Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 70
-
Conclusions and Recommendations
The California Opal lment of Pesticide Regulation (DPR) has put consider-
able time and effort into the development of its risk characterization document
for methyl bromide. The subcommittee agrees that development of a risk
characterization, and subsequent risk assessment, is an appropriate approach
to be used to protect agricultural workers and the general population from
potential adverse effects associated with this widely used pesticide. Below
are specific conclusions reached by the subcommittee based on DPR's presen-
tation of the toxicology, exposure, and risk assessment and risk appraisal in-
formation for methyl bromide as detailed in DPR's report. Recommendations
on improving both the data quality and the analytical approaches used in the
risk assessment are presented as a means to assist DPR in identifying at-risk
populations and, subsequently, developing regulations to protect them.
TOXICOLOGICAL INFORMATION
Conclusions
· The subcommittee agrees with DPR's selection of the toxicological end-
points and the NOAELs used to derive the inhalation reference concentrations
(RfC). The subcommittee considers the NOAELs to be protective and conser-
vative.
70
OCR for page 71
CONCLUSIONS AND RECOMMENDATIONS 71
· The subcommittee agrees that it is appropriate to use a developmental
study for the derivation of an acute RfC for the general population.
· DPR's selection of the dog study (Newton 1994b) with a neurotoxicity
endpoint is appropriate for developing a subchronic RfC, but the subcommit-
tee is concerned about whether the decrease in responsiveness seen at expo-
sure to 5 ppm of methyl bromide in two of eight dogs is a true LOAEL or
even an effect at all. Nevertheless, the subtle neurological deficits observed in
occupationally exposed humans (Anger et al., 1986) supports these animal
data that neurotoxic responses can occur at Tow exposure concentrations.
Therefore, the subcommittee concurs with the conservative assignment of the
5 ppm value in this dog study as a LOAEL.
· The rabbit developmental study had toxicity endpoints of gallbladder
agenesis and fused sternebrae, which are not considered major malformations;
however, the subcommittee feels that these are indicators of developmental
toxicity, and therefore, are appropriate endpoints for the developmental RfC
(Breslin et al. 1990b).
· The subcommittee agrees with DPR's selection of nasal epithelial hyper-
plasia as the toxicity endpoint for the chronic RfC, but notes that the effect is
mild and might be closer to a NOAEL than a LOAEL.
· In general, DPR's presentation of the toxicological information is clear
and easy to follow and permits the reader to follow DPR's logic in selecting
critical studies and NOAELs.
Recommendations
· Methyl bromide is a methylating agent that is a direct-acting mutagen in
vitro. However, there are good animal studies that indicate it is not carcino-
genic. DPR should review the literature for any discussion on methyl bromide
and other methylating agents as to why an in vitro mutagen is not an in vivo
carcinogen. This could aid in understanding the mechanism of methyl bro-
mide toxicity and lend confidence when extrapolating from the animal data to
humans.
· The dog study from which the 6-week subchronic RfC is derived
(Newton 1994b) had a small number of animals and some subjective observa-
tions that led to a LOAEL of 5 ppm. The subcommittee recommends that a
new study be conducted to verify the neurotoxicity endpoints of decreased
responsiveness at 5 ppm.
· Further developmental studies on methyl bromide would help to clarify
severe . mayor issues
Does in utero or early postnatal exposure to methyl bromide affect
OCR for page 72
72 METHYL BROMIDE RISK CHARA CTERIZA TION IN CALIFORNIA
adult reproductive function? This question arises from the observation
of apparently reduced fertility in the F ~ offspring, but not the F0 parents
in a two-generation study (American Biogenics Corporation 1986;
Hardisty 1992; Busey 1993~.
What are the critical exposure periods for expression of reduced pup
weights found during lactation and decreased offspring brain weights
and dimensions (i.e., are they due to gestational or lactational exposure
to methyl bromide?)
—Is methyl bromide excreted in breast milk? This question could be
answered by measuring methyl bromide concentrations in the breast
milk of lactating animals exposed to methyl bromide by inhalation.
Does gallbladder agenesis occur following a single exposure to meth-
y] bromide during the critical period for gallbladder development?
EXPOSURE ASSESSMENT
Conclusions
· Although the exact levels of exposure for workers and residents are not
known, DPR has collected a substantial amount of data that indicate that some
of these exposures are significant, exceeding current regulatory limits, and
therefore are of concern.
· The measures of exposure are frequently based on a single value with no
accompanying information on ambient air temperature, relative humidity, and
wind conditions. The lack of representativeness of the measurements is not
assessed in the main text of the DPR report and is only acknowledged as a
possible confounder in an appendix.
· In general, the subcommittee is highly critical of the analysis and pre-
sentation of the available exposure data, finding it seriously deficient in un-
derstanding and application of modern concepts of variability and uncertainty,
and in the fair evaluation of the magnitude and distribution of existing expo-
sures relative to exposure levels intended to be achieved by current regulatory
controls.
· There is considerable room for improvement in the methods used by
DPR to obtain monitoring data, particularly with regard to good measurement
techniques and sampling strategies that assess variability of actual exposure.
· Information is lacking on exposures to residents living near application
areas end exposures for populations subject to aggregate applications (e.g.,
those living in basin area where multiple fields have been treated). Available
data and modeling suggest that for some populations, exposures might exceed
regulatory limits.
OCR for page 73
CONCLUSIONS AND COMMENDS TIONS 73
· A substantial ambiguity exists for current methods used to measure
methyl bromide in air, particularly with respect to recovery values and the
field conditions during air sampling. As a result, actual measured air concen-
trations of methyl bromide and potential exposure levels are uncertain.
· DPR's use of 24-hr averaging for 8-fur exposures adds a further uncer-
tainty to the protectiveness of the regulations.
· DPR's documentation of their exposure assessment is difficult to follow
and requires searching through numerous appendices and other documents
(many of which were requested by the subcommittee at a later date) to deter-
mine the data sources used by DPR and the approach that was used to evaluate
and model the data. A roadmap of the information in the appendices and a
more systematic presentation of the data would be helpful to the reader. In
particular, DPR's discussion of buffer zones and the measurements taken at
them, is confusing and appears to be missing important pieces of information.
Recommendations
· DPR should explicitly state what populations or subpopulations are ex-
pected to be represented by the scenarios.
· Identify the best analytical methods for determining methyl bromide
concentrations in air under a variety of field conditions. The entire risk assess-
ment process is fundamentally dependent on the quality of the analytical in-
formation on exposure conditions. A substantial effort is needed to develop
rigorous and robust field analytical methods for determining concentrations of
methyl bromide. This will require a complete multilaboratory series of tests
that can allow a determination of the reliability of analytical information from
field samples.
· Conduct systematic recovery analyses of field and laboratory air samples
under a variety of air temperature, wind, and relative humidity conditions.
· Establish a new sampling program to determine the representativeness of
exposure data with an emphasis on residential (including house fumigations)
and high-exposure occupations.
· DPR should consider quantifying at the very least- the potentially ex-
posed populations in its occupational categories, and if possible, the number
of residents near fields, fumigation facilities, and residents returning to fumi-
gated homes.
· DPR should evaluate its exposure data using modern distributional con-
cepts- including both variability and uncertainty to quantify how accurately
the observed measurements represent the real distributions of exposure con-
centrations and durations. The subcommittee believes that analyses intended
to support regulations should frankly disclose the expected degree of confi-
OCR for page 74
74 METHYL BROMIDE RISK CHAR/4 CTERIZ}4 TION [N CA LIFORNIA
dence the public should have that real exposures will be kept below regulatory
levels for defined percentiles of exposed populations.
RISK CHARACTERIZATION
Conclusions
· The subcommittee overall agrees with the risk characterization for inha-
lation exposure of methyl bromide. The subcommittee believes that the toxic-
ity endpoints used might be overly conservative due to their equivocal nature,
but also believes that the exposure assessments might understate the actual
exposures, particularly for residents living near fields where methyl bromide
is applied.
· The subcommittee agrees that DPR's use of factors of ~ O for intraspecies
variation and for animal to human variation, as well as a benchmark margin of
exposure (MOE) of 100, is consistent with traditional risk management prac-
tices.
· The subcommittee believes that the uncertainties associated with DPR's
exposure levels call into question the validity of its MOE values. Given the
likelihood that the error in the measurements will underestimate some expo-
sures, the subcommittee anticipates that some MOEs will be lower than those
calculated by DPR, some of which already indicate there is a cause for con-
cern (i.e., they are currently less than 100~.
· Given the lack of information on methyl bromide drift off-site from fu-
migated fields, it is unclear to the subcommittee how DPR can develop a co-
herent and protective plan for buffer zones and injection times for field fumi-
gation as specified in Section 6450 of Title 3 of the California Code of Regu-
lations.
· The subcommittee concludes that DPR has failed to conduct a true risk
assessment in that it does not combine both exposure assessments and dose-
response assessments to estimate the probability of specific harm to exposed
individuals or populations. Furthermore, DPR does not characterize the distri-
bution of risk to the exposed populations.
Recommendations
~ Buffer zones should be derived so that they appropriately protect those
persons who might spend appreciable amounts of time near treated areas (e.g.,
residential, schools, offices). These buffer zone distances will need to be
OCR for page 75
CONCLUSIONS AND ~COMMENDATION5 75
based on reasonable worst-case scenarios. Additional field studies should be
undertaken to validate these buffer zones.
· At the very least, DPR should characterize occupational and residential
exposures with distributions, that is, estimate how many people are likely to
be exposed at what levels relative to levels of concern for a given duration of
exposure. DPR should also conduct some uncertainty analyses to determine
what level of confidence in the exposure values is appropriate given the exist-
ing data.
~ More neurological testing among those occupationally exposed, particu-
larly at various time intervals after methyl bromide exposures have occurred
(instead of during exposures), would enable DPR to look for possible Tong-
term or permanent effects.
~ To protect workers and residents from the adverse effects of methyl bro-
mide, DPR must be more explicit about linking its methodology for exposure
and MOE analysis to the regulatory levels that are based upon the risk assess-
ment or MOE values. The subcommittee recommends that DPR state at the
beginning of its risk characterization document the regulatory goals it hopes
to achieve and how its risk characterization will meet them.
in conclusion, the subcommittee recognizes that conducting additional tox-
icity testing and exposure monitoring is somewhat problematic given the
phase-out of methyl bromide in the United States by 2005. Nevertheless, the
subcommittee believes that extensive use of this pesticide at this time in Cali-
fornia and elsewhere warrants an acknowledgment of existing data gaps that
must be addressed to ensure that agricultural workers and residents living near
areas where methyl bromide is used are protected against the short-term and
Tong-term health effects of this pesticide. These data gaps might require the
combined efforts of regulatory agencies such as DPR and the methyl bromide
industry, including manufacturers and pesticide applicators.
Representative terms from entire chapter:
risk characterization
