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International Commission on Radiological Protection (ICRP) publications 56 (ICRP 1990), 71 (ICRP
1996a), and 72 (ICRP 1996b); and the ICRP CD-ROM system (ICRP 2001).
3.2 DISCUSSION OF HEALTH EFFECTS OF PLUTONIUM BY ROUTE OF EXPOSURE
To help public health professionals and others address the needs of persons living or working near
hazardous waste sites, the information in this section is organized first by route of exposure (inhalation,
oral, and dermal) and then by health effect (death,
systemic, immunological, neurological, reproductive,
developmental, genotoxic, and carcinogenic effects). These data are discussed in terms
of three exposure
periods: acute (14 days or less), intermediate (15–364 days), and chronic (365 days or more).
Levels of significant exposure for each route and duration are presented in tables and illustrated in
figures. The points in the figures showing no-observed-adverse-effect levels (NOAELs) or lowest-
observed-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the studies.
LOAELs have been classified into "less serious" or "serious" effects. "Serious" effects are those that
evoke failure in a biological system and can lead to morbidity or mortality (e.g.,
acute respiratory distress
or death). "Less serious" effects are those that are not expected to cause significant dysfunction or death,
or those whose significance to the organism is not entirely clear. ATSDR acknowledges that a
considerable amount of judgment may be required in establishing whether an end point should be
classified as a NOAEL, "less serious" LOAEL, or "serious" LOAEL, and that in some cases, there will be
insufficient data to decide whether the effect is indicative of significant dysfunction. However, the
Agency has established guidelines and policies that are used to classify these end points. ATSDR
believes that there is sufficient merit in this approach to warrant an attempt at distinguishing between
"less serious" and "serious" effects. The distinction between "less serious" effects and "serious" effects is
considered to be important because it helps the users of the profiles to identify levels
of exposure at which
major health effects start to appear. LOAELs or NOAELs should also help in determining whether or not
the effects vary with dose and/or duration, and place into perspective the possible significance of these
effects to human health.
The significance of the exposure levels shown in the Levels of Significant Exposure (LSE) tables and
figures may differ depending on the user's perspective. Public health officials and others concerned with
appropriate actions to take at hazardous waste sites may want information on levels of exposure
associated with more subtle effects in humans or animals (LOAELs) or exposure levels below which no
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adverse effects (NOAELs) have been observed. Estimates of levels posing minimal risk to humans
(Minimal Risk Levels or MRLs) may be of interest to health professionals and citizens alike.
A User's Guide has been provided at the end of this profile (see Appendix B). This guide should aid in
the interpretation of the tables and figures for Levels of Significant Exposure and the MRLs.
3.2.1
Inhalation Exposure
Possible associations between exposure to plutonium and adverse health outcomes have been
examined in
studies of workers at the U.S. plutonium production and/or processing facilities (Hanford, Los Alamos,
Rocky Flats), as well as facilities in Russia (e.g., Mayak) and the United Kingdom (e.g., Sellafield).
Strengths and weaknesses of each study must be considered in interpreting the overall weight of evidence
for plutonium-associated health outcomes in these populations. Studies that have individual subject
plutonium dose or exposure measurements and that present exposure- or dose-response analyses are much
stronger than those that simply compare risks for a group of exposed subjects with those for a group of
unexposed subjects. A common study design has been to construct plutonium worker cohorts based
solely on whether the individuals had been monitored for plutonium. However,
this strategy may result in
inclusion of workers who have been monitored but never experienced an internal plutonium deposition.
The magnitude of the doses received in the study population is also an important design factor. In
general, studies of populations that experienced relatively small plutonium radiation doses have limited
statistical power for detecting plutonium effects; this includes all of the U.S. and U.K. worker studies.
Failure to find significant associations between plutonium exposure and/or radiation dose in low-dose
studies does not mean that such associations do not exist. In addition to statistical power,
biological
plausibility of findings must be considered. Effects observed in organs that receive relatively large
plutonium radiation doses (e.g., lung, liver, bone) are more credible than effects observed in organs that
are likely to have received relatively small plutonium radiation doses and may have been caused by other
uncontrolled factors in the study (e.g.,
other forms of radiation, chemical exposures). Similarly,
associations to plutonium exposure are more uncertain when observed effects are limited to tissues that
receive relatively small doses of plutonium (i.e., in the absence of effects in tissues that received much
higher plutonium radiation doses). Elevated risk in plutonium-exposed workers does not necessarily
imply causal association to plutonium. Demonstration of a consistent increase in risk in association with
increasing plutonium radiation dose is far stronger evidence of a causal relationship than a
simple
elevation of risk in an exposed group compared to an unexposed referent group. Common to the
interpretation of any epidemiological studies of workers are factors such as the “healthy worker effect"