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Eight female rats received a single dose of either 100 or 1000 mg/kg radiolabeled 2-ethylhexanoic acid by gavage. Four female rats received doses of 100 mg/kg radiolabeled 2-ethylhexanoic acid by gavage for 15 days. Eight female rats received a single dermal application of either 100 or 1000 mg/kg radiolabeled 2-ethylhexanoic acid. Eight female rats received a single intravenous application of 1 mg/kg radiolabeled 2-ethylhexanoic acid.

 

After oral administration of 2-ethylhexanoic acid, peak blood levels are achieved after 15-30 minutes, and declined triphasically with half-lives of ca. 0.3, 7 and 98 h. Approximately 72-75% of the oral dose was excreted in the urine within 24 hours. Little radioactivity (<10%) was excreted after 24 hours. The dose influenced the rate of excretion such that 50% of the radioactivity was excreted in the first 8 hours after the 100 mg/kg dose versus 20% after the 1000 mg/kg dose. Faecal excretion accounted for 7-12% in both cases. Repeated dosing with unlabelled 2-ethylhexanoic acid altered excretion of radioactivity to approximately 55% in urine and 15% in faeces within the first 24 hours.

 

Dermal application of 2-ethylhexanoic acid results in slower absorption with peak blood levels occurring 5.7 hours after application and a half-life of approximately 3 hours. Elimination is bi-phasic with half-lifes of ca. 4 and 251 hours. After dermal application, approximately 30% of the dose was excreted in the urine during the first 24 hours followed by an additional 8 or 17% from 24-96 hours for the 100 and 1000 mg/kg doses, respectively. After dermal application, approximately 30% of the dose was excreted in the urine during the first 24 hours followed by an additional 8 or 17% from 24-96 hours for the 100 and 1000 mg/kg doses, respectively. Faecal excretion was 7% regardless of the dose level. Dermal absorption was estimated to be 63-70% relative to intravenous administration.

 

Blood levels after intravenous injection appear to decay in a triphasic manner with half-lives of 0.2, 6.6, and 117 hours. Slightly less radioactivity was excreted as either urine (64%) or faeces (2%) after intravenous injection, compared to oral administration.

 

2-Ethylhexanoic acid is excreted via the urine as a glucuronide conjugate of 2-ethylhexanoic acid, as a glucuronide conjugate of hydroxylated and diacid derivatives of 2-ethylhexanoic acid (possibly 2-ethyl-6-hydroxyhexanoic acid and 2-ethyl-1,6-hexanedioic acid), and for a very minor part as unmetabolized 2-ethylhexanoic acid (English et al., 1987).