Sufficient Evidence for the Carcinogenicity of Chromium - Research Paper Example

 Table of content Introduction 2 Literature review 3 Methods 6 Budget 7 Timetable 7 Annotated bibliography 7 Introduction Chromium is a natural metal used in a wide variety of industrial activities It is known in different oxidation states: ranging from -2 to +6, where + 3 and +6 are the most frequent. +1,+4 and +5 are rare. Elemental chromium do not occur naturally in the environment, but in the form as chromium compound it occurs in the earth crust and is widely distribute in air, water and soil. Chromium (III) is an essential factor for animal and human being; it has a biologically active form which facilitates the insulin interaction with his receptors sites influencing glucose, protein, and lipid metabolism. Chromium deficiency may cause changes in the metabolism of glucose and lipids. (EPA, 1998) The hexavalent status is rarely found in nature; his compounds are a very strong oxidizing agents and highly corrosive. In the environment they generally are reduced to chromium (III) compounds. Chromium hexavalent compounds are widely diffused in the industry in form of calcium chromate, chromium trioxide, sodium chromate and dichromate, potassium chromate and dichromate, lead chromate, strontium chromate, and zinc chromate; this compounds are used as corrosion inhibitors, in the manufacture of pigments, in metal finishing and chrome plating, in stainless steel production, in leather tanning and in wood preservation. Exposure to Cr(VI) has been associated with increase of lung cancer risk for more than 50 year. The first pathology that pointed the attention on hexavalent chromium was the perforation of nasal septum in worker employed in chromate production. In 1943 American National Standard Institute recommended an exposure standard of 52 microgram of Cr(VI) per cubic meter of as a level adequate to prevent nasal perforation in acute chromium-exposed worker. (OSHA,2006) Suddenly epidemiological studies demonstrated a correlation among lung cancer and chromium (VI) by the inhalation route exposure; this statement is particularly related to chromate production, chromium plating, and chromate pigment production. Epidemiological studies in stainless steel welder found an increased risk of lung cancer, however this studies are limited by the co-exposure of this worker to other potential carcinogens. On February 28, 2006 OSHA (Occupational Safety & Health Administration) issued the final rule addressing occupational exposure to Cr (VI) in 5 microgram/cubic meter. (OSHA,2006) The findings in humans are supported by studies in experimental animals. Benign and malignant lung tumours were observed in mouse, rats, guinea pigs, hamster and rabbits treated with salts of Cr(VI). Chromosomal aberration where observed in worker exposed to Cr(VI) compound. The genetic damage was demonstrated in several laboratory tests: mutagenic effect in bacteria, yeast and insects, human and animal cells In 1990 IARC concluded that there sufficient evidence for the carcinogenity of chromium (VI) in humans based on the combined result of epidemiological studies, Carcinogenity studies in experimental animals, and evidence that chromium(VI) ions generated critical sites in the target cells are responsible for the carcinogenic action observed.(IARC 1991) Today the categories of workers exposed to chromium hexavalent are: chromate plater, welder, spray painter, ship/boat builder repairer abrasive blaster, paint mixer/maker, metal sprayer, plastic formulator, paint scraper, leather tanner, printer, pigment and dye maker, ferrochome metal caster, textile worker. Cr(VI9 can enter the body by breathing air containing the contaminant or being swallowed; the main route are: 1) Mist: droplets of liquid containing hexavalent chromium get into the air if a liquid containing Cr(VI) is vigorously sprayed. 2) Dust: solid particles containing Cr(VI) get into the air if powered Cr(VI) materials dumped, scooped or by grinding a material containing Cr(VI). 3) Fume: very fine particles containing Cr(VI) get into the air by melting or welding metal containing chromium. Hexavalent chromium can get on cigarettes; if contaminate d cigarettes are smoked, the smoker inhales additional chromium along with the tobacco smoke. Particle of chromium ca be swallowed if dust get on hands, clothing or beard or in food o beverage. Excretion of chromium occurs primarily via urine; the kidney excretes about 60% of an absorbed Cr(VI) dose in form of Cr (III) within 8 hour of ingestion resulting in a rapid plasma clearance. Elimination from tissue is slower with a half life of several days. Pathologies other than cancer are associated to the corrosive and irritant characteristics of chromium hexavalent; exposure can result in a sensitization of the breathing system leading an asthmatic response. Repeated or prolonged exposure can damage the mucous membranes of the nasal passage and cause ulcer to form. Furthermore on the skin a penetrating round ulcer can develop; the most common sites of this ulcers are nail root, knuckles and finger web, back of the hand and forearms. Studies on welder and chromium platers have found that workers with higher levels of exposure to airborne chromium (typically grater than 20 microgram/m3 show damage to renal tubules) (U.S. Department of Heath and Human Service,2000.) Literature review With the purpose to advance the knowledge of the involvement of Cr (VI) in human health it is essential to perform a bibliographic research about this issue. An important topic is the possibility to consult the documents of Public Health Institution, national and international, like Center of Disease Control (CDC), Environmental Protection Agency (EPA), U.S. Department of Labour Occupational Safety and Health Administration (OSHA), IARC (International Agency of Research on Cancer); here we can find report and other documents of interest. A quick way to find scientific articles and papers is to use electronic resources like scientific online database like Medline (http://medlineplus.gov ) NIOSH (http://www2a.cdc.gov/nioshtic-2 ) Highwire (http://highwire.stanford.edu/) Biomed central (http://www.biomedcentral.com/) Scirus (http://www.scirus.com ) Toxnet (http://toxnet.nlm.nih.gov/) ; in this way it is possible to collect a pool of publication in which to select what is of interest. The document and the scientific paper selected are of two types: 1) effects of hexavalent exposure; 2) specific topics addressed by the type 1 documents. Study Author Reference Health Outcome Analysis Category Other Toxicological review of hexavalent chromium EPA U.S. Environmental Protection Agency. “Toxicological review of hexavalent hromium1998. Cancer, dermatitis an other pathology - conclusive - ”Chromium, Nickel and Welding” IARC Monograph on the Evaluation of carcinogenic Risk of Chemicals to Humans IARC IARC. 1990 Cancer - conclusive - “Toxicological profile of Chromium” U,S Department of Heath and Human Service U.S Department of Heath and Human Service.2000 Cr(VI) pathological effects - conclusive - Occupational Exposure to Hexavalent Chromium OSHA Federal Register,Rules and regulations,2006,vol.71, n°39 - - Conclusivr - Mortality in leather tanning worker: an update Stern-FB  Am J Ind Med 2003 Aug; 44(2):197-206  Lung cancer Discordant result conclusive Cancer incidence in the Swedish leather tanning industry: updated finding 1958-99 Mikoczy Z.and Gagmar L. Occup.environ.Med.2005;62;461-464 Lung and Prostate cancer - Conclusive for lung cancer and suggestive for other type of cancer - Cancer mortality among shoe manufacturing workers: an analysis of two cohorts. Fu H.,Demes PA, Costantini A, Winter S., Colin D., Kogevinas M., Moffetta P: Occup Environ Med. 1996, Jun; 53(6):394-8 Nasal cancer leukemia Discordant results Suggestive - Boot and shoe manufacture and repair IARC IARC Monographs on the evaluation of the carcinogenic risk of chemicals to humans Vol:25 (1981) pp 249-77 suggestive Analysis of Dust in the Leather Industry with Reference to the Presence of Possible Oncogenic Agents Lahiri VL, Khanna P., Elhence BR, Singh K, Singh K., Mehrotra KN, Gupta A Annals of the New York Academy of Sciences, 1988Vol. 534, pages 792-807 Dust carcinogenity - Suggestive - A Case-Control Study of Cancer of the Nose and Paranasal Sinuses and Occupational Exposures Comba P., Battista G., Belli S., De Capua B., Merler E., Orsi D., Rodell S., Vindigni C., Axelson O., American Journal of Industrial Medicine, 1992,Vol. 22, No. 4, pages 511-520, Nasal cancer - Suggestive Survey n°3, 2002: Investigation of the content of Cr(VI) and Cr(III)in leather Products on the Danish Market Danish Environmental Agency http://glwwwmst.dk/chemi/01080300 - - conclusive - Leather industries: Boot- and shoe manufacture and repair (Group 1) Anonymous IARC Monographs on the evaluation of the carcinogenic risk of chemicals to humans Vol:Suppl. 7 (1987) pp 232-4 A review on the different pathologies suggestive Cancer risks associated with employment in the leather and leather products industry. DecoufleP: Arch Environ Health. 1979 Jan-Feb; 34(1):33-7 suggestive Formation, prevention and determination of Cr(VI) in Leather UNIDO http://www.unido.org/userfiles/PuffK/overview.pdf - - conclusive The reports and the toxicological studies confirm Cr(VI) is linked to lung cancer. .( U.S. Department of Heath and Human Service,2000)( EPA,U.S. Environmental Protection Agency.1998)(IARC 1991) Regarding the leather tanning industry there are strong evidences of the Cr(VI) involvement mainly in lung and rare sinonasal cancer; other type of cancer are not excluded, but the related data are inconclusive. A study reports an increase of prostate cancer.(IARC 1981)(IARC 1987) (Comba et al 1998)( Decoufle P,1979)( Fu H,1986(Mikoczy Z.and Gagmar L.,2005)( Stern-F.B,2003 ) With the purpose to reduce the worker exposure Guidelines for Health and Safety in leather tanning were elaborated; an example is the guideline produced by International Finance Corporation; applying these guidelines also the content of Cr (VI) of the final product was reduced. In 2001 Danish Environmental Agency performed an investigation to evaluate the possible content of hexavalent and trivalent chromium in leather product in Danish market.( Danish Environmental Agency Survey n°3, 2002) The results were surprising: the number of the leather products containing Cr (VI) was not expected, taking in consideration that CR (VI) can be easily avoided applying the health and safety guideline. Probably these result may be extended to other market because the leather use in this kind d of manufacture are imported from other country like in Denmark. . In 2000 United Nation Industrial Development Organization (UNIDO) published a short overview of recent publication on formation, prevention and determination of C (VI) in leather. (UNIDO. 2000) The review shows the formation of Cr (VI) is possible in leather tanned following the safety guidelines to avoid hexavalent chromium; the main factors involved are storage conditions (low humidity and temperature) of finished products. This finding can explain the pathologies reported among the shoes and boot manufactures; this employer are exposed to leather dust and some authors linked this factor to rare nasal cancers. The epidemiological studies involving these categories of workers reported discordant results. Objective In the light of this last issue an epidemiological study on the potential health outcome of Cr (VI) in leather manufacture workers (shoes, gloves, and other article of clothing) is performed. One of the risk factors in this workers is the leather dust, but they are exposed to a number of other chemical such as calcium-oxide, ammonia,), n-nitroso compounds, chromium, benzidine based dyes, organic solvents such as formaldehyde and benzene. Employment in boot and shoes industry is supposed linked bladder, lung and oral cavity, farinx and stomach cancer; nasal adenocarcinoma (probably due to leather dust) and leukaemia (due to benzene) are well documented. The aim of this study is to evaluate the risk to cancer other than nasal adenocarcinoma, trying to distinguish the worker employed in the different activities in leather manufacture. Methods The previous researches are mainly case-control studies, evaluating different type of cancer. In our study is performed a cohort for each type of industries (boot, shoes, clothing article) owing to the different type of manufacture and materials used. Company records provide demographic and work history of each worker; the workers employed for less than two years were excluded. The vital status can be ascertained by different font: company records, Social Security Administration Death master file (DMF), National Death Index Plus (NDI Plus). The cause of death are documented by death certificate and NDI plus. The Standard Mortality Ratio ( SMR) and 95% confidence intervals (CI) for each cohort are calculate for each cause of death referring the population of the area where the industries are placed.; in addition data are stratified by year of hire, duration of employment., work place and job task. . Result It is presumable to find a certain number of sinonasal, bladder and prostate cancer as found in the literature data. The probability to find other type of cancer is not excluded. The presence of important result lead to the analysis of incidence in the different type of manufacture; this evaluation, with data stratified by the work place and job task, may suggest the chemical of factor involved, addressing a new study about the exposition of workers. The main weakness of this study is the lack of exposure data for the main chemicals involved. This kind of analysis may be very expensive and must be justified by an epidemiological research demonstrating a real risk for workers. Budget The budget is linked to the hours of work needed to collect the data. There are three main categories of manufacture: shoes, boots and clothing article; the first step of this study is the recruitment the manufacture industries that can provide the data. Until the number and the location of manufacture and the number of worker are not known it is impossible to calculate an exact budget. Timetable Week 1: selection of industries to contact. Week 2: request of data Week 6: data collection and tabulation Week 9: data analysis Week 12: result As for budget, the timetable is linked to the number of data to be collected and analyzed Annotated bibliography World Halth Organisation . 1990 IARC Monographs on the evaluation of carcinogenic risks to humans - Chromium, nickel and welding, Geneve The monograph reviews the biological data available on the carcinogenity of chromium, nickel and their compounds in the welding industry. My study uses this monograph as grneral information about Cr(VI) Anonimous, 1981”Boot and shoe manufacture and repair “IARC Monographs on the evaluation of the carcinogenic risk of chemicals to humans Vol:25 (1981) pp 249-77 In this review are summarized the carcinogenicity of chemical in wood, leather and associated industries. The epidemiological available data are reviewed; the evaluation is made most exclusively on epidemiological data. The aim of this review is to identify the role of single chemical in carcinogenic effect. My study uses this monograph as a resume of knowledge about Cr(VI) Anonimous 1987”Leather industries: Boot and shoe manufacture and repair (Group 1) IARC Monographs on the evaluation of the carcinogenic risk of chemicals to humans Vol:Suppl. 7 (1987) pp 232-4 The monograph reports the evidence of nasal cancer mortality of workers employed in boot and shoes manufactures. This evidence comes from a cohort and case studies England, Italy, Switzerland, France, Massachuset, Japan., Sweden. Other type of cancer is reported: leukaemia, bladder, rectum, lung, mesotelioma. The results among these studies are not concordant: each study report different type of tumour among worker employed in the same type o manufacture. The co-responsibility of solvents and glue are suggested. My study uses this monograph as a resume of knowledge about Cr(VI) Comba P.,Battista G.,Belli S.,De Capua B.,Merler E.,Orsi D., Rodell S.,Vindigni C.,Axelson O.,1992”A Case-Control Study of Cancer of the Nose and Paranasal Sinuses and Occupational Exposures” American Journal of Industrial Medicine, ,Vol. 22, No. 4, pages 511-520 The study describes the cases of nasal cancer admitted in hospital of Verona in the period 1982-1987. All the patients had the same occupational history. My study uses this article as a reference about nose and paranasal cancer Danish Environmental Agency Survey n°3, 2002:” Investigation of the content of Cr(VI) and Cr(III)in leather Products on the Danish Market“ http://glwwwmst.dk/chemi/01080300 In 2001the Danish Environmental Agency initiated an investigation about the content of hexavalent and trivalent chromium in leather products on the Danish market. The results were surprising: 34% of the examined product contained hexavalent chromium above the detection limit of 3mg/kg... This numbers were unexpected because the method to produce leather without Cr(VI) is diffuse worldwide. This report is important for my study because it highlight an unexpected problem about Cr(VI) Decoufle P, “Cancer risks associated with employment in the leather and leather products industry”. Arch Environ Health. 1979 Jan-Feb; 34(1):33-7 The cancer risk in the leather industry detected in this study seems to be linked to cancer of buccal cavity, larynx, pharynx and malignant lymphoma. The nature of the carcinogenic substance is not clear and further studies are suggested. My study uses this study as a reference of correlation between leather product and cancer. EPA, U.S. Environmental Protection Agency.1998 “Toxicological review of hexavalent chromium This review provides a scientific support and rationale for the hazard identification and dose-response assessment in the Integrated Risk Information System to chronic exposure Cr(VI). Knowledge gaps, uncertainties, quality of data and scientific controversies are considered. My study uses this monograph as a resume of knowledge about Cr(VI) Fu H.,Demes PA, Costantini A, Winter S., Colin D.,Kogevinas M.,Moffetta P. 1996 “Cancer mortality among shoe manufacturing workers: an analysis of two cohorts.” Occup Environ Med,, Jun.; 53(6):394-8 The two cohort studies performed in England and in Italy are presented. They confirm the mortality due to nasal cancer. The cohort study in Florence confirms the risk of leukaemia linked to benzene contained in the glue. My study uses this study as a reference of correlation between leather product and cancer Lahiri VL,Khanna P., Elhence BR, Singh K, Singh K., Mehrotra KN, Gupta A,1988 “ Analysis of Dust in the Leather Industry with Reference to the Presence of Possible Oncogenic Agent” Annals of the New York Academy of Sciences, Vol. 534, pages 792-807 An interesting study that demonstrated the presence of carcinogenic substances in the leather dust; cancer developed by animal dermally exposed to dust extract confirmed the findings. My study uses this article because it demonstrate the presence of cancerogenic substances in leather dust. Mikoczy Z.and Gagmar L., 2005” Cancer incidence in the Swedish leather tanning industry: updated finding 1958-99” Occup.environ.Med.62; 461-464 In this study the workers of three leather tanneries were followed for two period of time: 1958- 1989 and 1990 1999. The first period is shows an increase of sinonasal cancer and multiple mieloma; the second one shows the increase of prostate cancer. My study uses this study as a reference of correlation between leather product and cancer OSHA, 2006,” Occupational Exposure to Hexavalent Chromium” Federal Register, Rules and regulations vol.71, n°39 As we can read in the summary of the document “The final rule establishes an 8-hourtime-weighted average (TWA) exposure limit of 5 micrograms of Cr(VI) per cubic Meter of air (5 μg/m3)”. Further the document contain the “OSHA’s legal obligations, the analyses and rationale supporting the Agency’s determination, including a summary of and response to comments and data submitted during the rulemaking”. This document is important for my study because it is the official documents that astablish the exposure limits Stern-F.B,2003 “Mortality in leather tanning worker: an update” Am J Ind Med 2003 Aug; 44(2):197-206  In this update of a previous study the follow up of two tanneries was prolonged with the add of eleven. year period. The analysis of data show no priori cause of is significantly elevated. My study uses this study as a reference of correlation between leather product and cancer U.S. Department of Heath and Human Service,2000“Toxicological profile of Chromium” The toxicological profile describes the toxicological and adverse effects of chromium and his compounds. My study uses this monograph as a resume of knowledge about Cr(VI) UNIDO. “Formation, prevention and determination of Cr(VI) in Leather http://www.unido.org/userfiles/PuffK/overview.pdf This paper provide a short overview of recently published articles in international leather magazines. The main finding is: despite the leather tanning may be performed producing final product chromium(VI) free, it is possible that Cr(VI) can be formed in leather as consequence of storage conditions. This review is important for my study because it explain why Cr(VI) is found in finished leather products. Read More