Vinyl Chloride: Still a cause for Concern

Vinyl Chloride was first used commercially in the 1920's, but id was not until the 1930's that techniques were devised to polymerize VC into stable forms of PVC. Polymerization is a batch process and takes place in a reactor under controlled conditions. Once the polymerization has ended, VC is emptied into degassing tanks. The reactor has to be cleaned periodically because a film of PVC forms on the inside wall of the reactor. Although this is now performed with solvents or high pressure jets, this task was a manual process requiring workers to use spatulas or hammers and chisels. The workers were exposed to high concentrations of VC up to 1,000 ppm and sometimes higher peak exposures.

New aspects of VC are reported in high levels in soil, ground water, aquifers, and wells near landfills and industrial disposal sites that were not located near VC/PVC production facilities. Vinyl chloride can be formed microbially, under anaerobic conditions from reductive dehalogenation of more highly chlorinated chloroethenes. Careless handling, storage, and disposal of these chemical stable compounds have made them the most frequent encountered ground water contaminants.

Exposure of the general population to VC is possible by several routes: inhalation of air polluted with VC around production plants,ingestion of food, contaminated water, medicament packed in PVC, and absorption through skin from PVC- wrapped cosmetics.

Hemangioendothelial sarcoma of the liver (ASL) is an extremely rare liver tumor and is difficult to diagnose. ASL constitutes for only 2% of all primary tumors of the liver in the general population. Cases of ASL in VC workers could be directly attributable to exposure to VC in epidemiologic studies.

The methodology of studies was a accumulation of data by epidemiologic studies on VC/PVC workers, IPCS task groups, and Pharmacokinetic model were performed to find the effects of VC in the general population. VC has been shown to be a carcinogenic and toxic in both oral and inhalation experimental reports, as well as in human epidermiologic studies. For VC, dose response analyses have been based on data of ASL because it is the most critical and sensitive effect.

Vinyl chloride is a chemical of interest in many fields of study. Even in some parts of the world workers are still being exposed to high levels, and is known as a carcinogen. ASL is correlated only to high levels over long periods of time.

The detectionof VC as a degradation product of some chlorinated solvents is an indication of the intricate problems that may be attributed to past and future chemical waste deposits. Progress in remediation processes should be able, at least in to resolve these problems.

references: Environmental Health Perspectives. volume 108.number 7, July 2000

Wikipedia encyclopedia vinyl chloride, picture of chemical structure.

2-NAPHTHYLAMINE

2-Naphthylamine is a known human carcinogen formerly used commercially as an intermediate in the manufacture of dyes, as an antioxidant in the rubber industry, and to produce 2-chloronaphthylamine(IARC 1974, HSDB 2003)

It was First Listed in the First Annual Report on Carcinogens (1980) after sufficient evidence of carcinogenicity in humans was established. Epidemiological studies have shown that occupational exposure to 2-naphthylamine, either alone or present as an impurity in other compounds, causes bladder cancer. Studies of dyestuff workers and of chemical workers exposed mainly to 2-naphthylamine found increased risks of bladder cancer. At one of the dyestuff plants, the risk increased with increasing exposure to 2-naphthylamine, which gives us information on the dose response relationship that this toxic chemical has. In these studies, the increased risk of bladder cancer could not be explained by workers’ smoking habits (IARC 1974, 1987).

Additional Information Relevant to Carcinogenicity has also been found. 2-Naphthylamine caused genetic damage in various test systems, including mutations in bacteria, yeast, insects, plants, cultured human and other mammalian cells, and experimental animals. Other types of genetic damage observed in some of these systems included DNA strand breaks, chromosomal aberrations (changes in chromosome structure or number), micronucleus formation (a sign of chromosome damage or loss), aneuploidy (extra or missing chromosomes), sister chromatid exchange, and cell transformation (a step in tumor formation) (IARC 1987, Gene-Tox 1998). The mechanism by which 2-naphthylamine causes cancer is thought to require its metabolism to a reactive form. When arylamines, such as 2-naphthylamine, are metabolized, they can be either activated via N-hydroxylation (by cytochrome P-450 liver enzymes) or detoxified via pathways such as N-acetylation. The Nhydroxylamine metabolites can form adducts with blood-serum proteins (such as hemoglobin), which circulate freely, or they can undergo further metabolism (conjugation) to form reactive compounds that can be transported to the bladder and can bind to DNA (Yu et al. 2002). 2-Naphthylamine DNA adducts have been found in bladder and liver cells from exposed dogs (IARC 1987)

2-Naphthylamine was commercially produced in the United States from at least the early 1920s to the early 1970s. In 1955 (the latest year for which production data were found), 581,000 kg (1.3 million pounds) were produced by four manufacturers (IARC 1974). Since its commercial manufacture and use were banned in the early 1970s, 2-naphthylamine has been available only in small quantities for laboratory research. Six U.S. suppliers of 2-naphthylamine were identified in 2003 (ChemSources 2003).

The potential for exposure is low since the commercial production and use of 2-naphthylamine are banned,. The general population may be exposed through inhalation of emissions from sources where nitrogen-containing organic matter is burned, such as coal furnaces and cigarettes (HSDB 2003). Mainstream cigarette smoke from eight different U.S. conventional market cigarettes contained 2-naphthylamine at concentrations of 1.5 to 14.1 ng per cigarette (Stabbert et al. 2003); other investigators reported levels as high as 35 ng per cigarette (Hoffman et al. 1997). In sidestream smoke, a concentration of 67 ng per cigarette was reported (Patrianakos and Hoffmann 1979). 2-Naphthylamine also occurs as an impurity (0.5% or less) in commercially produced 1-naphthylamine. At greatest risk of occupational exposure to 2-naphthylamine are laboratory technicians and scientists who use it in research. Before U.S. commercial production of 2-naphthylamine and its use in the dye and rubber industries were banned, workers in these industries potentially were exposed. The National Occupational Hazard Survey (1972–1974) estimated that 420 workers potentially were exposed to 2-naphthylamine in the workplace (NIOSH 1976), and the National Occupational Exposure Survey (1981–1983) estimated that 275 workers, including 265 women, potentially were exposed (NIOSH 1984).

Guidelines for 2-Naphthylamine are as follows:

ACGIH: Threshold Limit Value - Time-Weighted Average Limit (TLV-TWA) = as low as possible

NIOSH: Listed as a potential occupational carcinogen

REFERENCES: 

1) Wikipedia, the online encyclopedia: http://en.wikipedia.org/wiki/2-Naphthylamine

2) 11th ROC - 2-Naphthylamine: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s117naph.pdf

Asbestos

Although many carcinogens have been well studied, particularly organic chemicals. Asbestos, while not being well studied appears to be a new type of carcinogen, that of particulate. Asbestos and other mineral fibers are carcinogenic to humans and animals but differ from many carcinogens in that they do not induce gene mutations. Evidence exists that asbestos is a complete carcinogen, an initiator and a promoter. Although asbestos is inactive as a gene mutagen, there is now clear evidence that it induces chromosomal mutations. Much the same as is discussed in our test on page 199, “The presence of these solid bodies creates the conditions for the transformation of normal…cells to malignancies.” From studies reported in the late 1960's and early 1970's, the chemical composition and crystallographic characteristics of asbestos are not now considered to be relevant to the carcinogenic potential of asbestos fibers. The major properties determining carcinogenic potential of asbestos fibers are their size and shape. The chemical composition has minimal relevance. It is when the cell attempts to “eat” the asbestos fiber through a process called phagocytosis that the long thin fibers essentially stab the cell, compromising the cell membranes ability to regulate calcium levels that are required for proper cellular reproduction. The presence of an inward leakage pathway for calcium caused by the presence of an asbestos fiber penetrating the cell's membrane is capable of both initiating the cell division cycle in a resting cell, and severely interfering with subsequent, calcium requiring reactions and programmed changes. Should the cell be unable to control this up-and-down progression of its internal calcium ion concentration, it would suffer from many unplanned and uncoordinated events which would be triggered out of sequence. Damage at the chromosomal level would be inevitable.
These studies of HOW asbestos induces mutations and hence cancer in cells were done in the laboratory of course. The actual human studies could very likely be biased due to the fact that only those individuals actually exposed to asbestos could develop asbestos induced cancer. Typically the only way to be exposed to asbestos is through industrial settings where asbestos is only one of many substances the workers are exposed to. Confounding, while similar to bias could also be at play in cancer development. What if some other factor is associated with the asbestos exposure? For example cutting fluid in brake manufacturing or tile cutting. Another factor that must be considered when studying asbestos as a possible carcinogen, in-vivo, is the limited sample size. There are only so many people exposed to asbestos that develop cancer where other factors can be ruled out.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1567531
http://209.85.173.132/search?q=cache:r8uvcMWbPQkJ:jhguth1942.tripod.com/sitebuildercontent/sitebuilderfiles/Mechanism_of_Asbestos_Carcinogenesis.rtf+asbestos+carcinogen&cd=11&hl=en&ct=clnk&gl=us
http://www.asbestos.net/medical-glossary/carcinogenic.html
http://www.epa.gov/ttn/atw/hlthef/asbestos.html

Vinyl Chloride

Vinyl Chloride is the key component for polymerization to polyvinyl chloride (PVC), a $19 billion/year industry. It has a rich history that dates back to 1835 however it is over the past 50 years that we have identified just how dangeous it is. Classified a a known human carcinogen, vinyl chloride is strictly monitored for airborne and waterborne exposures in the workplace and general public.

The major metabolic pathway for vinyl chloride cytochrom P-450 and the two major metabolites are choroethylene oxide and chloroacetaldehyde. Both are excreted in urine through saturable processes. Vinyl chloride must be metabolized to produce carcinogenicity and appears to be dose dependent.

The first carcinogenic effects published was from experimental research in 1971 to rats exposed to vinyl chloride. Numerous studies have followed, all focused on inhalation exposure with high positive findings from those exposed to industrial processes with high concentrations for prolonged periods of time. Most cases resulted in angiosarcoma of the liver (which is rare in the general population). In the years to follow, the International Agency for Research on Cancer (IARC) established an international study to investigate dose-response relations between liver cancer and vinyl chloride exposure. The result was increased liver cancer was clearly associated with exposure to vinyl chloride during normal time frames and unrestricted levels.

In 1981, one of the most comprehensive bioassay's was conducte targeting the ingestion of vinyl chloride. A group of 80 Sprague-Dawley rats were studied (40 male/40 female). Varying doses of vinyl chloride was administered four to five times per day for 52 weeks via gastric intubation tube and at 136 weeks, 27 liver angiosarcomas were identified in only the rats administered vinyl chloride at the 16 and 50 mg/kg body weight rate.

Another study was one ment for the silver screen. Though studies were underway identifying the possible and later confirmed health risks associated with exposure to vinyl chloride, it wasn't until 1974 the public was made aware of this. Then 10 years in what can only be coined a political move, the Chemical Manufacturers Association pushed the lead researchers to withdraw some of their findings due to a failure to obtain permission from the sponsor.

Currently, it is suggested exposure to vinyl chloride is associated with certain brain cancers. In 2000, there was a fourth study opened and the conclusion was it remains unclear. That said, vinyl chloride is one of the few chemicals listed as a known human carcinogen. The EPA requires the amount of vinyl chloride in drinking water to not exceed 0.002 mg/L of water. OSHA has set a limit of 1ppm vinyl chloride (air) in the workplace. The Food and Drug Administration monitors and regulates the amount of vinyl chloride contained in various plastics that carry food and liquids.

References:

Agency for Toxic Substances and Disease Registry (ATSDR). 2006. Toxicological Profile for Vinyl Chloride. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service. http://www.atsdr.cdc.gov/tfacts20.htm

Environmental Health Perspectives (Vol 113/No 7). July 2005. Vinyl Chloride: A Case Study of Data Suppression and Misrepresentation. http://dx.doi.org

Environmental and Workplace Health, Vinyl Chloride. 1992. http://www.hc-sc.gc.ca/ewh-semt/pubs/water-eau/vinyl_chloride/index-eng.php

Vinyl Chloride. Winkipedia. 2009. http://en.wikipedia.org/wiki/Vinyl_chloride

Carcinogenicity Bioassay of Vinyl Chloride Monomer. A model of Risk Assessment on an experimental basis. C. Maltoni. www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1568874

AFLATOXINS

Aflatoxins are a known carcinogen that first appeared in the First Annual Report on Carcinogens published in 1980 by the National Toxicology Program/U.S. Department of Health and Human Services.  At the time there were 26 chemicals listed as known human carcinogens.

Aflatoxins are a type of mycotoxin that grow in decaying vegetation when ideal conditions of high moisture content and temperature exist.  Aflatoxins grow naturally and can be found in cereals, oilseeds, spices, tree nuts, and the milk of animals that are fed contaminated feed.  A small amount (100 grams per year) is produced for research purposes.

The effects of aflatoxins are either acute or chronic.  Acute effects are hemorrhage, acute liver damage, edema, and possibly death.  Acute effects occur when moderate to high levels of aflatoxins are consumed.  Chronic effects occur due to low to moderate levels of consumption of aflatoxins and the effects are more difficult to recognize.  Some effects are impaired food conversion and slower growth rates.

All animals (including humans) are susceptible to the effects of aflatoxins, though mortality in developed countries is rare.  In fact, a laboratory worker attempted suicide by ingesting 12 ug/kg of body weight of aflatoxin per day for 2 days, and 6 months later ingested 11 ug/kg for 14 days.  The worker only suffered rash, nausea, and headache, and 12 months later a physical exam showed all body functions were normal. 

In 1974 an outbreak of aflatoxicosis due to contaminated corn occurred in India that affected 397 people, 108 of which died.  The daily amount ingested was estimated to have been 55 ug/kg of body weight for an unknown number of days.

In 1982 another outbreak of aflatoxicosis occurred in Kenya.  20 people were admitted to the hospital, 12 of whom died.  The estimated intake of aflatoxin was 38ug/kg of body weight for an unknown number of days.

Studies and research

In one study, 7% of monkeys given aflatoxin B1 for over 2 years developed liver cancer.  Another study showed what could be considered safe levels of aflatoxin by exposing liver tissues to aflatoxins B1 and M1.  Using the HPLC method, results showed that at the level of .71 mg/100grams for aflatoxin B1 and 1.1  mg/100 grams of M1, some contamination was present but not at a toxic level. 

Statistical research done on aflatoxic rates in areas with high incidences of hepatitis B should take into account possible confounding due to the carcinogenic effect both have on the liver.  Many of the underdeveloped areas in which exposure to aflatoxin from contaminated foods is common also have a high rate of hepatitis B.  However, even when taking into account the effect of hepatitis B on the liver, there was a high association of aflatoxin and liver cancer.

Chemical structure and properties of aflatoxins

18 different types of aflatoxins have been identified.  They are divided into two categories based on their chemical structure – see images for which group some of the more common types fall into.

Aflatoxins are destroyed with bleach or by autoclaving with ammonia.  They will not be destroyed by cooking and food preparation.  Aflatoxins are slightly soluble in water, soluble in moderately polar organic solvents, and insoluble in nonpolar solvents.  They are unstable in UV light, pH below 3 or above 10, and when exposed to oxidizers.   

Sources:
http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s006afla.pdf
National Toxicology Program – Department of Health and Human Services Substance Profiles

http://www.cfsan.fda.gov/~mow/chap41.html
US Food and Drug Administration – Center for Food Safety and Applied Nutrition

http://www.ncbi.nlm.nih.gov/pubmed/63557
 J Natl Cancer Inst.CARCINOGENICITY OF AFLATOXIN B1 IN RHESUS MONKEYS: TWO ADDITIONAL CASES OF PRIMARY LIVER CANCER.

http://www.jmedcbr.org/archives/CBMTSIII/cbmts3-37.pdf
Journal of Medical Chemical, Biological and Radiological Defense                                                  DETERMINATION OF AFLATOXINS BL AND ML IN CHICKEN LIVER BY HPLC

http://www.aflatoxin.info/aflatoxin.asp
PROPERTIES OF AFLATOXIN AND IT PRODUCING FUNGI

Vinyl Chloride

A Summation of IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 97, 1,3-Butadiene, Ethylene Oxide and Vinyl Halides (Vinyl Fluoride, Vinyl Chloride and Vinyl Bromide).

Background: The International Agency for Research on Cancer (IARC) was created in 1965 by the World Health Organization (WHO). Since their inception, the IARC constantly “…received requests for advice on the carcinogenic risk of chemicals, including requests for lists of known and suspected carcinogens” (IARC, 2008, p. 9).
Thus, in 1970, the IARC Governing Council determined that the IARC will provide government authorities with expert scientific opinion on carcinogenesis. The Governing Council’s determination led to the development of the IARC Monographs on the Evaluations of Carcinogenic Risks to Humans.

The multiple volumes of monographs are used by government authorities worldwide for making risk assessments, deciding preventive measures, and providing cancer control programs (IARC, 2008). A working group of experts publish the monographs after a critical review process and evaluation of evidence on the carcinogenicity of human exposure to an agent. An evaluation of an agent is based on scientific findings of evidence from extensive studies in humans and experimental animals. The agent is categorized and set to a criterion of the following groups:

Group 1: The agent is carcinogenic to humans. Meaning there is sufficient evidence of carcinogenicity in humans or less the sufficient in humans but sufficient in experimental animals and strong evidence in exposed humans.

Group 2A: The agent is probably carcinogenic to humans. Meaning there is limited evidence of carcinogenicity in humans and sufficient in experimental animals.

Group 2B: The agent is possibly carcinogenic to humans. Meaning there is limited evidence of carcinogenicity in humans and less than sufficient in experimental animals.

Group 3: The agent is not classifiable as to its carcinogenicity to humans. Meaning there is inadequate evidence of carcinogenicity in humans and inadequate or limited in experimental animals.

Group 4: The agent is probably not carcinogenic to humans. Meaning there is evidence suggesting lack of carcinogenicity in humans and in experimental animals.

Introduction: The IARC Monograph Vol. 97 classified Vinyl Chloride as a Group1 agent, “Carcinogenic to Humans.” Vinyl chloride is used for making Polyvinyl Chloride (PVC) and PVC resin is used primarily for the production of plastics for consumer and industrial products. Vinyl chloride is produced worldwide and has been in production in the U.S. for over 70 years. The primary route of occupational exposure is inhalation which normally occurs at vinyl chloride and PVC production plants. The IARC Monograph, Table 4 displays workplace exposure levels in the U.S. as followed: CGIH TWA = 1 ppm; OSHA PEL = 1 ppm and STEL = 5 ppm (IARC, 2008, p. 322).

Overview: Studies of cancer in humans for vinyl chloride were highlighted in a 1974 case report from the Journal of Occupational Medicine. The report identified an extremely rare tumor (angiosarcoma) of the liver which had developed in three men who had worked in a PVC resin manufacturing plant. Since then, several cohort studies have been conducted which include two epidemiological multicentric investigations of workers employed in the vinyl chloride industry. One epidemiological study was conducted in Europe and one in North America. The following link is the outline of data on the studies of cancer in humans: http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8B.pdf

The initial North American multicentric study included 10,173 workers from 37 plants. Eligible study participants were male employees who were exposed to vinyl chloride for at least one year and who worked at the plants from 1942 – 1972. A second follow-up study was conducted with statistics through 1989 (with original 10,173 participant data) and a third major update (after minor corrections to study records, included 10,109 of the test subjects). The IARC Monograph, Table 5 displays the data of the cohort studies of liver and biliary tract cancer in vinyl chloride production workers (IARC, 2008, p. 333). Additionally, Table 7, displays the data of the cohort studies of brain and central nervous system (CNS) cancer (p. 350); Table 8, data of cohort studies of lung cancer (p. 356); Table 10, data of lympho-haematopoietic neoplasms (p. 366); and Table 11, data of cohort studies of malignant melanoma (p. 370).

A case-study of focused on a vinyl chloride processing plant in Louisville, KY and observed 2,200 workers who had been exposed to vinyl chloride for at least one year from 1942 – 1972. A follow-up study was conducted to include data through 1995. The IARC Monograph, Table 5 included statistics for this case-study as Table 6, displays the data of the case-control study of liver cancer (p. 346); and Table 9, data of case-control studies of lung cancer (p. 362).

The European multicentric study was conducted in four countries (Italy, Norway, Sweden and the U.K.). The initial multicentric study included 12,700 workers from 19 plants. Eligible study participants were male employees who were exposed to vinyl chloride for at least a year and who worked at the plants from 1950 – 1985. A follow-up study was conducted with statistics from 1955 – 1997.

Extensive studies in experimental animals have also been conducted. The following link is the outline of the data on the studies of cancer in experimental animals: http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8C.pdf

Summation: Data conclusions of all the studies were based on a standardized mortality ratio (SMR) compared to state reference rates. The results of the North American multicentric cohort study, revealed alarming SMR results. The SMR for liver and biliary tract cancer was relatively high at 3.59; well above the nominal rate (1.0) since death from liver cancer was not expected to be above 23 and 80 deaths occurred among the 10,109 subjects. On the other hand, the SMR for lung cancer was 0.82, since death from lung cancer was anticipated even though 303 deaths were observed. The SMR for brain and CNS cancer was 1.42 (36 deaths); SMR for lympho-haematopoietic neoplasms was 0.86 (71 deaths); and SMR for malignant melanoma was 0.64 (12 deaths).

The results of the Louisville, KY case-study revealed the SMR was 4.00 for liver and biliary tract cancer (24 deaths opposed to 6 expected). The IARC Monograph stated,
“The occurrence of angiosarcoma was strongly associated with exposure to vinyl chloride but not with exposure to other chemicals; the risk for brain cancer was highest among workers who had been hired before 1950 but was not associated with exposure to vinyl chloride” (p.325).

The results of the European study revealed the SMR was 2.40 for liver cancer (53 deaths); SMR was 0.93 for brain cancer (24 deaths); SMR was 0.95 for lung cancer (272 deaths); and SMR for lymphatic and haematopoeitic cancer was 0.94 (62 deaths).

Metabolic Pathway: Vinyl chloride is primarily metabolized in the liver as an oxidation reaction. The mediated oxidation is catalyzed by the enzyme cytochrome P450. A Phase I mixed function oxidase occurs during biotransformation of vinyl chloride in the liver to form the highly reactive chloroethylene oxide which then spontaneously rearranges to chloroacetalhyde and both metobolites will bond to DNA and RNA. The following link is the outline for mechanistic and other relevant data: http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8D.pdf

Conclusion: The IARC Monograph, Volume 97 highlights the sufficient epidemiological evidence from the two multicentric cohort studies that identifies vinyl chloride has a Group 1 agent, “Carcinogenic to Humans.” The IARC Monograph Chapters 5 and 6 outline the summary of data and the evaluation of vinyl chloride. The following link is for Ch. 5 & 6 respectively: http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8E.pdf
http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8F.pdf

Reference:
International Agency for Research on Cancer (IARC). (2008). Vinyl Chloride. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 97, 1,3-Butadiene, Ethylene Oxide and Vinyl Halides (Vinyl Fluoride, Vinyl Chloride and Vinyl Bromide). Retrieved March 23, 2009 from: http://monographs.iarc.fr/ENG/Monographs/vol97/mono97-8.pdf, a link retrieved from: http://monographs.iarc.fr/

Vinyl Chloride

This is a brief look at Vinyl Chloride. It was first reported in 1974, in open scientific literature, that vinyl chloride induces angiosarcoma of the liver in human beings and animals. As of 1983, additional research has demonstrated the carcinogenicity of vinyl chloride to other organs at lower concentrations.

In 1971, 44 years after vinyl chloride was introduced into American commerce, Dr. P.L. Viola reported the induction of tumors of the skin, lung, and bone in rats exposed by inhalation of 30,000 PPM of vinyl chloride but warranted little response because of the testing at the unrealistically high dosage. Methods of testing included exposing male albino rats (about 150 g body weight) to vinyl chloride vapors for 4 hours a day, 5 days a week, for 12 months, in a box with a constant flow of air containing 3% or 30,000 PPM of vinyl chloride.

Later that same year Dr. Viola presented to several US companies, unpublished findings of an increased incident of tumors in rats that were exposed to vinyl chloride at concentrations down to and including 500 PPM.

Hundreds of other experiments carried out through the 1970s had similar finding for vinyl chloride. In 1979, IARC concluded, “Vinyl Chloride is a human carcinogen. Its target organs are the liver, brain, lung, and haemo-lymphopoietis system.”

Vinyl Chloride can be commonly found. It is used to make pvc pipe, plastic automotive parts, furniture, medical supplies and the list goes on and on.

The OSHA Permissible Exposure Limit (PEL) for General Industry: 29 CFR 1910.1017 - Vinyl Chloride = 1 ppm TWA; 0.5 ppm Action Level. Vinyl chloride exposure route is mainly inhalation.


Structure is trigonal because there are only 3 atoms attached to the carbon.
The rotation is restricted because of the double bond.
The geometry is planar.
Bond Angle is 120 degrees
Bond length is 1.34 Angstroms or 1.34 x 10-8 centimeters long.




References

Hart, H., Craine, L. E., & Hart, D. J. (1999). Organic chemistry (10th ed.). Boston, New York: Houghton Mifflin Company.

Viola, P. L., Bigotti, A., & Caputo, A. (1971). Oncogenic response of rat skin, lungs, and bones to vinyl chloride. Cancer Research, 31, 516-522. Retrieved from http://cancerres.aacrjournals.org.ezproxy1.lib.asu.edu/cgi/reprint/31/5/516

Wagner, J. K. (1983). Toxicity of vinyl chloride and poly(vinyl chloride): A critical review. Environmental Health Perspectives, 52, 61-66. Retrieved from http://www.ehponline.org/members/1983/052/52009.PDF

Benzidine

BENZIDINE MOLECULE
Source: http://www.steve.gb.com/images/molecules/amines/benzidine.png

4’4’-diaminobiphenyl, commonly know as Benzidine, is an aromatic amine utilized for the production of fabric, paper and leather dyes. Benzidine is a manufactured chemical that does not occur naturally. In the environment, this chemical may be found as an organic base or as a salt. Production of Benzidine in the US was discontinued in the 1970s. However, larger quantities of the chemical had already been dumped in water sources and soils for a long time. Benzidine attaches easily to soil particles, and when in water sources it sinks to the bottom and found in the silt, mud and soil. The general population is not at great risk of Benzidine exposure, except for residents of contaminated areas (water and soil). Children are at risk of exposure to Benzidine only if they come into contact with contaminated media.

An increased incidence of cancer of the urinary bladder was first associated with human occupational exposure to dyes and dye chemicals manufacturing in 1895. These tumors, initially referred to as aniline cancers because of the extensive use of aniline in dye chemistry, were attributed to exposure to either the starting materials or to the finished dyes. Benzidine was identified as a carcinogen for the human urinary bladder in 1973 (National Toxicology Program 1994). Benzidine exposure effects on human health do not initiate until they have been bioactivated in the body.

Exposure to Benzidine occurs mainly through ingestion and inhalation. Dermal contact to the substance is said to cause allergic eczematous dermatitis, although extensive research of the effects of exposure via this route has not been carried out. Ingestion and inhalation were determined to be the main routes of exposure because most of the dye factory workers that showed severe health effects came into contact with Benzidine in that manner. Once proper industrial hygiene measures were put in place at these factories, harmful health effects diminished. Ingestion effects were identified when Kimono hand painters in Japan who wetted the paintbrushes with saliva by putting them in their mouth, later developed bladder cancer.

Extensive bioassays have been carried out for decades with mice, rats, hamsters and dogs, the results of which vary considerably according to the test species. On mice, rats and hamsters Benzidine exposure indicates liver and mammary malign carcinogenicity. On dogs, same as in humans, urinary bladder cancer was identified. Human exposure conclusions have been derived from actual exposure cases in the US, Europe and Japan.

The IARC identified the following cases of human exposure:

- Dyestuffs factory in Italy, it was possible to distinguish a very high bladder cancer risk (5 deaths observed, 0.06 expected) associated with benzidine production. The study was extended and updated, but the role of exposure to benzidine alone in the dramatically increased bladder cancer risk could not be examined further.
- Of 25 benzidine 'operators' at a plant in the USA, 13 developed bladder cancer; all cases had been exposed for six years or more. Other investigations have shown high incidences of cancer of the bladder and urinary tract after concomitant exposure to benzidine and 2-naphthylamine. Exposure to these two compounds was also associated with an increase in the occurrence of second primary cancers at sites other than the bladder, including the liver.
- Among 1601 workers in the chemical-dye industry in China who were exposed to benzidine, methylnaphthylamine and dianisidine 21 cases of bladder carcinoma were found. All had a history of exposure to benzidine, while no carcinoma was found among workers exposed to methylnaphthylamine or dianisidine. Suggestions of a dose response relationship were provided by analysis according to length of exposure.

The EPA Summary of Risk Estimates explains:

Oral Slope Factor — 2.3E+2 per mg/kg-day
Drinking Water Unit Risk — 6.7E-3 per ug/L
Extrapolation Method: One-hit with time factor, extra risk
Drinking Water Concentrations at Specified Risk Levels:

Risk Level Concentration
E-4 (1 in 10,000) 2E-2 ug/L
E-5 (1 in 100,000) 2E-3 ug/L
E-6 (1 in 1,000,000) 2E-4 ug/L

(Source: http://www.epa.gov/iris/subst/0135.htm)

In summary, Benzidine was established as a known human carcinogen in 1973 after its production had been discontinued. Human cases as well as bioassays have been carried out extensively to provide proof of the human health effects caused by the chemical. Carcinogenicity varies according to species, but in humans urinary bladder cancer occurs after long-term exposure via ingestion or inhalation takes place.

Sources:

-Morgan, Dunnick et al (1994). Summary of the National Toxicology Program Benzidine Dye Initiative. National Institute of Environmental Health Services. North Carolina. Source: http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1567082&blobtype=pdf

- Josephy, David (1985). Oxidative Oxidation of Benzidine and its Derivatives by Peroxidiases. Environmental Health Perspectives. Source: http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1568598&blobtype=pdf

- US Environmental Protection Agency (1987). Benzidine. Source: http://www.epa.gov/iris/subst/0135.htm

- US Environmental Protection Agency (1987). Benzidine Hazard Summary. Source: http://www.epa.gov/ttn/atw/hlthef/benzidin.html

- Agency for Toxic Substances and Disease Registry (2001). Benzidine ToxFAQs. Source: http://www.atsdr.cdc.gov/tfacts62.pdf

- Agency for Toxic Substances and Disease Registry (2001). Toxicological Profile for Benzidine. Source: http://www.atsdr.cdc.gov/toxprofiles/tp62.pdf

- Vesselinovitch S.D., Rao K., and Mihailovich N. (1975). Factors Modulating Benzidine Carcinogenicity Bioassay. Cancer Research 35, 2814-2819. Source: http://cancerres.aacrjournals.org/cgi/reprint/35/10/2814

- International Agency for Research on Cancer. Benzidine Monograph. Source: http://monographs.iarc.fr/ENG/Monographs/suppl7/Suppl7-25.pdf

Benzene

Benzene is an aromatic hydrocarbon with chemical formula C6H6. It is used as an organic solvent and as a starting and intermediate material in the production of many synthetic products. First derived from coal tars in the mid 1800’s, benzene has been produced from petroleum since the late 1950’s. (11th, 2009)



image downloaded from wikipedia: http://en.wikipedia.org/wiki/File:Benz1.png

Benzene is classified as a known human carcinogen by the EPA, IARC and NTP. In 1980 benzene was listed in the the National Toxicology Program’s First Annual Report on Carcinogens. (NTP) Benzene is a bone marrow suppressant. The effects of benzene on bone marrow can range from mild and reversible to deadly. The main cancer associated with long term exposure to high levels of benzene in the air is acute myelogenous leukemia: AML. (Toxfaqs, 2007)

Although benzene is listed as the carcinogenic agent, it is actually the metabolites of benzene that are the actual culprits in the suppression of and damage to bone marrow. Benzene is first metabolized in the liver via cytochrome P450 to benzene oxide. Benzene oxide is then converted to a number of metabolites such as phenol, hydroquinone, muconic acid, muconaldehyde, catechol, and trihydroxy benzene. Hydroquinone and muconaldehyde can interfere at many points with the production of blood in the bone marrow. This inefficient production of red blood cells can lead to several blood disorders ranging from anemia to preleukemia and if unchecked, leukemia. Once in the bone marrow, phenolic metabolites of benzene can be further metabolized to form free radicals. These free radicals have the ability to damage bone marrow and lead to cancer, namely AML. (Williams et al., 2000, pp. 102-103)

The population most at risk for adverse health effects from benzene are those who are exposed to benzene in industrial settings. The hematotoxic effects of benzene, including benzenes causal role in AML, have been well documented in several case studies the most notable being the Ohio Pliofilm workers of the 1940’s and 1950’s. The pliofilm fim cohort is of significant importance because the work histories of the workers was well documented, workers were minimally exposed to other carcinogenic chemicals (thus reducing confounding) and the workers were exposed to a wide range of benzene levels. (Toxicological, 2007)

Pliofilm is a thin transparent sheet of chlorinated rubber used for packaging that was produced by the Goodyear Tire and Rubber Company at three different plants in Ohio throughout the twentieth century. Benzene was used on the “wetside” of the plant in the precasting phase of Pliofilm production. Those who worked on the “wetside” part of production were the ones who had direct exposure to benzene and included in the study. Initial results were published in 1987 with a followup based on six years of additional data published in 1996. (Paxton, 1996)

The following table (Paxton, 1996) compares the findings between the two:



As can be seen by the results, the observed noncancer deaths from nonmalignant diseases of the blood and blood forming organs (bone marrow) did not change from 1981to 1987. However, what is significant about the data is that the expected deaths from noncancer blood disorders were 4.65 (1981) and 3.31(1987) times higher for those exposed to benzene than for those who were not. This data is supportive of the noncancerous hematotoxic effects of benzene.
Observed total cancer deaths for 1981 (72) were not statistically higher than the expected deaths (70.88) as can be seen in the Standard Mortaility Ratio of 1.02. However, it is when the deaths are broken down by types of cancer that a suspected role of benzene in the development of hematological malignacies becomes apparent. Fifteen deaths from lymphatic and hematopoietic cancers were observed compared to 6.93 expected with a Standard Mortaility Ratio of 2.16 and a Confidence Interval of 1.21-3.57 (95%). Of the other cancers listed, only male genital organs and “other and unspecified” types of cancers had higher observed than expected rates. However, in both incidents, the range of Confidence Intervals included 1 which indicate that exposure to benzene could not be statistically linked one way or another to these results.

Six years later, once again it is when the deaths from cancer are broken down by type that the observed deaths (21) from lymphatic and hematopoietic cancers far exceed the expected deaths (9.51). The Standard Mortality Ratio is slightly higher at 2.21. The 95% Confidence Interval is slighlty narrower (ranging from 1.37-3.38) bolstering the credibility of the data from 1981.


References:

11th Report on Carcinogens: Benzene. (2009, February 13). Retrieved March 19, 2009, from National Toxicology Program Department of Health and Human Services website: http://ntp.niehs.nih.gov/index.cfm?objectid=32BA9724-F1F6-975E-7FCE50709CB4C932

Paxton, M.B. (1996, December). Leukemia risk associated with benzene exposure in the pliofilm cohort. Environmental Health Perspectives, 104 (6), 1431-1436. Retrieved March 19, 2009, from PubMed Central: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1469754

ToxFAQs for benzene. (2007, October 5). Retrieved March 19, 2009, from Department of Health and Human Services Agency for Toxic Substances and Disease Registry website: http://www.atsdr.cdc.gov/tfacts3.html

Toxicological profile for benzene. (2007, August). Retrieved March 19, 2009, from Agency for Toxic Substances and Disease Registry website: http://www.atsdr.cdc.gov/toxprofiles/tp3.pdf

Williams, P. L., James R. C., Roberts, S. M., (2000). Principles of toxicology, 2nd edition. United States of America: John Wiley & Sons, Inc.

Vinyl Chloride

Vinyl chloride is an organic compound widely used in a number of industries. The most common use being the production of PVC pipe and material. Due to it’s boiling point of -13°C, at room temperature it is a gas easily detectable by it’s distinct sweet odor. On combustion it produces several gases including carbon monoxide, carbon dioxide, hydrogen chloride and small amounts of phosgene. (Health 2001) OSHA regulations limit the permissible exposure limit (PEL) to 1ppm as an 8 hour time weighted average and a 5ppm ceiling for any 15 minute period.
Research into the health effects of vinyl chloride has been ongoing for many years. Due to it’s known toxicity and carcinogenic effects most of the studies were done on groups who had previous exposure, primarily workers in the chemical and PVC industries. Other studies were conducted on animal subjects which allowed more control over the exposure method, time and dose.
In determining the carcinogenicity of vinyl chloride two methods were primarily used, ingestion studies and inhalation studies. These studies used various doses and time spans to determine carcinogenicity. In these studies vinyl chloride was shown to cause tumors in a dose related manner at several sites including liver, lung and mammary glands. The response appears as a function of a number factors including site, chemical concentration, test subject and route of exposure. (Assessment 2000) One study exposed rats of various ages to identical levels of vinyl chloride. Rats and mice were exposed at 8 weeks, 6 months or 1 year of age. The subjects exposed at 8 weeks showed decreased survival rates while the 2 other groups showed no decrease in survival rates. (Assessment 2000)
The studies of human subjects have not been as controllable due to the known toxicity of vinyl chloride. Because of factors such as lifestyle and genetics there may be other factors contributing to the carcinogenicity of vinyl chloride. Alcohol use and aflatoxins have both been shown to cause liver damage but cannot be controlled in human study groups to the degree animal studies allow.


References

Agency, Environmental Protection. Vinyl Chloride TEACH Chemical Summary. 10 1, 2007. http://www.epa.gov/teach/chem_summ/VC_summary.pdf (accessed 03 19, 09).
Assessment, Office of Environmental Health Hazard. Public Health Goals for Chemicals in Drinking Water. 10 01, 2000. http://www.oehha.ca.gov/water/phg/pdf/vinylch.pdf (accessed 03 19, 2009).
Diseases, Agency for Toxic Substances &. Toxicological Profile. July 1, 2006. http://www.atsdr.cdc.gov/toxprofiles/tp20.html#bookmark11 (accessed 03 19, 2009).
Health, National Institute of. Vinyl Chloride. 10 07, 2001. http://www.mindfully.org/Plastic/Vinyl-Chloride-9thROC.htm (accessed 03 19, 2009).
Services, New Jersey Department of Health and Senior. Hazardous Substance Fact Sheet. 12 01, 2001. http://nj.gov/health/eoh/rtkweb/documents/fs/2001.pdf (accessed 03 1, 2009).

Vinyl Chloride

4-Aminobiphenyl

4-Aminobiphenyl

CAS number
92-67-1
Molecular formula
C12H11N
Molar mass
169.22 g mol−1

4-Aminobiphenyl is a derivative of biphenyl. It is used to manufacture azo dyes. It is a known human carcinogen and so it has been largely replaced by less toxic compounds. It is similar to benzidine.

Because of its carcinogenic effects, 4-aminobiphenyl has not been produced commercially in the United States since the mid 1950s, and is used only for research purposes. Since 4-aminobiphenyl was reviewed for listing in the First Annual Report on Carcinogens, most research on its carcinogenicity has focused on exposure from cigarette smoking. Epidemiological studies have reported the incidence of bladder cancer to be 2 to 10 times as high among cigarette smokers as among nonsmokers. Higher levels of 4-aminobiphenyl adducts (4-aminobiphenyl metabolites bound to DNA or protein) were detected in bladder tumors (DNA adducts) and red blood cells (hemoglobin adducts) from smokers than from nonsmokers (as reviewed by Feng et al. 2002).

In a case-control study, levels of 4-aminobiphenyl hemoglobin adducts were higher in smokers with bladder cancer than in a control group of similarly exposed smokers (Del Santo et al. 1991). A Taiwanese study reported that 4-aminobiphenyl hemoglobin adducts were associated with increased risk of liver cancer (Wang et al. 1998).

There is sufficient evidence for the carcinogenicity of 4- aminobiphenyl in experimental animals as demonstrated by studies showing that 4-aminobiphenyl causes cancer in rats, mice, rabbits, and dogs. When administered orally, 4-aminobiphenyl caused bladder tumors in rabbits and dogs and dose-related incidences of angiosarcoma (blood-vessel tumors), liver tumors, and bladder tumors in mice. When administered to rats by subcutaneous injection, 4-aminobiphenyl caused mammary-gland and intestinal tumors (IARC 1987).

Mainstream cigarette smoke was reported to contain 4-aminobiphenyl at levels of 2.4 to 4.6 ng per cigarette (unfiltered) and 0.2 to 23 ng per cigarette (filtered), and sidestream
smoke to contain up to 140 ng per cigarette (Patrianakos and Hoffmann 1979, Hoffman et al. 1997).

Health Factors

NTP: Human Carcinogen

IARC: Group 1, carcinogenic to humans (4-Aminobiphenyl)

SYMPTOM(s): Headaches, lethargy, dizziness; dyspnea; ataxia, weakness; methemoglobinemia; urinary burning; acute hemorrhage cystitis, (carcinogenic)

HEALTH EFFECTS: Cancer---Currently regulated by OSHA as carcinogen; chiefly work practice standards (HE1) LD50 (oral, rat) 500 mg/kg

SKIN ABS: Yes

ORGAN: Bladder, skin

http://www.osha.gov/dts/chemicalsampling/data/CH_218100.html

Detection limits are 10.5 fg/injection . These are the amounts of each analyte that will produce peaks with heights that are approximately five times the baseline noise.

The dose-response relationship for 4-Aminobiphenyl is sigmoidal or hockey-stick shaped. That is, responses are seen at the higher levels. For example, incidences of angiosarcomas and liver tumors were significantly higher at the three highest level doses when mice were treated with drinking water contaminated with 4-Aminobiphenyl.

Recent information is becoming available also that 4-Aminobiphenyl can also contribute to breast cancer. A recent study done in 2003 showed that smoking is associated with increased levels of 4-ABP–DNA adducts in human mammary tissue, or increased risk of breast cancer. (Faraglia et all, 2003)

References

Del Santo, P., G. Moneti, M. Salvadori, C. Saltutti, A. Delle Rose and P. Dolara. 1991. Levels of the adducts of 4-aminobiphenyl to hemoglobin in control subjects and bladder carcinoma patients. Cancer Lett 60(3): 245-51.

Evaluation of 4-aminobiphenyl-DNA adducts in human breast cancer: the influence of tobacco smoke, Beatrice Faraglia, Shu Yuan Chen, Marilie D. Gammon, Yujing Zhang, Susan L. Teitelbaum, Alfred I. Neugut, Habibul Ahsan, Gail C. Garbowski, Hanina Hibshoosh, Dongxin Lin, Fred F. Kadlubar and Regina M. Santella, Carcinogenesis, Vol. 24, No. 4, 719-725, April 2003 Oxford University Press.

Feng, Z., W. Hu, W. N. Rom, F. A. Beland and M. S. Tang. 2002. 4-aminobiphenyl is a major etiological agent of human bladder cancer: evidence from its DNA binding spectrum in human p53 gene Carcinogenesis 23(10): 1721-7.

IARC. 1987. Overall Evaluations of Carcinogenicity. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, Supplement 7. Lyon, France: International Agency for Research on Cancer. 440 pp.

Wang, L. Y., C. J. Chen, Y. J. Zhang, W. Y. Tsai, P. H. Lee, M. A. Feitelson, C. S. Lee and R. M. Santella,1998. 4-Aminobiphenyl DNA damage in liver tissue of hepatocellular carcinoma patients and controls. Am J Epidemiol 147(3): 315-23.

Vinyl Chloride

Vinyl Chloride
By Dan South

Vinyl chloride is classified by the U.S. Environmental Protection Agency (USEPA) as a Class A - known human carcinogen, but how did it get so classified and why? It is a widely used chemical, being critical in the production of polyvinyl chloride (PVC). Unfortunately, it is a powerful carcinogen that many people are exposed to every day. Having been around for many years and used so commonly, vinyl chloride is a relatively well-studied and well-understood chemical compound.

Vinyl chloride was first produced in the 1920’s, but became widely used after the introduction of PVC in the 1930’s (Kielhorn, 2000). Since then, its production has grown tremendously until approximately 15 billion pounds were reported produced in the United States in 1995 (ATSDR, 2009). Its primary use remains in the production of PVC, although it is also used in the production of other chlorinated solvents such as 1,1,1-trichloroethane (Kielhorn, 2000). It is also found in groundwater as a breakdown product of these chlorinated solvents at sites such as industrial facilities and landfills where the contaminants have been released to the aquifers (Kielhorn, 2000).

Vinyl chloride, with molecular weight 62.5 grams per mole, is a sweet-smelling, colorless gas at room temperature and 1 atmosphere of pressure. The chemical formula for this chlorinated solvent is C2H3Cl.

The carcinogenicity of vinyl chloride has been established through both human cohort studies and animal testing (USEPAIRIS, 2009). The data from these two systems agrees quite well.
Several independent studies of cohorts of workers in PVC plants have documented significant increases in rates of angiosarcoma, a rare cancer of the liver lining, and less commonly, cancers of the brain and lung for people exposed to vinyl chloride. The USEPA IRIS document at http://www.epa.gov/iris/subst/1001.htm goes into great detail about these different studies. A brief overview of the findings, however, is in order. The first clear linking of vinyl chloride to liver cancer came in 1974 when scientists named Creech and Johnson studied workers in a PVC plant (USAEPAIRIS, 2009). They found an unusually high number of incidents for a very rare form of cancer (angiosarcoma). Since then other studies throughout the world have found the same results, confirming the link. Always, the most common cancer linked to vinyl chloride is angiosarcoma. These studies are considered reliable by USEPA because the methods were well-documented and the cohort sizes were generally large. The size of the cohorts ranged from hundreds to more than 7,000 in one German study (USEPAIRIS, 2009).

With possible links to cancer in humans reported, the next step was to conduct testing on animals. Tests have been conducted on Wistar rats as well as Sprague-Dawley rats that have resulted in significant increases in liver and other cancers by both ingestion and inhalation delivery methods. These results were confirmed with other species including mice and hamsters. As with the human studies, the sample sizes for these animal experiments were appropriate. The USEPA rated the different studies to assess the quality of the data. For example it reports:
“Confidence in the study of Til et al. (1983, 1991) is high because it used adequate numbers of animals, was well controlled, and reported in detail on the histological effects on the liver. Bi et al. (1985) and Sokal et al. (1981) both give corroborative information on liver effects following inhalation exposure. Because of the close similarity of the pharmacokinetics via the inhalation and oral routes and the use of a PBPK model, inhalation data can be used to fill gaps in the inhalation database and vice versa” (USAEPAIRIS, 2009).

These tests included different methods of delivering the vinyl chloride. Some studies used inhalation for exposure, others used ingestion. For the ingestion exposures, the scientists mixed very specific amounts of the chemical in the form of PVC in the food or water for the test subjects. Being long-term studies, the researchers generally used doses well below the level that causes significant effect such as 0.014 mg VC/kg bw/day to 14.1 mg VC/kg-day. At least one study exposed Sprague-Dawley rats to 0, 1, 5, 10, 25, 50, 100, 150, 200, 250, 500, 2500, 6000, or 10,000 ppm VC by inhalation for 4 hours/day, 5 days/week for 52 weeks to see if the number of tumors was concentration dependent (USAEPAIRIS, 2009). He concluded that it was.

The primary exposure route for humans for vinyl chloride is through inhalation (ATSDR, 2007). A secondary, but much less significant route of exposure is through ingestion of contaminated well water.

Vinyl chloride is rapidly and well absorbed after inhalation or oral exposure (UN World Health Organization, 1999). In studies of both animals and humans, under steady-state conditions, it was calculated that approximately 40% of inspired vinyl chloride is absorbed after exposure by inhalation. Animal studies indicated that more than 95% of vinyl chloride was absorbed after oral exposure (UN World Health Organization, 1999). Absorption of vinyl chloride in the gaseous state through the skin is not significant when compared to the amount entering the body from inhalation (UN World Health Organization, 1999). Prior to 1974 and the establishment of tighter standards, workers in the plastic industry were the population most at risk for exposure to vinyl chloride. Currently with the existing PEL in place, exposure to workers and nearby residents in the United States and Western Europe is low. In less developed countries, however, such as China and Croatia, residents and neighbors of facilities have been shown to have been exposed to excessive levels of airborne vinyl chloride (Kielhorn, 2000).

The USEPA IRIS document has dose-response data for ingestion and inhalation routes of entry that do not copy well to the blog. I encourage you to view them at: http://www.epa.gov/iris/subst/1001.htm
There is a 1 in 10,000 chance that someone exposed to 2.4 micrograms per liter per day since birth to vinyl chloride will develop cancer.

Results from several studies on the metabolism of vinyl chloride by rats indicate that the primary route of metabolism is believed to be by Cytochrome P450 (Reitz, 1996). The Phase I reaction oxidizes vinyl chloride to chloroethylene oxide (C2H3ClO). This highly reactive epoxide is inherently unstable and reforms to 2-chloroacetaldehyde (C2H3ClO) (Reitz, 1996 and Kielhorn, 2000). These two metabolites are further metabolized through a phase II process of conjugation binding with glutathione (Reitz, 1996) resulting in excretion through the urine (Reitz, 1996). Two of the urinary metabolites are N-acetyl-S-(2-hydroxyethyl)cysteine and thiodiglycolic acid (Reitz, 1996). The metabolism of a person can be saturated with high enough concentrations (~3000 parts per million according to Reitz, 1996) that the body then eliminates the compound in other ways, especially through exhalation of the parent compound (Reitz, 1996).

The mechanism for carcinogenicity of vinyl chloride again involves the metabolites chloroethylene oxide and chloroacetaldehyde. These short-lived, highly reactive compounds are believed to react with the body’s deoxyribonucleic acid (DNA) which leads to a mistranscription during cell division (Reitz, 1996). This causes a loss of information for the daughter cell. The major DNA adduct induced by vinyl chloride reportedly was 7-(2-oxoethyl)guanine (Bolt, 2005). However, 7-(2-oxoethyl)guanine is not mutagenic and it may be lesser adducts that cause the miscoding (Dogliotti, 2006). It is proposed that these mutations on the tumor-suppressor genes prevent the body from opposing the growth of tumors (Bolt, 2005).

Due to its carcinogenic nature, the permissible exposure limit (PEL) from the Occupational Health and Safety Administration (OSHA, 2009) is 1 part per million (ppm) per 8 hour period. The short term exposure limit (STEL) for vinyl chloride is 5 ppm per 15 minute period (OSHA, 2009). Since the odor of vinyl chloride becomes detectable at approximately 3,000 ppm, the odor threshold is too high to be of use (ATSDR, 2009). If a person can smell vinyl chloride, then that person has already been exposed above the PEL. As with the PEL, the carcinogenic nature of vinyl chloride has caused the maximum contaminant level (MCL) in drinking water set by the USEPA to be very low. The MCL for vinyl chloride is 0.002 milligrams per liter (mg/L) (USEPA, 2009).

We have learned a lot about vinyl chloride from both human case studies of workers exposed to the compound as well as well-documented, carefully controlled animal studies. Each source of information adds to the overall understanding of how this powerful carcinogen damages the body. Hopefully the study of vinyl chloride can serve as a guide for the study of other potential carcinogens.

References
Bolt, H.M., (2005), Vinyl chloride-a classical industrial toxicant of new interest. Critical Reviews in Toxicology, v.35(4):307-323

Environmental Protection Agency . (2009). "Environmental protection agency drinking water standards". Retrieved on March 18, 2009, from http://www.epa.gov/.

Environmental Protection Agency Integrated Risk Information System (EPAIRIS, 2009), Retrieved on March 18, 2009 from http://www.epa.gov/iris/subst/1001.htm .

Dogliotti, E. (2006). Molecular mechanisms of carcinogenesis by vinyl chloride. Annali dell'Istituto Superiore di Sanita, 42(2), 163-169.

Kielhorn, Janet, Melber, Christine, Wahnschaffle, Ulrich, Aitio, Antero, Mangelsdorf, Inga. (2000) Vinyl chloride: still a cause for concern. Environmental Health Perspectives, V.108, n.7.

Occupational Safety and Health Administration. (2007). Permissible Exposure Limits. Retrieved from http://www.osha.gov/ on March 18, 2009.

Reitz, R. H., Gargas, M. L., Anderson, M. E., Provan, W. M., & Green, T. L. (1996). Predicting cancer risk from vinyl chloride exposure with a physiologically based pharmacokinetic model. Toxicology and Applied Pharmacology, 137, 253-267.

Toxicological profile vinyl chloride. (2009). Agency for Toxic Substances & Disease Registry (ATSDR), retrieved on March 18, 2009 from http://www.atsdr.cdc.gov/.

United Nations Environment Programme, World Heath Organization. (1999) Vinyl chloride. Health and Safety Guide, No. 109,

Assignment #7 - Asbestos

According to Roberta Barbalace from EnvironmentalChemistry.com Asbestos is a naturally occuring mineral with long fibrous crystals. Wikipedia stated that the Greeks used to believe that Asbestos was a miracle mineral because it was soft and contained pliant properties, as well as it’s ability to withstand heat. Asbestos became increasingly popular among manufacturers and builders in the late 19th century due to it’s resistance to heat and it’s tensile strength. Asbestos can be used in heat resistance products, electric ovens in the past, hotplate wiring and in buildings for it’s flame-retardant capabilities. There are six different minerals that are defined as “asbestos” including: chrysotile, amosite, cricidolite, tremolite, anthophyllite and actinolite.
As found on HealthDangers.com the "history of Asbestos is long and scientists have found that it has been around and used for hundreds possibly thousands of years.
Prior to 1900 – Greeks and Romans have discovered that slaves involved in the weaving of asbestos cloth were afflicted with a sickness of the lungs
1900s-1910s – London doctor H. Montague Murray conducted a post mortem exam on a young asbestos factory worker who died in 1899. Dr. Murray gave testimony on this death in connection with an industrial disease compensation hearing. Post-moretem findings showed presence of asbestos in the lung tissue. Dr. Murry believed that the inhalation of asbestos had at least contributed to, if not actually caused the death of the worker.
1920s-1930s - Widespread recognition of the occupational risks of asbestos in Britain was reported in 1924 by a Dr. Cooke, a pathologist, who introduced a case description of a 33-year old female asbestos worker with the following: 'Medical men in areas where asbestos is manufactured have long suspected the dust to be the cause of chronic bronchitis and fibrosis..." Dr. Cooke then went on to report on a case in 1927 involving a 33-year old male worker who was the only survivor out of ten workers in an asbestos carding room. In the report he named the disease "asbestosis". The first known US workers' compensation claim for asbestos disease was in 1927. In 1930, the first reported autopsy of an asbestosis sufferer was conducted in the United states and later presented by a doctor at the Mayo Clinic, although in this case the exposure involved mining activities somewhere in South America.
1950s - In 1951, asbestos companies removed all references to cancer before allowing publication of research they sponsored. In 1952, Dr. Kenneth Smith, Johns-Manville medical director, recommended (unsuccessfully) that warning labels be attached to products containing asbestos.
1960s - early 1980s - Through the 1970s, asbestos was used to fireproof roofing and flooring, for heat insulation, and for a variety of other purposes
Mondern Regulation - In 1989 the United States EPA issued the Asbestos Ban and Phase Out Rule."
"A brief history of Asbestos use." Environmental Chemistry. 17 Mar. 2009 environmentalchemistry.com
AD, the first century," Wikipedia, the free encyclopedia. 17 Mar. 2009 http://en.wikipedia.org/wiki/asbestos."History of Asbestos."
Health Dangers.com 17 Mar. 2009 .