Expert Report Writing in Toxicology

Forensic, Scientific and Legal Aspects

Michael D. Coleman

• Publisher: Wiley-Blackwell
• Year: 2014
• ISBN:
  9781118432334
• Edition: 1
• Topic: Medicine
• Subtopic: Forensic Medicine

Every year throughout the world, individuals' health is damaged by their exposure to toxic chemicals at work. In most cases these problems will resolve, but many will sustain permanent damage. Whilst any justified claim for compensation requires medical and legal evidence a crucial and often controversial component of this process is the establishment of a causal link between the individual's condition and exposure to a specific chemical or substance. Causation, in terms of how a substance or substances led the claimant to his or her current plight, can be difficult to establish and the main purpose of this book, is to provide the aspiring expert report writer with a concise, practical guide that uses case histories to illuminate the process of establishing causation in occupational toxicity proceedings.

In summary:

• A practical, accessible guide to the preparation of balanced, scientifically sound expert reports in the context of occupational toxicology.
• Focuses on the scientist's role in establishing a causal link between exposure to toxins and an individual's ill health.
• Includes real-life case histories drawn from the Author's 15 years experience in this area to illustrate the principles involved.

Expert Report Writing in Toxicology: Forensic, Scientific and Legal Aspects proves invaluable to scientists across a range of disciplines needing guidance as to what is expected of them in terms of the best use of their expertise and how to present their findings in a manner that is authoritative, balanced and informative.

1
A brief history of occupational toxicology

1.1 Occupational toxin exposure in antiquity

There are several activities essential to a civilised society, such as reliable food production as well as some provision for manufacturing and processing goods and foodstuffs. Whilst farming came comparatively late in human evolution, perhaps 8000–10,000 years bc, manufacturing of some recognisable sort appeared even later, when humans started to mine and process various metals. Of course, recovering metal ores from underground exposes the individual to many physical dangers, such as rock falls, floods and toxic gases. However, the significant energy input required for the extraction and processing of pure metals presented new hazards, such as the hot gases and dangers of the molten product. Many ancient cultures soon developed what we might recognise as a production process, where metals were mined, smelted and processed, including copper and tin, which were eventually combined to make bronze, which was more durable than either metal alone.

Whilst the process of smelting is inherently dangerous, neither copper nor tin is especially directly toxic to man. Indeed, the metal that replaced both of them in tool and weapon manufacture, iron, was also not particularly toxic to process in itself. These metals do not tend to accumulate in the body and cause acute or chronic toxicity during normal processing techniques. Lead, however, is very toxic, and the mining and smelting of this malleable and useful metal were probably the first activities where there were significant acute and chronic toxic hazards encountered during its handling. Lead is usually found as its sulphide (galena), which contains silver, so lead production at first was a by-product of silver recovery. Lead usage was fairly widespread before the ascendancy of the Romans, with many ancient peoples such as the Egyptians, using it for a variety of tasks; these included fishing weights, water piping and the basis of a form of early mascara.

Hippocrates (460–379 bc) [1] was the iconic founder of modern medicine, and it has been thought that he was the first to describe occupational lead poisoning; however, this is not actually true [2] as his description was not as precise as some authors would have it. The first detailed surviving description of lead intoxication appeared (in verse, apparently) around the second century bc, in the physician and poet Nicander of Colophon’s Alexipharmaca. As the reach of the Roman Empire extended, by the beginning of the first century ad, lead usage increased dramatically. Indeed, the impact on health of any toxic process is directly related to its scale, and the Romans used vast amounts of lead in their grandiose, but impressively durable building projects. For instance, thousands of tonnes of lead were involved in the construction of a siphon unit in the great aqueduct at Lyon [3]. To supply lead on such a scale meant processing which we would even now recognise as ‘industrial’. Consequently, it is not surprising that several Roman figures described the appalling environmental impact of lead processing, as well as the toxicity of the actual processes used for purifying the metal. Towards the end of the first century bc, the architect known today as Vitruvius (Marcus Vitruvius Pollio; ~75 bc to ~ ad 15) described the severe impact on local water supplies of metal processing, and he stated his opposition to the use of lead piping because of its toxicity to the lead workers, as he noticed how pale they looked. The philosopher and scientist Pliny the Elder (Gaius Plinius Secundus; ad 23–79), writing around 70 years later, commented that lead produced ‘noxious and deadly fumes’ when it was heated and processed. Pliny also designed masks that could be worn by workers to protect them from fumes. Interestingly, as with many toxins, although the dangers of lead were well documented, it continued to be used on a large scale for centuries after the deaths of its early critics. As we know, lead was used in piping and paints until well into the twentieth century and remains in many houses today, carrying drinking water all over the United Kingdom. Whilst it remains useful as a roofing material, perhaps most remarkably, lead was employed in its tetraethyl form for more than 80 years as an anti-detonation agent in fuels, such as petrol (gasoline); unfortunately, vast amounts were released into the atmosphere via this route. Since its removal from fuels in most countries before the year 2000, this source of lead pollution has declined dramatically in developed economies. Currently, lead is much less of a toxic threat than before, although human exposure in foodstuffs will probably never entirely be eradicated.

1.2 The Middle Ages and the Renaissance: The beginnings of modern occupational toxicology

Although always a crucial part of metal industries, mining in general broadened in scope up to the Middle Ages and beyond, as many more materials were actively recovered from deeper and deeper pits. The mining of coal for energy began in earnest after the thirteenth century, and by the end of the fifteenth century, metal mining to support the armaments industry was growing rapidly, as cumbersome cannon evolved towards more intricate hand-firearms. All this increased demand for iron, lead and copper, along with other metals. In 1473, the German physician Ulrich Ellenbog (1435–1499) wrote the landmark paper Von den gifftigen Besen Tempffen un Reuchen (On the Poisonous Wicked Fumes and Smokes), where he described the various toxic processes found in the gold mining industry, which involved fuming acids, as well as lead and mercury vapours. A more systematic exploration of mining and its hazards was then made by another German physician Georgius Agricola (Georg Bauer; 1494–1555), who developed a lifelong fascination with these subjects. He even bought a share of a silver mine and published several books on mining and various minerals, including De Re Metallica [4], which took him more than 20 years to write and was only published after his death. Although the book’s main focus is its extraordinary detail of the methods of mining and metal processing of the time, he did investigate and document many of the occupational hazards of mining, including the various types of pneumoconiosis, such as silicosis, as well as other mining health dangers. Agricola is regarded now as a particularly able and methodical scientist, whose enthusiasm (Section 1.11) and understanding of the value of the observation of phenomena in making appropriate deductions were far ahead of his time.

A contemporary of Agricola was the much better known Paracelsus, and variations of his ubiquitous quote “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy” have adorned many a text and student submission over the centuries. Philippus Theophrastus Aureolus Bombastus von Hohenheim was born in Zurich in 1493. His physician father, Wilhelm Bombast von Hohenheim, became an expert in occupational medicine in much the same way as Agricola, through researching his mining patients’ experience. Strongly influenced by his father, young Philippus nevertheless began his studies with the controversial subject of alchemy. Today, the idea of making gold and silver from base metals in an ordinary laboratory sounds as quaint as it is impossible, without the aid of a Nuclear Research Facility. However, as late as the seventeenth century, it was taken deadly seriously, and most of the front rank of scientists at that time, such as Isaac Newton and Robert Boyle, considered themselves alchemists, although in secret.

Philippus Von Hohenheim travelled widely and studied surgery and, through his alchemy activities, chemistry. He began to pioneer the role of chemistry in medicine, rejecting various contemporary ‘cures’, in favour of a more systematic approach to the use of remedies such as opium, as well as metals such as lead and antimony. He advocated the use of small doses of mercury for syphilis, which was essentially the right idea with the wrong agent, as mercury was eventually proven ineffective for syphilis in the 1940s.

Philippus’s ideas were revolutionary for his time, and he is credited with not only ‘inventing’ pharmacology, through his concept of dose and how its related to response, but also toxicology and even the idea of the ‘target organ’ for toxicity [5]. Sadly, he managed to combine aggression, certainty, excessive fondness for alcohol, flamboyance and arrogance in his personality and even styled himself Paracelsus, or greater than Aulus Cornelius Celsus (~25 bc–ad 50; the Roman author of the medical treatise De Medicina). This, combined with contempt for accepted wisdom and a theatrical and sometimes incendiary lecturing style, he ensured that he surpassed all his peers in his ability to make seriously powerful enemies. His drinking led to fatal liver cirrhosis at only 48 years of age, having spent his life challenging and usually failing to defeat medical orthodoxy. However, although he remains controversial to this day, I think it can be said that he made a significant contribution to occupational medicine, not least through his ideas on the specific mechanisms whereby toxins impact the body, as well as a book on miners’ diseases. Perhaps it is characteristic of his personality and ambition that he entitled his last major work, Die Grosse Wundartznei (The Great Surgery Book) of 1536, which restored his fortunes and public image.

As mining became more industrialised, many more debilitating conditions emerged, not least vibration ‘white finger’ and noise-related deafness, which were linked with cutting and boring machinery, as well as toxicity associated with the fumes of explosives and more recently, underground vehicles. In recent times, whilst mining has all but disappeared in the United Kingdom, it remains a major industry in more than 50 countries worldwide, although fatality rates and occupational disease remain several fold higher than other industries [6, 7]. In the United Kingdom, the legacy of ‘black lung’, which is the form of pneumoconiosis caused by coal dust, continues to blight and shorten the lives of retired miners. As there remains several hundred years of supply of coal under the United Kingdom, it is likely that this energy will be exploited in the future, not by manual labour, but with the application of new technology applied to underground coal gasification (UCG), which can be carried out from the surface using bore holes. Interestingly, the concept of UCG is far from new; one of its early proponents was Lenin (Vladimir Illych Ulyanov; 1870–1924), who sought in 1913 to make presumably irony-free political capital out of the possible benefits of UCG, in claiming that it would free the proletariat from the dangers of working underground in Tsarist mines [8].

The individual who is regarded now as the father of occupational medicine was the Italian physician and Professor of Medicine at the Universities of Modena and subsequently Padua, Bernadino Ramazzini (1633–1714) [9]. He was the first physician to devote his career to a systematic investigation of over 50 occupations, involving visiting places of work and questioning workers. He exhorted his fellow physicians to routinely enquire after occupation, as well as symptoms. His career culminated in De Morbis Artificum Diatriba (Discourse on the Diseases of Workers; first edition, 1700, second edition, 1713). This work described many different occupations, their consequences and ideas for alleviation of the damage and the processes that caused it. Importantly, he not only understood that the various noxious materials, gases and vapours to which workers were exposed were actually responsible for their health problems, but also that unusual specific movements and postures required by the occupation contributed to morbidity and mortality. In this latter area, he was the first to recognise repetitive strain injuries, which remain a workplace hazard today. His work anticipated the Industrial Revolution, where manufacturing grew in scale beyond anything that preceded it, involving large numbers of individuals, vast amounts of processing and long periods of exposure to noxious agents, particularly those related to polycyclic aromatic hydrocarbons (PAHs) from coal and petrochemicals.

1.3 The Industrial Revolution

Whilst it is generally accepted that the Industrial Revolution began in Britain, industrialisation and mining expansion occurred in many other countries, and several scientists around Europe made notable contributions to the emerging science of occupational health in the eighteenth century. Gradually, very early concepts, such as Pliny’s ideas on protective measures in the workplace, became re-discovered and reinforced, whilst the understanding of specific links between certain toxins and particular conditions and their mechanisms of toxicity, pioneered by Paracelsus, also gathered pace. The brilliant Russian polymath Mikhail Vasilyevich Lomonosov (1711–1765) outlined measures to be taken to ensure occupational safety in mining in a 1763 treatise, although he could be of a similar disposition to Paracelsus and was imprisoned for eight months for abusing his University’s administrators (sounds harsh) and was even briefly forcibly retired by the personal order of Catherine The Great. In England, a major step forward in the understanding of how pollutants from a specific occupation can cause permanent and even lethal injury was made by Sir Percivall Pott (1714–1788). Dr Pott was an extremely well-liked, industrious and technically proficient surgeon, who among many other achievements gave his name to a particular type of compound fracture. The image of eighteenth-century medicine is somewhat tarnished by its obsessions with bleeding, purging and, of course, amputation, for a surprisingly wide range of conditions. However, Dr Pott did his very best with what he had, made highly significant additions to medical knowledge and worked tirelessly right up to his death, which was actually hastened by his devotion to his patients.

Today, in the developed world, many developing countries are criticised for allowing dangerous child labour practices; however, from the end of the seventeenth century in England, after being sold to master chimney sweeps by their parents, boys as young as seven years old were sent up naked into extremely cramped chimneys to clean them. They were sometimes ‘encouraged’ by the sweep lighting a straw fire beneath them [10]. It was not uncommon for these children to die of asphyxiation, and survivors were treated appallingly, with no access to washing facilities. Hence, they would develop scrotal soot warts, which they would sometimes remove by themselves with a knife. These warts would sometimes become cancerous, usually many years later. The idea of employing children in this way was actually considered repugnant even by the end of the eighteenth century, but was not outlawed until 1842 due to the resistance of the master chimney sweeps. Whilst Dr Pott was not the first person to describe the tumours, he made the link between the soot exposure and the tumours, so becoming first to recognise that a malignant disease was caused by a specific occupation [11]. One interesting and important perception he also made was that because the signs of the disease appeared after puberty, it was commonly ascribed by doctors to venereal disease and thus treated with mercury, which of course made things worse. Such understandable misdiagnosis continues today in areas such as idiosyncratic drug reaction, as well as in occupational health, and it still costs the patient time, allowing the disease to progress whilst increasing suffering. As the nineteenth century progressed, it became apparent that scrotal cancers usually presented decades after exposure had finished and although such long lag-times in cancer presentation are still studied even today we do not understand all the processes involved. Interestingly, it was realised as early as the 1890s that chimney sweeps’ scrotal cancer was very much an ‘English Disease’ because in every other country in Europe (even in Scotland), sweeps wore effective protective clothing. Tragically, it took more than a century from the discovery of this cancer towards some means of alleviating it, and right up to the end of the nineteenth century, English sweeps were at an eightfold greater risk of scrotal cancer than other males....