Review of the Environmental Protection Agency's Draft IRIS Assessment of Tetrachloroethylene (2010) / Chapter Skim
Currently Skimming:
10 Reference Values for Tetrachloroethylene
10 Reference Values for Tetrachloroethylene
Pages 86-97
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 86... ...
Although the committee supports EPA's decision to use neurotoxicity as a critical end point, it recommends more focused assessments of specific criteria related to study design and methods as part of the process of selecting critical studies for deriving reference values. The committee found that EPA reviewed all the relevant studies available at the time that the draft was written and agrees with many of the limitations that are noted, beginning on page 4-101.
|
From page 87... ...
It also limits the extrapolation of the results to other populations exposed to tetrachloroethylene." The committee judged that although there was no unexposed comparison group, the use of an internal comparison group (the group with the lowest exposure) has the advantage that any selection and confounding factors related to working in drycleaning facilities are present in both groups and reduces potential confounding by unmeasured factors.
|
From page 88... ...
of the two groups so that differences between the groups can be correctly attributed to exposure. On the basis of the study selection criteria noted earlier -- which emphasized validity, methodology, and consistency with the literature -- the human studies that the committee judged most appropriate to use as points of departure for derivation of the RfC are Altmann et al.
|
From page 89... ...
do suggest that the three PBPK models collectively describe the variation in blood and exhaled-breath concentrations of tetrachloroethylene observed in controlled human exposures. That provides confidence that later calculations of the tetrachloroethylene AUC during various exposure scenarios are accurately captured.
|
From page 90... ...
CHARACTERIZATION OF UNCERTAINTIES The committee reviewed EPA's application of uncertainty factors in deriving sample reference values on the basis of different studies. It found that the narrative made it clear what uncertainty factors were used but that there were some instances in which a supporting rationale was not provided for departure from the default option and other instances in which departures from the default option should have been considered.
|
From page 91... ...
Its use is appropriate and in accordance with EPA guidance. Extrapolation from Subchronic Exposure to Chronic Exposure The criteria for selecting the value of the uncertainty factor for extrapolating from subchronic exposure to chronic exposure were not clear, and this uncertainty was handled inconsistently in the draft IRIS assessment.
|
From page 92... ...
The committee recommends that EPA revisit and defend more clearly its decision to apply a factor of 3 for database deficiencies in light of new data and the committee's findings in Chapter 3. New studies include, for example, recent papers from researchers in EPA's National Health and Environmental Effects Research Laboratory provide excellent data from well-designed studies using controlled, acute exposures that link deficits in visual function and signal detection with atmospheric tetrachlorethylene concentrations and instantaneous concentrations in the brain.
|
From page 93... ...
study is not described, but it appears to be an adjustment from exposures 6 hours/day 5 days/week to 24 hours/day 7 days/week. GRAPHICAL PRESENTATION OF REFERENCE VALUES The draft IRIS assessment provides graphical presentations of noncancer reference values for tetrachloroethylene (Figures 5-1, 5-2, and 5-4)
|
From page 94... ...
Thick, horizontal lines represent studies identified by the committee as most applicable to the development of an RfC. The right end of a bar is at the "point of departure" and is based on concentrations used in the referenced study after conversion to "human equivalencies" or, in the case of animal studies, after adjustment for continuous exposure.
|
From page 95... ...
The convergence of sample reference values into clusters would confer confidence on the use of a critical study if other studies led to similar conclusions. The points of departure for the pre-2004 studies came from Tables 4-4 and 5-2 of the draft document, so they were human adjusted equivalent concentrations or, in the case of animal studies, adjustments for continuous exposures as appropriate.
|
From page 96... ...
Despite the use of different exposure regimens and concentrations among animal studies, human chamber studies, and occupational and environmental studies, there is a reasonable coherence in the sample reference values. Finally, to keep the maximum uncertainty factor to 3,000, the "database" factor of 3 was omitted from four estimates for the pur
|
From page 97... ...
The graphical display in Figure 10-1 shows a distribution of sample reference values based on neurotoxic effects observed in epidemiologic studies, controlled human experiments involving healthy volunteers, and animal experiments involving different species. Exposure ranged from chronic to acute.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.