Ethylene glycol monoethyl ether acetate(EGEEA)—a reproductive toxicant

Ethylene glycol monoethyl ether acetate (CAS: 111-15-9), also called EGEEA is used in automobile lacquers and also as a solvent for nitrocellulose, oils and resins [1]. Ethylene glycol monoethyl ether acetate appears as a clear colorless liquid with a pleasant odor. It is less dense than water [2]. Evidence showed that EGEEA is classified as a Group 2 reproductive toxicant [3]. Here, we describe national toxicology program studies conducted on mice to support this idea.  

Ethylene Glycol Monoethyl Ether Acetate (EGEEA) was tested for reproductive toxicity in Swiss CD-1 mice using the RACB protocol. It was part of a series of glycol ethers & congeners evaluated for structure-activity correlations using this design. Data collected on body weights, clinical signs, & food/water consumption during the dose-range-finding segment (Task 1) were used to set concns for the main study (Task 2) at 0.5%, 1.0%, & 2.0% EGEEA in drinking water. These concns produced calculated consumption estimates of nearly equal to 0.93, 1.86, & 3.0 g/kg/day. 

During Task 2, body weights were slightly reduced (<10%) only at the top dose, the same level at which water consumption was reduced by nearly equal to 20%. During Task 2, the mean number of litters/pair was reduced in the middle & high dose groups by 8% & 70%, respectively. The number of live pups/litter in these groups was reduced by 27% & 98%. In these two dose groups, the adjusted live pup weight also was reduced, by 5% & 13%, respectively. Thus, animals consuming 1% or 2% EGEEA delivered fewer, lighter pups in the presence of no or modest changes in body weight. 

The Task 3 crossover used control & 2% EGEEA mice, & found that the EGEEA-treated females produced fewer fertile matings, & these had 94% fewer pups, & only 7% of them were born alive. There were no effects seen with EGEEA-treated males. The control & 2% EGEEA F0 mice were killed & necropsied. There were no treatment-related changes in female body or organ weights, while treated males weighed 7% less than controls, & absolute testis weight was reduced by 9%. While there were no changes in sperm motility or density, the % abnormal forms doubled in the 2% EGEEA group at necropsy (from a control level of 3% abnormal forms). 

There were insufficient live pups from the 2% EGEEA group to provide pups for an evaluation of the second generation at that concn, so in Task 4, mice were evaluated from the control, 0.5% EGEEA-treated, & 1% EGEEA-treated groups. There was no indication of treatment-related reductions in growth to weaning, or in growth to mating at 74 +/- 10 days of age. At the mating trial, there was a 50% reduction in the number of pairs that were confirmed sperm positive in the 1% group, but no change in the fertility of those pairs, & no change in the pup indices as a result of those matings. After delivery of the F2's, all the mice were killed, & the F1's were necropsied. While there were no reductions in body weight, there was a 6% reduction in female relative liver weight at 1%. In males, liver weight was increased by 9% & 7% in the 0.5% & 1% EGEEA-treated groups, respectively, while epididymis weight was reduced by 9% in the 1% EGEEA group. Cauda epididymal sperm density was reduced by 30% at the top dose.

In summary, EGEEA was a reproductive toxicant in F0 mice, based on the large reductions in pup number in treated females & increased abnormal sperm in males. It was also a reproductive toxicant in the F1's, reducing epididymis weight & sperm number. The effects in the second generation were seen in the presence of changes in liver weight [4].

Reference

[1] https://www.biesterfeld.com/en/at/product/ethylene-glycol-monoethyl-ether-acetate/
[2] https://pubchem.ncbi.nlm.nih.gov/compound/8095
[3] https://www.sanei.or.jp/images/contents/328/EGEEA_rep.pdf
[4] https://pubchem.ncbi.nlm.nih.gov/compound/8095#section=Ecotoxicity-Excerpt

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