Age-Specific Absolute and Relative Organ Weight Distributions For B6C3F1 Mice

Abstract

The B6C3F1 mouse is the standard mouse strain used in toxicology studies conducted by the National Cancer Institute (NCI) and the National Toxicology Program (NTP). While numerous reports have been published on growth, survival, and tumor incidence, no overall compilation of organ weight data is available. Importantly, organ weight change is an endpoint used by regulatory agencies to develop toxicity reference values (TRVs) for use in human health risk assessments. Furthermore, physiologically based pharmacokinetic (PBPK) models, which utilize relative organ weights, are increasingly being used to develop TRVs. Therefore, all available absolute and relative organ weight data for untreated control B6C3F1 mice were collected from NCI/NTP studies in order to develop age-specific distributions. Results show that organ weights were collected more frequently in NCI/NTP studies at 2-wk (60 studies), 3-mo (147 studies), and 15-mo (40 studies) intervals than at other intervals, and more frequently from feeding and inhalation than drinking water studies. Liver, right kidney, lung, heart, thymus, and brain weights were most frequently collected. From the collected data, the mean and standard deviation for absolute and relative organ weights were calculated. Results show age-related increases in absolute liver, right kidney, lung, and heart weights and relatively stable brain and right testis weights. The results suggest a general variability trend in absolute organ weights of brain < right testis < right kidney < heart < liver < lung < spleen < thymus. This report describes the results of this effort.

Characterization of age-associated changes in peripheral organ and brain region weights in C57BL/6 mice

“…In agreement with several studies, we observe an increase in body weight until 12 months of age after which body weight then remains constant (Cameron et al, 1985;Cao et al, 2003;Fahlstrom et al, 2011;Glatt et al, 2007;Halloran et al, 2002;Marino, 2012;Reynolds et al, 2002). However, other studies have noted a decrease in body weight at the end of life in various mammals including humans (Eurich and Lindner, 1984;Marino, 2012;Sawabe et al, 2006).…”

“…However, other studies have noted a decrease in body weight at the end of life in various mammals including humans (Eurich and Lindner, 1984;Marino, 2012;Sawabe et al, 2006). Although the influence of the environment certainly affects body weight, differences between species can also partly be explained by differences in rate of metabolism.…”

“…Age-related weight and volume modifications of the whole brain, and some cerebral regions, have also previously been observed in human and different animal species (Armstrong, 1990;Carroll et al, 2011;Courchesne et al, 2000;Eurich and Lindner, 1984;McNelly, 1977, 1981;Ho et al, 1980;Marino, 2012;Mirich et al, 2002;Penzes et al, 1989;Rowlatt et al, 1976;Sawabe et al, 2006;Scahill et al, 2003;Svennerholm et al, 1997;Walhovd et al, 2011). However, there is no data compiled for the C57BL/6 strain of mice concerning age-associated changes in specific regions of the brain, in particular for the striatum and hippocampus.…”

A Physiologically Based Pharmacokinetic Model of Rifampin in Mice

“…The model parameters and probability distributions are given in Tables 1 and 2. The distribution types and coefficients of variation chosen were consistent with those typically used for PBPK models (46)(47)(48)(49). Distributions were truncated at the mean Ϯ 3 standard deviations (SD) to exclude biologically implausible values.…”

Generating Background Information of Laboratory Chinese Jue-ma Minipigs, a Plateau Swine Species

“…Compared to the Gottingen minipigs, the absolute organ weights of Jue-ma are significant higher than Gottingen minipigs, while most relative organ weights are lower than Gottingen minipigs. Previous reports demonstrated that the absolute and relative organ weights are affected by many factors, such as sex, age class, body weight, and nutritional status (Marino, 2012;Lessard-Beaudoin et al, 2015). The differences between Jue-ma and Gottingen minipigs might cause by body weights.…”