Home >Documents >Beryllium and Beryllium Compounds (NTP

Beryllium and Beryllium Compounds (NTP

Date post:29-Dec-2016
Category:
View:216 times
Download:1 times
Share this document with a friend
Transcript:
  • FINAL

    Report on Carcinogens Background Document for

    Beryllium and Beryllium Compounds

    December 16 - 17, 1999

    Meeting of the NTP Board of Scientific Counselors Report on Carcinogens Subcommittee

    Prepared for the: U.S. Department of Health and Human Services Public Health Service National Toxicology Program Research Triangle Park, NC 27709

    Prepared by: Technology Planning and Management Corporation Canterbury Hall, Suite 310 4815 Emperor Blvd Durham, NC 27703 Contract Number NOI-ES-85421

  • RoC Background Document for Beryllium and Beryllium Compounds

    Criteria for Listing Agents, Substances or Mixtures in the Report on Carcinogens

    U.S. Department of Health and Human Services National Toxicology Program

    Known to be Human Carcinogens:

    There is sufficient evidence of carcinogenicity from studies in humans which indicates a causal relationship between exposure to the agent, substance or mixture and human cancer.

    Reasonably Anticipated to be Human Carcinogens:

    There is limited evidence of carcinogenicity from studies in humans which indicates that causal interpretation is credible but that alternative explanations such as chance, bias or confounding factors could not adequately be excluded; or

    There is sufficient evidence of carcinogenicity from studies in experimental animals which indicates there is an increased incidence of malignant and/or a combination of malignant and benign tumors: (1) in multiple species, or at multiple tissue sites, or (2) by multiple routes of exposure, or (3) to an unusual degree with regard to incidence, site or type of tumor or age at onset; or

    There is less than sufficient evidence of carcinogenicity in humans or laboratory animals, however; the agent, substance or mixture belongs to a well defined, structurally-related class of substances whose members are listed in a previous Report on Carcinogens as either a known to be human carcinogen, or reasonably anticipated to be human carcinogen or there is convincing relevant information that the agent acts through mechanisms indicating it would likely cause cancer in humans.

    Conclusions regarding carcinogenicity in humans or experimental animals are based on scientific judgment, with consideration given to all relevant information. Relevant information includes, but is not limited to dose response, route of exposure, chemical structure, metabolism, pharmacokinetics, sensitive sub populations, genetic effects, or other data relating to mechanism of action or factors that may be unique to a given substance. For example, there may be substances for which there is evidence of carcinogenicity in laboratory animals but there are compelling data indicating that the agent acts through mechanisms which do not operate in humans and would therefore not reasonably be anticipated to cause cancer in humans.

    i

  • RoC Background Document for Beryllium and Beryllium Compounds

    ii

  • RoC Background Document for Beryllium and Beryllium Compounds

    Summary Statement

    Beryllium and Beryllium Compounds

    Beryllium and beryllium compounds were first listed in the Second Report on Carcinogens as reasonably anticipated to be human carcinogens

    Carcinogenicity

    Beryllium and beryllium compounds are known to be human carcinogens, based on findings of increased risk of lung cancer in occupational groups exposed to beryllium or beryllium compounds (Steenland and Ward 1991; Ward et al. 1992) and supporting animal data (IARC 1993; Finch et al. 1996). The epidemiologic evidence supports a conclusion that beryllium and beryllium compounds are carcinogenic to humans. An association with lung cancer has been consistently observed in several populations, with an excess risk of 1.2 to 1.6. Higher risks are found in groups with greater exposure or longer time since first exposure, which are dose-response patterns that support a causal relationship. Acute beryllium pneumonitis, a marker for high exposure to beryllium, is associated with elevated lung cancer rates, with an excess risk of 2.3 (Steenland and Ward 1991). Although smoking is a potential confounder, no evidence was found in any of the published epidemiology studies to indicate that the prevalence of smoking in any of the exposed cohorts was substantially greater than in the referent populations.

    Animal experiments have shown consistent increases in lung cancers in rats, mice and rabbits chronically exposed to beryllium and beryllium compounds by inhalation or intratracheal instillation. Osteosarcomas have been produced in mice and rabbits exposed to various beryllium salts by intravenous injection or implantation into the bone.

    Other Relevant Information

    Beryllium compounds were not mutagenic in a variety of Salmonella tester strains. However, beryllium compounds induced genetic transformations in a variety of mammalian cells, in vitro. The genetic transformation effects of beryllium may be mediated by binding of ionic beryllium to nucleic acids that can produce infidelity in DNA replication.

    iii

  • RoC Background Document for Beryllium and Beryllium Compounds

    iv

  • RoC Background Document for Beryllium and Beryllium Compounds

    Table of Contents

    Criteria for Listing Agents, Substances or Mixtures in the Report on Carcinogens........................ i

    Summary Statement .......................................................................................................................iii

    1 Introduction ............................................................................................................................... 1

    1.1 Chemical identification .............................................................................................. 1 1.2 Physical-chemical properties...................................................................................... 1 1.3 Identification of metabolites....................................................................................... 9

    2 Human Exposure ..................................................................................................................... 11

    2.1 Use............................................................................................................................ 11 2.1.1 Beryllium .................................................................................................. 11 2.1.2 Beryllium-copper alloy ............................................................................. 12 2.1.3 Other beryllium alloys .............................................................................. 12 2.1.4 Beryllia ceramics....................................................................................... 12

    2.2 Production ................................................................................................................ 12 2.3 Analysis.................................................................................................................... 13 2.4 Environmental occurrence........................................................................................ 14

    2.4.1 Soil ............................................................................................................ 14 2.4.2 Water......................................................................................................... 15 2.4.3 Air ............................................................................................................. 15

    2.5 Environmental fate ................................................................................................... 16 2.5.1 Air ............................................................................................................. 16 2.5.2 Water......................................................................................................... 17 2.5.3 Soil ............................................................................................................ 17

    2.6 Environmental exposure........................................................................................... 17 2.6.1 Environmental sources of beryllium......................................................... 18

    2.7 Occupational exposure ............................................................................................. 18 2.7.1 Processing and manufacturing .................................................................. 19 2.7.2 Machining ................................................................................................. 21 2.7.3 Other occupational exposure scenarios..................................................... 22

    2.8 Biological indices of exposure ................................................................................. 23 2.9 Regulations............................................................................................................... 24

    3 Human Cancer Studies ............................................................................................................ 33

    3.1 IARC Evaluations .................................................................................................... 33 3.2 Current epidemiologic studies.................................................................................. 36 3.3 Case-control studies ................................................................................................. 36 3.4 Cohort studies........................................................................................................... 37 3.5 Other studies............................................................................................................. 37 3.6 Discussion ...............................................................................

Click here to load reader

Embed Size (px)
Recommended