Pharmplex animal health - manufacturers of trace mineral supplements

The Treatment of Copper Deficiency in Sheep and Cattle

Dr Barry Patten B.V.Sc., PhD

Introduction

W.M Allen In Copper in Animals and Man Vol II provides a summary of the causes of copper deficiency and the various means of therapy. Copper deficiency usually arises due to a lack of copper in the animals diet, particularly the dry matter component eg. plants. Deficiency can also arise, particularly in ruminants, from an antagonistic relationship between copper and molybdenum that reduces the availability of copper from the soil.

Treatment of copper deficiency relies on the supply of supplementary copper in the diet or by systemic means. Supplementation of the diet is often difficult and not economically viable. Systemic supplementation has been undertaken using several treatment methods:

oral copper drenches, which are short acting and have to be administered on a regular basis
copper injections that can cause tissue damage and
copper oxide particles (aka copper oxide rods or copper oxide needles) in gelatine capsules that provide a 12 month sustained release copper supplement

Use of Copper Oxide Particles in Sheep

Dewey (1977) showed that copper oxide particles were capable of providing supplementary copper for sheep. A sustained release preparation consisting of copper oxide particles of 0.5mm to 5mm length and specific gravity of between 2.0 and 7.0 was developed by the CSIRO and patented in 1978 (Treating Copper Deficiency In Ruminants, CSIRO, Australian Patent AU520489).

In this invention CSIRO found that compressed copper pellets that lodged in the rumen were soon coated with an insoluble copper sulphide, however small particles of copper oxide could pass through the rumen and lodge in the abomasum where the acid environment caused the dissolution of the copper oxide. The copper was taken up into the systemic circulation and subsequently stored in the liver. Langlands et al., (1986a) demonstrated that copper oxide particles held in the rumen were ineffective and that the particles, to be effective, passed to the abomasum. Langlands et al., (1986a) also demonstrated that a 6 week residence time in the rumen did not effect the uptake of the copper from the copper oxide particles and molybdenum and sulphate in the diet of the animal did not effect that uptake of the copper.

Copper oxide powder was shown to be ineffective as a copper supplement in comparison to the copper oxide particles principally due to the low residence time of the powder in the abomasum and gut (Langlands et al., (1989)).

Copper oxide particles, released in the rumen pass through to the abomasum where they remain in the folds of the abomasum. CSIRO (1978) and Judson et al., (1982) demonstrated that the particles remained for a period of at least 32 days. CSIRO (1978) showed that the excretion rate of copper from the copper oxide particles was about 0.2 grams by weight per day which allowed for the safe absorption of copper without toxicity being apparent. The absorbed copper was stored in the liver and thereafter available metabolically over a longer period of time.

Initial trials on the efficacy and safety of copper oxide particles used particles produced from scrap copper and which were of a variable length, mass and specific gravity. (Judson et al., (1982), Judson et al., (1983), Judson et al., (1984)). The variable length, ranging from 2.1 to 7mm, was thought to affect the residence time of the particles in the abomasum and so cause a wide variation in terms of the storage of copper by the liver such that a copper oxide particle of uniform length (3mm to 4mm) was more efficacious (p< 0.001) than those of variable length (2.1 mm to 7mm) in raising the liver copper levels (Judson et al., (1984)).

The efficacy of various copper supplements was examined by Judson et al., (1984) who showed that the storage of copper in the liver was greatest in sheep treated with copper oxide particles of < 5mm in length and approx. 1mm diameter, whereas the use of copper injection, oral copper sulphate or copper oxychloride produced only a small, if any, rise in liver copper levels.

Judson et al., (1982) showed that the release of the copper from the liver was linear in sheep over a 40 week period after oral dosing with copper oxide particles. Judson et al., (1983) showed a significant rise in liver copper levels for a 29 week period after treatment with copper wire particles and subsequently Judson et al., (1984) showed a significant rise in liver copper levels above control animal levels for a period of 80 weeks post treatment. Langlands et al., (1986b) suggested that a single 2.5g dose of copper oxide particles was effective in stimulating hepatic copper reserves for a period of 8 months to 12 months depending on a number of factors, including the copper status of the animals.

Treatment of ewes pre-partum with copper oxide particles was demonstrated to increase lambs' hepatic copper stores (Langlands et al., 1982, Whitlaw et al., (1982)) whereas treatment of ewes post-partum did not effect the lambs' hepatic copper store (Langlands et al.,(1986b)).

Langlands et al., (1986a) showed that a 2.5g dose of copper oxide particles of uniform length produced liver copper levels ranging from 832 mg/kg to 1003 mg/kg DM which were significantly greater than control sheep for a period of 150 days to 240 days. Dosing animals at 6 monthly intervals with 2.5g of copper oxide particles showed a significant rise in liver copper levels for a period of 338 days to 369 days (Langlands et al., (1986a)).

Langlands et al., (1986a) showed that a 2.5g dose of copper oxide particles of uniform length produced liver copper levels ranging from 832 — 1003 mg/kg DM which were significantly greater than control sheep for a period of 150 days to 240 days. Dosing animals at 6 monthly intervals with 2.5g of copper oxide particles showed a significant rise in liver copper levels for a period of 338 to 369 days (Langlands et al., 1986a).

Judson et al., (1982) showed that a 2.5g dose of copper oxide particles administered to sheep was more efficacious than an injection of 12mg copper per sheep. Langlands et al., (1986b) however showed that a dose of 50mg of copper per sheep by subcutaneous injection did increase liver copper storage in a similar manner as a 2.5g dose of copper oxide particles, the disadvantage of the copper injection were severe site reactions frequently reported with this type of product.

Langlands et al., (1986b) suggested that recommended maximum liver copper levels would not be exceeded and that response to treatment would be more uniform where the copper status of the animals was known to be deficient and that the treatment interval was 12 months. Six monthly treatments could only be recommended where the animals were shown to be clinically deficient (Langlands et al., (1986b)).

Use of Copper Oxide Particles in Cattle

Copper oxide particles have been shown to reside in the gut of cattle for a period of up to 100days (Costigan and Ellis (1980), Deland et al.,(1986)).

MacPherson (1984) suggested that a dose of copper oxide particles of 20g for adults, 10g for yearlings and 5g for calves would protect against hypocupraemia for a period of at least 6 months. A 20g dose of copper oxide particles to a group of suckler cows caused a rise in plasma copper levels above adequate levels for at least 330 days (MacPherson (1984)).

Whitewall et al., (1984) demonstrated that a 20g dose of copper oxide needles administered to cattle approx. 190kg bodyweight effectively prevented growth retardation and severe hypocuprosis that were found in a group of untreated control animals.

Langlands et al., (1986b) showed that the use of oxidised copper particles produced a rise in hepatic copper storage and that the period that the oxidised copper particles were effective in stimulating hepatic copper reserves was in the order of 8 to 12 months depending on a number of factors, including the copper status of the animals.

The efficacy of the copper oxide needles was further confirmed by Richards et al., (1985) in the UK and Rodgers and Poole (1988) in Ireland where it was demonstrated that a 24g dose of copper oxide needles (Richards et al., 1985) and a dose of 13g copper oxide / 100kg b/w (Rodgers and Poole 1988) maintained plasma and liver copper levels in cattle for periods of at least 6 months with no signs of copper toxicosis.

Safety

Copper oxide particles, released in the rumen pass through to the abomasum where they remain for a period of at least 32 days (CSIRO (1978), Judson et al., (1982)). CSIRO (1978) showed that the excretion rate of copper in sheep from the copper oxide particles was about 0.2 grams by weight per day that allowed for the safe absorption of copper without toxicity being apparent.

Due to the slow absorption of the copper from the copper oxide particles in the abomasum it has shown by CSIRO (1978) that doses as high as 15 grams in sheep and by Judson et, al., (1982) that doses in sheep as high as 20g failed to elicit symptoms of toxicity.

Langlands et al., (1986a) also showed that dosing sheep with one 2.5g dose or 2 doses at 6 monthly intervals produced liver copper levels exceeding 700 mg/kg DM in non-copper deficient sheep with no signs of copper toxicosis. Langlands et al., (1986b) repeated these observations in showing that doses of copper oxide particles of 2.5g and 5.0g in non-copper deficient lambs and sheep raised liver copper levels in a proportion of animals to above 700 mg/kg DM without demonstrating any clinical signs of copper toxicosis.

Deland et al., (1986) reported that a dose of 300g of a 10% oxidised copper wire particles produced a rise in liver copper levels without any clinical signs of toxicosis nor of any accumulation of copper in muscle.

Use of Pharmplex Copper Oxide Particles

Pharmplex Copper oxide needles (wire form) in a gelatine capsule are registered in Australia for the prevention and treatment of copper deficiency in adult sheep and lambs, goats and adult cattle and calves.

In Australia, sheep and goats are treated with 2.5g copper oxide particles, calves 10g copper oxide and adult cattle 20g copper oxide.

In other countries, a dose rate of 2g, 2.5g or 4g copper oxide is used for sheep and goats. Calves are administered a 10g dose of copper oxide and Adult cattle receive either 20g, 24g, 27g or 30g copper oxide depending on body weight and management. Animals are dosed once per year.

Copper oxide particles should not be administered to animals of unknown copper status or those treated with any other source of copper within the previous 12 months. Do not repeat the dose within 12 months.

Do not administer to animals suffering from any form of liver disease such as jaundice or liver fluke or to animals grazing plants containing toxic alkaloids eg. Heliotrope, Ragwort, Patersons Curse (Salvation Jane).

Do not administer to animals less than 2 months of age.

It is recommended to seek veterinary advice to verify the copper status of the animals before treatment.

To be effective, the copper particles must be swallowed, administer using a bolus gun that delivers the capsule direct into the gullet.

Dose animals late winter or early spring unless copper supplementation is required immediately. Dose pregnant females early in pregnancy to allow protection of the lamb or kid or calf against copper deficiency.

In Liver Fluke endemic areas treat animals with a flukicide at least 3 weeks before using copper oxide particles.

The meat-withholding period is Nil.

Pharmplex Copper oxide needles (wire form) are packed in bulk 25kg net pails for filling into gelatine capsules or as filled gelatine capsules:

Size 0 gelatine capsules, 2g copper oxide
Size 00 gelatine capsules, 2.5g copper oxide
Size 000 gelatine capsules, 4g copper oxide
Size 13 gelatine capsules, 10g copper oxide
Size 12el or Size 11 gelatine capsules, 20g copper oxide
Size 11 gelatine capsules, 24g to 30g copper oxide

Capsules are supplied in packs of 50 or 100 capsules or according to the client's requirements or in bulk packs for repacking.

References

Allen, W. M., Therapy for Deficiency and Excess of Copper. Copper in Animals and Man Vol II

CSIRO (1978) Treating Copper Deficiency In Ruminants., Australian Patent 520,498.

Costigan , P., and Ellis, K.J., (1980) Proc. Aust. Soc. Anim. Prod. 13: 451

Dewey, D.W., (1977) An effective method for the administration of trace amounts of copper to ruminants. Search 8: 326-7.

Deland, M.P.B., Lewis, D., Cunningham, P.R., and Dewey, D.W., (1986) Use of Orally administered copper wire particles for copper therapy in cattle. Aust Vet. J: 63: 1-3.

Judson, G.J., Brown, T.H., Gray, D., Dewey, D.W., Edwards, J.B., and McFarlane, J.D., (1982) Oxidised Copper for Oral Copper Therapy in Sheep. Aust. J. Agric. Res. 33: 1073

Judson, G.J., Vandergraaff, R., Inglis, S.W., and McLaren, L.D., (1983) Oxidised copper wire particles as an oral copper supplement for sheep. Agricultural Rec., 10: 12 - 14.

Judson, G.J., Trengove, C.L., Langman, M.W., and Vandergraaff, R., (1984) Copper Supplementation in Sheep. Aust. Vet. Journal, 61: 40-43.

Langlands, J.P., Bowels, J.E., Donald, G.E., Smith, A.J., Paull, D.R., and Davies, H.I., (1982) Deposition of copper, manganese, selenium and zinc in the ovine foetus and associated tissues. Aust. J. Agric. Res. 33: 591-605

Langlands, J.P., Bowles, J.E., Donald,G.E., and Smith, A.J., (1986a) Trace Element Nutrition of Grazing Ruminants. I. Degree of Oxidation, Frequency of Dosing and Location in the Gastro-Intestinal Tract as Factors affecting the Ability of Oxidised Copper Wire to Promote Hepatic Copper Storage. Aust, J. Agric Res., 37: 179-188

Langlands, J.P., Bowles, J.E., Donald,G.E., and Smith, A.J., (1986b) Trace Element Nutrition of Grazing Ruminants. I. Hepatic Copper storage in Young Sheep and Adult Sheep and Cattle Given Varying Quantities of Oxidised Copper Particles and Other Copper Supplements. Aust, J. Agric Res., 37: 189-200

Langlands, J.P., Donald, G.E., Bowels, J.E., and Smith, (1989) Trace Element Nutrition of Grazing Ruminants. III Copper Oxide Powder as a Copper Supplement. Aust. J. Agric. Res. 40: 187-193

MacPherson A., (1984) Long term Effectiveness of graded doses of copper oxide needles to suckler cows. Vet. Rec: 115: 354-355

Richards, D.H., Hewett, G.R., Parry, J.M., and Yeoman, G.H (1985) Bovine copper deficiency: Use of copper oxide needles. Vet Rec. 116: 618-619

Rodgers, P/.A.M., and Poole, D.B.R., (1988) Copper oxide needles for cattle: A comparison with parenteral treatment. Vet. Rec. 123: 147-151

Whitlaw, A., Fawcett, A.R., and Macdonald, A.J., (1982) Cupric oxide needles in the prevention of swayback. Vet Rec. 110: 552

Whitlaw, A., Fawcett, A.R., and Macdonald, A.J., (1984) Cupric oxide needles in the prevention of bovine hypocuprosis. Vet Rec. 115: 357

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