Triphenyl phosphate (TPP) is used globally as an additive to furniture, foams, electrical cables and electronics products either as a flame retardant or plasticizer. TPP is a major component of the flame retardant mixture, Firemaster 550 (FM 550), which is widely used in products available throughout the United States, yet very few studies have assessed its presence in environmental or human samples. Analysis of household dust samples has shown TPP concentrations as high as 1800 µg/g of dust. This could have adverse health effects as developmental exposure to FM 550 resulted in an increase in body mass, altered thyroid hormones, and insulin resistance in rats. In this study we hypothesized that developmental exposure to the commercial flame retardant TPP would increase the rate of type 2 diabetes mellitus (T2DM) onset, cause endocrine disruption, and obesity in a well characterized rat model of type 2 diabetes (UCD-T2DM rats). We administered TPP to UCD-T2DM rats from gestational day 8.5 to postnatal day 21 (weaning) and studied their metabolic phenotype from either 3.5 or up to 6 months to assess obesity and T2DM, respectively. Perinatal TPP exposure increased body weight and adiposity, in both male and female rats at 3.5 months of age, while leptin and cumulative energy intake were elevated in males and females, respectively. At 6 months of age 79% of male rats, perinatally exposed to TPP, developed T2DM and had lower fasting blood glucose while only 33% of the vehicle treated rats developed T2DM. Time to T2DM was not assessed in female rats. These observations suggest that perinatal exposure to TPP causes obesity in both male and female UCD-T2DM rats and accelerates type 2 diabetes mellitus onset in male UCD-T2DM rats. We have also shown that the UCD-T2DM rat is an effective model for testing developmental exposure to environmental pollutants and their effects on diabetes and obesity.
|Advisor:||La Merrill, Michele|
|Commitee:||Havel, Peter, Newman, John|
|School:||University of California, Davis|
|Department:||Pharmacology and Toxicology|
|School Location:||United States -- California|
|Source:||MAI 55/02M(E), Masters Abstracts International|
|Subjects:||Toxicology, Surgery, Developmental biology|
|Keywords:||Obesity, Perinatal exposure, Triphenyl phosphate, Type 2 diabetes|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be