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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 System (IRIS). An 

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

Libby Amphibole asbestos, found in vermiculite ore deposits near Libby, MT, is 

comprised of a mixture of related mineral forms of amphibole asbestos: primarily winchite, 

richterite and tremolite with trace amounts of magnesioriebeckite, edenite, and magnesioarfvedsonite. 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 consumer products, some of which 

may remain in place (e.g. vermiculite attic insulation in homes.)

The current draft Toxicological Review of 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 exposure 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 does 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 concise? Has EPA clearly, and in sufficient 

detail, presented and synthesized the scientific evidence for health hazards from Libby

Amphibole asbestos?

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. Radiographic evidence of localized pleural 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. Exposures were reconstructed by the University of Cincinnati from the industrial hygiene data 

collected in 1972 and afterwards for workers in the Marysville, OH facility. Exposures to Libby 

Amphibole were estimated for 1957 to 1971. Please comment on whether the methodology used 

for the exposure reconstruction is scientifically supported and clearly described. [As a crossreference, note that EPA used the subcohort of employees first exposed after 1972 as the basis 
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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 Libby Amphibole asbestos in 1972 (when 

measurements of fiber levels in the workplace began) or later. Has 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 pleural 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 alternative 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 rationale for presenting these alternative approaches 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 modeled POD estimate is based on cumulative exposure estimates for the worker cohort 

examined (for the preferred subcohort, exposures were concentrated in the period 1972-1980, 

although some low level of exposure is assumed to occur from after this time). For 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 scientifically 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 the methodology 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 humans” by the inhalation route of exposure. Please comment on 

whether the cancer weight of evidence characterization is scientifically supported and clearly 

described.

2. The draft assessment concludes that data are not sufficient to characterize the mode of 

carcinogenic action of Libby Amphibole asbestos. 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 Libby 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)

3. An occupational cohort of vermiculite miners 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 different study is recommended as the preferred basis for the IUR, please identify 

and provide scientific support for this choice.

4. From this cohort, mortality from mesothelioma and lung cancer in humans was selected to 

serve as the basis for the quantitative 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 lifetable analysis was used to determine the 

points of departure (PODs) for each type of cancer for the various exposure metrics. Have the 
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exposure-response modeling and determination of the PODs 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 scientific 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. Has this 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 exposure dependent competing risks from asbestos-related noncancer mortality. Has EPA 

appropriately considered these issues?