{"id":12,"date":"2008-03-18T08:21:11","date_gmt":"2008-03-18T13:21:11","guid":{"rendered":"http:\/\/blogs.edf.org\/nanotechnology\/2008\/03\/18\/on-the-road-to-in-vitro-testing-are-we-there-yet\/"},"modified":"2024-02-12T11:00:10","modified_gmt":"2024-02-12T16:00:10","slug":"on-the-road-to-in-vitro-testing-are-we-there-yet","status":"publish","type":"post","link":"https:\/\/blogs.edf.org\/health\/2008\/03\/18\/on-the-road-to-in-vitro-testing-are-we-there-yet\/","title":{"rendered":"On the Road to In Vitro Testing: Are We There Yet?"},"content":{"rendered":"

John Balbus, M.D., M.P.H.<\/em><\/span>, is Chief Health Scientist.<\/em><\/p>\n

EPA\u2019s recently released draft Nanotechnology Research Strategy (NRS)<\/a> proposes a tiered testing system to evaluate human toxicity of nanomaterials.\u00a0 It puts in vitro<\/em> tests, or those done in test tubes and petri dishes as opposed to living animals, front and center.\u00a0 EPA says the results of the first, in vitro<\/em> tier will be used for guidance on \u201cwhat health endpoints to monitor\u201d and the second, in vivo<\/em> tier will then help \u201cidentify those in vitro<\/em> assays that correlate with in vivo nanomaterial toxicity or health effects.\u201d<\/p>\n

Wait a second.\u00a0 If the in vivo<\/em> testing is necessary in order to figure out what the in vitro<\/em> testing results really mean, how can the agency use the in vitro<\/em> testing results to figure out what health endpoints to monitor?\u00a0 This cart and horse confusion is a serious matter. <\/p>\n

The recent National Academy of Sciences (NAS) report, \u201cToxicity Testing in the 21st Century,\u201d<\/a> lays out a compelling vision of a toxicology future far less reliant on animal testing.\u00a0 The prominence of in vitro<\/em> testing in the EPA\u2019s NRS is partly explained as a response to NAS recommendations.\u00a0 But NAS emphasizes that there\u2019s a decades-long road to get there, which will require a huge influx of research dollars that has yet to materialize.<\/p>\n

A recent paper by Fischer and Chan<\/a> highlights the current limitations of in vitro<\/em> testing for nanomaterials.\u00a0 The authors note that \u201cthe combined results from multiple studies of different cells in vitro<\/em> cannot be assumed to capture the same behavior as the same cells arranged in situ in an organ.\u201d\u00a0 They also point out the difficulty of using cellular and acellular systems to model impacts on coordinated cell signaling pathways and the influence of transport mechanisms via blood, lymph and bile.\u00a0 It\u2019s even harder to imagine how in vitro<\/em> tests can assess toxicity to complex biological processes like reproduction, development and immune response.\u00a0 And yet nanoparticles, by virtue of their transport properties and protein coatings, may very well have subtle but serious effects on all these systems.<\/p>\n

While the desire to push the science of in vitro<\/em> testing is admirable, EPA has to be careful not to push so hard that it all topples over like a house of cards.\u00a0 There\u2019s no escaping the fact that a huge amount of scientific research will be required to identify and characterize the myriad pathways and mechanisms operating in mammals that may produce toxicity \u2013 let alone to develop assays for all them that use cultured cells or acellular systems, which is what would be needed to replace animal testing.<\/p>\n

In vitro<\/em> assays are already proving themselves valuable for elucidating mechanisms and explaining observed effects, and they serve as a critical supplement to in vivo<\/em> testing.\u00a0 For acute effects like corrosivity and eye damage, they are definitely preferred over in vivo<\/em> tests, and that list should grow rapidly over the next few years.\u00a0 But they can\u2019t stand alone to predict many critical types of toxicity in humans, certainly not for the foreseeable future.<\/p>\n

The best way for in vitro<\/em> screening approaches to move forward is through parallel testing approaches using side-by-side in vitro<\/em> and in vivo<\/em> assays.\u00a0 Only in this way can we develop the data needed to determine how predictive in vitro<\/em> assays are of in vivo<\/em> behavior, and to understand how and to what extent the two approaches can work in concert to deepen our understanding of nanomaterial behavior.<\/p>\n

Done correctly, the development of rapid, inexpensive in vitro<\/em> screening tests will facilitate far more comprehensive and rapid assessment of potential risks from nanomaterials; however, done poorly, not only will there be potential for missing critical toxic effects, but the realization of the dream of effective in vitro<\/em> testing will be set back for many years.\u00a0 In its haste to get to an answer, it\u2019s not at all clear the EPA is prepared to do the hard work needed to get from here to there.<\/p>\n","protected":false},"excerpt":{"rendered":"

John Balbus, M.D., M.P.H., is Chief Health Scientist. EPA\u2019s recently released draft Nanotechnology Research Strategy (NRS) proposes a tiered testing system to evaluate human toxicity of nanomaterials.\u00a0 It puts in vitro tests, or those done in test tubes and petri dishes as opposed to living animals, front and center.\u00a0 EPA says the results of the …<\/p>\n","protected":false},"author":40,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[56094,5009,56087],"tags":[39169,39170,39160],"coauthors":[],"class_list":["post-12","post","type-post","status-publish","format-standard","hentry","category-new-testing-methods","category-health-science","category-nanotechnology","tag-in-vitro","tag-in-vivo","tag-national-academy-of-sciences-nas"],"acf":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/posts\/12","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/users\/40"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/comments?post=12"}],"version-history":[{"count":1,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/posts\/12\/revisions"}],"predecessor-version":[{"id":12506,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/posts\/12\/revisions\/12506"}],"wp:attachment":[{"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/media?parent=12"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/categories?post=12"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/tags?post=12"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/blogs.edf.org\/health\/wp-json\/wp\/v2\/coauthors?post=12"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}