U.S. Federal Agency interests and key considerations for new approach methodologies for nanomaterials

Abstract

of such State, or (B) which affects trade, traffic, transportation, or commerce described in clause (A).(4) The terms "distribute in commerce" and "distribution in commerce"' when used to describe an action taken with respect to a chemical substance or mixture or article containing a substance or mixture mean to sell, or the sale of, the substance, mixture, or article in commerce ; to introduce or deliver for introduction into commerce, or the introduction or delivery for intr-oduction into commerce of, the substance, mixture, or article; or to hold, or the holding of, the substance, mixture, or article after its introduction into commerce.(5) The term "environment" includes water, air, and land and the i interrelationship which exists among and between water, air, and land and all living things.(6) The term "health and safety study" means any study of any effect of a chemical substance or mixture on health or the environment or on both, including underlying data and epidemiological studies, studies of occupational exposure to a chemical substance or mixture, toxicological, clinical, and ecological studies of a chemical substance or mixture, and any test performed pursuant to this Act.(7) The term "manufacture" means to import into the customs territory of the United States (as defined in general headnote 2 of the Tariff Schedules of the United States), produce, or manufacture. 19 USC 1202.(8) The term "mixture" means any combination of two or more chemical substances if the combination does not occur in nature and is not, in whole or in part, the result of a chemical reaction; except that such term does include any combination which occurs, in whole or in part, as a result of a chemical reaction if none of the chemical substances comprising the combination is a new chemical substance and if tlie combination could have been manufactured for commercial purposes without a chemical reaction at the time the chemical substances comprising the combination were combined.(9) The term "new chemical substance" means any chemical substance which is not included in the chemical substance list compiled and published under section 8 (b).Post, p. 2027. (10) The term "process" means the preparation of a chemical substance or mixture, after its manufacture, for distribution in commerce-(A) in the same form or physical state as, or in a different form or physical state from, that in which it was received by the person so preparing such substance or mixture, or (B) as part of an article containing the chemical substance .;;:;>• or mixture. (11) The term "processor" means any person who processes a chemical substance or mixture.(12) The term "standards for the development of test data" means a prescription of-(A) the-(i) health and environmental effects, and (ii) information relating to toxicity, persistence, and other characteristics which affect health and the environment, for which test data for a chemical substance or mixture are to be developed and any analysis that is to be performed on such data, and -(B) to the extent necess...

IVIVE: Facilitating the Use of In Vitro Toxicity Data in Risk Assessment and Decision Making

“…One topic that has generated widespread research interest is IVIVE of studies using ENMs, including how to assess ENM dosimetry [ 195 ]. Similar approaches would typically also work for microplastic and nanoplastic particles with some exceptions (for example, larger microplastic particles becoming trapped during passage through an exposure system) [ 196 ].…”

Technical framework for enabling high-quality measurements in new approach methodologies (NAMs)

“…Another example of a one-time preliminary measurement is for ELISA when evaluating particles to assess if cytokines produced by the cell could be adsorbed by particles, thereby reducing the apparent cytokine concentration in the overlying media (Petersen et al, 2020). A third example of a one-time preliminary measurement is to perform a 0-h experiment immediately after the test substance is added, after which the remaining steps in the assay are performed and the results are compared to those of the negative control (no test substance added) (Petersen et al, 2022b). A fourth example is to perform preliminary experiments to assess the potential for losses in the exposure concentration during the course of an experiment such as for compounds that bind to the test plates or are volatile.…”

Neurotoxicity of Engineered Nanomaterials: Testing Considerations

“…In Table 1 , we have summarized intrinsic characteristics and properties of ENM in biological systems that may affect neurotoxicity assay outcomes as well as approaches that can be used to avoid such assay artifacts and potential misclassification. Above all, the reliability of in vitro testing approaches for neurotoxicity relies heavily on the use of appropriate ENM dispersion protocols which have been developed over many years for in vitro testing in general [e.g., ( 35 , 36 )]. Neurotoxicity testing should also incorporate the necessary control experiments to ensure that assay readouts are not disturbed due to interference of ENM with assay components such as, for instance, by adsorption of dyes, inactivation of reagents or scattering or quenching of (fluorescence) light.…”

“…Neurotoxicity testing should also incorporate the necessary control experiments to ensure that assay readouts are not disturbed due to interference of ENM with assay components such as, for instance, by adsorption of dyes, inactivation of reagents or scattering or quenching of (fluorescence) light. Approaches for such control experiments have been proposed and described by various investigators [e.g., (36)(37)(38)] and can be used as a basis when developing novel neurotoxicity assays. A particularly great progress in improving in vitro assays for ENM has been made following the recognition of the role of the protein/lipid corona in the toxicity of ENMs.…”

“…In vitro assays Effects of agglomeration status and dissolution rate on ENM toxicity Use of standardized dispersion protocols; characterization of the physicochemical properties of ENM in test environment (e.g., cell culture medium) (35,36) Interferences with in vitro assays (e.g., adsorption and/or inactivation of assay reagents, disturbance of assay readouts by quenching, auto-fluorescence)…”