Epidemiology and Toxicology - Essay Example

Epidemiology and Toxicology Name Institution Course Date Epidemiology and Toxicology: AMES Assay, Health Effects Question I Introduction Life is combination of chemicals comprised of different substances. Numerous but varied molecules are required and are vital for cellular processes of involving plants, animals, and microorganisms absence of which, life is impossible (Hill,1965). However due to the complexity of chemicals, there arises a need for certainty over the safety of different chemicals, whether synthetic or natural. various chemicals have distinct others varied toxicity effects on life (plants, animals and microorganisms).Some toxic levels are so fatal that they induce changes in genetic make-up (gene mutations)of organisms thus affecting the germ line ultimately via mutations, others are carcinogenic hence induce growth of malignant cells pausing a healthy risk on the environment and organisms. Toxicity identification of chemicals is an important safety assessment test. However, more emphasis has been put upon mutagens, due to their effect on the hereditary material. In addition, mutagens have a capacity to induce cancers. This has led to global concerns of coming up with mutagen testing modules. The use of the Ames assay and animal bioassays tests have for long been used in satisfying this noble purpose. The Ames Assay Description The Ames assay test, developed by a scientist named Bruce Ames has been used extensively for many years to predict the safety of synthetic chemicals. It is centered on the supposition that any substance that is mutagenic for the bacteria used in this procedure has the capacity to be carcinogenic. Nonetheless, some cancer-causing elements in lab animals fail to attest the Ames procedure, however, the simplicity and inexpensive nature attributed to this test marks it is helpful for screening elements with carcinogenic potential. The bacterium that is used in the Ames assays test is a inoculum of Salmonella typhimurium (S. typhimurium.) that has amutant gene which thus makes it impossible to manufacture the amino acid histidine given the elements in the culture medium e.g. agar. But, some forms of gene alterations can be retreated; a principle called, aback/reverse mutation, which allows these reversed-genes develop on medium deficient of histidine (Ames, 1990). Ames procedure The sample strains are explicitly fashioned that they exhibit both gene mutations and frame-shift in the genes essential to produce histamine, allowing the mutagens detection acting done diverse mechanisms. Reversions may result in just a single strain or two once the compounds are quite precise. The genes responsible for triggering lipopolysaccharide synthesis remain carried within the mutated genes of the sample strains which make the cell wall of the bacteria permeable and sensitive since this is in the deletion repair system. In stimulating the result of metabolism, liver samples extracted from rat/rodent are added, since benzopyrene and other compounds are not mutagenic by themselves but the metabolites are (Ames, 1990). The bacteria then are spread upon an agar petri dish having trivial quantity of histidine, which at as a growth stimulant at a preliminary stage, and have capacity to mutate. The mutated bacteria that are allowed to have the chance to synthesize their own histidine will survive upon the depletion of the inoculated one. The dish containing the bacteria is then incubated for 48 hours. Finally the number of colonies formed is established. The number of colonies in directly proportional to the toxicity/mutagenic potent of the test sample (Elberg, 1984). Advantages of the Ames assay i. About 90% of chemicals that test positive also are carcinogenic in animal bioassays tests ii. It is short-term, low-cost test that easy to perform According to Elberg (1984) disadvantages of the Ames Assay include: i. Negative results are common for metals and some chlorinated organics ii. Difficult to test volatile compounds iii. Mutagenesis is not directly linked with carcinogenesis Animal bioassays’ description According to IARC (1988) animal bioassays the determination of potency of a substances by measurement and comparison of the scale of the reaction of the assessment with that of set normal standard using suitable biological agents; in this case animals such as rodents(rats, mouse, guinea pig, rabbits) Animal bioassays are based on a number of techniques and procedures. They are grouped into three main types: i. In vivo methods: this method employs the usage of an animal specifically recommended for a particular assay. With a goal to study the bio effect of a given compound upon direct screening in animal e.g. rodents and rabbits. ii. In vitro method: it employs a cell culturing of commended animal/biological system in order to ascertain the impact of a substance under standard situation dissimilar to that of a natural living environment. The cell culture endures by consuming of the nourishment in the media. Examples are cell cultures and bacterial cultures. iii. Ex vivo methods: it makes use of cells or tissues of animals in studying the influence of compound in question under suitable conditions in the specified period of survival of an outer of the animal body. Example: use of separated part or organ of an animal in the lab under sufficient oxygen levels glucose provision and isotonic salts in ensuring stable cell integrity (Elberg, 1984). Advantages of animal bioassays The adoption and use of animal bioassays use of animal bioassays is argued sensible foundation because. a. Test animals and humans are beings sharing many genetic, pharmacologic, toxicological, and oncogenic reactions; b. Results from autonomously steered bioassays on the similar chemicals are reliable. c. Entirely all recognized human cancer-causing agents that have been tried sufficiently are also carcinogenic in animals and, and share the same target sites d. Nearly one-third of anthropological carcinogens were first revealed to induce cancer via tests in animals (e.g.2-naphthylamine, diethylstilbestrol, formaldehyde 1,3-butadiene dioxins, ethylene oxide, , and vinyl chloride) Disadvantages of animal bioassays i. A lack of sensitivity, particularly with whole animal studies, which require a lot of hormone to produce a response ii. Poor reproducibility, due to the wide variability in response that is obtained with different animals. iii. High cost, difficulty and ethical consideration for use animals and animal preparations. Due largely to the limited number of animals per test (generally 50-60 animals of each sex of two species, rats and mice, in each experimental group), bioassays are conducted at relatively high exposure concentrations to optimize the probability of detecting a carcinogenic response (Cohen, 2004). iv. Long-term bioassays are designed to expose rodents to chemicals or environmental mixtures that cause only minimal toxic effects. The highest doses elected for these studies has been termed the "maximum endured dose" (MTD), when, it actually signifies a minimally toxic exposure dose (Cohen, 2004). v. Carcinogenesis bioassays have been criticized for identifying "too many rodent carcinogens" but not humans, largely because of purported differences in exposures and lack of discrimination due to high-dose effects. Other assay methods Syrian Hamster Embryo Assay (SHE) It is a cell transformation assay (CTA) that is used to identify phenotypic changes in lab-cultured cells that are distinctive of tumorigenic cells. Since malformed cells do have the capacity to prompt tumors in vulnerable animals, they remain apparently the solitary in-vitro systems in which tumor production can be of usage as an end-point (OECD 2006). Malfunctioned cells have uncharacterized and undifferentiated growth pattern that cause variations in cell form due to forfeiture of contact reticence and tumorigenicity upon transplanting into animals of the similar strain (OECD 2006). The advantage of using these tests is the capacity to examine if a chemical acts as a motivator or a promoter. Motivators or initiators can result to the first alteration in a cell. Pre-treatment can be done on cells using an initiating cause to ascertain tumor-promoting action of examination chemicals. Measurable studies are likely with SHE cells; the proportion of change is relative to the concentration of the chemical cancer-causing agent and also shows the strength of the in-vivo action of the carcinogen Sample chemicals determined positive when; i. On the least two test groups exhibit an increase in in morphological alteration frequency ii. A single group exhibits a statistically important upsurge with the trend analysis test being significant (NTP 2007). L5178Y Mouse Lymphoma Assay (MLA) This assay is majorly done on mammalian cells hence similar to chemical mutagenicity in people. These cells (L5178Y mouse lymphoma) employed in this test are heterozygous for thymidine kinase gene (tk+/). Forfeiture of the tk+ allele via mutation is similar to trifluorothymidine (TFT) cells’ resistance hence gives a way to choose for this genotype amongst the heterozygous wild-type cells (Clements 2000). Two different colonies are identified upon scoring this media i.e. large and small that is presumed to indicate variances of alterations incurred. Small ones signify ML mutants that are growing at a sluggish rate compared to the larger ones. The concept here is that it is as the consequence growth call mutation near to tk+ (Clements 2000). Otherwise, colony magnitude can be indicator to chromosome abnormalities, equally minor colony mutants be likely to exhibit a developed frequency of these types of transformations compared to the larger ones (Clements, 2000). Moreover, it can be a result temporary cell cycle stoppage in pursuit of energy for cellular functions such as repair and divisions. iii. Top of FormBottom of Form  Relevance of Animal bioassays tests to Humans Agents recognized as carcinogenic to persons, tests in animals have shown outstanding target organ concordance .Nearly a third of these agents confirmed to as instigating cancer in humans remained acknowledged first in experimentations by means of laboratory animals (Huff, 2008). Nevertheless, recaps that there are undeniably differences in carcinogenic responses of numerous types and strains to carcinogens, though these variances have not up till now been explained. The generalization that all compounds known to cause cancer in humans toanimals, leads to a convincing assumption that the observation does hold true because chemicals presented to clearly induce cancer in test animals, particularly in manifold species, must be deliberated capable of initiating cancer in humans. However, further evaluations are called for. The International Agency for Research on Cancer espoused this widely recognized scientific view: "In the lack of satisfactory data in persons, it is biologically reasonable and prudent to favor agents and combinations for which there is adequate indication of carcinogenicity in trial animals as if they existing a carcinogenic hazard to humans. Limits to Animal Bioassay Generalization Huff et al (1994) recognizes that although conclusions across various tests and administration draw on the relevance of bioassays’ generalization, there come some issues to mind; i. The necessary dosage levels done to animal with 2 to 3 years of lifespan are greater than species with a large life span e.g. 70 years. Moreover, the dosage must be high enough to satisfy statistical power among small animal cohort. This thus gives some uncertainty on dose effects and short term exposure in test species to a low dose against human’s long term exposure. ii. Inhalation is a primary carcinogens exposure to humans but it is difficult to employs to test in animals. Variance in part specific bioavailability of test substances affects the validity of conclusion of tests. iii. There is difference of metabolism and hence metabolites between animals and humans which may result to dissimilar results thereof. iv. Test animals unlike human are exposed to pure carcinogens instead of human’s environmental mixtures which also may present unclear conclusions. Relevance of Ames Assay to Humans Elberg (1984) recognizes that due to its simplicity, in expensive nature and adaptability, to an array of samples, potential uses have been suggested i. Mass screening of commercial chemicals before their release to the market ii. Identifying mutagenic impurities in otherwise non-mutagenic products iii. Surveying air, water and soil samples for mutagenic potency, moreover with chemistry methods, identifying the mutagenic proportions iv. Testing of urine ,fecal matter and other bio samples in relation to diet , environment and medical exposure to suspect compounds and substances v. Screening substances to decide which ought to be tested in animal bioassays. These applications depend on the predictive validity of the Ames assay for Human cancer potential. However, important to note is that this test is only applicable to non-metallic compounds whose carcinogenic potency derives from chemical properties. So, substances whose potency is from their physical attributes cannot be detected by Ames assay e.g. asbestos (Elberg, 1984). Conclusion The Ames assay and the animal based assay will continue to elucidate a number of reactions from scientists and numerous research into them as well as more trials in finding more conclusive and accepted way of testing carcinogenic potency in the environment and in chemicals, However, the Ames assay does provide a shorter, quick and acceptable way of preliminary testing compared to animal bioassays which face a lot of critics based on ethical foundations and the procedure as a whole. Nevertheless, the two methods are vital for assurance of human health and safety and therefore need to be developed further for an even safer environment. Question II Introduction Employers have a legal duty to stop or prevent workers’ exposure to harmful substances at work. If impractical, then endeavor to reduce the exposure to a minimum low that may not lead to health complications in both short term and long term. A number of organic solvents are used in the process for cleaning printing blankets and heads as well as ink solvents. Organic solvents are essential to the printing industry they have a number of toxicological and epidemiological effects to the employees. The solvents in this context are toluene, n-hexane, xylene, ethyl ether and methyl ethyl ketone (MKT) (Klaassen & Pearce1995). As a manager therefore, I am legally bound to provide a safe working place to all employees by safeguarding their health with regard to exposure to such toxic chemicals. To achieve this, I shall mobilize the management in all the organization’s production facilities in a bid to identify the risk and more importantly coming up with a collective, revised regulations and commitment workplace safety with regard to organic chemicals of suspect. Literature review Solvents are either classified as aqueous or organic but each class is subdivided further to account for different structures .Toluene, ethyl alcohol, xylene, n-Hexane and methyl ethyl ketones, each falls under individual sub class of organic solvents: straight or branched chains of carbon and hydrogen (e.g. hexane,); aromatic hydrocarbons (e.g. toluene, xylene); ketones (e.g., methyl ethyl ketone) and alcohols (e.g. Ethyl alcohols) (Klaassen & Pearce1995). Organic chemicals evaporate at ambient temperatures due to their volatility; hence inhalation and absorption through the skin are the most significant routes of human exposure to these chemicals (McFarland & Bates 2002). Health Hazards of the Chemicals due to Exposure The nature of hazards can be divided into acute (short-term) or chronic (long-term). Respiratory Irritation: Accorsing to McFarland & Bates (2002) Respiratory irritation often occurs on the mucous membrane leading to inflammatory sensational long the respiratory tract which is characterized by coughing with difficulty in breathing. At high exposure concentration, it may cause a higher irritation which leads to pulmonary oedema or bronchitis at a chronic level e.g. n-hexane. Eye Irritation: High concentrations exposure of all the four solvent vapors can lead to eye irritation, a burning itchy sensation. Dermatitis: Toluene, xylene,-Hexane, ethyle alcohol and methyl ethyl ketone all have the potency to dermatitis. But at acute levels they dissolve the skin lipids making the skin lethargic, blistered or itchy with long exposure it leads to chronic dermatitis characterized by flaky skin (Riihimaki and Pfaffli 1978). Central Nervous System Depression: Like alcohol, printing-based solvent exposure affects the brain. Exposure to high concentrated exposure leads to euphoria, faintness, lack of body synchronization, headaches, tiredness, and nausea (Gamberale, 1978). Long-term exposure is associated with results like trouble in thinking and personality transformations. N-hexane and methyl ethyl ketone, can injure the peripheral nerves to sensory organs and muscles. Indications of nerve harm comprise of pain, sensation failure, and weakness, often starting in the toes, then the fingers up the legs and hands. Ototoxicity: toluene, and xylene have been found to have the have an ototoxic potential, damaging the sensory cells of the inner ear (Hoet & Lison 2008). Strategy to Identify, Control And Mitigate the Hazard Identification of Hazard In order for the organization to identify the hazard, the management shall mobilize a risk assessment task that shall involve the operational employees since they are in, supervisors and the Joint Safety Committees across the facilities. It can be achieved by reviewing each solvent’s Material Safety Data Sheet (MSDS) for relevant toxicological data, then by scoring safety assessment checklists, and lastly by air and biological monitoring. Atmospheric air monitoring is a preliminary way of ascertaining the levels of solvent toxicity in the working environment by use of testing gadgets. Exposure to solvents will be most accurately measured by personal sampling. The personal sample should be collected as close as possible to the “breathing zone’’ so that it gives an accurate reading. Use miniature equipment carried by the worker during normal work operations (McDermott and Ness2004). Biological monitoring involves testing for the existence of the toxic solvents, or their metabolites body materials (e.g. body tissue, blood, urine, breath) to determine the amount of chemical in the body upon exposure. Primary detection of high exposures or symptoms of adverse health impacts allows employers to proactively put in place timely corrective and precautionary actions that reduce further damaging exposures to employees (Great Britain, 1997). Control Measures Deciding on the control measures of identified hazard(s), the hierarchy of controls principle shall come into play by placing each control in accordance to priority. Elimination has to be regarded as the top priority, down to the use of personal prevention equipment (PPEs) (Safe Work Australia 2009). Elimination: Removal of a hazardous substance that I not essential (e.g. cleaning by the use of ultrasound instead of a chemical solvent). Substitution: Wherever possible, aqueous solvents should be substituted for solvents-based chemicals; although substitution is the most certain and direct method of eliminating or reducing an occupational health risk, it at times impractical. Isolation: Operations have to be moved from one area to a different one where worker exposures are held to minimum. Engineering controls: The usage of capable local exhaust aeration, where the solvents are pulled into a one- or dual-side top or both might be attainable by a re-circulation/ cleansing system. Engineering control procedures may include: Use of automatic handling methods; use of local exhaust ventilation source of hazard and Isolation, or enclosure of process producing the toxin (Dikshith 2010). Administrative controls/safe work practices: Shifting the way workers do the job or putting into practice measures about how to do the work safely (e.g. permits to work method, limited access to risky areas, employees cleaning skin contamination). Personal protection: Use of protective equipment or clothing e.g. respirators, gloves, eye protection. The management must ensure that the PPE provide fits with the solvent used must comply with relevant Australian Standards. Workers’ trainings are essential so that they become of the essence of the equipment, how and when to use it. However, the management shall not rely on the PPE for employees’ safety because they are meant to protect the worker where the top priority control measures are impractical like in emergency operations. Adequate control however requires an integrated approach of all measures (Standards Association of Australia 1994). Identification and Treatment Program for Affected Workers To ensure that safety is upheld, the management has to make sure free and regular workers’ health surveillance functions. This shall help identify the whether the control measures are effective as well as identify matters of health that may need immediate corrective ,curative attention or compensation with regard to provisions of Employment Injury Benefits Convention,1964 (No. 121). Biological monitoring, by sampling individuals’ urine, blood and saliva, shall be the major approach (Safe Work Australia 2009). However, in developing countries where facility branches may be located in the event that lab testing becomes challenging priority shall be given to environmental measure based on over biological criteria. Types of assessments A return-to-work health assessment; has to be in place to determine worker’s condition after an ailment and so if ready to return to work. Post-assignment health: they are done after completion of a risky task. Periodic health evaluations: has to be conducted at uniform intervals to ensure a sound health to all workers (Standards Association of Australia 1994). Treatment Curative treatment is not included in occupational safety but the company/organization is liable to compensate at-job ill worker or provide a health scheme for workers and their family. However fist-aid program is essential for emergency purposes or on short-term reversible health complications. Moreover, actions should be taken to promote programmes and systems aimed at the free rehabilitation and reintegration, of employees not capable to take on their normal responsibility due to occupational injury (Safe Work Australia 2009). Conclusion Occupational exposure management should be best based on the ‘hierarchy of controls’ principle for limiting workers’ exposure. The hierarchy categorizes controls mechanisms according to their probable effectiveness based on the degree to which each control relies on the behavioral attitude of each workers. For example, use of control mechanism that is independent of worker’s behavior is most effective. Practically, an integration of controls ensures workers’ safety. Bibliography Top of Form Top of Form Bottom of Form Top of Form Bottom of Form Ames BN, Gold LS. Too many rodent carcinogens: Mitogenesis Increases Mutagenesis. Science 249:970-971 (1990). Bonehill, J. A. (2010). Managing health and safety in the dental practice a practical guide. Chichester, West Sussex, Blackwell Pub. http://public.eblib.com/EBLPublic/PublicView.do?ptiID=543022 Clements, J. (2000). The mouse lymphoma assay.Mutation Research.455, 1-2. Cohen S.M. (2004). Human carcinogenic risk evaluation: an alternative approach to the two-year rodent bioassay. Toxicological Sciences: an Official Journal of the Society of Toxicology. 80, 225-9. Dikshith, T. (2010). Handbook of Chemicals and Safety. Hoboken, CRC Press. http://www.SLQ.eblib.com.au/patron/FullRecord.aspx?p=665573. Elberg, L. (1984). Ames test. Great Britain. Health And Safety Executive. (1997). Biological monitoring for chemicals in the work place: information for employees on its application to chemical exposure. Sheffield, Health and Safety Executive. Hill, A.B. (1965). The environment and disease: Association or causation? Proc. R. Soc. Med. 58, 295–300. Hoet, P., & Lison, D. (2008). Ototoxicity of Toluene and Styrene: State of Current Knowledge. Critical Reviews in Toxicology. 38, 127-170. Huff et al, The Limits of Two-Year Bioassay Exposure Regimens for Identifying Chemical Carcinogens (2008). Huff J.E, Bucher J.R, Schwetz BA, Barrett JC. Optimum exposure levels for chemical carcinogenesis experiments: concepts, principles, guidelines, and experience. Toxicologist 14:139 (1994). IARC. IARC preamble, 13-33. In: IARC monographs on the evaluation of carcinogenic Risks to humans, vol 60. Some industrial chemicals. Lyon:International Agency for Research on Cancer, 1994; 21. International Agency for Research on Cancer, & IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. (1988). IARC monographs on the evaluation of carcinogenic risks to humans.Lyon, France, IARC. International Course on Safety and Health Aspects of Organic Solvents, RiihimäKi, V., & Ulfvarson, U. (1986). Safety and Health aspects of organic solvents: proceedins of the International Course on Safety and Health Aspects of Organic Solvents, held in Espoo, Finland, April 22-26, 1985. New York, A.R. Liss. International Labour Office. (1980). Amendment of the list of occupational diseases appended to the employment injury benefits convention, 1964 (no. 121): seventh item on the agenda. Geneva, International Labour Office.. J.J. Keller & Associates. (1987). Your right to know the material safety data sheet. Neehah, Wis, J.J. Keller & Associates. McDermott, H. J., & Ness, S. A. (2004). Air monitoring for toxic exposures. Hoboken, New Jersey, Wiley-Interscience. Mcdermott, H. J., & Ness, S. N. (2004). Air monitoring for toxic exposures: an integrated approach. New York, Wiley. McFarland, M., & Bates, N. (2002). Toxicology of solvents. Shawbury, U.K., Rapra Technology Ltd. http://public.eblib.com/EBLPublic/PublicView.do?ptiID=485250. Mcfarland, M., & Bates, N. (2002). Toxicology of solvents. Shawbury, U.K., Rapra Technology RiihimäKI V, & PfäFFLI P. (1978). Percutaneous absorption of solvent vapors in man. Scandinavian Journal of Work, Environment & Health. 4, 73-85 Safe Work Australia. (2009). Safe work Australian. Canberra, Safe Work Australia. http://www.safeworkaustralia.gov.au/swa/newsevents/newsletters. Sontag J. M, Page N.P, Saffiotti, U. Guidelines for carcinogen bioassay in small rodents. NCI carcinogenesis technical report series no 1. DHEW publication no. (NIH) 76-801. Spellman, F. R., & Bieber, R. M. (2009). Occupational safety and health simplified for the chemical industry. Lanham, Md, Government Institutes/Scarecrow Press. Squires, E. J. (2010).Applied animal endocrinology. Wallingford, Oxfordshire, CABI. Pg 60. Standards Association of Australia. (1994). Occupational personal protection. Homebush, N.S.W., Standards Australia. Winder, C., & Stacey, N. H. (2004). Occupational toxicology. Boca Raton, Fla, CRC Press. Bottom of Form Bottom of Form Bottom of Form Read More