WWW.DISSERTATION.XLIBX.INFO
FREE ELECTRONIC LIBRARY - Dissertations, online materials
 
<< HOME
CONTACTS



Pages:   || 2 | 3 | 4 |

«1,4-DIOXANE 9 2. RELEVANCE TO PUBLIC HEALTH 2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO 1,4-DIOXANE IN THE UNITED STATES 1,4-Dioxane is a stable, ...»

-- [ Page 1 ] --

1,4-DIOXANE 9

2. RELEVANCE TO PUBLIC HEALTH

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO 1,4-DIOXANE IN THE

UNITED STATES

1,4-Dioxane is a stable, clear liquid at ambient temperatures and is miscible with water. It is used

primarily as a solvent for chemical processing. It has also been used as a laboratory reagent; in plastic, rubber, insecticides, and herbicides; as a chemical intermediate; as part of a polymerization catalyst; and as an extraction medium of animal and vegetable oils. 1,4-Dioxane may also be found as a contaminant in ethoxylated surfactants, which are used in consumer cosmetics, detergents, and shampoos. Currently, manufacturers remove 1,4-dioxane from ethoxylated surfactants to low levels by vacuum stripping.

Current levels of 1,4-dioxane in ambient air, drinking water, and food samples are not available. In the mid 1980s, levels of 1,4-dioxane in ambient outdoor air ranged from 0.1 to 0.4 μg/m3 (0.028–0.11 ppb).

Mean concentrations of 1,4-dioxane in indoor air were a factor of 10 higher at 3.704 μg/m3 (1.029 ppb).

In the 1970s, municipal water supplies in the United States were reported to contain 1 μg/L (ppb) of 1,4-dioxane. 1,4-Dioxane has been detected in food volatiles which may indicate that 1,4-dioxane may be a natural constituent in some foods. Volatiles from chicken, meat, tomatoes, and small shrimp have been reported to contain 1,4-dioxane at unquantified levels. Dermal exposure to 1,4-dioxane may occur with the use of consumer cosmetics, detergents, and shampoos containing ethoxylated surfactants. Between the years 1992 and 1997, the average concentration of 1,4-dioxane in cosmetic finished products was reported to fluctuate from 14 to 79 ppm (mg/kg). In a more recent survey reported by the Campaign for Safe Cosmetics, the levels of 1,4-dioxane in cosmetic products that were tested were found to be lower (1.5–12 ppm in baby and children’s products and 2–23 ppm in adult products) than in the survey done by the FDA in the 1990s.

2.2 SUMMARY OF HEALTH EFFECTS Limited information exists regarding the health effects of 1,4-dioxane in humans. Yet, the available data are sufficient to clearly identify the liver and kidneys as the target organs for 1,4-dioxane toxicity following short-term exposure to relatively high amounts of 1,4-dioxane, regardless of the route of exposure. This has been corroborated in studies in animals. Workplace exposures to undetermined, but presumably high concentrations of 1,4-dioxane have resulted in death. Inhalation was the most likely route of exposure, although considerable dermal contact may also have taken place in one of these cases.

Evaluation of the subjects prior to death did not provide a picture that could be considered unique t

–  –  –

1,4-dioxane. Subjects often complained of gastrointestinal pain, had high blood pressure, anuria, and leukocytosis, and exhibited signs of nervous system involvement. The deaths occurred 5–8 days after the initial symptoms of illness. Postmortem evaluation revealed extensive liver and kidney damage and in three out of five cases described in one study, kidney disease was considered to be the direct cause of death. Controlled exposures of volunteers to airborne 1,4-dioxane for periods ranging from a few minutes to 6 hours produced eye, nose, and throat irritation. The lowest exposure concentration that produced eye irritation was 50 ppm during a 6-hour exposure, but exposure in a much older study to 2,000 ppm for 3 minutes produced no complaints of eye or nasal discomfort. In a more recent study, exposure of volunteers to 20 ppm for 2 hours did not induce eye or respiratory irritation. Little is known about longterm exposure to lower concentrations of 1,4-dioxane. A study of workers exposed to 0.006–14.3 ppm 1,4-dioxane for an average of 25 years found no evidence of liver or kidney disease or any other clinical effects. An additional study that examined mortality rates among workers employed at a manufacturing and processing facility found no differences between observed and expected incidences of cancer.

However, this study was limited in size and exposure duration. Although no information was available regarding reproductive, developmental, or immunological effects specific to 1,4-dioxane in humans, some occupational studies of workers exposed to 1,4-dioxane in combination with other solvents have reported elevated rates of spontaneous abortion, stillbirths, premature births, and low birth weights. These effects cannot be attributed either solely or in part to 1,4-dioxane.

Results from a recent 13-week study in rats and a 2-year study in rats indicate that the tissues in the nasal cavity are the most sensitive target for 1,4-dioxane following inhalation exposure. Adverse nasal effects were seen in rats exposed to ≥100 ppm in the 13-week study and in rats exposed to ≥50 ppm in the 2-year study. These exposure concentrations were the lowest tested. The liver and kidneys are also targets of 1,4-dioxane toxicity in animals following inhalation, oral and dermal exposure. There are no studies of the effects of 1,4-dioxane on reproductive function or immunocompetence in animals, and only one study in rats evaluated developmental end points following oral exposure during gestation. Slight fetotoxicity occurred at 1,033 mg/kg/day, a dose level that also affected the mothers. Chronic inhalation exposure of male rats to 1,4-dioxane induced benign tumors in the liver (1,250 ppm but not 250 ppm), squamous cell carcinoma in the nasal cavity (1,250 ppm but not 250 ppm), and mesothelioma in the peritoneum (≥250 ppm but not 50 ppm). Chronic administration of 1,4-dioxane in the drinking water produced liver cancer in rats (range, 398–1,015 mg/kg/day), mice (range, 77–380 mg/kg/day), and guinea pigs (1,014 mg/kg/day), and cancer of the nasal cavity in rats (range, 429–833 mg/kg/day). However, a 2-year inhalation study in rats exposed to 111 ppm 1,4-dioxane (equivalent to oral doses of approximately 105 mg/kg/day), provided no evidence of carcinogenicity or any other health effect. The mechanism of 1,4-DIOXANE 11





2. RELEVANCE TO PUBLIC HEALTH

carcinogenicity of 1,4-dioxane has not been elucidated, but the lack of or weak genotoxicity of 1,4-dioxane, its strong promotion properties, and the extensive cytotoxicity observed in some studies at dose levels that induce tumors suggest that 1,4-dioxane may be acting through a non-genetic mode of action.

Liver and Cancer Effects. Liver effects have occurred in humans and animals exposed to 1,4-dioxane, and the data in animals suggest that they occur regardless of the route of exposure. An occupational study and a case report provided a detailed description of the liver pathology in subjects following exposure to 1,4-dioxane that resulted in deaths within 1–2 weeks after the exposure. Upon postmortem examination, enlarged and pale liver and centrilobular necrosis were commonly observed.

None of the subjects showed jaundice before death. Neither workers exposed to lower concentrations of 1,4-dioxane for many years nor volunteers exposed for a single 6-hour period to 50 ppm 1,4-dioxane showed indications of liver alterations.

One study provided detailed descriptions of liver pathology in several animal species exposed intermittently to 1,4-dioxane by inhalation for a period of up to 13 weeks and also exposed orally and by dermal contact. Both lethal and non-lethal concentrations (1,000–10,000 ppm) caused degrees of degeneration that varied from cloudy swelling to large areas of complete necrosis. Similar effects were seen following oral (1,428 mg/kg/day in rats) and dermal (143 mg/kg/day in guinea pigs; 57 mg/kg/day in rabbits) exposure. Hepatocyte vacuolation and swelling were reported in rats and mice dosed with 1,4-dioxane in the drinking water for 2 weeks (2,500 mg/kg/day) or 13 weeks (≥126 mg/kg/day in rats;

550 mg/kg/day in mice). Evidence of hepatic degenerative changes was seen in Sherman rats that died after 2–4 months of receiving doses of 1,015 mg/kg/day 1,4-dioxane via the drinking water in a 2-year bioassay. Chronic inhalation exposure of male F344 rats to 1,250 ppm induced hepatic centrilobular necrosis and nuclear enlargement. Long-term oral studies in animals described hepatocellular degeneration and necrosis in Sherman rats at about 94 mg 1,4-dioxane/kg/day and increased cell foci in F344 rats at ≥55 mg/kg/day; hepatocytomegaly was observed in female Osborne-Mendel rats treated with approximately 350 mg/kg/day. The apparent different lesions and thresholds for the effects in the liver may reflect strain differences.

–  –  –

suggested that highly reactive and toxic intermediates do not play a major role in the liver toxicity of 1,4-dioxane, even under conditions of enhanced metabolism. Conversely, it has also been reported that the metabolite, 1,4-dioxane-2-one, was several-fold more toxic than 1,4-dioxane based on intraperitoneal LD50 determinations in rats.

All long-term studies in rats dosed with 1,4-dioxane via the drinking water reported an increased incidence of liver tumors, generally in the high-dose groups. In the better reported studies, tumor development occurred at doses that produced extensive liver toxicity, including hepatocellular hyperplasia and degeneration and evidence of hepatic regeneration, which has led some to suggest that cell damage and degeneration may be a necessary occurrence for the formation of liver tumors in rats. Oral exposure to 1,4-dioxane also induced tumors in the nasal cavity in rats and liver tumors in mice and guinea pigs.

The relevance of the nasal tumors to humans following oral exposure to 1,4-dioxane has been questioned and some scientists suggested that the tumors resulted from inspiration of water containing 1,4-dioxane into the nasal cavity. A study reported that the addition of a fluorescent dye mixture to water containing 0.5% 1,4-dioxane and offered to rats as drinking water resulted in the fluorescent dye readily observed in numerous areas in the nasal cavity where bioassays have identified tumors. Little or no fluorescence associated with the dye mixture was found in a single rat that received the dye mixture by gavage. One study concluded that these results indicate that the rat nasal tissues are exposed by direct contact with drinking water under conditions of the bioassay. However, there is also evidence in support of the nasal alterations being caused, at least in part, by systemic delivery of either 1,4-dioxane or a metabolite (see Section 3.5.2). The lack of nasal cytotoxicity and nasal tumors in Wistar rats exposed intermittently to 111 ppm 1,4-dioxane in the air for 2 years suggests that the minimal effective dose may not have been reached, whether by direct contact alone or a combination of direct contact and internal exposure.

The mechanism of carcinogenicity of 1,4-dioxane has not been elucidated, but the results from several lines of investigation have led some to conclude that 1,4-dioxane has a non-genotoxic, yet unknown, mode of action. The EPA has developed cancer risk values for oral exposure to 1,4-dioxane, last revised in 2010, based on the increased incidence of hepatocellular adenoma and carcinomas in female Crj:BDF1 mice in a 2-year drinking-water bioassay.

–  –  –

for Research on Cancer (IARC) has determined that 1,4-dioxane is possibly carcinogenic to humans. The Department of Health and Human Services (DHHS) has stated that 1,4-dioxane is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity in experimental animals. The EPA has established that 1,4-dioxane is likely to be carcinogenic to humans based on inadequate evidence of carcinogenicity in humans and sufficient evidence in animals.

Renal Effects. Kidney lesions appeared to be the cause of death of five workers who were exposed to unknown concentrations of 1,4-dioxane primarily by the inhalation route. Death occurred 1–2 weeks after episodes of elevated exposure started at work. All five cases experienced oliguria or anuria. Post mortem examination revealed swollen kidneys with hemorrhages and necrosis of the cortex. Similar findings were reported in a fatal case report. No renal alterations, as judged by urinalyses, were described in other reports of long-term occupational exposure to low levels of 1,4-dioxane or in a group of volunteers following a single 6-hour exposure to 50 ppm 1,4-dioxane. Very similar kidney lesions were observed in animals exposed to 1,4-dioxane by several routes of exposure. Rodents exposed to acutely lethal concentrations of 1,4-dioxane (≥5,000 ppm) showed severe kidney damage consisting of marked patchy cell degeneration of the cortical tubules and intense vascular congestion and hemorrhages both inter- and intra-tubular. Well-marked kidney lesions were present in animals that survived intermittent inhalation exposure to 1,000 ppm 1,4-dioxane for up to 12 weeks. Similar observations were made in intermediate-duration studies in rats and mice exposed orally (1,400–2,900 mg 1,4-dioxane/kg/day) and in guinea pigs (143 mg/kg) and rabbits (57 mg/kg) following dermal application of 1,4-dioxane.

Evidence of renal degenerative changes was seen in Sherman rats that died after 2–4 months of treatment with 1,015 mg 1,4-dioxane/kg/day in a 2-year drinking water bioassay. Nuclear enlargement of the proximal tubule was reported in rats exposed to 657 mg 1,4-dioxane/kg/day in a 13-week study.

Increased incidence of degeneration and necrosis of the tubular epithelium was seen in rats that received 94 mg/kg/day and survived until termination of the study, and similar findings were reported in OsborneMendel rats that received 240 mg/kg/day. Nuclear enlargement in the proximal convoluted tubule was reported in male F344 rats exposed to ≥250 ppm 1,4-dioxane vapors for 2 years. No compound-related neoplastic lesions were observed in the kidneys in other long-term studies conducted with 1,4-dioxane in rodents. The mechanism(s) by which 1,4-dioxane induces kidneys lesions is not known, and virtually no discussion about this topic was found in the reviews available. The findings in the case studies are consistent with an acute nephritic syndrome, which is characterized by oliguria and acute renal failure. It is not expected that exposure to concentrations commonly in the environment would cause adverse kidney effects in humans.

1,4-DIOXANE 14

–  –  –



Pages:   || 2 | 3 | 4 |


Similar works:

«REFERÊNCIA: PARANHOS da COSTA, M. J. R.; ANDRIOLO, A.; SIMPLÍCIO DE OLIVEIRA, J. F.; SCHMIDEK, W. R. Suckling and allosuckling in river buffalo calves and its relation with weight gain. Applied Animal Behaviour Science, v. 66, p. 1-10. 2000. SUCKLING AND ALLOSUCKLING IN RIVER BUFFALO CALVES AND ITS RELATION WITH WEIGHT GAIN MATEUS J.R. PARANHOS DA COSTA a,e,*, ARTUR ANDRIOLOb,e, JOSÉ F. SIMPLÍCIO DE OLIVEIRA C, WERNER R. SCHMIDEK D a Departamento de Zootecnia, Faculdade de Ciências...»

«WHAT IS MILK? Milk is defined as the lacteal secretion obtained by the complete milking of one or more mammalian animals. Although in other parts of the world a variety of animals are used as sources for milk, in the United States almost all commercially available milk comes from cows. Milk is valued because it is an important source of many of the nutrients essential for the proper development and maintenance of the human body. Today, milk appears in American grocery stores in a wide variety...»

«State of California—Health and Human Services Agency Department of Health Care Services TOBY DOUGLAS EDMUND G. BROWN JR. DIRECTOR GOVERNOR November 16, 2012 TO: ALL COUNTY WELFARE DIRECTORS ALL COUNTY WELFARE ADMINISTRATIVE OFFICERS ALL COUNTY MEDI-CAL PROGRAM SPECIALISTS/LIAISIONS ALL COUNTY HEALTH EXECUTIVES ALL COUNTY MENTAL HEALTH DIRECTORS ALL COUNTY MEDS LIAISONS SUBJECT: Targeted Low-Income Children’s Program Letter No.: 12-33 The purpose of this All County Welfare Directors Letter...»

«DISTRICT ANALYTICAL REPORT LEDZOKUKU-KROWOR MUNICIPALITY Copyright © 2014 Ghana Statistical Service ii PREFACE AND ACKNOWLEDGEMENT No meaningful developmental activity can be undertaken without taking into account the characteristics of the population for whom the activity is targeted. The size of the population and its spatial distribution, growth and change over time, in addition to its socio-economic characteristics are all important in development planning. A population census is the most...»

«EMOTIONAL INTELLIGENCE WHY IT CAN MATTER MORE THAN IQ DANIEL GOLEMAN From the Library of Unviolent Revolution UnviolentPeacemaker at ThePirateBay 3/661 BLOOMSBURY For Tara, wellspring of emotional wisdom Contents Aristotle's Challenge PART ONE THE EMOTIONAL BRAIN 1. What Are Emotions For? 2. Anatomy of an Emotional Hijacking PART TWO THE NATURE OF EMOTIONAL INTELLIGENCE 3. When Smart Is Dumb 4. Know Thyself 5. Passion's Slaves 6. The Master Aptitude 7. The Roots of Empathy 8. The Social Arts...»

«MECHANISMS OF CHROMOSOMAL INSTABILITY INDUCED BY UNSTABLE DNA REPEATS IN YEAST S.CEREVISIAE A Dissertation Presented to The Academic Faculty By Yu Zhang In partial fulfillment Of the requirements for the degree Doctor of Philosophy in Biology Georgia Institute of Technology August 2013 Copyright © Yu Zhang, 2013 MECHANISMS OF GENOME INSTABILITY INDUCED BY UNSTABLE DNA REPEATS IN YEAST S.CEREVISIAE Approved by: Dr. Kirill Lobachev, Advisor Dr. Brian Hammer School of Biology School of Biology...»

«Bartleby, the Scrivener: A Story of Wall-Street HERMAN MELVILLE Page | 1 The summons to compassion and neighborliness is often most difficult to answer when the suffering we confront seems beyond our capacity to remedy. Poverty invites us to give money. Illness calls for medical care. But how do we respond to those maimed in soul and spirit—the homeless, helpless, and hopeless in our midst? No story presents this problem more powerfully than “Bartleby, the Scrivener” (1853) by Herman...»

«1 Course Syllabus HS 3050a Health-Related Quality of Life Fall 2014 Instructor: Dr. Philip C. Doyle Tuesdays 2:30 – 5:20 p.m.Lecture: Class Location: HSB 35 Office: Elborn College, Rm. 2518, Ext. 88942 Office Hours: Monday 8:00 -9:30 a.m. or by appointment Email: pdoyle@uwo.ca Course TA: Melissa Nash, MSc (mmandevi@uwo.ca) Thursday 2:00 – 3:30 TA Office Hours: Office: Elborn College, Rm. 1003 (main floor) Description of Course This course provides instruction related to comprehensive issues...»

«Lepr Rev (2004) 75, 357– 366 Neonatal BCG protection against leprosy: a study in Manaus, Brazilian Amazon ´ SE RGIO S. CUNHA*, **, LAURA C. RODRIGUES*, VALDERIZA PEDROSA þ, INEZ M. DOURADO**, MAURICIO L. BARRETO** & SUSAN MARTINS PEREIRA** *London School of Hygiene and Tropical Medicine, Keppel Street, London, UK ´ **Instituto de Saude Coletiva, Universidade Federal da Bahia, Brazil þFundacao Alfredo da Matta, Manaus, Brazil ¸˜ Accepted for publication 21 September 2004 Summary There...»

«PUBLISHED BY World's largest Science, Technology & Medicine Open Access book publisher 96,000+ 2750+ 89+ MILLION INTERNATIONAL AUTHORS AND EDITORS OPEN ACCESS BOOKS DOWNLOADS AUTHORS AMONG 12.2% BOOKS TOP 1% AUTHORS AND EDITORS DELIVERED TO MOST CITED SCIENTIST FROM TOP 500 UNIVERSITIES 151 COUNTRIES Selection of our books indexed in the Book Citation Index in Web of Science™ Core Collection (BKCI) Chapter from the book Climate Change Realities, Impacts Over Ice Cap, Sea Level and Risks...»

«TITLE “I drove after drinking alcohol” and other risky driving behaviours reported by young novice drivers in Queensland, Australia AUTHORS AND AFFILIATIONS Bridie Scott-Parker 1, 2, 3 T: +61 7 5456 5844, F: + 61 7 5430 2859, E: bscottpa@usc.edu.au Barry Watson2, 3 T: + 61 7 3138 4955, F: + 61 7 3138 0111, E: b.watson@qut.edu.au Mark J King2, 3 T: + 61 7 3138 4546, F: + 61 7 3138 0111, E: mark.king@qut.edu.au Melissa K Hyde 4, 5T: + 61 412 032 716, E: melissa.hyde@griffith.edu.au ¹...»

«Moscow/Beijing Embassy Frequently Asked Questions Frequently Asked Questions Q: How much do jobs at the Embassy pay? A: Salary will be dependent on the type of job, level of expertise, and experience. You can send an e-mail along with your resume to paemoscow@pae.com to find out the current salary for your position. Q: Can you tell me more about the benefits – medical, dental, etc.? A: Details of our benefit packages are available at http://www.pae.com/careers-embassies-benefits Q: How long...»





 
<<  HOME   |    CONTACTS
2016 www.dissertation.xlibx.info - Dissertations, online materials

Materials of this site are available for review, all rights belong to their respective owners.
If you do not agree with the fact that your material is placed on this site, please, email us, we will within 1-2 business days delete him.