Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water
- PMID: 25605026
- PMCID: PMC4521608
- DOI: 10.3109/10408444.2014.973934
Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water
Abstract
Toxicogenomics is proposed to be a useful tool in human health risk assessment. However, a systematic comparison of traditional risk assessment approaches with those applying toxicogenomics has never been done. We conducted a case study to evaluate the utility of toxicogenomics in the risk assessment of benzo[a]pyrene (BaP), a well-studied carcinogen, for drinking water exposures. Our study was intended to compare methodologies, not to evaluate drinking water safety. We compared traditional (RA1), genomics-informed (RA2) and genomics-only (RA3) approaches. RA2 and RA3 applied toxicogenomics data from human cell cultures and mice exposed to BaP to determine if these data could provide insight into BaP's mode of action (MOA) and derive tissue-specific points of departure (POD). Our global gene expression analysis supported that BaP is genotoxic in mice and allowed the development of a detailed MOA. Toxicogenomics analysis in human lymphoblastoid TK6 cells demonstrated a high degree of consistency in perturbed pathways with animal tissues. Quantitatively, the PODs for traditional and transcriptional approaches were similar (liver 1.2 vs. 1.0 mg/kg-bw/day; lungs 0.8 vs. 3.7 mg/kg-bw/day; forestomach 0.5 vs. 7.4 mg/kg-bw/day). RA3, which applied toxicogenomics in the absence of apical toxicology data, demonstrates that this approach provides useful information in data-poor situations. Overall, our study supports the use of toxicogenomics as a relatively fast and cost-effective tool for hazard identification, preliminary evaluation of potential carcinogens, and carcinogenic potency, in addition to identifying current limitations and practical questions for future work.
Keywords: benchmark dose; carcinogens; dose–response; environmental pollutant; genomics; human health risk assessment; mode of action; point of departure; polycyclic aromatic hydrocarbon; transcriptomics.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4521608/bin/nihms-706216-f0001.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4521608/bin/nihms-706216-f0002.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4521608/bin/nihms-706216-f0003.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4521608/bin/nihms-706216-f0004.gif)
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4521608/bin/nihms-706216-f0005.gif)
![Figure 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4521608/bin/nihms-706216-f0006.gif)
![Figure 7](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4521608/bin/nihms-706216-f0007.gif)
![Figure 8](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4521608/bin/nihms-706216-f0008.gif)
![Figure 9](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4521608/bin/nihms-706216-f0009.gif)
![Figure 10](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4521608/bin/nihms-706216-f0010.gif)
Similar articles
-
Integrating toxicogenomics into human health risk assessment: lessons learned from the benzo[a]pyrene case study.Crit Rev Toxicol. 2015 Jan;45(1):44-52. doi: 10.3109/10408444.2014.973935. Crit Rev Toxicol. 2015. PMID: 25605027 Review.
-
Neurotoxicity may be an overlooked consequence of benzo[a]pyrene exposure that is relevant to human health risk assessment.Mutat Res Rev Mutat Res. 2015 Apr-Jun;764:64-89. doi: 10.1016/j.mrrev.2015.03.001. Epub 2015 Mar 21. Mutat Res Rev Mutat Res. 2015. PMID: 26041267 Review.
-
Recommended approaches in the application of toxicogenomics to derive points of departure for chemical risk assessment.Arch Toxicol. 2017 May;91(5):2045-2065. doi: 10.1007/s00204-016-1886-5. Epub 2016 Dec 7. Arch Toxicol. 2017. PMID: 27928627 Free PMC article.
-
Impact of Genomics Platform and Statistical Filtering on Transcriptional Benchmark Doses (BMD) and Multiple Approaches for Selection of Chemical Point of Departure (PoD).PLoS One. 2015 Aug 27;10(8):e0136764. doi: 10.1371/journal.pone.0136764. eCollection 2015. PLoS One. 2015. PMID: 26313361 Free PMC article.
-
Toxicogenomic outcomes predictive of forestomach carcinogenesis following exposure to benzo(a)pyrene: relevance to human cancer risk.Toxicol Appl Pharmacol. 2013 Dec 1;273(2):269-80. doi: 10.1016/j.taap.2013.05.027. Epub 2013 Jun 2. Toxicol Appl Pharmacol. 2013. PMID: 23735875
Cited by
-
Toxicological Mechanisms and Potencies of Organophosphate Esters in KGN Human Ovarian Granulosa Cells as Revealed by High-throughput Transcriptomics.Toxicol Sci. 2023 Nov 6;197(2):170-85. doi: 10.1093/toxsci/kfad114. Online ahead of print. Toxicol Sci. 2023. PMID: 37941476
-
From vision toward best practices: Evaluating in vitro transcriptomic points of departure for application in risk assessment using a uniform workflow.Front Toxicol. 2023 May 23;5:1194895. doi: 10.3389/ftox.2023.1194895. eCollection 2023. Front Toxicol. 2023. PMID: 37288009 Free PMC article.
-
Application of a new approach methodology (NAM)-based strategy for genotoxicity assessment of data-poor compounds.Front Toxicol. 2023 Jan 23;5:1098432. doi: 10.3389/ftox.2023.1098432. eCollection 2023. Front Toxicol. 2023. PMID: 36756349 Free PMC article.
-
Pilot testing and optimization of a larval fathead minnow high throughput transcriptomics assay.Curr Res Toxicol. 2022 Dec 22;4:100099. doi: 10.1016/j.crtox.2022.100099. eCollection 2023. Curr Res Toxicol. 2022. PMID: 36619288 Free PMC article.
-
The Role of Systems Biology in Deciphering Asthma Heterogeneity.Life (Basel). 2022 Oct 8;12(10):1562. doi: 10.3390/life12101562. Life (Basel). 2022. PMID: 36294997 Free PMC article. Review.
References
-
- Aboutabl ME, Zordoky BN, Hammock BD, El-Kadi AO. Inhibition of soluble epoxide hydrolase confers cardioprotection and prevents cardiac cytochrome P450 induction by benzo(a)pyrene. J Cardiovasc Pharmacol. 2011;57(3):273–281. - PubMed
-
- Allan LL, Schlezinger JJ, Shansab M, Sherr DH. CYP1A1 in polycyclic aromatic hydrocarbon–induced B lymphocyte growth suppression. Biochem Biophys Res Commun. 2006;342(1):227–235. - PubMed
-
- Anderson KE, Kadlubar FF, Kulldorff M, et al. Dietary intake of heterocyclic amines and benzo(a)pyrene: Associations with pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2005;14(9):2261–2265. - PubMed
-
- Arafa HM, Aly HA, Abd-Ellah MF, El-Refaey HM. Hesperidin attenuates benzo[α]pyrene-induced testicular toxicity in rats via regulation of oxidant/antioxidant balance. Toxicol Ind Health. 2009;25(6):417–427. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources