Toxicology and Endocrine Disruptors - Essay Example

Toxicology Answer Organic phosphate or OP compounds are a of chemicals used in both domestic and industrial sectors. They are commonly used in agriculture, chemical warfare and public health eradication programs. Some of the commonly used OP compounds are insecticides like parathion, malathion, dichlorvos, ethion, chlorpyrivos, diazinon and fenthion; antihelminthic agents like trichlorfon, herbicides like tricresyl phosphate and nerve gases like sarin, soman and tabun (Katz and Brooks, 2010). Most of these compounds are either amides, esters or thiol derivatives of phosphonic acid (Kamanyire and Karalliedde, 2004). These compounds are notorious for their health hazards. Most of the health effects are due to inhibition of cholinesterases (Kamanyire and Karalliedde, 2004). Other than this, inhibition of other enzymes and individual susceptibility also play a role. The compounds are highly lipid-soluble and can be absorbed from any route like skin, conjunctiva, mucus membranes, gastrointestinal tract and respiratory tract. The onset of illness, severity and duration of each phase of illness depends not only on the type of the OP compounds to which the individual has been exposed to, but also the dosage of exposure, route of exposure, characteristics of the cholinesterase enzyme, rate of metabolism in the body and the physico-chemical properties of the compound. Cholinesterase plays an important role in the cell-to-cell communication and is present in several parts of the body like blood, nerves, neuromuscular tissue and glandular tissues. Inactivation of acetyl cholinesterase causes accumulation of acetyl choline in ganglia and synapses leading to various clinical problems (Kamanyire and Karalliedde, 2004). Exposure to these OP compounds leads to triphasic illness in human beings. The first phase is the cholinergic phase. In most of the exposed individuals, only the cholinergic phase may be observed. This is followed by an intermediate phase in 20 percent of the cases, followed by a final phase. The initial 2 phases are associated with mortality and morbidity, while the final phase is not associated with mortality and may not be preceded by the initial 2 phases (Kamanyire and Karalliedde, 2004). In the acute cholinergic phase, accumulation of acetyl choline in the muscarinic sites leads to bronchoconstriction, increased bronchial secretions, increased gastrointestinal motility, vomiting, bradycardia and blurring of vision due to miosis. Accumulation in nicotinic sites like the neuromuscular junction results in flaccid paralysis and muscle fasciculations. Accumulation of acetyl choline within the central nervous system causes insomnia, headache, confusion, drowsiness, convulsions, slurring of speech, respiratory depression and coma (Kamanyire and Karalliedde, 2004). Intermediate syndrome occurs typically after 1- 4 days following the acute phase. It is characterized by cranial nerve palsies and proximal muscle weakness. Paralysis of the muscles of respiration and diaphragm can result in respiratory failure (Kamanyire and Karalliedde, 2004). Delayed neuropathy occurs 2- 21 days after exposure to OP compounds. It is characterized by symmetrical weakness of peripheral muscles in the hands and feet, with a variable degree of sensory impairment" (Kamanyire and Karalliedde, 2004). The damage can be permanent. Other health consequences include increased risk of upper respiratory tract infections, acute pancreatitis, cardiac arrhythmias, congestive cardiomyopathy, profuse diarrhoea, teratogenecity, hypothermia and hyperthermia (Kamanyire and Karalliedde, 2004). Chronic OP poisoning may go undetected and manifests areweakness, malaise, loss of appetite, dermatitis, bruning and tingling sensation in hands and feet which may be followeed by weakness in the legs and walking difficulty. Severe chronic OP poisoning can affects eyes and upper limbs too (OHS, 2009). Diagnosis of OP compound-related problems is established through history of exposure, clinical presentation and certain laboratory tests. Measurement of red blood cell acetyl cholinesterase and butyryl cholinesterase is a widely used diagnostic test. Other than these assays which determine the blood cholinesterase activity are also useful. For workers who work with OP compounds, monitoring and evaluation of the extent of exposure must be ascertained at regular intervals. Though many organizations estimate atmospheric concentration of pesticides, they are not reliable because of variations in routed of absorptions and extent of absorption. Cholinesterase assays are more reliable indicators of exposure. Many experts consider even this tool to be unreliable and have recommended tests like plasma beta-G levels and carboxylesterase estimation for critical evaluation of OP exposure. In those with parathion exposure, urinary p-nitrophenol is a useful test (Kamanyire and Karalliedde, 2004). Environmental monitoring can be done using air sampling, patch monitoring and hand washing. Fluorescent tracing using long-wave ultraviolet illumination is useful to ascertain quantitative estimation of skin deposition, efficiency of the clothes which have been worn for protection and acceptability of various workplace practices. Respiratory exposure can be monitored using trapping system developed based on the physico-chemical characteristics of the compound (Kamanyire and Karalliedde, 2004). Health suveillance is very essential for those who are exposed to OP componds in occupation. The suveillance consists of baseline estimation of cholinesterase enzyme levels in the red blood cells, prior to onset of exposure, testing of cholinesterase levels during periods of maximum pesticide use, medical examination of the workers whenever there is suspicion for increased exposure to OP compounds, when the worker is conserned or when the worker presents with clinical manifestation of OP poisoning (OHS, 2009). Medical examination will include medical history, occupational history and physical examination. Whnever it is established that there is OP poisoning, the worker must be shifted to area of non-exposure until the cholinesterase levels are satisfactory. The personal protective equipment must be monitored regularly with respect to the fit, type, availability, frequency of use and maintenance (OHS, 2009). Answer-2 AMES assay or bacterial Reverse Mutation Assay is a biological test that helps in the assessment of mutagenic potential of certain chemical compounds. The bacteria used for this test is Salmonella typhimurium and E.coli (GenPharmtox). Several strains of this bacteria which have histone-synthesis-related mutations (for salmonella) or tryptophan-synthesis-related mutations (for E.coli) are employed for the assay. The bacteria will need histidine, without which growth of the bacteria will not occur. When placed in a medium deficient of histidine, growth of these bacteria will not occur and no colonies will be formed. Colony growth in such a medium will occur only when there is reversal of mutation, resuming production of histidine (Mortelmans and Zeiger, 2000). Mutagenic compounds have a capacity to reverse the mutation and cause colonial growth. Thus, the assay gauges the mutagenic potential of the compounds through their ability to cause colonization (GenPharmtox). To perform the test, the bacteria is inoculated into the bacterial culture medium and incubated overnight. The test chemical is subjected to dose-range finder using TA-100 strain. Following this, the test chemical, bacterial culture and S9 mix are incubated for an hours. This is then mixed with soft agar and placed on minimal agar plates which are incubated for 48-72 hours, after which the reading is take. While taking the reading, the number of colonies and the precipitation and viability of revertant colonies per plate are recorded. The mutant frequency is "the quotient of the number of revertant colonies over the number of colonies in the negative control” (GenPharmtox) The test is made more sensitive by using additional genetic markers. S9 mix is a metabolic activator and is prepared from adult Sprague Dwawley rats (GenPharmtox). The control used for the test are strains with solvent or vehicle with known mutagens. If the mutant frequency is 2 or more than 2, the test chemical is mutagenic in nature, if it is between 1.7 to 1.9, it means that the test chemical has possible mutagenic potential, and less than 1.6 is indicative that the test chemical is non-mutagenic (GenPharmtox). The limitations of the test are that the tests are performed with prokaryotes which are not perfect models for human beings. The test cannot ascertain the mutagenic capacity of the metabolites formed in the hepatic system, although these properties are being assessed by including liver enzymes in the tests. Some false positive results can occur in compounds with nitrate moiety (GenPharmtox). Currently recombinant DN technology is widely used and has increased the speed of the test (GenPharmtox). Answer-3 Inhalable coal dust has many health hazards which can be experienced by col mine workers. According to the American Governmental Industrial Hygienists or ACGIH (cited in Health and Safety Executive, 2007), coal dust toxicity is similar to quartz, but greater than 5 percent silica. In experimental animals, it has been proved that the substance is a tumorigenic agent with potential to cause lymphomas and adrenal cortex tumors. In humans, the dust causes several respiratory-related diseases like acute and chronic bronchitis, pneumoconiosis, emphysema and Caplans syndrome (OSHA, 2002). These conditions cause detrimental ventilation, low diffusing capacity, low arterial oxygen tension, pulmonary hypertension and other problems which can contribute to premature death (OSHA, 2002). Signs and symptoms of acute exposure are wheezing, shortness of breath and coughing (OSHA, 2002). Thus it is evident that inhalable cost dust has significant health hard risk and every employer pertaining to coal industry must make every effort to protect the employees from these hazards. Several countries have made stringent rules and regulations pertaining to inhalable coal dust. Workers can get exposed to coal dust during mining of coal, transportation of coal and also during other operations like crushing, grinding or pulverizing. Four methods have been suggested to control the exposure of the worker to coal inhalation. These methods are personal protective equipment, local exhaust ventilation, process enclosure and general dilution ventilation. However, all the four methods may not be feasible for implementation all the time (OSHA, 2002). Medical surveillance is very essential is coal mine workers to prevent occupational disease. This includes education of the workers and employers about coal dust inhalation hazards, early detection of the diseases, primary preventive measures and medical evaluation prior to job placement (OSHA, 2002). Medical evaluation prior to employment must mainly aim to assess and evaluate the respiratory system. Certain medical conditions like bronchitis and asthma may get aggravated during employment in coal mines and hence individuals with such problems must not be employed. Periodic medical evaluation consists of occupational health interviews and physical examinations. In places where the hazard is minimal, the periodic evaluation must take place once in 3-5 years. Since occupational exposure to coal dust can cause diseases with prolonged latent period, termination medical evaluation including medical, occupational history and environmental history interviews, physical examination and laboratory tests must be done (OSHA, 2002). Monitoring and measurement at workplace must aim to determine the exposure of the worker to respirable fraction of coal dust that is airborne and contains less than 5 percent silica which is made using 5 microns filter of tared low ash polyvinyl chloride which is preceded by 10 mm cyclone (OSHA, 2002). The samples for evaluation must be collected at a maximum flow rate of 1.7 liters per minute. The maximum collection volume is 816 liters (OSHA, 2002). Certain personal hygiene procedures also must be followed like washing off the affected areas with water and soap following exposure to coal dust, removal of clothes contaminated with coal dust, through washing of hands, forearms and face before eating using toilet, smoking, taking medication and applying cosmetics. Also, while in place of operations, workers must not eat, drink, apply cosmetics, smoke or taking medication (OSHA, 2002). All coal mine organizations and employers must stick to the standard limits of exposure and make changes appropriately. According to OSHA, the limits for exposure to coal dust is 5 percent Sio2. According to NIOSH (1995), "exposures to respirable coal mine dust must be limited to 1 mg per m3 as a time-weighted average concentration for upto 10 hours a day during 40 hours work week." Any deviation from these standard international limits warrants medical evaluation and examination, environmental change and if necessary, termination of employment. References GenPharmTox. (n.d.). AMES test: Bacterial Reverse Mutation Assay. Retrieved on 10th April, 2010 from http://docs.google.com/viewer?a=v&q=cache:lASZbRp0JB4J:genpharmtox.de/downloads/AssaySheetAMESTEST.pdf+AMES+assay+procedure&hl=en&pid=bl&srcid=ADGEESjnoYSbsYEoytclkUmYBtnifUF2uEGKZWoHCgQzCgQlA58L33GhxM2DtLHko3UcQ9KJPOijZeVe-PGaVhuMKsroeY3ipw2C-YqWaVtSiiju12Clzvsfgl7nh-Rhr2qZZKBCjv5Y&sig=AHIEtbQmfqc6VEGGm2aa3n7ELEAg4zmc3w Health and Safety Executive. (2007). Inhalable dust in coal mines. Retrieved on 10th April, 2010 from http://news.hse.gov.uk/2007/11/26/inhalable-dust-in-coal-mines/ Kamanyire, R., and Karalliedde, L. (2004). Organophosphate toxicity and occupational exposure. Occupational Medicine, 54, 69- 75. Katz, K.D. and Brooks, D.E. (2010). Toxicity, Organophosphate. Emedicine from WebMD. Retrieved on 10th April, 2010 fromhttp://emedicine.medscape.com/article/167726-overview Mortelmans, K., and Zeiger, E. (2000). The Ames Salmonella/microsome mutagenicity assay. Mutat. Res., 455 (1-2), 29–60. OSHA. (2002). Occupational safety and health guideline for coal dust (less than 5 percent Sio2). Retrieved on 10th April, 2010 from http://www.osha.gov/SLTC/healthguidelines/coaldust-less5percent OHS. (2009). Health Surveillance Guideline for users of organophosphate pesticides. The University of Queensland: Occupational Health and Safety Unit. 1-4. NIOSH (1995). Occupational Exposure to Respirable Coal Mine Dust. Retrieved on 10th April, 2010 from http://docs.google.com/viewer?a=v&q=cache:qamAZC7vvNcJ:www.cdc.gov/niosh/pdfs/95-106a.pdf+coal+dust+recommended+limits&hl=en&gl=in&pid=bl&srcid=ADGEESiRxg_MxvU-jQCe_3NtkfV8ITkN-SXKsaQSwkCws0MjqjsHpO_K1ajNOn668mbLY9zDr3APrQCqytDyOIrkFJyD2qGZmFl7xYwt8Qz-2jBN58mvoWiR-Gh50sQpmYhSFkfFwcq5&sig=AHIEtbS1pIpM9FRYlY8Oi7wJzoEFQoQYLg Read More