Document ID: EPA-HQ-OPPT-2005-0049-0035
Agency: epa
Document Type: Supporting & Related Material
Title: 
Posted Date: 2006-01-10T05:00Z

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      <FORM name=fcol onsubmit="return validateForm()" 
      action=http://oaspub.epa.gov/webi/meta_first_new2.try_these_first 
      method=post><SELECT size=1 name=select> <OPTION value=reforal 
        selected>Reference Dose for Chronic Oral Exposure (RfD)<OPTION 
        value=refinhal>Reference Concentration for Chronic Inhalation Exposure 
        (RfC)<OPTION value=carc>Carcinogenicity Assessment for Lifetime 
        Exposure<OPTION value=bib>Bibliography<OPTION value=revhis>Revision 
        History<OPTION value=syn>Synonyms</OPTION></SELECT> <A 
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      <P><STRONG>0277</STRONG></P>
      <P><STRONG>Lead and compounds (inorganic); CASRN 
      7439-92-1</STRONG><BR><BR>Human health assessment information on a 
      chemical substance is included in IRIS only after a comprehensive review 
      of chronic toxicity data by U.S. EPA health scientists from several 
      program offices, regional offices, and the Office of Research and 
      Development. Sections I (Chronic Health Hazard Assessments for 
      Noncarcinogenic Effects) and II (Carcinogenicity Assessment for Lifetime 
      Exposure) present the positions that were reached during the review 
      process. Supporting information and explanations of the methods used to 
      derive the values given in IRIS are provided in the guidance documents 
      located on the IRIS website at <A 
      href="http://www.epa.gov/iriswebp/iris/backgr-d.htm">http://www.epa.gov/iriswebp/iris/backgr-d.htm</A>. 
      </P>
      <P>STATUS OF DATA FOR Lead and compounds (inorganic)</P>
      <P><STRONG>File First On-Line 03/01/1988</STRONG></P>
      <TABLE cellSpacing=0 cellPadding=2 width="100%" 
      summary="This table contains general substance status information." 
      border=0>
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        <TR>
          <TH id=header1 width=196>
            <DIV align=left>Category (section)</DIV></TH>
          <TH id=header2 width=55>
            <DIV align=left>Status</DIV></TH>
          <TH id=header3 width=99>
            <DIV align=left>Last Revised</DIV></TH></TR>
        <TR>
          <TD headers=header1 width=239>Oral RfD Assessment (I.A.)</TD>
          <TD headers=header2 width=81>discussion</TD>
          <TD headers=header3 width=109>07/08/2004</TD></TR>
        <TR>
          <TD headers=header1 width=239>Inhalation RfC Assessment (I.B.)</TD>
          <TD headers=header2 width=81>no data</TD>
          <TD headers=header3 width=109></TD></TR>
        <TR>
          <TD headers=header1 width=239>Carcinogenicity Assessment (II.)</TD>
          <TD headers=header2 width=81>on-line</TD>
          <TD headers=header3 width=109>11/01/1993</TD></TR></TBODY></TABLE>
      <H2><A name=noncar></A>_I.  Chronic Health Hazard Assessments for 
      Noncarcinogenic Effects</H2>
      <H2><A name=reforal></A>_I.A. Reference Dose for Chronic Oral Exposure 
      (RfD)</H2>
      <P>Substance Name -- Lead and compounds (inorganic)<BR>CASRN -- 
      7439-92-1<BR>Section I.A. Last Revised -- 07/08/2004<BR><BR>In general, 
      the oral Reference Dose (RfD) is an estimate (with uncertainty spanning 
      perhaps an order of magnitude) of a daily exposure to the human population 
      (including sensitive subgroups) that is likely to be without an 
      appreciable risk of deleterious effects during a lifetime. The RfD is 
      based on the assumption that thresholds exist for certain toxic effects 
      such as cellular necrosis and is expressed in units of mg/kg-day. Please 
      refer to the guidance documents at <A 
      href="http://www.epa.gov/iriswebp/iris/backgr-d.htm">http://www.epa.gov/iriswebp/iris/backgr-d.htm</A> 
      for an elaboration of these concepts. Since RfDs can be derived for the 
      noncarcinogenic health effects of substances that are also carcinogens, it 
      is essential to refer to other sources of information concerning the 
      carcinogenicity of this chemical substance. If the U.S. EPA has evaluated 
      this substance for potential human carcinogenicity, a summary of that 
      evaluation will be contained in Section II of this file. </P>
      <H2><A name=oralrfd></A>__I.A.1. Oral RfD Summary</H2>
      <P>Health effects associated with exposure to inorganic lead and compounds 
      include, but are not limited to, neurotoxicity, developmental delays, 
      hypertension, impaired hearing acuity, impaired hemoglobin synthesis, and 
      male reproductive impairment. Importantly, many of lead's health effects 
      may occur without overt signs of toxicity. Lead has particularly 
      significant effects in children, well before the usual term of chronic 
      exposure can take place. Children under 6 years old have a high risk of 
      exposure because of their more frequent hand-to-mouth behavior (Centers 
      for Disease Control and Prevention (CDC), 1991:<BR><A 
      href="http://www.cdc.gov/nceh/lead/publications/books/plpyc/contents.htm">http://www.cdc.gov/nceh/lead/publications/books/plpyc/contents.htm</A> 
      <A href="http://www.epa.gov/epahome/exitepa.htm"><IMG 
      alt="Exit EPA Disclaimer" 
      src="Lead and compounds (inorganic) (CASRN 7439-92-1), IRIS, Environmental Protection Agency_files/epafiles_misc_exitepadisc.gif" 
      border=0></A> ). </P>
      <P>EPA considered providing an RfD for inorganic lead in 1985, and 
      concluded that it was inappropriate to develop an RfD, as documented 
      online in the following statement in 1988: </P>
      <P>
      <BLOCKQUOTE>A great deal of information on the health effects of lead 
        has been obtained through decades of medical observation and scientific 
        research. This information has been assessed in the development of air 
        and water quality criteria by the Agency's Office of Health and 
        Environmental Assessment (OHEA) in support of regulatory decision-making 
        by the Office of Air Quality Planning and Standards (OAQPS) and by the 
        Office of Drinking Water (ODW). By comparison to most other 
        environmental toxicants, the degree of uncertainty about the health 
        effects of lead is quite low. It appears that some of these effects, 
        particularly changes in the levels of certain blood enzymes and in 
        aspects of children's neurobehavioral development, may occur at blood 
        lead levels so low as to be essentially without a threshold. The 
        Agency's RfD Work Group discussed inorganic lead (and lead compounds) at 
        two meetings (07/08/1985 and 07/22/1985) and considered it inappropriate 
        to develop an RfD for inorganic lead.</BLOCKQUOTE>
      <P></P>
      <P>EPA is not providing a review of current literature concerning the 
      health effects of lead at this time (June, 2004), given the ongoing effort 
      of the CDC to re-evaluate the blood lead level of concern (CDC, 2004: <A 
      href="http://www.cdc.gov/nceh/lead/spotLights/changeBLL.htm">http://www.cdc.gov/nceh/lead/spotLights/changeBLL.htm</A> 
      <A href="http://www.epa.gov/epahome/exitepa.htm"><IMG 
      alt="Exit EPA Disclaimer" 
      src="Lead and compounds (inorganic) (CASRN 7439-92-1), IRIS, Environmental Protection Agency_files/epafiles_misc_exitepadisc.gif" 
      border=0></A>). A screening-level review of the more recent toxicology 
      literature pertinent to noncancer effects associated with oral exposure to 
      Lead and compounds (inorganic) was conducted by an EPA contractor in 
      September 2002, and identified one or more significant new studies since 
      the 1985 assessment. IRIS users may request the references for those 
      studies from the IRIS Hotline at <A 
      href="mailto:hotline.iris@epa.gov">hotline.iris@epa.gov</A> or 
      (202)566-1676.</P>
      <P>Current knowledge of lead pharmacokinetics indicates that risk values 
      derived by standard procedures would not truly indicate the potential 
      risk, because of the difficulty in accounting for pre-existing body 
      burdens of lead. Lead bioaccumulates in the body, primarily in the 
      skeleton. Lead body burdens vary significantly with age, health status, 
      nutritional state, maternal body burden during gestation and lactation, 
      etc. For this reason, and because of the continued apparent lack of 
      threshold (CDC, 2004: <A 
      href="http://www.cdc.gov/nceh/lead/spotLights/changeBLL.htm">http://www.cdc.gov/nceh/lead/spotLights/changeBLL.htm</A> 
      <A href="http://www.epa.gov/epahome/exitepa.htm"><IMG 
      alt="Exit EPA Disclaimer" 
      src="Lead and compounds (inorganic) (CASRN 7439-92-1), IRIS, Environmental Protection Agency_files/epafiles_misc_exitepadisc.gif" 
      border=0></A>), it is still inappropriate to develop reference values for 
      lead.</P>
      <P>The purpose of this 2004 update is to assist IRIS users in finding 
      relevant risk information and risk assessment methods that have been 
      developed within EPA for media-specific applications. Most of these 
      methods focus on blood lead levels, through the development of several 
      media-specific lead exposure levels for risk management and regulatory 
      purposes. Further information on these lead risk assessment methods and 
      tools is described in Section 1.A.4.</P>
      <H2><A name=studoral></A>__I.A.2. Principal and Supporting Studies (Oral 
      RfD)</H2>
      <P>Not applicable.</P>
      <H2><A name=umforal></A>__I.A.3. Uncertainty and Modifying Factors (Oral 
      RfD)</H2>
      <P>Not applicable.</P>
      <H2><A name=addoral></A>__I.A.4. Additional Studies/Comments (Oral 
      RfD)</H2>
      <P>As noted above, EPA is not providing a review of current literature at 
      this time. In addition to information developed by CDC and the Agency for 
      Toxic Substances and Disease Registry (ATSDR), described below, EPA has 
      developed a number of lead exposure limits in support of regulatory 
      decision-making, and has developed methods to assess risk from lead in 
      situations not covered by these limits, also described below.</P>
      <P>The CDC identified 10 µg/dL as the blood lead level of concern in 
      children in their 1991 report "Preventing Lead Poisoning in Young 
      Children" (<A 
      href="http://www.cdc.gov/nceh/lead/publications/books/plpyc/contents.htm">http://www.cdc.gov/nceh/lead/publications/books/plpyc/contents.htm</A> 
      <A href="http://www.epa.gov/epahome/exitepa.htm"><IMG 
      alt="Exit EPA Disclaimer" 
      src="Lead and compounds (inorganic) (CASRN 7439-92-1), IRIS, Environmental Protection Agency_files/epafiles_misc_exitepadisc.gif" 
      border=0></A>), and provided risk management options for categories of 
      blood lead levels higher than 10 µg/dL. In view of the fact that health 
      effects were and continue to be identified below the level of concern, the 
      CDC convened an Advisory Committee on Childhood Lead Poisoning Prevention 
      to consider whether the level of concern should be changed. The Advisory 
      Committee's progress reports can be found at <A 
      href="http://www.cdc.gov/nceh/lead/ACCLPP/acclpp_main.htm">http://www.cdc.gov/nceh/lead/ACCLPP/acclpp_main.htm</A> 
      <A href="http://www.epa.gov/epahome/exitepa.htm"><IMG 
      alt="Exit EPA Disclaimer" 
      src="Lead and compounds (inorganic) (CASRN 7439-92-1), IRIS, Environmental Protection Agency_files/epafiles_misc_exitepadisc.gif" 
      border=0></A>. At this time, CDC has not changed the blood lead level of 
      concern for three reasons (March 23, 2004, <A 
      href="http://www.cdc.gov/nceh/lead/spotLights/changeBLL.htm">http://www.cdc.gov/nceh/lead/spotLights/changeBLL.htm</A> 
      <A href="http://www.epa.gov/epahome/exitepa.htm"><IMG 
      alt="Exit EPA Disclaimer" 
      src="Lead and compounds (inorganic) (CASRN 7439-92-1), IRIS, Environmental Protection Agency_files/epafiles_misc_exitepadisc.gif" 
      border=0></A>):</P>
      <P>
      <UL>
        <LI>'No effective clinical interventions are known to lower blood lead 
        levels for children with levels less than 10 µg/dL or to reduce the 
        risks for adverse developmental effects.' ‘
        <LI>Children cannot be accurately classified as having blood lead levels 
        above or below 10 µg/dL because of the inaccuracy inherent in laboratory 
        testing.' ‘
        <LI>Finally, there is no evidence of a threshold below which adverse 
        effects are not experienced. Thus, any decision to establish a new level 
        of concern would be arbitrary and provide uncertain benefits.'</LI></UL>
      <P></P>
      <P>In addition to the ongoing CDC effort, the ATSDR is mandated by 
      Congress under CERCLA (1980) and SARA (1986) to develop toxicological 
      profiles for all hazardous waste sites on the National Priorities List 
      (NPL) (PB/99/166704, NTIS PB-99-66704; <A 
      href="http://www.atsdr.cdc.gov/toxprofiles/tp13.html">http://www.atsdr.cdc.gov/toxprofiles/tp13.html</A> 
      <A href="http://www.epa.gov/epahome/exitepa.htm"><IMG 
      alt="Exit EPA Disclaimer" 
      src="Lead and compounds (inorganic) (CASRN 7439-92-1), IRIS, Environmental Protection Agency_files/epafiles_misc_exitepadisc.gif" 
      border=0></A>). Lead is the most common toxic metal at these sites. The 
      ATSDR Toxicological Profile for Lead was last updated in 1999.</P>
      <P>EPA has developed a number of lead exposure levels in support of 
      regulatory decision-making, which limit the amount of lead that can be 
      present in various environmental media. Under the National Primary 
      Drinking Water Regulations, EPA established a Maximum Contaminant Level 
      (MCL) for lead in drinking water due to any source. Under the Toxic 
      Substances Control Act (TSCA) as amended by the Residential Lead-Based 
      Paint Hazard Reduction Act, EPA established standards for lead in paint, 
      house dust, and outdoor soil. The following links provide more 
      information:</P>
      <P>Action level for lead in drinking water: <A 
      href="http://www.epa.gov/safewater/mcl.html#mcls">http://www.epa.gov/safewater/mcl.html#mcls</A> 
      </P>
      <P>Regulation for lead in paint housedust, and outdoor soil: <A 
      href="http://www.epa.gov/opptintr/lead/leadhaz.htm">http://www.epa.gov/opptintr/lead/leadhaz.htm</A></P>
      <P>National ambient air quality standard: <A 
      href="http://www.epa.gov/ttn/naaqs/">http://www.epa.gov/ttn/naaqs/</A></P>
      <P>Note that additional relevant information will be found by following 
      links provided at these websites, such as dose-response relationships 
      relating blood lead levels to changes in IQ (children) and hypertension 
      (men).</P>
      <P>Due to the likelihood of simultaneous exposure to various sources of 
      lead, EPA recommends a case-by-case evaluation of the relative 
      contributions of relevant lead exposures in a particular setting. The 
      Superfund Program has guidelines for identifying lead-contaminated soil 
      (<A 
      href="http://www.epa.gov/superfund/programs/lead/products.htm">http://www.epa.gov/superfund/programs/lead/products.htm</A>), 
      and facilitates site-specific risk assessments at contaminated waste sites 
      on the National Priority List, where the major sources of soil 
      contamination are activities such as disposal of mining and manufacturing 
      wastes contaminated with lead and deposition of lead from air, rather than 
      presence of lead-based paint in residences (see: <A 
      href="http://www.epa.gov/superfund/programs/lead/trwhome.htm">http://www.epa.gov/superfund/programs/lead/trwhome.htm</A>). 
      The Superfund Program uses the Integrated Exposure Uptake Biokinetic 
      (IEUBK) Model for Lead in Children. The IEUBK Model provides estimates of 
      the risk of elevated blood lead associated with particular combinations of 
      relevant sources of lead exposure. This interactive model is described in 
      more detail and provided for downloading at <A 
      href="http://www.epa.gov/superfund/programs/lead/products.htm">http://www.epa.gov/superfund/programs/lead/products.htm</A>. 
      Note that the IEUBK model was used in direct support of the lead-based 
      paint regulation cited above.</P>
      <P>The Superfund Program has also developed an Adult Lead Model, for use 
      when lead exposures to adults, especially pregnant women, are of greater 
      concern. This model is described and provided for downloading at <A 
      href="http://www.epa.gov/superfund/programs/lead/adult.htm">http://www.epa.gov/superfund/programs/lead/adult.htm</A>. 
      </P>
      <P>EPA maintains a lead resources page (<A 
      href="http://www.epa.gov/opptintr/lead/resources.htm">http://www.epa.gov/opptintr/lead/resources.htm</A>). 
      Links are provided to many other EPA offices, government agencies, and 
      other organizations involved in efforts to reduce exposure to lead in the 
      environment.</P>
      <H2><A name=conoral></A>__I.A.5. Confidence in Risk Values</H2>
      <P>Not applicable.</P>
      <H2><A name=docoral></A>__I.A.6. EPA Documentation and Review of the Oral 
      RfD</H2>
      <P>Agency Completion Date – 05/26/2004</P>
      <H2>__I.A.7. EPA Contacts (Oral RfD)</H2>
      <P>Please contact the IRIS Hotline for all questions concerning this 
      assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 
      (fax), or <A href="mailto:hotline.iris@epa.gov">hotline.iris@epa.gov</A> 
      (email address). </P>
      <P align=center><A href="http://www.epa.gov/iris/subst/0277.htm#top">Back 
      to top</A> </P>
      <HR>

      <H2><A name=refinhal></A>_I.B. Reference Concentration for Chronic 
      Inhalation Exposure (RfC)</H2>
      <P>Substance Name -- Lead and compounds (inorganic)<BR>CASRN – 
      7439-92-1<BR>
      <P>In general, the Reference Concentration (RfC) is an estimate (with 
      uncertainty spanning perhaps an order of magnitude) of a daily inhalation 
      exposure of the human population (including sensitive subgroups) that is 
      likely to be without an appreciable risk of deleterious effects during a 
      lifetime. The RfC considers toxic effects for both the respiratory system 
      (portal-of-entry) and for effects peripheral to the respiratory system 
      (extrarespiratory effects). The inhalation RfC (generally expressed in 
      units of mg/m3) is analogous to the oral RfD and is likewise based on the 
      assumption that thresholds exist for certain toxic effects such as 
      cellular necrosis. </P>
      <P>Inhalation RfCs are derived according to the <EM>Interim Methods for 
      Development of Inhalation Reference Doses</EM> (EPA/600/8-88/066F, 1989) 
      and subsequently, according to <EM>Methods for Derivation of Inhalation 
      Reference Concentrations and Application of Inhalation Dosimetry</EM> 
      (EPA/600/8-90/066F, 1994). Since RfCs can also be derived for the 
      noncarcinogenic health effects of substances that are carcinogens, it is 
      essential to refer to other sources of information concerning the 
      carcinogenicity of this chemical substance. If the U.S. EPA has evaluated 
      this substance for potential human carcinogenicity, a summary of that 
      evaluation will be contained in Section II of this file.</P>
      <H2><A name=inhalrfc></A>__I.B.1. Inhalation RfC Summary</H2>
      <P>No RfC is available. See Section I.A. for additional information.</P>
      <H2><A name=studinhal></A>__I.B.2. Principal and Supporting Studies 
      (Inhalation RfC)</H2>
      <P>Not applicable.</P>
      <H2><A name=umfinhal></A>__I.B.3. Uncertainty and Modifying Factors 
      (Inhalation RfC)</H2>
      <P>Not applicable.</P>
      <H2><A name=addinhal></A>__I.B.4. Additional Studies/Comments (Inhalation 
      RfC)</H2>
      <P>Not applicable.</P>
      <H2><A name=coninhal></A>__I.B.5. Confidence in the Inhalation RfC</H2>
      <P>Not applicable.</P>
      <H2><A name=docinhal></A>__I.B.6. EPA Documentation and Review of the 
      Inhalation RfC</H2>
      <P>Agency Completion Date -- Not applicable.</P>
      <H2>__I.B.7. EPA Contacts (Inhalation RfC)</H2>
      <P>Please contact the IRIS Hotline for all questions concerning this 
      assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 
      (fax), or <A href="mailto:hotline.iris@epa.gov">hotline.iris@epa.gov</A> 
      (email address). </P>
      <P align=center><A href="http://www.epa.gov/iris/subst/0277.htm#top">Back 
      to top</A> </P>
      <HR>

      <H2><A name=carc></A>_II.  Carcinogenicity Assessment for Lifetime 
      Exposure</H2>
      <P>Substance Name -- Lead and compounds (inorganic)<BR>CASRN -- 
      7439-92-1<BR>Section II Last Revised -- II.A. introductory paragraph 
      revised 07/08/2004. II.A.1 - II.D. last revised 11/01/1993 </P>
      <P>Section II provides information on three aspects of the carcinogenic 
      assessment for the substance in question; the weight-of-evidence judgment 
      of the likelihood that the substance is a human carcinogen, and 
      quantitative estimates of risk from oral exposure and from inhalation 
      exposure. The quantitative risk estimates are presented in three ways. The 
      slope factor is the result of application of a low-dose extrapolation 
      procedure and is presented as the risk per (mg/kg)/day. The unit risk is 
      the quantitative estimate in terms of either risk per µg/L drinking water 
      or risk per µg/cu.m air breathed. The third form in which risk is 
      presented is a concentration of the chemical in drinking water or air 
      associated with cancer risks of 1 in 10,000, 1 in 100,000, or 1 in 
      1,000,000. The rationale and methods used to develop the carcinogenicity 
      information in IRIS are described in the Risk Assessment Guidelines of 
      1986 (EPA/600/8-87/045) and in the IRIS Background Document. IRIS 
      summaries developed since the publication of EPA's more recent Proposed 
      Guidelines for Carcinogen Risk Assessment also utilize those Guidelines 
      where indicated (Federal Register 61(79):17960-18011, April 23, 1996). 
      Users are referred to Section I of this IRIS file for information on 
      long-term toxic effects other than carcinogenicity. </P>
      <H2><A name=evid></A>_II.A. Evidence for Human Carcinogenicity</H2>
      <P>Note that the National Toxicology Program's Report on Carcinogens 
      Review Committee has recommended that lead and lead compounds be 
      considered "reasonably anticipated to be human carcinogens" (<A 
      href="http://ntp-server.niehs.nih.gov/NewHomeRoc/roc11Bkgrnd2003.html">http://ntp-server.niehs.nih.gov/NewHomeRoc/roc11Bkgrnd2003.html</A> 
      <A href="http://www.epa.gov/epahome/exitepa.htm"><IMG 
      alt="Exit EPA Disclaimer" 
      src="Lead and compounds (inorganic) (CASRN 7439-92-1), IRIS, Environmental Protection Agency_files/epafiles_misc_exitepadisc.gif" 
      border=0></A>; July 2003). Also, the International Agency for Research on 
      Cancer (IARC) has undertaken a reevaluation of lead's carcinogenicity (<A 
      href="http://monographs.iarc.fr/htdocs/announcements/vol87.htm">http://monographs.iarc.fr/htdocs/announcements/vol87.htm</A> 
      <A href="http://www.epa.gov/epahome/exitepa.htm"><IMG 
      alt="Exit EPA Disclaimer" 
      src="Lead and compounds (inorganic) (CASRN 7439-92-1), IRIS, Environmental Protection Agency_files/epafiles_misc_exitepadisc.gif" 
      border=0></A>).</P>
      <H2><A name=woe></A>__II.A.1. Weight-of-Evidence Characterization</H2>
      <P>Classification -- B2; probable human carcinogen</P>
      <P>Basis -- Sufficient animal evidence. Ten rat bioassays and one mouse 
      assay have shown statistically significant increases in renal tumors with 
      dietary and subcutaneous exposure to several soluble lead salts. Animal 
      assays provide reproducible results in several laboratories, in multiple 
      rat strains with some evidence of multiple tumor sites. Short term studies 
      show that lead affects gene expression. Human evidence is inadequate.</P>
      <H2><A name=humcarc></A>__II.A.2. Human Carcinogenicity Data</H2>
      <P>Inadequate. There are four epidemiologic studies of occupational 
      cohorts exposed to lead and lead compounds. Two studies (Dingwall-Fordyce 
      and Lane, 1963; Nelson et al., 1982) did not find any association between 
      exposure and cancer mortality. Selevan et al. (1985), in their 
      retrospective cohort mortality study of primary lead smelter workers, 
      found a slight decrease in the total cancer mortality (SMR=95). Apparent 
      excesses were observed for respiratory cancer (SMR=111, obs=41, p>0.05) 
      and kidney cancer (SMR=204, obs=6, p>0.05). Cooper and Gaffey (1975) 
      and Cooper (1985 update) performed a cohort mortality study of battery 
      plant workers and lead smelter workers. They found statistically 
      significant excesses for total cancer mortality (SMR=113, obs=344), 
      stomach cancer (SMR=168, obs=34), and lung cancer (SMR=124, obs=109) in 
      the battery plant workers. Although similar excesses were observed in the 
      smelter workers, they were not statistically significant. Cooper and 
      Gaffey (1975) felt it was possible that individual subjects were monitored 
      primarily on the basis of obvious signs of lead exposure, while others who 
      showed no symptoms of lead poisoning were not monitored. </P>
      <P>All of the available studies lacked quantitative exposure information, 
      as well as information on the possible contribution from smoking. All 
      studies also included exposures to other metals such as arsenic, cadmium, 
      and zinc for which no adjustment was done. The cancer excesses observed in 
      the lung and stomach were relatively small (<200). There was no 
      consistency of site among the various studies, and no study showed any 
      dose-response relationship. Thus, the available human evidence is 
      considered to be inadequate to refute or demonstrate any potential 
      carcinogenicity for humans from lead exposure. </P>
      <H2><A name=anicarc></A>__II.A.3. Animal Carcinogenicity Data</H2>
      <P>Sufficient. The carcinogenic potential of lead salts (primarily 
      phosphates and acetates) administered via the oral route or by injection 
      has been demonstrated in rats and mice by more than 10 investigators. The 
      most characteristic cancer response is bilateral renal carcinoma. Rats 
      given lead acetate or subacetate orally have developed gliomas, and lead 
      subacetate also produced lung adenomas in mice after i.p. administration. 
      Most of these investigations found a carcinogenic response only at the 
      highest dose. The lead compounds tested in animals are almost all soluble 
      salts. Metallic lead, lead oxide and lead tetraalkyls have not been tested 
      adequately. Studies of inhalation exposure have not been located in the 
      literature.</P>
      <P>Azar et al. (1973) administered 10, 50, 100, and 500 ppm lead as lead 
      acetate in dietary concentrations to 50 rats/sex/group for 2 years. 
      Control rats (100/sex) received the basal laboratory diet. In a second 
      2-year feeding study, 20 rats/group were given diets containing 0, 1000, 
      and 2000 ppm lead as lead acetate. No renal tumors were reported in the 
      control groups or in treated animals of either sex receiving 10 to100 ppm. 
      Male rats fed 500, 1000, and 2000 ppm lead acetate had an increased renal 
      tumor incidence of 5/50, 10/20, and 16/20, while 7/20 females in the 2000 
      ppm group developed renal tumors.</P>
      <P>The Azar et al. (1973) study is limited by the lack of experimental 
      detail. The possibility of environmental contamination from lead in the 
      air or drinking water was not mentioned. The strain of rats used was not 
      specified in the study, but the Health Effects Assessment for Lead (U.S. 
      EPA, 1984) indicates the rats were Wistar strain. The weight gain at 1000 
      and 2000 ppm was reported to be depressed, but details were not given. 
</P>
      <P>Kasprzak et al. (1985), in investigating the interaction of dietary 
      calcium on lead carcinogenicity, fed 1% lead subacetate (8500 ppm Pb) to 
      male Sprague-Dawley rats in the diet for 79 weeks. Of the rats surviving 
      (29/30) in this treatment group beyond 58 weeks, 44.8% had renal tumors. 
      Four rats had adenocarcinomas; the remaining nine had adenomas. Bilateral 
      tumors were noted. No renal tumors were noted among the controls. </P>
      <P>As part of a study to determine interactions between sodium nitrite, 
      ethyl urea and lead, male Sprague-Dawley rats were given lead acetate in 
      their drinking water for 76 weeks (Koller et al., 1986). The concentration 
      of lead was 2600 ppm. No kidney tumors were detected among the 10 control 
      rats. Thirteen of 16 (81%) lead-treated rats had renal tubular carcinoma; 
      three tumors were detected at 72 weeks and the remainder detected at the 
      termination of the study. </P>
      <P>Van Esch and Kroes (1969) fed basic lead acetate at 0, 0.1%, and 1.0% 
      in the diet to 25 Swiss mice/sex/group for 2 years. No renal tumors 
      developed in the control group, but 6/25 male mice of 0.1% basic lead 
      acetate group had renal tumors (adenomas and carcinomas combined). In the 
      1.0% group, one female had a renal tumor. The authors thought that the low 
      incidence in the 1.0% group was due to early mortality. </P>
      <P>Hamsters given lead subacetate at 0.5% and 1% in the diet had no 
      significant renal tumor response (Van Esch and Kroes, 1969). </P>
      <H2><A name=supdat></A>__II.A.4. Supporting Data for Carcinogenicity </H2>
      <P>Lead acetate induces cell transformation in Syrian hamster embryo cells 
      (DiPaolo et al., 1978) and also enhances the incidence of simian 
      adenovirus induction. Lead oxide showed similar enhanced adenovirus 
      induction (Casto et al., 1979). </P>
      <P>Under certain conditions lead compounds are capable of inducing 
      chromosomal aberrations in vivo and in tissue cultures. Grandjean et al. 
      (1983) showed a relationship between sister chromatid exchange and lead 
      exposure in exposed workers. Lead has been shown, in a number of DNA 
      structure and function assays, to affect the molecular processes 
      associated with the regulation of gene expression (U.S. EPA, 1986b). </P>
      <P align=center><A href="http://www.epa.gov/iris/subst/0277.htm#top">Back 
      to top</A> </P>
      <HR>

      <H2><A name=quaoral></A>_II.B. Quantitative Estimate of Carcinogenic Risk 
      from Oral <BR>Exposure</H2>
      <P>Not available.</P>
      <P>Quantifying lead's cancer risk involves many uncertainties, some of 
      which may be unique to lead. Age, health, nutritional state, body burden, 
      and exposure duration influence the absorption, release, and excretion of 
      lead. In addition, current knowledge of lead pharmacokinetics indicates 
      that an estimate derived by standard procedures would not truly describe 
      the potential risk. Thus, the Carcinogen Assessment Group recommends that 
      a numerical estimate not be used.</P>
      <P align=center><A href="http://www.epa.gov/iris/subst/0277.htm#top">Back 
      to top</A> </P>
      <HR>

      <H2><A name=quainhal></A>_II.C. Quantitative Estimate of Carcinogenic Risk 
      from Inhalation Exposure</H2>
      <P>Not available.</P>
      <P align=center><A href="http://www.epa.gov/iris/subst/0277.htm#top">Back 
      to top</A> </P>
      <HR>

      <H2><A name=doccar></A>_II.D. EPA Documentation, Review, and Contacts 
      (Carcinogenicity Assessment)</H2>
      <H2>__II.D.1. EPA Documentation</H2>
      <P>Source Document -- U.S. EPA, 1984, 1986, 1989</P>
      <P>U.S. EPA, 1989 has received OHEA and SAB review. </P>
      <P>The 1986 Air Quality Criteria Document for Lead has received Agency and 
      External Review. </P>
      <H2>__II.D.2. EPA Review (Carcinogenicity Assessment)</H2>
      <P>Verification Date -- 05/04/1988</P>
      <P>Screening-Level Literature Review Findings -- A screening-level review 
      of the more recent toxicology literature pertinent to the cancer 
      assessment for Lead and compounds (inorganic), conducted by an EPA 
      contractor in September 2002, did not identify any critical new studies. 
      IRIS users who know of important new studies may provide that information 
      to the IRIS Hotline at <A 
      href="mailto:hotline.iris@epa.gov">hotline.iris@epa.gov</A> or 
      (202)566-1676.</P>
      <H2>__II.D.3. EPA Contacts (Carcinogenicity Assessment</H2>
      <P>Please contact the IRIS Hotline for all questions concerning this 
      assessment or IRIS, in general, at (202)566-1676 (phone), (202)566-1749 
      (fax), or <A href="mailto:hotline.iris@epa.gov">hotline.iris@epa.gov</A> 
      (email address). </P>
      <P align=center><A href="http://www.epa.gov/iris/subst/0277.htm#top">Back 
      to top</A> </P>
      <HR>

      <H2>_III.  [reserved]<BR>_IV.  [reserved] <BR>_V.  
      [reserved]</H2>
      <HR>

      <H2><A name=bib></A>_VI.  Bibliography </H2>
      <P>Substance Name -- Lead and compounds (inorganic)<BR>CASRN -- 
      7439-92-1<BR>Section V.I. Last Revised -- 07/08/2004</P>
      <H2>_VI.A. Oral RfD References</H2>
      <P>None.</P>
      <P align=center><A href="http://www.epa.gov/iris/subst/0277.htm#top">Back 
      to top</A> </P>
      <HR>

      <H2>_VI.B. Inhalation RfC References</H2>
      <P>None.</P>
      <P align=center><A href="http://www.epa.gov/iris/subst/0277.htm#top">Back 
      to top</A> </P>
      <HR>

      <H2>_VI.C. Carcinogenicity Assessment References</H2>
      <P>Anderson, E.L., and CAG (Carcinogenic Assessment Group). 1983. 
      Quantitative approaches in use to assess cancer risk. Risk Analysis. 3: 
      277-295. </P>
      <P>Azar, A., H.J. Trochimowicz and M.E. Maxfield. 1973. Review of lead 
      studies in animals carried out at Haskell Laboratory - Two year feeding 
      study and response to hemorrhage study. In: Barth D., A. Berlin, R. Engel, 
      P. Recht and J. Smeets, Ed. Environmental health aspects of lead: 
      Proceedings International Symposium; October 1972; Amsterdam, The 
      Netherlands. Commission of the European Communities, Luxemberg. p. 
      199-208. </P>
      <P>Casto, B.C., J. Meyers and J.A. DiPaolo. 1979. Enhancement of viral 
      transformation for evaluation of the carcinogenic or mutagenic potential 
      of inorganic metal salts. Cancer Res. 39: 193-198. </P>
      <P>Cooper, W.C. 1985. Mortality among employees of lead battery plants and 
      lead producing plants, 1947-1980. Scand. J. Work Environ. Health. 11: 
      331-345. </P>
      <P>Cooper, W.C. and W.R. Gaffey. 1975. Mortality of lead workers. In: 
      Proceedings of the 1974 Conference on Standards of Occupational Lead 
      Exposure, J.F. Cole, Ed., February, 1974. Washington, DC. J. Occup. Med. 
      17: 100-107. </P>
      <P>Dingwall-Fordyce, I. and R.E. Lane. 1963. A follow-up study of lead 
      workers. Br. J. Ind. Med. 20: 313-315. </P>
      <P>DiPaolo, J.A., R.L. Nelson and B.C. Casto. 1978. In vitro neoplastic 
      transformation of Syrian hamster cells by lead acetate and its relevance 
      to environmental carcinogenesis. Br. J. Cancer. 38: 452-455. </P>
      <P>Grandjean, P., H.C. Wulf and E. Niebuhr. 1983. Sister chromatid 
      exchange in response to variations in occupational lead exposure. Environ. 
      Res. 32: 199-204. </P>
      <P>Kasprzak, K.S., K.L. Hoover and L.A. Poirier. 1985. Effects of dietary 
      calcium acetate on lead subacetate carcinogenicity in kidneys of male 
      Sprague- Dawley rats. Carcinogenesis. 6(2): 279-282. </P>
      <P>Koller, L.D., N.I. Kerkvliet and J.H. Exon. 1986. Neoplasia induced in 
      male rats fed lead acetate, ethyl urea and sodium nitrate. Toxicol. 
      Pathol. 13: 50-57. </P>
      <P>Nelson, D.J., L. Kiremidjian-Schumacher and G. Stotzky. 1982. Effects 
      of cadmium, lead, and zinc on macrophage-mediated cytotoxicity toward 
      tumor cells. Environ. Res. 28: 154-163. </P>
      <P>Selevan, S.G., P.J. Landrigan, F.B. Stern and J.H. Jones. 1985. 
      Mortality of lead smelter workers. Am. J. Epidemiol. 122: 673-683. </P>
      <P>U.S. EPA. 1984. Health Effects Assessment for Lead. Prepared by the 
      Office of Health and Environmental Assessment, Environmental Criteria and 
      Assessment Office, Cincinnati, OH, for the Office of Emergency and 
      Remedial Response, Washington, DC. EPA/540/1-86/055. NTIS PB85-163996/AS. 
      </P>
      <P>U.S. EPA. 1986a. Guidelines for Carcinogen Risk Assessment. 
      Environmental Protection Agency, Washington, DC. 51 FR 33992-34003. </P>
      <P>U.S. EPA. 1986b. Air Quality Criteria Document for Lead. Volumes III, 
      IV. Prepared by the Office of Health and Environmental Assessment, 
      Environmental Criteria and Assessment Office, Research Triangle Park, NC, 
      for the Office of Air Quality Planning and Standards. EPA-600/8-83/028dF. 
      </P>
      <P>U.S. EPA. 1989. Evaluation of the potential carcinogenicity of lead and 
      lead compounds: In support of reportable quantity adjustments pursuant to 
      CERCLA Section 102. Prepared by the Office of Health and Environmental 
      Assessment, Washington, DC. EPA/600/8-89/045A. (External Review Draft). 
      </P>
      <P>Van Esch, G.J. and R. Kroes. 1969. The induction of renal tumors by 
      feeding of basic lead acetate to mice and hamsters. Br. J. Cancer. 23: 
      265-271. </P>
      <P align=center><A href="http://www.epa.gov/iris/subst/0277.htm#top">Back 
      to top</A> </P>
      <HR>

      <H2><A name=revhis></A>_VII.  Revision History</H2>
      <P>Substance Name -- Lead and compounds (inorganic)<BR>CASRN -- 
      7439-92-1<BR>File First On-Line 03/01/1988 </P>
      <P>
      <TABLE cellSpacing=0 cellPadding=2 width="100%" 
      summary="This table contains revision history information." border=0>
        <TBODY>
        <TR vAlign=top>
          <TH id=header1 width=69>
            <DIV align=left>Date</DIV></TH>
          <TH id=header2 width=68>
            <DIV align=left>Section</DIV></TH>
          <TH id=header3 width=261>
            <DIV align=left>Description</DIV></TH></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>09/26/1988</TD>
          <TD headers=header2 width=68>II.</TD>
          <TD headers=header3 width=261>Carcinogen summary on-line</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>02/01/1989</TD>
          <TD headers=header2 width=68>IV.B.1.</TD>
          <TD headers=header3 width=261>Effect level corrected in 
        discussion</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>06/01/1989</TD>
          <TD headers=header2 width=68>II.D.3.</TD>
          <TD headers=header3 width=261>Primary contact changed</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>06/01/1989</TD>
          <TD headers=header2 width=68>IV.A.1.</TD>
          <TD headers=header3 width=261>Reference corrected - changed number 
            for part in CFR</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>12/01/1989</TD>
          <TD headers=header2 width=68>II.A.3.</TD>
          <TD headers=header3 width=261>Last paragraph - Correct Van Esch 1969 
            citation</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>12/01/1989</TD>
          <TD headers=header2 width=68>VI.</TD>
          <TD headers=header3 width=261>Bibliography on-line</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>07/01/1990</TD>
          <TD headers=header2 width=68>I.A.</TD>
          <TD headers=header3 width=261>Changed contact J. Cohen's office and 
            telephone number</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>07/01/1990</TD>
          <TD headers=header2 width=68>IV.F.1.</TD>
          <TD headers=header3 width=261>EPA contact changed</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>02/01/1991</TD>
          <TD headers=header2 width=68>I.A.</TD>
          <TD headers=header3 width=261>Message revised to include new EPA 
            document</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>02/01/1991</TD>
          <TD headers=header2 width=68>I.A.</TD>
          <TD headers=header3 width=261>EPA contacts changed</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>05/01/1991</TD>
          <TD headers=header2 width=68>II.A.</TD>
          <TD headers=header3 width=261>Text edited</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>01/01/1992</TD>
          <TD headers=header2 width=68>IV.</TD>
          <TD headers=header3 width=261>Regulatory actions updated</TD></TR><BR>
        <TR vAlign=top>
          <TD headers=header1 width=69>06/01/1992</TD>
          <TD headers=header2 width=68>IV.B.2.</TD>
          <TD headers=header3 width=261>MCL monitoring reqs. and BAT 
          corrected</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>07/01/1993</TD>
          <TD headers=header2 width=68>II.D.3.</TD>
          <TD headers=header3 width=261>Secondary contact's phone number 
            changed</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>07/01/1993</TD>
          <TD headers=header2 width=68>VI.C.</TD>
          <TD headers=header3 width=261>References alphabetized 
correctly</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>11/01/1993</TD>
          <TD headers=header2 width=68>II.D.1.</TD>
          <TD headers=header3 width=261>U.S. EPA 1987 replaced with 1989; rev. 
            state. revised</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>11/01/1993</TD>
          <TD headers=header2 width=68>VI.C.</TD>
          <TD headers=header3 width=261>U.S. EPA 1987 deleted; U.S. EPA 1989 
            added</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>04/01/1997</TD>
          <TD headers=header2 width=68>III., IV., V.</TD>
          <TD headers=header3 width=261>Drinking Water Health Advisories, EPA 
            Regulatory Actions, and Supplementary Data were removed from IRIS on 
            or before April 1997. IRIS users were directed to the appropriate 
            EPA Program Offices for this information.</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>12/03/2002</TD>
          <TD headers=header2 width=68>I.A., II.D.2.</TD>
          <TD headers=header3 width=261>Screening-Level Literature Review 
            Findings message has been added.</TD></TR>
        <TR vAlign=top>
          <TD headers=header1 width=69>07/08/2004</TD>
          <TD headers=header2 width=68>I.A., I.B., II.</TD>
          <TD headers=header3 width=261>Previous reference value discussions 
            replaced with links to EPA websites containing regulatory 
            information and other websites with risk assessment information; 
            cancer discussion retained, added links to agencies conducting 
            reviews of lead carcinogenicity.</TD></TR></TBODY></TABLE></P>
      <P align=center><A href="http://www.epa.gov/iris/subst/0277.htm#top">Back 
      to top</A> </P>
      <HR>

      <H2><A name=syn></A>_VIII.  Synonyms</H2>
      <P>Substance Name -- Lead and compounds (inorganic)<BR>CASRN -- 
      7439-92-1<BR>Last Revised -- 07/08/2004</P>
      <P>7439-92-1<BR>Lead<BR>Lead and compounds<BR>plumbum</P>
      <P align=center><A href="http://www.epa.gov/iris/subst/0277.htm#top">Back 
      to top</A> </P></TD>
    <TD vAlign=top noWrap align=left width=130 colSpan=2>
      <TABLE cellPadding=0 width=117 border=0>
        <TBODY>
        <TR>
          <TD><BR><IMG height=27 alt="Substance Summary Index" hspace=3 
            src="Lead and compounds (inorganic) (CASRN 7439-92-1), IRIS, Environmental Protection Agency_files/sub_right.gif" 
            width=117 align=top></TD></TR>
        <TR>
          <TD height=377>
            <TABLE cellPadding=0 width=117 border=0>
              <TBODY>
              <TR>
                <TD bgColor=#8494ad height=2>
                  <TABLE cellSpacing=1 cellPadding=2 width=117 align=center 
                  border=0>
                    <TBODY>
                    <TR align=left bgColor=#8494ad>
                      <TD class=epaFooterText vAlign=top height=19><A 
                        href="http://www.epa.gov/iris/subst/0277.htm#noncar">Chronic 
                        Health Hazards for Non-Carcinogenic Effects</A></TD></TR>
                    <TR bgColor=white>
                      <TD class=epaFooterText><A 
                        href="http://www.epa.gov/iris/subst/0277.htm#reforal">Reference 
                        Dose for Chronic Oral Exposure (RfD)</A> <BR><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#oralrfd">Oral 
                        RfD Summary </A><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#studoral">Principal 
                        and</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#studoral">Supporting 
                        Studies</A><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#umforal">Uncertainty 
                        and</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#umforal">Modifying 
                        Factors</A><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#addoral">Additional 
                        Studies/</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#addoral">Comments</A><BR>- 
                        <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#conoral">Confidence 
                        in the</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#conoral">Oral 
                        RfD</A><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#docoral">EPA 
                        Documentation</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#docoral">and 
                        Review</A><BR><BR><A 
                        href="http://www.epa.gov/iris/subst/0277.htm#refinhal">Reference 
                        Concentration for Chronic Inhalation Exposure (RfC)</A> 
                        <BR><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#inhalrfc">Inhalation 
                        RfC</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#inhalrfc">Summary 
                        </A><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#studinhal">Principal 
                        and</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#studinhal">Supporting 
                        Studies</A><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#umfinhal">Uncertainty 
                        and</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#umfinhal">Modifying 
                        Factors</A><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#addinhal">Additional 
                        Studies/</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#addinhal">Comments</A><BR>- 
                        <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#coninhal">Confidence 
                        in the</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#coninhal">Inhalation 
                        RfC</A><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#docinhal">EPA 
                        Documentation</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#docinhal">and 
                        Review</A> <BR></TD></TR></TBODY></TABLE></TD></TR></TBODY></TABLE>
            <TABLE cellPadding=0 width=117 border=0>
              <TBODY>
              <TR>
                <TD bgColor=#8494ad height=2>
                  <TABLE cellSpacing=1 cellPadding=2 width=117 border=0>
                    <TBODY>
                    <TR align=left bgColor=#8494ad>
                      <TD class=epaFooterText vAlign=top><A 
                        href="http://www.epa.gov/iris/subst/0277.htm#carc">Carcinogenicity 
                        Assessment for Lifetime Exposure</A></TD></TR>
                    <TR bgColor=white>
                      <TD class=epaFooterText height=55><A 
                        href="http://www.epa.gov/iris/subst/0277.htm#evid">Evidence 
                        for Human Carcinogenicity</A> <BR><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#woe">Weight-of-Evidence</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#woe">Characterization</A><BR>- 
                        <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#humcarc">Human</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#humcarc">Carcinogenicity 
                        Data</A><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#anicarc">Animal</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#anicarc">Carcinogenicity 
                        Data</A><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#supdat">Supporting 
                        Data for</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#supdat">Carcinogenicity</A> 
                        <BR><BR><A 
                        href="http://www.epa.gov/iris/subst/0277.htm#quaoral">Quantitative 
                        Estimate of Carcinogenic Risk from Oral Exposure</A> 
                        <BR><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#quaoral">Summary 
                        of Risk</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#quaoral">Estimates</A><BR>- 
                        <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#quaoral">Dose-Response 
                        Data</A><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#quaoral">Additional 
                        Comments</A><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#quaoral">Discussion 
                        of</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#quaoral">Confidence</A> 
                        <BR><BR><A 
                        href="http://www.epa.gov/iris/subst/0277.htm#quainhal">Quantitative 
                        Estimate of Carcinogenic Risk from Inhalation 
                        Exposure</A><BR><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#quainhal">Summary 
                        of Risk</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#quainhal">Estimates</A><BR>- 
                        <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#quainhal">Dose-Response 
                        Data</A><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#quainhal">Additional 
                        Comments</A><BR>- <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#quainhal">Discussion 
                        of</A><BR>  <A 
                        href="http://www.epa.gov/iris/subst/0277.htm#quainhal">Confidence</A> 
                        <BR><BR><A 
                        href="http://www.epa.gov/iris/subst/0277.htm#doccar">EPA 
                        Documentation, Review and, 
                  Contacts</A><BR></TD></TR></TBODY></TABLE></TD></TR></TBODY></TABLE>
            <TABLE cellSpacing=1 cellPadding=2 width=117 border=0>
              <TBODY>
              <TR align=left bgColor=#8494ad>
                <TD class=epaFooterText vAlign=top>
                  <LI class=epaFooterText><A 
                  href="http://www.epa.gov/iris/subst/0277.htm#bib">Bibliography</A><BR>
                  <LI class=epaFooterText><A 
                  href="http://www.epa.gov/iris/subst/0277.htm#revhis">Revision 
                  History</A><BR>
                  <LI class=epaFooterText><A 
                  href="http://www.epa.gov/iris/subst/0277.htm#syn">Synonyms</A> 
                  </LI></TD></TR></TBODY></TABLE></TD></TR></TBODY></TABLE></TD></TR></TBODY></TABLE><!-- END CONTENT AREA -->
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