March 1998 - SAP Meeting FInal Report
A Set of Scientific Issues Being Considered by the Agency in Connection with Post Application Exposure Guidelines: Series 875-Group B.
The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) has completed its review of the set of scientific issues being considered by the Agency in connection with Post Application Exposure Guidelines: Series 875-Group B. The review was conducted in an open meeting held in Arlington, Virginia, on March 25, 1998. The meeting was chaired by Dr. Ernest E. McConnell (ToxPath, Inc). Other Panel Members present were: Dr. John Adgate (University of Minnesota), Dr. Julian Andelman (University of Pittsburgh), Dr. Charles Capen (The Ohio State University), Dr. Amira Eldefrawi (University of Maryland), Dr. Natalie Freeman (EOHSI/University of Medicine and Dentistry of New Jersey), Dr. Ronald Kendall (Texas Tech University), Dr. John Kissel (University of Washington), Dr. Paul Kuznesof (Food and Drug Administration), Dr. Robert Kreiger (University of California at Riverside), Dr. Herbert Needleman (University of Pittsburgh), Dr. Christopher Portier (NIEHS), Dr. J. Routt Reigart (Medical University of South Carolina), Dr. Howard Rockett (University of Pittsburgh), Dr. Mary Anna Thrall (Colorado State University), and Dr. John Wargo (Yale University).
Public Notice of the meeting was published in the Federal Register on February 11, 1998.
Post-Application Exposure Guidelines: Series 875-Group B
Oral statements were received from the following:
Mr. Kevin Drake, Chemical Manufacturers Association.
Dr. Dennis Klonne, Agricultural Reentry Task Force and Outdoor Residential Exposure Task Force.
Written statements were received from the following:
Agricultural Reentry Task Force.
Outdoor Residential Exposure Task Force.
General Comments from SAP Members
The Panel felt that adequate time was not available at this session to discuss the post application exposure guidelines (i.e. background document), particularly with respect to the scope and content of the guidelines. Although time for discussion was limited, it was obvious that much of the Agency's presentation concerned material not included in the current guidelines. Due to time constraints, the Agency did not provide a better explanation (than that presented in the background document) of how procedures will be used to simulate exposure and/or adsorbed dose for risk assessment nor new exposure data. It is unclear to the Panel if there are new data that would have been presented for evaluation by the scientific community, and the extent to which the methods were evaluated. The lack of time for discussion is also reflected in this SAP report indicating differing opinions of various Panel Members and the challenge to develop consensus due to time constraints. Thus, the Panel concludes that this session topic should be revisited by the SAP when adequate time and full participation are possible.
The Panel did not identify any deficiencies in the agricultural requirements of the post-application exposure guidelines. Specific comments concerning the background guideline document are presented below:
- Pages D2-23 to D2-25 (Part D 2.6.4: Swimmer Exposure). The equation
D2-27 used to determine the vapor concentration of a chemical
in air is invalid and will greatly overestimate the air concentration
a swimmer is likely to inhale. There are two reasons why this
is the case:
a) Equation D2-27 is invalid as a predictor of equilibrium air concentrations because it does not take into account the effect of limited solubility of pesticides in water by assuming infinite miscibility. Accordingly, it can greatly overestimate the equilibrium air concentration of a pesticide above the surface of the water in a swimming pool.
b) Equilibrium will not be attained in the air just above the pool water surface because of air movement diluting the air concentration.
These effects invalidate the use of equation D2-27, as was discussed at the September, 1997 SAP meeting and in the Panel s report. The current Panel is greatly concerned that the serious error in the equation, as well as its inapplicability to estimating swimmers inhalation exposures, has not been dealt with in the current document, in spite of criticisms of it elaborated by the Panel in September, 1997.
- Page D3-3. The background document states "Chemical properties, such as volatility, reactivity, and the ability of a chemical to decay and produce other chemicals can be used to determine if and how much, if any, of the chemical has evaporated into the surrounding air." This is not a valid statement. Although the rate of emission depends on these properties, they are insufficient, in themselves, to determine the rate. Because the material and the surface from which the emission occurs is complex and inhomogeneous, it is usually necessary to actually measure such rates of emission in test chambers.
- In the introduction section of the background document, the term "absorbed" or "internal dose" should be used as opposed to "delivered dose" since many exposures are accidental, unintentional or unavoidable. The simple presence of chemicals in the environment does not need to be further documented, and does not constitute exposure (i.e. a chemical crossing a boundary layer and entering the body).
Questions to the Scientific Advisory Panel
The Agency EPA poses the following questions to the SAP concerning the post application exposure guidelines.
- Should the guidelines include a short section which summarizes
areas that require generic research (e.g., quantifying children
s activities and evaluating sampling method ruggedness) versus
areas which reflect routine data needs in support of specific
pesticide products (e.g., collection of product specific surface
residue dissipation data)?
The regulatory overview in part A of the document is excellent. In general, the Panel believes that better data are needed to develop adequate residential exposure risk assessments. Some on the Panel feel that the need for conducting residential exposure analyses based on the hypothetical situations cited in the document and illness data should not be the foundation for risk assessments.
The major shortcoming of the document directly relevant to determining and prioritizing research needs is that it does not critically review the available materials or establish criteria for critical review. The background document should include a more comprehensive literature review, including registration documents, when feasible. The Panel recognizes that new studies are always appearing, and that the guidelines cannot include all recent studies. In evaluating the existing literature, however, the guidelines need to represent not so much a comprehensive, up-to-date review as a critical evaluation of the available studies. To help identify current and future research priorities and needs, the document should include guidance on how to critically evaluate data sources.
The background document could be considerably improved by providing better summaries and evaluations of existing data on children's activities by ages, gender, and the various socio-demographic variables. It could also provide more explicit advice on existing data bases, such as which exposure scenarios they are relevant to, and some indication of the data quality in each. Thus, the background document should address general exposure research issues such as:
(a) evaluation of data quality and applicability;
(b) comparison of methodologies for collecting and reporting laboratory and field data;
(c)aggregation of multipathway exposures to obtain meaningful assessments of pesticides with common mechanisms of toxicity;
(d) methods for performing distributional assessments (i.e., methods for estimating plausible upper bound exposures);
(e) time dependence and mass balance in dermal absorption scenarios. Fixed absorption is not plausible and is especially inappropriate when exposure (accumulation on skin) is presumed to be time dependent;
(f) exposure to "inerts" in pesticide products, since they are often present in much higher concentrations than the active ingredients and are not the focus of evaluations in most residential exposure evaluations.
- Two unresolved issues of immediate interest are: (a) the
use of wet versus dry hand presses to assess the nondietary ingestion
exposure and (b) hand exposure monitoring methods (i.e., hand
washes and gloves). Given the current state-of-the-art, does the
document adequately discuss the potential use of these specific
The Panel concludes that the guidelines do not adequately address either the wet versus dry hand press or the hand exposure monitoring methods. There is reason to believe that wet and dry hands differ (at least some of the time). There are no activity pattern data on the frequency or duration of wet or otherwise "sticky" versus dry hand events. In Part B Chapter 7 of the background document, there is no discussion of hand washes (e.g., rinses, wipes, etc.) Nor of the efficiency of washes in 18.104.22.168. Reference and expansion of material in the Introduction Section (7.2.5) is needed. In addition, guidance on use of information on the effect of skin conditions (e.g., sebum content) on transfer rates must also be developed.
The guidance document should detail exposure evaluation methods and indicate how they relate to absorbed dose. Without an indication of absorbed dose exposure, evaluations have limited usefulness in risk assessment or risk management. The Panel will provide the Office of Pesticide Programs (OPP) and the OPP Docket with a list of references to be included in the document. These references should be reviewed and included in the document since they would provide basic knowledge that applicants would need to design and interpret useful studies.
- The 1996 Food Quality Protection Act requires the Agency
to implement risk assessment measures to protect infants and children.
A critical need for conducting risk assessments for these sensitive
populations is to define the number of hand-to-mouth and object-to-mouth
events for different age groups. This is conducted in order to
refine estimates of acute and chronic exposures from nondietary
ingestion. Is the equation and assumptions used to estimate nondietary
ingestion dose attributable to hand to mouth activity (i.e. equation
D2-21) adequately protective of infants and children until additional
research is conducted to refine the assumptions? To what extent
should the guidelines address: (a) replenishment of the hands
from repetitive contacts on treated surfaces; (b) surface area
contacted per event (i.e., dermal, object mouthing, and hand-to-mouth);
and acceptable data collection methodologies (i.e., videotape,
direct observation, and diary data)?
While all Panel Members agreed this is an important research area, the Panel could not reach consensus on this question. Some Panel Members believed that data are not available to validate the assumptions of the exposure data, a more useful approach would be to examine what pediatricians are telling the scientific community about the health of infants and children. Other Panel Members felt that chronic and acute exposure estimates of nondietary exposure cannot be developed without a better understanding of how exposure takes place. Definition of these contact events is important for developing estimates of contact and transfer rates from environmental media to food or skin. Panel Members believed that integrating hand-to-mouth event data, transfer coefficients, and biomonitoring data should be the general goal of assessments in this area. Here, as elsewhere, the background document should establish criteria and methods used to evaluate data.
Most Panel Members could not determine if the equation (i.e., equation D2-21) was sufficiently conservative. It is not clear how the equation should be used and whether the defaults are reasonable since no example calculations are presented. All Panel Members believed that exposure projections need to anchored with biomonitoring data as the current state of the art is simply speculation.
Equation 2-22 as written has potentially serious conceptual shortcomings. Does the equation apply to objects, such as children's toys? If so, surface area of objects should be considered in the equation. Evaluations of exposure from residues on objects should include object-to-mouth contact that includes both ingestion of the object and mouthing of objects too large to be ingested.
Most importantly, the guidelines should address the issues of data quality and criteria used for evaluation. Whether these data reported are adequate will depend on methods used, age of children, and the exposure setting. As an example, duration of contacts of young children with surfaces typically range from two to four seconds, so direct observations of multiple children or parental recall of behaviors will be inadequate to quantify these behaviors.
Finally, the background document should also address the following issues:
a) evaluation of the efficiency of chemical residue transfer;
b) timing of exposures;
c) hand to mouth and object mouthing data exists in the published literature but is not cited in the guidelines;
d) repetitive contact and replenishment of hands after contact with surfaces.
- The guidelines recommend a small chamber test method for
quantifying airborne emissions from antimicrobial pesticide treated
articles (e.g., paint, wood preservatives, adhesives). Is this
methodology sufficiently sensitive to detect low air concentrations
of antimicrobial pesticides that are potentially released into
In general, one cannot evaluate whether methods are sufficiently sensitive without knowing the specific exposure scenario, analytical method, and sample volume available for analysis. The Panel concluded that chambers should be used to establish rates of emission only. The rates of emissions should be linked to indoor air models to establish indoor air concentrations and subsequent exposures. In general, whether a method is sufficiently sensitive cannot be evaluated until the level of sensitivity required for a meaningful assessment has been determined.
The duration of exposure is likely to be the most important parameter for this exposure scenario. Methods need to be developed to model both initial emission rates and, for chronic exposure scenarios, changes in emission rates over time.
- The guidelines recommend the existing FDA migration cell
method that was developed for quantifying flux rates from antimicrobial
pesticide treated articles, particularly impregnated plastics
(e.g., toys, cutting boards). Does this method require further
This question pertains to Section 22.214.171.124 (Migration Method) of the draft Guidelines (Version 5.4). The Panel commented on the migration of chemicals into food from articles intended for direct food contact. Section 126.96.36.199 suggests that migration studies similar to those described in FDA's "Recommendations for Chemistry Data for Indirect Food Additive Petitions," June 1995, could have "applicability in assessing migration of pesticides from impregnated materials to surfaces to which humans have non-dietary contact." The purpose, vis-a-vis FDA, of a migration study is to determine the concentration of a chemical in food that could result from its migration out of a food-contact article under conditions simulating actual conditions of contact (time, temperature, food type) between food and article.
Section 188.8.131.52 refers to toys and textiles and states that "the Series 875, Group B Guidelines are not intended to address dietary exposures...". However, the question put to the Panel mentions cutting boards, i.e., food-contact articles, and this speaks directly to dietary exposure. Migration studies similar to those described in FDA's "Recommendations" for use in estimating exposure to components of repeat-use articles would be most appropriate for the Agency's consideration. For scenarios relating to the contact of food with a pesticide-impregnated article (e.g., cutting boards, food conveyor belts), FDA's "Recommendations" note that migration studies should be performed over a ten-day period using the appropriate food simulant(s) in contact with the article of interest at the highest intended temperature of use. Information on the ratio of the mass of food contacting a unit surface area, the average contact time, and the service life of the article should accompany the migration study. In lieu of migration studies, the "Recommendations" indicate that a "worst case" calculation made by assuming 100% migration of the chemical into food over the service life of the article may be adequate for assessing exposure. Information on the initial amount of the chemical in the article and on the total quantity of food contacting the article during its service life is used to obtain the chemical's concentration in food. Exposure can then be calculated by combining concentration in food with appropriate data on food consumption.
For assessing migration of pesticides from impregnated materials to surfaces to which humans have non-dietary contact, new protocols for performing migration studies that simulate actual contact conditions and new mathematical models to characterize the migration process from the article to a non-food external phase would need to be developed. This issue is recognized in the background document. The new models and protocols would clearly need to be validated for these non-dietary scenarios.
FDA's migration protocols were developed in part under contracts with the National Institute of Standards and Technology (formerly The National Bureau of Standards) and with Arthur D. Little, Inc. and in part by FDA's in-house research during the late 1970's and 1980's. They have been extensively tested and validated. FDA has more recently been developing theoretical techniques for modeling diffusion in order to estimate migration of chemicals from various polymeric materials into food in the absence of experimental data.
Migration experiments for children's exposure should include the use of extraction media simulating body fluids (simulants for saliva, sweat, and urine). New protocols for exposure scenarios would need to be developed (e.g., migration from specific wide use products into body fluids).
FOR THE CHAIRPERSON:
Certified as an accurate report of findings:
Paul I. Lewis
Designated Federal Official
FIFRA/Scientific Advisory Panel