Neodymium di(2-ethylhexyl) phosphate

Endpoint summary

Additional information

 

General information   Name: neodymium tris(di-2-ethylhexylphosphate) Molecular weight: ca. 1107 – 1108 g Molecular formula: C48 H102 Nd O12 P3 Physical state: powder Water solubility: 0.87 mg/L at 20°C n-octanol/water partition coefficient Log Pow = 3.43 Vapour pressure: < 2.0 x 10E-5 Pa at 25°C Relative density: 1.171 Particle size distribution: MMAD = 202 µm, diameter > 29 µm for 100% of the particles   Toxicological information Local effects: -      Eye irritation: A slight chemosis and a slight redness of the conjunctiva were noted on days 1 and 2. -      Skin irritation: after a 4-hour exposure, a very slight erythema was noted in 2/3 animals on day 1 only. -      After a cutaneous administration at the dose of 2000 mg/kg bw, crusts were noted in 1/10 animals from day 11 until day 15. -      In a Guinea Pig Maximisation Test, no deaths and no clinical signs were noted. A dryness of the skin was observed up to 48 hours after the challenge, but the test item is not a skin sensitizer. -      In a subacute oral toxicity study, lesions of the forestomac (suggestive of a local irritant effect) were observed (multifocal epithelial cells hyperplasia, erosion, hyperkeratosis, squamous crusts, submucosal inflammation) at all doses tested and thus no NOEL (< 150 mg/kg bw/day) can be determined in this study for local effects .   Systemic effects: -      After a single dermal application at 2000 mg/kg bw, the only potential systemic effect observed was a slightly lower body weight gain in 1/10 animal between day 8 and day 15. -      After a single oral administration, at 300 mg/kg, piloerection and dyspnea were noted in all animals (3/3) one hour after treatment. Piloerection was still observed 2 hours after treatment. At 2000 mg/kg, piloerection was observed in 3/6 animals 4 hours after treatment only, and a slightly lower body weight gain was noted between day 8 and day 15 in 1/6 animals. -      In a subacute oral toxicity study in which neodymium tri (di-2-ethylhexyl phosphate) was administered by gavage at dose levels of 150, 450 and 1000 mg/kg bw/day, a smaller landing foot splay was observed at 1000 mg/kg/day in all males and in one female and the mean white blood cell count of both males and females was lower than concurrent control values at this dose level.. Furthermore, the absolute and relative liver weight was increased in the male rat treated at 1000 mg/kg/day. Minimal focal subcapsular hepatocellular coagulative necrosis were observed in the liver of 1/5 and 3/5 males treated at 450 and 1000 mg/kg/day respectively. However, this finding were considered of low toxicological importance since it wasconsidered secondary to slight increase in liver weights (with no microscopic correlate) and consequential compression of the hepatocytes adjacent to the capsule. Based on these results, a NOAEL for systemic toxicity could be established at 450 mg/kg bw/day. -      No indication of genetic toxicity was observed in an in vivo micronucleus assay, where mice were given neodymium tris (di-2-ethylhexylphosphate) in corn oil at dose-levels of 500, 1000 and 2000 mg/kg/day by oral route, over a 2-day period. -      No in-vitro genotoxicity assays are available, as it was technically impossible to perform the tests.

 

The following basic toxicokinetic information can be extrapolated from the experimental toxicology data available on neodymium tris(di-2-ethylhexylphosphate), an insoluble organo mineral substance:

- Regarding its absorption:

As systemic effects are observed in rats after a single oral administration (piloerection, dyspnea, slightly lower body weight gain) and after a repeated oral administration (smaller landing foot splay, lower mean white blood cell count, increase in liver weight with minimal focal subcapsular hepatocellular coagulative necrosis), the absorption of neodymium tris(di-2-ethylhexylphosphate) is expected by oral route.

A slightly lower body weight gain in 1/10 animal between day 8 and day 15 was observed after a single dermal application. This effect could be a sign of systemic effect, even if the physical and chemical properties of the neodymium tris (di-2-ethylhexylphosphate) do not indicate a potential for dermal absorption: high molecular weight and size of the particles, low water solubility and high Log Kow.

Even if drying properties of the substance on the skin may theoretically increase the passage of the skin barrier, the cutaneous absorption of neodymium tris (di-2-ethylhexylphosphate) is considered as negligible to moderate.

- Regarding its distribution:

No data are available regarding the concentration of neodymium tris (di-2-ethylhexylphosphate) in organs or tissues after exposure to this substance.

Based on the local effects observed in stomach after repeated oral exposure, a significant concentration of the test item or its metabolites in the stomach wall (mucosa and submucosa) can be expected.

Based on a high Log Kow, neodymium tris (di-2-ethylhexylphosphate) is potentially bioaccumulable. Moreover neodymium is known for its ability to accumulate in the liver.

- Regarding its metabolism:

The increase in liver weight accompanied by minimal focal subcapsular hepatocellular coagulative necrosis observed after repeated oral administration suggests that neodymium tris(di-2-ethylhexylphosphate) is metabolized by the liver. As no in-vitro genotoxicity tests are available, this hypothesis can not be confirmed with results with or without S9 microsomal fraction.

Based on the chemical structure, it could be possible that the biotransformation of neodymium tris (di-2-ethylhexylphosphate) pass through a cleavage of the phosphate groups to release on the one hand alcohols, and on the other hand the central portion of the molecule bearing the neodymium atom. The phosphate groups would then be integrated into the physiological metabolism.

- Regarding its elimination:

Urinary excretion of the unchanged substance is excluded, considering the absence of effects on the urinary tract and the low water solubility. The hypothetical metabolites could be excreted in urine (phosphates), bile or even by exhalation (derived from three side chains).