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NCEA’s Proposed Draft Charge to External Reviewers for the IRIS Toxicological Review of Libby Amphibole Asbestos

May 2011

The U.S. Environmental Protection Agency (EPA) is seeking an external peer review of the scientific basis supporting the human health assessment of Libby Amphibole asbestos that will appear on the Agency’s online database, the Integrated Risk Information S ystem (IRIS)

. An existing IRIS assessment for asbestos was posted on IRIS in 1988

. Th e draft on which we are now seeking review is the first IRIS assessment specific to Libby Amphibole asbestos.

IRIS is a human health assessment program that evaluates quantitative and qualitative risk information on effects that may result from exposure to specific chemical substances found in the environment. Through the IRIS Program, EPA provides quality science

- based human health assessments to support the Agency’s regulatory activities. Combined with specific exposure information, government and private entities use IRIS to help characterize public health risks of
chemical substances in site

- specific situations in support of risk management decisions.

Li bby Amphibole asbestos, found in vermiculite ore deposits near Libby, MT , is comprised of a mixture of related mineral forms of amphibole asbestos: primarily winchite,
richt e rite and tremolite with trace amounts of magnesioriebeckite, edenite, and magnesio

arfvedsonite . Libby Amphibole asbestos is a potential concern for former vermiculite processing and waste disposal sites which may have handled vermiculite mined in Libby, MT. Additionally vermiculite from Libby, MT was incorporated into various consume r products, some of which may remain in place (e.g. vermiculite attic insulation in homes.)

The current draft Toxicological Review o f Libby Amphibole asbestos is based on a comprehensive review of the available scientific literature on the health effects of Libby Amphibole asbestos and was developed in adherence with general guidelines for risk assessment set forth by the National Research Council in 1983 (NRC, 1983) and numerous guidelines and technical reports published by EPA (see Section 1 of the assessment). Specifically, this draft IRIS assessment provides an overview of sources of exposure to Libby amphibole asbestos, characterizes the hazard posed by expo sure to Libby Amphibole asbestos for carcinogenicity and

non

- cancer health effects based on the available scientific evidence, and presents a quantitative risk assessment, including the derivations of a chronic inhalation reference concentration (RfC)
and an inhalation unit risk (IUR) of carcinogenic mortality

. The assessment do es not address oral exposure

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Below is a set of charge questions that address scientific issues in the human health risk

assessment of Libby Amphibole asbestos . Please provide detailed explanations for responses to the charge questions. Please consider the accuracy, objectivity, and transparency of EPA’s analyses and conclusions in your review.

General Charge Questions :

1. Is the Toxicological Review logical, clear
, and conc ise? Has EPA clearly , and in sufficient
detail
, presented and synthesized the scientific evidence for health hazard s from L i b b y A m p h i b o l e a s b e s t o s ?

2. If there are any additional , existing, studies that would have a significant impact on the conclusions of the Toxicological Review , please identify and provide the rationale for their
inclusion

.

Chemical

- Specific Charge Questions:

(A) Inhalation Reference Concentration (RfC) for Libby Amphibole Asbestos

1. An occupational cohort of workers in a Marysville, OH facility exposed to Libby Amphibole
asbestos was selected as the basis for the derivation of the RfC (Lockey et al., 1984; Rohs et al., 2008)

. Please comment on whether the selection of this study population is scientifically supported and clearly described. If a different study is recommended as the preferred basis for
the RfC , please identify this study and provide scientific support for this choice.

2. R adiographic evidence of localized pleur al thickening in humans was selected as the critical
effect for the derivation of the RfC. Please comment on whether the selection of this critical
effect is scientifically supported and clearly described. If a different health endpoint is
recommended as the preferred critical effect for deriving the RfC, please identify this effect and provide scientific support for this choice.

3. E xposure s were reconstruct ed by the University of Cincinnati from the industrial hygiene data
collected in 1972 and afterw ards for w orkers in the Marysville, OH facility . E xposure s to Libby Amphibole were estimated f or 1957 to 1971. Please comment on whether the methodology used for the exposure reconstruction is scientifically supported and clearly de scribed

. [As a cross

reference, note that EPA used the subcohort of employees first exposed after 1972 as the basis3

for its preferred statistical analysis in support of the RfC.]

4. Exposure

- response modeling was conducted using the incidence of localized pleural thickening in humans and cumulative exposure to derive the point of departure (POD) for the
RfC. EPA’s estimate of the POD is based upon a log

- logistic model applied to the subcohort of
workers examined in 2002

- 2005 and first exposed to L ibby Amphibole asbestos in 1972 (when measurements of fiber levels in the workplace began) or later

. Ha s the modeling been appropriately conducted and clearly described? Is the benchmark response (BMR) selected for use in deriving the POD (i.e. a 10% extra risk of localized pleur al thickening ) scientifically appropriate for the assessment and clearly described? Please comment on whether the rationale for selecting the preferred POD is scientifically justified and clearly described.

5. EPA ’s assessment provides results of altern ative modeling approaches to provide information

on the sensitivity of the POD to cohort selection criteria and modeling form. Are these alternative approaches and their strengths and weaknesses clearly described? Please comment on whether EPA’s rational e for presenting these alternat iv e ap proaches is scientifically justified and clearly described. If a different modeling approach is recommended as the basis for estimating a POD, please identify specifically and provide scientific support.

6. The mo deled POD estimate is based on cumulative exposure estimates for the worker cohort
examined (for the preferred sub cohort, exposures were concentrated in the period 1 9 72

- 1980
, although some low level of exposure is assumed to occur from after this time )

. F or application
in derivation of the RfC, this cumulative exposure is prorated over the period of environmental

exposure (lifetime or shorter duration chronic exposure when appropriate )

. The RfC is provided
in units of continuous air concentration for lifetime exposures . Is the basis for this conversion clearly explained and scientifically justified ?

7. Please comment on the rationale for the selection of the uncertainty factors (UFs) applied to
the POD for the derivation of the RfC. Are the UFs s cientifically supported and clearly
described? If changes to the selected UFs are proposed, please identify and provide scientific support

.

8. Please comment on whether, overall, the document describes the uncertainties and limitations
in t he methodolog y used to derive RfC in a transparent manner

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( B ) Carcinogenicity of Libby Amphibole Asbestos

1. Under the EPA’s 2005 Guidelines for Carcinogen Risk Assessment (www.epa.gov/iris/backgrd.html), the draft IRIS assessment characterizes Libby Amphibole
asbestos as “ carcinogenic to human s” by the inhalation route of exposure

. Please comment on
whether the cancer weight of evidence characterization is scientifically supported and clearly
described

.

2. T he draft assessment concludes that data are not sufficient to characterize the mode of carcinogenic action of Libby Amphibole asb estos

. Please comment on whether this determination is scientifically supported and clearly described. If it is judged that a mode of
action can be established for L ibby Amphibole asbestos , please specifically identify this mode and its scientific support ( as discussed in EPA Guidelines for Carcinogen Risk Assessment (2005), Section 2.4.3).

Inhalation Unit Risk (IUR)

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. An occupational cohort of vermiculite miner s and millers exposed to Libby Amphibole asbestos (Sullivan, 2007) was selected as the basis for the derivation of the IUR

. Please comment on whether the selection of this study population is scientifically supported and clearly
described. If a diff

erent study is recommended as the preferred basis for the IUR , please identify and provide scientific support for this choice.

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. From this cohort, m ortality from mesothelioma and lung cancer in humans was selected to
serve as the basis for the quantitat ive inhalation cancer assessment. Please comment on whether
this selection is scientifically supported and clearly described. If other health endpoints are recommended as the preferred basis for the IUR, please identify and provide scientific support
for this choice.

5. Exposure

- response modeling was conducted separately for lung cancer and mesothelioma mortality. The preferred point of departure (POD) estimates for these endpoints are based upon analysis of the subcohort of workers first exposed post 1960 when the exposure data was judged
to be better characterized . The exposure

- response modeling included consideration of a variety
of dose metrics that varied with time and incorporated different lag and decay parameters. Based on the results of the exposure

- response modeling, a l ifetable analysis was used to determine the points of departure (PODs) for each type of cancer for the various exposure metrics

. Ha ve the5

exposure

- response modeling and determination of the POD s from lifetable analysis been appropriately conducted and clearly described? If a different approach to exposure

- response analysis is recommended as the preferred basis for the estimating the IUR, please identify the recommended methods and provide scien tific support for this choice.

6. In order to derive an IUR which represents the combined risk of mortality from lung cancer or mesothelioma, a cancer

- specific unit risk for each tumor type was calculated by linear extrapolation from the corresponding POD (i.e., the lower 95% confidence limit on the exposure associated with 1% extra risk of lung cancer or 1% risk of mesothelioma mortality) . The IUR was then determined as a combined upper bound risk estimate for mortality considering both

cancers. Ha s thi s approach been appropriately conducted and clearly described?

7 . Please comment on the adjustment for mesothelioma mortality under

- ascertainment. Is this adjustment scientifically supported and clearly described ? If another adjustment approach is recommended as the preferred basis for the IUR, please identify that approach and provide scientific support for this choice.

8 . Please comment on whether, overall, the document describes the uncertainties and limitations in the methodology used to derive the IUR in a transparent manner. Examples of issues that warrant consideration include potential impacts from uncertainty in the historical exposure estimates for the Libby workers and the potential for “masking” of some of the cancer mortality by exposu re dependent competing risks from asbestos

- related noncancer mortality

. Has EPA appropriately considered these issues?