Toxicity Issues Associated With the Use of Ethanol Co-Products in Ruminant Rations
In recent years the federal mandate for increased use of renewable fuels has led to a rapid increase in the production capacity and distillation of fuel grade ethanol. The increased demand for corn to be used in ethanol production has led to a significant increase in shelled corn prices and has resulted in increased feed cost for many livestock producers. For instance, in Iowa the average per bushel cost of corn increased from a recent annual low of $1.78 in 2000 to $4.62/ bushel at present (Feb 2008).1 This change in market demand has resulted in renewed interest in the use of ethanol co-products as an alternative to corn in livestock rations. In many cases the use of these products is economically advantageous and results in comparable growth and health of livestock. The economic advantage afforded by individual co-products varies somewhat based on proximity to the ethanol plant, ability to transport the co-product and on-farm storage facilities. Increased time and energy has been focused on researching optimum inclusion rates and performance of livestock on rations including these products. For more information on these aspects of co-product use the reader is referred to other good sources.2,3,4 The focus of this manuscript will be a brief review of the ethanol production processes, their associated co-products and the health issues that have been recognized to be associated with the use of ethanol co-products in livestock rations. It is important to remember that the majority of these toxicological issues have only recently be recognized and research into these areas of by-product use is still in its infancy. As a result, very little peer-reviewed literature is available on this topic and the information presented in this manuscript is based on clinical experience and impressions. Future research is clearly necessary to define the pathophysiology and toxicological significance of many of these observations.
Ethanol Milling Processes and Their Associated Products
Although several different variations on ethanol production exist, two main types account for the majority of products that are included in livestock rations. Wet-milling systems start the process by steeping the corn in a liquid to soften the kernel prior to processing. After steeping, the germ is separated for use in production of corn oil and the remainder of the kernel is processed into corn gluten meal, corn gluten feed, sweeteners, cornstarch and ethanol. In contrast, the majority of the recent growth in the ethanol industry has been focused on a second production system that starts the process with grinding instead of steeping. Since the grinding process occurs without the addition of water this process is commonly termed "dry-milling". In the dry-mill process the corn is first ground then subjected to fermentation for 40-50 hours followed by distillation of ethanol. The remaining liquid is centrifuged to separate the soluble fraction from the solids resulting in the production of condensed distillers solubles (CDS, the remaining fluid portion with about 30% dry matter) and wet distillers grains (WDGs). Some plants will then heat the wet distillers grains to further increase the dry matter content and produce dry distillers grains (DDGs). In another variation the condensed solubles will be added back to the distillers grains to produce dry distillers grains with solubles (DDGS).
Corn gluten meal and corn gluten feed have been used for many years in various livestock rations. The recent growth in the dry-mill industry has resulted in increased use of WDGs, DDGs and CDS in livestock rations. As a result this has been the arena where many of the health-associated issues have been identified. Starch is the primary substrate for fermentation and subsequent ethanol production. Since starch accounts for 2/3 of the corn kernel the remainder of the nutrients and minerals found in a kernel of corn are concentrated three fold in the co-products when compared to whole-kernel corn. While the high protein content of many of the co-products increases their utility in ration formulation the majority of toxicity issues that have been identified are associated with the concentration of toxins, minerals or inappropriate mineral ratios in the as-fed ration.
Health Issues Associated With the Use of Ethanol Co-Products
Several health issues have been recognized with increased frequency in herds receiving rations that include ethanol co-products. In some cases these issues arise from an attempt to substitute one feed component with an ethanol co-product without paying appropriate attention to the mineral balance of the resulting feed. In many cases, the inconsistency of co-products from plant-to-plant and even load-to-load results in variability of the ration and changes in ration balancing that are not recognized until disease occurs. The industry is working hard to standardize the testing and variability of co-products however we still observe considerable differences in content of various minerals, fat and protein from batch-to-batch. Since the majority of income for the facility is from sale of ethanol the primary decision making tree focuses on consistent standardized ethanol production and not on consistent co-product production. The risk of disease also varies considerably by the particular co-product being used. For instance, the high moisture content of wet distillers grains makes them much more susceptible to fungal growth during storage compared to the dried product. The dried products are much easier to store and cheaper to transport (not transporting the weight of water), however, their cost is considerably higher due to the cost of drying. This makes dry distillers grains less attractive on an economic basis. Due to the cost of transport and storage issues the use of wet distillers grains is often limited to producers that live in close proximity to an ethanol plant. Several of the common issues arising from the use of ethanol co-products will be discussed in detail below.
As mentioned earlier the ethanol distillation process increases the sulfur concentration of co-products to approximately three fold that of corn. Additionally, the inclusion of sulfuric acid to promote fermentation in some systems provides further increases in the final sulfur concentration of the ration. Elevated sulfur intake levels have been associated with an increased risk of polioencephalomalacia and as a result total dietary intake of sulfur is not recommended to exceed 0.4% on a dry matter basis.5 H2S produced in the rumen environment is believed to interfere with normal cytochrome oxidase function in cellular respiration of the brain in a manner similar to that observed with cyanide.6 There is also some evidence suggesting that sulfate anion free radicals may be toxic to tissues and that H2S could act as an endogenous neuromodulator.6 At present the relative importance of sulfide ions that are absorbed across the rumen epithelium versus inhaled H2S from eructated rumen gases are unclear. There is at least one report of polioencephalomalacia associated with the inhalation of manure gassuggesting that the inhalation route may be important in the pathophysiology of this disease.7 Furthermore, there is an association of H2S with acute interstitial pneumonia8 which is sometimes seen with increased frequency in calves consuming distillers grains. There appears to be a role of rumen acidosis in this process since a decrease in rumen pH from 6.8 to 5.2 resulted in doubling the proportion of sulfur occurring as H2S in the rumen cap.9
In evaluating the role of ethanol co-products in clinical outbreaks of polioencephalomalacia it is important to consider the total dietary sulfur levels and not just those of the co-product. In most situations the sulfur contributed by the co-product is not sufficient on its own to exceed the 0.4% maximum but instead simply adds to the sulfur levels already contributed by water, forage, other grain products and in some cases ammonium sulfate added to the ration to prevent urolithiasis. Worksheets have been developed to aid in the calculation of total dietary sulfur and are available on our website (http://www.vetmed.iastate.edu/departments/vdpam/). In that context it is important to realize that some rations may have levels of sulfur as high as 0.6-0.7% dry matter with no clinical signs of polioencephalomalacia and conversely we recognize sulfur associated disease in some animals receiving rations below the 0.4% maximum. Recent research at Iowa State University has demonstrated that adult cattle may be able to consume high levels of dietary sulfur without developing clinical signs making it unclear if there is a role of age in this disease process. Definitive diagnosis of sulfur-associated polioencephalomalacia is difficult and for the most part relies on identification of the characteristic histopathologic changes in the brain. Other differential diagnoses that should be considered include thiamine deficiency, ingestion of thiaminase containing plants, toxicity with thiamine analogs, lead toxicosis and water deprivation. Techniques for the collection of rumen gas for H2S have been described but values change significantly over the course of the day and following feeding making clinical use somewhat difficult.10 Inclusion of molybdate in the diet may be beneficial at decreasing rumen sulfide concentrations and has been demonstrated to decrease rumen sulfide concentrations by 77% when added at 25 ppm in an in vitro system.11 This study did not however evaluate the role of the molybdate on rumen cap H2S concentrations. That same study demonstrated more modest reductions in rumen sulfide concentrations following the addition of oxytetracycline and chlorotetracycline to rations. Perhaps more important was the 50% increase in rumen sulfide observed with inclusion of monensin. Obviously, removal of high sulfur feed ingredients or water is warranted in clinical episodes and the entire ration (including water source) should be evaluated and reformulated to achieve an intake below 0.4%. No clinical studies have been reported concerning the use of exogenous thiamine in the treatment of sulfur toxicity. Many clinicians recommend its use and to our knowledge there is no contra-indication to thiamine therapy in these cases. Anecdotally, some clinicians indicate that they believe that sulfur associated polioencephalomalacia cases are less likely to respond compared to other apparently non-sulfur associated cases.
Mycotoxins are biologically active metabolites of fungal growth and accumulate in the local environment around areas of fungal growth. They are potential problems on two fronts with regards to the use of ethanol co-products. From a more traditional perspective the accumulation of mycotoxins on ear corn results in contamination of the whole kernel corn used for ethanol production. Mycotoxins have been demonstrated to be very stable and easily survive the fermentation process and like sulfur are concentrated three fold in the co-products compared to the kernel corn. Additionally, the growth of fungi on the surface of wet distillers grains during storage can result in the accumulation of mycotoxins that were not present in the corn prior to processing. The growth of mycotoxin producing fungi is an area of active research at Iowa State University and we hope to have additional data available on the role of this source in the future. The high moisture content of WDGs make them particularly prone to fungal growth and this issue is typically not observed in the much lower water content dried distillers grains. Mycotoxins of importance to animals and human health include aflatoxin, fumonisin and zearalenone. Due to its role as a known carcinogen aflatoxin has actionable milk levels of 0.5 ppb in milk. Data regarding rates of contamination of distillers' co-products is not widely available at this time. Given the contamination rates of kernel corn and the concentration effect of the distillation process it is likely that some of these products contain significant levels of mycotoxins.
The ratio of dietary calcium to phosphorous is important in prevention of the development of urinary calculi. Substitution of many feed ingredients with ethanol co-products will result in a change in calcium : phosphorous that needs to be addressed as part of the ration balancing. The concentration of corn phosphorous during the distillation process results in a product that can significantly increase total dietary phosphorous. An additional complication in this issue is the variability that is observed batch-to-batch. This variability makes ration formulation difficult for producers that will be buying multiple small volumes of co-product. Because of this ration balancing issue some commercial companies are now selling "balancers" designed to be used I conjunction with co-products to correct possible Ca:P issues.
Clinical experience suggests that the high rate inclusion of ethanol co-products is associated with an increased frequency of copper deficiency. It has been demonstrated that copper reacts with sulfur and molybdenum to form copper thiomolybdate in the rumen.12 Furthermore, copper forms a variety of other insoluble salts with zinc and sulfur. It is believed that the high sulfur content of many rations formulated with ethanol co-products contributes to decreased copper absorption from the gastrointestinal tract. Research conducted at Iowa State University demonstrates that liver copper levels tend to be decreased in animals offered free choice consumption of condensed solubles. These same animals do not appear to have decreased serum copper levels so the clinical significance of this issue is uncertain and requires more research. Experimentally, we have not at this time been able to reproduce copper deficiency in cattle receiving diets with ethanol co-products.
Antimicrobials are routinely added to the fermentation vat as a means of promoting more efficient fermentation and increasing ethanol production. The use of antimicrobials helps to control the growth of Lactobacillus and results in a 25% increase in ethanol yield.13 The two most commonly used antimicrobials are Virginiamycin and Penicillin. The FDA has issued a letter of "no objection" for a virginiamycin containing product known as Lactrol® which contains virginiamycin and dextrose. The letter allows for its inclusion at up to 2-6 parts per million (ppm) during the fermentation step and this dose was based on an acceptable residue of 0.2-0.5 ppm in the co-product and inclusion rates of less then 20% in livestock rations. Anecdotally, there are many reports of inclusion rates higher than that approved to improve yield. This has raised the concern that there may be a higher degree of contamination of the co-products then previously assumed and the FDA is currently collecting samples to further evaluate this issue. Despite these concerns it has been suggested that these antimicrobials will not withstand the heat and acidity of the ethanol distillation process and that detectable levels do not exist in at least dry distillers grains.13 Clearly this area deserves further attention and needs to be addressed by a well designed and controlled study.
The rapid increase in use of ethanol co-products as ration components has lead to the identification of a variety of health issues associated with their inclusion. In many cases specific controlled studies are lacking to demonstrate the pathophysiology responsible for the underlying problem. Despite the lack of research these issues are common in production systems in the areas of the country that are undergoing much of this growth in ethanol production. Veterinary clinicians should be aware of the potential issues that may be associated with the use of these products and should consider them in their diagnostic evaluations. Future research should provide a stronger evidence-based approach to dealing with these health concerns and is of high priority to the industry. It is possible that further research will demonstrate that some of the issues addressed in this discussion are less significant than they appear to be at this time. In the absence of this research clinical experience and diagnostic laboratory toxicology suggest that these issues should be evaluated as part of a disease outbreak investigation of herds utilizing these products.
1. Iowa Agricultural Statistics Service, http://www.nass.usda.gov/Statistics_by_State/Iowa/index.asp;
2. Iowa Beef Center; http://www.iowabeefcenter.org/;
3. Renewable Fuels Association Co-products page and link, www.ethanolrfa.org/industry/resources/coproducts/;
4. University of Minnesota Distillers Grains By-products in Livestock and Poultry Feed, http://www.ddgs.umn.edu/;
5. NRC. Nutrient Requirements of Beef Cattle, 2000, 7th Revised Edition;
6. Gould D. Polioencephalomalacia, 1998 J. Anim. Sci. 76:309-14;
7. Dahme E, et al. 1983.Zur neuropathologie der jauchegasvergiftung ( H 2S-vergiftung) bein rind ( neuropathology of manure gas [hydrogen sulfide] poisoning in cattle). Dtsch. Tieraerztl. Wochenschr. 90:316;
8. Kerr L, et al. A review of interstitional pneumonia in cattle. 1989, Vet. Human Toxic. 31:247;
9. Bray A, et al. Metabolism of sulphur in the gastro-intestinal tract. In I. W. McDonald and A.C.I. Warner, ( E d . ) 975, Proceedings of the IV International Symposium on Ruminant Physiology pg 243-260;
10. Gould D. In vivo indicators of pathologic ruminal sulfide production in steers with diet induced polioencephalomalachia. 1997. J. Vet. Diagn. Invest.9:72;
11. Kung, L et al. Effects of various compounds on the in vitro ruminal fermentation and production of sulfide. 2000, Animal Feed Science and Technology, 84:69-81;
12. Suttle N. The role of thiomolybdates in the nutritional interactions of copper, molybdenum and sulfur: Fact or fantasy? 1980, Ann N Y Acad Sci 335:195;
13. Shurson J. Quality issues related to DDGs. http://www.ddgs.umn.edu/.