Packaging materials are defined as any substance or item that comes in contact with food and drug including containers, cans, bottles, cartons, boxes, cases and covering material such as foil, film, metal, paper, wax paper or cloth. ¹ The main objective of packaging is to provide protection from foreign materials while in-transit and help in maintaining the shelf life of food products. Packaging is a field, combining science and technology used for protecting products during distribution, storage, sale and use. It can also be applied to the procedure of evaluating, designing and manufacturing a packed item. Storage and preservation instructions, directions for use, expiry or use by date, and design of packaging materials among others are crucial information which give cognoscibility to the brand and increase the visibility on the shelf. ^{2 , 3}

All the above processes result in migration of additives, adulterants and toxins such as colourants and adhesives from packaging material into the food, as shown by previous research. ^{4 – 6} Leaching can be explained as any process that allows transfer from surface to the core particles. ⁷ With reference to food packaging, the term “leaching” can be defined as the movement of undesirable particles from packaging materials to the packaged particle. The European Council Standard requires that various contaminants like aromatic amines, benzophenones, polyaromatic hydrocarbons, plasticizers and heavy metals be controlled and analyzed in food packages. ⁸ Heavy metals are a huge source of environmental pollution. ⁹ The toxicity of heavy metals has harmful effects on biological systems as they do not undergo biodegradation. They accumulate in living organisms, causing several diseases and disorders even when present in very low concentrations. ¹⁰

The toxic effects of vanadium are particularly seen in lung and stomach tissues, resulting in pneumonia, bronchitis and breach in the gastric mucosal lining. ¹¹ Increased concentration of arsenic in humans can induce epigenetic changes and genetic mutations causing cancer. ¹² Cadmium has been used in industries for a long time. Toxicity due to cadmium can affect kidneys, and the reproductive, skeletal, and respiratory systems, causing proteinuria, kidney stones, loss of bone density and mineralisation, destruction of mucous membranes, pneumonitis, testicular necrosis, and affects steroid hormone synthesis. ¹³ Mercury pollution impacts human health leading to developmental flaws in children and Minamata disease ¹⁴ Metals like vanadium and mercury may be added as additives as a part of manufacturing process or may be an unintentional adulterant released from the moulds used specifically in the plastic industry. ¹⁵

In this study locally procured food and drug packaging materials were used. The study started with digestion of packaging materials followed by preliminary qualitative analysis. All the samples were analysed for four heavy metals using spot test for vanadium, senSafe Boris’s mercury detection strips, swab test for cadmium and aquasol arsenic detector kit. After analysing the presence or absence of heavy metals all the samples were quantified using ICP -OES (Inductively coupled plasma optical emission spectrometry). The use of ICP-OES is advantageous for sample preparation since it eliminates the need for several dilutions because it can identify multiple components from an analysis. When plasma energy is applied externally to a sample, the constituent elements are stimulated and excited atoms return to their low energy positions leading to emission of rays and the spectrometer captures these to calculate the photon wavelength. The position of the photon rays determines the element type and the strength of the rays establishes the component of each element. ¹⁶ The detection for arsenic (As), vanadium (V), mercury (Hg) and cadmium (Cd) was quantified in ppm (parts per million). The detection limits are stated in the standard curves ( Figure 10) viz., V – 0.000011 ppm, As – 0.000156 ppm, Cd – 0.000442 ppm, Hg – <0.001ppm. ¹⁷

Considering the wide applications of the packaging material, stringent regulation is necessary due to elevated concentration of heavy metals in them. The Environmental Defence Fund ¹⁸ states that these heavy metals can be toxic and the route of ingestion can be packaging materials. ¹⁹ Sometimes, odorous compounds from the food packaging may get transferred to the food items and affect the foods’ flavour. This results in considerable nutritional loss and consumer dissatisfaction. Although food and drug packaging are a multi-billion industry, studies on the presence of heavy metal in these packaging materials in India are lacking. The assessment of heavy metals vanadium, cadmium, arsenic and mercury in thirteen types of locally procured food and drug packaging materials was done by qualitative analysis showcasing presence or absence of heavy metals in them and then confirming their presence using quantitative technique of ICP-OES (Inductively coupled plasma optical emission spectrometry).

This study was conducted at the Department of Biochemistry, Kasturba Medical College, Mangalore, Karnataka and Department of Chemical Engineering, National Institute of Technology, Suratkal, Karnataka. The Institutional Ethics Committee (IEC) approval was obtained prior to the conduct of the study.

A total of eleven food packaging samples and two drug packaging materials were bought from the local market. The samples included aluminium cans, leak-proof bags, cardboard, tetrapaks, cellophane, tissues, sachets, aluminium bags and boxes, plastic bags and containers, as well as medicinal blister packets and medicinal closures. The packaging materials were collected, cleaned with distilled water and dried in a hot air oven. The samples were cut into small pieces using scissors and metal cutters, and 10 grams each of the sample were weighed using a calibrated electronic weighing scale.

All tests were run in triplicates to ensure consistency in results. The average of the three readings was taken for computation and analyses.

In the current study, eleven commercially available food packaging materials and two drug packages were analysed for the presence of four heavy metals, namely vanadium, arsenic, mercury and cadmium. Packaging materials constitute the mainstay of the modern food industry. Hence, it is important to study their interference with food/drug present within the packaging material. As research has shown leaching of toxins from packaging materials, monitoring the heavy metal leaching is essential to prevent harmful effects to the human body. ⁶

Vanadium is a heavy metal which is used as an additive in stainless steel as well as a catalyst for manufacturing sulfuric acid. It is also used in glass coating and lacquering in aluminum cans to give strength to the material. Vanadium is used as an amalgam in manufacturing cans with stainless steel to give it tensile strength. Vanadium toxicity is known to cause abdominal discomfort by interfering with mucosal lining leading to nausea, bloating, diarrhoea and vomiting in the initial stages. Prolonged exposure can result in renal and neural damage. ²⁸ Qualitative tests detected the presence of vanadium in only three samples. However, ICP-OES values showed presence of vanadium higher than permissible amounts in 10 samples. The study by Imtiaz et al. ²⁹ stated that vanadium causes oxidative stress in human cells and alteration in human metabolism, reduces enzymatic activities and disturbs membrane integrity in humans. ²⁹ This oxidative stress leads to the formation of pentavalate vanadium which is its most toxic and mobile form.

Arsenic, found in higher concentration in all the study materials (detected by six samples qualitatively), is a heavy metal that can act as a toxin due to its high presence in water which is used for material cleaning and lacquering processes. ³⁰ Arsenic is also known to be present as one of the food packaging colorants used in the packaging industry. ³¹ Arsenic could enter the food packaging material during the cleaning process or as an adulterant of iron source. Arsenic has been used as a common ingredient in many pesticides and herbicides in the past. It is known to cause skin lesions and cancer in humans. ³² The International Agency for Research on Cancer (IARC), a part of the World Health Organisation (WHO) has stated that exposure to arsenic is the leading cause of lung, bladder and skin cancer. ³³ The National Toxicology Programme (NTP) is composed of several different government agencies, including the National Institute of Health (NIH), the Center for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA). In its most recent Report on Carcinogens, the NTP classifies arsenic and inorganic arsenic compounds as known to be human carcinogens. The study by Park et al. stated that arsenic is present in paper in contact with food such as any kind of wrapping, and paper board, and presents a risk to consumer safety as increased ingestion in humans can cause skin lesions and gastric cancers. ³⁴

Mercury dissolves in aluminum at room temperature and is added as an additive in aluminum cans and foils to enhance the shelf-life of the seafood packed inside. ³⁵ Ingestion of mercury is the leading cause of Minamata disease. Mercury was detected qualitatively in eight samples and quantitatively in amounts greater than those permissible in sachet and plastic bag only. The mercury absorbed in the body mainly concentrates in the kidneys and brain. ³⁶ The half-life of mercury in the body is about 70 days. Inorganic mercury is mainly absorbed through the respiratory tract, but is also absorbed through the skin to a small extent (3-4%) or gastrointestinal (GI) tract (2–10%). Methylmercury is easily absorbed into the GI tract (≥95%) and into the respiratory tract (≈80%). About 90% of methylmercury is excreted through the faeces via bile, and less than 10 % through urine. The absorbed mercury is distributed throughout all tissues within 30 hours. Its half-life ranges from 45 to 70 days. ³⁷ Higher concentrations (more than 100 ppm) of mercury have been known to cross the placenta and result in foetal defects. ¹⁴ Toxic effects of mercury have been reported even at lower concentrations in humans. ^{38 – 40} Therefore, it would be worthwhile to study the leaching from the packaging material and reconsider the permissible limit if proven.

Ingestion of cadmium in higher concentration creates oxidative stress in the cells and increases the level of antioxidant uptake to protect against macromolecular cell damage, thus leading to prolonged exposure to cadmium, causing depletion of antioxidant levels in the body. Cadmium is generally a contaminant present as residues of the recycling and manufacturing processes, and hence determining their suitability in packaging materials coming in direct contact with foodstuffs is imperative. During the recycling process and cooling of cans, cadmium enters the food production system due to changes in temperature or as an additive used in the metal and glass industry. Cadmium can cause respiratory illnesses, lung fibrosis and cancer. ⁴¹ Huff et al., found cadmium to be the major causative agent of lung cancer, and possibly prostate cancer. Studies in experimental animals have demonstrated that cadmium concentrations higher than those set by regulations (100 ppm) cause tumours at multiple tissue sites, by various routes of exposure, and in several species and strains. ⁴²

Further, these studies offer important context for our findings and support the urgent need for remedial action to mitigate heavy metal exposure through packaging materials. Studies by Sood et al., and Marcelo Enrique Conti, have reported similar trends in heavy metal presence, emphasizing the need for improved quality control measures and regulatory oversight in the packaging industry. ^{43 , 44} Muhammad et al. conducted research on heavy metals in food-contact papers in 2019. This study looked at the levels of heavy metals in papers that come into touch with food, including paperboard and wrapping paper used in packaging. ⁴⁵ Concerns over consumer exposure to these contaminants were raised by the researchers' discovery that a sizable portion of the samples tested had increased levels of heavy metals, including cadmium and arsenic. A thorough investigation of heavy metal contamination in plastic materials used to package food and pharmaceutical goods was carried out by Khan et al. in 2015. ⁴⁶ Their research showed that heavy metals, such as lead and mercury, were widely present in a variety of plastic packaging types, raising the possibility of health risks related to these substances. The amounts of heavy metals in glass packaging materials that are often used for food and medicine goods were assessed by Turner and Andrew (2016). ⁴⁷ Their study brought attention to the prevalence of heavy metals in glass packaging, specifically lead and cadmium, and emphasized the necessity of regulation and oversight to protect consumers. ⁴⁷ A thorough assessment of research examining the effects of heavy metal pollution on food and medication packaging materials was carried out by Scutarasu and Trinca in 2023. Their findings emphasized that in order to reduce the dangers associated with heavy metal exposure through packing materials, more stringent quality control procedures and regulatory oversight are required. ⁴⁸ Together, these investigations offer insightful information about the frequency of heavy metal contamination in food and medicine packaging materials, emphasizing the necessity of regulatory action to safeguard the health and safety of consumers.

It is alarming to find high concentrations of toxic metals in several of the packaging materials studied. While cadmium seemed to be the least abundant contaminant, arsenic was the most prevalent heavy metal contaminant. Of all the types of packaging materials studied, sachets, which are manufactured using a plastic and aluminium amalgam, had the highest concentration of all the heavy metals.

In summary, a wide variety of food and drug packaging materials from an Indian market were tested for the presence of heavy metal, namely vanadium, arsenic, cadmium and mercury. Our study shows the presence of heavy metals in routinely used food packaging materials, measured quantitatively and qualitatively. All samples, irrespective of the results of qualitative analysis, were subjected to quantitative analysis, as ICP-OES is a sensitive technique for the detection of heavy metals. Of the thirteen samples analysed, arsenic, mercury and cadmium were found in all samples at concentrations above the regulated limits. Vanadium was present in lower concentration in tissue, cellophane and sachets. Leaching of these heavy metals into the packaged food/drug may be potential health hazard that severely compromise the well-being of humans and the environment. This study calls for stringent regulatory guidelines and strict monitoring of packaging materials at all stages, starting from raw material selection, storage and production until it reaches the consumer. The post-packaging handling, transport, storage and conservation of the supply chain requirements further add to prospective leaching, which may be the scope of future studies.