Teratologic potential of 2-methoxyethanol and transplacental distribution of its metabolite, 2-methoxyacetic acid, in non-human primates.
The embryotoxic effects of 2-methoxyethanol (2-ME) were studied in non-human primates to better assess the risk for women of child-bearing age exposed to this agent. Macaca fascicularis females were treated daily throughout the organogenetic phase of pregnancy (days 20-45) by gavage and the fetuses collected at day 100 by Caesarean section. At the highest dose (0.47 mmole/kg), all eight pregnancies ended in death of the embryo. One of these dead embryos was abnormal, missing a digit on each forelimb. At the middle dose (0.32 mmole/kg), three of 10 pregnancies ended in embryonic death, presumably due to 2-ME exposure and three of 13 pregnancies met a similar fate at the low dose (0.16 mmole/kg). In each of these two groups, an additional pregnancy was lost to abortion, but both were thought to be spontaneous, which usually occurs in 10-20% of untreated macaque pregnancies. These results indicate that 2-ME is a potent toxin to the developing primate embryo and thereby furthers the concern about exposure of pregnant women to this agent, although maternal toxicity was evident in nearly all treated pregnancies and was especially severe in the high-dosage animals. Distribution of the major metabolite of 2-ME, 2-methoxyacetic acid (2-MAA), indicated a long half-life (ca. 20 h), resulting in accumulation of metabolite in maternal serum after repeated daily dosing. Transplacental studies revealed uniform distribution in the embryo and extraembryonic fluids at a concentration similar to that in maternal serum. The yolk sac, on the other hand, accumulated a very high concentration of 2-MAA, but the embryotoxic significance of this observation is unknown.
Scott
W J
WJ
Department of Pediatrics, Children's Hospital Research Foundation, Cincinnati, Ohio 45229-2899.
Fradkin
R
R
Wittfoht
W
W
Nau
H
H
D000085:Acetates / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism; D005026:Ethylene Glycols / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D008252:Macaca fascicularis; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D012997:Solvents / Q000493:pharmacokinetics / Q000633:toxicity*; D013723:Teratogens
D000085:Acetates; D005026:Ethylene Glycols; D012997:Solvents; D013723:Teratogens; C005219:methyl cellosolve; C013598:methoxyacetic acid