Effects of Miglyol 812 on rats after 4 weeks of gavage as compared with methylcellulose/Tween 80

Rani S. Sellers, M. Antman, J. Phillips, K. N. Khan, S. M. Furst

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Miglyol 812 is a medium-chain triglyceride used in toxicology studies as an excipient to improve test compound solubility/absorption. As part of a larger toxicology study, 15 Wistar Han IGS rats/sex/group were dosed by oral gavage for 4 weeks with 10 mL kg-1 day-1 of 100% Miglyol 812 or 0.5% methylcellulose/0.1% Tween 80 in water (MC-T) followed by 4 weeks without treatment to evaluate the potential effects of this excipient in long-term toxicology studies relative to a traditional excipient such as MC-T. Clinical signs evident during the dosing phase included soft and/or mucoid stool in 12/15 males and 11/15 females treated with Miglyol 812 but in no animals treated with MC-T. Animals treated with Miglyol 812 had a 6-7% statistically significant reduction in body weight gain as compared to MC-T-treated animals. Statistically significant changes in clinical chemistry parameters as compared to MC-T included decreased blood urea nitrogen (50% and 29% in males and females, respectively), increased cholesterol (1.6-fold and 1.5-fold in males and females, respectively), decreased total protein (6% and 8% in males and females, respectively), decreased globulins (15% and 11% in males and females, respectively), and increased triglycerides (2.8-fold and 1.7-fold in males and females, respectively). Absolute and relative thymic weights decreased 28% and 24%, respectively, in males, and 18% and 17%, respectively, in females without histological alterations. Histopathology revealed increased alveolar histiocytosis with focal interstitial inflammation in lungs in 5/10 males and 7/10 females treated with Miglyol 812 compared to only 1/10 males and 1/10 females treated with MC-T. All effects were reversible during the recovery period. Results of this study indicate that 100% miglyol 812 produces reversible gastrointestinal effects and decreases in body weight gains along with changes in several serum chemistry parameters. Therefore, it should not be considered innocuous when delivered by oral gavage in long-term rodent toxicology studies.

Original languageEnglish (US)
Pages (from-to)423-432
Number of pages10
JournalDrug and Chemical Toxicology
Volume28
Issue number4
DOIs
StatePublished - 2005
Externally publishedYes

Fingerprint

Methylcellulose
Polysorbates
Rats
Animals
Excipients
Toxicology
Cholesterol
Urea
Triglycerides
Blood
Solubility
Nitrogen
Proteins
Recovery
Weight Gain
Globulins
Body Weight
Histiocytosis
miglyol 812
Water

Keywords

  • Drug delivery
  • Excipients
  • Methylcellulose-tween
  • Miglyol
  • Rat

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmacology
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Effects of Miglyol 812 on rats after 4 weeks of gavage as compared with methylcellulose/Tween 80. / Sellers, Rani S.; Antman, M.; Phillips, J.; Khan, K. N.; Furst, S. M.

In: Drug and Chemical Toxicology, Vol. 28, No. 4, 2005, p. 423-432.

Research output: Contribution to journalArticle

Sellers, Rani S. ; Antman, M. ; Phillips, J. ; Khan, K. N. ; Furst, S. M. / Effects of Miglyol 812 on rats after 4 weeks of gavage as compared with methylcellulose/Tween 80. In: Drug and Chemical Toxicology. 2005 ; Vol. 28, No. 4. pp. 423-432.
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