راهنمای عملی سم شناسی: ارزیابی ، پیش بینی و ریسک ها
A Guide to Practical Toxicology: Evaluation, Prediction, and Risk
این متن کاربردی، کاربر پسند و متناقضی، اصول اولیه سم شناسی را بررسی می کند. این راهنمای ارزشمند برای ارزیابی سمیت و داده های مربوطه، نزدیک شدن به آزمایش و تفسیر سمیت و درک مفاهیم پیش بینی خطر و ارزیابی و مدیریت ریسک است.
بررسی چگونگی ارزیابی گروه های مختلف مواد شیمیایی-دارویی، لوازم آرایشی و شیمیایی کشاورزی را بررسی می کند
بینش درباره تعیین سمیت، عادی بودن و طبیعی بودن، پیش بینی و مقررات را فراهم می کند
دو فصل جدید جدید شامل:
ارزیابی کلاس های شیمیایی مختلف
سم شناسی یک وسیله برای یک هدف مهم است: ایمنی. سم شناسان مؤثر با این موضوع در ذهن شروع می شوند و از درک روشن ی از ایمنی به عنوان یک مفهوم نسبی استفاده می کنند، همراه با دیدگاه عقلانی از پارادایم ارزیابی ایمنی فعلی جهت هدایت کار آنها. اغلب این رویکرد توسط روش سنتی نادیده گرفته می شود یا از بین می رود.
این کتاب روشن و قابل خواندن، هر دو سم شناسان با تجربه و کسانی را که در زمینه آموزش در زمینه چگونگی بررسی سم شناسی در چنین چارچوب هستند، تشویق می کند. این به اهمیت عادی بودن سموم شیمیایی، بررسی روشهای تست سمیت و روشهای جدید و جایگزین برای ارزیابی ایمنی می پردازد. تفسیر یافته های سمیت در مطالعات فردی و بسته های داده ها و پیش بینی خطرات مربوط به انسانی مورد بررسی قرار می گیرد، و پس از آن مقدمه ای بر ریسک و نحوه برداشت و ارزیابی ریسک در پرتو خطرات شناخته شده و احتمال وقوع آنها بررسی می شود. مرحله نهایی فرایند سم شناسی، ارزیابی و مدیریت ریسک، به ویژه با توجه به محل کار بررسی می شود.
راهنمای سم شناسی کاربردی با استفاده از جعبه های متن برای ارائه اطلاعات پس زمینه در موضوعات خاص و یا به عنوان راهنمایی ساده به روش سموم و یا فرایند عمل می کند؛ این توسط جداول و مطالعات موردی برای نشان دادن روش، مطالعه طراحی و تفسیر مورد استفاده قرار می گیرد. این ویژگی ها به این معنی است که کتاب در سطوح مختلف، مناسب برای سم شناسان حرفه ای و دانشجویی و همچنین افرادی که از خارج از این زمینه هستند، نیاز به دانش خاصی از روش سم شناسی و تفسیر دارند، به عنوان مثال در بهداشت حرفه ای و جراحی پزشکی و دامپزشکی.
TABLE OF CONTENTS
Chapter 1|36 pages
Introduction to Toxicology: The Necessity of Measurement
We live in a chemical world. We are composed of chemicals and the vast majority of these chemicals are naturally occurring. However, an increasing number of those found in our bodies are persistent man-made chemicals such as polychlorinated biphenyls, bisphenol A, or organochlorine pesticides such as DDT and its metabolite DDE. It is comforting to believe that all man-made chemicals are poisonous and all-natural chemicals are safe. Sadly, this is not the case; for example, botulin toxin, the active principle in Botox injections is one of the most poisonous chemicals known but is found naturally. The ancient Greeks and Romans killed each other with natural poisons such as hemlock. Lead is a natural element but is also one of the most insidious poisons known with no level that can be described as safe.
Chapter 2|22 pages
Normality: Deﬁnition and Maintenance
The whole basis of the toxicological investigation is to detect differences from experimental normality that are attributable, with reasonable certainty, to the inﬂuence of the substance under investigation. This simplistic overview, however, then begs the question as to what is normal or, by association, natural. Dictionary deﬁnitions of normal use words such as usual, typical, or expected; the normal state or condition or conforming with a standard, for instance, as shown by body temperature. Natural is deﬁned as existing in or derived from nature; not artiﬁcial; following nature, or normal. In terms of public perception, normality is seen so routinely that it may be more useful to think of abnormality, which can provoke a reaction that is not seen in response to the normal. Equally, there are degrees of abnormality. Someone in a wheelchair, with shortened limbs due to exposure to thalidomide, may be seen as more abnormal than a person in a wheelchair because of an accident; the former will always be disabled while the latter may be “normal” again. Such simple judgment is based on perception, which may not be readily supportable in scientiﬁc terms. In toxicological terms, normality can usually be deﬁned by numerical data, means, or incidence data or, less veriﬁably, experience. For characteristics that are deﬁned by presence or absence or narrow ranges of values, deﬁnition of normality is relatively simple in comparison with those that are present on a graduated scale or have a wide range of value.
Chapter 3|30 pages
Determination of Toxicity: The Basic Principles
The following chapters examine the various areas of toxicity investigation that are routinely undertaken in a development program starting with a review of basic principles. A short chapter on in vitro systems is followed by chapters covering the main areas of regulatory toxicology, namely general and reproductive toxicity, genotoxicity, carcinogenicity, and dermal toxicity. There is also a brief chapter on environmental toxicology, the intention being to give a complete picture of toxicological investigation without going into detail in these specialist areas.
Chapter 4|26 pages
Chapter 4. Determination of Toxicity: In Vitro and Alternatives
The expansion of in vitro techniques continues as they become more reﬁned and reliable and as an understanding of their meaning and utility grows. To cover the subject area adequately would require a separate book; the main difference from the previous edition, where I said the same thing, is that the book would now be much fatter. One aspect has not changed and that is the limited amount of regulatory acceptance of in vitro or alternative techniques.
Chapter 5|16 pages
Chapter 5. Safety Pharmacology
This is a brief review of safety pharmacology as required for the development of most types of pharmaceutical under the guidelines promulgated by ICH-The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. Although I have referred extensively to the text of these guidelines, I have also attempted to put safety pharmacology in its proper context in terms of practice, interpretation, and the pitfalls that may be encountered. A review by Redfern et al. (1) helps to put the subject more deeply into context and is a very useful text.
Chapter 6|30 pages
Determination: General and Reproductive Toxicology
In broad terms, general toxicology is something of the poor relation of toxicology. It can be seen as lacking the glamour or intellectual rigour of other areas of toxicological investigation because it sets out to be a catch-all, to paraphrase Gerhard Zbinden, “it looks for everything but hopes for nothing.” However, it is central to the safety evaluation of novel chemicals, as effects that may be seen in other more specialized areas can also be detected or supported by well-designed general toxicity studies. For example, the microscopic evaluation of testes in a general toxicity study may indicate the potential for effects in formal fertility studies in the program of reproductive toxicity studies.
Chapter 7|38 pages
Determination: Genotoxicity and Carcinogenicity
The intention in testing for genotoxicity is to determine the potential for damage to DNA and thereby to highlight any effects that might, with administration or exposure, lead to an increased incidence of tumours or birth defects through heritable effects in the germ cells. In the latter context, it is worth considering that changes in chromosomal numbers are usually fatal in laboratory animals but not in humans where conditions, such as Down’s syndrome, are associated with an extra chromosome but do not lead to abortion. The genetic changes associated with some cancers are given in Table 1 (1).
Chapter 8|14 pages
Chapter 8. Determination: Dermal Toxicity—Sensitization, Irritation, and Corrosion
For the most part, this chapter deals with dermal toxicology but in the specialist sense of the three main aspects of dermal effects that are examined in regulatory toxicology: sensitization, irritation, and corrosion. It does not seek to cover general, reproductive toxicity or carcinogenicity studies that may be needed in the development of a pharmaceutical or agrochemical and which are very similar to other studies of that type, the only real difference being the route of administration. This chapter deals with study types that are most relevant to occupational health, which is a fairly specialized area that is sometimes poorly understood by people unfamiliar with the unsuspected complexities of successful study conduct and interpretation. It does not cover respiratory sensitization, which is a factor in occupational disease, for instance, allergy to animals in testing facilities or farmer’s lung, which is associated with breathing the dust from mouldy hay.
Chapter 9|16 pages
Determination: Environmental Toxicology and Ecotoxicology
The environment may be loosely deﬁned as the surroundings and conditions in which we live; environmental toxicology is the study of toxic chemicals within that environment and the effects that they have on humans and populations. Ecotoxicology is speciﬁcally the study of environmental toxins on the ﬂora and fauna that make up an ecosystem. The former has an implied human slant while the latter is oriented more toward the effects of chemicals on the natural ecosystem studied as a whole, which includes mankind.
Chapter 10|22 pages
Interpretation: Basic Principles
This chapter intends to give guidelines on the basic principles of interpretation of toxicological data and to indicate an overall philosophy to this sometimes seemingly black art. Interpretation is distinct from prediction, for example, in the attribution of cause/effect before versus after the event: “She smokes a lot, so she may get lung cancer” versus the ﬁnding that she has lung cancer. Did she smoke? Yes, 20 a day. We have a possible contributing factor for this cancer.
Chapter 11|40 pages
Interpretation: Different Data Types
The following sections give an overview of the types of toxicological data and attempt a basic guide on how to approach each type. Unfortunately, although a guide can be attempted, it is most unlikely to cover every set of circumstances.
Chapter 12|28 pages
Prediction of Hazard
The previous chapters have covered the background and process of testing that seeks to show differences from normality, which may represent toxicity and the interpretation of the resulting ocean of data. This chapter sets out to explore the process of hazard prediction that takes place once the results of toxicological investigations have been collated and reported. In the context of this book, it is seen as a high-level interpretation of the whole data set that takes place after the interpretation of individual studies, but before risk assessment and management. The emphasis here is on defensive toxicology, showing lack of relevance to humans or other target species, as that is a major driver for continuing the development of a chemical, particularly new pharmaceuticals. However, it has to be said that defensive toxicology does not mean saving a compound at any cost; clearly, there is an ethical and moral line that should not be crossed. Data should be explained, not ignored or concealed.
Chapter 13|18 pages
Background to Risk Due to Toxicity
The use of any chemical is associated with risk, whether it is a novel drug, an established pesticide, an intermediate in a synthetic pathway, an industrial byproduct, or table salt. The next four chapters outline the basic tenets of risk analysis (risk assessment and risk management) concerning toxicity. This chapter examines various aspects of risk, including how it is perceived and described, that are critical in successful communication and subsequent management of risks due to toxicity, either in the workplace or in a wider context. The relevant factors and processes by which the risks associated with the hazards relevant to humans (or another target species) are assessed are then reviewed.
Chapter 14|34 pages
Risk Assessment in Practice and Setting Exposure Limits
We are now at the point where the hazards have been predicted to be human-relevant (see chapter 12). The information from these earlier stages is assessed to indicate the probability that the toxicities were seen will be expressed in the target population under the anticipated conditions of exposure, which are usually assessed and evaluated on a worst-case basis. This probability is governed by factors such as safety margins, working practices, and the form of chemical (see Box 1). In essence, in a risk assessment, the toxicity of the chemical, related to dose levels in safety tests, is considered in conjunction with anticipated exposure levels for the target population. This should lead to an assessment of the likelihood that toxicity will be expressed in the target population (a margin of safety), facilitating decisions on risk (risk evaluation) and hence exposure limits (which are set as the maximum exposure considered to represent a “broadly acceptable” risk/safe for that particular type of exposure). These limits and controls must be reevaluated in the light of the intended measures to be taken to control exposure in the target population and when new information/new interpretations come to light.
Chapter 15|14 pages
Risk Assessment and Management in the Workplace
Exposure to chemicals occurs in all workplaces, whether they are in industry or agriculture (including chemical production plants), ofﬁces, shops, builders, or railway premises. Although the home is not classiﬁed as a workplace, exposure to chemicals occurs there as well, in the form of disinfectants, cleaners, and do-it-yourself materials.
Chapter 16|22 pages
Risk Assessment: Carcinogenicity, the Environment, Evolution, and Overview of Risk Assessment
This chapter looks at the use of risk assessment in carcinogenicity and the environment (including its international aspects) and moves on to consider the evolution of risk assessment and offer an overview of the ﬁeld. The intention is to look at factors that are relevant to each of these areas rather than write a standard operating procedure, as dogmatic rules for “how to do it” are unlikely to be relevant in every case.
Chapter 17|28 pages
Evaluation of Speciﬁc Classes of Chemical
This chapter attempts a whistle-stop tour of the safety evaluation of different classes of chemicals. While I have attempted to focus on the practicalities of evaluation, there is, inevitably, a fair amount of regulatory detail. However, this should be seen as offering guidance rather than deﬁnitive regulatory advice in each area. The classes of chemicals covered in this chapter are as follows:
Human pharmaceuticals Veterinary pharmaceuticals Medical devices Agrochemicals/Plant protection products Biocides Cosmetics General and industrial chemicals-REACH
This list is necessarily incomplete due to restrictions of time and space. For instance, consumer products such as toys and detergents are not covered. Toys, which have been very much in the news recently due to their content of regulated or banned substances, are regulated through the EU Toy Directive 88/378/EC and associated safety standards for toys (1,2).
Chapter 18|10 pages
The Future of Toxicity Testing and Risk Assessment
In the years since the ﬁrst edition of this book was published, there have been numerous developments in toxicological science and technique. During this time, the principle pressures have not changed and may have become more intense. Regardless of your point of view, the pressure to avoid the use of animals is growing by the year. This point is exempliﬁed by the emphasis in REACH legislation in Europe to avoid the use of animals wherever possible; however, a cynic may dismiss this as pious hope rather than practicable expectation. The methods and philosophy of testing for toxicity are evolving constantly. The results of these tests form the foundations for toxicological risk assessment and this too has undergone evolutionary change, although perhaps not as blatantly as in toxicology.
- Publisher: Informa Healthcare; 2 edition (September 22, 2008)
- Language: English
- ISBN-10: 1420043145
- ISBN-13: 978-1420043143