Variations in Reproductive Toxicant Identification

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Variations in Reproductive Toxicant Identification

• Dave Quigley, Ph.D.
• BW Y-12
• March 11,2009

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Why are Reproductive Toxins Important?

• 29CFR1910.1200, Hazard Communication, requires
  hazards associated with chemicals in the
  workplace to be identified and employees trained
  upon those hazards
• 29CFR1910.1450, Occupational Exposure to
  Hazardous Chemicals in the Laboratory classifies
  reproductive toxins as a Particularly Hazardous
  Substance which requires additional controls for
  their use.

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Why are Reproductive Toxins Important? (cont.)

• Need to protect the employee
• Legal liabilities if not properly identified
• Extra costs associated with their management

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Reproductive Toxin Definition

• Definition depends upon who is asked
• Traditional Definition
• Typically limited to issues involving sperm, egg,
  fertilization and related issues
• Developmental effects (teratogens) and mutagens
  typically excluded from definition

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Reproductive Toxin Definition (cont.)

• RTECS
• Identifies seven major categories with sixty five
  specific effects
• Includes paternal and maternal effects, fertility
  effects, effects on the embryo or fetus,
  developmental effects, tumorgenic effects and
  effects upon the newborn

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Reproductive Toxin Definition (cont.)

• OSHA
• Assumes a middle ground
• Includes maternal and paternal effects as well as
  developmental effects including teratogens
• Since OSHA defines requirements for reproductive
  toxins, it is this definition that will be used
  in this discussion

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Difficulties in Reproductive Toxin Determination

• Many systems than can be involved in both sexes
• Clear end point such as an LD50 not always
  present
• Many studies require a statistically significant
  number of animals which becomes expensive

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Sources for Reproductive Toxin Identification

• MSDS
• If the MSDS claims the product to be a
  reproductive toxin or a teratogen, then it would
  be
• Many MSDSs indicate that the product May be a
  reproductive toxin
• Many MSDSs are silent on the issue

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Sources for Reproductive Toxin Identification
(cont.)

• RTECS
• Used by many, but RTECS does NOT make
  reproductive toxin determinations
• RTECS simply states if a study attempting to make
  a reproductive toxin determination has been
  performed no evaluation of the results is
  performed
• IF one uses RTECS as a source of reproductive
  toxin determination then it is like a speeding
  determination You are not speeding until your
  speed is measured and then you are speeding no
  matter how fast you are traveling

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Sources for Reproductive Toxin Identification
(cont.)

• Catalog of Teratogenic Agents
• Similar to RTECS in that it reports those
  products that have been tested
• Does not make any determinations or evaluations
  of the data
• Does not look at any other type or reproductive
  toxin other than teratogens

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Sources for Reproductive Toxin Identification
(cont.)

• California Proposition 65
• Published by the State of California
• Updated annually
• May be required for use in California facilities
• Contains approximately 250 agents
• Some are listed by class (e.g., tetracyclines)
• Very significant number are pharmaceuticals
• Criteria used to determine if something makes the
  list is not known

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Sources for Reproductive Toxin Identification
(cont.)

• Reprotext
• Data listing published by Micromedex
• Chemicals on list rated from A (known) to E
  (not thought to be a reproductive toxicant)
• Focuses on chemicals to which a worker could be
  exposed
• Selection and evaluation criteria are unknown

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Sources for Reproductive Toxin Identification
(cont.)

• Center for the Evaluation of Risks to Human
  Reproduction (CERHR)
• Published by the National Toxicology Program and
  the National Institute of Environmental Health
• Has only evaluated approx. 25 chemicals
• Evaluations are published as monographs that can
  run hundreds of pages in length
• No clear determination is made the reader must
  make up their own mind

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Sources for Reproductive Toxin Identification
(cont.)

• Development and Reproductive Toxicology Database
  (DART)
• Maintained by the U.S. National Library of
  Medicine
• Tool for researchers in that is lists journal
  articles
• Only provides a short portion of the article

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Sources for Reproductive Toxin Identification
(cont.)

• Jankovic and Drake
• Research paper published in 1996 in Am. Ind. Hyg.
  Assoc. J.
• Defines a method for determining is a product is
  a reproductive toxin
• Involves searching RTECS for studies with
  positive results in multiple mammalian species
• Authors identified 213 reproductive toxins
• Ignores chemicals identified in only one species

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Sources for Reproductive Toxin Identification
(cont.)

• American Conference of Governmental and
  Industrial Hygienists (ACGIH)
• Reproductive toxicity is identified in TLV
  Basis Critical Effect data element
• Few chemicals identified
• Effects listed in TLV Basis Critical Effect
  data element are the effects causing ACGIH to
  make a TLV determination
• If reproductive toxicity is a lesser effect in a
  chemical, then ACGIH will not identify it as a
  reproductive toxin

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Sources for Reproductive Toxin Identification
(cont.)

• Haz-Map
• Database published by the National Library of
  Medicine via the National Institute of Health
• Provides information for the general public
• Lists 136 chemicals with links to more
  information
• Criteria used for inclusion on the list are
  unknown

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Sources for Reproductive Toxin Identification
(cont.)

• Scorecard
• A web source published by the advocacy group
  Environmental Defense
• List included suspected and known
  reproductive toxins
• Information culled from other public sources such
  as California Proposition 65
• Does not include private sources such as ACGIH or
  Reprotext

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Sources for Reproductive Toxin Identification
(cont.)

• U.S. Navy and Marine Corps Public Health Center
  Technical Manual
• Published by USN and USMC
• Provides one table for reproductive toxins and
  another for developmental toxins
• Excellent source in that it provides toxic
  effects
• Data obtained from other lists (e.g., California
  65), but some entries are removed for unknown
  reasons
• Provides good information on how to manage
  reproductive toxins

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WOW!

• With all these sources, one would think making a
  determination about reproductive toxicity easy
• Not Necessarily!

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Comparing Data

• Reproductive toxins identified from
• California Proposition 65
• Reprotext (A and B graded toxins)
• ACGIH
• Haz-Map
• Jankovic and Drake
• U.S. Navy and Marine Corps Public Health Center
  Technical Manual
• Data combined into one table

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Results
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Results (cont.)

• Combining information results in 944 items
• Most were discrete chemicals, some chemical types
  

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What Does This Mean?

• Over 90 are listed in only one or two sources
  and almost two thirds are listed in one source
• Consistency in reproductive toxin identification
  not present

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Path Forward

• Each organization needs to determine what method
  they are going to use for reproductive toxin
  identification
• Using the MSDS would be the minimum
• Some are contractually bound to use other sources
  such as California Proposition 65
• Use other sources such as those listed here?
• Depends!

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Take Home Message

• Reproductive toxin definitions differ
• Reproductive toxin identification is difficult
• Each source has their own methods for adding
  reproductive toxins to their list
• Method used by each organization for reproductive
  toxin identification needs to be carefully chosen
  realizing the limitations and uncertainties
  surrounding the issue

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Publication

• Variations in Reproductive and Developmental
  Toxicant Identification, David Quigley, Fred
  Simmons, Helena Whyte, Janeen Robertson, and
  David Freshwater, Journal of Chemical Health and
  Safety (In Press)
• Handouts containing the complete reproductive
  toxin table (In both alphabetical order and in
  order of CAS number) available

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Participants

• David Quigley, Y-12
• Fred Simmons, SRS
• Helena Whyte, LANL (retired)
• Janeen Robertson, LLNL
• David Freshwater, DOE-HQ (NA-41)
• Sam Bigger, DOE-HQ (NA-41)

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Next Action

• Overpressurized Drums What to do when they are
  found (besides run away)
• Interested in getting involved?

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Disclaimer

• This work of authorship and those
  incorporated herein were prepared by Contractor
  as accounts of work sponsored by an agency of the
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  of the United States Government or any agency or
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