FDA and EPA Development of a Joint Advisory for Methyl mercury-containing Fish Consumption for Women of Childbearing Age and Children

Summary and Purpose: Between July 29 through July 31, 2003, FDA and EPA held four meetings with interested parties regarding methyl mercury in fish. The meetings were held at the FDA, Center for Food Safety and Applied Nutrition, Harvey W. Wiley Federal Building, College Park, Maryland. FDA and EPA are developing a joint fish consumption advisory about the risks of methyl mercury in commercial and recreational fish for women of childbearing age and young children. As part of this initiative, the two agencies invited selected participants to a series of meetings to obtain stakeholder views on the issues associated with developing this joint federal advisory. FDA and EPA briefed stakeholders on their progress in positively responding to the FDA Food Advisory Committee (FAC) recommendations, the new exposure assessment, and the current approach FDA and EPA are taking to develop the joint advisory.

The meeting consisted of a series of formal presentations from FDA and EPA followed by a general discussion in which participants provided comment on the progress toward a joint advisory.

The format for each meeting was the same with the following agenda:

1. Welcome and purpose of the meeting
2. Background: 2001 advisory and 2002 FAC
3. The "at risk" population as currently defined
4. Estimating exposure from consumption data
5. The desired "level of protection" issue
6. Elements and process for developing a joint federal message
7. General discussion
8. Next steps

Note: The complete presentations are posted on the web at http://www.cfsan.fda.gov/~lrd/pestadd.html and http://www.epa.gov/waterscience/fish.

Summary of the main comments from the four meetings

FDA and EPA appreciate these comments and interaction and will as appropriate refer and reflect on those specifically dealing with the development and implementation of the joint advisory, scientific review of the exposure assessment and other factors.

Tuesday July 29^th, meeting with Industry representatives:

Points of clarification related to the presentations:

• It was stated that the 300 tuna samples will be collected to measure total mercury, not methyl mercury specifically.
• The age distribution of children in the NHANES data is 1-5 years of age, with the majority of children surveyed between 2-5 years of age.
• For calculation of a benchmark dose, EPA considered the lowest 5 percent of response values as abnormal or adverse. This is not relatively standard for tests of learning or intelligence. A doubling of the percentage of a population (5 to 10 percent) with abnormal scores was considered to be above background and indicative of an adverse effect.
• The lowest 5 percent of response values are typically omitted in neurotoxicity tests, as well as in other intelligence tests: these lowest values are considered abnormal. So in the models we doubled the value and used it for the benchmark.
• The NHANES data include mercury effects in children with in utero exposure.
• The benchmark level is not a "no effect level." The method used can be referenced through the EPA online in the IRIS entry for methyl mercury as well as in the Water Quality Criterion for Protection of Human Health: Methyl mercury .
• The reference dose builds in an uncertainty factor, not a "safety factor."
• The NHANES data on daily fish consumption includes sensitive subgroups. Children were oversampled in one year's data.
• The FAC recommended that FDA develop specific recommendations for canned tuna based on a detailed analysis of what contribution canned tuna makes to overall methylmercury levels in women.
• Market Survey data is used to estimate the fish consumed pattern.
• The estimated mean blood mercury levels in the model scenarios show levels that are similar for scenarios 2, 3, and 4, with the best difference between scenarios 1 and 2. Scenario 1 is the pre FDA advisory period. Scenario 2 is the FDA advisory.
• The reference dose is applied to the entire population, including sensitive subgroups.
• The advisory focus is the developing nervous system, with the mother considered the vehicle.
• EPA's goal is to reduce exposure to mercury in non-commercial and subsistence fishing, and to work with FDA to develop a clear message for both commercial and non-commercial fish.
• The current advisory does not define children by age. Getting authorities to agree on exact ages for children is not likely at this point.
• The schedule for the focus groups will be published.
• The FAC recommended bringing commercial and recreational fish advisories under the same umbrella. EPA and FDA envision it as one piece of paper-one advisory and they are determining how to merge their advisories.
• EPA has very limited information on the consuming habits from noncommercial fishing.
• Some participants commented that the presented timeline seemed ambitious.
• The distinction was made between the milestones for announcing the new advisory and implementing the new advisory. The implementation stages will entail deeper dissemination of the advisory material to more people, including public health professionals.

Summary of comments following the formal presentations:

• A goal is to use the presented model as a tool to see effects on different levels.
• The earlier inquiry whether there is any movement to look at and incorporate findings from two substantial events, the Seychelles Study and the WHO JECFA study, which occurred after the 2002 FAC meeting was raised. There are a number of new pieces of information published and to consider in developing an advisory. There is also ongoing data mining on NHANES. Advisories will be revisited periodically and updated as needed.
• A prompt advisory could put to rest some misleading or confusing information. Emphasis on high, medium, and low categories, as opposed to specific fish species, could be confusing. An advisory should consider what alternatives people will be pushed toward if they aren't eating fish.
• The exact coordination of the umbrella advisory with state advisories is yet to be worked out; however, the hope is to coordinate with states.
• The next set of NHANES data and results should provide an opportunity to examine response to the existing 2001 advisory, but it is going to take a few years to get data on the impact of any advisory.
• FDA and EPA are not trying to make the message more complicated or conservative, but trying to make the message clearer through more details.
• Other plans to get more data and to do more research: Some options for obtaining data to hone in on these consumers include: (1) Better mining of NHANES data, (2) revising or adding to questions in NHANES, or (3) designing a separate study apart from NHANES. However, we should not wait for more data to issue the next advisory.
• Actual tuna measurement: Presenting tuna amounts in ounces and not in terms of cans is better. Ounce cans are drained and there are fewer than 6 consumable ounces in a 6-ounce can. The drained weight, particularly given the variability (e.g., pouches, small cans) of tuna on the market, should be the focus. There is a need to communicate messages clearly and clarify whether it is cooked weight or "as is, right out of the can."
• Other stakeholder groups, e.g., American Lobster, may want to be included in future communication. Industry stakeholders will give thought to other groups that should be included as well.
• The meeting was considered very helpful to help understand where things are.

Wednesday July 30, 2003, meeting with Consumer groups and Health Professionals:

Points of clarification related to the presentations:

• Current focus is to respond to FAC recommendations.
• At risk population remains women of childbearing age and children.
• Clarify and verify that these and only these were the FAC recommendations.
• FDA has ongoing sampling/testing that includes tuna and a variety of other species.
• The term "Children" is not defined by age at this time; divergent views on age span remain.
• FDA and EPA continue to data-mine NHANES.
• Also considering additional changes to NHANES to answer certain demographic and consumption questions- earliest change will be 2006
• While other mercury clinical data is worthwhile and important, the NHANES remains the prime data source for FDA and EPA.
• The scenarios were developed based on consuming prescribed amounts and or varieties of fish; scenarios did not focus on high end consumers.
• Scenario #1, i.e., unrestricted consumption of fish and varieties, results likely reflect lack of knowledge and or adherence to FDA's 2001 advisory
• Comparison of probabilistic models routinely range 10-00 x; therefore, the 2X risk exposure model comparison with NHANES is very favorable.
• The model profiles consumption of varieties of fish; the model also allowed the methyl mercury to range between its high and low end.
• The exposure model is available as a poster and submitted to all participants prior to the meeting; the model and data are currently undergoing peer review and the authors intend to publish in a scientific journal this year. Data and model parameters are described in each publication.
• FDA and EPA welcome receipt of additional clinical or seafood residue data.
• Format of joint message has not been established; and as much information as can be conveyed will be incorporated.
• The venues and messengers are important features to an effective message.
• FDA routinely conducts consumer surveys to discern effectiveness of its regulations and messages. FDA plans to evaluate its methyl mercury message in this manner.
• Aug 2003 article in an OB and GYN journal showing reduced fish consumption by women of childbearing age following FDA's 2001 fish advisory.
• Some questioned the accuracy of the fish tissue mercury concentration data used in the model. They compared the data to values in EPA's Report to Congress, and saw that the model values were roughly half of EPA's values which originated from FDA and NMFS data.

Summary of comments following the formal presentations:

• The goal is for consumers to make smart choices.
• EPA distinguishes between child and adult serving sizes (2 versus 6 ounces).
• Low level in the model scenarios was set to include light tuna in this group. This was in response to the FAC's recommendation to consider distinguishing light from other tuna in an advisory.
• FDA anticipates working triangularly in its outreach with health professionals and the media to reach consumers.
• California requires grocers to display advisories. FDA also works with grocers via brochures and other means.
• Some studies of pediatric patients and highly illiterate groups has indicated that pictorial messages may be very useful in reaching certain groups.
• The upcoming advisory is part of an iterative process. It is important that we move forward with advice, knowing that we will not resolve the complete issue immediately. The advisory role will continue into the future and be refined over time.
• The current advisory does not specifically address the high-fish consumption by various groups. More advice could be provided to the fisheries industry so that they will catch fewer high-mercury-level fish.
• While neurotoxicity is the current sentinel endpoint for mercury, other endpoints may be considered in the future.
• Since pregnant women are bombarded with advice about what to do and what to avoid in their first prenatal visit, it is most motivating for them to adjust their behavior accordingly when there is clear information about what happens if they don't adhere to the advice. The example of listeriosis was used. What happens if the advisory is not followed seems to be missing from the current advisory.
• The proposed timeline seemed ambitious to some; it could shorten coordination capabilities with states and others. Since states help coordinate health professional and WIC information, it will be important for there to be federal and state consistency.
• The historical nature of tuna data and data on other fish species were discussed.
• Suggested FDA consider issues raised outside the FAC meeting
• Suggested advisory recommend higher consumption levels (> 12 oz/week) if people eat low mercury containing fish
• Asked to see scenario where all the population ate 12 oz fish/week.

Thursday, July 31, 2003, meeting with States

Points of clarification related to the presentations:

• While "children" have not yet been defined, many state advisory programs, including the Gulf of Mexico Mercury Advisory Taskforce, have defined ages for "young children."
• The 300 tuna samples collected will distinguish light versus other tuna.
• NHANES data do not distinguish commercial from non-commercial fish consumed.
• The 7.8 percent figure for the estimated portion of the population with blood mercury levels above the reference dose is based on a larger data sample than an earlier estimate of 10 percent. NHANES data are most robust considered as 2-year blocks.
• The model showed that only 3.9 percent of the fish-consuming public would have blood mercury levels above the reference dose by comparison to the NHANES measured figure of 7.8 percent above the reference dose. This is considered good for such modeling exercises. However, some states still see this as a concern.
• The data on high-quantity fish consumers was not teased out. NHANES data may be further mined to provide basis for further revisions to the advisory.
• It would be useful to model as a covariant the impact of reduced fish consumption on omega-3-fatty acid consumption.
• A "wish list" for further analysis and advice would include that it reflect variation in regions, servings, etc.
• The trade off of decreasing fish consumption, particularly regarding omega-3-fatty acids, should be considered.
• It was recommended that the analysis and advisory focus on decreasing certain types of fish, i.e., those with high mercury levels, instead of decreasing overall fish consumption.
• No single-species consumption, e.g., children eating a tuna sandwich every day, analysis was performed. The goal was to model what happens in retail. It is possible to run the model for one species. However, scenarios did try to account for consumption of fish distributed across light, canned, albacore, and fresh tuna.
• The advisory will be disseminated using a multifaceted approach: to physicians, health and women's magazines, nurse midwives, grocers, media, and states.
• North Carolina is following the current advisory and is recommending that pregnant women avoid seven species listed as having high mercury levels.
• Any message should be carefully crafted not to discourage people from consuming fish in general.
• One option for advice is to say something like "If you eat more than 12 ounces of fish a week, then eat these fish...."
• State advisories generally follow a species-specific approach (as opposed to a mixed-fish diet scenario), and by considering all contaminants such as mercury, PCBs, banned pesticide levels, and other contaminants.
• State advisories follow species by PCB levels and other factors.
• The proposed timeline seemed ambitious to some, not allowing enough time for review for the advisory.

Summary of comments following the formal presentations:

• Data are available from a food survey of 23,000 people in Florida.
• Maine tells residents to follow state advisories. Any federal advisory should not override state advisories.
• A comprehensive advisory on PCBs, omega-3-fatty acids, etc., to use in informing pregnant women about seafood consumption would be useful.
• Should report advisory as meals rather than weight.
• Suggest using focus groups convened by Maine as one of our focus groups.
• Suggest advice for school age children.
• Need to consider regional differences I fish.

Thursday, July 31, 2003, meeting with Tribes

Points of clarification related to the presentations:

• The model can be used by others.
• There are data from a 5-year study of Chippewa tribe fish consumption with lake, species, harvest information, and size data. The data can be shared. The data include commercial fish for 3 years.
• Another 3-year STAR grant will commence soon (PIs are Jeff Forham and Neil Kimasec).

Summary of comments following the formal presentations:

There were no additional questions or comments.

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Presentation: FDA and EPA Development of a Joint Advisory for Methylmercury-containing Fish Consumption for Women of Childbearing Age and Children July 2003
List of Meeting Attendees