BRIEF OVERVIEW STUDIES ON ENDOCRINE DISRUPTORS POLYCYCLIC AROMATIC HYDROCARBONS WITH SPECIAL REFERENCE TO NEWSPAPER INK

BRIEF OVERVIEW STUDIES ON ENDOCRINE DISRUPTORS POLYCYCLIC AROMATIC HYDROCARBONS WITH SPECIAL REFERENCE TO NEWSPAPER INK

Anita Singh Purvia * and Vinoy Kumar Srivastava

Laboratory of Endocrinology, Department of Bioscience, Barkatullah University, Bhopal, Madhya Pradesh, India.

ABSTRACT: Now a day’s food materials are packaged and wrapped in paper that is the dangerous practice of wrapping, covering or processing foods with newspaper and printed recycled paper materials remains commonplace worldwide, as seen in the plethora of photographs in advertisements online or in magazines showing newspaper wrapped foods. The health hazard of ink contamination to foods and long-term contact with complex chemicals should always be considered because of the potentially diverse array of biological and toxicological effects. Polycyclic aromatic hydrocarbons inhibit the function of thyroid, adrenal and male reproductive system, like secreted hormonal imbalance due to this several disorders occurs in human body. However, proposed studies will be helpful to human health especially to thyroid, adrenal and male reproductive system deficiency caused by polycyclic aromatic hydrocarbons because we have avoided ink-based newspaper wrapped food materials to minimize the endocrine glands diseases. We will initiate systematic campaigns for generating awareness among all the stakeholders to discourage the use of newspapers for packing, serving and storing food items. Therefore, this proposed study is useful to generate knowledge in the peoples to avoid the wrapped and covering process of food materials by paper inks and also avoid adulterate food materials for betterment of health.

Keywords: Food materials, Endocrine disruptors, Polycyclic aromatic hydrocarbons, Newspaper ink

INTRODUCTION: Endocrine glands are glands of the endocrine system that secrete their products, hormones, directly into the blood rather than through a duct. Endocrine disruptors are chemicals that interfere with human and animal hormone systems, and are capable of altering hormone balance and embryo development, with the risk of adverse effects on the health of organisms and their offspring.

The term endocrine disruptor chemical (EDC) was coined some 50 years later, in 1991, during the Wingspread Conference, when a group of endocrinologists, toxicologists, epidemiologists, and other health experts met to assess harmful effects on humans. Food as a basic need for all people must be wholesome and safe.

Food adulteration is a major public hazard which affects the quality of life of people. The packaging and processing of food materials mostly are by paper. Paper is a versatile material with many uses, including writing, printing, packaging, cleaning, decorating and a number of industrial and construction processes. In India the peoples consuming food in printed papers served by street vendors and small hotels as there is a higher risk of contracting cancers at an early age. Foods contaminated by newspaper ink raise specific health concerns since the ink contains multiple bioactive materials with known negative health effects. Polycyclic aromatic hydrocarbons are hydrocarbons-organic compounds containing only carbon and hydrogen that are composed of multiple aromatic rings. Phthalates are industrial chemicals that are extensively used as plasticizers in a variety of consumer products like food. For instance, Di-(2-ethylhexyl) phthalate (DEHP) is usually used for polyvinyl chloride material, food packaging and medical and diethyl phthalate (DEP) ¹. Several researchers have been reported that Endocrine disruptors are chemicals that interfere with human and animal hormone systems, and are capable of altering hormone balance and embryo development, with the risk of adverse effects on the health of organisms and their offspring. The Food Safety and Standards Authority of India (FSSAI) has banned the use of newspapers and other printed papers, still several hotels and eateries are using it without knowing the consequences.  Hence, the proposed study is essential for Endocrine Glands disorders and hormones deficiency related to consumption of adulterated food in human diet through preservatives, chemicals and paper inks especially polycyclic aromatic hydrocarbons.

Food Adulteration and Endocrine Glands: Food adulteration is a major public hazard that affects the quality of life of people ². The nature of food adulteration and contamination may vary from place to place or there could be newer adulterants, as a result of changing environmental factors, like non-seasonal rains or improved production/ cultivation practices and also reported that some of the adulterants which are used for malpractices including starch, stones, chips, saw dust, urea, caustic soda, kesaridal, mineral oil, argemone oil, synthetic colours asbestos, mycotoxins and aflatoxins

Endocrine glands are glands that secretes a substance (a hormone) into the bloodstream. They include the hypothalamus, pituitary gland, pineal gland, thyroid, parathyroid glands, heart, the stomach and intestines, islets of Langerhans in the pancreas, the adrenal glands, the kidney, fat cells and the testes, the ovarian follicle (estrogens) and the corpus luteum in the ovary. Hormones produce their effects on target tissues by binding to specific proteins called hormone receptors located in the target tissues only. Each receptor is specific to one hormone only and hence receptors are specific and formed hormone-receptor complex that leads to certain biochemical changes in the target tissue. Hormones are regulated physiological and metabolic function on target tissue. On the basis of their chemical nature, hormones can be divided into groups:

• Peptide, polypeptide, protein hormones (Pituitary hormones, Insulin, glucagon, hypothalamic hormones, etc.).
• Steroids (Cortisol, progesterone estradiol and testosterone).
• Iodo-thyronines (thyroid hormones).
• Amino-acid derivatives (Epinephrine).

Hormones that interact with membrane-bound receptors normally do not enter the target cell, but generate second messengers (e.g., cyclic AMP, IP3, Ca++ etc) which in turn regulate cellular metabolism.

Modes of Action of Endocrine Disruptor Chemicals (EDCs): From a toxicological perspective, endocrine disruptor chemical (EDCs) can be classified according to their sources or their modes of action.  The first classification of EDCs proposed by scientists are Natural (Phytoestrogen: genistein and coumestrol) and Synthetic (Polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), dioxins; dichlorodiphenyltrichloroethane (DDT), diethylstilbestrol (DES), vinclozolin, BPA and Phthalates ^{3, 4}. The second classification of EDCs ^{5, 6} was already reported based on EDCs that affect the central nervous system; thyroid; pancreas; reproductive system; and affect other systems.

Several scientific institutions including European Commission, European Environmental Agency and Endocrine Society, WHO/UNEP, IARC have shown interest for the association between EDCs and cancer affecting testis, prostate, thyroid and breast for suggesting that the exposure to some EDCs may be a risk factor in the development of these tumours as reported by number of pioneer researchers ^{7, 8, 9}. Fungicides, pesticides, PDBE, organochlorides, PCB, DDT, dichloro diphenyl dichloroethylene (DDE), arsenic and cadmium are played roles in important roles in food adulteration and may be cause testicular cancer with etiopathogenetic role in the onset of TDS.

PCB also reported forms of dioxins, cadmium, phytoestrogens, DES, furans, ethylene oxide may also contribute to the field of food adulteration and may also cause breast cancer. Finally arsenic, cadmium, PCB, and pesticides seem to contribute importantly to prostate carcinogenesis ¹⁰.

Every endocrine axis may be a target for each EDCs and their action is not limited to a single axis or organ but it is now quite clear that hypothalamus-pituitary gland-thyroid (HPT), hypothalamus-pituitary gland-gonads (HPG) and hypothalamus-pituitary gland-adrenal (HPA) represent the main targets of EDCs. Nevertheless, evidence also shows that some EDCs may affect the central nervous system (CNS) impairing hypothalamic and pituitary functions ^{8, 11}.  The report EDCs disrupt the proper actions of peripheral glands reported by some researchers ^{8, 10, 11}. Recent evidence has reported that EDCs may disrupt energy metabolic homeostasis altering adipose tissue that may increase in number and size of adipose cells, impairing endocrine regulation of adipose tissue, adipocytokine production, reducing basal metabolic rate and changing the regulation of appetite and satiety ^{12, 13}.

Effect of Paper ink in Human Endocrine Glands and other Disorders: The use of newspapers to wrap, pack or serve food is quite common in India. Indian populations are huge fan to street food like chatpata golgappa, chaats, samosa bhel puri, pakoras, batata paos, posa jalebi etc. The Safety and Standard Authority of India (FSSAI) found in recent investigations that most street vendors, small hotels, and homes also serving food in the newspaper. FSSAI advises and share that wrapping food items in newspapers is bad for our health as the ink used in printing has multiple bioactive materials with known negative health effects. "Printing inks may also contain harmful colors, pigments, binders, additives and preservatives. Some reports have been reported that contamination of foods by newspaper ink raises specific health concerns and the ink contains multiple bioactive materials with known negative health effects ^{14, 15}. Naphthylamine and aromatic hydrocarbons are the major concerns and have reported endocrine disruptors are defined as exogenous substances that alter functions of the endocrine system and consequently cause adverse health effects in an intact organism, or its ¹⁶.

The ink and dye industry is an increased risk of lung cancer among newspaper printing workers who have been exposed to ink mist containing these chemicals. Bladder cancer is another notable disease found to be associated with ink and dye ¹⁷. The exposure to Naphthylamine, Benzidine, and 4-Aminobiphenyl has long been established as the major risk factor for bladder cancer with this risk being proportional to the length of exposure ^{18, 19, 20}.

Research has also shown health concerns regarding exposure to some other specific ink chemicals (example 2-Naphthylamine induced rat bladder cancer) ²¹. The arylamines have reported exposure (cigarette smokers, hairdressers, and workers of dye and textile industries) has been linked to a significantly higher risk for bladder cancer in men ²². In addition to the above-mentioned carcinogenic effects of printing ink, other research shows that newspapers and newspaper ink contain agonists for the AhR ²³.  The AhR pathway is a ligand-dependent, basic helix-loop-helix, Per-Arnt-Sim-containing transcription factor that mediates a diverse array of biological and toxicological effects in a variety of species ²⁴.

Some evidence indicates that chronic exposure to relatively high doses of a metabolically labile polycyclic aromatic hydrocarbon (PAH) AhR agonist, i.e. b-Naphthoflavone can be as effective at producing AhR-dependent toxicity as a single exposure to those that are metabolically persistent have reported time to time ^{25, 26, 23}.

After that other researchers have reported and indicated that when a PAH metabolizing enzyme, such as CYP1A (cytochrome P450, family 1, subfamily A) is either chemically inhibited or knocked down, metabolically labile AhR ligands will produce AhR-dependent toxic effects ^{27, 28}. Some researchers showed that the direct contact between the greasy food and the newspaper increases the risk of newspaper ink and chemicals being absorbed by the food through the cooking oil (lipid), which acts as a good medium for the transfer of ink ingredients ²⁹.

The majority of printing inks are based on mineral oils (MOs) which contain complex mixtures of saturated and aromatic hydrocarbons. Consumer exposure to these oils occurs either through direct skin contact or, more frequently, as a result of MO migration into the contents of food packaging that was made from recycled newspaper. Despite this ubiquitous and frequent exposure little is known about the potential toxicological effects, particularly with regard to the aromatic MO fractions ³⁰.

The inks used can be categorized into water-based, solvent-based and mineral oil (MO)-based. With more than 420,000 ton used in 2012 the latter on majority of inks used for printing in institute of Europe and world-wide as reported by EuPIA. Some scientists proposed some applications comprising, amongst others, newspaper printing as well as the labeling and decoration of food packaging ³¹. Hence it comes as little surprise that residues of MOs are detectable in cardboard packages for food. Without further barriers the respective MOs can migrate into the packaged foodstuffs and compounds from mineral oils have indeed been detected in dry foods such as rice and noodles in concentrations as high as tens to hundreds of mg/kg have reported ^{32, 33}.

The naphthenes, n-alkanes and iso-alkanes isolated by LC-GC analysis of the aromatics in a mineral oil fraction and batching oil for jute bags, whereas the latter contains highly alkylated monoand polycyclic aromatic hydrocarbons (PAHs) ^{34, 35}.

In an investigation found that the most of the newspapers are printed with soy-based inks and rest of the papers are printed with vegetable oils (cooking oils) and is still most widely used raw material in the ink industry. Furthermore, they have explained both the direct contact and relatively long contact time (more than 24 hours) increase the level of the food been contaminated by the ink. Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BP), are detectable in certain consumer products, including newspapers ¹⁴.

In one studies of PAHs BP which were able to migrate from newspaper inks and to penetrate into deeper and viable layers of the skin. In addition it could be shown that the molecular weight of the PAHs is strongly influencing its cutaneous migration. Human skin cells and 3D skin models were proven to be capable of metabolizing BP toward a range of phenols, diols, quinones and the hydrolysis product of the ultimate carcinogenic intermediate (BPDE), that is, the 7,8,9,10-tetraol. They have alternatives of bisphenol A (BPA) which is more being used in thermal paper receipts for getting an overview of the situation in Switzerland ³⁶.

A substitution of BPA by BPF and BPS should be thus considered with caution and exhibits almost a similar endocrine activity as BPA. D-8 and Pergafast®- 201 could be alternatives to replace BPA, however further analyses are needed to better characterize their effects on the hormonal system ³⁷.

The thermal paper contains potentially toxic additives, such as bisphenol A (BPA), as a common color developer has reported, because of its known endocrine disrupting effects, structural analogues to bisphenol A (BPA), such as bisphenol S (BPS), D-8 and Pergafast 201, which have been used as alternatives ³⁸. A study suggested some epidemiological evidence for several groups of common contaminants, including PCBs, brominated flame retardants, phthalates, BPA and perfluorinated chemicals, are associated with reduced serum thyroid hormone levels in humans. Moreover, a much longer list of chemicals has caused a reduction in circulating levels of thyroid hormones or interfered directly with thyroid hormone action in experimental animals. Severe thyroid hormone deficiency causes severe brain damage, such that universal screening of thyroid hormone levels in serum occurs all over the world ¹⁶.

Phthalates reported as one of the industrial chemicals that is extensively used as plasticizers in a variety of consumer products. For instance, diethyl phthalate (DEP) and di-n-butyl phthalate (DBP) are used for personal care and pharmaceutical products ¹.

Di-(2-ethylhexyl) phthalate (DEHP) reported that it is usually used for polyvinyl chloride material, food packaging and medical device ^{39, 40, 41}.  The EDCs is represented by its ability to bind endocrine nuclear receptors acting as total, partial, or inverted agonist proposed the most documented mechanism ^{42, 43, 10, 8}.

The effect of endocrine disrupters (EDCs) reported earlier that EDCs can bind to activate various hormone receptors including androgen receptor, estrogen receptor, aryl hydrocarbon receptor, pregnane X receptor, constitutive androstane receptor, estrogen-related receptor, glucocorticoid receptor, thyroid hormone receptor, retinoid X receptor-AR, ER, AhR, PXR, CAR, ERR, GR, TR and RXR) that mimic the action of natural hormone’s ^{42, 43, 44, 45}.

Effect of Endocrine Disrupters on Thyroid Glands: Thyroid is essentially a gland that produces stores and releases two important hormones, which are Tri-iodothyronine (T3) and Thyroxine (T4).  The amount of thyroid hormones secreted is controlled by another hormone, called thyroid stimulating hormone (TSH), which is released from the pituitary gland in your brain.

Thyroid hormones as Triiodothyronine (T3) and Thyroxine (T4), basically are important regulators for differentiation, growth and metabolism of virtually all tissues and organs of human body including the ovaries and endometrium ⁴⁶. Researchers have noticed and defined the proper thyroid function is essential to have a healthy and normal reproduction, therefore, the female reproduction is inhibited by both hyperthyroidism and hypothyroidism ^{47, 48}. Some report highlighted that the hypothyroidism is the leading cause of impaired female fertility as it causes ovulatory dysfunction and most of the women who have polycystic ovarian syndrome (PCOS) which is one of the most common endocrinopathy, in women of reproductive age, seem to be concomitantly affected by thyroid dysfunction ⁴⁹.

In India, hypothyroidism was usually categorized under the cluster of iodine deficient disorders (IDDs), which were represented in terms of total goiter rates and urinary iodine concentrations, typically assessed in school-aged children and it is also prevalence of iodine deficiency disorders in adolescents ^{50, 51, 52}.

The researcher reported that ever since India adopted the universal salt iodization program in 1983, there has been a decline in goiter prevalence in several parts of the country, which were previously endemic ^{53, 54, 55}.

Phthalates are industrial chemicals like diethyl phthalate (DEP) and di-n-butyl phthalate (DBP), Di- (2-ethylhexyl) phthalate (DEHP) is usually used for polyvinyl chloride material, food packaging and medical device  that’s  are effects on endocrine glands ^{39, 40, 41}. Thyroid disease, as a chronic illness which is affecting approximately 200 million people worldwide ⁵⁶. The prevalence of thyroid disease is much higher among women than among men ⁵⁷.

Phthalates may have antagonistic effect on the thyroid function both in vivo and in vitro through a variety of mechanisms, such as down-regulation of the human sodium/iodide symporter (NIS) promoter ^{58, 59, 60, 61, 62, 63, 64}. Ice cream is adultered by pepper oil, ethylacetate, butraldehyde, acetate, nitrate, washing powder etc. Pepper oil is used as a pesticide and ethyl acetate causes terribble diseases affecting lungs, kidneys and heart due to hormonal imbalance reported earlier ⁶⁵.

Effect of Endocrine Disrupting Chemicals on Pituitary Gland: The pituitary gland secretes two gonadotropic (gonad-stimulating) hormones that control ovarian functions: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Growth of the ovarian follicles is regulated by FSH, whereas both LH and FSH are necessary for estrogen synthesis (the major estrogen is estradiol). LH also stimulates progesterone and androgen synthesis in the ovary. The androgen is a precursor for estrogen synthesis and this step is regulated by FSH. In addition, LH is responsible for ovulation. Release of LH and FSH from the pituitary is regulated by a single hypothalamic hormone called gonadotropin-releasing hormone (GnRH; formerly called luteinizing hormone-releasing hormone, or LHRH).  Several EDCs which act on the pituitary gland, for influencing the different endocrine axes, as a result, a wide spectrum of clinical manifestations were found to be has been associated with exposure to pollutants, such as precocious/delayed puberty and circadian disruption as reported ^{66, 67}.

Effect of Endocrine Disrupting Chemicals on Reproductive System: The chemical structure of most of EDCs mimics sex gonadal hormones showed the ability to bind to endocrine receptors interfering with hormonal signals, reproductive system represents the most vulnerable endocrine axis to EDCs actions have been reported ⁴⁴. The US EPA described five classes of EDCs endowed with anti-androgenic properties and, simultaneously, with weak estrogenic activity:

1. Drugs or synthetic estrogens (17 b estradiol, diethylstilbestrol).
2. Phytoestrogens (Isoflavonoids, cumestans, lignans, stilbens).
3. Pesticides (Organophosphates, carbamates, organochlorines, synthetic pyrethroids).
4. Plasticizers and chemicals produced by incomplete combustion of polyvinyl chloride (PVC), paper and putrescible substances (dioxin).

Researcher have isolated some industrial substances and their by-products (i.e. Phenols, dioxins, heavy metals, perfluorooctanoic acid, flames retardants) ^{68, 69}.

Phthalates, diethylstilbestrol, bisphenol A (BPA), TCCD that are involved in the onset of endometriosis occurring in 10% of fertile women, causing infertility in 50% of affected subjects reported ⁷⁰. Study carried out on female infertility are endocrine disruptors and observe some changes histopathology of ovary that seems to be related to the exposure to: PCB, phtalates, atrazine, genistein, BPA, TCDD, parabens, triclosan, dichlorodiphenyltrichloroethane (DDT) and metoxychloride (MXC) ^{71, 72}. Males, reproductive function may affected by pollutants and EDCs, but evidence is scarce; EDCs, such as phthalates, bisphenol A, biphenyls, and vinclozolin, widespread use of therapeutic drugs, obesity and sedentary life-style may play a crucial role in this supposed decrease of male fertility studied reported ^{73, 74}.

CONCLUSION: On the basis of above mentioned reviews it can be concluded that food adulteration is a major public hazard which affects the quality of life of people.  It is also well known fact that in present scenario human being are depend on fast food products which are being preserved by the manufacturing companies to preserve for longest duration and for the improvement of tastes therefore, manufactures are adding some toxic substances/chemical substances including polycyclic aromatic hydrocarbons, nitrate, nitrate, SCN and phthalates which are causing several side effects is indicating endocrine glands toxicity.  All toxic substances competitively inhibit the function of endocrine glands, like secreted hormonal imbalance due to this several disorders occurs in human body.

Now a day’s food materials packaged and wrapped in paper that is the dangerous practice of wrapping, covering or processing foods with newspaper and printed recycled paper materials remains commonplace worldwide, as seen in the plethora of photographs in advertisements online or in magazines showing newspaper wrapped foods. The health hazard of ink contamination to foods and long-term contact with complex chemicals should always be considered because of the potentially diverse array of biological and toxicological effects.

Present study, reveals that chemicals are a serious health hazard and important cause of morbidity and mortality in developing countries. The study also showed that the increased incidence of contaminated food by paper inks and others chemicals like polycyclic aromatic hydrocarbons effect on endocrine glands and causes several disorders in humans body. We will initiate systematic campaigns for generating awareness among all the stakeholders to discourage the use of newspapers for packing, serving and storing food items.  Therefore this study is useful to generate knowledge in the peoples to avoid the wrapped and covering process of food materials by paper inks and also avoid adulterate food materials for betterment of health.

ACKNOWLEDGEMENTS: The Authors would like to thank the Vice Chancellor for supporting and providing the research facilities.

CONFLICTS OF INTEREST: The Authors declared no conflict of interest.

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    Purvia AS and Srivastava VK: Brief overview studies on endocrine disruptors polycyclic aromatic hydrocarbons with special reference to newspaper ink. Int J Pharm Sci & Res 2024; 15(2): 302-10. doi: 10.13040/IJPSR.0975-8232.15(2).302-10.

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