Dosimetry, in the context of inhalation toxicity testing, is the accurate determination of test article dose (whether that be whole smoke or any other inhalable aerosol) reaching the target cells, and is one of the key components in the establishment of a reliable dose response [19].
In the initiation phase of the I/P bioassay, groups of CD-1 mice received an initiating dose of 50 microl of test article for 5 consecutive days, followed by promotion with 50 microl of phorbol-12-myristate-13-acetate phorbol-12-myristate-13-acetate phorbol-12-myristate-13-acetate phorbol-12-myristate-13-acetate phorbol-12-myristate-13-acetate
In the chronic bioassay, groups of 50 C3H/HeJ mice received twice weekly applications of 50 microl of test article for at least 2 years.
HJP and SEL participated in sample collection, laboratory testing and drafting of article.
AH participated in sample collection, laboratory testing and drafting of article with inputs from MV, V di M, EC and PD.
AA participated in sample collection, laboratory testing and drafting of article with inputs from MV, V di M, EC, JV and PD.
Primary Irritation Index (P.I.I). of test article was calculated following test completion.
There is an approximate 2-week rest period followed by a Challenge phase of a single 24-h patch application of test article applied to a naïve site on the back.
RNA recovery was determined using a set of blood samples spiked with a known amount of test article (MRX34) in a serial dilution (spike-in samples).
However, a disadvantage of whole-body exposure is that possible deposition of test article on animal fur or skin may result in additional unquantified oral exposure to the animals as a result of grooming behavior.
These analytical methods are used to assess the concentration of test article in nonclinical formulation, formulation homogeneity and formulation stability in support of regulated nonclinical studies (for example: safety, toxicokinetic, and pharmacokinetic studies).
