Endocrine disruptors (ED) are exogenous agents that interfere with hormone synthesis, metabolism, and/or action. There is growing evidence of increasing exposure to these substances over the decades. Associated with this, an increase in the incidence and prevalence of diseases associated with ED1 has been observed. Some examples are hormonally mediated cancers, such as breast, prostate, and testicles, insulin resistance, metabolic syndrome, diabetes mellitus, obesity, allergies, autoimmune diseases, infertility and male genital malformations.2

Epidemiological studies that correlate ED with diseases must take into account that they are found ubiquitously in the air, water or soil.3 Therefore, it is possible that food can be contaminated at the different stages that precede its consumption, from obtaining (contamination of soil, rivers, oceans), handling, transportation, processing and production. Recently, contamination by chemical substances present in food packaging has been investigated.4 More than 10,000 chemicals are authorized in the United States to come into contact with food.5 Many of these substances, both intentionally and unintentionally added, have not been adequately tested for their ED effect. One of the factors responsible for the increase in exposure may be related to the increase in consumption of ultra-processed (UP) foods, due to changes in eating habits in recent decades. Fresh or minimally processed foods have been replaced by UP ones, which have been introduced earlier and earlier into children's diets. UP foods correspond to around 65 % of the daily energy consumption of a school-age child in the UK and USA.6 In Brazil, more specifically in the city of Pelotas, state of Rio Grande do Sul, data from the participants in the 1982, 1993 and 2004 cohorts demonstrated that UP food consumption was higher in younger cohorts (25.1 %, 29.8 %, and 33.7 % at ages 30, 22, and 11, respectively).7

Children constitute a particularly vulnerable group to exposure to these compounds due to higher relative consumption compared to adults, an immature clearance system, and longer exposure throughout life.8 This becomes evident when evaluating data from the National Health and Nutrition Examination Survey (NHANES) 2013–2014, which evaluated the 24-h dietary recall of children over six years of age, to correlate UP food intake with ED, including phthalates and bisphenols. For every 10 % increase in UP food consumption, there was an 8 % increase in the intake of chemical substances, with a stronger association in children and adolescents than in adults. Ultra-processed foods such as sandwiches, hamburgers, fries and ice cream were associated with higher concentrations of multiple chemicals.9

Although establishing causality between chronic exposure to chemical substances present in packaging and their adverse effect on human health is a difficult task, it is known that food packaging is an important source of exposure to ED, due to contamination of the packaging itself and the contamination of the environment after its disposal.2 Therefore, this article aims to describe the importance of food packaging and its role as a potential route of ED contamination, describe the ED most frequently found in food packaging, their adverse effects on the endocrine system, and recommend measures to prevent contamination by these agents.

Despite these precautions, food packaging can be an important source of contamination by chemical substances used in its manufacture, which can potentially migrate into food. These substances can be those legally and intentionally added to packaging or those unintentionally added that occur from chemical reactions or degradation.27 Many of them have not been identified or sufficiently studied in relation to their ED effect. The risk of ED contamination is greater due to the fact that they are capable of causing adverse events even in small concentrations, making it difficult to establish an exposure threshold.2 Often, the duration of exposure for an adverse effect to be identified is prolonged, making longitudinal studies that show a causal relationship difficult. Another concern is the additive effect of mixing substances with similar action, meaning that the mixture can be toxic even if the concentration of its individual components is within the recommended limits.12 Aggregate exposure from other sources and previous contamination, before the food is placed inside the packaging, contribute to this difficulty. For instance, food contaminated at its origin with those exposed to pesticides in its agricultural cultivation, or fish contaminated by environmental pollutants.

The contamination of food by chemical substances and ED also varies according to the type of packaging used:

• -

  Plastic packaging: most food packaging is made of plastic. BPA and phthalates are EDs used in the manufacture of plastic packaging such as bottles, plastic containers for storing food and PVC films.28 Contamination occurs when these EDs migrate from packaging materials to food, especially when there is heating, prolonged contact, repeated use of the packaging, or when the food is fatty or acidic.29

• -

  Metal packaging: these packages, usually cans, are made of aluminum or steel, many internally coated with resins containing BPA to prevent corrosion and contamination of the food.8 However, BPA can migrate from the resin into the canned food, especially if the food is fatty or acidic.30

• -

  Paper and cardboard packaging: these packaging may contain phthalates, paint residues, stickers, labels, glues and other chemicals with ED action that can contaminate the packaged food.31 Contamination is more likely to occur when using recycled paper and cardboard that uses chemical substances that are not recommended for food packaging.27

• -

  Glass packaging: as glass is an inert material that does not release chemical substances, it is considered safe packaging for packaging food. However, glass containers may have sealing lids or internal linings made of plastic and metal can cause ED contamination.32

Figure 1 illustrates the food packaging cycle, ED, migration into food, consumption, and potential adverse effects.

Figure 1.

Food packaging cycle, ED, migration into food, consumption and potential adverse effects.

(0.32MB).

Before being packaged, food can be contaminated at different stages, such as transportation (fuel exhaustion from vehicles, cross-contamination in transport used for other purposes), processing (contamination by disinfectants and cleaning products), production (water used, heating producing acrylamides and nitrosamines) and storage (exposure to naphthalenes).32

Because they are present in packaging, chemical substances, including ED, can migrate from packaging into food. This transfer depends on the chemical substance and its solubility, pH of the food (acidic, alkaline), whether the food is liquid or dry, fat content of the food, type of packaging, storage time and temperature or heating.26 Small packages, such as those intended for children, have a higher surface/volume ratio, therefore having a higher migration rate of chemical substances per kg of food22. The main mechanisms for ED migration from packaging to food are:33

• -

  Direct contact: this is the most common form of migration when the ED comes into direct physical contact with the food.

• -

  Diffusion: it occurs when the ED present in the packaging diffuses and enters the food. This mechanism is influenced by the difference in concentration, chemical characteristics of the substance, temperature and duration of contact.

• -

  Leaching: leaching occurs when plastic chemicals are not firmly bonded to their polymer cores, breaking off and escaping into the food environment. Heating food in a microwave oven and prolonged contact between food and packaging increases leaching and the likelihood of contamination.

• -

  Heating: the increase in temperature caused by heating accelerates the processes of migration and transfer of ED present in packaging to the food, by altering the structure of the chemical substance, facilitating contamination by molecules resulting from this metabolism.

• -

  Volatilization: this contamination occurs when a substance converts into vapor or gas and disperses into the surrounding environment. In theory, it is possible that ED in food packaging could volatilize and disperse into the air near other foods, contaminating them.

Therefore, food contaminated by chemical substances present in the packaging is consumed daily, which has a greater impact on the most vulnerable groups such as children and pregnant women. Contamination continues in nature when the packaging is discarded. Although it is difficult or even impossible to prevent exposure to chemical substances present in food packaging, it is important to further study potential contaminants and how to avoid them.

To test the migration of a chemical substance from packaging into food, global migration and specific migration are evaluated. In global migration, the total quantity of substances that migrate is assessed, without identifying which substances they are. In specific migration, the amount of migration of a given substance is specifically evaluated. These tests use food simulators, being carried out in a standardized way, under contact conditions of time and temperature similar to the actual contact conditions between the packaging material and the food. Testing the presence of ED in food cannot inform whether it came from the packaging, as there may have been previous contamination.

It is important that all chemical substances present in packaging are tested for their potential ED effects, including tests from low to high doses, avoiding extrapolating results from a single dose, and considering the additive effect caused by the mixture of substances.29

To detect the presence of ED in foods, several analytical methods are used, both chemical and biological tests. These techniques require obtaining a sample of the food, purifying it, and preparing it before the analysis to remove potential interferents. The main techniques used are:

• -

  Gas chromatography with mass spectrometry (GC–MS): consists of the separation of compounds by gas chromatography, followed by their detection and identification using mass spectrometry. This method has high sensitivity and specificity, allowing the detection of very small amounts of ED present in the food.34

• -

  Liquid chromatography with mass spectrometry (LC-MS): this method is used to evaluate the presence of polar and non-volatile ED in food matrices. It has excellent sensitivity and specificity to detect a wide variety of chemical compounds.35

• -

  High-performance liquid chromatography (HPLC): a widely used method to quantify ED in foods. It can be coupled to ultraviolet, fluorescent and electrochemical detectors to assist in the identification and quantification of the ED under investigation.36

• -

  Enzyme-linked immunosorbent assay (ELISA): it is based on the interaction between an antibody and the analyte being measured. Although it has a lower cost and is quick to test, it has low sensitivity and specificity compared to the two previously mentioned methods.37

• -

  Biosensors: they use biological components, such as enzymes, antibodies or cells to detect and identify the presence of ED in food. They can be targeted to specific EDs, having good sensitivity and specificity.38

• -

  Nuclear magnetic resonance with spectroscopy: a more expensive technique, which can be used to identify and quantify ED present in foods.39

There is increasing evidence that exposure to ED when it occurs during critical periods of embryological development, can cause permanent changes in gene expression programming. This perhaps explains the increasing numbers of endocrinological diseases in childhood, and the long-term effects can be felt long after the exposure.40 It should also be recalled that exposure to ED from food packaging is proportional to the volume of food in relation to the surface of the packaging and the volume ingested in relation to total body weight and that this relationship is greater in children.

Some specific activities also seem to be at greater risk. A case-control study compared the occupation of the parents of 73 boys with hypospadias with 146 control boys, chosen because they were the same age and came for consultation at the same clinic for minor illnesses. Children with hypospadias had twice as many fathers and five times as many mothers working in activities exposed to ED, such as farmers, hairdressers, painters or mechanics, suggesting that exposure to pesticides during preconception and prenatal life is associated with hypospadias and exposure to phthalates and alkylphenolic compounds are potentially risk factors.41

The main measure to reduce contact with ED is through regulation by public health and safety policies. Regulation has the potential to achieve a more far-reaching impact than recommendations that place all the onus on individuals to modify patterns of behavior and consumption.42

Pediatricians can contribute individually by raising awareness in families to identify ways through which children may be exposed to ED and help these parents find less toxic alternatives. The following strategies can be suggested to reduce exposure and contamination by endocrine disruptors (Table 1).43,44

It is evident from this narrative review that food packaging is a source of numerous chemical substances, several of which have documented ED effects on human health, especially when contact occurs during periods of greater vulnerability, such as during pregnancy or childhood or when it is systematic and in large proportions, as demonstrated in some groups of exposed workers.

A series of studies correlate exposure to ED and changes in childhood related to growth, development, puberty, weight and metabolism. Because they are correlation studies, they suggest, but cannot affirm, that these substances are triggering factors for these pathologies. However, when observing the increase in the prevalence of these endocrine diseases, the question arises as to which environmental factor may be contributing to this increase and what must be done to change this situation.

Everyone wants to enjoy the comfort and practicality of modern life, for instance, using packaged food, and everyone wants a “greener” and sustainable future. However, to reduce exposure to ED it is necessary to change one's lifestyle, habits and consumption patterns. These attitudes, in addition to reducing individual exposure, can also pressure commerce, industry and governments to improve public and private policies that will lead to the production of safer packaging.