Grouping of UVCB substances with new approach methodologies (NAMs) data

Main Article Content

John S. House
Fabian A. Grimm
William D. Klaren
Abigail Dalzell
Srikeerthana Kuchi
Shu-Dong Zhang
Klaus Lenz
Peter J. Boogaard
Hans B. Ketelslegers
Timothy W. Gant
Fred A. Wright
Ivan Rusyn

Abstract

One of the most challenging areas in regulatory science is assessment of the substances known as UVCB (unknown or variable composition, complex reaction products and biological materials). Because the inherent complexity and variability of UVCBs present considerable challenges for establishing sufficient substance similarity based on chemical characteristics or other data, we hypothesized that new approach methodologies (NAMs), including in vitro test-derived biological activity signatures to characterize substance similarity, could be used to support grouping of UVCBs. We tested 141 petroleum substances as representative UVCBs in a compendium of 15 human cell types representing a variety of tissues. Petroleum substances were assayed in dilution series to derive point of departure estimates for each cell type and phenotype. Extensive quality control measures were taken to ensure that only high-confidence in vitro data were used to determine whether current groupings of these petroleum substances, based largely on the manufacturing process and physico-chemical properties, are justifiable. We found that bioactivity data-based groupings of petroleum substances were generally consistent with the manufacturing class-based categories. We also showed that these data, especially bioactivity from human induced pluripotent stem cell (iPSC)-derived and primary cells, can be used to rank substances in a manner highly concordant with their expected in vivo hazard potential based on their chemical compositional profile. Overall, this study demonstrates that NAMs can be used to inform groupings of UVCBs, to assist in identification of repre­sentative substances in each group for testing when needed, and to fill data gaps by read-across.

Article Details

How to Cite
House, J. S., Grimm, F. A., Klaren, W. D., Dalzell, A., Kuchi, S., Zhang, S.-D., Lenz, K., Boogaard, P. J., Ketelslegers, H. B., Gant, T. W., Wright, F. A. and Rusyn, I. (2021) “Grouping of UVCB substances with new approach methodologies (NAMs) data”, ALTEX - Alternatives to animal experimentation, 38(1), pp. 123–137. doi: 10.14573/altex.2006262.
Section
Articles
References

ASTM International (2014). Standard Test Method for Determining Carcinogenic Potential of Virgin Base Oils in Metalworking Fluids. E1687-10. doi:10.1520/E1687-10 (accessed 01.07.2019).

Ball, N., Bartels, M., Budinsky, R. et al. (2014). The challenge of using read-across within the EU REACH regulatory framework; how much uncertainty is too much? Dipropylene glycol methyl ether acetate, an exemplary case study. Regul Toxicol Pharmacol 68, 212-221. doi:10.1016/j.yrtph.2013.12.007

Carrillo, J. C., van der Wiel, A., Danneels, D. et al. (2019). The selective determination of potentially carcinogenic polycyclic aromatic compounds in lubricant base oils by the DMSO extraction method IP346 and its correlation to mouse skin painting carcinogenicity assays. Regul Toxicol Pharmacol 106, 316-333. doi:10.1016/j.yrtph.2019.05.012

Catlin, N. R., Collins, B. J., Auerbach, S. S. et al. (2018). How similar is similar enough? A sufficient similarity case study with Ginkgo biloba extract. Food Chem Toxicol 118, 328-339. doi:10.1016/j.fct.2018.05.013

Chen, Z., Liu, Y., Wright, F. A. et al. (2020). Rapid hazard characterization of environmental chemicals using a compendium of human cell lines from different organs. ALTEX 37, 623-638. doi:10.14573/altex.2002291

Clark, C. R., McKee, R. H., Freeman, J. J. et al. (2013). A GHS-consistent approach to health hazard classification of petroleum substances, a class of UVCB substances. Regul Toxicol Pharmacol 67, 409-420. doi:10.1016/j.yrtph.2013.08.020

CONCAWE (1994). The use of the dimethyl sulphoxide (DMSO) extract by the IP 346 method as an indicator of the carcinogenicity of lubricant base oils and distillate aromatic extracts. Report No. 94/51. European Petroleum Refiners Association – Concawe Division. https://www.concawe.eu/wp-content/uploads/2017/01/rpt9451ocr-2005-00417-01-e.pdf (accessed 01.05.2020).

CONCAWE (2017). Hazard classification and labelling of petroleum substances in the European Economic Area – 2017. Report No. 13/17. Concawe Classification and Labelling Task Force (STF-23). https://www.concawe.eu/wp-content/uploads/2017/11/Rpt_17-13.pdf (accessed 28.08.2020).

CONCAWE (2019). REACH roadmap for Petroleum SUbstances. European Petroleum Refiners Association – Concawe Division. https://www.concawe.eu/wp-content/uploads/REACH-Roadmap-for-Petroleum-Substances-2019-update.pdf (accessed 15.05.2020).

Dimitrov, S. D., Georgieva, D. G., Pavlov, T. S. et al. (2015). UVCB substances: Methodology for structural description and application to fate and hazard assessment. Environ Toxicol Chem 34, 2450-2462. doi:10.1002/etc.3100

ECHA – European Chemical Agency (2015). Read-Across Assessment Framework (RAAF). doi:10.2823/546436 (accessed 24.08.2015).

ECHA (2017). Read-Across Assessment Framework (RAAF) – Considerations on multi-constituent substances and UVCBs. https://echa.europa.eu/documents/10162/13630/raaf_uvcb_report_en.pdf/3f79684d-07a5-e439-16c3-d2c8da96a316 (accessed 25.08.2020).

ECHA (2020). Testing Proposal Decision on Substance EC 295-332-8 “Extracts (petroleum), deasphalted vacuum residue solvent”. https://echa.europa.eu/documents/10162/6cda0e05-11af-541b-6dfa-b2101db95a5a (accessed 02.09.2020).

Feder, P. I. and Hertzberg, R. C. (2013). Assessing the mammalian toxicity of high-boiling point petroleum substances. Regul Toxicol Pharmacol 67, Suppl 2, S1-3. doi:10.1016/j.yrtph.2013.08.006

Fowlkes, E. B. and Mallows, C. L. (1983). A method for comparing two hierarchical clusterings. J Am Stat Assoc 78, 553-569. doi:10.1080/01621459.1983.10478008

Goyak, K. O., Kung, M. H., Chen, M. et al. (2016). Development of a screening tool to prioritize testing for the carcinogenic hazard of residual aromatic extracts and related petroleum streams. Toxicol Lett 264, 99-105. doi:10.1016/j.toxlet.2016.10.001

Gray, T. M., Simpson, B. J., Nicolich, M. J. et al. (2013). Assessing the mammalian toxicity of high-boiling petroleum substances under the rubric of the HPV program. Regul Toxicol Pharmacol 67, Suppl 2, S4-9. doi:10.1016/j.yrtph.2012.11.014

Grimm, F. A., Iwata, Y., Sirenko, O. et al. (2016). A chemical-biological similarity-based grouping of complex substances as a prototype approach for evaluating chemical alternatives. Green Chem 18, 4407-4419. doi:10.1039/c6gc01147k

Grimm, F. A., Russell, W. K., Luo, Y. S. et al. (2017). Grouping of petroleum substances as example UVCBs by ion mobility-mass spectrometry to enable chemical composition-based read-across. Environ Sci Technol 51, 7197-7207. doi:10.1021/acs.est.6b06413

Herrmann, K., Pistollato, F. and Stephens, M. L. (2019). Beyond the 3Rs: Expanding the use of human-relevant replacement methods in biomedical research. ALTEX 36, 343-352. doi:10.14573/altex.1907031

Kamelia, L., de Haan, L., Ketelslegers, H. B. et al. (2019). In vitro prenatal developmental toxicity induced by some petroleum substances is mediated by their 3- to 7-ring PAH constituent with a potential role for the aryl hydrocarbon receptor (AhR). Toxicol Lett 315, 64-76. doi:10.1016/j.toxlet.2019.08.001

Kavlock, R. J., Bahadori, T., Barton-Maclaren, T. S. et al. (2018). Accelerating the pace of chemical risk assessment. Chem Res Toxicol 31, 287-290. doi:10.1021/acs.chemrestox.7b00339

Kutsarova, S. S., Yordanova, D. G., Karakolev, Y. H. et al. (2019). UVCB substances II: Development of an endpoint-nonspecific procedure for selection of computationally generated representative constituents. Environ Toxicol Chem 38, 682-694. doi:10.1002/etc.4358

Low, Y., Uehara, T., Minowa, Y. et al. (2011). Predicting drug-induced hepatotoxicity using QSAR and toxicogenomics approaches. Chem Res Toxicol 24, 1251-1262. doi:10.1021/tx200148a

Low, Y., Sedykh, A., Fourches, D. et al. (2013). Integrative chemical-biological read-across approach for chemical hazard classification. Chem Res Toxicol 26, 1199-1208. doi:10.1021/tx400110f

Luo, Y. S., Ferguson, K. C., Rusyn, I. et al. (2020). In vitro bioavailability of the hydrocarbon fractions of dimethyl sulfoxide extracts of petroleum substances. Toxicol Sci 174, 168-177. doi:10.1093/toxsci/kfaa007

Malloy, T. F., Zaunbrecher, V. M., Batteate, C. M. et al. (2017). Advancing alternative analysis: Integration of decision science. Environ Health Perspect 125, 066001. doi:10.1289/EHP483

Marvel, S. W., To, K., Grimm, F. A. et al. (2018). ToxPi Graphical User Interface 2.0: Dynamic exploration, visualization, and sharing of integrated data models. BMC Bioinf 19, 80. doi:10.1186/s12859-018-2089-2

McKee, R. H. and White, R. (2014). The mammalian toxicological hazards of petroleum-derived substances: An overview of the petroleum industry response to the high production volume challenge program. Int J Toxicol 33, Suppl 1, 4S-16S. doi:10.1177/1091581813514024

McKee, R. H., Nicolich, M., Roy, T. et al. (2014). Use of a statistical model to predict the potential for repeated dose and developmental toxicity of dermally administered crude oil and relation to reproductive toxicity. Int J Toxicol 33, Suppl 1, 17S-27S. doi:10.1177/1091581813504226

McKee, R. H., Adenuga, M. D. and Carrillo, J. C. (2015). Characterization of the toxicological hazards of hydrocarbon solvents. Crit Rev Toxicol 45, 273-365. doi:10.3109/10408444.2015.1016216

McKee, R. H., Tibaldi, R., Adenuga, M. D. et al. (2018). Assessment of the potential human health risks from exposure to complex substances in accordance with REACH requirements. “White spirit” as a case study. Regul Toxicol Pharmacol 92, 439-457. doi:10.1016/j.yrtph.2017.10.015

Murray, F. J., Roth, R. N., Nicolich, M. J. et al. (2013). The relationship between developmental toxicity and aromatic-ring class profile of high-boiling petroleum substances. Regul Toxicol Pharmacol 67, Suppl 2, S46-59. doi:10.1016/j.yrtph.2013.05.003

National Academies of Sciences Engineering and Medicine (2017). Using 21st Century Science to Improve Risk-Related Evaluations. Washington, DC, USA: The National Academies Press.

National Research Council (2014). A Framework to Guide Selection of Chemical Alternatives. Washington, DC, USA: The National Academies Press.

Nicolich, M. J., Simpson, B. J., Murray, F. J. et al. (2013). The development of statistical models to determine the relationship between aromatic-ring class profile and repeat-dose and developmental toxicities of high-boiling petroleum substances. Regul Toxicol Pharmacol 67, Suppl 2, S10-29. doi:10.1016/j.yrtph.2012.11.015

Onel, M., Beykal, B., Ferguson, K. et al. (2019). Grouping of complex substances using analytical chemistry data: A framework for quantitative evaluation and visualization. PLoS One 14, e0223517. doi:10.1371/journal.pone.0223517

Redman, A. D., Parkerton, T. F., Comber, M. H. et al. (2014). PETRORISK: A risk assessment framework for petroleum substances. Integr Environ Assess Manag 10, 437-448. doi:10.1002/ieam.1536

Reif, D. M., Martin, M. T., Tan, S. W. et al. (2010). Endocrine profiling and prioritization of environmental chemicals using ToxCast data. Environ Health Perspect 118, 1714-1720. doi:10.1289/ehp.1002180

Reif, D. M., Sypa, M., Lock, E. F. et al. (2013). ToxPi GUI: An interactive visualization tool for transparent integration of data from diverse sources of evidence. Bioinformatics 29, 402-403. doi:10.1093/bioinformatics/bts686

Roth, R. N., Simpson, B. J., Nicolich, M. J. et al. (2013). The relationship between repeat-dose toxicity and aromatic-ring class profile of high-boiling petroleum substances. Regul Toxicol Pharmacol 67, Suppl 2, S30-45. doi:10.1016/j.yrtph.2013.05.010

Roy, T. A., Johnson, S. W., Blackburn, G. R. et al. (1988). Correlation of mutagenic and dermal carcinogenic activities of mineral oils with polycyclic aromatic compound content. Fundam Appl Toxicol 10, 466-476. doi:10.1016/0272-0590(88)90293-x

Rusyn, I. and Greene, N. (2018). The impact of novel assessment methodologies in toxicology on green chemistry and chemical alternatives. Toxicol Sci 161, 276-284. doi:10.1093/toxsci/kfx196

Sirenko, O., Cromwell, E. F., Crittenden, C. et al. (2013). Assessment of beating parameters in human induced pluripotent stem cells enables quantitative in vitro screening for cardiotoxicity. Toxicol Appl Pharmacol 273, 500-507. doi:10.1016/j.taap.2013.09.017

Tibshirani, R., Hastie, T., Narasimhan, B. et al. (2002). Diagnosis of multiple cancer types by shrunken centroids of gene expression. Proc Natl Acad Sci U S A 99, 6567-6572. doi:10.1073/pnas.082099299

UNECE – United Nations Economic Commission for Europe (2020). Globally Harmonized System of Classification and Labelling of Chemicals (GHS). http://www.unece.org/trans/danger/publi/ghs/ghs_welcome_e.html (acessed 01.04.2020).

U.S. EPA (2012). Benchmark Dose Technical Guidance. Risk Assessment Forum, US EPA. EPA/100/R-12/001. http://www.epa.gov/raf/publications/pdfs/benchmark_dose_guidance.pdf (accessed 10.04.2018).

Zhu, H., Bouhifd, M., Donley, E. et al. (2016). Supporting read-across using biological data. ALTEX 33, 167-182. doi:10.14573/altex.1601252

Most read articles by the same author(s)