Robert H. Heflich
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Also affiliated: United States Food and Drug Administration (1982–2026); Center for Drug Evaluation and Research (2009); University of Utah (1991); The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (1986); Letterman Army Medical Center (1973); Instituto Superior Técnico (2005); The Ohio State University (1986); Michigan State University (1977–1980)
Research Areas
Biomedical Subjects
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Biography and Research Information
OverviewAI-generated summary
Robert H. Heflich's research focuses on genetic toxicology and the assessment of mutagenicity and carcinogenicity of various chemical agents. His work has investigated the mechanisms by which environmental mutagens interact with DNA, leading to adduct formation and subsequent mutations. This includes studies on arylamines and nitroarenes, examining their metabolic activation and their role in bacterial mutagenesis and mammalian carcinogenesis, particularly in the urinary bladder.
Dr. Heflich has contributed to the development and application of various genotoxicity assays, including the Ames test and in vivo transgenic mutation assays like the Pig-a assay. His research also extends to evaluating the genotoxicity of emerging materials, such as silver nanoparticles. Furthermore, his work has explored the derivation of point of departure (PoD) estimates from genetic toxicology studies for their application in risk assessment. He has maintained an active research group and collaborated extensively with colleagues at the National Center for Toxicological Research, including Nan Mei, Ji‐Eun Seo, Xiaoqing Guo, and Xilin Li.
With a h-index of 52 and over 8,800 citations from nearly 300 publications, Dr. Heflich is recognized as a highly cited researcher. His work spans several decades, demonstrating a sustained contribution to the field of toxicology and mutagenesis.
Metrics
- h-index: 52
- Publications: 295
- Citations: 8,856
Selected Publications
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Adjusting the Preincubation Conditions to Enhance the Ames Test for Detecting the Mutagenicity of <i>N</i> ‐Nitrosamines (2026)
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Mutagenicity of EAT-positive NDSRIs in HepaRG spheroids (2026)
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Comparative genotoxicity assessment of ortho-phthalaldehyde using human in vitro organotypic airway epithelial cultures and standard in vitro genotoxicity assays (2026)
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Mutagenicity of <i>N</i> -nitroso-fluoxetine and <i>N</i> -nitroso-varenicline in human HepaRG cell models (2026)
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Nitrosamine Ames Data Review and Method Development: proceedings of a US FDA/HESI workshop (2026)
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Detection of In Vivo Mutation in the Hprt and Pig-a Genes of Rat Lymphocytes (2025)
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Mutation accumulation following extended exposure of human HepaRG cells to a genotoxic carcinogen (2025)
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Genotoxicity evaluation of ten nitrosamine drug substance-related impurities using 2D and 3D HepaRG cell models (2025)
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N-nitroso-ethylisopropylamine mutagenicity in rat liver using the cII transgenic mutation assay and duplex sequencing analysis of genomic DNA (2025)
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Comparative DNA damage induced by eight nitrosamines in primary human and macaque hepatocytes (2025)
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HESI GTTC ring trial: Concordance between Ames and rodent carcinogenicity outcomes for N-nitrosamines (NAs) with rat and hamster metabolic conditions (2025)
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Characterizing the Pulmonary Toxicity and Potential Mutagenicity of Formaldehyde Fumes in a Human Bronchial Epithelial Tissue Model (2025)
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Integration of the rat liver micronucleus assay into a 28-day treatment protocol: testing the genotoxicity of 4 small-molecule nitrosamines with different carcinogenic potencies and tumor target specificities (2025)
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Mutagenicity and genotoxicity evaluation of 15 nitrosamine drug substance-related impurities in human TK6 cells (2024)
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Optimizing the detection of N-nitrosamine mutagenicity in the Ames test (2024)
Collaboration Network
Top Collaborators
- The in vivo Pig-a assay: A report of the International Workshop On Genotoxicity Testing (IWGT) Workgroup
- Development of an in vivo gene mutation assay using the endogenous Pig‐A gene: I. Flow cytometric detection of CD59‐negative peripheral red blood cells and CD48‐negative spleen T‐cells from the rat
- The in vivo pig‐a gene mutation assay, a potential tool for regulatory safety assessment
- Genotoxicity of malachite green and leucomalachite green in female Big Blue B6C3F1 mice
- Accumulation and persistence of Pig-A mutant peripheral red blood cells following treatment of rats with single and split doses of N-ethyl-N-nitrosourea
Showing 5 of 41 shared publications
- Genotoxicity of silver nanoparticles evaluated using the Ames test and in vitro micronucleus assay
- Genotoxicity of malachite green and leucomalachite green in female Big Blue B6C3F1 mice
- Induction of 6‐thioguanine‐resistant lymphocytes in fischer 344 rats following in vivo exposure to n‐ethyl‐n‐nitrosourea and cyclophosphamide
- Development of an in vivo gene mutation assay using the endogenous Pig‐A gene: II. Selection of Pig‐A mutant rat spleen T‐cells with proaerolysin and sequencing Pig‐A cDNA from the mutants
- In vivo genotoxicity of furan in F344 rats at cancer bioassay doses
Showing 5 of 37 shared publications
- The orientation of the nitro substituent predicts the direct-acting bacterial mutagenicity of nitrated polycyclic aromatic hydrocarbons
- The In Vitro Metabolic Activation of Nitro Polycyclic Aromatic Hydrocarbons
- Nitro group orientation, reduction potential, and direct‐acting mutagenicity of nitro‐polycyclic aromatic hydrocarbons
- Fungal metabolism and detoxification of fluoranthene
- Metabolism of the mutagenic environmental pollutant, 6-nitrobenzo[a]pyrene: Metabolic activation via ring oxidation
Showing 5 of 31 shared publications
- The orientation of the nitro substituent predicts the direct-acting bacterial mutagenicity of nitrated polycyclic aromatic hydrocarbons
- The In Vitro Metabolic Activation of Nitro Polycyclic Aromatic Hydrocarbons
- Genotoxicity of malachite green and leucomalachite green in female Big Blue B6C3F1 mice
- Rapid isolation, hydrolysis and chromatography of formaldehyde-modified DNA
- Mutagenicity and carcinogenicity in relation to DNA adduct formation in rats fed leucomalachite green
Showing 5 of 27 shared publications
- Genotoxicity of malachite green and leucomalachite green in female Big Blue B6C3F1 mice
- In vivo genotoxicity of furan in F344 rats at cancer bioassay doses
- Genotoxicity of furan in Big Blue rats
- Comparative analysis of micronuclei and DNA damage induced by Ochratoxin A in two mammalian cell lines
- DNA adduct formation and induction of micronuclei and mutations in B6C3F1/Tk mice treated neonatally with acrylamide or glycidamide
Showing 5 of 24 shared publications
- Induction of 6‐thioguanine‐resistant lymphocytes in fischer 344 rats following in vivo exposure to n‐ethyl‐n‐nitrosourea and cyclophosphamide
- Correlation between specific DNA-methylation products and mutation induction at the HGPRT locus in Chinese hamster ovary cells
- Metabolism of the mutagenic environmental pollutant, 6-nitrobenzo[a]pyrene: Metabolic activation via ring oxidation
- Tk+/− mouse model for detecting in vivo mutation in an endogenous, autosomal gene
- Comparison of the types of mutations induced by 7,12-dimethylbenz[a]anthracene in thelacI andhprt genes of Big Blue® rats
Showing 5 of 21 shared publications
- DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver
- Genotoxicity of malachite green and leucomalachite green in female Big Blue B6C3F1 mice
- Mutagenicity of comfrey (Symphytum Officinale) in rat liver
- Nitroxide TEMPO: A genotoxic and oxidative stress inducer in cultured cells
- Mutations Induced by the Carcinogenic Pyrrolizidine Alkaloid Riddelliine in the Liver cII Gene of Transgenic Big Blue Rats
Showing 5 of 20 shared publications
- Accumulation of point mutations in mitochondrial DNA of aging mice
- Transgenic Animal Models in Toxicology: Historical Perspectives and Future Outlook
- Mutagenicity and carcinogenicity in relation to DNA adduct formation in rats fed leucomalachite green
- In vivo genotoxicity of furan in F344 rats at cancer bioassay doses
- Flow cytometric detection of Pig‐A mutant red blood cells using an erythroid‐specific antibody: Application of the method for evaluating the in vivo genotoxicity of methylphenidate in adolescent rats
Showing 5 of 16 shared publications
- In vivo genotoxicity of furan in F344 rats at cancer bioassay doses
- Report on stage III Pig‐a mutation assays using N‐ethyl‐N‐nitrosourea – comparison with other in vivo genotoxicity endpoints
- Report on stage IIIPig‐amutation assays using benzo[a]pyrene
- Quantitative dose–response analysis of ethyl methanesulfonate genotoxicity in adult gpt‐delta transgenic mice
- Manifestation and persistence of Pig‐a mutant red blood cells in C57BL/6 mice following single and split doses of N‐ethyl‐N‐nitrosourea
Showing 5 of 15 shared publications
- Invited review: human air-liquid-interface organotypic airway tissue models derived from primary tracheobronchial epithelial cells—overview and perspectives
- Tight junction disruption by cadmium in an in vitro human airway tissue model
- Report on stage III Pig‐a mutation assays using N‐ethyl‐N‐nitrosourea – comparison with other in vivo genotoxicity endpoints
- Report on stage IIIPig‐amutation assays using benzo[a]pyrene
- Genetic toxicity testing using human in vitro organotypic airway cultures: Assessing DNA damage with the CometChip and mutagenesis by Duplex Sequencing
Showing 5 of 14 shared publications
- Accumulation of point mutations in mitochondrial DNA of aging mice
- Induction of 6‐thioguanine‐resistant lymphocytes in fischer 344 rats following in vivo exposure to n‐ethyl‐n‐nitrosourea and cyclophosphamide
- In vivo genotoxicity of furan in F344 rats at cancer bioassay doses
- The effect of time after treatment, treatment schedule and animal age on the frequency of 6-thioguanine-resistant T-lymphocytes induced in Fischer 344 rats by N-ethyl-N-nitrosourea
- Comparison of the types of mutations induced by 7,12-dimethylbenz[a]anthracene in thelacI andhprt genes of Big Blue® rats
Showing 5 of 14 shared publications
- Current and Future Application of Genetic Toxicity Assays: The Role and Value of In Vitro Mammalian Assays
- Revisiting the mutagenicity and genotoxicity of N-nitroso propranolol in bacterial and human in vitro assays
- Optimizing the detection of N-nitrosamine mutagenicity in the Ames test
- Genotoxicity evaluation of nitrosamine impurities using human TK6 cells transduced with cytochrome P450s
- Genotoxicity assessment of eight nitrosamines using 2D and 3D HepaRG cell models
Showing 5 of 14 shared publications
- Revisiting the mutagenicity and genotoxicity of N-nitroso propranolol in bacterial and human in vitro assays
- Optimizing the detection of N-nitrosamine mutagenicity in the Ames test
- Genotoxicity evaluation of nitrosamine impurities using human TK6 cells transduced with cytochrome P450s
- Genotoxicity assessment of eight nitrosamines using 2D and 3D HepaRG cell models
- Mutagenicity and genotoxicity evaluation of 15 nitrosamine drug substance-related impurities in human TK6 cells
Showing 5 of 14 shared publications
- Nitroxide TEMPO: A genotoxic and oxidative stress inducer in cultured cells
- Revisiting the mutagenicity and genotoxicity of N-nitroso propranolol in bacterial and human in vitro assays
- Quantitative analysis of the relative mutagenicity of five chemical constituents of tobacco smoke in the mouse lymphoma assay
- Genotoxicity evaluation of nitrosamine impurities using human TK6 cells transduced with cytochrome P450s
- Genotoxicity assessment of eight nitrosamines using 2D and 3D HepaRG cell models
Showing 5 of 13 shared publications
- DNA adduct formation and induction of micronuclei and mutations in B6C3F1/Tk mice treated neonatally with acrylamide or glycidamide
- Effect of the nitro group conformation on the rat liver microsomal metabolism and bacterial mutagenicity of 2- and 9-nitroanthracene
- Levels of 4‐aminobiphenyl‐induced somatic H‐ras mutation in mouse liver DNA correlate with potential for liver tumor development
- Transplacental drug transfer and frequency of Tk and Hprt lymphocyte mutants and peripheral blood micronuclei in mice treated transplacentally with zidovudine and lamivudine
- Liver tumors induced in B6C3F1 mice by 7-chlorobenz[a]anthracene and 7-bromobenz[a]anthracene contain K-ras protooncogene mutations
Showing 5 of 12 shared publications
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