United States Environmental Protection 1=1 m m Agency EPA/690/R-12/009F Final 12-12-2012 Provisional Peer-Reviewed Toxicity Values for Cyanogen Bromide (CASRN 506-68-3) Superfund Health Risk Technical Support Center National Center for Environmental Assessment Office of Research and Development U.S. Environmental Protection Agency Cincinnati, OH 45268 ------- AUTHORS, CONTRIBUTORS, AND REVIEWERS CHEMICAL MANAGER Harlal Choudhury, DVM, PhD, DABT National Center for Environmental Assessment, Cincinnati, OH DRAFT DOCUMENT PREPARED BY ICF International 9300 Lee Highway Fairfax, VA 22031 PRIMARY INTERNAL REVIEWERS Ghazi Dannan, PhD National Center for Environmental Assessment, Washington, DC Anuradha Mudipalli, MSc, PhD National Center for Environmental Assessment, Research Triangle Park, NC This document was externally peer reviewed under contract to Eastern Research Group, Inc. 110 Hartwell Avenue Lexington, MA 02421-3136 Questions regarding the contents of this document may be directed to the U.S. EPA Office of Research and Development's National Center for Environmental Assessment, Superfund Health Risk Technical Support Center (513-569-7300). l Cyanogen Bromide ------- TABLE OF CONTENTS COMMONLY USED ABBREVIATIONS iii BACKGROUND 1 DISCLAIMERS 1 QUESTIONS REGARDING PPRTVs 1 INTRODUCTION 2 REVIEW OF POTENTIALLY RELEVANT DATA (CANCER AND NONCANCER) 6 HUMAN STUDIES 8 Oral Exposures 8 Inhalation Exposures 8 ANIMAL STUDIES 8 Oral Exposures 8 Inhalation Exposure 8 OTHER DATA (SHORT-TERM TESTS, OTHER EXAMINATIONS) 9 DERIVATION 01 PROVISIONAL VALUES 9 DERIVATION OF ORAL REFERENCE DOSES 9 DERIVATION OF INHALATION REFERENCE CONCENTRATIONS 9 Derivation of Subchronic and Chronic Provisional RfC 9 CANCER WOE DESCRIPTOR 10 DERIVATION OF PROVISIONAL CANCER POTENCY VALUES 10 REFERENCES 10 li Cyanogen Bromide ------- COMMONLY USED ABBREVIATIONS BMC benchmark concentration BMCL benchmark concentration lower bound 95% confidence interval BMD benchmark dose BMDL benchmark dose lower bound 95% confidence interval HEC human equivalent concentration HED human equivalent dose IUR inhalation unit risk LOAEL lowest-observed-adverse-effect level LOAELadj LOAEL adjusted to continuous exposure duration LOAELhec LOAEL adjusted for dosimetric differences across species to a human NOAEL no-ob served-adverse-effect level NOAELadj NOAEL adjusted to continuous exposure duration NOAELhec NOAEL adjusted for dosimetric differences across species to a human NOEL no-ob served-effect level OSF oral slope factor p-IUR provisional inhalation unit risk POD point of departure p-OSF provisional oral slope factor p-RfC provisional reference concentration (inhalation) p-RfD provisional reference dose (oral) RfC reference concentration (inhalation) RfD reference dose (oral) UF uncertainty factor UFa animal-to-human uncertainty factor UFC composite uncertainty factor UFd incomplete-to-complete database uncertainty factor UFh interhuman uncertainty factor UFl LOAEL-to-NOAEL uncertainty factor UFS subchronic-to-chronic uncertainty factor WOE weight of evidence 111 Cyanogen Bromide ------- FINAL 12-12-2012 PROVISIONAL PEER-REVIEWED TOXICITY VALUES FOR CYANOGEN BROMIDE (CASRN 506-68-3) BACKGROUND A Provisional Peer-Reviewed Toxicity Value (PPRTV) is defined as a toxicity value derived for use in the Superfund Program. PPRTVs are derived after a review of the relevant scientific literature using established Agency guidance on human health toxicity value derivations. All PPRTV assessments receive internal review by a standing panel of National Center for Environment Assessment (NCEA) scientists and an independent external peer review by three scientific experts. The purpose of this document is to provide support for the hazard and dose-response assessment pertaining to chronic and subchronic exposures to substances of concern, to present the major conclusions reached in the hazard identification and derivation of the PPRTVs, and to characterize the overall confidence in these conclusions and toxicity values. It is not intended to be a comprehensive treatise on the chemical or toxicological nature of this substance. The PPRTV review process provides needed toxicity values in a quick turnaround timeframe while maintaining scientific quality. PPRTV assessments are updated approximately on a 5-year cycle for new data or methodologies that might impact the toxicity values or characterization of potential for adverse human health effects and are revised as appropriate. It is important to utilize the PPRTV database flittp://hhpprtv.ornl.gov) to obtain the current information available. When a final Integrated Risk Information System (IRIS) assessment is made publicly available on the Internet (http://www.epa.eov/iris). the respective PPRTVs are removed from the database. DISCLAIMERS The PPRTV document provides toxicity values and information about the adverse effects of the chemical and the evidence on which the value is based, including the strengths and limitations of the data. All users are advised to review the information provided in this document to ensure that the PPRTV used is appropriate for the types of exposures and circumstances at the site in question and the risk management decision that would be supported by the risk assessment. Other U.S. Environmental Protection Agency (EPA) programs or external parties who may choose to use PPRTVs are advised that Superfund resources will not generally be used to respond to challenges, if any, of PPRTVs used in a context outside of the Superfund program. QUESTIONS REGARDING PPRTVs Questions regarding the contents and appropriate use of this PPRTV assessment should be directed to the EPA Office of Research and Development's National Center for Environmental Assessment, Superfund Health Risk Technical Support Center (513-569-7300). 1 Cyanogen Bromide ------- FINAL 12-12-2012 INTRODUCTION Cyanogen bromide, CAS Number 506-68-3, is an inorganic cyanide compound with a pungent odor and occurs as colorless or white crystals at room temperature (see Figure 1). CNBr has applications in industry and in the laboratory, acting as potential sources for exposure. In industry, it has been used in gold extraction, organic synthesis, cellulose technology, textile treatment, and as a fumigant and pesticide/parasiticide. In the laboratory, it has been used to immobilize proteins for chromatography, for protein structure analysis, and as a reagent in the Niacin production test for identifying strains of Mycobacterium tuberculosis. CNBr decomposes upon heating or contact with acids, producing toxic HCN gas and corrosive hydrogen bromide (International Labour Organization, 2000). It reacts slowly with water and moisture to produce hydrogen bromide and HCN. Consistent with the pKa for HCN listed below, HCN exists primarily in its nondissociated form at pH values less than 7, and the concentration of CN increases as pH increases above 7. A table of physicochemical properties for CNBr is provided below (see Table 1). N=C-Br Figure 1. Cyanogen Bromide Structure Table 1. Physicochemical Properties of Cyanogen Bromide (CASRN 506-68-3) Property (unit) Value Boiling point (°C) 61.5a Melting point (°C) 52a'b Density (g/cm3) 2.0b Vapor pressure (at 25°C) 16.2 kPab, 122 mm Hga pKa (at 25°C) HCN, 9.22b Solubility in water (g/100 mL at 25°C) 10.8a Relative vapor density (air =1) 3.6b Molecular weight (g/mol) lOS.^h aChemTDP1iis (2011). international Labour Organization (2000). Although no Reference Concentration (RfC) or cancer assessment for CNBr are included on U.S. EPA IRIS, a Reference Dose (RfD) value of 9 x io~2 mg/kg-day, based on HCN toxicity, is provided (U.S. EPA, 2010). This online IRIS document state that a subsequently conducted comprehensive review of toxicological studies published prior to 2004 found no new relevant data for CNBr. A more recent revision of the IRIS summary for HCN and cyanide salts (i.e., U.S. EPA, 2010) includes chronic RfD and RfC values for HCN of 6 x 10~4 mg/kg-day and 8 x 10~4 mg/m3, respectively. The justification for using HCN to derive values for CNBr is stated as follows (U.S. EPA, 1988): 2 Cyanogen Bromide ------- FINAL 12-12-2012 Despite the lack of studies that evaluate the toxicity of chronic oral exposure to cyanogen bromide specifically, the available data indicate that cyanogen bromide is soluble in water and dilute acid, that full dissociation would result in a maximum of one mole equivalent of cyanide and that of the three possible breakdown products of cyanogen bromide (cyanide, bromide and cyanogen bromide), cyanide is probably the most toxic to mammals. Therefore, until specific data on cyanogen bromide become available, the RfD for cyanogen bromide is derived by analogy to cyanide. However, current risk assessment practices for using information on analogy and uncertainty in mode of action do not provide sufficient scientific support for the approach used in the IRIS assessment for CNBr (U.S. EPA, 1988) to derive a subchronic p-RfD or provisional inhalation toxicity values. A summary of available toxicity values for cyanogen bromide from U.S. EPA and other agencies/organizations is provided in Table 2. 3 Cyanogen Bromide ------- FINAL 12-12-2012 Table 2. Summary of Available Toxicity Values for Cyanogen Bromide (CASRN 506-68-3) Source/Parameter" Value (Applicability) Notes Reference Date Accessed Cancer IRIS NV "Inadequate Information to Assess Carcinogenic Potential" U.S. EPA, 2010 1-18-2011 HEAST NV NA U.S. EPA, 2011b 1-18-2011 IARC NV NA IARC, 2010 1-18-2011 NTP NV NA NTP, 2011 1-18-2011 CalEPA NV NA CalEPA. 2008 1-18-2011 Drinking Water Standards and Health Advisories Cancer designation "D" "Not Classifiable as to Human Carcinogenity" U.S. EPA, 2011a 5-5-2011 Drinking Water Criteria Cancer designation "D" "Not Classifiable as to Human Carcinogenity" U.S. EPA, 1992 5-5-2011 Noncancer ACGIH TLV-TWA: 5 mg/m3 (4.7 ppm) TLV-TWA: 0.6 mg/m3 (0.3 ppm) DEL (Cyanides) EL (Cyanogen chloride) ACGIH, 2008 1-18-2011 ATSDR NV NA ATSDR, 2011 1-18-2011 CalEPA PHG: 0.15 mg/L MCL: 0.2 mg/L (Cyanide) (Cyanide) CalEPA. 2009 1-18-2011 NIOSH REL-TWA: 5 mg/m3 (4.7 ppm) REL-TWA: 0.6 mg/m3 (0.3 ppm) DEL 10-minute ceiling (cyanides) EL (Cyanogen chloride) NIOSH, 2010 1-18-2011 OSHA PEL-TWA: 5 mg/m3 (4.7 ppm) DEL: 8-hour TWA (cyanides) OSHA, 2004 1-18-2011 IRIS RfD: 9 x 10"2 mg/kg-day (Hydrogen cyanide) U.S. EPA, 2010 1-18-2011 Drinking Water Standards and Health Advisories 0.05 mg/L RfD: 0.05 mg/kg-day DWEL: 2 mg/L 1- and 10-day exposure limits (cyanogen chloride) (Cyanogen chloride) Value for a 10-kg child (cyanogen chloride) U.S. EPA, 2011a 5-5-2011 4 Cyanogen Bromide ------- FINAL 12-12-2012 Table 2. Summary of Available Toxicity Values for Cyanogen Bromide (CASRN 506-68-3) Source/Parameter" Value (Applicability) Notes Reference Date Accessed Drinking Water Criteria 0.2 mg/L DWEL: 0.7 mg/L 1- and 10-day exposure limits for a 10-kg child (Cyanide) U.S. EPA, 1992 5-5-2011 DOE Protective Action Criteria (PAC) TEEL-0: 20.4 mg/m3 Threshold concentration below which most people will experience no adverse health effects ChemlDPlus, 2011 HEAST RfD: 9 x 10"2 mg/kg-day (Hydrogen cyanide) U.S. EPA, 2011b 1-18-2011 CARA HEEP NV NA U.S. EPA, 1994 1-18-2011 WHO NV NA WHO, 2011 1-18-2011 "Sources: Integrated Risk Information System (IRIS) database; Health Effects Assessment Summary Tables (HEAST); International Agency for Research on Cancer (IARC); National Toxicology Program (NTP); California Environmental Protection Agency (CalEPA); American Conference of Governmental Industrial Hygienists (ACGIH); Agency for Toxic Substances and Disease Registry (ATSDR); National Institute for Occupational Safety and Health (NIOSH); Occupational Safety and Health Administration (OSHA); Department of Energy (DOE); Chemical Assessments and Related Activities (CARA) list; Health and Environmental Effects Profile (HEEP); World Health Organization (WHO). IDLH= immediately dangerous to life or health; NA = not applicable; NV = not available; PEL-TWA = permissible exposure level-time weighted average; REL-TWA = recommended exposure level-time weighted average; TLV-TWA = threshold limit value-time weighted average; PHG = Public Health Goal; MCL = Maximum Contaminant Level; DWEL = lifetime drinking water equivalent level; DEL = dermal exposure limits; EL = exposure limit; PAC = Protective Action Criteria; TEEL-0 = Temporary Emergency Exposure Limit value (no effects). Literature searches were conducted on sources published from 1900 through September 2012, for studies relevant to the derivation of provisional toxicity values for CNBr, CAS Number 506-68-3. Searches were conducted using U.S. EPA's Health and Environmental Research Online (HERO) database of scientific literature. HERO searches the following databases: AGRICOLA; American Chemical Society; BioOne; Cochrane Library; DOE: Energy Information Administration, Information Bridge, and Energy Citations Database; EBSCO: Academic Search Complete; GeoRef Preview; GPO: Government Printing Office; Informaworld; IngentaConnect; J-STAGE: Japan Science & Technology; JSTOR: Mathematics & Statistics and Life Sciences; NSCEP/NEPIS (EPA publications available through the National Service Center for Environmental Publications [NSCEP] and National Environmental Publications Internet Site [NEPIS] database); PubMed: MEDLINE and CANCERLIT databases; SAGE; Science Direct; Scirus; Scitopia; SpringerLink; TOXNET (Toxicology Data Network): ANEUPL, CCRIS, ChemlDplus, CIS, CRISP, DART, EMIC, EPIDEM, ETICBACK, FEDRIP, GENE-TOX, HAPAB, HEEP, HMTC, HSDB, IRIS, ITER, LactMed, Multi-Database Search, NIOSH, NTIS, PESTAB, PPBIB, RISKLINE, TRI, and TSCATS; Virtual Health Library; Web of Science (searches Current Content database among others);WHO; and Worldwide Science. The following databases outside of HERO were searched for relevant health information: ACGIH, ATSDR, CalEPA, U.S. EPA IRIS, U.S. EPA HEAST, U.S. EPA HEEP, U.S. EPA OW, U.S. EPA TSCATS/TSCATS2, NIOSH, NTP, OSHA, and RTECS. 5 Cyanogen Bromide ------- FINAL 12-12-2012 REVIEW OF POTENTIALLY RELEVANT DATA (CANCER AND NONCANCER) CNBr can enter the bloodstream via oral, inhalation, or dermal absorption and then be broken down into bromide and cyanide (Luttrell, 2009). CNBr possesses some of the same properties as HCN and its soluble salts regarding effects on the central nervous system (CNS), although CNBr is also a highly irritating vesicant gas, producing severe lacrimatory effects and pulmonary irritation and edema (Hartung, 1982). However, other than data from acute exposures (see Table 3), no studies investigating the toxicity of CNBr were located. In the absence of any directly relevant data, and based on the argument presented above, data from studies on HCN and cyanide salts are not considered for the derivation of reference values for CNBr. Table 3 provides an overview of the relevant database for CNBr. 6 Cyanogen Bromide ------- FINAL 12-12-2012 Table 3. Summary of Potentially Relevant Data for Cyanogen Bromide (CASRN 506-68-3) Category Number of Male/Female, Strain, Species, Study Type, Study Duration Dosimetry Critical Effects NOAEL BMDL/ BMCL LOAEL Reference" (Comments) Notesb Human 1. Oral (mg/kg-d) Acute0 ND Short-termd ND Long-term6 ND Chronicf ND 2. Inhalation (mg/m3) Acute0 Numbers and sex unspecified 6, 35, 85,400 400, fatal after 10 min; 85, intolerable after 1 min; 35, intolerable after 10 min; 6, lowest irritant concentration after 10 min NA NA NA Hartung (1982) as cited in IRIS (2010) NA Short-termd ND aUnless otherwise stated, study summaries are available in Toxicological Review ofHCN and Cyanide Salts in Support of IRIS (U.S. EPA, 2010). bNotes: IRIS = Utilized by IRIS, date of last update; PS = principal study, PR = peer reviewed, NPR = not peer reviewed. The form of CN used for dosing is reported. 0 Acute = Exposure for 24 hr or less (U.S. EPA, 2002). dShort-term = Repeated exposure for >24 h <30 d (U.S. EPA, 2002). "Long-term = Repeated exposure for >30 d <10% lifespan (based on 70 yr typical lifespan) (U.S. EPA, 2002). fChronic = Repeated exposure for >10% lifespan (U.S. EPA, 2002). DU = data unsuitable; NA = not applicable; NV = not available; ND = No data; NDr = Not determinable; NI = not identified; NP = not provided; NR = not reported; NR/Dr = not reported but determined from data; NS = not selected. 7 Cyanogen Bromide ------- FINAL 12-12-2012 HUMAN STUDIES Oral Exposures No studies were identified. Inhalation Exposures Aside from acute exposures (Hartung, 1982), no studies examining the effects of inhalation exposure to CNBr in humans were located. Acute Studies Hartung (1982) In a book chapter by Hartung (1982) cited by IRIS (U.S. EPA, 1988), human responses to inhalation of CNBr were described as follows: "0.4 mg/L, fatal after 10 minutes; 0.085 mg/L, intolerable concentration, 1-minute exposure; 0.035 mg/L, intolerable concentration, 10-minute exposure; 0.006 mg/L, lowest irritant concentration, 10-minute exposure." No further information was provided. Short-Term Studies No studies were identified. Long-Term Studies No studies were identified. ANIMAL STUDIES Oral Exposures Acute Studies In acute oral toxicity studies using CNBr, 20 rats and 24 mice (sex and strain not specified) were dosed with CNBr at 1-100 mg/kg bw for rats and 0.5-100 mg/kg bw for mice (Eastman Kodak Co., 1992). Toxic symptoms included weakness, rapid prostration, squirming, ataxia, tremors, convulsions, and rough coat. Mortality data were not provided; however, the study report included an LD50 value between 25-50 mg/kg bw CNBr (approximately 6-12 mg/kg bw CN ) for both species. This LD50 range for CNBr, in CN equivalents (6-12 mg/kg bw), is similar to the LD50 range for CN~ (3-8 mg/kg bw) reported in U.S. EPA (2010). Subchronic-Duration Studies IRIS (U.S. EPA, 2010) has provided a chronic RfD based on analogy to HCN toxicity data. However, lack of data pertinent to the mode of action of CNBr and available information on CNBr raise several uncertainties using the approach previously considered by the IRIS (1988) to derive a subchronic p-RfD. Inhalation Exposure Acute Studies In an acute inhalation toxicity study, Dow Chemical Company (1992, as cited in U.S. EPA, 2010) exposed S-D rats (8-10 per sex per group) via whole body inhalation to CNBr at 10, 35, 45, 56, or 65 ppm for 6 hours or at 112 ppm for 2.5 hours. Chamber concentrations of CNBr were verified by gas chromatography. Rats were observed prior to and during exposure, and for up to 2 weeks after exposure. Two rats per sex from the 10-, 35-, 45-, and 56-ppm groups were sacrificed for gross pathologic examination 24 hours after exposure. Gross 8 Cyanogen Bromide ------- FINAL 12-12-2012 pathological examinations were also performed on any rats that died and all rats remaining alive at the end of the 2-week observation period. No mortality was observed in the 10- and 35-ppm groups following the 6-hour exposure; however, substantial mortality was observed at 45 ppm (8/8 M, 2/8 F), 56 ppm (5/8 M, 2/8 F), 65 ppm (8/10 M, 10/10 F), and 112 ppm (10/10 M, 10/10 F). Transient nasal irritation was observed at 35 ppm, and moderate-to-severe respiratory tract irritation was observed at >45 ppm, with rats gasping for breath during and after exposure, and "severe weight loss with a slow recovery." Necropsy revealed severe respiratory tract irritation, congested lungs and liver, and distended stomachs due to mouth breathing. The LC50 3 3 was reported to be 39.3 ppm (170.3 mg/m ) for males and 52.7 ppm (228.3 mg/m ) for females (equivalent to 43.4 and 58.3 mg/m3 HCN, respectively). The LC50 for CNBr in HCN equivalents "3 is similar in magnitude to the range of LC50 values for HCN (151-579 mg/m ) reported in U.S. EPA (2010). OTHER DATA (SHORT-TERM TESTS, OTHER EXAMINATIONS) No studies were identified with regard to the genotoxicity of CNBr. DERIVATION OF PROVISIONAL VALUES DERIVATION OF ORAL REFERENCE DOSES Because CNBr dissociates to cyanide, IRIS (U.S EPA, 1988) used cyanide data for derivation of an RfD for CNBr by analogy to HCN. Thyroid toxicity was the critical effect used for developing the RfD, with a POD of 12.5 mg/kg-day. However, further evaluation of data presented in the revised assessment for HCN, IRIS (U.S. EPA, 2010) presented a much lower POD (BMDL =1.9 mg/kg-day) based on reproductive effects reported in the same NTP (1993a,b) study. Associated reproductive effects at this POD (BMDL =1.9 mg/kg-day), were not evaluated in the earlier IRIS assessment. Furthermore, human male fertility is established to be at doses lower than the rodent test species, suggesting that effects on human fertility may be more susceptible than rodents following exposure to toxic substances (Working, 1988). Additionally, available data discussed earlier indicated major differences in acute toxicity of cyanides and CNBr, as well as dermal and respiratory effects produced by CNBr resulting from direct interaction with proteins and slow dissociation of cyanogen bromide in water, raising debate as to how quickly dissociation may take place in vivo. Furthermore, given the absence of pharmacokinetic information on CNBr, the issues surrounding the linkage between CNBr and simple cyanides introduces incertitude in the prudence of deriving a subchronic p-RfD. Because of the aforementioned uncertainties and unavailability of toxicity data specifically for CNBr, derivation of a subchronic p-RfD value is precluded at present. DERIVATION OF INHALATION REFERENCE CONCENTRATIONS Derivation of Subchronic and Chronic Provisional RfC IRIS (U.S. EPA, 2010) recommended that the RfC for HCN should not be used to estimate an RfC for cyanide salts due to considerations of inhalation uncertainties. Specifically, exposure to HCN occurs as a gas, whereas the extremely high boiling points and vapor pressure of cyanide salts (e.g., CNBr) predict inhalation exposure as aerosols. Thus, lack of data on inhalation exposure to CNBr precludes the derivation of provisional inhalation toxicity values. 9 Cyanogen Bromide ------- FINAL 12-12-2012 CANCER WOE DESCRIPTOR Limitations in the available data preclude development of a WOE descriptor. DERIVATION OF PROVISIONAL CANCER POTENCY VALUES No long-term studies were found examining the effects of CNBr via oral or inhalation exposure in humans or rats. REFERENCES ACGIH (American Conference of Governmental Industrial Hygienists). (2008) Threshold limit values for chemical substances and physical agents and biological exposure indices. Cincinnati, OH. As cited in HSDB (Hazardous Substances Data Bank). Available online at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen7HSDB. Accessed on January 18, 2011. 594308 ATSDR (Agency for Toxic Substances and Disease Registry). (2011) Toxicological profile information sheet. U.S. Department of Health and Human Services, Public Health Service, Atlanta, GA. Available online at http://www.atsdr.cdc.gov/toxprofiles/index.asp. Accessed on January 18, 2011. 684152 CalEPA (California Environmental Protection Agency). (2008) All OEHHA acute, 8-hour and chronic reference exposure levels (chRELs) as on December 18, 2008. Office of Environmental Health Hazard Assessment, Sacramento, CA. Available online at http://www.oehha.ca.gov/air/allrels.html. Accessed on January 18, 2011. 595416 CalEPA (California Environmental Protection Agency). (2009) OEHHA toxicity criteria database. Office of Environmental Health Hazard Assessment, Sacramento, CA. Available online at http://www.oehha.ca.gov/riskAChemicalDB/index.asp. Accessed on January 18, 2011. 595417 ChemlDplus Advanced. (2011) United States Library of Medicine, Specialized Information Services. Available online at http://chem.sis.nlm.nih.gov/chemidplus/. Accessed on January 6, 2011. 629639 Eastman Kodak Company. (1992) Initial submission: Toxicity studies with cyanogen bromide in rats, mice, and guinea pigs with cover letter dated 081092 (Report No. 88920005161). Rochester, NY: Eastman Kodak Company. (NTIS No. OTS0544135). 705060 Hartung, R. (1982) Cyanides and nitriles. In: GD Clayton; FE Clayton (Eds.), Patty's Industrial Hygiene and Toxicology (pp. 4845-4900). New York, NY: John Wiley and Sons, Inc. 689872 IARC (International Agency for Research on Cancer). (2011) Monographs on the evaluation of carcinogenic risks to humans. Lyon, France: IARC. Available online at http://monographs.iarc.fr/ENG/Monographs/PDFs/index.php. Accessed on January 18, 2011. 783869 10 Cyanogen Bromide ------- FINAL 12-12-2012 International Labour Organization. (2000) International Occupational Safety and Health Information Centre (CIS), International Chemical Safety Cards (ICSC). Available online at http://www.ilo.org/legacv/english/protection/safework/cis/products/icsc/dtasht/ icsc01/icsc0136. htm. Accessed on January 14, 2011. Luttrell, WE. (2009) Cyanogen bromide. J Chem Health Safety 16(4):29-30. Available online at http://dx.doi.ore/10.1016/ijchas.2009.05.012. 723650 NIOSH (National Institute for Occupational Safety and Health). (2010) NIOSH pocket guide to chemical hazards. Index of chemical abstracts service registry numbers (CAS No.). Center for Disease Control and Prevention, U.S. Department of Health, Education and Welfare, Atlanta, GA. Available online at http://www.cdc.gov/niosh/npg/npgdcas.html. Accessed on January 18, 2011. 625692 NTP (National Toxicology Program). (2011) Report on carcinogens, 12th edition. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC. Available online at http://ntp.niehs.nih.eov/ntp/roc/twelfth/rocl2.pdf. 737606 OSHA (Occupational Safety and Health Administration). (2004) Cyanide. OSHA/EPA Occupational Chemical Database, Chemical Sampling Information. Available online at http://www.osha.eov/dts/chemicalsampline/data/CH 230400.html. Accessed on January 18, 2011. OSHA (Occupational Safety and Health Administration). (2010) Air contaminants: occupational safety and health standards for shipyard employment, subpart Z, toxic and hazardous substances. U.S. Department of Labor, Washington, DC; OSHA Standard 1915.1000. Available online at http://www.osha.gov/pls/oshaweb/owadisp.show document?p table STA\l)ARDS&p id 102 86. Accessed on January 18, 201 1. 625691 U.S. EPA (Environmental Protection Agency). (1986) Guidelines for carcinogen risk assessment. Risk Assessment Forum, Washington, DC; EPA/630/R-00/004. September 1986. Available online at http://epa.gov/raf/publications/pdfs/CA%20GUIDELINES 1986.PDF. 199530 U.S. EPA (Environmental Protection Agency). (1988) IRIS Summary for cyanogen bromide (CASRN 506-68-3). Integrated Risk Information System (IRIS), Office of Research and Development, National Center for Environmental Assessment, Washington, DC. Available online at http://www.epa. gov/iris/subst/03 58.htm. Accessed on January 18, 2011. U.S. EPA (Environmental Protection Agency). (1992) Drinking water criteria document for cyanide. Environmental Criteria and Assessment Office, Cincinnati, OH; EPA/600/X-84/192. Available online at http://nepis.epa.gov/Exe/ZvPURL.cei?Dockev=900Q0D00.txt. 677130 U.S. EPA (Environmental Protection Agency). (1994) Chemical assessments and related activities (CARA). Office of Health and Environmental Assessment, Washington, DC; EPA/600/R-94/904. Available online at nepis.epa.eov/Exe/ZvPURL.cei?Dockev=6000lG8L.txt. 596444 11 Cyanogen Bromide ------- FINAL 12-12-2012 U.S. EPA (Environmental Protection Agency). (2002) A review of the reference dose and reference concentration process. Final report. Risk Assessment Forum, Washington, DC; EPA/630/P-02/002F. Available online at http://www.epa.gov/raf/publications/pdfs/rfd-final.pdf. 088824 U.S. EPA (Environmental Protection Agency). (2010) Toxicol ogical review of hydrogen cyanide and cyanide salts. Integrated Risk Information System (IRIS), Office of Research and Development, National Center for Environmental Assessment, Washington, DC; EPA/635/R-08/016F. Available online at http://www.epa.gov/iris/toxreviews/0060tr.pdf. 723657 U.S. EPA (Environmental Protection Agency). (201 la) 2011 Edition of the Drinking Water Standards and Health Advisories. Office of Water, Washington, DC; EPA/820/R-11/002. Available online at http://water.epa.gov/action/advisories/drinking/upload/dwstandards2011.pdf http://www.epa.gov/waterscience/drinking/standards/dwstandards2009.pdf. Accessed on May 5, 2011. U.S. EPA (Environmental Protection Agency). (201 lb) Health effects assessment summary tables (HEAST). Prepared by the Office of Research and Development, National Center for Environmental Assessment, Cincinnati OH for the Office of Emergency and Remedial Response, Washington, DC. Available online at http://epa-heast.ornl.gov/. Accessed on January 18, 201 1. 595422 WHO (World Health Organization). (2011) Online catalogs for the Environmental Health Criteria series. Available online at http://www.who.int/topics/environmental health/en/. Accessed on January 18, 2011. 783977 Working, P.K. (1988) Male reproductive toxicology. Comparison of human and animal models. Environ Health Perspect 77:37-44. 12 Cyanogen Bromide ------- |