Disposition and metabolism of Ethylene glycol 2-ethylhexyl ether in Sprague Dawley rats, B6C3F1/N mice, and in vitro in rat hepatocytes

Atlee T. D. Watson, Benjamin C. Moeller, Melanie Doyle-Eisele, C. Edwin Garner, Chad R. Blystone, Jacob D. McDonald, and Suramya Waidyanatha

Radiolabel Description:
Carbon-14 in 2 positions: Ethylene glycol 2-ethylhexyl ether, [2-ethylhexyl-1-¹⁴C, ethylene glycol-1-¹⁴C]- 

Vehicles:
Oral, corn oil; Dermal, ethanol.

DOI: https://doi.org/10.22427/NTP-DATA-002-03310-0005-0000-4

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Publication

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Abstract

Ethylene glycol 2-ethylhexyl ether (EGEHE) is a glycol ether used in a number of industrial and commercial products including paints, coatings, and sealants. Given the absence of data, the present studies were conducted to characterize disposition and metabolism of EGEHE following oral and dermal exposure in male and female rats and mice. [14C]EGEHE was administered via a single oral gavage to Hsd:Sprague Dawley®SD® (HSD) rats (male: 50, 150, 500 mg/kg; female: 50 mg/kg) and B6C3F1/N mice (50 mg/kg, both sexes); disposition was investigated following dermal application of 50 mg/kg [14C]EGEHE in both species and sexes. EGEHE was well absorbed following oral exposure (rats: 80-96%, mice: 91-95%) and moderately absorbed following dermal exposure (rats: 25-37%, mice: 22-24%), and was rapidly excreted in urine with the majority of dose in urine recovered within 24 h. In both species, [14C]EGEHE-derived radioactivity was distributed to tissues with distribution relatively even (oral: 2.3-7.2% , dermal: 0.7-2.2%) with liver and kidney containing the highest levels. Metabolite profiling in urine from male rats administered 500 mg/kg demonstrated that EGEHE was extensively metabolized through numerous phase I and phase II metabolism with little to no parent EGEHE detected in urine. EGEHE did not appear to be metabolized to an alkoxyacetic acid metabolite, which have previously been shown to mediate toxicities of other shorter-chain ethylene glycol ethers. There were no apparent dose, species or sex differences in excretion and metabolism of EGEHE, except for the exhaled VOC fraction which was significantly greater in mice (19-20%) compared with rats (<2%) following oral exposure. These studies address a critical gap in the scientific literature and provide data that will inform future studies designed to evaluate toxicity of EGEHE.

ADME Data

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Data Summary - Male Rats

• Gavage Single Dose Group 1 (50 mg/kg, Study Duration 48 hours) (61 KB)
• Gavage Single Dose Group 2 (150 mg/kg, Study Duration 48 hours) (77 KB)
• Gavage Single Dose Group 3 (500 mg/kg, Study Duration 72 hours) (63 KB)
• Gavage Single Dose Group 4 (50 mg/kg, Study Duration 24 hours) (55 KB)
• Gavage Single Dose Group 8 (50 mg/kg, Study Duration 24 hours) (27 KB)
• Gavage Single Dose Group 9 (50 mg/kg, Study Duration 72 hours) (64 KB)
• Gavage Single Dose Group 10 (50 mg/kg, Study Duration 72 hours) (82 KB)

Data Summary - Female Rats

• Dermal Single Dose Group 11 (50 mg/kg, Study Duration 72 hours) (66 KB)
• Gavage Single Dose Group 5 (50 mg/kg, Study Duration 48 hours) (88 KB)

Data Summary - Male Mice

• Dermal Single Dose Group 12 (50 mg/kg, Study Duration 72 hours) (85 KB)
• Gavage Single Dose Group 6 (50 mg/kg, Study Duration 48 hours) (59 KB)

Data Summary - Female Mice

• Dermal Single Dose Group 13 (50 mg/kg, Study Duration 72 hours) (81 KB)
• Gavage Single Dose Group 6 (50 mg/kg, Study Duration 48 hours) (58 KB)