History of Food and Nutrition Toxicology

By A. Wallace Hayes

History of Food and Nutrition Toxicology, part of the History of Toxicology and Environmental Health series, provides an overview of history in the field to help readers better understand future applications for evaluating newer and valuable approaches and their impacts on human health. The book explores issues associated with chemical contaminants, toxicants, the use of dietary supplements and pharmaceuticals, and increasing concerns surrounding food toxicity and safety. The addition of historical case studies and end-of chapter questions make the book ideal for toxicologists, food scientists, pharmaceutical scientists, and other researchers who want to understand current state and future challenges in the field.

• Offers thought-provoking, forward thinking end-of-chapter questions
• Provides illustrations of historical products, individuals and processes
• Discusses case studies that help provide historical perspectives

• Language: English
• Publisher: Academic Press
• Release date: Aug 23, 2023
• ISBN: 9780128212622

Book preview

Chapter 1: The interrelationships between food, nutrition, and toxicology

Esther Haugabrooks    Scientific and Regulatory Affairs, Risk Assessment and Toxicology, The Coca-Cola Company, Atlanta, GA, United States

Abstract

Toxicology is one of the oldest disciplines that was arguably first informed by poisonous plants mistaken for food, which paved our understanding of the intricate interrelationships between food, nutrition, and toxicology. Nutritional toxicology elucidates how various nutrients in the diet modulate health, while food toxicology encompasses the general principles of toxicology as it relates to substances in food or in contact with food through packaging, processing, or manufacturing. This chapter delves into the origins of food and nutritional toxicology, overviews the distinction between the fields, and investigates their impact on human health. Understanding the interconnections between these disciplines allows researchers, healthcare professionals, and policymakers to gain valuable insights into the mechanisms used to inform decisions that promote human health within a balanced diet. It will also empower the public with an understanding of how to apply hazard versus risk to establish confidence in selecting safe and nutritious foods.

Keywords

History of toxicology; Food toxicology; Nutritional toxicology; Toxins; Toxicants; Hazard; Food safety; Food additives; Contaminants; Allergens; Dose-response; Regulatory science

In the beginning was food toxicology.

A simplistic definition of food toxicology is the study of adverse reactions from the consumption of food. From a creationist point of view, the principles of food toxicology are present as early as when Adam and Eve ate the fruit and were promised an adverse reaction—death (Genesis 1). From an evolutionary or survival of the fittest perspective, plants developed physical and chemical defenses that have been documented throughout the millennium to cause varied physiological effects. Subsequently, from our understanding of plants and their graded effects, we have passed down the knowledge on how to classify potential sources of foods and defined what amounts are inedible, poisonous, or nutritious.

Our observations of how food and nutrients can harm or improve health have established the overarching field of toxicology. In the same manner it was from the start of early civilization that the concepts of food toxicology were connected to our understanding of survival, nutrition, medicine, and evolution.

It is generally accepted that materials defined as food are not perceived to be toxic or may not be thought to contain toxic substances. However, foods are complex matrices comprised of thousands of chemical constituents, some of which can be problematic under varied circumstances or could prompt the development of a variety of toxicities at elevated concentrations. Thankfully, the majority of the substances found in food are not toxic when consumed in appropriate amounts and are vital to maintaining health or proper growth, otherwise called nutrients.

It may be easy to use food toxicology and nutritional toxicology as synonyms since both disciplines deal with food. However, nutritional toxicology is the study of how nutrients impact health, while food toxicology deals with the general principles of toxicology as it relates to substances in food or in contact with food through packaging, processing, or manufacturing.

In this chapter, we will investigate the origins of food and nutritional toxicology and overview the distinction between the fields. We will show how advancements in the field of toxicology from antiquity to the 21st century are closely related to our understanding and relationship with food.

The historical significance of the dose makes the poison applied to foods

It may be primarily through trial and error, not significant formal scientific evaluations that conventional wisdom developed regarding what is acceptable to eat and should be deemed food versus what could cause harm. Early civilizations identified poisonous plants and animals and utilized their extracts for warfare or hunting. As time progressed, there are documented accounts where substances like certain metals (e.g., lead, copper), arsenic, phosphorus, opium, and hemlock were used as poisons. Although some accounts are disputed, there are several famous and notable people whose deaths are attributed to poisoning: Socrates in 399 BC may have been forced to drink Hemlock (Dayan, 2009), Cleopatra is believed to have died by suicide via a poisonous snake bite in 30 BC, and Claudius (Tiberius Claudius Caesar Augustus Germanicus) died in 54 AD by either a poisonous or poisoned mushroom or by a poisoned feather used to induce vomiting (Marmion and Wiedemann, 2002).

Through documentation of poisonous substances and anecdotal stories regarding plants and their ability to provide basic sustenance, it became evident that some plants could kill while others could impart medicinal benefits. This may be one of the primary reasons the medical field and nutrition are closely linked. Throughout the centuries, as plants informed medicinal therapies and recreational pass times, the distinction between food toxicology and pharmacology became more defined. Notwithstanding, much of what we know in the field of food and nutritional toxicology is attributed to the early pioneers of toxicology.

Shennong, born Jiang Shinian (c.2695 BC), the Yan Emperor and regarded as the father of Chinese medicine, has been attributed to discovering tea potentially on a quest to discover medicinal plants for his collection of herbal remedies. It is believed he tasted over 365 herbs in his lifetime and died from an accidental overdose while trying to uncover the beneficial properties of ingested herbs or other plants. As a result, the Chinese Materia Medica (202 BC–220 AC) is believed to have originated from Shennong’s teachings and research. There are very few written accounts of his life, thus it’s not always clear what aspects of his legacy became a historical account or legend.

Hippocrates (c.460–375 BC), a Greek physician, created many connections to nutrition, medicine, and pharmacology through his written work of more than 60 texts known as the Hippocratic Corpus (Corpus Hippocraticum). It may be through this work that he has been falsely attributed to saying, let thy food be thy medicine and thy medicine be thy food, despite no account of the specific saying in any of his written works (Cardenas, 2013).

Pedanius Dioscorides (c.40–90 AD), a Greek physician, pharmacologist, and botanist, is known for similar work characterizing plants according to toxic or therapeutic effects. Employed as an army surgeon by the Roman emperor Nero, Dioscorides expanded the existing knowledge of medicinal herbs and minerals through his travels, which lead to De Materia Medica (On Medical Matters), a compilation of botany and pharmacology learnings from local medicinal herbs he encountered throughout his travels. The information from De Materia Medica compiled in the 1st century AD became the most extensive and reliable herbal encyclopedias available for centuries and the inspiration for many pharmacopeias.

Mangarasa (c.1350 AD), a South Indian scholar, is attributed with writing the world’s first complete work dedicated to understanding Ayurveda and toxicology through pan-Indian heritage, the Khagendra Mani Darpana (Bhat and Udupa, 2013).

Theophrastus Bombastus Von Hohenheim, or Paracelsus (1493–1541), is often regarded as one of the fathers of toxicology. Known for his work as a medical scientist, physician, alchemist, and at the time, a radical philosopher in Western Europe, Paracelsus gave the field of toxicology the most quoted phrase or paraphrase, the dose makes the poison, which can be derived from his German writings that roughly translate to

What is not poison? All things are poison, and nothing is without poison. Only the dose determines if something is not a poison.

This same attribution has been translated in a different way to read

Poison is in everything, and nothing is without poison. The dosage makes it either a poison or a remedy.

Irrespective of the preferred translation, this ideology is a valuable foundational cornerstone in food and nutritional toxicology, particularly regarding components that constitute a nutritious diet where nutritious constituents have an ideal dose that is deemed beneficial. However, when extremely high concentrations are introduced, it could produce toxic effects detrimental to the maintenance of good health.

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Paracelsus (Source: Wellcome Library London. Retrieved from Michaleas et al., 2021.)

Mathieu Joseph Bonaventure Orfila (1787–1853), a Spaniard, is generally regarded as the father of modern toxicology. He identified toxicology as a separate science, and in 1814 published the first textbook devoted exclusively to systematically correlating biological and chemical characteristics of poisons entitled Traité des Poisons Tirés des Règnes Minéral, Végétal et Animal ou Toxicologie Générale (A treatise on poisons found in the mineral, vegetable and animal kingdoms, or, a general system of toxicology). Orfila is attributed to being one of the first scientists in the field of toxicology to introduce animal experimentation, which was already in use for medical research. Even then, experimental methodologies that used animals as models for humans were questioned for relevance and a common critique for Orfila’s application of animal models in research. Orfila primarily used canines as a model to study absorption and elimination of poisons from internal organs and the activity of antidotes (Michaleas et al., 2022).

It was during the Renaissance (14th century–17th century) and the Age of Enlightenment (17th and 18th centuries), through the contributions of scientists like Orfila, that the fundamental principles of toxicology began to develop. Much information was derived from therapeutic studies, or conversely, the use of poisons. Although poisonings are not considered scientific contributions, many women of that time made it into a career. Some popular examples are:

Giulia Tofana (died 1651) sold an arsenic concoction, Aqua Tofana, primarily to women who came to Tofana expressing interest in killing their husbands or other people death would result in personal gain.

Catherine Monvoisin (c.1640–1680), infamously known as "La Voisin, sold love potions and fatal poisons, also known as inheritance powders." She became the center of the Affair of the Poisons, which was a French scandal spanning c.1677 and 1682, where some prominent and common people were accused and charged with poisoning and witchcraft.

Maria Catherina van der Linden-Swanenburg (1839–1915), Good Mie, is believed to have poisoned over 90 people with arsenic. She was only convicted of causing the death of three people, with the intent to collect on their insurance policy or inheritance.

Good Mie and others primarily used food or beverages as their vehicle to administer the poison. This kind of food adulteration, though intentional and intended to be fatal, was not the only kind of adulteration of its time. In the 1300s, mass food production began to emerge along with common practices of food adulteration. Chemical doctoring of foods may have initially emerged to improve the appearance, stability, and profitability of foods, but without consideration of the effects on human health, food safety quickly became a major public health concern. At the beginning of the 14th century, there was very little regulatory oversight for food production, and over time some unscrupulous practices threatening public health and sometimes claiming lives surfaced.

Lead, arsenic, copper, and chrome were popular colorings. Lead was used to color candies, and red lead to color cheese. Aniline dyes, which were aniline derivatives, derived from coal tar benzene, were also used in candies, butter, and alcohol. Leaves from cherry laurels, a poisonous plant, were used in custards to impart a nutty flavor. In the 1700s adding alum (a group of hydrated double salts that usually consist of aluminum sulfate, water, and another elemental sulfate) was a popular practice among bread bakers to improve appearance and texture.

In addition to adulterating food with unsavory substances, foods were also misbranded with very little oversight. Cherry leaves were used in tea as a filler which acted as an undesired and strong laxative. Dairy cream was thickened with flour. Butter was often composed of gypsum, gelatin fat, and mashed potatoes. Beef hearts and other organ meats were canned and labeled as chicken. Oleomargarine or bogus butter could be made from hog fat, beef tallow, bleach, and other unlikely substances. Milk was watered down and sometimes sold with added chalk to improve the color of milk produced from diseased cows.

Cooking, salting, canning, fermentation, and chemical modifications such as the addition of preservatives are all techniques that were employed to control food safety and decrease the risk of foodborne illness. However, it wasn’t enough to protect public health with no strict laws to be enforced. As food adulteration continued to threaten public health and safety, some unethical practices were used to mask spoilage or unwanted contamination. Sodium sulfates were used as meat preservatives and to induce a fresh red color despite the fact that they have been known to cause kidney damage. Yellow dye was used in butter often to mask the potential presence of foreign matter (e.g., insects, mold).

By the turn of the 19th century, there was a rapid increase in the industrial preparation and packaging of foods. Although there were some international examples of regulatory oversight for food safety, there were still many dangerous practices leading to fatalities without proper liability to merchants. In 1820, Frederick Accum (1769–1838), a German-born chemist working in London, shed a detailed spotlight on harmful food additives through his monograph entitled A Treatise on Adulterations of Food and Culinary Poisons. Accum is lauded for using dramatic imagery to bring attention to a grave situation that, at the time, remained largely unchecked. The first edition sold out relatively quickly after 1000 copies; the cover of the first edition and subsequent editions depicted imagery similar to a skull and bones with a caption that read:

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There is death in the Pot. Kings 4:40 (1st Photo Courtesy of Science History Institute, https://digital.sciencehistory.org/works/zp38wd737; 2nd Photo title page of fourth addition from https://www.pbagalleries.com/view-auctions/catalog/id/100/lot/27089/A-Treatise-on-Adulterations-of-Food-and-Culinary-Poisons-Exhibiting-the-Fraudulent-Sophistications-of-Bread-Beer-Wine-Spiritous-Liquors-Tea-Coffee-Cream-Confectionary-Vinegar-Mustard-Pepper-Cheese-Olive-Oil-Pickles-and-Other-Articles-Employed-in-Domestic-Economy-and-Methods-of-Detecting-Them; Email: [e-mail].)

The candor, passion, and eccentric methods in which Accum obtained information, coupled with the serious allegations presented in his work, made him an unliked man who, by his own account, received many threats. Despite the loyal support of some, Accum’s reputation declined, and he ran into legal troubles. Shortly after the wild success of his books, Accum left Britain to return to Germany. He was one of the first effective advocates for legislative change. However, the British government did not implement meaningful legislation to protect the food supply until 1875, more than half a century after his book and over 30 years after Accum’s death.

Ellen Henrietta Richards (1842–1911), a chemist and a professor at Massachusetts Institute of Technology (MIT), became interested in food chemistry during her tenure at MIT and significantly contributed to exposing the pervasive culture of food adulteration with her book Food Materials and Their Adulterations, published in 1885 which led to the passage of the first Pure Food and Drug Act in Massachusetts (Luma, 2021). Her contributions to food science and chemistry are largely underrated as her target demographic was women and a more general audience to teach them how to identify adulterated foods. At the core Richards was advocating to empower the public to identify food hazards to the best of their ability in an effort to mitigate risk.

Paracelsus and Orfila are broadly considered the fathers of toxicology; however, indirectly, Accum was one of the many initial pioneers in food toxicology. Similarly, Harvey Washington Wiley (1844–1930) is considered the father of Pure Food. Wiley’s most notable work was mainly during his tenure as the chief chemist in the Chemistry Division of the U.S. Department of Agriculture (USDA), which would later become the Bureau of Chemistry in 1901, and the Food and Drug Administration (FDA) in 1906. Wiley devised and led a notorious government experiment on human volunteers dubbed the Poison Squad, a group of young men who in exchange for free meals agreed to eat controlled amounts of chemical preservatives like borax, formaldehyde, and benzoates in prepared meals in effort to assess their health effects after consumption.

If ever you should visit the Smithsonian Institute,Look out that Professor Wiley doesn’t make you a recruit. He’s got a lot of fellows there that tell him how they feel, They take a batch of poison every time they eat a meal. For breakfast they get cyanide of liver, coffin shaped, For dinner, undertaker’s pie, all trimmed with crepe; For supper, arsenic fritters, fried in appetizing shade, And late at night they get a prussic acid lemonade.

O, they may get over it but they’ll never look the same,

That kind of bill of fare would drive most men insane.

Next week he’ll give them mothballs,

a la Newburgh or else plain;

O, they may get over it but they’ll never look the same.

The Song of the Poison Squad Lew Dockstader’s Minstrels, October 1903

It is through his life’s work and advocacy that the Pure Food and Drugs Act of 1906 was passed in the US, also establishing what we know as the US FDA. The Pure Food and Drugs Act is considered the first comprehensive US law addressing food safety, prohibiting adulteration, and misbranding of food and drugs in interstate commerce. The Pure Food and Drugs Act demonstrated substantial progress but was not perfect and later amended by the Federal Food, Drug, and Cosmetic Act of 1938. The same year the Pure Food and Drug Act was passed, the Federal Meat Inspection Act of 1906 was also passed, specifically prohibiting the sale of alternated or misbranded meat and meat products intended for food. The act also ensured that meat was slaughtered and processed under sanitary conditions.

The passage of the Federal Meat Inspection Act is attributed in part to Wiley but also to the advocacy of Upton Sinclair (1878–1968), a writer and non-scientist who in 1906 published his graphic political fiction, The Jungle. The novel depicts the unsanitary practices and conditions of the meat industry. Although a fictitious novel, The Jungle was an unfortunate example of art imitating life as America was already acquainted with the embalmed beef scandal where US troops were fed low-quality, heavily adulterated beef during the Spanish-American War of 1898.

There was never the least attention paid to what was cut up for sausage; there would come all the way back from Europe old sausage that had been rejected, and that was moldy and white—it would be dosed with borax and glycerine, and dumped into the hoppers, and made over again for home consumption. There would be meat that had tumbled out on the floor, in the dirt and sawdust, where the workers had tramped and spit uncounted billions of consumption germs. There would be meat stored in great piles in rooms; and the water from leaky roofs would drip over it, and thousands of rats would race about on it. It was too dark in these storage places to see well, but a man could run his hand over these piles of meat and sweep off handfuls of the dried dung of rats.

Excerpt from Chapter 14 of  The Jungle by Upton Sinclair

As the field of toxicology moved out of predominate observational stages, scientists like René Truhaut (1909–1994), a French toxicologist, became more refined in evaluating toxic reactions and mechanisms. Truhaut devoted most of his research to understating carcinogenic substances in environmental products and foodstuffs. He supported novel toxicological methodologies and through his innovative spirit was the originator of the concept Acceptable Daily Intake (ADI). Truhaut was also part of a small founding group of individuals who created the vision for the establishment of the Joint FAO/WHO Expert Committee on Food Additives (Anon., 1994).

Toxicology: Food and nutrition

Toxicology, by and of itself, is a rather large branch of science that primarily studies the deleterious effects of substances on living systems. Under the umbrella of toxicology are many subdisciplines such as forensics, environmental science, and food science that quantify and qualify chemical interactions, mechanisms of action, and graded effects. In general, toxicology follows an effect or mechanism after exposure to a hazard. Common hazards are chemical substances such as drugs, poisons, toxicants, toxins, pesticides, and colorants. Other types of hazards that are not considered chemical hazards, like physical and biological hazards, are also covered in the overarching field of toxicology. However, physical hazards are generally not a predominant concern in food or nutritional toxicology, outside of specific choking hazards and/or foreign materials that may be unintentionally introduced into foods. Biological hazards such as pathogenic bacteria and viruses are a main concern in food toxicology as they often produce chemical substances that are toxic to humans.

Chemical substances can come from natural or anthropogenic sources and produce varied effects primarily thorough associated physicochemical properties. Thus chemical substances can be grouped based on intended use (e.g., industrial chemicals), risk of adverse effects (e.g., mutagen), or chemical origin (e.g., toxins). In most branches of toxicology, chemical substances known to cause harm or adverse effects are generally called toxicants. Toxins, however, are a specific class of toxicants that are classified as an organic substance, particularly a small molecule, peptide, or conjugated protein that originates from metabolic activities of living cells or organisms (e.g., plants, animals, or microorganisms), see Table 1. Mycotoxins, like aflatoxin, are secondary metabolites of fungi and are classified as toxins based on their origin of a living organism the same as grayanotoxins (mad honey), solanine, or urushiol (poison ivy, poison oak, and poison sumac, raw cashews), which are of plant origin.

Table 1