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Effects of Food Preservatives and Hormones Present In Meat on the Bodies Hormonal Balance

Contents

Introduction

The hormonal balance of humans is regulated by many factors and even a slight change in the chemical composition of the body can upset this balance. Food preservatives are used all across the world in every aspect of the food industry to prolong shelf life and ensure a “fresher” taste in food. Hormones such as oestrogen, testosterone and progesterone occur naturally in animals. However, their synthetic versions and other man made hormones are added to animals before culling to promote growth.

The Main Food Preservatives Present in Meat Products

Here we describe the most commonly used food preservatives found in meat. Food preservatives appear in meat in both natural and artificial forms. Their role is to extend the shelf-life, enhance the flavour and appearance of food and to prevent botulism.

Natural Food Preservatives

Natural preservatives include sugar,salt and bacteriocins which are added to meat during the processing phase. While they have a direct effect on our health, they are also essential to maintain a balanced and healthy diet. However, high amounts accumulating in the body could have adverse effects on our body. For this reason, the use of all food preservatives is regulated and monitored by the FDA.

Sugar

Red meat, particularly pork, beef and lamb are associated with a rich sugar content, mainly in the form of N-glycolylneuraminic acid. Neu5GC is a sugar carbohydrate that is naturally produced in mammals but not humans. Therefore, they evoke an immune response in the human body by activating the plasma B-cells. Plasma cells secrete large glycoproteins that function as an antibody and bind to the Neu5GC during active immunity. These immunoglobulins are the IGg type immunoglobulins and by inducing this immune response in the body, the physical effects of Neu5GC are seen through chronic inflammation and other related diseases such as atherosclerosis and colon cancer. (Microbiology, 2020)

Sodium Chloride(NaCl)

Sodium chloride is a metal halide commonly known as a ‘table salt.’ It is a white crystalline solid and is the most important non-meat ingredient in processed meats due to its dissociation. It’s optimal concentration is about 2%. Sugar and salt are incorporated into meat through the processing techniques of curing and fermentation.Sodium chloride has an essential function to the homeostasis of the body. Sodium has an important role in transporting ions in and out of the cell based on actual needs. In this way, it maintains normal blood pressure and regulates fluid balance in the body. However, processed meats contain sodium in the form of salt and at a much higher level than necessary. When this occurs, the increased amount of sodium causes hypertension in blood vessels, increasing the risk of strokes and other cardiovascular disease.(Ruusunen et Puolanne, Meat science, 2005)

Enterocins

Enterocins are bacteriocins strained from the Enterococci species of bacteria. Derived from Enterococci faucium, E.herae, E.faecalis, E. avians, E.Durans,E. casseliflavus and E.mundtii strains, Enterocin type structural genes were found to have an antimicrobial effect.. Through PCR conductance, it was observed that the B type was always associated with the A type effects (Özdemir et al., 2011)These enterocins are often used in the production of fermented meat. They serve as a pathogen to microorganisms such as Clostridium species, E.coli, staphylococcus aureus, bacillus cereus and listeria monocytogenes. They essentially prolong the half- life of meat. The advantage of using these in comparison to other bacteriocins is that they remain stable in extreme conditions and varying temperatures. Their inhibitory effect can be strengthened when used in conjunction with a chemical or physical process. (Hugas, Garriga and Aymerich, 2003)

Rosemary Extract

Rosemary extract comes from the rosemary wooden evergreen shrub. It is extensively used as a preservative in all meat products, mainly for its active phenolic compounds. Rosemary contains approximately twenty four flavanoids, organised under the subclasses flavones, flavanols and flavanones. Flavones are the main constituent, containing 17 compounds of conjugated forms from luteolin, apigenin and hispidulin. The composition of these flavones varies depending on the agronomic and processing conditions undergone.(Alvarez et al., 2011). It improves the meat quality through its inhibition of lipid oxidation and rancidity and according to (Bañón et al.,, 2012)it also prevented sensory deterioration and microbial spoilage to a certain degree. It has an antimicrobial effect, slowing the activity of gram- positive bacteria. The antibacterial property is associated with compounds extracted with hexane. The antibacterial effect is strongly dependent on the composition media but heat had little effect on it. (CAMPO et al., 2000)

Synthetic food preservatives

Sodium Nitrate(NaNO3) and Nitrite(NaNO2)

Nitrates are not permitted to be added directly to heat-treated meat products however, they may be present in some heat-treated meat products resulting from natural conversion of nitrites to nitrates in a low-acid environment (The Use and Removal of Nitrite in Meat Products | FAQs | The Food Safety Authority of Ireland, 2020). In meat, nitrites turn into nitric oxide. It travels through the artery walls and sends signals to the tiny muscle cells around the arteries, telling them to relax. When these cells relax, the blood vessels dilate, and blood pressure goes down. Nitric Oxide reacts with proteins in the meat, changing its color and helping preserve it.Without nitrites and other additives, the meat would turn brown quickly.Nitrates and nitrites are essential compounds, but they can become hazardous if they form nitrosamines. Nitrosamines can form if you cook nitrates or nitrites at high heat.There are different types of nitrosamines, and many can increase the risk for cancer.Nitroglycerin is a drug that contains nitrates. Healthcare providers use it to treat heart failure and other conditions. Nitroglycerin can prevent or reverse angina, a type of chest pain that occurs when the heart muscle doesn’t get enough oxygen due to low blood flow.(Kim, Kerndt and Schalller, 2020)

Sodium Acetate(CH3COONa)

Sodium Acetate is the anhydrous sodium salt of acetic acid. It can be obtained by the neutralisation of acetic acid. It’s a hydroscopic powder that dissociates in water to form sodium and acetate ions. It is added to meat, especially raw poultry, to inhibit growth of microorganisms in order to prolong its shelf life and it also improves the sensory attributes of injected beef (Miller et Acuff,2006), providing a sour taste. It is commonly used in cured and deli meats against spoilage microorganisms and also in uncooked and marinated pork cuts. It is currently permitted up to a level of 0.25%. (Sebranak 2015).

Sodium Citrate

Sodium citrate is a derivative of citric acid, produced by its fermentation or neutralisation. It appears as a crystalline white powder with a melting point >300 degrees celsius. It is included in the ‘FDA’s approved list for handling and usage. It is collected during the slaughtering of livestock and used as an anticoagulant for blood meal production. It may be added with water to catalyse the reaction. It is used as a soil amendment for organic crops as it is a non-synthetic product. (Méndez-Vilas, 2011) When it is absorbed by the body, it dissociates into sodium cations and citrate anions which may further metabolise into bicarbonates and increase the level of them in the body.(Sodium citrate, 2020)

Sodium Tetraborate/ Borax (Na2[B4O5(OH)4].8H2O)

Borax is a colourless, salt-like substance that readily dissolves in water. It is used in meat as a firming agent, meat rub and tenderiser (Méndez-Vilas, 2011) Its structure consists of regular chains of octahedra formed by water molecules around Na running parallel to the c-axis. These chains are then held together by hydrogen bonds. (Morimoto, 1956). After gaining a reputation for its toxicity, it was banned in several countries. Today, it is permitted in the use of caviar in the EU but it is still not permitted in many countries including Australia, mainland China, Canada and New Zealand. (MA, 2020)

Sodium Benzoate(C7H5NaO2)

Sodium benzoate is a white crystalline powder that is more soluble in water than benzoic acid and thus, more preferable as a preserver in meat. It has a metabolic effect that is only marginally dependent on pH. (Stanojevic, Bulgarian culture of Agricultural Science, 2009.) It has an antimicrobial effect against Listeria Monocytogenes but it is only permitted in meat and poultry up to an amount of 0.5%. (Whitworth, 2013) The inhibitory effects of it depend on both the limitations of its actions and the sensitivity of the microorganisms themselves. (Stickler and Thomas,1982)

Propyl Gallate

Propyl gallate is the n-propyl ester of gallic acid. It is only slightly soluble in water but dissolves in ethanol, ethyl ether, oil and aqueous solutions. It is absorbed after ingestion, methylation and conjugation and is finally excreted in the urine. It has a slight toxic effect when ingested so is only permitted as an antioxidant up to a maximum concentration of 0.1%. (Int J Toxicol,2007).This phenolic antioxidant is able to effectively prevent rancidity in oily foods by interrupting the radical chain oxidation process and helps to prevent oxygen molecules from mixing with oil in food stuffs. The use of propyl gallate in food products is strictly banned in the European Union while in the USA it is permitted up to a level of 0.1%.(Xu, Hoy and Nissen, 1998)

Methyl Paraben(C8H8O3)

This chemical compound is the methyl ester of p hydroxybenzoic acid. It can be synthesised by p hydroxybenzoic acid and methanol with vitamin C as a catalyst or from the methylation of p-hydroxy benzoic acid in the presence of sulfuric acid. By experimental results, (Liao et al., 2013) showed that the optimal molar ratio of alcohol to acid is 4:1, a reaction time of 4 hours and 15% catalyst, there will be a yield of over 92.3%. The chemical is resistant to hydrolysis in water but can hydrolyse in alkaline solutions. It is added to meat and then easily absorbed through the gastrointestinal tract where it exerts its dangerous effects(Soni et al.,2002)

The Main Hormones Present in Meat Products

The utilization of hormones in the livestock and animal food production industry (‘anabolics’), are to ensure growth promotion, the formation of lean tissue with the metabolization of fat stores in the animals. This, in turn, increases quality and decreases cost of production. The use of hormonal compounds in the production of beef is now prohibited in the European Union. This is not the same in North America. Therefore, the importation of beef products, derived from cattle treated with hormones, from North America to the EU is banned. This ban is in place in the European Union because of concerns for the harmful effects that the metabolites and residual hormones, residing in the meat, may have on the health of humans that consume it. The effects were studied in regards to the digestive, absorptive, post-absorptive and excretory processes of the human body.(Galbraith, 2002)

The most common hormones used to administer to the animals are as follows; estradiol-17β, progesterone, testosterone, zeranol, trenbolone, and melengestrol acetate (MGA). These hormones are both naturally occurring in the animal and synthetically produced. These anabolics, in particular the natural sex hormones, increase the rate of growth by 8-15% and enhance feed efficiency by 5-10% (Buttery and Dawson, 1990).

Naturally Occurring Hormones

Oestradiol

Oestradiol is a naturally occurring hormone in the body and demonstrates oestrogenic activity.(Galbraith, 2002)It is administered by subcutaneously inserting an implant in the ear of cattle. 60 μg is released a day, (to total an amount of 8~24 mg), in order to increase the rate of weight gain and improve feed efficiency. Oestradiol works by binding to intracellular receptors, directly in the muscle tissue or indirectly by stimulation of growth hormone from the pituitary gland and other growth factors from organs. It also improves mineral absorption in the gut, as well as increasing the development of the reproductive system and secondary sexual traits, such as enlarged breasts, in females(Meyer, 2011). Oestradiol can cause between two-fold and several ten-fold increases in growth. There is 11~280 ng/kg of oestradiol, in muscle tissue of oestradiol-treated veal calves, heifers and steers, as opposed to 3~35 ng/kg, in these non-treated animals. Humans then consume approximately forty to thousands of times more oestradiol from the treated meat than that of the daily human production amount. However, as this hormone is consumed orally it is inactivated in the Gastrointestinal tract.

Progesterone

Progesterone is also a naturally occurring hormone in the body that has progestogenic activity.(Galbraith, 2002). 100~200 mg of Progesterone is given to animals in a mixture with 10~20 mg estradiol using an ear implant to again increase the rate of weight gain and improve feed efficiency.(Jeong et al., 2010) In addition to this progesterone is also inserted in dairy cows via an intravaginal sponge in order to synchronize the estrus cycle of lactating and non-lactating animals. Exogenous progesterone is mostly used for it’s reproductive benefits. Studies have shown that there is no difference between the concentration of progesterone present in the edible tissues of treated veal calves, heifers and steers, and non- treated meat. However, the concentration of progesterone present in adipose tissue is several times higher in treated meat than non-treated animals.

Testosterone

Testosterone is naturally occurring in the body, it shows androgenic activity(Galbraith, 2002). 200 mg of testosterone propionate is mixed with 20 mg of estradiol propionate and administered via an ear implant to promote the growth of the animal. Naturally, testosterone is synthesised in the body in leydig cells of the testicles, thecal cells of the ovaries and in the adrenal cortex It binds to androgen receptors to exert its function. It also binds to intracellular receptors in the muscle tissue and stimulates growth hormone and growth factors in the body.(Meyer, 2011) Testosterone is a precursor of other steroids. In a study, it was reported that the amount of testosterone residue in muscle tissue of treated veal calves/ heifers was 0.031~0.360 μg/kg, in contrast to 0.006~0.029 μg/kg in non-treated animals (Jeong et al., 2010)The human intake of testosterone via treated beef is significantly lower than the average daily intake of testosterone.

Synthetic Hormones

Zeranol, Melengestrol and Trenbolone are among the synthetic hormones added to meat. They are xenobiotic substances, meaning they are not naturally produced in the body. They are used for growth promotion in animals.

Trenbolone

Trenbolone is a synthetic anabolic steroid used to increase feed efficiency. Trenbolone is highly efficient due to its androgenic and antiglucocorticoid activity(Meyer, 2011). It is administered, at a dose of 200 mg/implant per heifer, in a subcutaneous ear implant either alone or in a mixture with estradiol-17B or zeranol. It works by binding to androgen receptors and glucocorticoid receptors. The stereoisomers 17α-trenbolone (found in liver and bile excretion) and 17β-trenbolone (found in muscle tissue) are the main metabolites produced by TBA. These metabolites have a lower binding affinity to progesterone and androgen receptors. TBA is a weak toxic chemical. It has an oral LD50 of 1,000~1,500 mg/kg bw. 2 μg/kg of β-trenbolone is the MRL of TBA in cattle muscle and 10 μg/kg of α-trenbolone in cattle liver. (Jeong et al., 2010)

Zeranol

Zeranol is a non steroidal anabolic substance. It is an oestrogenic substance that is derived from the fungal metabolite(Buttery and Dawson, 1990). It is metabolized to zearalenone taleranol in mammals. It demonstrates estrogenic activity. It is administered in an ear implant. The amount of zeranol residual in tissue is 0.01~1.21μg/kg. (Jeong et al., 2010)

Melengestrol

Melengestrol is a synthesised progesterone used to improve feed efficiency. It is given to the animal orally in doses of 0.25~0.50 mg/heifer per day during fattening and finishing periods. Melengestrol works via a high affinity for progesterone receptors and increases prolactin secretion and activates estrogen receptors. It works indirectly by stimulating endogenous oestradiol in the ovaries in non-pregnant heifers(Meyer, 2011). The main metabolite of MGA is 2β-hydroxy MGA, which is nine times less potent than MGA itself (WHO, 2004). The amount of MGA residue left in treated Canadian beef heifers, treated at a rate of 0.4 mg/animal per day, was on average 2.8 pg/kg. 4.6 % of all samples had an MGA residue of >10 pg/kg of fat (Jeong et al., 2010).MGA was found to be a low acute toxic chemical in rodents, however, not a genotoxic chemical in a range of in vitro and vivo assays in mice. The MRLs are 1, 10, 2 and 18 μg/kg for cattle muscle, liver, kidneys and fat, as recommended by JECFA in 2006.

Hormone Balance Regulation in Humans and how it is effected by:

Normal hormonal balance is maintained by many different factors. For example, hormones secreted in the adenohypophysis and neurohypophysis are regulated by inhibiting and releasing factors released from the hypothalamus. While other hormones produced from other endocrine glands such as the adrenal glands can be regulated by plasma K+ and Na+ concentration. The effect of hormones are exerted through receptors found in the cytoplasm and on the membrane. For example, the receptor may be an ion channel, it can be G-protein independent or dependent, it can be an anion receptor etc.. Hormones effects can also be manifested through different mechanisms such as the phospholipase C mechanism or adenylate cyclase mechanism.Some food preservatives and hormones used in food today act as so-called “Endocrine Disruptors” and inhibit the normal action of hormones leading to multiple effects.

(i)Food Preservatives

Methyl paraben(E218)- Parabens are esters of para-hydroxybenzoic acid and are used as preservatives in the cosmetic, pharmaceutical and food industries. Methylparaben is found in alcoholic beverages and some cosmetic products. Parabens are known to exert estrogenic effects and have been classified as endocrine disruptors. Research has illustrated a positive association of methylparaben with the plasma adipsin levels (KOLATOROVA et al., 2018). This suggested that methylparaben could be associated with obesity as adipsin levels are elevated in those who are overweight (Ruiz-Ojeda et al 2018). Adipsin(Factor D) controls the rate-limiting step in the alternative complement pathway where it cleaves factor B and is suggested that it regulates fat metabolism. It acts on free lipoproteins associated with fat oxidation. Parabens are therefore considered obesogenic endocrine disrupters or obesogens. Recent research also suggests that exposure to parabens such as methylparaben in early pregnancy can lead to the development of gestational diabetes mellitus as presence of parabens was associated with high glucose levels, however further research is required to confirm this (Liu et al., 2019)

Sodium Citrate- Sodium Citrate is found in gelatine mix, ice-cream, jams, sweets, milk powder, processed cheeses, carbonated beverages, and wine. Sodium Citrate is also used as an emulsifier for oils in the cheesemaking process. It has been shown that ingesting sodium citrate pre-exercise leads to a decrease in the serum aldosterone concentration at rest and has a blocking effect on the aldosterone response during incremental running to volitional exhaustion. Sodium citrate is thought to exhibit an effect on the serum aldosterone level by causing an increase in plasma volume and changing of serum Na+ concentration(Ööpik et al., 2010).Low aldosterone levels cause a low blood sodium level and a high potassium level, while also causing dehydration and low blood pressure.

Sodium Tetraborate/Borax- Borax has been banned all over the world as a food additive and preservative, however it is still currently allowed in the EU today to be used in sturgeon eggs(caviar). Boron is thought to be almost completely absorbed after ingestion and quickly appears in the blood and tissues of the body. A report commissioned by the EU to review the safety of adding sodium tetraborate(E285) to food concluded that because people are unlikely to incur caviar on a regular basis, borax was safe to use. However during their research, testicular damage and disruptive effects on male fertility were observed during feeding studies on different animals as it causes a decrease in sperm motility and testicular atrophy. (Scientific Opinion on the re‐evaluation of boric acid (E 284) and sodium tetraborate (borax) (E 285) as food additives, 2013)

Sodium Benzoate(E211)- This chemical is often used in acidic foods such as salad dressings, carbonated drinks,condiments and jams and fruit juices. Interestingly recent research suggests an alarming correlation between high intake of sodium benzoate with the development of attention deficit hyperactivity disorder (ADHD) in children. It was noted in mice that sodium benzoate reduced glutathione (GSH) and significantly increased the malondialdehyde (MDA) level in the brain. Results also noted that sodium benzoate hindered both memory and motor coordination. (Khoshnoud et al.,, 2017) Other research suggests that over consumption of sodium benzoate activates a change in serum clinical parameters, showing hepatocellular damage as it is conjugated with glycine in the liver and excreted as hippuric acid in the kidney and is thought also to affect glucose homeostasis(Lennerz et al., 2015). However, further research is needed to confirm this theory. In-vitro studies showed that sodium benzoate can potentially inhibit Kidney D-amino oxidase (Cyr & Tremblay,1989). Exposure to sodium benzoate can lead to the suppression of T helper 1-type immune response in the peripheral blood mononuclear cells in humans. (Maier et al., 2010). An abnormal intake of sodium benzoate can result in metabolic difficulties such as carnitine shortage due to the increase in the excretion of benzoylcarnitine and the depletion of hepatic ATP in animals (Lennerz et al., 2015).

Sodium Acetate(E262)- A chemical that is added as a preservative in liquorice, meat products, baked goods etc. and is also used as a flavour-enhancer. It was noted that the interaction between sodium acetate and human serum albumin(HSA) has an effect on the metabolism and absorption of chemical compounds. The increased ingestion of sodium acetate in the company of glucose may lead to complex formation with HSA and negatively affect organs such as the brain and heart by accelerating the onset of cancer, diabetes, brain damage and cardiac disease (Mohammadzadeh-Aghdash et al., 2019) The research suggested that sodium acetate exerts its effect through it’s interaction with albumin and leads to the activation of inflammatory processes which accelerates the development of aforementioned diseases and diabetes.

Propyl gallate(E310)- Propyl gallate is an antioxidant used in foods such as corn, especially animal fats and vegetable oils. However the toxicity of propyl gallate has mainly been demonstrated in animals. In dose levels above 10,000mg/kg feed in animals significant effects on the kidney and liver also leading to growth retardation (van der Heijden, Janssen and Strik, 1986). There are standards to restrict human exposure to propyl gallate, like the available daily intake(ADI) however most worryingly through exposure to cosmetic or makeup removal products many people may exceed the maximal dose. The lipophilic character of propyl gallates structure indicates a high affinity to biological membranes such as that of the mitochondrion (Eler et al., 2013). Research published in 2019 indicated that in mice propyl gallate significantly affects male fertility inflicting testicular dysfunction in both Leydig and Sertoli cells. Normal testis functioning was inhibited by mitochondrial dysfunction caused by propyl gallate and calcium homeostasis dysregulation. In this study it was also demonstrated that propyl gallate caused mRNA expression changes in steroidogenesis enzymes and hormone receptors in vitro and in vivo(Ham et al., 2019) A study conducted in 2014 illustrated that propyl gallate exhibits both estrogenic and anti-estrogenic (an antagonist to oestrogen receptors) effects. It was concluded that in the same range of concentrations propyl gallate has the potential to act as an agonist-antagonist. If propyl gallate was administered alone it bound to the oestrogen receptor and activated gene expression however when it was in the presence of a more potent oestrogen such as oestradiol it can block the oestrogen receptors. (Pop et al., 2014)

Sodium Nitrate and Nitrite- The use of sodium nitrite and nitrate as an antioxidant is highly regulated and is currently used in the curing of meats such as bacon and hot-dogs etc. In high amounts sodium nitrite can be incredibly toxic for humans as it oxidizes haemoglobin to methaemoglobin(MHb) which is similar to poisoning by carbon monoxide as it disrupts the normal release of oxygen from haemoglobin(Cvetković et al., 2018) Bacteria in the oral cavity induces the reduction of nitrate into nitrite which proceeds down the alimentary canal into the intestines where it is absorbed and leads to an increased plasma nitrite concentration (Kramkowski et al., 2016).However food isn’t the only source of nitrates for humans they can be present in food and air ,with the a reported human lethal dose of 4-50g (67-833mg kg-1 body weight). According to the WHO toxic doses range from 2-5g of NO3 (RIVM, 1989, WHO, 2011). As exposure to nitrates is so prevalent, much research has been done on human exposure to it. A study conducted in India concluded that among the many potential dangers the ingestion of nitrites and nitrates can inflict, the presence of nitrate in the thyroid completely inhibits the uptake of iodine by disrupting the sodium-iodine symporter and potentially causing goitre. (Gupta and Raghuram, 2010) Some studies have suggested a correlation between the uptake of nitrate/nitrites and the development of Type 1 diabetes as nitric oxide can inhibit the insulin production stimulated by glucose, however further research is needed to confirm this theory.

(ii)Hormones

Oestrogen- It has been indicated in many studies that the consumption of high levels of oestrogen from meat products may promote oestrogen accumulation in humans and potentially be related to the development of hormone-dependent cancers (Handa et al., 2010). High levels of oestrogen in females can lead to the development of breast cancers (Cleary and Grossmann, 2009). High levels of oestrogen in males can lead to a condition called gynaecomastia which causes breast tissue to grow. The main oestrogen steroid hormone is oestradiol 17β.Critics of the consumption of meats produced on such a large scale have suggested that the oestrogen present in the food can lead to the development of breast cancer, early puberty in teenagers and an hormonal imbalance. However no distinct connection has been made yet to indicate that the oestrogen present in chicken meat etc. that is consumed leads to the development of any of these conditions. The most tangible evidence against the negative effects of oestradiol 17 β is that it leads to the development of tumour cells (Kumar et al 2018) however no research confirming that the ingestion of estradiol-17 β disrupts the normal hormonal balance.

Progesterone- Progesterone is metabolised in the liver and the main metabolites found in the plasma are pregnanediol 3-glucuronide, 20a-dihydroporgesterone and 17-hydroporgesterone. In a study using female mice, progesterone was given subcutaneously for 5 days starting 26h after birth. This led to hyperplasia in the vaginal and cervical epithelia and a much higher incidence of the development of tumours in mammary tumour-virus bearing mice (Jones and Bern, 1977). It was concluded that progesterone increased the potential of developing ovarian, uterine and mammary tumours due to hormonal activity disrupted by progesterone (IARC, 1979). However it was concluded that that the amount of progesterone present in adipose tissue of meats such as beef is much lower than the daily production in both sexes and it therefore did not significantly affect the hormonal balance(Jeong et al., 2010)

Testosterone- It was found that testosterone is deposited in the liver, muscle, kidney and fat of animals. In human’s testosterone mainly undergoes oxidative metabolism in the liver. The active metabolite of testosterone is dihydrotestosterone (DHT) . This is further metabolised to androstenedione, androsterone and 3α- and 3β-androstanediol. According to a study completed on the effects of over-consumption of chicken presented strong evidence which suggested that it may lead to the development of polycystic ovary syndrome (condition in which women typically have a number of small cysts around the edge of their ovaries leading to different issues such as reduced fertility and excess hair growth) due to an imbalance of the steroid hormones (Ahmed et al., 2017). A study in 2010 highlighted that for years testosterone was perceived as a possible carcinogen due to its lack of adequate date in humans, the article outlined the use of testosterone in human medicine to treat issues such as deficient testicular function in men and, in postmenopausal woman to replace hormones in combination with oestrogen. (Jeong et al., 2010). High levels of testosterone in males can lead to the development of oily skin, acne and sleep apnea, while high levels in females can lead to the deepening of the voice and increased muscle mass etc. However this report concluded that the amount of testosterone we ingest from beef is so far below the established ADI(acceptable daily intake) that it does not lead to a hormonal imbalance.

Zeranol - Zeranol can affect oestrogen target organs and has the ability to disrupt reproductive patterns when it is administered to susceptible hosts (Lindsay, 1985). In animals the main metabolites of zeranol were found to be taleranol and zeralenone. It was found that the excretion of these was mainly through urine and consisted of glucuronide and sulphate compounds. This report also highlighted that zeranol and its metabolites have a half-life of 22h and if ingested by humans on a regular basis it can accumulate (Bircher et al., 2015). In 1999 a study on mice found that administering zeranol can lead to the disruption of the ovarian cycle and endometrial hyperplasia in females while in adult males it led to a decrease in the weight of the testis, prostate and seminal vesicle while also leading to the suppression of spermatogenesis (Newbold, 1999). As an oestrogen zeranol could promote the proliferation of breast tissues (Sheffield and Welsch,1985), and cause a lesion in the testes (Veeramachaneni et al., 1988; Pérez-Martínez et al., 1996) . In 2001 the lack of definitive data on the effect of growth hormones such as zeranol on human health and our hormonal balance was highlighted (Leffers et al., 2001).However the addition of zeranol to animals pre-slaughter is regulated intensively with an ADI outlined for human consumption. In 2004 research on the effects of prepubertal exposure to zeranol in rats concluded that it could lead to the significant damage of ovarian structure and function. This report also warned that the ingestion of zeranol in early life as an infant has the potential to cause severe endocrine disruption in later life (Yuri et al., 2004)

Melengestrol Acetate(MGA)- This is metabolized to more than 20 compounds in women with around 74% of the metabolites being excreted in the urine and faeces (Bircher et al., 2015). A study undertaken in 1989 outlined that MGA has the ability to block the menstrual or oestrous cycle in different species and block ovulation. The report also concluded that with a daily intake of 0.2-0.8mg of MGA in mice can lead to an increase in the serum prolactin concentration (Patterson et al., 1989). In 2000 JECFA (Joint FAO/WHO Expert Committee on Food Additives) described that MGA possessed many harmful characteristics such as its ability to exert fetotoxic, embryotoxic and teratogenic effects (agent that can disturb the development of the embryo or foetus) such as malformation of viscera, insufficient skeletal ossification in rabbits, resorption and deceased foetuses (JECFA,2000c). Previous studies declared that MGA exhibited both progestational and glucocorticoid activity (Lauderdale et al.,1977) however it was concluded that the plasma concentration of MGA in humans after ingestion would be so far below the minimal concentration needed to exert these effects and disrupt the hormonal balance.(JECFA 2009)

Trenbolane Acetate(TCA)- This is metabolized into it’s free active form, alpha and beta Trenbolone hydroxide (TBOH).However it’s metabolism in humans hasn’t been extensively researched but the metabolites that were present were found in the form of glucuronides consisting mainly of trendione, 17α-trenbolone and 17β-trenbolone (Bircher et al., 2015). A study conducted on the effects of 17β-trenbolone concluded that it is an influential environmental androgen and most worryingly it can induce abnormalities in the development of the foetus (Wilson et al., 2002). TBA (0.9-9 mg/kg bw/day ) administered to mice induced liver hyperplasia and in rats induced islet-cell tumours in the pancreas as a direct result of its hormonal activity (Schiffman et al., 1985, 1988). A higher amount of TBA was administered to pigs (2 μg/kg bw/day) which led to significant issues in the sexual organs such as decreased testosterone serum level and reduction in weight of the testes in male, and in females it led to the suppression of cyclic ovarian activity, in the uterine endometrium glandular development was inhibited and in the mammary glands there was a noticeable decrease in its secretion (JECFA, 1988; van Leeuwen, 1993). In male rhesus macaque monkeys that were castrated β-trenbolone demonstrated anti-gonadotropic activity (suppresses the activity of FSH OR LH) as it maintained the morphology of seminal vesicles and ,the testosterone and oestradiol levels in the serum remained unchanged(Wilson et al., 2002). From the aforementioned reports the ADI(acceptable daily intake)of TBA was concluded to be 0-0.02 μg/kg bw/day (JECFA (1988)). The MRLS(maximum residue level) of TBA were, in cattle muscle of 2 μg/kg of β-trenbolone and in the cattle liver 10 μg/kg of α-trenbolone. This report concluded that the despite the potentially harmful effects that TBA could inflict the amount we receive from ingested meat is too little to incur damage.( Jeong et al., 2010)

Conclusion

We can conclude that the addition of preservatives to food is an unfortunate necessity. Preservatives are absolutely required to prevent the growth of microbials and prevent the oxidation of perishable goods. We outlined harmful effects of different food preservatives on our hormonal balance, however we feel that to maintain the supply of food for today’s population it is impossible to eradicate the use of preservatives. We suggest where possible, we should also try to keep a balance of organic goods in our diet. It would also be beneficial for our producers to use more natural preservatives as they do not disrupt our normal hormonal balance. However, it was much more difficult to come to a definitive conclusion about the dangers associated with the presence of natural and additional hormones in meat consumed. Despite our best efforts to find distinct evidence that the hormones present in meat disrupts the normal hormonal functioning of humans, we did not find enough evidence to completely support our theory. We feel that there exists much research on methods to measure the hormonal accumulation in the body and track its metabolism in different chromatography and spectrometry journals. However, there is a gap in the research of the potentially negative effects these hormones have on the normal hormonal functioning of humans. This is most likely because food safety regulators have clearly outlined the ADI (acceptable daily intake) of each of these hormones in meat to prevent the potential disruptive effects. Some observers also believe that it is because the long term damage of these hormones will not be seen immediately but instead through adverse effects in our offspring and future generations to come. While we focused primarily on the hormonal effects associated with these different preservatives and hormones, we are most aware that some of the compounds possess more unfavourable foetal characteristics such as being a carcinogen or fetotoxic etc. We are also aware that exposure to ingestion of hormones comes not only from meat but also from things such as oestrogen in drinking water and the administration of certain growth hormones into the human body to build muscle mass. While these were not discussed in our report we feel that the aforementioned exposures pose a much larger threat to human health as the level of hormones people are administering to themselves is unregulated and there is no exact ADI.

References

Ahmed, S., Ahmed, I., Haider, S., Batool, Z. and Ahmed, S., 2017. Daily Consumption of Commercial Chicken Feed and Meat Lead to Alterations in Serum Cholesterol and Steroidal Sex Hormones in Female Rats. Pakistan Journal of Pharmaceutical Science, pp.257-261.

Alvarez, Y., Sainz, T., Wacher, C. and Fernández, F., 2011. Enterocins: bacteriocins with applications in the food industry. In: Science against microbial pathogens: communicating current research and technological advances.. FORMATEX.

Bañón, S., Méndez, L. and Almela, E., 2012. Effects of dietary rosemary extract on lamb spoilage under retail display conditions. Meat Science, 90(3), pp.579-583.

Bircher, S., Card, M.L., Zhai, G., Chin, Y.P. and Schnoor, J.L. 2015. Sorption, uptake, and biotransformation of 17β‐estradiol, 17α‐ethinylestradiol, zeranol, and trenbolone acetate by hybrid poplar. Environmental Toxicology and Chemistry 34(12): 2906-2913. Buttery, P. and Dawson, J., 1990. Growth promotion in farm animals. Proceedings of the Nutrition Society, 49(3), pp.459-466.

CAMPO, J., AMIOT, M. and NGUYEN-THE, C., 2000. Antimicrobial Effect of Rosemary Extracts. Journal of Food Protection, 63(10), pp.1359-1368.

Cleary, M. and Grossmann, M., 2009. Obesity and Breast Cancer: The Estrogen Connection. Endocrinology, 150(6), pp.2537-2542.

Cvetković, D., Živković, V., Lukić, V. and Nikolić, S., 2018. Sodium nitrite food poisoning in one family. Forensic Science, Medicine and Pathology, 15(1), pp.102-105. Cyr, D. M., & Tremblay, G. C. (1989). Potentiation of benzoate toxicity by glyoxylate. Inhibition of pyruvate carboxylase and the urea cycle. Biochemical Pharmacology, 38, 2919–2923 Final Report on the Amended Safety Assessment of Propyl Gallate1. (2007). International Journal of Toxicology, 26(3_suppl), 89–118. https://doi.org/10.1080/10915810701663176

Fsai.ie. 2020. The Use And Removal Of Nitrite In Meat Products | Faqs | The Food Safety Authority Of Ireland. [online] Available at: <https://www.fsai.ie/faq/use_and_removal_of_nitrite.html>

G.J. Eler, I.S. Santos, A.G. de Moraes, M.S. Mito, J.F. Comar, R.M. Peralta, A. BrachtKinetics of the transformation of n-propyl gallate and structural analogs in the perfused rat liver

Galbraith, H., 2002. Hormones in international meat production: biological, sociological and consumer issues. Nutrition Research Reviews, 15(2), pp.293-314.

Gupta, S. and Raghuram, N., 2010. Pathophysiology Of Nitrate Toxicity In Human And Its Mitigation Measures. Noida: Published by Indian Nitrogen Group, Society for Conservation of Nature in association with South Asian Nitrogen Centre, International Nitrogen Initiative.

Ham, J., Lim, W., Park, S., Bae, H., You, S. and Song, G., 2019. Synthetic phenolic antioxidant propyl gallate induces male infertility through disruption of calcium homeostasis and mitochondrial function. Environmental Pollution, 248, pp.845-856.

Handa, Y., Fujita, H., Watanabe, Y., Honma, S., Kaneuchi, M., Minakami, H. and Kishi, R., 2010. Does dietary estrogen intake from meat relate to the incidence of hormone-dependent cancers?. Journal of Clinical Oncology, 28(15_suppl), pp.1553-1553.

Hugas, M., Garriga, M. and Aymerich, M., 2003. Functionalty of enterococci in meat products. International Journal of Food Microbiology, 88(2-3), pp.223-233.

IARC. IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Vol. 21 Sex Hormones (II) IARC Press.; Lyon: 1979. pp. 35–82. 139-547

Jeong, S., Kang, D., Lim, M., Kang, C. and Sung, H., 2010. Risk Assessment of Growth Hormones and Antimicrobial Residues in Meat. Toxicological Research, 26(4), pp.301-313.

Joint FAO/WHO Expert Committee on Food Additives (JECFA) . Toxicological evaluation of certain veterinary drug residues in food: Melengestrol acetate. WHO Food AdditivesSeries. 2000c;45

• Joint FAO/WHO Expert Committee on Food Additives (JECFA) . Toxicological evaluation of certain veterinary drug residues in food: Tylosin. WHO Food Additives Series. 2009c;61

Joint FAO/WHO Expert Committee on Food Additives (JECFA). 1988. Evaluation of certain veterinary drug residues in food. WHO Technical Report Series 763: 16–33. Jones L.A. Bern H.A. Long-term effects of neonatal treatment with progesterone alone and in combination with estrogen on the mammary gland and reproductive tract of female BALB/cfc3H mice. Cancer Res. 1977;37:67–75

Khoshnoud, M., Siavashpour, A., Bakhshizadeh, M. and Rashedinia, M., 2017. Effects of sodium benzoate, a commonly used food preservative, on learning, memory, and oxidative stress in brain of mice. Journal of Biochemical and Molecular Toxicology, 32(2), p.e22022.

Kim, K., Kerndt, C. and Schalller, D., 2020. Nitroglycerin. [online] NCBI. Available at: <https://www.ncbi.nlm.nih.gov/books/NBK482382/>

KOLATOROVA, L., SRAMKOVA, M., VITKU, J., VCELAK, J., LISCHKOVA, O., STARKA, L. and DUSKOVA, M., 2018. Parabens and Their Relation to Obesity. Physiological Research, pp.S465-S472.

Kramkowski, K., Leszczynska, A., Przyborowski, K., Proniewski, B., Marcinczyk, N., Rykaczewska, U., Jarmoc, D., Chabielska, E. and Chlopicki, S., 2016. Short-term treatment with nitrate is not sufficient to induce in vivo antithrombotic effects in rats and mice. Naunyn-Schmiedeberg's Archives of Pharmacology, 390(1), pp.85-94.

Kumar, S., Rajan, V., Divya, C. and Sasikumar, P., 2018. Adverse effects on consumer’s health caused by hormones administered in cattle. International Food Research Journal,

• Lauderdale J.W. Studies of a progestogen (MGA) as related to residues and human consumption. J. Toxicol. Environ.Health. 1977;3:5–33. doi: 10.1080/15287397709529546.

Leffers, H., Naesby, M., Vendelbo, B., Skakkebaek, N. and Jørgensen, M., 2001. Oestrogenic potencies of Zeranol, oestradiol, diethylstilboestrol, Bisphenol-A and genistein: implications for exposure assessment of potential endocrine disrupters. APMIS, 109(S103), pp.S463-S472.

Lennerz, B., Vafai, S., Delaney, N., Clish, C., Deik, A., Pierce, K., Ludwig, D. and Mootha, V., 2015. Effects of sodium benzoate, a widely used food preservative, on glucose homeostasis and metabolic profiles in humans. Molecular Genetics and Metabolism, 114(1), pp.73-79.

Liao, C., Liu, F. and Kannan, K., 2013. Occurrence of and Dietary Exposure to Parabens in Foodstuffs from the United States. Environmental Science & Technology, 47(8), pp.3918-3925.

Lindsay, D.G. 1985. Zeranol—a ‘nature-identical’ oestrogen? Food and Chemical Toxicology 23(8): 767-774

Liu, W., Zhou, Y., Li, J., Sun, X., Liu, H., Jiang, Y., Peng, Y., Zhao, H., Xia, W., Li, Y., Cai, Z. and Xu, S., 2019. Parabens exposure in early pregnancy and gestational diabetes mellitus. Environment International, 126, pp.468-475. MA, J., 2020. Boric Acid And Borax In Food. [online] Cfs.gov.hk. Available at: <https://www.cfs.gov.hk/english/multimedia/multimedia_pub/multimedia_pub_fsf_37_01.html>

Maier E., Duschl A., Horejs-Hoeck J. STAT6-dependent and -independent mechanisms in Th2 polarization. Eur. J. Immunol. 2012;42:2827–2833. doi: 10.1002/eji.201242433

Méndez-Vilas, A., 2011. Science And Technology Against Microbial Pathogens: Research, Development And Evaluation: Proceedings Of The International Conference On Antimicrobial Research (ICAR2010), Valladolid, Spain, 3-5 Novem. World Scientific.

Microbiology, C., 2020. Strip Steak: Bacterial Enzyme Removes Inflammation-Causing Meat Carbohydrates. [online] Phys.org. Available at: <https://phys.org/news/2019-09-steak-bacterial-enzyme-inflammation-causing-meat.html> [Accessed 19 April 2020].

Miller RK, Acuff GR(2006) Sodium lactate affects pathogens in cooked beef. J.Food Sci.,59:15-19 Mohammadzadeh-Aghdash, H., Akbari, N., Esazadeh, K. and Ezzati Nazhad Dolatabadi, J., 2019. Molecular and technical aspects on the interaction of serum albumin with multifunctional food preservatives. Food Chemistry, 293, pp.491-498.

Morimoto N (1956) The crystal structure of borax, Mineralogical Journal, 2, 1-18 National Center for Biotechnology Information. PubChem Database. Sodium citrate, CID=6224, https://pubchem.ncbi.nlm.nih.gov/compound/Sodium-citrate

Newbold, R.R. 1999. Diethylstilbestrol (DES) and environmental estrogens influence the developing female reproductive system. In Rajesh, K. N. (Ed.) Endocrine Disruptors, p. 39-53. New York: CRC Press.

Ööpik, V., Timpmann, S., Hackney, A., Kadak, K., Medijainen, L. and Karelson, K., 2010. Ingestion of sodium citrate suppresses aldosterone level in blood at rest and during exercise. Applied Physiology, Nutrition, and Metabolism, 35(3), pp.278-285.

Özdemir, G., Oryaşın, E., Bıyık, H., Özteber, M. and Bozdoğan, B., 2011. Phenotypic and Genotypic Characterization of Bacteriocins in Enterococcal Isolates of Different Sources. Indian Journal of Microbiology, 51(2), pp.182-187.

Patterson, D.J., Kiracofe, G.H., Stevenson, J.S. and Corah, L.R. 1989. Control of the Bovine Estrous Cycle with Melengestrol Acetate. Journal of Animal Science 67: 1895-1906.

Pérez-Martínez, C., García-Iglesias, M.J., Ferreras-Estrada, M.C. et al. (1996). Effects of in-utero exposure to zeranol or diethylstilbooestrol on morphological development of the fetal testis in mice. J. Comp. Pathol. , 114, 407–418. Pop, A., Drugan, T., Gutleb, A., Lupu, D., Cherfan, J., Loghin, F. and Kiss, B., 2016. Individual and combined in vitro (anti)androgenic effects of certain food additives and cosmetic preservatives. Toxicology in Vitro, 32, pp.269-277.

Ruiz-Ojeda, F., Olza, J., Gil, á. and Aguilera, C., 2018. Oxidative Stress and Inflammation in Obesity and Metabolic Syndrome. In: Oxidative Stress and Dietary Antioxidants. Pp.1-15.

Ruusunen, M. and Puolanne, E., 2005. Reducing sodium intake from meat products. Meat Science, 70(3), pp.531-541.

Schiffmann, D., Metzler, M., Neudecker, T. and Henschler, D. 1985. Morphological transformation of Syrian hamster embryo fibroblasts by the anabolic agent trenbolone. Archives of Toxicology 58(1): 59-63.

Scientific Opinion on the re-evaluation of boric acid (E 284) and sodium tetraborate (borax) (E 285) as food additives EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS).

Sebranek J. G. An overview of functional non-meat ingredients in meat processing: The current toolbox; Proceed. 68th Recip. Meat Conf.; Lincoln, NE, USA. 2015. pp. 42–46

Sheffield, L.G. and Welsch, C.W. (1985) Zeranol (beta-resorcylic acid lactone), a common residuous component of natural foodstuffs, stimulates developmental growth of the mouse mammary gland. Cancer Lett., 28, 77–83

Soni, M.G. & Taylor, Steve & Greenberg, Norman & Burdock, George. (2002). Evaluation of the health aspects of methyl paraben: A review of the published literature. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 40. 1335-73. 10.1016/S0278-6915(02)00107-2.

STANOJEVIC, D., COMIC, L., STEFANOVIC, O. and SOLUJIC-SUKDOLAK, S., 2009. ANTIMICROBIAL EFFECTS OF SODIUM BENZOATE, SODIUM NITRITE AND POTASSIUM SORBATE AND THEIR SYNERGISTIC ACTION IN VITRO. Bulgarian Journal of Agricultural Science,, 15(4), pp.307-311.

Stickler, D. and Thomas, B., 1982. Intrinsic resistance to non-antibiotic antibacterial agents. Toxicol. Appl. Pharmacol., 273 (2013), pp. 35-46

van der Heijden, C., Janssen, P. and Strik, J., 1986. Toxicology of gallates: A review and evaluation. Food and Chemical Toxicology, 24(10-11), pp.1067-1070.

van Leeuwen F.X.R. Endocrine Toxicology: A review of the application of endocrinology in experimental toxicology. Comp. Haematol. Int. 1993;3:8–13 Veeramachaneni, D.N., Sherman, G.B., Floyd, J.G. et al. (1988) Zeranol and oestradiol induce similar lesions in the testes and epididymides of the prepubertal beef bull. Fundam. Appl. Toxicol. , 10, 73–81.

Whitworth, J., 2013. FSIS Allows Three Substances To Help Meat And Poultry Safety. [online] foodnavigator.com. Available at: <https://www.foodnavigator.com/Article/2013/03/11/Food-ingredients-and-sources-of-radiation-approved> Wilson, V., Lambright, C., Ostby, J. and Gray, L., 2002. In Vitro and in Vivo Effects of 17beta-Trenbolone: A Feedlot Effluent Contaminant. Toxicological Sciences, 70(2), pp.202-211.

Xu, X., Hoy, C. and Nissen, J., 1998. Effects of lipid-borne compounds on the activity and stability of lipases in microaqueous systems for the lipase-catalyzed interesterification. Progess in Biotechnology, 15, pp.441-446.

Yuri, T., Nikaido, Y., Shimano, N., Uehara, N., Shikata, N. and Tsubura, A., 2004. Effects of Prepubertal Zeranol Exposure on Estrogen Target Organs and N-Methyl-N-nitrosourea-induced Mammary Tumorigenesis in Female Sprague-Dawley Rats. International Journal of Experimental and clinical pathophysiology and Drug research, 18(6), pp.755-762.