Variations in Reproductive Toxicant Identification

1. Variations in Reproductive Toxicant Identification Dave Quigley, Ph.D. B&W Y-12 March 11,2009

2. 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.

3. Why are Reproductive Toxins Important? (cont.) Need to protect the employee Legal liabilities if not properly identified Extra costs associated with their management

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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�

19. 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

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

21. 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

22. Results

23. Results (cont.) Combining information results in 944 items Most were discrete chemicals, some chemical types

24. 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

25. 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!

26. 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

27. 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

28. 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)

29. Next Action Overpressurized Drums � What to do when they are found (besides run away) Interested in getting involved?

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