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4 Evaluating Hazards and Assessing Risks in the Laboratory 4.A INTRODUCTION 47 4.B SOURCES OF INFORMATION 47 4.B.1 Chemical Hygiene Plan (CHP) 47 4.B.2 Material Safety Data Sheets (MSDSs) 47 4.B.3 Globally Harmonized System for Hazard Communication 49 4.B.4 Laboratory Chemical Safety Summaries 50 4.B.5 Labels 51 4.B.6 Additional Sources of Information 51 4.B.7 Computer Services 52 4.B.7.1 The National Library of Medicine Databases 53 4.B.7.2 Chemical Abstracts Databases 53 4.B.7.3 Informal Forums 53 4.B.8 Training 53 4.C TOXIC EFFECTS OF LABORATORY CHEMICALS 53 4.C.1 Basic Principles 53 4.C.1.1 Dose-Response Relationships 54 4.C.1.2 Duration and Frequency of Exposure 56 4.C.1.3 Routes of Exposure 57 4.C.2 Assessing Risks of Exposure to Toxic Laboratory Chemicals 58 4.C.2.1 Acute Toxicants 59 4.C.3 Types of Toxins 60 4.C.3.1 Irritants, Corrosive Substances, Allergens, and Sensitizers 60 4.C.3.2 Asphyxiants 62 4.C.3.3 Neurotoxins 62 4.C.3.4 Reproductive and Developmental Toxins 62 4.C.3.5 Toxins Affecting Other Target Organs 63 4.C.3.6 Carcinogens 63 4.C.3.7 Control Banding 64 4.D FLAMMABLE, REACTIVE, AND EXPLOSIVE HAZARDS 65 4.D.1 Flammable Hazards 65 4.D.1.1 Flammable Substances 65 4.D.1.2 Flammability Characteristics 65 4.D.1.3 Classes of Flammability 68 4.D.1.4 Causes of Ignition 69 4.D.1.5 Special Hazards 69 4.D.2 Reactive Hazards 70 4.D.2.1 Water Reactives 70 4.D.2.2 Pyrophorics 70 4.D.2.3 Incompatible Chemicals 70 4.D.3 Explosive Hazards 70 4.D.3.1 Explosives 70 4.D.3.2 Azos, Peroxides, and Peroxidizables 72 45

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46 PRUDENT PRACTICES IN THE LABORATORY 4.D.3.3 Other Oxidizers 73 4.D.3.4 Powders and Dusts 73 4.D.3.5 Explosive Boiling 73 4.D.3.6 Other Considerations 73 4.E PHYSICAL HAZARDS 74 4.E.1 Compressed Gases 74 4.E.2 Nonflammable Cryogens 74 4.E.3 High-Pressure Reactions 74 4.E.4 Vacuum Work 75 4.E.5 Ultraviolet, Visible, and Near-Infrared Radiation 75 4.E.6 Radio Frequency and Microwave Hazards 75 4.E.7 Electrical Hazards 76 4.E.8 Magnetic Fields 76 4.E.9 Sharp Edges 76 4.E.10 Slips, Trips, and Falls 77 4.E.11 Ergonomic Hazards in the Laboratory 77 4.F NANOMATERIALS 77 4.G BIOHAZARDS 79 4.H HAZARDS FROM RADIOACTIVITY 79

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47 EVALUATING HAZARDS AND ASSESSING RISKS IN THE LABORATORY 4.A INTRODUCTION ous Chemicals in Laboratories, 29 CFR § 1910.1450) to have a written CHP, which includes provisions A key element of planning an experiment is assess- capable of protecting personnel from the ‘’health ing the hazards and potential risks associated with hazards presented by hazardous chemicals used in the chemicals and laboratory operations to be used. that particular workplace.” All laboratory personnel This chapter provides a practical guide for the trained should be familiar with and have ready access to their laboratory personnel engaged in these activities. Sec- institution’s CHP. In some laboratories, CHPs include tion 4.B introduces the sources of information for data standard operating procedures for work with specific on toxic, flammable, reactive, and explosive chemical chemical substances, and the CHP may be sufficient substances. Section 4.C discusses the toxic effects of as the primary source of information used for risk as- laboratory chemicals by first presenting the basic prin- sessment and experiment planning. However, most ciples that form the foundation for evaluating hazards CHPs provide only general procedures for handling for toxic substances. The remainder of this section de- chemicals, and prudent experiment planning requires scribes how trained laboratory personnel can use this that laboratory personnel consult additional sources understanding and the sources of information to assess for information on the properties of the substances that the risks associated with potential hazards of chemical will be encountered in the proposed experiment. Many substances and then to select the appropriate level of laboratories require documentation of specific hazards laboratory practice as discussed in Chapter 4. Sections and controls for a proposed experiment. 4.D and 4.E present guidelines for evaluating hazards associated with the use of flammable, reactive, and ex- plosive substances and physical hazards, respectively. 4.B.2 Material Safety Data Sheets (MSDSs) Finally, nanomaterials, biohazards, and radioactivity Federal regulations (OSHA Hazard Communication hazards are discussed briefly in sections 4.F and 4.G, Standard 29 CFR § 1910.1200) require that manufactur- respectively. ers and distributors of hazardous chemicals provide The primary responsibility for proper hazard evalu- users with material safety data sheets (MSDSs),1 which ations and risk assessments lies with the person per- are designed to provide the information needed to forming the experiment. That being said, the respon- protect users from any hazards that may be associated sibility is shared by the laboratory supervisor. The with the product. MSDSs have become the primary actual evaluations and assessments may be performed vehicle through which the potential hazards of mate- by trained laboratory personnel, but these should be rials obtained from commercial sources are commu- checked and authorized by the supervisor. The super- nicated to trained laboratory personnel. Institutions visor is also responsible for ensuring that everyone are required by law (OSHA Hazard Communication involved in an experiment and those nearby under- Standard) to retain and make readily available the stand the evaluations and assessments. For example, MSDSs provided by chemical suppliers. The MSDSs depending on the level of training and experience, the themselves may be electronic or on paper, as long as immediate laboratory supervisor may be involved in employees have unrestricted access to the documents. the experimental work itself. In addition, some orga- Be aware that some laboratories have been asked by nizations have environmental health and safety (EHS) local emergency personnel to print paper copies in the offices, with industrial hygiene specialists to advise event of an emergency. trained laboratory personnel and their supervisors in As the first step in risk assessment, trained labora- risk assessment. When required by federal regulation, tory personnel should examine any plan for a proposed Chemical Hygiene Officers (CHOs) play similar roles experiment and identify the chemicals with toxicologi- in many organizations. As part of a culture of safety, cal properties they are not familiar with from previous all of these groups work cooperatively to create a safe experience. The MSDS for each unfamiliar chemical environment and to ensure that hazards are appropri- should be examined. Procedures for accessing MSDS ately identified and assessed prior to beginning work. files vary from institution to institution. In some cases, MSDS files are present in each laboratory, but often 4.B SOURCES OF INFORMATION complete files of MSDSs are maintained only in a central location, such as the institution’s EHS office. 4.B.1 Chemical Hygiene Plan (CHP) Many laboratories are able to access MSDSs electroni- Beginning in 1991, every laboratory in which haz- 1In the Globally Harmonized System for Hazard Communication, ardous chemicals are used has been required by federal the term “material safety data sheet” has been shortened to “safety regulations (Occupational Safety and Health Adminis- data sheet (SDS).” This book will continue to use the term MSDS as tration [OSHA] Occupational Exposure to Hazard- it is more recognizable at the time of writing than SDS.

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48 PRUDENT PRACTICES IN THE LABORATORY cally, either from CD-ROM disks, via the internet, or usually consists of a list of precautions to be from other computer networks. Laboratory personnel taken in handling and storing the material. Par- can always contact the chemical supplier directly and ticular attention is devoted to listing appropriate request that an MSDS be sent by mail. control measures, such as the use of engineering MSDSs are technical documents, several pages long, controls and personal protective equipment nec- typically beginning with a compilation of data on the essary to prevent harmful exposures. Because an physical, chemical, and toxicological properties of the MSDS is written to address the largest scale at substance and providing concise suggestions for han- which the material could conceivably be used, dling, storage, and disposal. Finally, emergency and the procedures recommended may involve first-aid procedures are usually outlined. At present, more stringent precautions than are necessary there is no required format for an MSDS; however, in the context of laboratory use. OSHA recommends the general 16-part format created 8. Emergency and first-aid procedures. This sec- by the American National Standards Institute (ANSI tion usually includes recommendations for Z400.1). The information typically found in an MSDS firefighting procedures, first-aid treatment, follows: and steps to be taken if the material is released or spilled. Again, the measures outlined here 1. Supplier (with address and phone number) are chosen to encompass worst-case scenarios, and date MSDS was prepared or revised. Toxic- including accidents on a larger scale than are ity data and exposure limits sometimes undergo likely to occur in a laboratory. revision, and for this reason MSDSs should be 9. Disposal considerations. Some MSDSs provide reviewed periodically to check that they contain guidelines for the proper disposal of waste ma- up-to-date information. Phone numbers are terial. Others direct the users to dispose of the provided so that, if necessary, users can contact material in accordance with federal, state, and the supplier to obtain additional information on local guidelines. hazards and emergency procedures. 10. Transportation information. This chapter only 2. Chemical. For products that are mixtures, this evaluates the hazards and assesses the risks as- section may include the identity of most but not sociated with chemicals in the context of labora- every ingredient. Hazardous chemicals must tory use. MSDSs, in contrast, must address the be identified. Common synonyms are usually hazards associated with chemicals in all possible listed. situations, including industrial manufacturing 3. Physical and chemical properties. Data such operations and large-scale transportation acci- as melting point, boiling point, and molecular dents. For this reason, some of the information weight are included here. in an MSDS may not be relevant to the handling 4. Physical hazards. This section provides data and use of that chemical in a laboratory. For ex- related to flammability, reactivity, and explosion ample, most MSDSs stipulate that self-contained hazards. breathing apparatus and heavy rubber gloves 5. Toxicity data. OSHA, the National Institute and boots be worn in cleaning up spills, even of for Occupational Safety and Health (NIOSH), relatively nontoxic materials such as acetone. and the American Conference of Governmental Such precautions, however, might be unneces- Industrial Hygienists (ACGIH) exposure lim- sary in laboratory-scale spills of acetone and its (as discussed in section 4.C.2.1) are listed. other substances of low toxicity. Many MSDSs provide lengthy and compre- hensive compilations of toxicity data and even Originally, the principal audience for MSDSs was references to applicable federal standards and constituted of health and safety professionals (who are regulations. responsible for formulating safe workplace practices), 6. H ealth hazards. A cute and chronic health medical personnel (who direct medical surveillance hazards are listed, together with the signs and programs and treat exposed workers), and emergency symptoms of exposure. The primary routes of responders (e.g., fire department personnel). With entry of the substance into the body are also the promulgation of federal regulations such as the described. In addition, potential carcinogens are OSHA Hazard Communication Standard (29 CFR § explicitly identified. In some MSDSs, this list of 1910.1200) and the OSHA Laboratory Standard (29 toxic effects is quite lengthy and includes every CFR § 1910.1450), the audience for MSDSs has ex- possible harmful effect the substance has under panded to include trained laboratory personnel in the conditions of every conceivable use. industrial and academic laboratories. However, not 7. Storage and handling procedures. This section

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49 EVALUATING HAZARDS AND ASSESSING RISKS IN THE LABORATORY all MSDSs are written to meet the requirements of this the Department of Transportation, the EPA, and the new audience effectively. Consumer Product Safety Commission. At the time this In summary, among the currently available re- book was written, the agencies had not yet provided fi- sources, MSDSs remain the best single source of infor- nal guidance on use of GHS. The revised Hazard Com- mation for the purpose of evaluating the hazards and munication Standard (29 CFR § 1910.1200) is expected assessing the risks of chemical substances. However, to be issued by OSHA in the near future. laboratory personnel should recognize the limitations GHS classifies substances by the physical, health, of MSDSs as applied to laboratory-scale operations. If and environmental hazards that they pose, and pro- MSDSs are not adequate, specific laboratory operating vides signal words (e.g., Danger), hazard statements procedures should be available for the specific labora- (e.g., may cause fire or explosion), and standard tory manipulations to be employed: pictogram-based labels to indicate the hazards and their severity. When transporting hazardous chemicals, 1. The quality of MSDSs produced by different use the pictograms specified in the UN Recommenda- c hemical suppliers varies widely. The util- tions on the Transport of Dangerous Goods, Model ity of some MSDSs is compromised by vague Regulations. For other purposes, the pictograms in and unqualified generalizations and internal Figure 4.1 should be used. Container labels should inconsistencies. have a product identifier with hazardous ingredient 2. Unique morphology of solid hazardous chemi- disclosure, supplier information, a hazard pictogram, cals may not be addressed in MSDSs; for exam- a signal word, a hazard statement, first-aid informa- ple, an MSDS for nano-size titanium dioxide may tion, and supplemental information. Three of these not present the unique toxicity considerations for elements—the pictograms, signal word, and hazard these ultrafine particulates. statements—are standardized under GHS. The signal 3. MSDSs must describe control measures and pre- words, either “Danger” or “Warning,” reflect the sever- cautions for work on a variety of scales, ranging ity of hazard posed. Hazard statements are standard from microscale laboratory experiments to large phrases that describe the nature of the hazard posed manufacturing operations. Some procedures by the material (e.g., heating may cause explosion). outlined in an MSDS may therefore be unneces- sary or inappropriate for laboratory-scale work. An unfortunate consequence of this problem is that it tends to breed a lack of confidence in the relevance of the MSDS to laboratory-scale work. 4. Many MSDSs comprehensively list all conceiv- able health hazards associated with a substance without differentiating which are most sig- nificant and which are most likely to actually be encountered. As a result, trained laboratory personnel may not distinguish highly hazard- ous materials from moderately hazardous and relatively harmless ones. 4.B.3 Globally Harmonized System (GHS) for Hazard Communication The GHS of Classification and Labeling of Chemicals is an internationally recognized system for hazard clas- sification and communication. (Available at http:// www.unece.org.) It was developed with support from the International Labour Organization (ILO), the Organisation for Economic Co-operation and Devel- opment, and the United Nations Sub-Committee of Experts on the Transport of Dangerous Goods with the goal of standardizing hazard communication to improve the safety of international trade and com- merce. Within the United States, the responsibility for FIGURE 4.1 GHS placards for labeling containers of haz- implementing the GHS falls to four agencies: OSHA, ardous chemicals.

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50 PRUDENT PRACTICES IN THE LABORATORY GHS recognizes 16 types of physical hazards, 10 4. first-aid measures, types of health hazard, and an environmental hazard. 5. firefighting measures, 6. accidental release measures, 7. handling and storage, Physical hazards include 8. exposure controls/personal protection, • explosives; 9. physical and chemical properties, • flammable gases; 10. stability and reactivity, • flammable aerosols; 11. toxicological information, • oxidizing gases; 12. ecological information, • gases under pressure; 13. disposal considerations, • flammable liquids; 14. transport information, • flammable solids; 15. regulatory information, and • self-reactive substances; 16. other information. • pyrophoric liquids; • pyrophoric solids; As with current MSDSs, these sheets are intended • self-heating substances; to inform employers and personnel of the hazards • substances which, in contact with water, emit associated with the chemicals they are handling, and flammable gases; to act as a resource for management of the chemicals. • oxidizing liquids; Trained personnel should evaluate the information and • oxidizing solids; use it to develop safety and emergency response poli- • organic peroxides; and cies, protocols, and procedures that are tailored to the • corrosive to metals. workplace or laboratory. Health hazards include 4.B.4 Laboratory Chemical Safety Summaries (LCSSs) • acute toxicity, • skin corrosion or irritation, As discussed above, although MSDSs are invaluable • serious eye damage or eye irritation, resources, they suffer some limitations as applied to • respiratory or skin sensitization, risk assessment in the specific context of the labora- • germ cell mutagenicity, tory. Committee-generated LCSSs, which are tailored • carcinogenicity, to trained laboratory personnel, are on the CD accom- • reproductive toxicology, panying this book. As indicated in their name, LCSSs • target organ systemic toxicity—single exposure, provide information on chemicals in the context of • target organ systemic toxicity—repeated expo- laboratory use. These documents are summaries and sure, and are not intended to be comprehensive or to fulfill the • aspiration hazard. needs of all conceivable users of a chemical. In conjunc- tion with the guidelines described in this chapter, the LCSS gives essential information required to assess the Environmental hazard includes risks associated with the use of a particular chemical • Hazardous to the aquatic environment: in the laboratory. acute aquatic toxicity or The format, organization, and contents of LCSSs chronic aquatic toxicity with are described in detail in the introduction on the CD. • bioaccumulation potential Included in an LCSS are the key physical, chemi- • rapid degradability. cal, and toxicological data necessary to evaluate the relative degree of hazard posed by a substance. LCSSs In addition to the labeling requirements, GHS re- also contain a concise critical discussion, presented in quires a standard format for Safety Data Sheets (SDS) a style readily understandable to trained laboratory that accompany hazardous chemicals. Note the change personnel, of the toxicity, flammability, reactivity, and in terminology from MSDS. SDSs must contain a mini- explosivity of the chemical; recommendations for the mum of 16 elements: handling, storage, and disposal of the title substance; and first-aid and emergency response procedures. 1. identification, The CD contains LCSSs for 91 chemical substances. 2. hazard(s) identification, Several criteria were used in selecting these chemicals, 3. composition/information on ingredients, the most important consideration being whether the

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51 EVALUATING HAZARDS AND ASSESSING RISKS IN THE LABORATORY substance is commonly used in laboratories. Preference 1. International Chemical Safety Cards from the Inter- was also given to materials that pose relatively serious national Programme on Chemical Safety (IPCS, hazards. Finally, an effort was made to select chemicals 2009). The IPCS is a joint activity of the ILO, the representing a variety of classes of substances, so as to United Nations Environment Programme, and provide models for the future development of addi- the World Health Organization. The cards con- tional LCSSs. A blank copy of the form is provided for tain hazard and exposure information from rec- development of laboratory-specific LCSSs. ognized sources and undergo international peer review. They are designed to be understandable to employers and employees in factories, agri- 4.B.5 Labels culture, industrial shops, and other areas, and Commercial suppliers are required by law (OSHA can be considered complements to MSDSs. They Hazard Communication Standard) to provide their are available in 18 languages and can be found chemicals in containers with precautionary labels. online through the NIOSH Web site, www.cdc. Labels usually present concise and nontechnical sum- gov/niosh, or through the ILO Web site, www. maries of the principal hazards associated with their ilo.org. contents. Note that precautionary labels do not replace 2. NIOSH Pocket Guide to Chemical Hazards (HHS/ MSDSs and LCSSs as the primary sources of informa- CDC/NIOSH, 2007). This volume is updated tion for risk assessment in the laboratory. However, regularly and is found on the NIOSH Web site labels serve as valuable reminders of the key hazards (http://www.cdc.gov/niosh). These charts associated with the substance. As with the MSDS, the are quick guides to chemical properties, reac- quality of information presented on a label can be tivities, exposure routes and limits, and first-aid inconsistent. Additionally, labeling is not always re- measures. quired for chemicals transferred between laboratories 3. A Comprehensive Guide to the Hazardous Proper- within the same building. ties of Chemical Substances, 3rd edition (Patnaik, 2007). This particularly valuable guide is writ- ten at a level appropriate for typical laboratory 4.B.6 Additional Sources of Information personnel. It covers more than 1,500 substances; The resources described above provide the founda- sections in each entry include uses and exposure tion for risk assessment of chemicals in the laboratory. risk, physical properties, health hazards, expo- This section highlights the sources that should be con- sure limits, fire and explosion hazards, and dis- sulted for additional information on specific harmful posal or destruction. Entries are organized into effects of chemical substances. Although MSDSs and chapters according to functional group classes, LCSSs include information on toxic effects, in some and each chapter begins with a general discus- situations laboratory personnel should seek additional sion of the properties and hazards of the class. more detailed information. This step is particularly im- 4. 2009 TLVs and BEIs: Based on the Documentation of portant when laboratory personnel are planning to use the Threshold Limit Values for Chemical Substances chemicals that have a high degree of acute or chronic and Physical Agents and Biological Exposure Indices toxicity or when it is anticipated that work will be (ACGIH, 2009). A handy booklet listing ACGIH conducted with a particular toxic substance frequently threshold limit values (TLVs) and short-term or over an extended period of time. Institutional CHPs exposure limits (STELs). These values are under include the requirement for CHOs, who are capable continuous review, and this booklet is updated of providing information on hazards and controls. annually. The multivolume publication Docu- CHOs can assist laboratory personnel in obtaining and mentation of the Threshold Limit Values and Bio- interpreting hazard information and in ensuring the logical Exposure Indices (ACGIH, 2008b) reviews availability of training and information for all labora- the data (with reference to literature sources) tory personnel. that were used to establish the TLVs. (For more Sections 4.B.2 and 4.B.4 of this chapter provide information about TLVs, see section 4.C.2.1 of explicit guidelines on how laboratory personnel use this chapter.) the information in an MSDS or LCSS, respectively, to 5. Fire Protection for Laboratories Using Chemicals recognize when it is necessary to seek such additional (NFPA, 2004). This is the national fire safety information. code pertaining to laboratory use of chemicals. The following annotated list provides references on It describes the basic requirements for fire pro- the hazardous properties of chemicals and which are tection of life and property in the laboratory. useful for assessing risks in the laboratory. For example, the document outlines technical

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52 PRUDENT PRACTICES IN THE LABORATORY requirements for equipment such as fire sup- is written with the industrial hygienists and first pression systems and ventilation systems for responder in mind, covers 2,100 substances. flammables and defines the maximum allow- 13. Clinical Toxicology, 1st edition (Ford et al., 2001). able quantities for flammable materials within This book is designed for clinicians and other the laboratory. health care providers. It describes the symp- 6. Fire Protection Guide to Hazardous Materials, 13th toms and treatment of poisoning from various edition (NFPA, 2001). This resource contains sources. hazard data on hundreds of chemicals and guid- 14. Casarett and Doull’s Toxicology: The Basic Science ance on handling and storage of, and emergency of Poisons, 7th edition (Klaassen, 2007). This procedures for, those chemicals. complete and readable overview of toxicology 7. is a good textbook but is not arranged as a ready Bretherick’s Handbook of Reactive Chemical Haz- ards, 7th edition (Urben, 2007). This handbook reference for handling laboratory emergencies. is a comprehensive compilation of examples of 15. C atalog of Teratogenic Agents , 11th edition violent reactions, fires, and explosions due to (Shepard and Lemire, 2004). This catalog is one unstable chemicals, as well as reports on known of the best references available on the subject of incompatibility between reactive chemicals. reproductive and developmental toxins. 8. H azardous Chemicals Handbook , 2nd edition 16. Wiley Guide to Chemical Incompatibilities , 2nd (Carson and Mumford, 2002). This book is geared edition (Pohanish and Greene, 2003). Simple- toward an industrial audience. It provides basic to-use reference listing the incompatibilities of information about chemical hazards and syn- more than 11,000 chemicals. Includes informa- thesizes technical guidance from a number of tion about chemical incompatibility, conditions authorities in chemical safety. The chapters are that favor undesirable reactions, and corrosivity organized by hazard (e.g., “Toxic Chemicals,” data. “Reactive Chemicals,” and “Cryogens”). 17. Occupational Health Guidelines for Chemical Haz- 9. Sax’s Dangerous Properties of Industrial Materials, ards (HHS/CDC/NIOSH, 1981) and a supple- 11th edition, three volumes (Lewis, 2004). Also ment (HHS/CDC/NIOSH, 1995). The guide- available on CD, this compilation of data for lines currently cover more than 400 substances more than 26,000 chemical substances contains and are based on the information assembled much of the information found in a typical under the Standards Completion Program, MSDS, including physical and chemical prop- which served as the basis for the promulga- erties; data on toxicity, flammability, reactivity, tion of federal occupational health regulations and explosivity; and a concise safety profile de- (“substance-specific standards”). Typically five scribing symptoms of exposure. It also contains pages long and written clearly at a level readily immediately dangerous to life or health (IDLH) understood by trained laboratory personnel, levels for approximately 1,000 chemicals, and each set of guidelines includes information on for laboratory personnel it is a useful reference physical, chemical, and toxicological properties; for checking the accuracy of an MSDS and a signs and symptoms of exposure; and consider- valuable resource in preparing a laboratory’s able detail on control measures, medical surveil- own LCSSs. lance practices, and emergency first-aid proce- 10. Patty’s Industrial Toxicology, 5th edition (Bingham dures. However, some guidelines date back to et al., 2001). Also available on CD, this authori- 1978 and may not be current, particularly with tative reference on the toxicology of different regard to chronic toxic effects. These guidelines classes of organic and inorganic compounds are available on the NIOSH Web site (http:// focuses on health effects; hazards due to flam- www.cdc.gov/niosh/). mability, reactivity, and explosivity are not covered. A number of Web-based resources also exist. Some of 11. these are NIOSH Databases and Information Resources Proctor and Hughes’ Chemical Hazards of the Work- place, 5th edition (Hathaway and Proctor, 2004). (www.cdc.gov/niosh) and TOXNET through the Na- This resource provides an excellent summary of tional Library of Medicine (NLM; www.nlm.nih.gov). the toxicology of more than 600 chemicals. Most entries are one to two pages and include signs 4.B.7 Computer Services and symptoms of exposure with reference to specific clinical reports. In addition to computerized MSDSs, a number of 12. computer databases are available that supply data for Sittig’s Handbook of Toxic and Hazardous Chemicals and Carcinogens, 5th edition, two volumes (Po- creating or supplementing MSDSs, for example, the hanish, 2008). This very good reference, which NLM and Chemical Abstracts (CA) databases. These

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53 EVALUATING HAZARDS AND ASSESSING RISKS IN THE LABORATORY and other such databases are accessible through vari- This database provides information on toxicity of ous online computer data services; also, most of this chemicals to aquatic life, terrestrial plants, and wildlife. information is available as CD and computer updates. Searching any database listed above is best done Many of these services can be accessed for up-to-date using the CAS registry number for the particular toxicity information. chemical. Governmental sources of EHS information include 4.B.7.3 Informal Forums • NIOSH (www.cdc.gov/niosh), • OSHA (www.osha.gov), The “Letters to the Editor” column of Chemical & • Environmental Protection Agency (EPA; www. Engineering News (C&EN), published weekly by the epa.gov). American Chemical Society (ACS), was for many years an informal but widely accepted forum for reporting anecdotal information on chemical reactivity hazards 4.B.7.1 The National Library of Medicine and other safety-related information. Although less Databases frequently updated, the ACS maintains an archive of The databases supplied by NLM are easy to use and all safety-related letters submitted to C&EN on the free to access via the Web. TOXNET is an online col- Web site of the Division of Chemical Health and Safety lection of toxicological and environmental health da- (CHAS) of ACS. CHAS also publishes the Journal of tabases. TOXLINE, for example, is an online database Chemical Health and Safety. Additional resources include that accesses journals and other resources for current the annual safety editorial called “Safety Notables: toxicological information on drugs and chemicals. Information from the Literature” in the Organic Process It covers data published from 1900 to the present. Research and Development and community Listservs Databases accessible through TOXNET include the relating to laboratory safety. Hazardous Substance Data Base (HSDB) Carcinogenic Potency Database (CPDB), the Developmental and Re- 4.B.8 Training productive Toxicology Database (DART), the Genetic Toxicology Data Bank (GENE-TOX), the Integrated One important source of information for labora- Risk Information System (IRIS), the Chemical Carcino- tory personnel is training sessions, and the critical genesis Research Information System (CCRIS), and the place it holds in creating a safe environment should International Toxicity Estimates for Risk (ITER). Other not be underestimated. Facts are only as useful as databases supplied by NLM that provide access to one’s ability to interpret and apply them to a given toxicological information are PubMed, which includes problem, and training provides context for their use. access to MEDLINE, PubChem, and ChemIDPlus. Free Hands-on, scenario-based training is ideal because it text searching is available on most of the databases. provides the participants with the chance to practice activities and behaviors in a safe way. Such training is especially useful for learning emergency response 4.B.7.2 Chemical Abstracts Databases procedures. Another effective tool, particularly when Another source of toxicity data is Chemical Abstracts trying to build awareness of a given safety concern, is Service (CAS). In addition to the NLM, several services case studies. Prior to beginning any laboratory activity, provide CAS, including DIALOG, ORBIT, STN, and it is important to ensure that personnel have enough SciFinder. Searching procedures for CAS depend on training to safely perform required tasks. If new equip- the various services supplying the database. Searching ment, materials, or techniques are to be used, a risk costs are considerably higher than for NLM databases assessment should be performed, and any knowledge because CAS royalties must be paid. Telephone num- gaps should be filled before beginning work. (More bers for the above suppliers are as follows: information about training programs can be found in Chapter 2, section 2.G.) DIALOG, 800-334-2564; Questel, 800-456-7248; 4.C TOXIC EFFECTS OF STN, 800-734-4227; LABORATORY CHEMICALS SciFinder, 800-753-4227. 4.C.1 Basic Principles Additional information can be found on the CAS Web site, www.cas.org. The chemicals encountered in the laboratory have Specialized databases also exist. One example is the a broad spectrum of physical, chemical, and toxico- ECOTOX database from EPA (www.epa.gov/ecotox). logical properties and physiological effects. The risks associated with chemicals must be well understood

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54 PRUDENT PRACTICES IN THE LABORATORY prior to their use in an experiment. The risk of toxic 4.C.1.1 Dose-Response Relationships effects is related to both the extent of exposure and the Toxicology is the study of the adverse effects of inherent toxicity of a chemical. As discussed in detail chemicals on living systems. The basic tenets of toxi- below, extent of exposure is determined by the dose, cology are that no substance is entirely safe and that all the duration and frequency of exposure, and the route chemicals result in some toxic effects if a high enough of exposure. Exposure to even large doses of chemicals amount (dose) of the substance comes in contact with with little inherent toxicity, such as phosphate buffer, a living system. As mentioned in Chapter 2, Paracelsus presents low risk. In contrast, even small quantities of noted that the dose makes the poison and is perhaps chemicals with high inherent toxicity or corrosivity the most important concept for all trained laboratory may cause significant adverse effects. The duration and personnel to know. For example, water, a vital sub- frequency of exposure are also critical factors in deter- stance for life, results in death if a sufficiently large mining whether a chemical will produce harmful ef- amount (i.e., gallons) is ingested at one time. On the fects. A single exposure to some chemicals is sufficient other hand, sodium cyanide, a highly lethal chemical, to produce an adverse health effect; for other chemicals produces no permanent (acute) effects if a living sys- repeated exposure is required to produce toxic effects. tem is exposed to a sufficiently low dose. The single For most substances, the route of exposure (through the most important factor that determines whether a sub- skin, the eyes, the gastrointestinal tract, or the respira- stance is harmful (or, conversely, safe) to an individual tory tract) is also an important consideration in risk is the relationship between the amount (and concen- assessment. For chemicals that are systemic toxicants, tration) of the chemical reaching the target organ, and the internal dose to the target organ is a critical factor. the toxic effect it produces. For all chemicals, there is Exposure to acute toxicants can be guided by well- a range of concentrations that result in a graded effect defined toxicity parameters based on animal studies between the extremes of no effect and death. In toxi- and often human exposure from accidental poisoning. cology, this range is referred to as the dose-response The analogous quantitative data needed to make deci- relationship for the chemical. The dose is the amount sions about the neurotoxicity and immunogenicity of of the chemical and the response is the effect of the various chemicals is often unavailable. chemical. This relationship is unique for each chemi- When considering possible toxicity hazards while cal, although for similar types of chemicals, the dose- planning an experiment, recognizing that the combina- response relationships are often similar. (See Figure tion of the toxic effects of two substances may be significantly 4.2.) Among the thousands of laboratory chemicals, a greater than the toxic effect of either substance alone is wide spectrum of doses exists that are required to pro- important. Because most chemical reactions produce duce toxic effects and even death. For most chemicals, mixtures of substances with combined toxicities that a threshold dose has been established (by rule or by have never been evaluated, it is prudent to assume that consensus) below which a chemical is not considered mixtures of different substances (i.e., chemical reaction to be harmful to most individuals. mixtures) will be more toxic than their most toxic ingre- In these curves, dosage is plotted against the per- dient. Furthermore, chemical reactions involving two cent of the population affected by the dosage. Curve or more substances may form reaction products that A represents a compound that has an effect on some are significantly more toxic than the starting reactants. percent of the population even at small doses. Curve This possibility of generating toxic reaction products B represents a compound that has an effect only above may not be anticipated by trained laboratory personnel a dosage threshold. in cases where the reactants are mixed unintentionally. Some chemicals (e.g., dioxin) produce death in For example, inadvertent mixing of formaldehyde (a laboratory animals exposed to microgram doses and common tissue fixative) and hydrogen chloride results therefore are extremely toxic. Other substances, how- in the generation of bis(chloromethyl)ether, a potent ever, have no harmful effects following doses in excess human carcinogen. of several grams. One way to evaluate the acute toxic- All laboratory personnel must understand certain ity (i.e., the toxicity occurring after a single exposure) basic principles of toxicology and recognize the ma- of laboratory chemicals involves their lethal dose 50 jor classes of toxic and corrosive chemicals. The next (LD50) or lethal concentration 50 (LC50) value. The LD50 sections of this chapter summarize the key concepts is defined as the amount of a chemical that when in- involved in assessing the risks associated with the use gested, injected, or applied to the skin of a test animal of toxic chemicals in the laboratory. (Also see Chapter under controlled laboratory conditions kills one-half 6, section 6.D.) Box 4.1 provides a quick guide for per- (50%) of the animals. The LD50 is usually expressed forming a toxicity-based risk assessment for laboratory in milligrams or grams per kilogram of body weight. chemicals. For volatile chemicals (i.e., chemicals with sufficient

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55 EVALUATING HAZARDS AND ASSESSING RISKS IN THE LABORATORY BOX 4.1 Quick Guide for Toxicity Risk Assessment of Chemicals The following outline provides a summary of the steps enough to present a significant risk of exposure discussed in this chapter that trained laboratory personnel through inhalation? If liquid, can the substances be should use to assess the risks of handling toxic chemicals. absorbed through the skin? Is it possible that dusts Note that if a laboratory chemical safety summary (LCSS) is or aerosols will be formed in the experiment? Does not already available, this enables a worker to prepare his the experiment involve a significant risk of inadver- or her own LCSS. tent ingestion or injection of chemicals? 5. E valuate quantitative information on 1. Identify chemicals to be used and circum- toxicity. Consult the information sources to deter- stances of use. Identify the chemicals involved mine the LD50, discussed in section 4.C.1.1 of this in the proposed experiment and determine the chapter, for each chemical via the relevant routes amounts that will be used. Is the experiment to be of exposure. Determine the acute toxicity hazard done once, or will the chemicals be handled repeat- level for each substance, classifying each chemi- edly? Will the experiment be conducted in an open cal as highly toxic, moderately toxic, slightly toxic, laboratory, in an enclosed apparatus, or in a chemi- and so forth. For substances that pose inhalation cal fume hood? Is it possible that new or unknown hazards, take note of the threshold limit value–time substances will be generated in the experiment? Are weighted average (TLV-TWA), short-term exposure any of the trained laboratory personnel involved in limit, and permissible exposure limit values. (See the experiment pregnant or likely to become preg- section 4.C.2.1.) nant? Do they have any known sensitivities to specific 6. Select appropriate procedures to minimize chemicals? exposure. Use the basic prudent practices for 2. Consult sources of information. Consult an handling chemicals, which are discussed in Chapter up-to-date LCSS for each chemical involved in the 6, section 6.C for all work with chemicals in the planned experiment or examine an up-to-date mate- laboratory. In addition, determine whether any of rial safety data sheet (MSDS) if an LCSS is not avail- the chemicals to be handled in the planned experi- able. In cases where substances with significant or ment meet the definition of a particularly hazardous unusual potential hazards are involved, consult more substance due to high acute toxicity, carcinogenic- detailed references such as Patnaik (2007), Bingham ity, and/or reproductive toxicity. If so, consider the et al. (2001), and other sources discussed in section total amount of the substance that will be used, the 4.B. Depending on the laboratory personnel’s level expected frequency of use, the chemical’s routes of of experience and the degree of potential hazard exposure, and the circumstances of its use in the associated with the proposed experiment, obtain proposed experiment. As discussed in this chapter, the assistance of supervisors and safety professionals use this information to determine whether it is ap- before proceeding with risk assessment. propriate to apply the additional procedures for 3. Evaluate type of toxicity. Use the above sources work with highly toxic substances and whether of information to determine the type of toxicity asso- additional consultation with safety professionals is ciated with each chemical involved in the proposed warranted (see Chapter 6, section 6.D). experiment. Are any of the chemicals to be used 7. Prepare for contingencies. Note the signs acutely toxic or corrosive? Are any of the chemicals and symptoms of exposure to the chemicals to be to be used irritants or sensitizers? Will any select used in the proposed experiment. Note appropriate carcinogens or possibly carcinogenic substances be measures to be taken in the event of exposure or encountered? Consult the listings of the resources accidental release of any of the chemicals, including described in section C.4.6 of this chapter to identify first aid or containment actions. chemical similarities to known carcinogens. Are any Note: See Box 4.2 for a quick guide for assessing chemicals involved in the proposed experiment sus- the physical, flammable, explosive, and reac- pected to be reproductive or developmental toxins tive hazards in the laboratory and Box 4.3 for a or neurotoxins? 4. Consider possible routes of exposure. De- quick guide for assessing biological hazards in the laboratory. termine the potential routes of exposure for each chemical. Are the chemicals gases, or are they volatile

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72 PRUDENT PRACTICES IN THE LABORATORY pose explosively when exposed to a ground glass joint Classes of Chemicals That Can Form TABLE 4.8 or other sharp surfaces (Organic Syntheses, 1973, 1961). Peroxides Class A: Chemicals that form explosive levels of peroxides without concentration 4.D.3.2 Azos, Peroxides, and Peroxidizables Isopropyl ether Sodium amide (sodamide) Butadiene Tetrafluoroethylene Organic azo compounds and peroxides are among Chlorobutadiene (chloroprene) Divinyl acetylene the most hazardous substances handled in the chemi- Potassium amide Vinylidene chloride cal laboratory but are also common reagents that often Potassium metal are used as free radical sources and oxidants. They are Class B: These chemicals are a peroxide hazard on concentration generally low-power explosives that are sensitive to (distillation/evaporation). A test for peroxide should be shock, sparks, or other accidental ignition. They are performed if concentration is intended or suspected.* (See far more shock sensitive than most primary explosives Chapter 6, section 6.C.3) Acetal Dioxane (p-dioxane) such as TNT. Inventories of these chemicals should Cumene Ethylene glycol dimethyl be limited and subject to routine inspection. Many Cyclohexene ether (glyme) require refrigerated storage. Liquids or solutions of Cyclooctene Furan these compounds should not be cooled to the point at Cyclopentene Methyl acetylene which the material freezes or crystallizes from solution, Diaacetylene Methyl cyclopentane Dicyclopentadiene Methyl-isobutyl ketone however, because this significantly increases the risk Diethylene glycol dimethyl Tetrahydrofuran of explosion. Refrigerators and freezers storing such ether (diglyme) Tetrahydronaphthalene compounds should have a backup power supply in Diethyl ether Vinyl ethers the event of electricity loss. Users should be familiar Class C: Unsaturated monomers that may autopolymerize as a with the hazards of these materials and trained in their result of peroxide accumulation if inhibitors have been removed proper handling. or are depleteda Certain common laboratory chemicals form per- Acrylic acid Styrene oxides on exposure to oxygen in air (see Tables 4.8 Butadiene Vinyl acetate Chlorotrifluoroethylene Vinyl chloride and 4.9). Over time, some chemicals continue to build Ethyl acrylate Vinyl pyridine peroxides to potentially dangerous levels, whereas Methyl methacrylate others accumulate a relatively low equilibrium con- *These lists are illustrative, not comprehensive. centration of peroxide, which becomes dangerous only SOURCES: Jackson et al. (1970) and Kelly (1996). after being concentrated by evaporation or distillation. (See Chapter 6, section 6.G.3.) The peroxide becomes concentrated because it is less volatile than the par- and under the proper conditions of ultraviolet light, ent chemical. A related class of compounds includes temperature, and oxygen concentration, high concen- inhibitor-free monomers prone to free radical poly- trations of an explosive peroxide can be formed. The merization that on exposure to air can form peroxides chemicals described in Table 4.9 represent only those or other free radical sources capable of initiating materials that form peroxides in the absence of such violent polymerization. Note that care must be taken contaminants or otherwise atypical circumstances. when storing and using these monomers—most of the Although not a requirement, it is prudent to discard inhibitors used to stabilize these compounds require old samples of organic compounds of unknown origin the presence of oxygen to function properly, as de- or history, or those prone to peroxidation if contami- scribed below. Always refer to the MSDS and supplier nated; secondary alcohols are a specific example. instructions for proper use and storage of polymeriz- Class A compounds are especially dangerous when able monomers. Essentially all compounds containing C—H bonds Types of Compounds Known to TABLE 4.9 pose the risk of peroxide formation if contaminated Autoxidize to Form Peroxides with various radical initiators, photosensitizers, or catalysts. For instance, secondary alcohols such as Ethers containing primary and secondary alkyl groups (never isopropanol form peroxides when exposed to normal distill an ether before it has been shown to be free of peroxide) Compounds containing benzylic hydrogens fluorescent lighting and contaminated with photosen- Compounds containing allylic hydrogens (C=C—CH) sitizers, such as benzophenone. Acetaldehyde, under Compounds containing a tertiary C—H group (e.g., decalin and normal conditions, autoxidizes to form acetic acid. 2,5-dimethylhexane Although this autoxidation proceeds through a per- Compounds containing conjugated, polyunsaturated alkenes and oxy acid intermediate, the steady-state concentrations alkynes (e.g., 1,3-butadiene, vinyl acetylene) Compounds containing secondary or tertiary C—H groups of that intermediate are extremely low and pose no adjacent to an amide (e.g., 1-methyl-2-pyrrolidinone) hazard. However, in the presence of catalysts (Co2+)

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73 EVALUATING HAZARDS AND ASSESSING RISKS IN THE LABORATORY peroxidized and should not be stored for long periods and present difficulties for disposal. Their use should in the laboratory. Good practice requires they be dis- be avoided if at all possible. A common substitute is carded within 3 months of receipt. Inventories of Class a sulfuric acid–peroxydisulfate solution, and com- B and C materials should be kept to a minimum and mercial cleaning solutions that contain no chromium managed on a first-in, first-out basis. Class B and C are readily available. Confusion about appropriate materials should be stored in dark locations. If stored cleaning bath solutions has led to explosions due to in glass bottles, the glass should be amber. Contain- mixing of incompatible chemicals such as potassium ers should be marked with their opening date and permanganate with sulfuric acid or nitric acid with inspected every 6 months thereafter. alcohols. For information about how to clean glassware Class B materials are often sold with autoxidation in- appropriately, consider contacting the manufacturer of hibitors. If the inhibitor is removed, or if inhibitor-free the equipment. material is purchased, particular care must be taken in their long-term storage because of the enhanced prob- 4.D.3.4 Powders and Dusts ability of peroxide formation. Purging the container headspace with nitrogen is recommended. Several Suspensions of oxidizable particles (e.g., flour, coal procedures, including test strips, are available to check dust, magnesium powder, zinc dust, carbon powder, Class B materials for peroxide contamination. (For and flowers of sulfur) in the air constitute a powerful information about testing for peroxides, see Chapter explosive mixture. These materials should be used with 6, section 6.G.3.2.) No special disposal precautions are adequate ventilation and should not be exposed to required for peroxide-contaminated Class B materials. ignition sources. Some solid materials, when finely di- In most cases, commercial samples of Class C ma- vided, spontaneously combust if allowed to dry while terials are provided with polymerization inhibitors exposed to air. These materials include zirconium, that require the presence of oxygen to function and titanium, Raney nickel, finely divided lead (such as therefore are not to be stored under inert atmosphere. prepared by pyrolysis of lead tartrate), and catalysts Inhibitor-free samples of Class C compounds (i.e., the such as activated carbon containing active metals and compound has been synthesized in the laboratory or hydrogen. the inhibitor has been removed from the commercial sample) should be kept in the smallest quantities 4.D.3.5 Explosive Boiling required and under inert atmosphere. Unused mate- rial should be properly disposed of immediately, or if Not all explosions result from chemical reactions; long-term storage is necessary, an appropriate inhibitor some are caused physically. A dangerous explosion can should be added. occur if a hot liquid or a collection of very hot particles (For more information about handling of peroxides, comes into sudden contact with a lower boiling-point see Chapter 6, section 6.G.3.) material. Sudden boiling eruptions occur when a nucle- ating agent (e.g., charcoal, “boiling chips”) is added to a liquid heated above its boiling point. Even if the 4.D.3.3 Other Oxidizers material does not explode directly, the sudden forma- Oxidizing agents may react violently when they tion of a mass of explosive or flammable vapor can be come into contact with reducing materials and some- very dangerous. times with ordinary combustibles. Such oxidizing agents include halogens, oxyhalogens and organic 4.D.3.6 Other Considerations peroxyhalogens, chromates, and persulfates as well as peroxides. Inorganic peroxides are generally stable. The hazards of running a new reaction should be However, they may generate organic peroxides and considered especially carefully if the chemical species hydroperoxides in contact with organic compounds, involved contain functional groups associated with react violently with water (alkali metal peroxides), explosions or are unstable near the reaction or work-up and form superoxides and ozonides (alkali metal per- temperature, if the reaction is subject to an induction oxides). Perchloric acid is a powerful oxidizing agent period, or if gases are byproducts. Modern analytical with organic compounds and other reducing agents. techniques (see Chapter 6, section 6.G) can be used Perchlorate salts are explosive and should be treated as to determine reaction exothermicity under suitable potentially hazardous compounds. conditions. Baths to clean glassware generally contain strong Even a small sample may be dangerous. Further- oxidizers and should be handled with care. For many more, the hazard is associated not with the total energy years, sulfuric acid–dichromate mixtures were used to released but with the remarkably high rate of a detona- clean glassware. These solutions are corrosive and toxic tion reaction. A high-order explosion of even milligram

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74 PRUDENT PRACTICES IN THE LABORATORY quantities can drive small fragments of glass or other traps or from ice plug formation or lack of functioning matter deep into the body; therefore, use minimum vent valves in storage Dewars. Because 1 volume of amounts of these hazardous materials with adequate liquid nitrogen at atmospheric pressure vaporizes to shielding and personal protection. A compound is apt 694 volumes of nitrogen gas at 20 °C, the warming of to be explosive if its heat of formation is more than 100 such a cryogenic liquid in a sealed container produces cal/g less than the sum of the heats of formation of enormous pressure, which can rupture the vessel. (See its products. In making this calculation, a reasonable Chapter 6, section 6.G.4, and Chapter 7, section 7.E.2, reaction should be used to yield the most exothermic for detailed discussion.) products. Scaling up reactions introduces several hazards. 4.E.3 High-Pressure Reactions Unfortunately, the current use of microscale teaching methods in undergraduate laboratories increases the Experiments that generate high pressures or are car- likelihood that graduate students and others are un- ried out at pressures above 1 atm can lead to explosion prepared for problems that arise when a reaction is run from equipment failure. For example, hydrogenation on a larger scale. These problems include heat buildup reactions are frequently carried out at elevated pres- and the serious hazard of explosion from incompatible sures, and a potential hazard is the formation of explo- materials. The rate of heat input and production must sive O2/H2 mixtures and the reactivity/pyrophoricity be weighed against that of heat removal. Bumping the of the catalyst (see section 6.G.5). High pressures can solution or a runaway reaction can result when heat also be associated with the use of supercritical fluids. builds up too rapidly. When evaluating whether a reaction generates high Exothermic reactions can run away if the heat pressures, it is important to consider not just the initial evolved is not dissipated. When scaling up experi- reaction conditions, but the kinetics and thermody- ments, sufficient cooling and surface for heat exchange namics of the reaction as a whole. Is any stage of the should be provided, and mixing and stirring rates reaction exothermic? What are the characteristics of should be considered. Detailed guidelines for circum- the reactants, products, intermediates, and synthetic stances that require a systematic hazard evaluation and byproducts (explosive, gaseous, etc.)? What are the thermal analysis are given in Chapter 6, section 6.G. temperature and pressure requirements for equipment Another situation that can lead to problems is a used during the reaction? If scaling up a reaction, care- reaction susceptible to an induction period; particu- fully calculate the expected temperatures and pressures lar care must be given to the rate of reagent addition that will be generated and the rates at which any pres- versus its rate of consumption. Finally, the hazards of sures will be generated. Be sure to choose laboratory exothermic reactions or unstable or reactive chemicals equipment that is appropriate for every stage of the are exacerbated under extreme conditions, such as high reaction, and consult with the manufacturer if there temperature or high pressure used for hydrogenations, are any questions or concerns about whether a given oxygenations, or work with supercritical fluids. reactor or piece of equipment is appropriate for high- pressure work. (For more information about using high-pressure equipment, see Chapter 7, section 7.E.) 4.E PHYSICAL HAZARDS In many cases, barricading is not necessary if the ap- propriate reaction vessel, fittings, and other equipment 4.E.1 Compressed Gases are used. However, the laboratory environment must Compressed gases can expose the trained laboratory be designed to accommodate the failure of the equip- personnel to both mechanical and chemical hazards, ment: ventilation must be adequate to handle discharge depending on the gas. Hazards can result from the from a high-pressure reaction to prevent asphyxiation, flammability, reactivity, or toxicity of the gas; from the laboratory personnel may require hearing protection to possibility of asphyxiation; and from the gas compres- guard against the sound of a rupture disc failure, and sion itself, which could lead to a rupture of the tank or barricades are necessary if catastrophic failure could valve. (See Chapter 7, section 7.D.) result in injury or death of laboratory personnel. For specific information regarding barricade design, see Porter et al. (1956); Smith (1964); and the Handbook of 4.E.2 Nonflammable Cryogens Chemical Health and Safety (Alaimo, 2001). Nonflammable cryogens (chiefly liquid nitrogen) can cause tissue damage from extreme cold because of 4.E.4 Vacuum Work contact with either liquid or boil-off gases. In poorly ventilated areas, inhalation of gas due to boil off or Precautions to be taken when working with vacuum spills can result in asphyxiation. Another hazard is lines and other glassware used at subambient pressure explosion from liquid oxygen condensation in vacuum are mainly concerned with the substantial danger of

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75 EVALUATING HAZARDS AND ASSESSING RISKS IN THE LABORATORY injury in the event of glass breakage. The degree of new designation in parentheses. Class I (1) lasers are hazard does not depend significantly on the magnitude either completely enclosed or have such a low output of the vacuum because the external pressure leading of power that even a direct beam in the eye could not to implosion is always 1 atmosphere. Thus, evacuated cause damage. Class II (2) lasers, can be a hazard if systems using aspirators merit as much respect as a person stares into the beam and resists the natural high-vacuum systems. Injury due to flying glass is not reaction to blink or turn away. Class IIIA (1M, 2M, or the only hazard in vacuum work. Additional dangers 3R, depending on power output) lasers can present an can result from the possible toxicity of the chemicals eye hazard if a person stares into the beam and resists contained in the vacuum system, as well as from fire the natural reaction to blink or turn away or views following breakage of a flask (e.g., of a solvent stored the beam with focusing optical instruments. Class IIIB over sodium or potassium). (For more information (3B) lasers can produce eye injuries instantly from about working with equipment under vacuum, see both direct and specularly reflected beams, although Chapter 7, section 7.E.) diffuse reflections are not hazardous. The highest class Because vacuum lines typically require cold traps of lasers, Class IV (4), presents all the hazards of Class (generally liquid nitrogen) between the pumps and the III (3B) lasers but because of their higher power output vacuum line, precautions regarding the use of cryogens may also produce eye or skin damage from diffuse scat- should be observed also. Health hazards associated tered light. In addition to these skin and eye hazards, with vacuum gauges have been reviewed (Peacock, Class IV (4) lasers are a potential fire hazard. 1993). The hazards include the toxicity of mercury used Select protective eyewear with the proper optical in manometers and McLeod gauges, overpressure and density for the specific type of laser in use. Dark lenses underpressure situations arising with thermal conduc- can be hazardous because of the risk of looking over tivity gauges, electric shock with hot cathode ionization the top of the glasses. Leave laser safety glasses in a systems, and the radioactivity of the thorium dioxide bin outside the laboratory so that people entering use used in some cathodes. (For information about reduc- the appropriate laser safety glasses. When operating or ing the presence of mercury in laboratories, see Chapter adjusting a laser, remove or cover any reflective objects 5, section 5.B.8.) on hands and wrists to reduce the chance of reflections. Consider using beam blocks and containment walls to reduce the chance of stray reflections in the laboratory. 4.E.5 Ultraviolet, Visible, and Near- When using a laser-based microscope, consider using Infrared Radiation a camera and computer display to view the sample Ultraviolet, visible, and infrared radiation from rather than direct viewing through the eyepiece. lamps and lasers in the laboratory can produce a Anyone who is not the authorized operator of a laser number of hazards. Medium-pressure Hanovia 450 Hg system should never enter a posted laser-controlled lamps are commonly used for ultraviolet irradiation in laboratory if the laser is in use. Visitors may be present photochemical experiments. Ultraviolet lights used in when a laser is in use, but they must be authorized by biosafety cabinets, as decontamination devices, or in the laboratory supervisor. Visitors must not operate the light boxes to visualize DNA can cause serious skin and equipment and should be under the direct supervision corneal burns. Powerful arc lamps can cause eye dam- of an approved operator. age and blindness within seconds. Some compounds (e.g., chlorine dioxide) are explosively photosensitive. 4.E.6 Radio Frequency and Microwave When incorrectly used, the light from lasers poses a Hazards hazard to the eyes of the operators and other people present in the room and is also a potential fire hazard. Radio frequency (rf) and microwaves occur within Depending on the type of laser, the associated hazards the range 10 kHz to 300,000 MHz and are used in rf can include mutagenic, carcinogenic, or otherwise toxic ovens and furnaces, induction heaters, and microwave laser dyes and solvents; flammable solvents; ultraviolet ovens. Extreme overexposure to microwaves can result or visible radiation from the pump lamps; and electric in the development of cataracts or sterility or both. Mi- shock from lamp power supplies. crowave ovens are increasingly being used in labora- At the time of this publication, two systems for tories for organic synthesis and digestion of analytical classifying lasers are in use. Before 2002, lasers were samples. Only microwave ovens designed for labora- classified as I, II, IIIA, IIIB, and IV. From 2002 forward, tory or industrial use should be used in a laboratory. a revised system is being phased in which classifies la- Use of metal in microwave ovens can result in arcing sers as 1, 1M, 2, 2M, 3R, 3B, and 4. Although they have and, if a flammable solvent is present, in fire or explo- different designations, both systems classify lasers sion. Superheating of liquids can occur. Capping of based on their ability to cause damage to individu- vials and other containers used in the oven can result als. The older designation is given in the text with the

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76 PRUDENT PRACTICES IN THE LABORATORY 4.E.8 Magnetic Fields in explosion from pressure buildup within the vial. Inappropriately selected plastic containers may melt. Increasingly, instruments that generate large static magnetic fields (e.g., NMR spectrometers) are present in research laboratories. Such magnets typically have 4.E.7 Electrical Hazards fields of 14,000 to 235,000 G (1.4 to 23.5 T), far above that The electrocution hazards of electrically powered of Earth’s magnetic field, which is approximately 0.5 G. instruments, tools, and other equipment are almost The magnitude of these large static magnetic fields falls eliminated by taking reasonable precautions, and the off rapidly with distance. Many instruments now have presence of electrically powered equipment in the internal shielding, which reduces the strength of the laboratory need not pose a significant risk. Many elec- magnetic field outside of the instrument (see Chapter 7, trically powered devices are used in homes and work- Table 7.1). Strong attraction occurs when the magnetic places in the United States, often with little awareness field is greater than 50 to 100 G and increases by the of the safety features incorporated in their design and seventh power as the separation is reduced. However, construction. But, in the laboratory these safety features this highly nonlinear falloff of magnetic field with should not be defeated by thoughtless or ill-informed distance results in an insidious hazard. Objects made modification. The possibility of serious injury or death of ferromagnetic materials such as ordinary steel may by electrocution is very real if careful attention is not be scarcely affected beyond a certain distance, but at a paid to engineering, maintenance, and personal work slightly shorter distance may experience a significant practices. Equipment malfunctions can lead to electri- attraction to the field. If the object is able to move cal fires. If there is a need to build, repair, or modify closer, the attraction force increases rapidly, and the electrical equipment, the work should ideally be per- object can become a projectile aimed at the magnet. formed or, at a minimum, inspected by a trained and Objects ranging from scissors, knives, wrenches, and licensed electrician or electrical expert. All laboratory other tools, keys, steel gas cylinders, buffing machines, personnel should know the location of electrical shutoff and wheelchairs have been pulled from a considerable switches and circuit breaker switches and should know distance to the magnet itself. how to turn off power to burning equipment by using Superconducting magnets use liquid nitrogen and these switches. Laboratory equipment should be cor- liquid helium coolants. Thus, the hazards associated rectly bonded and grounded to reduce the chances of with cryogenic liquids (see section 4.E.2) are of concern, electric shock if a fault occurs. as well. Some special concerns arise in laboratory settings. The health effects of exposure to static magnetic The insulation on wires can be eroded by corrosive fields is an area of active research. Currently, there is chemicals, organic solvent vapors, or ozone (from no clear evidence of a negative health impact from ex- ultraviolet lights, copying machines, and so forth). posure to static magnetic fields, although biological ef- Eroded insulation on electrical equipment in wet fects have been observed (Schenck, 2000), and recently, locations such as cold rooms or cooling baths must guidelines on limits of exposure to static magnetic be repaired immediately. In addition, sparks from fields have been issued by the International Commis- electrical equipment can serve as an ignition source in sion on Non-ionizing Radiation (ICNIRP, 2009), which the presence of flammable vapor. Operation of certain is a collaborating organization with the World Health equipment (e.g., lasers, electrophoresis equipment) Organization’s International Electromagnetic Field may involve high voltages and stored electrical energy. Project. The large capacitors used in many flash lamps and (For more information about magnetic fields, see other systems are capable of storing lethal amounts of Chapter 7, section 7.C.8.4.1.) electrical energy and should be regarded as live even if the power source has been disconnected. 4.E.9 Sharp Edges Loss of electrical power can produce extremely haz- ardous situations. Flammable or toxic vapors may be Among the most common injuries in laboratories released from freezers and refrigerators as chemicals are cuts from broken glass. Cuts can be minimized by stored there warm up; certain reactive materials may the use of correct procedures (e.g., the procedure for decompose energetically on warming. Laboratory inserting glass tubing into rubber stoppers and tubing, chemical hoods may cease to function. Stirring (mo- which is taught in introductory laboratories), through tor or magnetic) required for safe reagent mixing may the appropriate use of protective equipment, and by cease. Return of power to an area containing flammable careful attention to manipulation. Glassware should vapors may ignite them.

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77 EVALUATING HAZARDS AND ASSESSING RISKS IN THE LABORATORY 4.E.11 Ergonomic Hazards in the always be checked for chips and cracks before use and Laboratory discarded if any are found. Never dispose of glass in the general laboratory trash. It should only be placed General workplace hazards also apply in the labora- in specific glassware disposal bins. This will reduce the tory. For example, laboratory personnel are often in- chance of anyone changing the trash receiving a cut. volved in actions such as pipetting and computer work Other cut hazards include razors, box cutters, knives, that can result in repetitive-motion injuries. Working at wire cutters, and any other sharp-edged tool. When a bench or at a microscope without considering pos- working with these tools, it is important to wear ap- ture can result in back strain, and some instruments propriate eye protection and cut-resistant gloves. Fol- require additional in-room ventilation that may raise low basic safety procedures when using a cutting tool: the background noise level to uncomfortable or hazard- ous levels. With these and other issues such as high or • Inspect the tool prior to use. Do not use it if it is low room temperatures and exposure to vibrations, it is damaged. important to be aware of and to control such issues to • When cutting, always use a tool with a sharp edge. reduce occupational injuries. For example, microscope Dull edges are more likely to slip and cause harm. users may find that using a camera to view images on a • Keep hands out of the line of the cut. screen, rather than direct viewing through the eyepiece, • Stand off-line from the direction of the cut. reduces back and eye strain. • If using a box cutter or other tool with a mounted The Centers for Disease Control and Prevention blade, ensure that the blade is well seated before (CDC) and the National Institutes of Health have in- use. formation on their Web sites (www.cdc.gov and www. • Never use a cutting tool for a task for which it nih.gov, respectively) describing specific ergonomic was not designed, for example, as a screwdriver concerns for laboratories and proposed solutions. The or lever for opening a container. CDC provides a downloadable self-assessment form • Never submerge a sharp object in soapy or dirty to aid in evaluating these hazards. NIOSH (www. water. It can be difficult to see and poses a risk to cdc.gov/niosh) and OSHA (www.osha.gov) provide the dishwasher. information about vibration, noise levels, and other workplace hazards. 4.E.10 Slips, Trips, and Falls 4.F NANOMATERIALS Other common injuries in the laboratory arise from slipping, tripping, or improper lifting. Spills resulting Nanoscale materials are of considerable scientific from dropping chemicals not stored in protective rub- interest because some chemical and physical properties ber buckets or laboratory carts can be serious because can change at this scale. (See definition of engineered the laboratory worker can fall or slip into the spilled nanomaterials below.) These changes challenge the chemical, thereby risking injury from both the fall researcher’s, manager’s, and safety professional’s un- and exposure to the chemical. Chemical spills result- derstanding of hazards, and their ability to anticipate, ing from tripping over bottles of chemicals stored on recognize, evaluate, and control potential health, safety, laboratory floors are part of a general pattern of bad and environmental risks. Essentially any solid may be housekeeping that can also lead to serious accidents. formed in the nano size range, and in general, the term Wet floors around ice, dry ice, or liquid nitrogen dis- “nanomaterials” has been broadly accepted as includ- pensers can be slippery if the areas are not carpeted and ing a number of nanometer-scale objects, including: if drops or small puddles are not wiped up as soon as nanoplates, nanofibers (including nanotubes); and they form. nanoparticles. In addition to the conventional hazards Attempts to retrieve 5-gallon bottles of distilled wa- posed by the material, hazard properties may also ter, jars of bulk chemicals, and rarely used equipment change. stored on high shelves often lead to back injuries in Nanoparticles are dispersible particles that are be- laboratory environments. Careful planning of where tween 1 and 100 nm in size that may or may not to store difficult-to-handle equipment and containers exhibit a size-related intensive property. The U.S. (because of weight, shape, or overall size) reduces the Department of Energy (DOE, 2008, 2009) states that incidence of back injuries. engineered nanomaterials are intentionally created, in contrast with natural or incidentally formed, and en- gineered to be between 1 and 100 nm. This definition

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78 PRUDENT PRACTICES IN THE LABORATORY U.S. Department of Energy graded risk for nanomaterials matrix FIGURE 4.5 U.S. Department of Energy graded exposure risk for nanomaterials. This figure assumes that no disruptive force (e.g., sonication, grinding, burning) is applied to the matrix. SOURCE: Adapted from Karn (2008). excludes biomolecules (proteins, nucleic acids, and area. Thus, nanoparticles represent a greater toxic carbohydrates).3 Incidentally formed nanoparticles are hazard than an equivalent mass of the same material often called “ultrafine” particles. in larger form. In addition, the number of particles per As with hazardous chemicals, exposures to these unit mass is far greater than the number of particles in materials may occur through inhalation, dermal con- bulk material per unit mass, resulting in significantly tact, accidental injection, and ingestion, and the risk different inhalational hazards between the two forms. increases with duration of exposure and the concentra- Because of their size, nanoparticles can penetrate deep tion of nanoparticles in the sample or air. Inhalation into the lungs, and with a large number of particles in presents the greatest exposure hazard. Nanomaterials a small volume, can overwhelm the organ and disrupt suspended in a solution or slurry pose a lesser hazard, normal clearance processes. The greater surface reac- but because the solutions can dry into a powder, they tivity also plays a role in this disruption. Once inside should be handled with care. Nanomaterials sus- the lungs, nanoparticles may translocate to other or- pended in a solution or slurry present a hazard when- gans via pathways not demonstrated in studies with ever mechanical energy is imparted to the suspension larger particles. In addition, at the interface of the of slurry. Sonication, shaking, stirring, pouring, or nanoparticle and human cell surface, bioactivity may spraying of a suspended nanomaterial can result in occur. For example, nanometal particles have been an inhalation exposure. Suspensions also represent demonstrated to produce reactive oxygen species, im- a dermal exposure potential. Nanoparticles that are plicating the presence of free radicals, and causing the fixed within a matrix pose the least hazard as long as biological effects of inflammation and fibrosis. no mechanical disruption, such as grinding, cutting, or The nanoparticulate forms of some materials show burning, occurs. (See Figure 4.5.) unusually high reactivity, especially for fire, explosion, Nanoparticles can enter the laboratory in a variety of and catalytic reactions. Engineered nanoparticles and ways. For example, the materials may be imported into nanostructured porous materials have been used ef- the lab for characterizations or be incorporated into fectively for many years as catalysts for increasing the a study. Alternatively, they could be created (synthe- rate of reactions or decreasing the temperature needed sized) in the lab as part of an experiment. In either case, for reactions in liquids and gases. Depending on their it is important for laboratory personnel to know about composition and structure, some nanomaterials initiate the presence and physical state of the nanomaterial catalytic reactions that would not otherwise be antici- (i.e., powder, in solution, on a solid matrix, or in solid pated from their chemical composition. Note also that matrix) so they can manage the hazards accordingly. nanomaterials may be attached to the surface of larger Nanoparticles have significantly greater relative sur- particles. In those cases, the larger material may take face areas than larger particles of an equivalent mass, on the higher reactivity features of the engineered na- and animal studies have demonstrated a correlation noscale material, even though it is not in the form of a between biological effects (toxic response) and surface particle in the 1- to 100-nm size range. As noted above, because material properties can change at the nanoscale, nanomaterials should not 3Note that this definition is slightly different from the definition be assumed to present only those hazards known to of the International Organization for Standardization, where “nano- be associated with bulk forms of material having the object is defined as material with one, two, or three external dimen- same composition. Instead, they must be handled sions in the size range of approximately 1–100 nm. Subcategories of as though toxic and reactive until credible evidence nano-object are (1) nanoplate, a nano-object with one external dimen- eliminates uncertainty. Hazard information is avail- sion at the nanoscale; (2) nanofiber, a nano-object with two external dimensions at the nanoscale with a nanotube defined as a hollow able on a limited number of nano-size materials. For nanofiber and a nanorod as a solid nanofiber; and (3) nanoparticle, example, NIOSH has proposed special exposure limits a nano-object with all three external dimensions at the nanoscale. for nano-size titanium dioxide that are significantly Nano-objects are commonly incorporated in a larger matrix or more restrictive than for larger particles of titanium substrate referred to as a nanomaterial” (HHS/CDC/NIOSH, 2009a).

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79 EVALUATING HAZARDS AND ASSESSING RISKS IN THE LABORATORY dioxide. Determination of EHS issues is an ongoing Risk assessment for biohazardous materials can be effort. The CHO assisting with protection from the complicated because of the number of factors that must EHS hazards will need special education and training be considered. The things that must be accounted for to adequately assist in risk assessment and control of are the organism being manipulated, any alterations nanomaterial risks. Specialized monitoring equipment made to the organism, and the activities that will be is required to evaluate potential exposures or release performed with the organism. Risk assessment for of nanomaterials. biological toxins is similar to that for chemical agents Although there is limited specific guidance on and is based primarily on the potency of the toxin, the evaluation and control of risks posed by nanomateri- amount used, and the procedures in which the toxin is als, preliminary research suggests that a well-designed used. An example of a risk assessment for a material ventilation system with high-efficiency filtration is with unknown biological risks can be found in Backus effective at capturing nanoparticles. However, recent et al. (2001). See Box 4.3 for a quick guide to assessing studies (Ellenbecker and Tsai, 2008) have demonstrated risks from biohazards in the laboratory. that conventional laboratory chemical hoods may Certain biological toxins and agents are classified create turbulence that can push the materials back as select agents under 42 CFR Part 73 and have addi- into the laboratory space. Lower flow hoods with less tional regulatory and security requirements that must turbulence may be more appropriate. (For more in- be considered when receiving and working with these formation about engineering controls for handling of agents. For detailed information on risk assessment of nanoparticles, see Chapter 9, section 9.E.5. For further biohazards, consult the fifth and most recent edition information on transportation, see Chapter 5, section of Biosafety in Microbiological and Biomedical Laboratories 5.F.2 and Chapter 6, section 6.J for information about (BMBL; HHS/CDC/NIH, 2007a) and the NIH Guide- working with nanoparticles.) lines for Research Involving Recombinant DNA Molecules (NIH, 2009). BMBL is considered the consensus code of practice for identifying and controlling biohazards 4.G BIOHAZARDS and was first produced by the CDC and the National Biohazards are a concern in laboratories in which Institutes of Health in 1984. (Also see Chapter 6, section microorganisms, or material contaminated with them, 6.E, and Chapter 11.) are handled. Anyone who is likely to come in con- tact with blood or potentially infectious materials at 4.H HAZARDS FROM RADIOACTIVITY work is covered under OSHA’s Bloodborne Pathogen Standard, 29 CFR § 1910.1030. These hazards are usu- This section provides a brief primer on the potential ally present in clinical and infectious disease research hazards arising from the use of radioactivity in a labo- laboratories but may also be present in any laboratory ratory setting. A comprehensive treatment of this topic in which bodily fluids, tissues, or primary or immortal- is given in Radiation Protection: A Guide for Scientists, ized cell lines of human or animal origin are handled. Regulators, and Physicians (Shapiro, 2002). For an in- Biohazards are also present in any laboratory that uses troduction to health physics, see Cember and Johnson microorganisms, including replication-deficient viral (2008). Note that the receipt, possession, use, transfer, vectors, for protein expression or other in vitro applica- and disposal of most radioactive materials is strictly tions. Occasionally, biohazards are present in testing regulated by the U.S. Nuclear Regulatory Commission and quality control laboratories, particularly those (USNRC; see 10 CFR Part 20, Standards for Protection associated with water and sewage treatment plants Against Radiation) and/or by state agencies who have and facilities involved in the production of biological “agreements” with the USNRC to regulate the users products and disinfectants. Teaching laboratories may within their own states. Radioactive materials may introduce low-risk infectious agents as part of a course be used only for purposes specifically described in of study in microbiology. licenses issued by this agency to licensees. Individu- Synthetic biology makes it possible to synthesize mi- als working with radioactive materials should thus croorganisms from basic chemical building blocks, and be aware of the restrictions and requirements of these these microorganisms may have different hazards from licenses. Consult your radiation safety officer or other their naturally occurring relatives. If a microorganism designated EHS professional for training, policies, and identical or very similar to one found in nature is syn- procedures specific to uses at your institution. thesized, the risks are assumed to be similar to those Unstable atomic nuclei eventually achieve a more of the naturally occurring microorganism. If a novel stable form by emission of some type of radiation. microorganism is synthesized, however, extra caution These nuclei or isotopes are termed radioactive. The must be used until the characteristics of the agent are emitted radiation may be characterized as particulate (α, β, proton, or neutron) or electromagnetic (γ rays well understood.

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80 PRUDENT PRACTICES IN THE LABORATORY BOX 4.3 Quick Guide to Risk Assessment for Biological Hazards in the Laboratory The following steps are provided to assist trained labora- dentally exposed to the organism. Is the organism tory personnel in performing a risk assessment of activities now expressing oncogenes or toxins, or knocking involving biohazardous materials. This is not intended as a down expression of a tumor suppressor? 7. What volume and concentration of agent flowchart; rather, all questions should be considered before are handled at any one time? In general, arriving at the final risk assessment. higher volumes or concentrations call for stricter 1. Identify the risk group of the parent or- safety p recautions. R ecombinant o rganisms i n ganism (the American Biological Safety Association volumes greater than 10 L in a single vessel have has a database of risk groups from various sources additional regulatory requirements as well. online at http://absa.org). 8. Will research animals be used in any pro- 2. This Risk Group assignment is only a start- cedures? If so, will they be restrained or anesthe- ing point; the actual biosafety level at which the tized? What is the immune status of the research work is performed may be higher or lower depend- animals? Is there a possibility that research animals ing on the remainder of the risk assessment. will excrete potentially infectious or otherwise harm- 3. Refer to the Agent Summary Statement in ful substances? Biosafety in Microbiological and Biomedical 9. Are sharps utilized in any procedures? Use Laboratories (BMBL; HHS/CDC/NIH, 2007a) of sharps should be minimized whenever possible. if available. This will provide a recommended If sharps must be used with potentially infectious biosafety level as well as personal protective and materials, use caution. containment equipment to use while handling the 10. Will any manipulations generate aerosols organism. It will also summarize the frequency and (e.g., vortexing, centrifuging)? If so, perform route of laboratory-acquired infections. these operations in a biosafety cabinet or other 4. Identify the natural route of transmission appropriate containment equipment whenever for the parent organism. This will indicate the possible. most likely route of laboratory-acquired infections. 11. Are vaccinations or treatments available Be aware that at the volumes and concentrations for the agents in question? Consult with used in the laboratory, however, organisms can an o ccupational h ealth p rovider t o d etermine often be transmitted in ways other than their nor- the n ecessity f or v accination o r p ostexposure mal route of exposure (e.g., aerosol transmission of management. agents normally only transmitted via mosquito bite). 12. Are the organisms used particularly haz- 5. Consider any modifications made to the or- ardous for certain groups of people (e.g., ganism. Has the host range been modified? Have pregnant women, immunocompromised virulence factors been inserted or removed? Has individuals)? Notify any personnel who will work the organism been rendered replication-defective? with or around the organism(s) of these special If so, is there any possibility of recombination events concerns. with wild-type organisms to restore replication NOTE: For a quick guide for assessing the toxicity competency? 6. Consider the transgenes expressed by the hazards associated with laboratory chemicals, see organism. Think about the effect of aberrant Box 4.1. For a quick guide for assessing physical flammable, explosive, and reactive hazards in the expression of that protein if personnel were acci- laboratory, see Box 4.2. protons and two neutrons and are emitted from certain or X rays). Particulate radiations have both mass and heavy atoms such as uranium and thorium. These electromagnetic radiations, which are sometimes re- particles are relatively large, slow, heavy, and easily ferred to as photons. Radiation that has enough energy stopped by a sheet of paper, a glove, a layer of cloth- to ionize atoms and create ion pairs is referred to as ing or even a dead layer of skin cells, and thus present ionizing radiation. Ionizing radiation not only comes virtually no external exposure hazard to people. How- from unstable nuclei, but can also be produced by ever, because of the very large number of ionizations machines such as particle accelerators, cyclotrons, and that α particles produce in short distances, α emitters X-ray machines. can present a serious hazard when they come in contact Alpha particles are charged particles containing two

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81 EVALUATING HAZARDS AND ASSESSING RISKS IN THE LABORATORY of an α particle. Exposure to neutrons can be hazard- with internal living cells and tissues. Special precau- tions are thus taken to ensure that α emitters are not ous because the interaction of neutrons with molecules inhaled, ingested, or injected. Care must be taken with in the body can cause disruption to molecules and unsealed α-emitting sources to control contamination atoms. Because of its lack of charge, the neutron is and minimize the potential for internal uptakes. difficult to shield, can penetrate deeply into tissues, A β particle (see Table 4.10) is an electron emitted and can travel hundreds of yards in air depending on from the nucleus of a radioactive atom. Positively the kinetic energy of the neutron. A neutron is slowed charged counterparts of β particles are called posi- when it collides with the nucleus of other atoms. This trons. Beta particles are much less massive and less transfers kinetic energy of the neutron to the nucleus charged than α particles and interact less intensely of the atom. As the mass of the nucleus approaches the with atoms in the materials through which they pass, mass of the neutron, this reaction becomes more effec- which gives them a longer range than α particles. tive in slowing the neutron. Therefore water and other Examples of β emitters commonly used in biologi- hydrogen-rich materials, such as paraffin or concrete, cal research are hydrogen-3 (tritium) (3H), carbon-14 are often used as shielding material. (14C), phosphorus-32 (32C), phosphorus-33 (33P), and Radioactive decay rates are reported in curies (1 cu- sulfur-35 (35P). Although low-energy β particles are rie [Ci] = 3.7 × 1010 disintegrations per second [dps]) or usually stopped by the dead layer of skin, higher en- in the International System of Units (SI) in becquerels ergy β particles can penetrate more deeply and cause (1 Bq = 1 dps). The decay rate provides a characteriza- high exposures to the skin and eyes. The energy level tion of a given source but is not an absolute guide to of the β particle thus determines if shielding and expo- the hazard of the material. The hazard depends on the sure monitoring is required when working with these nature, as well as the rate of production, of the ionizing materials, as well as how contamination surveys are radiation. In characterizing human exposure to ioniz- performed. Table 4.10 provides typical examples of ing radiation, it is assumed that the damage is propor- high-energy, low-energy, and extremely low-energy tional to the energy absorbed. The radiation absorbed β-particle handling precautions. When shielding is dose (rad) is defined in terms of energy absorbed per used to reduce external exposures from β emitters, a unit mass: 1 rad = 100 ergs/g (SI: 1 Gy = 1 J/kg = 100 low-density shielding material such as Plexiglas, Lu- rads). For electromagnetic energy, the roentgen (R) pro- duces 1.61 × 1012 ion pairs per gram of air (SI: 1 C/kg cite, or acrylic works best. Gamma rays, x rays, and photon radiations have = 3.876 R). no mass or charge. Gamma rays are generally emit- Acceptable limits for occupational exposure to ion- ted from the nucleus during nuclear decay, and x rays izing radiation are set by the USNRC based on the are emitted from the electron shells. Extremely dense potential amount of tissue damage that can be caused material such as lead typically makes the best shields by the exposure. This damage is expressed as a dose for these electromagnetic forms of radiation. Iodine-125 equivalent; the common unit for dose equivalent is the (125I), indium-111 (111In), and chromium-51 (51Cr) are roentgen equivalent man (rem). The dose equivalent is a few examples of radionuclides sometimes used in determined by the rad multiplied by a weighting factor, research laboratories. called a quality factor, to account for the differences Neutrons are emitted from the nucleus during decay, in the nature of the ionizing radiation from different have no electrical charge, and are one-fourth the mass types of radiation. Table 4.11 shows the quality factors for different types of radiation. For γ rays and X rays, rad and rem are virtually equivalent. Examples of β Emitters TABLE 4.10 Damage may occur directly as a result of the radia- tion interacting with a part of the cell or indirectly by Extremely High-Energy Low-Energy Low Energy the formation of toxic substances within the cell. The Emitters Emitters Emitters extent of damage incurred depends on many factors, Examples Cl-35 C-14 H-3 including the dose rate, the size of the dose, and the P-32 S-35 site of exposure. Effects may be short term or long Sr-90 P-33 term. Acute short-term effects associated with large Shielding Shielding Not required Not required required Radiation Quality Factors TABLE 4.11 (Plexiglas) Type of Radiation Quality Factor (Q) Contamination Survey meter Survey meter Wipe sample survey type x, γ, or β radiation 1 α particles Exposure Recommended Not required Not required 20 dosimetry Neutrons of unknown energy 10

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82 PRUDENT PRACTICES IN THE LABORATORY doses and high dose rates—for example, 100,000 mrad U.S. Nuclear Regulatory Commission TABLE 4.12 (100 rad) in less than 1 week—may include nausea, Dose Limits diarrhea, fatigue, hair loss, sterility, and easy bruising. Occupational Dose Public Dose Limits In appropriately managed workplaces, such expo- Area of Dose Limits (mrem/year) (mrem/year) sures are impossible unless various barriers, alarms, Total effective dose 5,000 100* and other safety systems are deliberately destroyed equivalent (or whole or bypassed. Single-dose exposures higher than 500 body: external + rem are probably fatal. A single dose of ~100 rem may internal) cause a person to experience nausea or skin reddening, Committed dose 50,000 NA although recovery is likely. However, if these doses are equivalent (or any organ dose) cumulative over a period of time rather than a single dose, the effects are less severe. Long-term effects, Eye dose equivalent (or 15,000 NA which develop years after a high-dose exposure, are lens of the eye) primarily cancer. Exposure of the fetus in utero to radia- Shallow dose 50,000 NA tion is of concern, and the risk of damage to the fetus equivalent (or skin dose) increases significantly when doses exceed 15,000 mrem. The USNRC has set limits for whole-body occupa- Extremity dose (or 50,000 NA tional exposure at 5,000 mrem/year, with minors and shallow dose to any extremity) declared pregnant workers allowed only 500 mrem/ year (or 9-month gestation period), and members of the Minor (less than 18 10% of occupational NA years of age) limits for adults public allowed only 100 mrem/year (see Table 4.12). Exposure limits are lower in facilities operated by the Embryo/fetus of 500 NA U.S. Department of Energy and other agencies. Note declared pregnant woman (limit that properly managed work with radioactive materi- taken over time of als in the vast majority of laboratory research settings pregnancy) can be performed without any increase in a worker’s Personnel dosimetry is required if occupational dose is likely exposure to radiation. to exceed 10% of the limit (for embryo/fetus, it is required if As with all laboratory work, protection of labora- worker’s dose is likely to exceed 100 mrem during gestation tory personnel against the hazard consists of good period) facility design, operation, and monitoring, as well as *NOTE: For 10 CFR § 35.75 patient release, limit is 500 mrem. good work practices. The ALARA (as low as reason- ably achievable) exposure philosophy is central to both levels of protection. The amount of radiation or radioactive material used should be minimized. Ex- rials should be minimized. Physical distance between posures should be minimized by shielding radiation personnel and radiation sources should be maximized, sources, laboratory personnel, and visitors and by use and whenever possible, robotic or other remote opera- of emergency alarm and evacuation procedures. The tions should be used to reduce exposure of personnel. amount of time spent working with radioactive mate- (Also see Chapter 6, section 6.E.)