Quality assurance for nanomaterial inhalation toxicity testing.

ABSTRACT

The recent revision of OECD inhalation toxicology test guidelines 412 and 413 presents new challenges for both the study director (SD) and quality assurance (QA) personnel when conducting GLP (good laboratory practice) studies. In the case of nanomaterial inhalation exposure studies, GLP has rarely been applied, yet the new revisions are applicable to soluble and insoluble nanomaterials, as well as conventional chemicals. For example, the new guidelines require an additional bronchoalveolar lavage (BAL) fluid assay and lung burden measurement during the post-exposure observation (PEO) period, plus nanomaterial physicochemical characterization before and after nano-aerosol generation when exposing experimental animals. Implementing these revised guidelines will prove especially challenging for QA measures related to the physicochemical characterization and aerosolization of test nanomaterials. Therefore, this review examines the key elements involved in nanomaterial inhalation GLP testing under the revised OECD guidelines, suggests an alternative to the increased animal numbers, in consideration of animal welfare and with scientific merits, and discusses the limitation of toxicokinetic estimation using the new testing guidelines.