Standard (WES) Review

Transcription

1 Exposure Standard (WES) Review H E A LT H & S A F E T Y AT WO R K HSWA AC T Workplace VINYL BROMIDE (CAS NUMBER ) April 2017

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3 TABLE OF CONTENTS 01 INTRODUCTION 3 02 PHYSICAL AND CHEMICAL PROPERTIES 5 03 USES 7 04 HEALTH EFFECTS OF VINYL BROMIDE Non-cancer Cancer Absorption, distribution, metabolism and excretion IARC evaluation and rationale SCOEL evaluation EXPOSURE STANDARDS AND GUIDANCE VALUES IN USE AROUND THE WORLD New Zealand ACGIH SCOEL The Netherlands ANALYTICAL METHODS FOR THE ASSESSMENT OF AIRBORNE VINYL BROMIDE DISCUSSION AND RECOMMENDATION 18 APPENDICES 20 Appendix 1: Glossary 21 Appendix 2: Methods for setting OELs 23 Appendix 3: References 26

4 TABLES 1 Chemical and physical properties of vinyl bromide 6 2 Exposure standards for vinyl bromide from around the world 14

5 01/ INTRODUCTION 3

6 WORKPLACE EXPOSURE STANDARD (WES) REVIEW: VINYL BROMIDE This WorkSafe New Zealand (WorkSafe) review considers whether the WES for vinyl bromide should be changed. It considers, among other things, the potential for exposures to vinyl bromide in New Zealand, the health effects and risks, exposure standards in other jurisdictions, and the practicability of measuring vinyl bromide exposures given currently available analytical methods. The review includes a recommendation to change the current WorkSafe WES, which is currently set at a WES-TWA of 5 ppm (or 22 mg/m 3 ), as published in the Special Guide Workplace Exposure Standards and Biological Exposure Indices, 8th Edition (WorkSafe New Zealand, ). In New Zealand, vinyl bromide carries a 6.7A notation for carcinogenicity. This means it is a known or presumed human carcinogen the substance is either carcinogenic to humans, or the data indicate sufficient evidence in animal studies to demonstrate a causal relationship between exposure and the development of cancer, or an increase in tumours. > > Terms that are bold (first occurrence only) are further defined in the Glossary. > > Concentrations have been converted to ppm from mg/m 3 (using the conversion factor in Table 1) unless the latter is specified as an occupational exposure standard. > > Synonyms: vinyl bromide; bromoethene; bromoethylene; monobromoetheylene; ethylene, bromo. 4

7 02/ PHYSICAL AND CHEMICAL PROPERTIES 5

8 WORKPLACE EXPOSURE STANDARD (WES) REVIEW: VINYL BROMIDE Vinyl bromide is a colourless gas or liquid with an odour, variously described as pungent or pleasant. Under pressure it is a colourless liquid. Chemical and physical properties include: Molecular weight Specific gravity Formula; Structure at 20 C (liquid) C 2H 3Br; CH 2=CHBr Boiling point 15.8 C Vapour pressure 1033 torr (1.359 atm) at 20 C Vapour density 3.7 (air = 1) Solubility Conversion factors Reactivity Soluble in alcohol, ether, acetone, benzene, chloroform, tetrahydrofuran. Very low water solubility 1 ppm = 4.45 mg/m 3 ; 1 mg/m 3 = 0.23 ppm at 25 C and 760 torr Vinyl bromide is highly flammable and reacts violently with oxidisers. LEL = 9%, UEL = 15%. HSNO classifications 2.1.1A, 6.1D (All), 6.1D (O), 6.4A, 6.6A, 6.7A, 6.9A (All), 6.9A (I), 9.3B Table 1: Chemical and physical properties of vinyl bromide 6

9 03/ USES 7

10 WORKPLACE EXPOSURE STANDARD (WES) REVIEW: VINYL BROMIDE Vinyl bromide is used to manufacture bromopolymers mainly polyvinyl bromide. It is used as a flame retardant in the production of flame-resistant acrylic polymers. It is also used as an alkylation agent in the synthesis of organic compounds including pharmaceuticals, fumigants and leather products and it is used in the polymerisation of plastics, metal fabrication and lamination of fibres. Other uses include the manufacture of children s sleepwear and home furnishings. The number of persons exposed or potentially exposed in New Zealand is not expected to be high. According to the European Commission the number of people exposed in the EU is expected to be small (ie less than a few hundred) but there is not enough information to assess the actual extent of exposure (European Commission, ). Workers may be occupationally exposed to vinyl bromide via inhalation during its manufacture or use (US Department of Health and Human Services, ). Exposure may occur in the vicinity of facilities that manufacture or use this compound. Statistics New Zealand 2015 data indicate that 9610 New Zealand workers were working in the areas of leather production, organic chemical manufacture, basic polymer manufacture, film and sheet manufacture, rubber product manufacture and fabricated metal product manufacture. It is unlikely many of these are exposed, or potentially exposed, to vinyl bromide as it is expected it is not widely used. 8

11 04/ HEALTH EFFECTS OF VINYL BROMIDE IN THIS SECTION: 4.1 Non-cancer 4.2 Cancer 4.3 Absorption, distribution, metabolism and excretion 4.4 IARC evaluation and rationale 4.5 SCOEL evaluation 9

12 WORKPLACE EXPOSURE STANDARD (WES) REVIEW: VINYL BROMIDE 4.1 NON-CANCER HUMANS The only non-cancer toxic effects in humans, reported by the International Agency for Research on Cancer (IARC, ) are short-term inhalation of high concentrations of vinyl bromide (levels not provided) causing a loss of consciousness, and skin and eye contact causing a frost-bite type of burn. Although this IARC information 4 is now over 30 years old, there has been little if any data available that refutes IARC s statement. ANIMALS Vinyl bromide vapour has been found to be mutagenic when tested in two strains of Salmonella typhimurium (TA 1530 and TA 100) in the presence of postmitochondrial mouse-liver supernatant. Liver fractions from humans were also found to convert vinyl bromide into a mutagen (Bartsch et al., ). Additionally, vinyl bromide was found to be mutagenic when tested as a gas in two strains of Salmonella typhimurium (TA 1535 and TA 100) (Lijinsky and Andrews., ). In a single cell gel electrophoresis (SCG) assay, vinyl bromide was found to cause DNA damage, in vivo, in mouse liver, kidney, bladder, lung and brain (Sasaki et al., ). Vinyl bromide has been shown to be mutagenic in bacteria (Lijinsky and Andrews ) and in Drosophila (Vogel and Nivard, ). 4.2 CANCER HUMANS No data was available to the IARC working group relating to studies of cancer in humans (IARC, ). ANIMALS Inhalation studies were conducted in male and female Sprague-Dawley rats, using concentrations of approximately 10, 50, 250 or 1,250 ppm ± 5% vinyl bromide (purity 99.9%), exposed for six hours per day on five days per week for 104 weeks (Benya et al., ). 120 male and female rats were assigned to each treatment group. A group of 144 males and 144 females served as a control. Treatment-related increases in the incidence of liver angiosarcomas were observed in both sexes of exposed groups. An increased incidence of Zymbal gland squamous-cell carcinomas also occurred in both sexes of exposed rats (Benya et al., ) at and above 50 ppm exposure levels. The Zymbal gland is an accessory structure of the rodent ear, a sense organ. Zymbal glands are modified sebaceous glands that are located at the base of the external ear and secrete into the auditory canal. They are target tissues for carcinogenicity tests. The U.S. Department of Health and Human Services, Public Health Services National Toxicology Program (NTP) report work undertaken by Van Duuren in which dermal exposure studies were undertaken in a group of 30 female ICR/Ha Swiss mice. The mice received dermal applications of 15 mg of vinyl bromide of unstated purity in 0.1 ml of acetone three times a week for 60 weeks. No skin tumours were observed (NTP Board of Scientific Counselors, ). 10

13 SECTION 4.0 // HEALTH EFFECTS OF VINYL BROMIDE In a two-stage skin carcinogenesis study, groups of 30 female ICR/Ha Swiss mice received a single dermal application of 15 mg of vinyl bromide of unstated purity in 0.1 ml of acetone, followed by thrice-weekly applications of 2.5 g of 12-O-tetradecanoylphorbol-13-acetate (TPA) in 0.1 ml acetone for 60 weeks. Additional groups of mice received TPA alone or no treatment. One of 30 mice treated with TPA alone was observed to have a skin carcinoma at 44 days. No tumours were found in 160 untreated mice. Systemic carcinogenesis was not assessed (NTP Board of Scientific Counselors, ). Subcutaneous exposure studies were undertaken in a group of 30 female ICR/Ha Swiss mice. The mice (of unspecified age) received subcutaneous injections of zero or 25 mg of vinyl bromide of unspecified purity, in 0.05 ml trioctanoin for 48 weeks and were observed for up to 420 days. No tumours were reported in vinyl bromide-treated mice, or in vehicle-treated controls or in 60 untreated controls. Once again, systemic carcinogenesis was not assessed (NTP Board of Scientific Counselors, ). 4.3 ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION HUMANS No data were available to the IARC working group (IARC, ). ANIMALS AND EXPERIMENTAL SYSTEMS Vinyl bromide is metabolised in a manner similar to vinyl fluoride and vinyl chloride: oxidation via cytochrome P450 to bromoethylene oxide, followed by rearrangement to 2-bromoacetaldehyde, which is oxidised to bromoacetic acid. Vinyl bromide metabolises more slowly than does vinyl chloride (the K m for vinyl bromide metabolism is approximately an order of magnitude lower) (Bolt et al., ), which suggests that vinyl bromide s greater carcinogenic potency may be related to kinetic differences in metabolism. 4.4 IARC EVALUATION AND RATIONALE In 2008, on the basis of the research outlined above, the IARC concluded that there is inadequate evidence in humans for the carcinogenicity of vinyl bromide (IARC, ). They further concluded that there is sufficient evidence in experimental animals for the carcinogenicity of vinyl bromide. IARC s overall conclusion is that vinyl bromide is probably carcinogenic to humans (Group 2A). In making the overall evaluation, the IARC working group took into consideration the fact that all available studies showed a consistently parallel response between vinyl bromide and vinyl chloride. In addition, both vinyl chloride and vinyl bromide are activated via a human cytochrome P450 2E1-dependent pathway to their corresponding epoxides. For both vinyl chloride and vinyl bromide, the covalent binding of these compounds to nucleosides/dna yields pro-mutagenic etheno adducts. The weight of positive evidence for both compounds was also noted among the studies for genotoxicity, although the number and variety of tests for vinyl bromide were fewer. For practical purposes, vinyl bromide should be considered to act similarly to the human carcinogen, vinyl chloride. (IARC, ). 11

14 WORKPLACE EXPOSURE STANDARD (WES) REVIEW: VINYL BROMIDE 4.5 SCOEL EVALUATION In 2008, the Scientific Committee on Occupational Exposure Limits (SCOEL, ), concluded that on the basis of both the inhalation bioassay with vinyl bromide, (Benya, ), and the oral bioassay with vinyl chloride (Feron et al., ), when toxicokinetics are considered, that both compounds are similarly transformed in a first decisive step to the ultimate carcinogen, the respective epoxide. The carcinogenicity of the reactive metabolites produced per unit time from inhaled vinyl bromide is about 1.8-fold that of vinyl chloride metabolites. Because in the relevant low-dose range (below 50 ppm airborne exposure) vinyl bromide is about 1.7 times faster metabolised than vinyl chloride, it can be derived that vinyl bromide is 3 times more carcinogenic than vinyl chloride at occupationally relevant exposure levels. This ratio is in accordance with the higher blood/air partition coefficient and the resulting higher tissue affinity of vinyl bromide compared with vinyl chloride. This notion was supported by Storm & Rozman ( ), who introduced the bioassay data of vinyl chloride and vinyl bromide into different extrapolation models (no-threshold and threshold approaches). These authors claimed that humans were less susceptible to both vinyl halides than rats, and that vinyl bromide was more potent than vinyl chloride. The different approaches used, however, produced incongruent risk assessment figures. SCOEL 13 stated that It appears, therefore not possible to draw firm quantitative conclusions from these particular estimates. 12

15 05/ EXPOSURE STANDARDS AND GUIDANCE VALUES IN USE AROUND THE WORLD IN THIS SECTION: 5.1 New Zealand 5.2 ACGIH 5.3 SCOEL 5.4 The Netherlands 13

16 WORKPLACE EXPOSURE STANDARD (WES) REVIEW: VINYL BROMIDE Table 2 below shows the lead exposure standards from around the world, as published by the Institute for Occupational Safety and Health of the German Social Accident Insurance (Institut für Arbeitsschutz der Deutschen Gesetzlichen Unfallversicherung) and available at JURISDICTION OR ADVISORY BODY 8-HOUR LIMIT VALUE SHORT-TERM LIMIT VALUE ppm mg/m 3 ppm mg/m 3 Australia 5 22 Belgium Canada Ontario 0.5 Canada Quebec 5 22 Denmark Finland Hungary 22 Ireland New Zealand 5 22 Poland 0.4 Singapore 5 22 South Korea Spain Switzerland 5 22 The Netherlands ACGIH (1996) SCOEL (2008) US EPA None set RfC of ppm Table 2: Exposure standards for vinyl bromide from around the world It is noted that the only organisations from whom we get information as to how and why they set occupational exposures standards are ACGIH, SCOEL and DECOS. 5.1 NEW ZEALAND WorkSafe s WES for vinyl bromide has been unchanged since adoption in In 1996, ACGIH revised its TLV-TWA from 5 to 0.5 ppm, based on analogy to vinyl chloride, as discussed below. 14

17 SECTION 5.0 // EXPOSURE STANDARDS AND GUIDANCE VALUES IN USE AROUND THE WORLD 5.2 ACGIH ACGIH TLVs are health-based guidelines or recommendations to assist in the evaluation and control of potential workplace health hazards. The ACGIH TLV of 0.5 ppm for vinyl bromide is based largely on analogy to the TLV-TWA for vinyl chloride, where the value is intended to minimise the potential for liver cancer, observed in rodents exposed at 10 ppm (ACGIH, ). The ACGIH applies a notation of A2 to vinyl bromide Suspected Human Carcinogen. The A2 notation is used primarily when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals with relevance to humans. Sufficient data were not available to recommend SKIN or SEN notations or a TLV-STEL. The most recent review of the TLV for vinyl bromide by the ACGIH was conducted in SCOEL SCOEL accepts that vinyl bromide is clearly carcinogenic in experimental animals (SCOEL, ). They also conclude that in the occupationally relevant low exposure range (less than 50 ppm) vinyl bromide appears to be about three times more active than vinyl chloride. SCOEL conclude that based on the mode of action for vinyl chloride and considering the close similarity no threshold level can be supported for both vinyl halides. Consequently SCOEL have found it not feasible to set an OEL. Where there is no threshold established and no health based OEL, a risk assessment is used. SCOEL recommends using the existing vinyl chloride quantitative risk assessment (SCOEL/SUM/109) for vinyl bromide, taking into account the three times higher potency of vinyl bromide. Their hepatic angiosarcoma risk assessment for vinyl chloride (upon inhalation exposure for a working lifetime to 1 ppm vinyl chloride, inferred from epidemiological data) has been assessed to be 3 x Given that assessment, for a similar exposure to vinyl bromide, the hepatic angiosarcoma risk is considered by SCOEL to be 9 x 10-4, or 1 in 1,111. The close relation between vinyl chloride and vinyl bromide is supported by comparative data on metabolism, nucleic acid adduct formation and formation of pre-neoplastic hepatic foci. SCOEL has not recommended notations for sensitisation nor for the potential for absorption through the skin. 5.4 THE NETHERLANDS The Netherlands has the lowest exposure standard for vinyl bromide, of ppm, as shown in Table 2, above. In 1999, the Dutch Expert Committee on Occupational Standards (DECOS) reported that the estimated additional lifetime cancer risk for vinyl bromide is calculated to be: > > 4 x 10-5 for 40 years of occupational exposure to ppm (1 in 25,000), and > > 4 x 10-3 for 40 years of occupational exposure to 0.28 ppm (1 in 250) (DECOS, ). From these risk values it would appear that The Netherlands has set their exposure standard on the basis of a lifetime cancer risk of 4 x The Netherlands risk assessment took into account rat inhalation studies that showed the induction of angiosarcomas (primarily in the liver but also in lung, spleen nasal cavity and mesentery) and an increase in Zymbal gland neoplasms and primary hepatocellular neoplasms. 15

18 06/ ANALYTICAL METHODS FOR THE ASSESSMENT OF AIRBORNE VINYL BROMIDE 16

19 SECTION 6.0 // ANALYTICAL METHODS FOR THE ASSESSMENT OF AIRBORNE VINYL BROMIDE A common practice in New Zealand to measure airborne vinyl bromide is based on NIOSH Method 1009 (NIOSH, ). Using this method, an air sample of from 2 to 10 L is collected onto a coconut shell charcoal sorbent tube, using a sampling train set at a flow rate of up to 0.2 L of air per minute. Following desorption of analyte from the adsorbent, the analysis is carried out by gas chromatography using FID detection. The estimated limit of detection of this method is 3 g of vinyl bromide per sample. This would allow a minimum airborne concentration 0.3 mg/m 3 (0.07 ppm) to be detected. In practical terms, this method would allow compliance to be assessed against a WES-TWA as low as 0.3 ppm, but exposures close to this WES could not be assessed for extended shifts when taking into account the limit of quantification. It is noted that this method would allow compliance to be assessed against a WES-TWA as low as the ACGIH s TLV-TWA of 0.5 ppm. 17

20 07/ DISCUSSION AND RECOMMENDATION 18

21 SECTION 7.0 // DISCUSSION AND RECOMMENDATION In a 2016 fact sheet, the European Commission discusses their proposal to improve workers protection against cancer-causing chemicals (European Commission, ). In brief, they propose new EU-wide OELs for 13 priority chemical agents identified through a consultation process involving scientists, employers, workers, Member State representatives and labour inspectors. Their proposed new OEL for vinyl chloride is listed as 2.6 mg/m 3 (equivalent to 1 ppm), and this value, if adopted, would replace the current EU OEL of 3 ppm. With vinyl bromide considered by SCOEL to have three times the potency of vinyl chloride, there is a case for lowering the WES-TWA for vinyl bromide to a value at least as low as 1 ppm, and possibly as low as 0.3 ppm. WorkSafe does not consider its current WES-TWA of 5 ppm is acceptable. As discussed, SCOEL 12 have assessed the hepatic angiosarcoma risk assessment for vinyl bromide at 9 x 10-4 (1 in 1,111) for a lifetime of exposure to a concentration of 1 ppm. The risk of hepatic angiosarcoma could be expected to be much higher than 1 in 1,111, and possibly of the order of 1 in 222, at the current WorkSafe WES-TWA. It is proposed that WorkSafe New Zealand lower the WES-TWA to 0.3 ppm to minimise the potential for increases in the incidence of hepatic angiosarcomas based on inhalation studies in rats, and the pathway for the metabolism of vinyl bromide being similar to that of vinyl chloride and vinyl fluoride. At this concentration, the risk of hepatic angiosarcoma could be expected to be less than 1 in 1,111, and possibly of the order of 1 in 3,

22 APPENDICES IN THIS SECTION: Appendix 1: Glossary Appendix 2: Methods for setting WES Appendix 3: References 20

23 APPENDICES APPENDIX 1: GLOSSARY TERM ACGIH DECOS IARC FID K m mg mg/m 3 ml NIOSH OEL ppm RfC SCOEL SEN Skin TLV TLV-STEL TLV-TWA MEANING The American Conference of Governmental Industrial Hygienists (ACGIH ) is a 501(c)(3) charitable scientific organization, established in 1938, that advances occupational and environmental health. Examples of this include their annual edition of the TLVs and BEIs book and Guide to Occupational Exposure Values. Dutch Expert Committee on Occupational Standards. The International Agency for Research on Cancer an agency of the World Health Organisation, whose mission is to coordinate and conduct research on the causes of human cancer and to develop scientific strategies for cancer prevention and control. Flame Ionisation Detection a detection method used in conjunction with gas chromatography. The Michaelis-Menten constant which is a measure of how well a substrate complexes with a given enzyme. Otherwise known as a substrate s binding affinity. Milligram or one thousandth of a gram. Milligrams of substance per cubic metre of air. Millilitre, or thousandth of a litre. The National Institute for Occupational Safety and Health (NIOSH) is the United States federal agency responsible for conducting research and making recommendations for the prevention of work-related injury and illness. NIOSH is part of the Centers for Disease Control and Prevention (CDC) within the U.S. Department of Health and Human Services. Occupational Exposure Limit. Parts of vapour or gas per million parts of air. The RfC is an estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. The Scientific Committee on Occupational Exposure Limits is a committee of the European Commission, established in 1995 to advise on occupational health limits for chemicals in the workplace within the framework of Directive 98/24/EC, the chemical agents directive, and Directive 90/394/EEC, the carcinogens at work directive. A notation indicating the subject substance is a sensitiser. DSEN and RSEN are used in place of SEN when specific evidence of sensitisation by the dermal or respiratory route, respectively, is confirmed by human or animal data. An ACGIH term. A notation indicating the potential for significant contribution to the overall exposure, by the cutaneous route, including mucous membranes and the eyes, by contact with vapours, liquids and solids. An ACGIH term. Threshold Limit Value (see TLV-C, TLV-STEL and TLV-TWA below). An ACGIH term. TLV-Short-Term Exposure Limit; a 15 minute TWA exposure that should not be exceeded at any time during a work day, even if the 8-hour TWA is within the TLV-TWA. An ACGIH term. TLV Time-Weighted Average; the TWA concentration for a conventional 8-hour workday and a 40-hour work week, to which it is believed that nearly all workers may be repeatedly exposed to, day after day, for a working lifetime without adverse effect. An ACGIH term. 21

24 WORKPLACE EXPOSURE STANDARD (WES) REVIEW: VINYL BROMIDE TERM g WES WES-TWA MEANING Microgram, or millionth of a gram. Workplace Exposure Standard WESs are values that refer to the airborne concentration of substances, at which it is believed that nearly all workers can be repeatedly exposed to, day after day, without coming to harm. The values are normally calculated on work schedules of five shifts of eight hours duration over a 40 hour week. A New Zealand term. The average airborne concentration of a substance calculated over an eight-hour working day. A New Zealand term. 22

25 APPENDICES APPENDIX 2: METHODS FOR SETTING OELs ACGIH STATEMENT OF POSITION REGARDING THE TLVS AND BEIS The American Conference of Governmental Industrial Hygienists (ACGIH ) is a private notfor-profit, nongovernmental corporation whose members are industrial hygienists or other occupational health and safety professionals dedicated to promoting health and safety within the workplace. ACGIH is a scientific association. ACGIH is not a standards setting body. As a scientific organization, it has established committees that review the existing published, peer-reviewed scientific literature. ACGIH publishes guidelines known as Threshold Limit Values (TLVs ) and Biological Exposure Indices (BEIs ) for use by industrial hygienists in making decisions regarding safe levels of exposure to various chemical and physical agents found in the workplace. In using these guidelines, industrial hygienists are cautioned that the TLVs and BEIs are only one of multiple factors to be considered in evaluating specific workplace situations and conditions. Each year ACGIH publishes its TLVs and BEIs in a book. In the introduction to the book, ACGIH states that the TLVs and BEIs are guidelines to be used by professionals trained in the practice of industrial hygiene. The TLVs and BEIs are not designed to be used as standards. Nevertheless, ACGIH is aware that in certain instances the TLVs and the BEIs are used as standards by national, state, or local governments. Governmental bodies establish public health standards based on statutory and legal frameworks that include definitions and criteria concerning the approach to be used in assessing and managing risk. In most instances, governmental bodies that set workplace health and safety standards are required to evaluate health effects, economic and technical feasibility, and the availability of acceptable methods to determine compliance. ACGIH TLVs and BEIs are not consensus standards. Voluntary consensus standards are developed or adopted by voluntary consensus standards bodies. The consensus standards process involves canvassing the opinions, views and positions of all interested parties and then developing a consensus position that is acceptable to these parties. While the process used to develop a TLV or BEI includes public notice and requests for all available and relevant scientific data, the TLV or BEI does not represent a consensus position that addresses all issues raised by all interested parties (e.g., issues of technical or economic feasibility). The TLVs and BEIs represent a scientific opinion based on a review of existing peer-reviewed scientific literature by committees of experts in public health and related sciences. ACGIH TLVs and BEIs are health-based values. ACGIH TLVs and BEIs are established by committees that review existing published and peer-reviewed literature in various scientific disciplines (e.g., industrial hygiene, toxicology, occupational medicine, and epidemiology). Based on the available information, ACGIH formulates a conclusion on the level of exposure that the typical worker can experience without adverse health effects. The TLVs and BEIs represent conditions under which ACGIH believes that nearly all workers may be repeatedly exposed without adverse health effects. They are not fine lines between safe and dangerous exposures, nor are they a relative index of toxicology. The TLVs and BEIs are not quantitative estimates of risk at different exposure levels or by different routes of exposure. 23

26 WORKPLACE EXPOSURE STANDARD (WES) REVIEW: VINYL BROMIDE Since ACGIH TLVs and BEIs are based solely on health factors, there is no consideration given to economic or technical feasibility. Regulatory agencies should not assume that it is economically or technically feasible for an industry or employer to meet TLVs or BEIs. Similarly, although there are usually valid methods to measure workplace exposures at TLVs and BEIs, there can be instances where such reliable test methods have not yet been validated. Obviously, such a situation can create major enforcement difficulties if a TLV or BEI was adopted as a standard. ACGIH does not believe that TLVs and BEIs should be adopted as standards without full compliance with applicable regulatory procedures including an analysis of other factors necessary to make appropriate risk management decisions. However, ACGIH does believe that regulatory bodies should consider TLVs or BEIs as valuable input into the risk characterization process (hazard identification, dose-response relationships, and exposure assessment). Regulatory bodies should view TLVs and BEIs as an expression of scientific opinion. ACGIH is proud of the scientists and the many members who volunteer their time to work on the TLV and BEI Committees. These experts develop written Documentation that include an expression of scientific opinion and a description of the basis, rationale, and limitations of the conclusions reached by ACGIH. The Documentation provides a comprehensive list and analysis of all the major published peer reviewed studies that ACGIH relied upon in formulating its scientific opinion. Regulatory agencies dealing with hazards addressed by a TLV or BEI should obtain a copy of the full written Documentation for the TLV or BEI. Any use of a TLV or BEI in a regulatory context should include a careful evaluation of the information in the written Documentation and consideration of all other factors as required by the statutes which govern the regulatory process of the governmental body involved. POLICY STATEMENT ON THE USES OF TLVS AND BEIS The Threshold Limit Values (TLVs ) and Biological Exposure Indices (BEIs ) are developed as guidelines to assist in the control of health hazards. These recommendations or guidelines are intended for use in the practice of industrial hygiene, to be interpreted and applied only by a person trained in this discipline. They are not developed for use as legal standards and ACGIH does not advocate their use as such. However, it is recognized that in certain circumstances individuals or organizations may wish to make use of these recommendations or guidelines as a supplement to their occupational safety and health program. ACGIH will not oppose their use in this manner, if the use of TLVs and BEIs in these instances will contribute to the overall improvement in worker protection. However, the user must recognize the constraints and limitations subject to their proper use and bear the responsibility for such use. The Introductions to the TLV /BEI Book and the TLV /BEI Documentation provide the philosophical and practical bases for the uses and limitations of the TLVs and BEIs. To extend those uses of the TLVs and BEIs to include other applications, such as use without the judgment of an industrial hygienist, application to a different population, development of new exposure/ recovery time models, or new effect endpoints, stretches the reliability and even viability of the database for the TLV or BEI as evidenced by the individual Documentation. It is not appropriate for individuals or organizations to impose on the TLVs or the BEIs their concepts of what the TLVs or BEIs should be or how they should be applied or to transfer regulatory standards requirements to the TLVs or BEIs. (Approved by the ACGIH Board of Directors on March 1, 1988.) 24

27 APPENDICES Special Note to User: The values listed in the book are intended for use in the practice of industrial hygiene as guidelines or recommendations to assist in the control of potential workplace health hazards and for no other use. These values are not fine lines between safe and dangerous concentrations and should not be used by anyone untrained in the discipline of industrial hygiene. It is imperative that the user of this book read the Introduction to each section and be familiar with the Documentation of the TLVs and BEIs before applying the recommendations contained herein. ACGIH disclaims liability with respect to the use of the TLVs and BEIs. EUROPEAN SCIENTIFIC COMMITTEE ON OCCUPATIONAL EXPOSURE LIMITS (SCOEL) SCOEL adopts a case-by-case approach to setting OELs. Wherever possible SCOEL will attempt to establish a health-based OEL, using the following general procedure: > > assemble all relevant data on the hazards (experimental information, data on physical properties etc) > > determine whether the database is adequate for the setting of an OEL > > identify adverse effects that may arise from exposure, and establish those that are crucial in deriving an OEL > > identify, and review relevant human and animal studies > > establish whether the substance acts via a non-threshold mechanism or whether a conventional (threshold) toxicological model can be used. Where non-threshold mechanisms are involved, SCOEL considers that health-based OELs cannot be established and different considerations apply (such as applying a numerical risk assessment process) > > assess dose/response data for each key effect, establish no observed adverse effect levels (NOAELs) where possible, or lowest observed adverse effect levels (LOAELs), or benchmark doses > > decide whether a STEL is required in addition to an 8-hour TWA limit > > decide whether a biological limit value (BLV) might be established, and what it will be > > establish a numerical value for an 8-hour TWA OEL at or below the NOAEL (or LOAEL as the case may be), incorporating an appropriate uncertainty factor > > establish a numerical value for a STEL and for a BLV, if required > > document the process so the rationale for the OEL is clear > > assess the technical measurement feasibility of the air and biological values. 25

28 WORKPLACE EXPOSURE STANDARD (WES) REVIEW: VINYL BROMIDE REFERENCES 1 WorkSafe New Zealand (2016). Workplace Exposure Standards and Biological Exposure Indices, 8th Ed. 2 European Commission (2016). Commission Staff Working Document Impact Assessment, accompanying the document Proposal for a Directive of the European Parliament and of the Council amending Directive 2004/37/EC on the protection of workers from the risks related to exposure to carcinogens or mutagens at work. 3 U.S. Department of Health and Human Services. (1983) Hazardous Substances Data Bank (HSDB, online database). National Toxicology Information Program, National Library of Medicine, Bethesda, MD. sis/search2/f?./temp/~d1nx2k:3 4 IARC (1986). Vinyl bromide. Monographs Volume 71, Bartsch, H. et al. (1979). Mutagenic and alkylating metabolites of haloethylenes, chlorobutadienes and dochlorobutenes produced by rodent or human liver tissues. Arch. Toxicol. 41, Lijinsky, W. and Andrews, A. W. (1980). Mutagenicity of vinyl compounds in Salmonella typhimurium. Teratog. Carcinog. Mutagen 1, Sasaki, Y.F. et al. (1998). Detection of in vivo genotoxicity of haloalkanes and haloalkenes carcinogenic to rodents by the alkaline single cell gel electrophoresis (comet) assay in multiple mouse organs. Mutat. Res. 419(1-3), Vogel, E.W. and Nivard, M.J. (1993). Performance of 181 chemicals in a Drosophila assay predominantly monitoring interchromosomal mitotic recombination. Mutagenisis 8, IARC (2008). Vinyl bromide. Monographs Volume 97, Benya, T.J. et al. (1982). Inhalation carcinogenicity bioassay of vinyl chloride in rats. Toxicol. Appl. Pharmacol. 64, NTP Final Report on Carcinogens background document for vinyl bromide (2015). download;jsessionid=bfff3f a5d944e29d7fdd7979?doi= &rep=rep1&type=pdf 12 Bolt, H.M. et al. (1978). Rat liver microsomal uptake and irreversible protein binding of [1,2-14 C]vinyl bromide. Toxicol. Appl. Pharmacol. 44(3), SCOEL (2008). Recommendation from the Scientific Committee on Occupational Exposure Limits for Vinyl Bromide. SCOEL/SUM/ Feron, V.J. et al. (1981). Lifespan oral toxicity study of vinyl chloride in rats. Fd. Cosmet. Toxicol. 19, Storm, J.E. and Rozman, K.K. (1997). Evaluation of alternative methods for establishing safe levels of occupational exposure to vinyl halides. Reg. Toxicol. Pharmacol. 25, American Conference of Governmental Industrial Hygienists (ACGIH ), (2011). Vinyl bromide. Documentation of the Threshold Limit Values and Biological Exposure Indices. 7th Edition, ACGIH, Cincinnati, Ohio. Copyright Reprinted with permission. 17 Dutch Expert Committee on Occupational Standards (1999). Available on-line at files/osh15.pdf 18 NIOSH (1994). Manual of Analytical Methods (NMAM), 4th Ed. Analytical method 1009, issue European Commission (2016) Fact Sheet. Commission proposes better workers protection against cancer-causing chemicals American Conference of Governmental Industrial Hygienists (ACGIH ), (2016) TLVs and BEIs book. ACGIH, Cincinnati, Ohio. Copyright Reprinted with permission. 26

29 DISCLAIMER WorkSafe New Zealand has made every effort to ensure the information contained in this publication is reliable, but makes no guarantee of its completeness. WorkSafe may change the contents of this guide at any time without notice. This document is a guideline only. It should not be used as a substitute for legislation or legal advice. WorkSafe is not responsible for the results of any action taken on the basis of information in this document, or for any errors or omissions. Published: April 2017 Current until: 2019 PO Box 165, Wellington 6140, New Zealand Except for the logos of WorkSafe, this copyright work is licensed under a Creative Commons Attribution-Non-commercial 3.0 NZ licence. To view a copy of this licence, visit In essence, you are free to copy, communicate and adapt the work for non-commercial purposes, as long as you attribute the work to WorkSafe and abide by the other licence terms. WSNZ_2598_April 2017

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