Copper hydroxide nitrate (Cu2(OH)3(NO3))

Endpoint summary

Description of key information

No substantial accumulation of Cu was observed in tissues following oral administration of six copper substances. he mean (pre-dose) background concentration corrected apparent elimination half-life was 10 hours of Cu in the liver.































 No substantial accumulation of Cu was observed in tissues following oral administration of six copper substances. The mean (pre-dose) background concentration corrected apparent elimination half-life was 10 hours of Cu in the liver.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Substance-specific information on toxicokinetics of copper nitrate, basic is not available. Hence, read-across from data on copper substances with similar/comparable (water) solubility properties was done. The solubility of the substance copper nitrate, basic as given in this dossier is approx. 579 mg/L. For purposes of comparison, the following information on (water) solubility of other copper substances is available:

 

copper dihydroxide: (~1 mg/L)

copper chloride oxide: (~1 mg/L at pH 6.5 and 101 g/L at pH3.5)

copper sulfate: 220 g/L

The above listed substances, inter alia, were used in the study Himmelstein (2004). However, despite distinct differences water solubility of as much as 6 orders of magnitude, the study yielded statistically similar Cu absorption values for all tested substances.(see below). Hence, read-across from the results obtained with these substances to copper nitrate, basic appears justified without restriction.

In a toxicokinetic study rats were exposed with diets containing six different copper substances, namely copper sulfate, copper sulfate basic, copper chloride oxide, copper (I) oxide, copper(II) hydroxide and Bordeaux mix for 24 (absorption and disposition of Cu) and 48 hours (liver and plasma time course followingCu(OH)2administration), at 0 and 20 mg Cu/kg bw (nominal), respectively.

Total absorption for 5 Cu substances was statistically similar relative to CuSO4 and ranged from 10.7% to 12.9% of the administered dose. Blood plasma Cu concentrations at 20 mg Cu/kg bw nominal dosing after 24 hours ranged from 2.40 to 3.18μg Cu/g plasma across all post-dose time points (control: 2.76µg Cu/g plasma).

In a half-life experiment (20 mg Cu/kg body weight), Cu absorption by the liver was examined (mean peak concentration of ~10.2 µg Cu/g tissue; control approx. half that value) and the elimination half-life was determined with approximately 10 hours (inclusive background correction) in the liver. Plasma concentrations were unchanged indicating that systemic circulation was negligible.

The main route of copper excretion was via faeces with means of 64 – 76% of the dosage.

In bile-cannulated male Sprague Dawley rats (five per group) after oral administration of a single dose of the above mentioned substances (corresponding to a copper nominal dose of 20 mg Cu/kg BW; actual dose 22-24 mg Cu/kg BW), copper levels in excreta during the 24-h period after dosing were as follows:

bile 1.54-2.48% of dose;
urine 0.20-0.39% of dose;
faeces 64-76% of dose.

All values were similar for all six substances tested, the results demonstrating that faecal excretion is the major route of elimination for orally administered copper, urinary excretion being a minor route.