Questions on Determination of the Appropriate FQPA Safety Factor(s) for Use in the Tolerance-Setting Process
- Is a weight-of-the-evidence approach to making FQPA Safety Factor
decisions appropriate, taking into consideration the toxicology
and exposure databases for a pesticide and the potential risks
for the developing fetus, infant and child as well as other populations?
If not, why not? Given the scope of the evidence which OPP intends
to consider, are there any other types of scientific information
that OPP should consider in its FQPA Safety Factor determinations?
- Under what circumstances, if any, do you believe that OPP's
current approaches (the combination of empirical data, models,
and assumptions) fail to yield risk assessment which are sufficiently
conservative and do not understate the risks to infants and children?
Toxicology Database Issues
- Please comment on OPP's proposed criteria for defining the core
toxicology database and its approach to imposing a database uncertainty
factor if certain key studies are missing from the database.
- After having considered the recommendations from this Panel
and the Toxicology Working Group, OPP is beginning the process
of calling in data for three studies (the acute and subchronic
neurotoxicity studies in adult mammals and the developmental neurotoxicity
study) for a subset of conventional chemistry food-use pesticides-known
neurotoxicants. In addition, OPP will be proposing to require
the same set of studies for all conventional chemistry food-use
pesticides in the revision of the Part 158 regulations. Please
comment on this two-stage approach.
- The OPP Policy Guidance indicates that one of the critical issues
is whether or not to apply an FQPA Safety Factor pending receipt
of newly-required studies. In the absence of the results from
any of the studies to be required through data call-in notices
(i.e., the acute and subchronic neurotoxicity studies in adult
mammals and the developmental neurotoxicity study) what information
from existing studies on a specific chemical would increase or
decrease your concerns about the potential for pre- and post-natal
hazard, in general, and for neurotoxicity and developmental neurotoxicity,
in particular? Which, if any of the seven criteria discussed in
section V.A.1.a., footnote 4 and associated text of the OPP Guidance
are appropriate for judging whether there is increased concern
about the potential for a pesticide to cause developmental neurotoxicity?
- Please comment on whether you expect that the NOAELs that are
identified in the developmental neurotoxicity studies would, for
a substantial number of chemicals, be lower than those NOAELs
identified in the suite of studies historically required and used
for age-related comparisons and Reference Dose derivation (e.g.,
prenatal developmental toxicity or multigeneration reproduction
study, subchronic and chronic studies, etc.). Please explain the
basis of your opinion.
- OPP is proposing to adopt the framework and its criteria/factors
for assessing the degree of concern about the potential for pre-
and post-natal effects as recommended by the Toxicology Working
Group. Please comment on the appropriateness of the proposed criteria/factors
for use in this assessment process, and OPP's proposed approach
for accommodating its concerns in the Reference Dose derivation
and FQPA Safety Factor decision processes, in the near term, and
in the longer term. What scientific considerations relate to the
addition of a safety factor where the hazard to infants and children
is well characterized, and the data show that infants and/or children
are more susceptible than adults?
- Subject to the qualifications expressed in the OPP Policy document
and the report from the Exposure Working Group, OPP believes that
each of the tiers for estimating exposure to pesticides through
food, in almost all instances, will not underestimate exposure
to infants and children. Please comment on this conclusion, as
it applies to each of the tiers.
- OPP is developing a tiered approach to assessing the likelihood
and magnitude of contamination of drinking water and its sources
by pesticides. The Panel has been asked to comment on aspects
of this activity at previous meetings. As an interim approach
when direct assessment is not possible, is it reasonable and protective
to regard the estimates generated by OPP's current methodology
as upper bound pesticide concentrations for surface and ground
water and to assume that this concentration will be found in drinking
- OPP is developing approaches to assess the likelihood and magnitude
of exposure to pesticides in residential and other non-occupational
use scenarios. The Panel has been asked to comment on aspects
of this activity at previous meetings. When direct assessment
is not possible, is it reasonable and protective to regard the
estimates of exposure for the major residential and other non-occupational
exposure use scenarios developed by OPP as upper bound estimates
of the exposure received by infants and children from such use?
- In OPP's view, its aggregate exposure assessments generally do not underestimate the exposure to infants and children because the aggregate exposure is calculated by adding the high-end, probabilistic estimates of exposure to pesticides in food, to the high-end, deterministic estimates of exposure to pesticides both in water and as a consequence of pesticide use in residential and similar settings. Please comment on this view.