this task are reviewed and recommendations made for their application.

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Section: Advances In Understanding Both the Implications Of Genotoxicmentioning

confidence: 99%

Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and an approach for their re-evaluation

Boobis

Brown

Cronin

et al. 2017

Critical Reviews in Toxicology

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“…La respuesta endógena e inducida es dependiente del sexo. En ensayos similares pero evaluando la acción genotóxica de fármacos mediante está técnica tampoco fueron observadas diferencias entre sexos tanto en los grupos controles, tratados y grupo control positivo administrado con CF por igual vía (8,11,14,19,20).…”

Section: Discussionunclassified

Comparación entre líneas de ratones en el ensayo de aberraciones cromosómicas en médula ósea

2012

Rev MVZ Córdoba

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Rev.MVZ Córdoba 17(2):2957-2963, 2012. ORIGINAL RESUMENObjetivo. El objetivo de este trabajo fue comparar los índices espontáneos e inducidos en ratones de ambos sexos de las líneas Balb/c, NMRI, OF-1 y C57BL/6/cenp, mediante el ensayo de aberraciones cromosómicas en células de la médula ósea. Materiales y métodos. Con este fin se determinó la línea más eficiente, sobre la base de la aparición significativa de índices espontáneos más bajos e índices inducidos altos a sustancias mutagénicas como la ciclofosfamida (CF). Resultados. Se obtuvo como resultado que la línea Balb/c en ambos sexos difiere significativamente de las demás líneas evaluadas. En esta línea se encontró el menor número de células totales con aberraciones estructurales y un mayor número de inducción de aberraciones cromosómicas cuando es utilizada la CF como mutágeno. Conclusiones. Este trabajo permitirá utilizar la mejor línea de ratones como biomodelo en este ensayo de genotoxicidad, además que le confiere a esta técnica citogenética mayor veracidad y robustez.Palabras clave: Aberraciones cromosómicas, médula ósea, ratón (Fuente: AIMS). ABSTRACTObjective. The aim of this study was to compare spontaneous and induced rates in mice of both sexes of lines BALB / c, NMRI, OF-1 and C57BL/6/ cenp, by testing chromosomal aberrations in bone marrow cells. Materials and methods. For this purpose, the most efficient line was determined, based on the significant appearance of lower spontaneous rates and higher induced rates to mutagen substances such as cyclophosphamide (CP). Results. The result obtained was that line Balb / c, in both sexes, differs significantly from the other lines tested. The lesser total number of cells with structural aberrations was found in this line and a greater number of induction of chromosomal aberrations when CP was used as a mutagen. Conclusions. This work will give way to the use of the best line of mice as bio model in this genotoxicity test, and will also give this cytogenetic technique greater veracity and robustness.

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“…The international agency for research on cancer (IARC) has classified EMS and MMS in group 2B and 2A, respectively (Snodin, 2006;Gocke et al, 2009a). Gocke et al (2009a) reviewed both in vivo and in vitro genotoxicity, carcinogenicity, general toxicity, and the effects on reproductive and embryo fetal development of EMS. They reported that the genotoxic effects induced by EMS were observed in viruses/phages, bacteria, fungi, plant, insect, and mammalian cells.…”

Section: Genotoxic Impurities (Gis)mentioning

confidence: 99%

“…In the majority of studies the dose-response relationships appeared sub linear and a threshold below 50 mg/kg appeared possible. Gocke et al (2009a) demonstrated that EMS in various gene mutation tests such as induction of hprt, lacZ, and dlb-1 mutations in mice was mutagenic. The carcinogenicity of EMS was confirmed in several animal models.…”

Section: Genotoxic Impurities (Gis)mentioning

confidence: 99%

Genotoxic Impurities in Pharmaceuticals

Jouyban¹,

Parsa²

2012

Toxicity and Drug Testing

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Literature review on the genotoxicity, reproductive toxicity, and carcinogenicity of ethyl methanesulfonate

Cited by 79 publications

References 62 publications

Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and an approach for their re-evaluation

Origin of the TTC values for compounds that are genotoxic and/or carcinogenic and an approach for their re-evaluation

Comparación entre líneas de ratones en el ensayo de aberraciones cromosómicas en médula ósea

Genotoxic Impurities in Pharmaceuticals

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