ADVERTORIAL


Heavy metal impurities found in 94 % of tested injectable irons for piglets


In 15 of 16 widely used injectable iron products for piglets, the concentration of the heavy metals arsenic, chromium and/or lead exceeded the permitted daily exposure limit for humans, an analysis just published in Journal of Swine Health and Production shows. Only one product was free of elevated levels of all three heavy metal impurities. Product A


Table 1: Detected content of arsenic, chromium and/or lead in parenteral iron products for swine*


exceeded the human daily exposure limit by > 25% exceeded the human daily exposure limit by ≤ 25%


ISU = Iowa State University Veterinary Diagnostic Laboratory Lab 2 = independent laboratory


Brand Name Manufacturer†


Country Molecule Concentration (mg/ml)


US


– The data show that arsenic, chromium and lead can inadvertently be administered with iron injections to pigs depending on the product used. These substances should be avoided in the pork production chain, and it is up to the pig producers to make sure that arsenic, chromium and lead are not injected into piglets, says leading expert in swine health, Professor Jens Peter Nielsen, Production, Nutrition and Health at the University of Copenhagen, Denmark.


Product B Product C Product D Product E Product F Product G Only one product found free Product H Product I US Spain Canada US UK Iron dextran Iron dextran Iron dextran Iron dextran Belgium Gleptoferron Gleptoferron Germany Gleptoferron Gleptoferron


The analysis was carried out by an independent FDA-certified laboratory and the Iowa State University Veterinary Diagnostic Lab, one of the leading universities for veterinary medicine. 16 widely used injectable iron products for piglets were tested,


Uniferon® Product J 200 Pharmacosmos US Product K Product L Russia US Belgium Gleptoferron Iron dextran


and in 15 of them the concentration of the heavy metals Germany Gleptoferron arsenic, chromium and/or lead exceeded the FDA and EMA


permitted daily exposure limit for humans. Only one product - Gleptoferron Uniferon - had non-detectable levels of both arsenic and lead. Uniferon was also the only product where chromium levels did not exceed human permitted daily exposure limits.


Iron dextran Product M Product N Denmark Gleptoferron


Risk at low-level exposure A recent study published in The Lancet Public Health1 demonstrated that low-level lead exposure is an important and largely overlooked risk factor for death, particularly for cardiovascular disease deaths.


Product O** China China Iron dextran Iron dextran 100 100 200 Arsenic‡ AS


Permitted daily exposure¶ 0.3 µg/kg


ISU Lab 2# µg/200mg dose§


3.4 4.0 0.2 2.0 1.9


Table 1: Detected content of arsenic, chromium and/or lead in parenteral iron products for swine*


0.4 200


exceeded the human daily exposure limit by > 25% exceeded the human daily exposure limit by ≤ 25%


1.7


ISU = Iowa State University Veterinary Diagnostic Laboratory Lab 2 = independent laboratory


Brand Name 200 Product A Pr 200oduct B Product C Pr 200oduct D Product E Pr 200oduct F Product G Pr 200oduct H Product I Unif 2er0o0 n® 200 Product J Pr 200oduct K Product L Pr 200oduct M Product N Pr 100oduct O** * † Manufacturer†


< 0.1 < 0.1 US


Country US Molecule Iron dextran 0.9 < 0.1 Iron dextran Spain Iron dextran 2.2 Canada 1.2 Iron dextran Belgium 1.4 US Germany Gleptoferron 0.5 Gleptoferron Gleptoferron


< 0.1 < 0. Gle1ptoferron UK


Belgium Gleptoferron


Pharmacosmos < 0.1 < 0.1 Iron dextran US


Germany Gleptoferron


< 0.1 < 0. Gle1ptoferron Russia


US Iron dextran


0.1 < 0. Gle1ptoferron Denmark


China Iron dextran 2.0 China 2.2 Iron dextran Marketing Authorization holder/NADA owner.


‡ 2 Val0ues0 reported as < 0.1 µg/200 mg dose < 0.1 < 0.1 §


¶ were below the limit of detection for the assay. 29.0 29.0


For all 200 mg/ml products the reported elemental concentrations in µg/200 mg dose are equivalent to parts per million. For 100 mg/ml products, detected concentrations in parts per million were doubled to represent a typical 200 mg dose.


** 1 Sa0mpl0e was not available for testing at both l 1a.bo4ratories. 1.8 †† Not applicable. #


100


Permitted daily exposure is the published daily exposure limit for an adult human. Values were converted to µg/kg assuming 50 kg as a conservative adult human body weight and using inclusion limits reported in USP < 232 > and ICH Q3D for human pharmaceutical products.


65.4 39.8 15 of the products were also analysed at a second independent laboratory concurrently. 1.8 NA††


* All values are rounded to the nearest one significant figure. Yellow highlighted cells indicate the element was present at ≤ 25% higher than the daily limits established for humans. Red highlighted cells exceed the human daily exposure limit by > 25%.


† Marketing Authorization holder/NADA owner. ‡ Values reported as < 0.1 µg/200 mg dose were below the limit of detection for the assay.


§ For all 200 mg/ml products the reported elemental concentrations in µg/200 mg dose are equivalent to parts per million. For 100 mg/ml products, detected concentrations in parts per million were doubled to represent a typical 200 mg dose.


28.6 NA†† < 0.1 NA†† (Adapted from Radke, S.L. et al. Elemental


impurities in injectable iron products for swine. Journal of Swine Health and Production. 2018;26(3): 142-145, table 1)


¶ Permitted daily exposure is the published daily exposure limit for an adult human. Values were converted to µg/kg assuming 50 kg as a conservative adult human body weight and using inclusion limits reported in USP < 232 > and ICH Q3D for human pharmaceutical products.


** Sample was not available for testing at both laboratories. †† Not applicable.


1. Lanphear BP et al. Low-level lead exposure and mortality in US adults: a population-based cohort study. Lancet Public Health 2018; 3: e177–84


0.6 < 0.1 1.6 ChromiumCr


Permitted daily exposure¶ 22.0 µg/kg


ISU Lab 2# µg/200mg dose§


30.2 27.0 36.2 32.9 36.0 49.5


12.0 35.0ASArsenic‡ Permitted daily exposure¶


0.3 µg/kg Concentration


(mg/ml) 25.0 24.1 100


ISU 3.4 100 200 200 200 200 200 200 200 200 200 200 100 200 100 100 4.0 Lab 2# µg/200mg dose§ 2.0


32.4 29.6 1.9 0.2


0.4


21.0 28.9 1.6 < 0.1


1.7 < 0.1


18.0 2 < 07..10 2.2


0.9 1.2


33.2 28.9 0.5 < 0.1


1.4 < 0.1


0.4 < 0.1 0.7 < 0.1 < 0.1


< 0.1


25.0 3 < 06..10 2.0


0.1 2.2


19.0 2 < 01..19 1.4


< 0.1 1.8 19.4 3 N6.7 1.8 A ††


All values are rounded to the nearest one significant figure. Yellow highlighted cells indicate the element was present at ≤ 25% higher than the daily limits established for humans. Red highlighted cells exceed the human daily exposure limit by > 25%.


ChromiumCr ISU 30.2 36.2 36.0 12.0 25.0 32.4 21.0 18.0 33.2 0.4 25.0 19.0 19.4 29.0 65.4 28.6 Lab 2# µg/200mg dose§ 27.0 PbLead‡


Permitted daily exposure¶ 0.1 µg/kg


ISU Lab 2# µg/200mg dose§


< 0.1 < 0.1 < 0.1 < 0.1 4.9 5.8 0.3 < 0.1PbLead‡


Permitted daily exposure¶ 22.0 µg/kg


Permitted daily exposure¶ 0.1 µg/kg


2.0


ISU Lab 2# µg/200mg dose§


< 0.1


1.1 < 0.1


32.9 0.6 < 0.1 0.5 < 0.1 49.5 4.9 0.3 5.8


35.0 < 0.1 < < 0. 01.1 24.1


2.0 0.6 1.1


29.6 < 0.1 < 0.1 0.5 28.9


< 0.1 < 0.1 27.0 2.6 < 0.1 0.6 < 0.1 28.9 2.6 < 0.1 0.4 0.6


0.7 < 0.1 < < 0. 01.1 36.0


0.4 21.9 0.4 1.1 0 1..24 36.7 1.2 1.5 29.0 1.1 3.1 1 0..32 39.8 NA †† 0.6 < 0.1 1.2 < 0.1 1.5 NA††


(Adapted from Radke, S.L. et al. Elemental impurities in injectable iron products for swine. Journal of Swine Health and Production. 2018;26(3): 142-145, table 1)


3.1 0.3


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