Document Detail

Effects of Solutol (Kolliphor) and Cremophor in Polyethylene Glycol 400 Vehicle Formulations in Sprague-Dawley Rats and Beagle Dogs.
MedLine Citation:
PMID:  23616145     Owner:  NLM     Status:  Publisher    
When conventional vehicles (eg, methylcellulose and water) impart inadequate physical, chemical, and/or biological properties for proper toxicological assessment of test article formulations, nonconventional vehicles may be considered. Often toxicity data for nonconventional vehicle formulations are limited. Studies were conducted to collect toxicity data from a rodent and a non-rodent species given 2 nonconventional vehicles, Solutol HS15/polyethylene glycol (PEG) 400 and Cremophor RH40/PEG 400, with differing formulations and dose volumes (10 mL/kg for rats; 2 or 5 mL/kg for dogs). In rats, both vehicles caused increase in kidney weights (males only) and decrease in thymic weights (males only) without concurrent microscopic findings; altered urine electrolytes, minimally decreased serum electrolytes (males only), and increased serum total cholesterol (females only) were also present. The Cremophor formulation was also associated with increased serum urea (males only) and urine phosphorus: creatinine. For rats given the Solutol formulation, both genders had decreased urine glucose parameters and males had increased urine volume. In dogs, loose/watery feces and emesis were present given either vehicle, and mucus-cell hyperplasia of the ileum was present given the Solutol formulation. Increased red blood cell mass and decreased urine volume in dogs given 30% Solutol/70% PEG 400 (5 mL/kg/d) were likely due to subclinical dehydration and hemoconcentration. For the Cremophor formulations, dose volume-dependent increased incidence of minimal subepithelial gastric hemorrhage was noted in dogs, and dogs given 5 mL/kg/d showed increased serum urea nitrogen. Overall, regardless of the formulation or dose volume, neither vehicle produced overt toxicity in either species, but the Solutol formulation produced fewer effects in rats. Generally, lower dose volumes minimized the severity and/or incidence of findings.
Alan H Stokes; Daniel C Kemp; Brenda Faiola; Holly L Jordan; Christine L Merrill; James R Hailey; Randy E Brown; David W Bailey
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-4-24
Journal Detail:
Title:  International journal of toxicology     Volume:  -     ISSN:  1092-874X     ISO Abbreviation:  Int. J. Toxicol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-4-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9708436     Medline TA:  Int J Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Safety Assessment, Research Triangle Park, NC, USA.
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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