Toxicological Sciences, Vol 50, 249-258, Copyright © 1999 by Society of Toxicology
EW Carney, JW Crissman, AB Liberacki, CM Clements and WJ Breslin
This study evaluated propylene glycol monomethyl ether (PGME) in a rat
2-generation reproduction study, which included non-traditional study end
points, such as sperm count and motility, developmental landmarks, estrous
cyclicity, and weanling organ weights. Groups of 30 male and 30 female
Sprague-Dawley rats (6-weeks-old) were exposed to 0, 300, 1000, or 3000 ppm
of PGME vapors via inhalation for 6 hours/day, 5 days/week prior to mating,
and 6 hours/day, 7 days/week during mating, gestation, and lactation, for 2
generations. These concentrations corresponded to estimated oral equivalent
doses of 0, 396, 1325, or 3974 mg/kg/day. At 3000 ppm, toxicity in the P1
and P2 adults was marked, as evidenced by sedation during and after
exposure, and mean body weights which were as much as 21% lower than
controls. This marked parental toxicity was accompanied by lengthened
estrous cycles, decreased fertility, decreased ovary weights, and
histologic ovarian atrophy in maternal rats. In the offspring from these
dams, decreased body weights, reduced survival and litter size, slight
delays in puberty onset, and histologic changes in liver and thymus in the
F1 and F2 offspring were observed. The nature of the reproductive/neonatal
effects and their close individual animal correlation with decreased
maternal body weights suggested that these effects were secondary to
general toxicity and/or nutritional stress. No such reproductive/neonatal
effects were observed at 1000 ppm, a concentration which caused less
marked, but significant body weight effects without sedation. There were no
treatment-related effects of any kind noted at 300 ppm of PGME. Therefore,
the no-observable-effect level (NOEL) for reproductive/neonatal effects was
1000 ppm, and that for parental toxicity was 300 ppm.
ARTICLES
Assessment of adult and neonatal reproductive parameters in Sprague- Dawley rats exposed to propylene glycol monomethyl ether vapors for two generations
Health and Environmental Research Laboratories, The Dow Chemical Company, Midland, Michigan 48674, USA.
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