Effect of age toxicokinetics among human volunteers exposed to propylene glycol monomethyl ether (PGME)


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Inproceedings: an article in a conference proceedings.
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Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Effect of age toxicokinetics among human volunteers exposed to propylene glycol monomethyl ether (PGME)
Title of the conference
51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
Hopf Nancy B., Vernez David, Berthet Aurélie, Charrière Nicole, Arnoux Christine, Tomicic Catherine
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Issued date
The Toxicologist CD
Rationale: Aging adults represent the fastest growing population segment in many countries. Physiological and metabolic changes in the aging process may alter how aging adults respond to exposures compared to younger workers. Current preventive workplace exposure measures may therefore not be sufficiently protective for the aging workforce. In a controlled human toxicokinetic study (exposure chamber; 12m3), the volunteers (n=11) were men and women over the age of 58 years and exposed
to a commonly used, low neurotoxic glycol ether; PGME (CAS no. 107-98- 2) (50 ppm, 6 hours). Oxidative metabolism (Michaelis-Menten) is the major pathway and conjugation the minor in humans. Metabolites, conjugated and free PGME are eliminated through the kidneys, and the elimination kinetics is dose-dependent (0 order). Scope: (1) compare the toxicokinetic profile of PGME obtained in the aging volunteers (58- 62 years) to young volunteers (20-25 years) from a previous study; (2) Test the predictive power of an existing PGME toxicokinetic compartment model for aging persons against urinary PGME concentrations found in volunteers from our experimental study. Experimental procedure: Urine samples were collected before, every 2-hour during exposures for six hours, and ad-lib for additional 20 hours. Urinary analysis of free and total PGME was performed using capillary GC/FID. The toxicokinetic model (Berkley Madonna software) was ageadjusted. Results. Urinary free and total PGME concentration rose rapidly, and did not reach an apparent plateau level during exposure. Less conjugation was observed in the older group. The predictive model developed for the young group predicted
well total PGME in the aging group but not free PGME. The age adjusted toxicokinetic model's Vmax1 had to be changed for the aging group, implying slower enzymatic pathway. Conclusion: The toxicokinetic model did not predict well if only the physiological parameters were adjusted for aging adults (existing model); a substance specific metabolic rate parameter was also needed.
Age Factors, Aged, Aging/metabolism, Dose-Response Relationship, Drug, Inhalation Exposure/adverse effects, Propylene Glycols/pharmacokinetics, Propylene Glycols/toxicity, Sex Factors
Create date
07/05/2012 18:08
Last modification date
20/08/2019 15:42
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