Nickel bis(2-ethylhexanoate)

Endpoint summary

Additional information

Concerning Nickel compounds, three well-conducted toxicokinetic studies were selected, i.e. oral or intra-peritoneal dosing in mice (Nielsen et al., 1993), in rats (Ishimatsu et al., 1995) and via drinking water for 6 months in rats (Severa et al., 1995).

Absorption: After oral administration of NiCl₂, the Whole Body Retention (WBRs) of nickel decreased within 45-75 hr to 0.02-0.36% of the dose administered in mice. After intra-peritoneal administration, the WBR decreased within 20-50 hr to 1-6% of the dose administered. The estimated intestinal absorption ranged from 1.7 to 10% of the dose administered. In rats, the Ni compound absorbed fraction was between 0.09 and 34%. 

Distribution: All studies indicate that Ni compounds were concentrated mainly in the liver, kidney and testicles, and additionally in lungs when the test item was administered by intra-peritoneal route.

Excretion: Absorbed nickel is excreted in the urine, regardless of the route of exposure. Most ingested nickel is excreted via faeces due to the relatively low gastrointestinal absorption. Observation of these studies showed that the excretion of Ni levels occurs rapidly via the liver and kidneys after oral administration and via kidneys after intra-peritoneal administration. The longest retention was found in the testes for males, and ovaries for females. Furthermore, retention time of Ni in lung was also relatively longer than in other organs after intra-peritoneal administration. 

Concerning 2 -ethylhexanoic acid, one well-documented study was selected.

English et al., 2007 tested 2-ethylhexanoic acid by three routes: oral, dermal and intravenous. 2 -ethylhexanoic acid is mainly excreted in the urine (rats: 60-80%) and is readily absorbed as on the average 10% is excreted in the faeces. The major urinary metabolites of 2-ethylhexanoic acid were the glucuronic acid conjugate of EHA, 2-ethylhexanedioic acid, isomers of hydroxy-2-ethylhexanoic acid and 2 isomeric metabolites of MW 142, proposed to be lactones. The parent compound was present in the urine at approximately 1.5 to 6.7% of the dose, depending upon the dose level, indicating rapid metabolism of the substance absorbed. After dermal administration between 40 and 50 % of the absorbed substance is excreted in the urine and approximately 7 in the faeces. A relatively long terminal half-life of elimination from the blood recorded in this study suggests that the skin may have served as a depot for 2-ethylhexanoic acid.