Results of testing fifteen glycol ethers in a short-term in vivo reproductive toxicity assay.

Abstract

Fifteen glycol ethers were investigated for their potential to cause adverse reproductive toxic effects using an in vivo mouse screening bioassay. Pregnant mice were orally dosed once per day on days 7 through 14 of gestation at concentrations causing 0 to 41% maternal mortality. Reproductive endpoints included pup survival in utero (percent of live litters/pregnant survivors), pup perinatal and postnatal survival (number of live pups per litter, number of dead pups per litter, and pup survival to 2.5 days of age), and pup body weight statistics (weight at birth and weight at 2.5 days of age). The study was conducted in two phases: a dose range-finding phase using nonpregnant female mice, and a definitive reproductive phase using time-mated mice. The range-finding phase sought to identify, for each chemical, the maternal LD10 as the target dose. However, based upon reproductive phase results, such an exact dose was impractical to achieve. Thus, a range from the LD5 to the LD20 was considered a sufficient challenge dose that would not affect results due to high mortality, i.e., greater than the LD20. Glycol ethers were assigned to groups having different priorities for further testing based upon whether a sufficient challenge dose was administered and the degree of effects recorded for each chemical.(ABSTRACT TRUNCATED AT 250 WORDS)

Glymes as versatile solvents for chemical reactions and processes: from the laboratory to industry

“…McGregor et al 8 studied the exposure of male rats to 250 or 1000 ppm diglyme, and found diglyme was reproductive toxicant causing increased sperm abnormalities. Schuler et al 9 examined fifteen glycol ethers for their adverse reproductive toxic effects using an in vivo mouse screening bioassay; this group found that all mice receiving glycol ethers having terminal methyl groups, i.e., ethylene glycol monomethyl ether, monoglyme, diethylene glycol monomethyl ether, diglyme and triglyme produced few viable litters (0, 0, 16, 0, and 0% respectively); similar results were also observed for ethylene glycol monoether ether and ethyl monoglyme (0 and 11% viable litters respectively). However, other two ethyl ethers (diethylene glycol monoethyl ether and ethyl diglyme), three butyl ethers (ethylene glycol monobutyl ether, diethylene glycol monobutyl ether, butyl diglyme), and three glycol ethers with terminal hydroxyl groups (ethylene glycol, diethylene glycol and triethylene glycol) failed to show this kind of fetotoxicity.…”

A comparison of developmental toxicity evident at term to postnatal growth and survival using ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, and ethanol

“…(1) Inhalation or dermal exposure to maternally toxic levels of EGBE has been shown to produce embryo lethality but not a significant incidence of malformation in the rat [6-81. In the Chernoff-Kavlock assay, mice intubated with 1,180 mg EGBE/ kg had fewer litters (no confirmation of pregnancy given), but there were no significant differences in mean litter size, pup survival, or pup weight [17]. The current teratology probe showed an increase in embryo lethality only at maternally toxic doses, but there was no significant evidence of developmental toxicity in the postnatal study at the same dose levels.…”

Scientific Opinion on Flavouring Group Evaluation 10, Revision 2 (FGE.10Rev2): Aliphatic primary and secondary saturated and unsaturated alcohols, aldehydes, acetals, carboxylic acids and esters containing an additional oxygenated functional group and lactones from chemical groups 9, 13 and 30

“…The supporting and structurally related substances are listed in brackets. (Gulati et al, 1985b;Heindel et al, 1990) FGE.10 refers to (EPA, 1999;EU-RAR, 2004a (Gulati et al, 1985b;Heindel et al, 1990) FGE.10 refers to (EPA, 1999;EU-RAR, 2004a (Gulati et al, 1985b;Heindel et al, 1990) FGE.10 refers to (EPA, 1999;EU-RAR, 2004a (Hardin et al, 1987;Schuler et al, 1984;Smith, 1983) FGE.10 refers to (EPA, 1999;EU-RAR, 2004a (Hellwig, 1991b) EFSA Journal 2011; 9(7):2164 2 Dose range-finding phase: Based on the results of this dose range-finding study the highest concentration investigated further was 2 % in the drinking water.…”