Dicopper hydroxide phosphate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Further studies on various aspects of the use of high-copper supplements for growing pigs.

Author:

Allen, M.M., Barber, R.S., Braude, R. and Mitchell, K.G.

Year:

1961

Bibliographic source:

Brit. J. Nutr., 15: 507-522

Materials and methods

Objective of study:

absorption

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study compared the effects of 250 ppm copper, given in the diet as the sulphate or the carbonate.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Cu 1+ and Cu 2+ salts

Molecular formula:

Cu

IUPAC Name:

Cu 1+ and Cu 2+ salts

Specific details on test material used for the study:

Test material: Cu2+ as copper sulphate (CuSO4.5H2O). Cu2+as basic copper carbonate (CuCO3.Cu(OH)2.H2O).

Radiolabelling:

no

Test animals

Species:

pig

Strain:

other: Strain: Large White. Source: Shinfield, virus pneumonia-free.

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test Animal Age: weaners.
Number of animals: 8 pigs on each of 6 treatments [48 animals in total of both sexes].

Administration / exposure

Route of administration:

oral: feed

Details on exposure:

Oral administration of the test substances in the diet.

Duration and frequency of treatment / exposure:

Duration of treatment: Until bacon weight was reached. Frequency - with feed.

Doses / concentrations

Dose / conc.:

250 ppm (nominal)

Remarks:

Cu in feed as sulphate or carbonate salt.

No. of animals per sex per dose / concentration:

48 animals in total of each sex (8 per treatment)

Control animals:

yes

Details on study design:

Experimental design: The study consisted of 4 separate experiments; only experiment 2 (consisting of 6 separate treatments) is relevant to the purposes of this summary and is reported herein. Experiment 2 was designed as a 3 x 2 factorial. There were randomised blocks; blocks corresponding to litters, and treatments were allocated at random to the pens. There was no direct communication between pigs on different treatments.

Details on dosing and sampling:

Pigs on treatments 4, 5 and 6 were given twice daily as much meal as they would consume within 30 minutes up to a maximum of 61/2 lb/day, water at the rate of 3 lb to every 1 lb meal being added immediately before feeding. This system of feeding was termed semi-ad lib. Pigs on treatments 1, 2 and 3 were also given meal twice daily, 3 lb water per 1 lb of meal again being added immediately before feeding, but the amount of meal given was based on live weight and according to a scale, a daily maximum of 61/2 lb per pig being given to an animal weighing 170 lb. Sampling procedures and Analytical methods: All pigs were weighed once weekly throughout the experiment, the rations of the pigs in treatments 1, 2 and 3, which were fed to scale, being adjusted after each weekly weighing. All the pigs were sent to slaughter individually when their live weight at the weekly weighing exceeded 203 lb. A sample of liver tissue adjacent to the bile duct was taken at slaughter from each pig and stored at -20°C prior to determination of Cu.

Statistics:

Statistical analysis: Standard errors were calculated from randomised block analyses of variance, no adjustments being made for variation in either live weight or cold dead weight. The term 'treatment' is confounded with 'pen' but the pen effect was considered to be negligible.

Results and discussion

Preliminary studies:

Supplementation of the diet with either copper sulphate or copper carbonate resulted in large increases in the amount of Cu present in the livers at bacon weight, relative to un-supplemented controls. Mean liver copper concentrations of pigs fed diets to scale were 52, 843 and 624 mg/kg dry weight for control group, copper sulphate-treated and copper carbonate-treated animals, respectively. Corresponding Values for animals fed the semi-ad lib diet were 61, 779 and 383 mg Cu/kg dry weight.
Tox. behaviour: Copper derived from basic copper carbonate fed in the diet was somewhat less bioavailable than that from copper sulphate, when assessed in terms of liver copper concentration.

Main ADME results

Type:

other: bioavailability

Results:

Copper derived from basic copper carbonate fed in the diet was somewhat less bioavailable than that from copper sulphate, when assessed in terms of liver copper concentration.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The mean results for daily weight gain, food conversion efficiency, rate of food consumption and Cu content of the liver are shown in Table 1(attached), together with appropriate standard errors.
Recovery of labelled compound: Not applicable.

Metabolite characterisation studies

Metabolites identified:

not measured

Applicant's summary and conclusion

Conclusions:

Copper derived from basic copper carbonate fed in the diet was somewhat less bioavailable than that from copper sulphate, when assessed in terms of liver copper concentration.

Executive summary:

A study was carried out to evaluate the biological availability in pigs of Cu derived from basic copper carbonate, relative to that of Cu from copper sulphate pentahydrate. The study was not designed to follow internationally accepted guidelines, and was not carried out or reported in compliance with GLP.Fourty eight weaners were assigned to a 3 x 2 factorial arrangement in randomised blocks, with 8 animals in each of 6 treatment groups. Pigs in groups 1 and 3 (controls) received no supplementary copper in their diets; those in groups 2 and 5 received diets supplemented with 250 ppm copper sulphate pentahydrate and those in groups 3 and 6 received diets supplemented with 250 ppm basic copper carbonate. The manner of administration of these diets was varied as follows: Pigs on treatments 4, 5 and 6 were given twice daily as much meal as they would consume within 30 minutes up to a maximum of 6½ lb/day, water at the rate of 3 lb to every 1 lb meal being added immediately before feeding. This system of feeding was termed semi-ad lib.  Pigs on treatments 1, 2 and 3 were also given meal twice daily, 3 lb water per 1 lb of meal again being added immediately before feeding, but the amount of meal given was based on live weight and according to a scale, a daily maximum of 6½ lb/pig being given to an animal weighing 170 lb. All pigs were weighed once weekly throughout the experiment, the rations of the pigs in treatments 1, 2 and 3, which were fed to scale, being adjusted after each weekly weighing. All the pigs were sent to slaughter individually when their live weight at the weekly weighing exceeded 203 lb. A sample of liver tissue adjacent to the bile duct was taken at slaughter from each pig and stored at –20 °C prior to determination of Cu. Supplementation of the diet with either 250 ppm copper sulphate or 250 ppm copper carbonate resulted in large increases in the amount of Cu present in the livers at bacon weight, relative to unsupplemented controls. Mean liver copper concentrations of pigs fed diets to scale were 52, 843 and 624 mg/kg dry weight for control group, copper sulphate-treated and copper carbonate-treated animals, respectively. Corresponding Values for animals fed the semi-ad lib diet were 61, 779 and 383 mg Cu/kg dry weight. It was therefore considered that there was some indication that the increase in liver copper stores was not so great when copper was given as the carbonate instead of as the sulphate, particularly with semi-ad lib feeding. The mean measured concentration resulting from copper carbonate supplementation for animals fed the diet to scale was 74 % of that resulting from copper sulphate supplementation. The mean measured concentration resulting from copper carbonate supplementation for animals fed the diet semi-ad lib was 49 % of that resulting from copper sulphate supplementation. Copper derived from basic copper carbonate fed in the diet was somewhat less bioavailable than that from copper sulphate, when assessed in terms of liver copper concentration.