Update on human health concerns of recombinant bovine somatotropin use in dairy cows R. J. Collier and D. E. Bauman J ANIM SCI 2014, 92:1800-1807. doi: 10.2527/jas.2013-7383 originally published online February 10, 2014

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Update on human health concerns of recombinant bovine somatotropin use in dairy cows R. J. Collier*1 and D. E. Bauman† *School of Animal and Comparative Biomedical Sciences University of Arizona, Tucson 85719; and †Department of Animal Science, Cornell University, Ithaca, NY 14853

ABSTRACT: The 20 yr of commercial use of recombinant bovine somatotropin (rbST) in the United States provide the backdrop for reviewing the outcome of use on human health issues by the upcoming 78th meeting of the Joint Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) Expert Committee on Food Additives. These results and further advancements in scientific knowledge indicate there are no new human health issues related to the use of rbST by the dairy industry. Use of rbST has no effect on the micro- and macrocomposition of milk. Also, no evidence exists that rbST use has increased human exposure to antibiotic residues in milk. Concerns that IGF-I present in milk could have biological effects on humans have been allayed by studies showing that oral consumption of IGF-I by humans

has little or no biological activity. Additionally, concentrations of IGF-I in digestive tract fluids of humans far exceed any IGF-I consumed when drinking milk. Furthermore, chronic supplementation of cows with rbST does not increase concentrations of milk IGF-I outside the range typically observed for effects of farm, parity, or stage of lactation. Use of rbST has not affected expression of retroviruses in cattle or posed an increased risk to human health from retroviruses in cattle. Furthermore, risk for development of type 1 or type 2 diabetes has not increased in children or adults consuming milk and dairy products from rbST-supplemented cows. Overall, milk and dairy products provide essential nutrients and related benefits in health maintenance and the prevention of chronic diseases.

Key words: antibiotic residues, bovine somatotropin, cancer, diabetes, insulin-like growth factor I, retroviruses © 2014 American Society of Animal Science. All rights reserved. INTRODUCTION Use of recombinant bovine somatotropin (rbST), the first recombinant protein approved for use in production animals, has received unprecedented scrutiny. In the United States this surveillance included the traditional evaluation by the Food and Drug Administration (FDA) as well as public hearings, scientific evaluations, and legislative reviews (Bauman, 1992). It has been 20 yr since the introduction of Posilac, the commercial formulation of rbST (Elanco, Greenfield IN), into the dairy industry of several countries, and to date in the United States over 35 million dairy cows have received Posilac. Even though some countries have not approved 1Corresponding

author: [email protected] Received: November 14, 2013. Accepted: January 25, 2014.

J. Anim. Sci. 2014.92:1800–1807 doi:10.2527/jas2013-7383

commercial use of rbST (e.g., Canada and the European Union), dairy products from rbST-supplemented cows are imported by these countries and marketed with no restrictions or special label requirements. The Joint Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA) is an international expert scientific committee administrated jointly by the FAO and the WHO. This independent scientific committee performs risk assessments and provides advice to FAO, WHO, and member countries of both organizations for the development of international food standards and guidelines. The first JECFA review of rbST was the 40th conference and the committee concluded “the lack of oral activity of rbST and IGF-I and the low levels and non-toxic nature of the residues of these compounds, even at exaggerated doses, results in an extremely large margin of safety

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for humans consuming dairy products from rbST-treated cows” (JECFA, 1993, p. 3). Based on this the committee concluded that there was no need to establish an acceptable daily intake or minimum residue levels and that the use of rbST “does not represent a hazard to human health” (JECFA, 1993, p. 3). The committee “concluded that rbST can be used without any appreciable health risk to consumers” (p. 3). The 1998 committee also reaffirmed previous conclusions (JECFA, 1993) that there was no need to set an Acceptable Daily Intake or Minimum Residue Level for rbST. In early 2013, JECFA announced that it would be reevaluating rbST at the 78th JEFCA conference and requested new data and information related to human health and the use of rbST. Listed topics of particular interest were the possible increased use of antibiotics to treat mastitis in cows, the possibility of increased concentrations of IGF-I in the milk of cows treated with rbST, potential effects of rbST on the expression of certain viruses in cattle, and the possibility that exposure of human neonates and young children to milk from rbST-treated cows increases health risks, for example, development of insulin-dependent diabetes mellitus. The following is an update of the relevant literature on these topics. MILK ANTIBIOTIC RESIDUES Antibiotics are used by the dairy industry to treat mastitis, and residues occur when the milk is saved before the antibiotics have fully cleared from the animal. Major factors affecting the incidence of mastitis are related to environmental conditions and management practices (Hogan and Smith, 2012). There is also a small increase in mastitis incidence, expressed on a per cow basis, as milk production increases, and the FDA concluded that the use of rbST was also associated with an increase in the relative risk of mastitis. Relative risk is the ratio of the probability of an event occurring (i.e., mastitis in cows treated with rbST) in an exposed group to the probability of the event occurring in a comparison with a nonexposed group. To further evaluate the impact of rbST use on mastitis incidence in dairy cows, the FDA/Center for Veterinary Medicine (CVM) advisory committee held a public hearing (FDA/CVM, 1993). The public hearing pointed out that most incidences of mastitis (30 to 50%) occur during the first 60 d of lactation, a period when rbST is not used. Furthermore, the public hearing provided context and pointed out that compared to rbST, the relative risk of mastitis was at least 6.7x greater for effect of season, >4.4x greater for parity, >3.2x greater for herd, and >4.8x greater for stage of lactation. In 1998 the 50th JECFA conference also evaluated the relationship between rbST use and the potential for milk antibiotic residues. They concluded “that the use of rbST will not result in a higher

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risk to human health due to the use of antibiotics to treat mastitis and that the increased potential for drug residues in milk could be managed by practices currently in use by the dairy industry and by following label directions for use” (JECFA, 1998, p. 128). The following represents results from commercial use in the United States and related scientific publications since the 50th JECFA. Postapproval Monitoring Program Many of the environmental and management factors associated with risk of mastitis are herd specific. To control for this a Post-Approval Monitoring Program (PAMP) was established for Posilac to evaluate animal health under commercial use and determine adequacy of label directions. The PAMP was designed under the direction of the FDA/CVM as a controlled study involving herds located in primary dairy states representing the 4 major geographic regions of the United States. Final analyses had a total of 1,128 cows from 28 herds making it the largest single controlled study of rbST and herd health ever conducted (Collier et al., 2001). Relative to mastitis and antibiotic use, cows receiving Posilac did not differ in average total mastitis cases, total days of mastitis, or duration of each case of mastitis. After accounting for herd-specific effects, the relative risk of mastitis when supplemented with Posilac was 1.23, a value less than the FDA/CVM estimate based on preregulatory studies. Therefore, the PAMP study results indicated no unexpected increase in antibiotic use to treat mastitis when cows were given rbST under commercial conditions. United States Data for Milk Antibiotic Residues The national data summary of milk antibiotic residue violations provides some insight on the potential impact of rbST use. The National Milk Drug Residue Data program is a voluntary industry reporting program but state regulatory agencies report all data received to the National Conference on Interstate Milk Shipments (NCIMS; http://www.ncims.org/). The system includes all milk, Grade “A” and non-Grade “A,” commonly known as manufacturing grade. Grade “A” milk represents approximately 95% of the U.S. milk supply and is regulated through the NCIMS by the state regulatory agencies. Manufacturing grade milk is under the direction of the regulatory agencies in states where it is produced. The FDA and the NCIMS collaborate on a cooperative, federal–state program (Grade “A” Interstate Milk Shippers Program) to ensure the sanitary quality of Grade “A” milk and milk products shipped in interstate commerce. Results of milk drug residue testing by industry and state regulatory agencies form the database. The reporting does not necessarily represent 100% of the

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Figure 1. Percent of bulk milk tankers testing positive for antibiotic residues for 1995 to 2012. Adapted from National Milk Drug Residue Data program (NMDRD, 2013).

milk supply from every state, but as state and industry participation in the database has increased, the number of samples and tests has similarly increased. In 1995, the industry testing program switched to a more sensitive test for antibiotics and continued efforts to ensure uniform and accurate reporting of drugs and test methods among states. The pattern of milk antibiotic residue violations for the U.S. dairy industry from 1995 to 2012 is shown in Fig. 1. The percent of bulk milk tank trucks testing positive for antibiotic residues has steadily declined since 1996, and in 2012 was less than one-fifth of the level detected in 1995 (0.100% in 1995 vs. 0.017% in 2012). Therefore, there is no evidence of increased human risk for exposure to milk antibiotic residues from the use of rbST by the U.S. dairy industry. United States Data for Milk Somatic Cell Count Milk somatic cell count (SCC) is a measure of milk quality and a reflection of mammary health. The SCC refers to the number of white blood cells, secretory cells, and squamous cells per milliliter of raw milk. Leukocytes are white blood cells with macrophages being one type. Macrophages are the most predominant somatic cell found in the milk of healthy cows, but neutrophils, lymphocytes, and epithelial cells are also present (van Schaik et al., 2002). Somatic cells from an infected quarter of the udder, predominately leukocytes or white blood cells including neutrophils (major form), macrophages, and lymphocytes, are present in milk at much greater numbers (van Schaik et al., 2002). Therefore, SCC values provide insight related to milk quality and subclinical mastitis. The Animal and Plant Health Inspection Service Centers for Epidemiology and Animal Health of the USDA, in collaboration with the Agricultural Marketing Service of USDA and the Milk Quality Monitoring Committee of the National Mastitis Council, monitor

Figure 2. Pattern of somatic cell counts (SCC) in U.S. milk for 1998 to 2009. Adapted from USDA (2013) with bars representing Dairy Herd Improvement test day SCC and diamonds representing Federal Milk Marketing Order bulk tank SCC.

the U.S. milk quality using bulk-tank somatic cell count (BTSCC) data provided by 4 of the 10 Federal Milk Marketing Orders (FMO). The remaining 6 FMO do not collect BTSCC information. The BTSCC is used as a measure of milk quality and an indicator of overall udder health. An inverse relationship exists between BTSCC and cheese yield and the quality/shelf life of pasteurized fluid milk (Barbano et al., 1991). To ensure high-quality dairy products, BTSCC is monitored in milk shipments using standards outlined in the U.S. Pasteurized Milk Ordinance (APHIS Veterinary Service, Centers for Epidemiology and Animal Health, 2011). In the United States, the legal maximum BTSCC for Grade A milk shipments is 750,000 cells/mL. Milk is not accepted and producers are penalized if violations occur. Maximum allowable BTSCC for other countries include 400,000 cells/mL in the European Union, Australia, New Zealand, and Canada and a maximum BTSCC of 1,000,000 cells/mL for Brazil, (Norman et al., 2011). The U.S. pattern for milk SCC from 1998 to 2009 is shown in Fig. 2; one set of values represents those from the BTSCC national program and the second set of values represents an average of individual cows from herds in the national Dairy Herd Improvement testing program. The overall pattern is similar for both sources of SCC data and demonstrate that the average SCC in U.S. milk supply has declined steadily since 2001. More recent data indicate a continued decline; BTSCC averaged 224,000 cells/mL in 2010 and 206,000 cells/mL in 2011 (Norman et al., 2013) Therefore, SCC for the U.S. dairy herd has not increased over the interval of Posilac use. Rather, SCC has declined over the last decade indicating an improvement in milk quality and mammary health. Van Schaik et al. (2002, p. 782) demonstrated that “high SCC is a generic predictor of poor milk quality.” Herds with 200,000 cells per mL of milk or less had

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the lowest incidence of antibiotic residues. Therefore, the inference from SCC data over the last 15 yr is that the potential human threat from milk antibiotic residues has declined dramatically. Recent Related Publications Since the 50th JECFA report, 3 large scale studies with commercial dairy herds have been published in which the effect of rbST use on the incidence of mastitis, SCC, and/ or culling rate has been examined (Judge et al., 1997; Ruegg et al., 1998; Bauman et al., 1999). These investigations indicated that commercial use of Posilac had little or no effect on these variables. Overall, results provided no indication that commercial use of rbST poses a concern and by extension give no indication that antibiotic use or possible milk antibiotic residues would be increased in herds using Posilac. The Canadian Veterinary Medical Association also published results from a meta-analysis of rbST effects on relative risk of mastitis (Dohoo et al., 2003). Their analysis included studies previously considered for the 50th JECFA meeting and results of the meta-analysis indicated that use of rbST increased the relative risk of mastitis to an extent similar to that reported at the FDA/ CVM public hearing (FDA/CVM, 1993) and the PAMP study (Collier et al., 2001) Collectively, milk antibiotic residue violations and milk SCC have declined precipitously since rbST was commercialized in 1994 (Fig. 1 and 2). The improvement over this interval is not due to rbST per se but rather reflects the continued improvement in management practices on dairies and a heightened surveillance for antibiotic residues in milk by the U.S. regulatory authorities. These data, the PAMP study, and other postapproval studies conducted on commercial dairy farms provide no indication that use of rbST is associated with an unmanageable risk of mastitis. Overall, there is no evidence that the risk of human exposure to antibiotic residues is affected by the commercial use of rbST. Insulin-Like Growth Factor in Milk In humans, concentrations of circulating IGF-I vary throughout the life cycle, playing important roles in growth promotion, protein synthesis, and insulin-sensitizing actions (Thissen et al., 1994). Nutrition has a major effect on blood concentrations of IGF-I; serum IGF-I is decreased whenever dietary intake of nutrients is inadequate and increases as nutrient intake improves, especially intake of high quality protein (Thissen et al., 1994; Clemmons, 2006). Earlier research established that milk IGF-I concentrations varied according to herd and parity (Collier et

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al., 1991). More recent investigations have also shown that IGF-I concentrations in milk also vary several-fold according to stage of lactation, season, and milk SCC (Daxenberger et al., 1998; Liebe and Schams, 1998; Taylor et al., 2004; Collier et al., 2008). Nevertheless, the dietary intake of IGF-I from the consumption of milk is negligible when compared with the daily whole-body production of IGF-I or when compared with the daily IGF-I in saliva and digestive secretions in humans. For example, 1.5 L of milk would represent an IGF-I amount equal to approximately 0.09% of the daily IGF-I production in adults. The 50th conference report (JECFA, 1998, p. 142) concluded “that any increase of IGF-I in milk from rbST-treated cows is orders of magnitude less than the physiological amounts produced in the gastrointestinal tract as well as in other parts of the body.” The committee further concluded that “the intake of IGFI (from milk) will not increase either locally in the gut or systemically. Consequently, the potential for IGF-I to promote tumor growth will not increase when milk from rbST-treated cows is consumed, resulting in no appreciable risk for consumers” (JECFA, 1998, p. 142). Since the 1998 JECFA report, the absorption of orally consumed IGF-I has been directly examined in humans, specifically premature neonates and young adults; IGF-I is a protein and results are convincing and provide no evidence that orally consumed IGF-I is absorbed in humans (Mero et al., 2002; Corpeleijn et al., 2008). Almost every tissue in the body synthesizes IGF-I and this hormone plays many important roles. Whereas the IGF system is critical for normal growth and development, it can also have a key role in the survival and growth of malignant cells. Although outside the purview of this report, there has been a related interest in the possible role of milk consumption on the risk for various types of cancers. Milk is known to contain a number of components that have anticarcinogenic effects when tested in studies with animal biomedical models (e.g., Parodi, 2007). Likewise, epidemiology studies indicate that the consumption of milk and dairy products reduces the risk against many types of cancer including bladder, breast, and colon cancers (e.g., reviews by Kliem and Givens, 2011; Rice et al., 2013). An exception is prostate cancer where an overview of studies suggests a very modest positive association between milk consumption and the risk of prostate cancer; several mechanisms to explain this effect are being actively investigated (e.g., Parodi, 2009). Overall, results since the 50th JECFA have provided additional evidence of the minimal effects of rbST on milk concentrations of IGF-I and further demonstrated a lack of absorption of orally consumed IGF-I in premature neonates and young adults.

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Bovine Viruses The 1998 JEFCA conference concluded that there was no evidence that rbST affects the expression of bovine leukemia virus (BLV), a lentivirus, based on studies with a goat model that used caprine arthritis encephalitis virus. They also noted that BLV was destroyed by simulated pasteurization conditions when milk is heated to 60°C for 30 s and that there was no evidence of human susceptibility to ruminant retroviruses (JECFA, 1998). No new information on effect of rbST on expression of retroviruses in ruminants has been published since the 1998 conference. However, several new research models have been developed to study retroviruses (see review by El Hajj et al., 2012), which may provide additional information in the future. The important role of somatotropin in the immune system has been clearly established (see review by Kelley et al., 2007). Additionally, research has demonstrated that human somatotropin increases immune system function in human immunodeficiency virus–infected people (Lo et al., 2008; Napolitano et al., 2008; Tesselaar and Miedema, 2008), and somatotropin administration to chickens increased resistance to Marek’s virus (Liu et al., 2001). Therefore, there is no evidence of increased expression of retroviruses in cattle treated with rbST or that retroviruses in cattle would pose a risk to human health. POSSIBLE Recombinant Bovine Somatotropin–RELATED HEALTH RISKS FROM MILK CONSUMPTION BY NEONATES AND YOUNG CHILDREN Background and Impact of Recombinant Bovine Somatotropin on Milk Composition The value of milk and other dairy products in meeting the food security and nutritional needs of the global population is well recognized (Neumann et al., 2002; Randolph et al., 2007; Rice et al., 2013) and milk is included in dietary recommendations by governmental authorities and public health organizations around the world. Dairy products are nutrient-dense foods and represent the best source for many essential nutrients. National nutrition surveys indicate at current U.S. intakes, milk and other dairy products are a major source of daily requirements for protein and 9 other essential minerals and vitamins (Rice et al., 2013). Furthermore, the protein in milk and dairy products is of higher nutritional quality than plant sources (FAO, 2011). Effects of rbST on milk composition have been extensively examined and the results were considered by earlier committees (JECFA, 1993, 1998). In brief, nutritional components and manufacturing characteristics are

not altered by rbST supplementation (e.g., see reviews Bauman, 1992; Laurent et al., 1992). In the case of specific milk proteins, rbST supplementation increased the total yield of milk protein, but milk protein percent and the pattern of milk proteins was essentially unchanged (Barbano et al., 1992). More recent studies have compared retail milks and found no meaningful differences in the composition of milks labeled as rbST-free and organic or unlabeled conventional milk (Vicini et al., 2008; O’Donnell et al., 2010). Milk composition is affected by many factors including genetics, stage of lactation, breed, diet, environment, and season, and these factors affect milk composition in an identical manner in rbST-treated cows (Bauman, 1992; Burton et al., 1994). Milk and Child Development The nutrient composition of food sources is an essential dietary consideration and a clear indication of the importance of milk and dairy products comes from multidisciplinary studies of children in developing countries. When the diets of schoolchildren had little or no animal source foods, the intake of essential macroand micronutrients was inadequate resulting in negative health outcomes including severe problems such as poor growth, impaired cognitive performance, neuromuscular deficits, psychiatric disorders, and even death (see symposium introduced by Murphy and Allen [2003] and reviews by Neumann et al. [2002] and Randolph et al. [2007]). The 2010 Dietary Guidelines for Americans identified dairy products as a major source for 3 of 5 “nutrients of concern” recognized as being marginal or inadequate for diets of children and 4 of 7 “nutrients of concern” in adult diets (USDA, 2010). Given the aforecited lack of rbST effects on the nutrient composition of milk, the use of rbST has no impact on the value of milk and dairy products in supplying nutrients that are essential for the developmental needs of children. Infant Feeding and Risk of Type 1 Diabetes Type 1 diabetes, also known as insulin-dependent diabetes mellitus or juvenile diabetes, is a chronic autoimmune disease that is characterized by selective loss of pancreatic insulin-producing β-cells. Evidence suggests that environmental triggers may be integral in inducing the onset of the autoimmunity in genetically susceptible individuals. In a recent review, Eringsmark Regnell and Lernmark (2013, p. 155) concluded that “putative inductive mechanisms include viral, microbial, diet-related, anthropometric, and psychosocial factors.” However, at present no obvious candidate trigger of islet autoimmunity exists, although recent research has focused on a possible role for enteroviruses (Lempainen et al., 2012;

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Eringsmark Regnell and Lernmark, 2013; Pugliese, 2013). An initial focus for the cause of type 1 diabetes was on diet and the concept that the early introduction of complex foreign proteins might be a risk factor for β-cell autoimmunity that leads to type 1 diabetes. Infant intake of proteins from dairy products, fruits, berries, cereal grains (gluten or nongluten), and roots were suggested to be associated with increased risk of β-cell autoimmunity (Schrezenmeir and Jagla, 2000; Knip et al., 2010). While dietary proteins have been a major research focus, to date no specific dietary factor has been shown to be an unequivocal risk factor for β-cell autoimmunity and observations are contradictory with regard to the effect of various foods (Knip et al., 2010; Eringsmark Regnell and Lernmark, 2013; Skyler, 2013). For example, studies of bovine milk in relation to type 1 diabetes have led to contradictory results, with some reporting early exposure to bovine milk as a predisposing factor whereas others found no causality (see reviews by Knip et al., 2010; Virtanen et al., 2012; Eringsmark Regnell and Lernmark, 2013; Pugliese, 2013). The failure to identify any dietary factor that is an unequivocal risk factor for autoimmunity and type 1 diabetes has led to the initiation of several large-scale randomized controlled investigations. One of these is a multinational study involving 77 centers in 15 countries to see if the frequency of type 1 diabetes can be reduced by formulas using milk protein hydrolysates as compared to cow’s intact milk-protein based formula; this study is referred to as Trial to Reduce Incidence of Diabetes in Genetically at Risk (TRIGR), with expected completion of the study in 2017 (TRIGR Study Group et al., 2011). Relative to the call for data on this topic by JECFA, as discussed earlier studies indicate that the composition of milk, including milk proteins, is not altered by the use of rbST. Present science does not unequivocally establish a specific role for milk, dairy proteins, or any other food source as the cause of the autoimmunity that led to type 1 diabetes. Therefore, the use of rbST would not impact the risk for type 1 diabetes. Association of Milk IGF-I and Diabetes There is no basis for an involvement of IGF-I found in milk and the development of type 1 diabetes. Type 1 diabetes is a chronic autoimmune disease and potential candidate triggers may include complex foreign proteins as discussed earlier. While many of the proteins in bovine milk differ in structure from those in breast milk, the IGF-I in cow’s milk and human milk has an identical structure and hence the IGF-I would not be recognized as a foreign protein. No evidence exists that milk IGF-I is involved in type 2 diabetes. The affinity of IGF-I for the insulin re-

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ceptor is very low (Gauguin et al., 2008) and concentrations of IGF-I in milk are insufficient to alter insulin receptor activity even if all of the IGF-I in milk were absorbed. Insulin will bind and activate its receptor with subnanomolar affinity; insulin also binds the IGF-I receptor but with approximately 1,000-fold lower affinity than the insulin receptor and also with approximately 1,000-fold lower affinity than IGF-I (Kurtzhals et al., 2000). At normal physiological insulin concentrations, both metabolic and mitogenic effects of insulin can be mediated via the insulin receptor (Lammers et al., 1989). However, at supraphysiological insulin concentrations, insulin might also exert mitogenic effects via the IGF-I receptor, which transmits growth stimuli more efficiently than the insulin receptor. Combinations of insulin plus recombinant IGF-I have been experimentally tested for the treatment of type 1 and type 2 diabetes (see review by Keating, 2008). For these investigations, IGF-I and insulin were administrated twice daily via subcutaneous injection and consistent with the low affinity of IGF-I for insulin receptors, large daily doses of IGF-I were used (approximately 140 μg/ kg BW). In addition, an extensive number of publications show that excessive circulating concentrations of IGF-I result in hypoglycemia and an array of metabolism-related disorders. This is most often observed in the investigations where exogenous IGF-I is being injected, and hypoglycemia is listed as a major side effect of critical concern (see review by Keating, 2008). Given the very low concentration of IGF-I in milk and that little or no IGF-I is absorbed from the digestive tract, IGF-I in milk would not cause hypoglycemic effects in humans. Adolescent and Adult Health Maintenance and Prevention of Chronic Diseases In addition to providing essential nutrients, there is increasing recognition that consumption of milk and dairy products is associated with improvement in health maintenance and the prevention of chronic diseases. Chronic diseases where a moderate health benefit is observed from the consumption of milk and dairy products include a reduced risk of type 2 diabetes, improved bone health, reduced blood pressure, and reduced risk of cardiovascular disease (e.g., see summaries in Elwood et al., 2008; USDA, 2010; Kliem and Givens, 2011; Rice et al., 2013). Given that the macro- and microcomposition of milk is not altered by the use of rbST, the beneficial effects of dairy products on health maintenance and reductions in risk of chronic diseases should not be affected.

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Conclusions Recombinant bovine somatotropin is a technology that allows feed resources to be used more efficiently with less animal waste and a reduced carbon footprint. Twenty years of commercial use of rbST by the United States provides the backdrop to address human health issues being considered by the upcoming 78th JECFA. Use of rbST has not increased human exposure to milk antibiotic residues as evidenced by postapproval studies with commercial herds and by national data for antibiotic residue violations and milk SCC. Likewise, use of rbST has not affected expression of retroviruses in cattle. Concerns about IGF-I have been allayed by recent human studies showing that oral IGF-I has no biological activity. The use of rbST does not increase IGF-I outside the typical range for milk concentration and human production of IGF-I far exceeds intake of milk IGF-I. Finally, use of rbST does not increase risk for type 1 or type 2 diabetes in children or adults consuming milk and dairy products. Milk and dairy products provide many essential nutrients and chronic health benefits, and the use of rbST by the dairy industry raises no new human health concerns. LITERATURE CITED APHIS Veterinary Service, Centers for Epidemiology and Animal Health. 2011. Determining U.S. milk quality using bulk-tank somatic cell counts. http://www.aphis.usda.gov/ animal_health/nahms/dairy/downloads/dairy_monitoring/ BTSCC_2011infosheet.pdf. Barbano, D. M., J. M. Lynch, D. E. Bauman, G. F. Hartnell, R. L. Hintz, and M. A. Nemeth. 1992. Effect of prolonged-release formulation of N-methionyl bovine somatotropin (sometribove) on milk composition. J. Dairy Sci. 75:1775–1793. Barbano, D. M., R. R. Rasmussen, and J. M. Lynch. 1991. Influence of milk somatic cell count and milk age on cheese yield. J. Dairy Sci. 74:369–388. Bauman, D. E. 1992. Bovine somatotropin: Review of an emerging technology. J. Dairy Sci. 75:3432–3451. Bauman, D. E., R. W. Everett, W. H. Weiland, and R. J. Collier. 1999. Production responses to bovine somatotropin in Northeast dairy herds. J. Dairy Sci. 82:2564–2573. Burton, J. L., B. W. McBride, E. Block, D. R. Glimm, and J. J. Kennelly. 1994. A review of bovine growth hormone. Can. J. Anim. Sci. 74:167–201. Clemmons, D. R. 2006. Involvement of insulin-like growth factor-I in the control of glucose homeostasis. Curr. Opin. Pharmacol. 6:620–625. Collier, R. J., J. C. Byatt, S. C. Denham, P. J. Eppard, A. C. Fabellar, R. L. Hintz, M. F. McGrath, C. L. McLaughlin, J. K. Shearer, J. J. Veenhuizen, and J. L. Vicini. 2001. Effects of sustained release bovine somatotropin (sometribove) on animal health in commercial dairy herds. J. Dairy Sci. 84:1098–1108. Collier, R. J., M. A. Miller, J. R. Hildebrandt, T. C. White, K. S. Madsen, J. L. Vicini, P. J. Eppard, and G. M. Lanza. 1991. Factors affecting insulin-like growth factor I (IGF-I) concentration in bovine milk. J. Dairy Sci. 74:2905–2911.

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References

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