Advisory Board on Toxic Substances and Workers Health

Recommendation on Including Probable Human Carcinogens in the Site Exposure Matrices

The Advisory Board on Toxic Substances and Workers Health recommends that:

1. Toxic substances that are found to be probable human carcinogens (International Agency for 

Research on Cancer - IARC Group 2A) and that have limited human epidemiological evidence for 

specific human cancer sites as identified in table 1, should be linked to those cancer sites in the 

Site Exposure Matrices (SEM).

2. The SEM should specify that IARC and National Toxicology Program (NTP) evaluations have been 

used in addition to HAZ MAP for the purpose of asserting linkages between toxic substances and 

human cancer sites. 

3. Data from IARC and NTP should be used in addition to HAZ MAP for health effects and linkages 

of toxic substances to cancers. At least on a yearly basis going forward, future IARC Group 2A (as 

well as Group 1) substance-human cancer site linkages identified by IARC or NTP should be 

updated in the SEM. 

Report on Group 2A Carcinogens

Background

In 2019 a Working Group of the US DOL Advisory Board on Toxic Substances and Workers Health 

(ABTSWH)began an evaluation of agents rated as “Probably Carcinogenic in Humans (Group 2A)*” by 

the International Agency for Research on Cancer (IARC) for potential inclusion in decision-making under 

the Energy Employees Occupational Illness Compensation Program (EEOICP). Since 2016, IARC has 

updated 90 chemicals, including 22 agents in Group 2A. Of those 22 agents, 18 were toxic substances 

that could be encountered in the workplace and those became the focus of this Working Group. A toxic 

substance could be rated as a probable human carcinogen based upon data from human 

epidemiological studies, experimental animal data, mechanistic evidence, or a combination thereof. For 

worker compensation purposes, however, the Working Group determined that linking the toxic 

substances to specific human cancer sites requires, in most cases, at least limited evidence from human 

epidemiological studies in support of such linkage.

Questions

The Working Group reviewed these 18 toxic substances to determine the following:
1. Is there human epidemiological support, as cited by IARC or the National Toxicology Program 

(NTP), for an association between the toxic substance of concern and specific human cancer 

sites?

2. For the Group 2A toxic substances with limited links to human cancers, are these links identified 

or listed in the DOL Site Exposure Matrices (SEM)?

Findings

Of the 18 toxic substances rated IARC Group 2A:

• 11 toxic substances had limited evidence of human cancers in specific organs (Table1) 

• All of these 11 toxic substances are listed in the SEM, but none are linked in the SEM to the 

human cancer sites identified in the IARC review

• Of the cancers that are linked to toxic substances in the SEM, none are linked to the IARC Group 

2A toxic substances.

• Breast, Prostate and Testicular cancers were not listed at all in the SEM

Rationale

Review Sources: IARC Monographs; NTP Report on Carcinogens

Polybrominated biphenyls

• IARC monograph #107 (updated 2 August 2018) (https://monographs.iarc.who.int/wpcontent/uploads/2018/06/mono107-002.pdf)

• “Polybrominated biphenyls” or “polybromobiphenyls” (PBBs) is a group of halogenated 

hydrocarbons (HC’s) formed by substituting hydrogen with bromine on a biphenyl ring—209 

possible structural congeners—but only a few have been synthesized and used commonly- classified 

by positions of bromine on the double benzene rings (ortho, meta and para ) and number of 

bromines-same numbers are called homologue – 3 common mfg’ed: hexa, octa, deca. Example: 

“Firemaster” is a mixture of mostly hexabromobiphenyl and heptabromobiphenyl and smaller 

amounts of lesser brominated; sometimes present, contaminants or impurities (eg. toluene, 

naphthalene...). Commercial PBB mixtures created primarily to use as flame retardants—contain 

numerous congeners. Also used in acrylonitrile-butadiene-styrene (ABS) plastics. Environmental 

contamination when Firemaster mixed up with NutriMaster -animal feed supplement. Worker 

exposures-production PBB, PBB plastics, PBB fire retardants or processing e-waste.

• IARC summary of human carcinogenicity

“Most data from follow-up of resident exposure to contaminated food following industrial accident 

in Michigan-nested case-control analysis, positive findings for lymphoma and cancers of the 

digestive system combined (liver, stomach esophagus, and pancreas). Cohort was unique, but small 

and risk estimates are imprecise.”

• IARC Evaluation

o Cancer in humans:

Inadequate evidence for carcinogenicity of polybrominated biphenyls
o Cancer in experimental animals: 

Sufficient evidence for carcinogenicity of Firemaster FF-1

Limited evidence for PBB -153

inadequate for PBB-169, Firemaster BP-6

o Overall evaluation: PBB are probably carcinogenic to humans (Group 2A) on basis mostly of 

mechanistic similarities to PCB’s., also animal data

• NTP:

“Polybrominated biphenyls (PBBs) are reasonably anticipated to be human carcinogens based on 

sufficient evidence of carcinogenicity from studies in experimental animals”

Mention is made of the Hoque et al 1998 case-control student of exposure-level related increased in 

lymphoma and digestive-system cancers. Noted that other studies were uninformative. 

• SEM: Present in SEM, no link to cancers

• Since rated as “inadequate evidence” for Cancer in Humans, not included in list of 2A with 

limited evidence.

1,3-Propane sultone

• IARC monograph (https://monographs.iarc.who.int/wp-content/uploads/2018/06/mono110-

05.pdf) 2018 update

• Although the industrial use of 1,3-propane sultone was largely discontinued in the 1960s, it has 

been used more recently in the manufacture of lithium batteries, and for chemical synthesis in 

the laboratory. Workers involved in the formulation of compounds made from 1,3-propane 

sultone are at the greatest risk of potential exposure.

• Human carcinogenicity data:

Only one case series among 55 employees at a factory in Germany that manufactured 1,3-

Propane sultone in 1952-1963—number of expected cancers not presented, precluded 

interpretation of this study

• IARC Evaluation:

o Inadequate evidence in humans for carcinogenicity

o Sufficient evidence in experimental animals 

o Probably carcinogenic to humans (Group 2A)

Rationale -mechanistic in that 1,3 propane sultone is a strong, direct-acting alkylating 

agent that reacts with DNA and proteins, + genotoxic, and +experimental animal

• SEM: present, but no links to Cancer

• Since rated as “inadequate evidence” for Cancer in Humans, not included in list of 2A with 

limited evidence.

Glyphosate

• IARC monograph 112 (2015) https://publications.iarc.fr/549

• Herbicide widely used

• IARC: Evaluation

o Limited evidence in humans - + associations for non-Hodgkin Lymphoma

The evidence in humans is from studies of exposures, mostly agricultural, in the USA, 
Canada, and Sweden published since 2001. ARC Working group summarized the 

epidemiological data: case–control studies in the USA, Canada, and Sweden reported 

increased risks for NHL associated with exposure to glyphosate. The increased risk 

persisted in the studies that adjusted for exposure to other pesticides. The AHS cohort 

did not show an excess of NHL. The Working Group noted that there were excesses 

reported for multiple myeloma in three studies; however, they did not weight this 

evidence as strongly as that of NHL because of the possibility that chance could not be 

excluded; none of the risk estimates were statistically significant nor were they adjusted 

for other pesticide exposures." They also noted that there were no other significant 

associations with other cancers and exposure to glyphosate.

o Sufficient evidence in experimental animals

o Probably carcinogenic in humans (Group 2A) – because of strong evidence of 

genotoxicity in human invitro studies, experimental animals; also chromosomal damage 

in blood cells in a study of individuals exposed to glyphosate formulations

• SEM: Present, but no links to cancer; 

• Not listed under health effects: Lymphoma, Non-Hodgkin

• Include in list of 2A carcinogens with limited evidence in humans for specific cancer: nonHodgkin Lymphoma

Tetrafluoroethylene

• IARC monograph 110-02, update 6/2018 https://monographs.iarc.who.int/wpcontent/uploads/2018/06/mono110-02.pdf

• Occupational exposures to workers during primary manufacturing and later polymerization process

• IARC: Evaluation

o Inadequate evidence in humans for carcinogenicity

o Sufficient evidence in experimental animals

o Probably carcinogenic in humans (Group 2A) -absence of adequate data on cancer in 

humans or adequate mechanistic data, upgrade to 2A was based upon “unusual results” in 

animals: Tetrafluoroethylene induced neoplasms at multiple sites—cells of differing 

embryological origin, and also increase in rare liver haemangiosarcoma in mice even at 

lowest doses tested—implication that it is a potent carcinogen

• SEM: present in SEM, and no links to Cancer

• Since rated as “inadequate evidence” for Cancer in Humans, not included in list of 2A with limited 

evidence.

Malathion

• IARC monograph 112, meeting 2015, publication 2017 (https://publications.iarc.fr/Book-AndReport-Series/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans/SomeOrganophosphate-Insecticides-And-Herbicides-2017)

• Organophosphate insecticide – worker exposures during formulation, application

• IARC:evaluation

o Limited evidence in humans -positive associations observed with non-Hodgkin lymphoma 

and cancer of the prostate

Note: The evidence in humans is from studies of exposures, mostly agricultural,in the USA, 
Canada, and Sweden published since 2001. The IARC working group summarized the human 

epidemiological data: “ four case–control analyses found excesses of non-Hodgkin 

lymphoma associated with exposure to malathion in the USA, Canada, and Sweden, but no 

association with number of days of use was observed. In the Cross-Canada Case–control 

Study, there was an association with malathion, but in a pooled analysis of case–control 

studies in the USA there was little evidence of an association. No excess occurred in the 

Agricultural Health Study cohort.

o Sufficient evidence in experimental animals

o Probably carcinogenic in humans (Group 2) -based on mechanistic and other relevant datastrong evidence of several key characteristics of human carcinogen—genotoxic on studies in 

humans, in experimental animals, and in human and animal cells in vitro; also disrupted 

hormonal pathways; induces oxidative stress and other inflammation; other mechanisms

• SEM: In SEM, no mention cancer health effects

• Not listed under health effects: Lymphoma, Non-Hodgkin

• Include in list of 2A carcinogens with limited evidence in humans for specific cancer: Lymphoma, 

Non-Hodgkin

Diazinon

• IARC monograph, 112 (https://www.ncbi.nlm.nih.gov/books/NBK436774/)

• Diazinon is a wide-ranging organophosphate non-systemic insecticide, miticide, and nematicide. 

US- Currently used to control fire ants, and “plague infected fleas on squirrels -Used more in the 

past

• IARC evaluation

o Limited evidence in humans – positive associations for non-Hodgkin lymphoma, 

leukemia, and cancer of the lung

Note: IARC identified 9 reports from 3 cohort studies, and 14 reports on 6 case–control 

studies, that reported on associations between cancer and exposure to diazinon 

specifically. The IARC working group noted positive associations and exposure–response 

trends were noted for NHL, leukaemia, and cancer of the lung. Although studies 

reported on other cancers, IARC did not report increased risks for those cancers.

o Limited evidence in experimental animals

o Probably carcinogenic in humans (Group 2) -two key characteristics of human 

carcinogens: genotoxic from studies in experimental animals in vivo, and animal cell 

lines; human cell lines in vitro show chromosomal damage; positive results in study of 

small number volunteers; also can act to induce oxidative stress

• SEM: In SEM under different name: O,O-Diethyl-O-(2-isopropyl-4-methyl-6-pyrimidinyl) 

phosphorothioate. No mention of any cancers. 

• Diazinon not mentioned under health effects for Lymphoma, non-Hodgkin, cancer of the lung or 

leukemia

• Include in list of 2A carcinogens with limited evidence in humans for specific cancers: 

Lymphoma, Non-Hodgkin, cancer of the lung, and leukemia

Silicon carbide whiskers
• IARC monograph, 111 (https://www.ncbi.nlm.nih.gov/books/NBK436610/)

• Silicon carbide appears in two different crystalline forms: hexagonal α-silicon carbide is the main 

product, while cubic β-silicon carbide is formed at lower temperatures. Exposure to silicon 

carbide whiskers may occur during the manufacture of the whiskers or during the production, 

machining, and finishing of composite materials. Silicon carbide in fibrous and non-fibrous forms 

has been detected in occupational environments. Various forms of silicon carbide can comply 

with the WHO definition of a fibre (i.e. a particle longer than 5 μm with a diameter of less than 

3 μm and an aspect ratio of more than 3). “silicon carbide whiskers” specifically refers to 

monocrystalline forms produced at high cost for targeted high technology use.

• Inhalation is the primary route of exposure to fibrous silicon carbide in occupational settings. 

Exposures to both these respirable manufactured silicon carbide whiskers and silicon carbide 

fibres may occur during their production and the manufacturing, machining, finishing use of 

composite materials.

• Based on very limited evidence of fibrous silicon carbide; in Bugge et al. (2012), the standardized 

incidence ratio (SIR) for lung cancer in long-term workers (≥ 3 years of employment) was 1.6 

(95% CI, 1.3–2.1). Supported as well by evidence of similar structure to asbestos, known human 

carcinogen. However, working group considered fibers should be considered seperately from 

whiskers

• No data on cancer in humans exposed to silicon carbide whiskers was available for the IARC 

monograph 111. However, based on structural similarity to asbestos, a known human 

carcinogen, this structure was deemed a probable carcinogen in humans. In addition, available 

mechanistic studies were consistent with this conclusion.

• IARC working group considered fibers should be considered separately from whiskers

• Related chemical found in SEM, "Silicon Carbide Cas 409-21-2", but not associated with lung 

cancer in the SEM

• Include in list of 2A carcinogens with limited evidence in humans for specific cancers: Cancer of 

the lung

Dichloromethane

• IARC monograph, 110 (https://www.ncbi.nlm.nih.gov/books/NBK436263/)

• Dichloromethane is used for a variety of purposes and products including the making of 

polycarbonate plastics, paint stripping, metal cleaning, aerosol propellants, and synthetic fibres.

• Dichloromethane was classified as probably carcinogenic to humans (Group 2A) on the basis of 

limited evidence that it causes biliary-tract cancer and non-Hodgkin lymphoma in humans; 

coupled with strong evidence that the genotoxicity is mediated by GSTT1 metabolism that does 

occur in humans.

• These findings of carcinogenicity were corroborated with experimental animal model findings in 

rodents (mice)

• Chemical found in SEM, but no cancers associated in the SEM.

• Include in list of 2A carcinogens with limited evidence in humans for specific cancers: biliarytract cancer and Non-Hodgkin lymphoma

DDT (otherwise known as (4,4'-dichlorodiphenyltrichloroethane)
• IARC monograph, 113 (https://www.ncbi.nlm.nih.gov/books/NBK507424/)

• DDT has been widely used as an insecticide, use was banned in the 1970s, but due to 

persistence in the environment exposures still occur mostly via dietary routes.

• Associations between cancer and exposure to DDT have been investigated in more than 100 

cohort and case-control studies from diverse countries. Those associated include liver, 

testicular and NHL, but not breast.

• These findings of carcinogenicity were corroborated with experimental animal model findings in 

rodents (mice, rat and hamster)

• Chemical found in SEM, but no cancers associated in the SEM.

• Include in list of 2A carcinogens with limited evidence in humans for specific cancers: liver 

cancer, testicular cancer, Non-Hodgkin Lymphoma

2-Mercaptobenzothiazole

• IARC monograph, 115 (https://www.ncbi.nlm.nih.gov/books/NBK506754/)

• 2-Mercaptobenzothiazole is principally used as a reactant in the manufacture of rubber 

products, but is also used as a corrosion inhibitor in oils, greases and cooling fluids. It is added to 

polyether polymers as a stabilizer to resist damage by air and ozone. 2-mercaptobenzothiazole 

can be found as a contaminant in rubber products. 

• An English/Welsh population and USA chemical plant study found significant association for 

incidence or mortality from bladder cancer.

• These findings of carcinogenicity were supported with experimental animal model findings in 

rodents (mice and rat)

• Chemical found in SEM, but no cancers associated in the SEM.

• Include in list of 2A carcinogens with limited evidence in humans for specific cancers: bladder 

cancer

Hydrazine

• IARC monograph, 115 (https://www.ncbi.nlm.nih.gov/books/NBK506754/)

• Hydrazine is utilized as rocket propellant and aircraft fuel. In its hydrated form, hydrazine 

(solutions with concentrations ranging from 0.01% to 100%) serve as a reagent for the 

treatment of nuclear reactor wastes. 

• Two studies on overlapping cohort, outcome of incidence or mortality found association with 

lung cancer among workers based on facility history. Further humans rapidly absorb and 

metabolize hydrazine

• These findings of carcinogenicity were supported with experimental animal model findings in 

rodents (mice, rat and hamster). Mechanistic studies support these conclusions as well via 

evidence of oxidative stress, genotoxicity, and altered nutrient supply.

• Chemical found in SEM, but no cancers associated in the SEM.

• Include in list of 2A carcinogens with limited evidence in humans for specific cancers: cancer of 

the lung
N,N-Dimethylformamide

• IARC monograph, 115 (https://www.ncbi.nlm.nih.gov/books/NBK506754/)

• N,N-Dimethylformamide is used predominantly as an aprotic solvent in the manufacture of 

polyacrylonitrile fibres, and trends in its production parallel those of the polyacrylic fibre 

industry. 

• Two studies in specific aircraft repair workers and one with leather workers found increased 

incidence of testicular cancer. It is readily absorbed in humans.

• These findings of carcinogenicity were supported with experimental animal model findings in 

rodents (mice and rat). Mechanistic studies show N,N-Dimethylformamide induced oxidative 

stress and induces formation of adducts of the valine and lysine amino acids in human globin 

and in other contexts with cytosine. 

• Chemical found in SEM, but no cancers associated in the SEM.

• Include in list of 2A carcinogens with limited evidence in humans for specific cancers: testicular 

cancer

Tetrabromobisphenol A

• IARC Monograph 115. 

• It is a flame retardant reviewed 

• No human epidemiologic data were available to IARC in 2016 on carcinogenicity of TBBPA. It was 

classified as 2A probably carcinogenic in humans based on strong evidence that 

tetrabromobisphenol A demonstrates 3 “key” mechanistic characteristics of human carcinogens 

(Guyton et al, 2018), that it modulates receptor-mediated effects, induces oxidative stress and is 

immunosuppressive. There is sufficient evidence in experimental animals (male mice and female 

rats) for the carcinogenicity of tetrabromobisphenol A.

• Since rated as “inadequate evidence” for Cancer in Humans, not included in list of 2A with 

limited evidence.

Styrene

• Reviewed IARC Monograph 121 

• Finds limited evidence in human epidemiologic studies of increased risk of 

lymphohaematopoietic malignancies. Evidence was stronger and more consistent for AML and 

T-cell lymphoma, weaker and less consistent for other leukemia and lymphoma subtypes 

because case numbers were limited and effect estimates were small with low precision (wide 

confidence intervals). Evidence for lung cancer and other solid tumors was judged not 

convincing. Epidemiologic evidence was summarized as credible for lymphohaematopoietic

malignancies, but co-exposure to 1,3 butadiene, and confounding, bias and chance could not 

be ruled out as alternative explanations. Evidence for carcinogenicity in animal studies was 

judged sufficient with tumors of lung and mammary gland most commonly reported. Some of 

the mechanistic evidence for carcinogenicity was judged strong, including genotoxicity in 

human cell culture, however specific mechanistic events for lung tumor induction in mice were 

not considered established. 

• Chemical found in SEM but not associated cancers. 

• Styrene not listed under leukemia, lymphoma.
• Limited evidence in humans for lymphohaematopoietic malignancies

• Include in list of 2A carcinogens with limited evidence in humans for lymphohaematopoietic 

malignancies

Styrene-7,8-oxide 

• Reviewed IARC Monograph 121

• The chemical is closely related to, and a human metabolite of, Styrene. IARC considered 

evidence of human carcinogenicity of styrene-7,8-oxide to be inadequate. They classified 

styrene-7,8-oxide as “probably carcinogenic to humans” (Group 2A) based on sufficient 

evidence of carcinogenicity in experimental animals and strong evidence that styrene-7,8-oxide, 

an electrophile, forms DNA adducts and is genotoxic, a mechanism that also operates in 

humans. 

• Since rated as “inadequate evidence” for Cancer in Humans, not included in list of 2A with 

limited evidence.

• SEM, no list of any cancers 

3,3′,4,4′-Tetrachloroazobenzene (TCAB)

• Reviewed in IARC Monograph 117

• They did not identify any human epidemiologic studies of carcinogenicity of TCAB. TCAB was 

classified as 2A because of sufficient evidence of carcinogenicity at multiple sites in animals, 

and mechanistic considerations. It belongs to a class of agents that activate the Aryl 

Hydrocarbon Receptor AhR, and some members of this class have previously been 

evaluated as Group 1 or Group 2A carcinogens. 

• SEM: not listed

• Since rated as “inadequate evidence” for Cancer in Humans, not included in list of 2A with 

limited evidence.

Aldrin and its metabolite dieldrin

• Reviewed in IARC Monograph 117. 

• Aldrin is a synthetic organochlorine pesticide that rapidly metabolized in humans to dieldrin, 

which is sequestered in fat and slowly excreted. One epidemiologic study of dieldrin in Denmark 

reported increased risk of breast cancer with a dose response. A similar but smaller study in 

Norway did not find a significant increase. Associations of breast cancer risk with dieldrin 

exposure were reported wives of men who had used dieldrin in a US agricultural study, and in 

the highest exposure category of a case control study in Long Island. Evidence of breast 

carcinogenicity in humans was considered limited. Evidence for non-Hodgkin lymphoma and 

other cancers in humans was considered insufficient. Evidence of hepatocellular carcinogenicity 

in animals was considered sufficient and mechanistic studies provided moderate evidence for 

multiple key characteristics of carcinogens. So dieldrin is classified as 2A with breast as the best 

supported cancer site. Human epidemiologic data on carcinogenicity of aldrin were considered 

insufficient in the 2016 IARC review, mechanistic evidence was sparse, however evidence of 

carcinogenicity of aldrin in animal studies was considered sufficient. 

• IARC summary evaluation:

o There is inadequate evidence in humans for the carcinogenicity of aldrin.
o There is limited evidence in humans for the carcinogenicity of dieldrin. 

A positive association has been observed between dieldrin and cancer of the breast

o There is sufficient evidence in experimental animals for the carcinogenicity of aldrin and 

dieldrin

• IARC: Because aldrin is rapidly metabolized to dieldrin in humans and experimental animals, 

exposure to aldrin always leads to internal exposure to dieldrin

• SEM: both are present, but no link to breast cancer

• Breast cancer is not listed in SEM at all

• Include Dieldrin (and necessarily aldrin which metabolizes to dieldrin in list of 2A carcinogens 

with limited evidence in humans for specific cancers: Cancer of the breast

Glycidyl methacrylate

• Reviewed in IARC Monograph 125

• Glycidyl methacrylate is an intermediate used in production of epoxy polymers and vinyl and 

acrylic resins. 

• Human epidemiologic evidence of carcinogenicity was considered inadequate. Evidence of 

carcinogenicity in animal studies was considered sufficient. Mechanistic evidence was 

considered strong because “glycidyl methacrylate belongs to to a class of compounds (reactive 

glycidyl epoxides), a member of which (glycidol) has been classified as “probably carcinogenic 

to humans”. This determination was based on structural similarity to other glycidyl epoxides 

and the close concordance to glycidol with respect to the genotoxicity profile and the tumoursite profile in chronic animal bioassays.” (IARC, Lancet Oncology, 2019) Glycidyl methacrylate 

was classified as 2A primarily on this basis. 

• SEM: not listed in the SEM

• Since rated as “inadequate evidence” for Cancer in Humans, not included in list of 2A with 

limited evidence.
Table 1: Group 2A Carcinogens with Limited evidence in humans for cancers

2A Carcinogen Description Associated Cancers SEM Status

Glyphosate

(“Roundup”)

Herbicide-widely used Non-Hodgkin 

Lymphoma

Present in SEM

No Diseases (or 

cancers) listed in HazMap

Malathion Organophosphate 

insecticide

Non-Hodgkin 

Lymphoma; 

Cancer of the 

Prostate

Present in SEM

No associated cancers 

listed

Not listed under 

Lymphoma, NonHodgkin

Diazinon Organophosphate 

insecticide, miticide, 

and nematicide

Non-Hodgkin 

Lymphoma

Leukemia

Cancer of the Lung

Present in SEM as 

Haz-Map name:

O,O-Diethyl-O-(2-

isopropyl-4-methyl-6-

pyrimidinyl) 

phosphorothioate

No associated Cancers 

listed

Dichloromethane

(Methylene Chloride)

Solvent Biliary-Tract Cancer

Non-Hodgkin 

lymphoma

Present in SEM

No associated cancers 

listed

DDT 

4,4'-

dichlorodiphenyltrichloroethane

Insecticide Liver Cancer

Testicular Cancer

Non-Hodgkin 

Lymphoma

Present in SEM

No associated cancer 

listed

Not listed under Liver, 

Lymphoma-NonHodgkin; no testicular

2-Mercaptobenzothiazole Organosulfur 

compound used in the 

sulfur vulcanization of 

rubber

Urinary bladder 

cancer

Present in SEM

No associated cancer 

listed

Not listed under 

Bladder Cancer

Hydrazine Used in 

polymerization; 

precursor to pesticides 

and pharmaceuticals, 

other reactions

Lung Cancer Present in SEM

No associated cancer 

listed

Not listed under Lung 

Cancer
Table 1 Continued: Group 2A Carcinogens with Limited evidence in humans for cancers

2A Carcinogen Description Associated Cancers SEM Status

N, N-Dimethylformamide Solvent (used in mfg fo 

polyacrylonitrile fibers, 

polyurethane and 

polyamide coatings, 

electronics, other)

Testicular Cancer Present in SEM

No associated cancer 

listed

Styrene Lymphohematopoietic malignancies

(stronger and 

more consistent 

for AML and T-cell 

lymphoma)

Present in SEM

No associated Cancer 

listed

Styrene not listed 

under leukemia, 

lymphoma, or Lung 

cancer

Aldrin and its metabolite 

dieldrin

[Inadequate evidence for 

aldrin, but limited evidence 

for its metabolite dieldrin]

Synthetic 

organochlorine 

pesticides

Cancer of the Breast Present in SEM

No associated Cancer 

listed in Haz-Map

Breast Cancer not 

listed in SEM

Silicon Carbide “Whiskers” “Silicon carbide 

whiskers are 

monocrystalline and 

homogeneous in form, 

while fibrous silicon 

carbide is mostly 

polycrystalline and 

heterogeneous in 

form”. Given 

differences in 

physiochemical 

properties-Separate 

evaluation for “fibers” 

and “whiskers”

Lung Cancer Present in SEM

No associated cancer 

listed

Not listed under Lung 

Cancer
 Table 2: Cancers and Group 2A Carcinogens To Be Added to SEM

CANCER TYPE 2A Carcinogen*

Lung Cancer Hydrazine

Diazinon

Silicon Carbide “Whiskers”

Lymphoma, Non Hodgkin DDT

Diazinon

Dichloromethane

Glyphosate

Malathion

Styrene

Leukemia Diazinon

Lymphohematopoietic Styrene

Testicular Cancer

(need to add)

DDT

N, N-Dimethylformamide

Bladder Cancer 2-Mercaptobenzothiazole

Breast Cancer (need to add) Dieldrin (metabolite of Aldrin)

Liver Cancer DDT

Biliary Tract Cancer Dichloromethane
Advisory Board on Toxic Substances and Workers Health

Recommendation on COVID-19 as a Consequential Condition in EEOICP

The Board recommends that any chronic health condition or risk factor that is listed by the US Centers 

for Disease Control and Prevention (CDC) as being associated with severe COVID-19 disease by metaanalysis, systematic reviews, cohort studies, case control studies, cross sectional studies, case 

cases/series or mixed evidence be considered to be presumed to be more likely to lead to symptomatic 

COVID -19 disease. That is, the diagnosis of symptomatic COVID-19 disease is a consequence of those 

chronic health conditions when it follows or coincides with the onset of those conditions. The Board 

recognizes the need to periodically review (at a minimum, annually) and update this recommendation 

based on the evolving scientific and medical knowledge on this topic.

Rationale

The Department of Labor requested that the Board provide guidance on the types of medical conditions 

that may be accepted as claims under the Energy Employees Occupational Illness Compensation 

Program (EEOICP) that may, as a matter of consequence, increase the likelihood or severity of COVID-19 

disease. 

The US Centers for Disease Control has assembled and evaluated the published evidence on what 

chronic medical conditions may impact the risk of severe COVID-19 disease. This list and the supportive 

evidence were updated and published on the CDC website on March 29, 2021, making it very timely. See 

https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/underlying-evidence-table.html 

The CDC-listed conditions most relevant to EEOICP claims include: cancer, cerebrovascular disease, 

chronic kidney disease chronic obstructive pulmonary disease (COPD), asthma, other chronic lung 

disease (including interstitial lung disease, pulmonary fibrosis, pulmonary hypertension), neurologic 

conditions, heart disease, use of corticosteroids or other immunosuppressive medications, 

hypertension, liver disease, hypertension and diabetes. Details about specific type of diseases and the 

studies supporting their COVID-19 associations are provided by the CDC. The CDC lists additional health 

conditions (such as cystic fibrosis, Type 1 diabetes, and sickle cell disorders) as related to severe COVID19 disease, but these conditions are not or are unlikely to be the subject of successful EEOICP claims.

The cited health conditions increase the severity of COVID-19 disease. That is, studies of people with 

severe COVID-19 disease (usually defined as hospitalization or death) find a statistically significant high 

proportion or rate with one or more of the above-listed chronic diseases or conditions. The Board is 

unable to identify a similar scientific literature that examines the risk of mild COVID-19 disease (treated 

as an outpatient or not needing treatment) with relation to underlying medical conditions. However, the 

Board deems the existing literature about severe COVID-19 disease, to the extent that it has been 

studied, to be well-supported and believes that it is likely that the aforementioned chronic medical 

conditions increase the symptomatic expression of SARS CoV-2 infection at any level of symptoms. Or, 

to use an example that addresses the issue more directly, a person with COPD who becomes infected 

with the SARS CoV-2 virus will be more likely to have symptoms and require medical attention, even if 

the disease is mild, than a comparable person without COPD. Most of the chronic medical conditions 
that are associated with severe COVID-19 disease are cardiopulmonary diseases or their risk factors, so 

it is highly plausible, as in the case of COPD, that persons with such conditions are more likely to be ill if 

they acquire the SARS CoV-2 infection and thereby miss work or incur medical expenses, raising issues 

relevant to EEOICP claims.

The Board recognizes that knowledge about COVID-19 disease is substantial but incomplete and that 

much will be learned in the coming years about this disease. We therefore recognize the need to 

periodically review and update this recommendation based on the evolving scientific and medical 

knowledge on this topic.

The Board recommends that symptomatic COVID-19 disease be recognized as a consequence of relevant 

EEOICP-claimed conditions that correspond to the CDC-supported list of such conditions provided 

above.
1

Advisory Board on Toxic Substances and Workers Health

Recommendation on Asbestos Presumptions 

The Advisory Board on Toxic Substances and Workers Health recommends that:

1. The Department of Labor and contractor Paragon Technical Services (PTS) should re-evaluate 

the job titles of Chemical Engineers, Industrial, Health, & Safety Engineers, and Mechanical 

Engineers and add these titles to the list of occupations presumptively exposed to the asbestos 

under EEOICP.

2. We request access to the Generic Profiles, including the Asbestos Generic profile, as cited in the 

PTS report.

3. We recommend that DOL clarify how DOE jobs that correspond to the job title “Maintenance 

and Repair, General Helper” are classified within the SEM and whether they are linked to 

asbestos exposure. 

Rationale

These comments reflect the continued discussion between the Board and the Department of 

Labor concerning the use of asbestos presumptions by the EEOICP.

1. We are pleased that Paragon Technical Services, Inc. (PTS) agrees that four important job titles 

should be added to Exhibit 15-4 of DEEOICP PM 4.3 (p. iii).

2. We agree with the opinion of PTS that three selected job titles have no relevance to DOE (p. iii).

3. We note that the PTS report refers to Generic Profiles (p. 2). We request access to these 

profiles.

4. We note that there is an Asbestos Generic Profile (cited on p. 2 of PTS report) that addresses

asbestos exposure of certain work processes associated with job titles, including Janitorial 

activities, Laundry, Power/Communication line maintenance. These job titles are not listed in 

Exhibit 15-4 of DEEOICP PM 4.3. We request the Asbestos Generic profile in order to understand 

how asbestos exposure is addressed for these work processes/job.

5. The PTS report argues against presumptive asbestos exposure for some occupations identified in 

the National Occupational Mortality Surveillance (NOMS) as having excess mesothelioma risk on 

various rationales: 1) asbestos does not appear for the occupation in the SEM; b) some job titles 

in NOMS encompass work in diverse industries that may have limited and uncertain relevance 

to work at DOE sites; c) some job titles may not have widespread exposure to asbestos across 

many job settings; or d) the occupations are infrequent at DOE. These points make sense, 
2

subject to the caveats discussed below. PTS suggests that DOL review the death certificates from 

the NOMS for these job categories, which may be challenging due to data privacy issues and is 

unlikely, in the instances when the numbers of deaths are limited, to provide definitive answers. 

We do not recommend pursuing the review of NOMS death certificates.

Malignant mesothelioma (MM) is a very uncommon cause of death, even in industries and 

occupations where asbestos was routinely used. The notion that asbestos exposure in a limited 

subpopulation of a Standard Occupational Classification (SOC) occupational category confined to 

one or a small number of industries where the specific SOC is active is responsible for an 

elevated mesothelioma Proportionate Mortality Ratio (PMR) becomes less tenable when a) the 

Proportionate Morality Ratio (PMR) is substantially elevated (PMR> 250), and/or b) the numbers 

of deaths are considerable (> 30). Reviewing the NOMS PMR output provided in Table 3 of our 

recommendation, occupations meeting these criteria include: Chemical Engineers (PMR = 449; # 

MM deaths = 30); Industrial, Health, & Safety Engineers (PMR = 259; # MM deaths = 30) and

Mechanical Engineers (PMR = 250; # MM deaths = 50). We believe that PTS should re-consider 

the issue of presumptive asbestos exposure for these three occupations.

One of the reasons that PTS cites for not linking asbestos exposure to certain job categories is 

the failure of asbestos to appear in the SEM as a potential exposure for those occupations. It is 

uncertain if the SEM routinely recognizes bystander exposures, raising the question about 

whether the SEM can be expected to reliably link asbestos exposure to occupations whose only 

exposure was bystander in nature. This may well apply to the 3 job categories cited above: 

chemical and mechanical engineers and health and safety engineers. It seems quite likely that 

documentation provided by the DOE and, thus, the SEM, would not address bystander 

exposures.

We recommend that PTS re-examine the issue of presumptive asbestos exposure for Chemical 

Engineers, Industrial, Health, & Safety Engineers, and Mechanical Engineers.

6. The logic behind the rejection of “Maintenance and Repair, General Helper” as presumptively 

asbestos-exposed is unclear, since most maintenance workers and repair workers whom the 

general helpers assist will now be covered in the enlarged list of Exhibit 15-4. The SEM doesn’t 

appear to have this job title at many DOE sites. Are they considered by claims examiners as part 

of the maintenance workers and repair workers whom they assist? Or are they placed in a 

general category of “laborer”? If the latter, are they included in Exhibit 15-4?
1

Advisory Board on Toxic Substances and Workers Health

Recommendation on the Use of the Six Minute Walk Test in Impairment Evaluations

The Advisory Board on Toxic Substances and Workers Health recommends the following:

1. The Board advises that the 6MWT is an entirely acceptable to measure the VO2max for the 

purposes of impairment assessment. 

2. The best valid and available method to estimate a value of VO2max from the 6MWD for 

application in Table 5-12 of the AMA Impairment Guide is to use the equation derived by 

Ross et al (2010):

 Peak VO2 (ml / kg /min) = 4.948 + 0.023*6MWD (meters)

Rationale

The Department of Labor has requested assistance in answering the following questions:

We revised the questions very slightly and provide the following responses.

1. What are the permissible testing methodologies that a physician may use in assigning a VO2max 

for application in Table 5-12 of the Guides?

In the opinion of the Board, the permissible testing methodologies that a physician may use to assign a 

VO2max to an individual patient for application in Table 5-12 of the Guides include two types:
2

a. Direct measurement of VO2max or VO2peak, a satisfactory estimate of VO2max, in a 

pulmonary function laboratory that is experienced in performing Cardio-Pulmonary Exercise 

Tests (CPET) using a treadmill or cycle ergometer.

b. The 6 Minute Walk Test (6MWT) along with a regression equation to estimate VO2peak for 

application in Table 5-12 of the Guides.

A. CPET

Direct measurement of VO2max, or in many cases VO2peak, is the preferred method if the 

following conditions are met: a) an appropriately equipped and experienced exercise testing laboratory 

is readily available, b) the patient meets the pre-CPET medical clearance requirements (i.e., is well 

enough to undergo such testing and there are no medical contraindications), c) payment for the CPET 

(which is expensive) is covered. These conditions may or may not be achievable in practice. 

CPET-based measurement of VO2max is considered the “gold standard” of aerobic capacity and 

cardiorespiratory and pulmonary fitness assessment (American Thoracic Society; American College of 

Chest Physicians, 2003). The direct measurement of VO2max by CPET has also been proposed as a gold 

standard for measurement of impairment due to pulmonary disorders (Sood, 2014) and for that 

purpose, it is complementary to, but better than, at-rest pulmonary function testing including DLCO. In 

his review, Sood noted that resting PFTs and CPET for evaluating impairment due to occupational lung 

diseases often yield discrepant results. One of the classic textbooks of exercise testing, Wasserman and 

Whipp’s Principles of Exercise Testing and Interpretation, 6th edition (Sietsema, 2021) concurs with this

and provides more details, emphasizing the high frequency of indeterminate and inaccurate impairment 

decisions based on PFTs alone. In a study of 348 asbestos-exposed shipyard workers (Oren, 1987), the 

combination of history, physical examination, chest X-ray, resting electrocardiogram, and resting PFTs 

(including DLCO), performed poorly in predicting dichotomous work capacity status (impaired vs not 

impaired) using those variables plus CPET. The initial work capacity determination without CPET was 

indeterminate in 134/348 subjects, 39% of the total group. Among the remaining 214 subjects, it was 

erroneous for 22/66 (33%) of cases initially classified as impaired and for 44/148 (30%) of cases who 

were initially classified as not impaired. Of the indeterminate group, 49/134 (37%) were ultimately 

found to be impaired by CPET, and 81/134 (60%) were unimpaired. Only 5 (1.4%) of the total group 

remained as indeterminate impairment status after the CPET. The authors concluded that exercise 

testing was advantageous for accurate assessment of work capacity in impairment evaluations.

In that study, impairment was due to cardiovascular disease in 69% of those found to be impaired, 

though the assessment of cardiovascular disease was not confirmed by measurements of ejection 

fraction or other additional cardiovascular testing. This explains some of the inaccuracy of the PFTs in 

predicting impairment since some of the subjects with impairment due to cardiovascular disease would 

have had normal PFTs. It does not explain the high frequency of indeterminate impairment status based 

on PFTs, especially the 60% of the indeterminate group found to be unimpaired by CPET. It is important 

to note that the CPET, ideally a maximal effort test, would yield a VO2peak rather than a VO2max in most 

or all patients with significant lung disease since they can rarely achieve the maximal anaerobic level of 

exertion needed to generate a true VO2max.

Measuring VO2max requires achieving a plateau in oxygen intake vs work rate graph, i.e., a 

maximal anaerobic level of effort beyond which even with a further increase in power output the 
3

muscles cannot metabolize more oxygen and rely on anaerobic ATP-based metabolism. This is often 

clinically contraindicated or unachievable in patients with lung disease or other comorbidities like heart 

disease. In these common situations, VO2peak measurement has been shown to be a valid index of 

VO2max (Day, 2003) and is often used interchangeably (Singh, 2014).

The CPET laboratory requires personnel trained specifically in CPET, which is beyond the routine 

training of pulmonary function laboratory technicians. The American College of Sports Medicine (ACSM) 

lists cognitive skills required of personnel supervising the test as well as medical contraindications to the 

CPET and conditions requiring physician supervision. It is recommended by the ACSM that the person 

doing the test has performed at least 50 (Rodgers, 2000) tests in the past, and more recently

recommended 200 tests in the past (Myers, 2014) and continues to perform 25 to 50 tests per year to 

maintain competency (Liguri (ACSM), 2021, p. 115-117). It is our impression, without hard data, that 

many otherwise available PFT laboratories near where claimants live may not meet these minimal 

criteria, and, therefore, CPET may not be accessible for some claimants. Therefore, there is a need for a 

second line test to estimate VO2max for the purpose of classifying impairment in patients with lung 

disease.

B. Six Minute Walk Test 

If CPET is not available or feasible for a given claimant, in the opinion of the Board, the Six 

Minute Walk Test (6MWT) would be the best available method for estimating VO2max in patients with 

medical impairment due to pulmonary disease, such as those applying for compensation. The 6MWT has 

been well studied for patients with a variety of lung disorders and is reported to have acceptable 

repeatability, reproducibility, safety and precision to predict mean VO2max of a group (Singh, 2014; 

Sood, 2014; Ross, 2010; Cahalin, 1995). The evidence was systematically reviewed by the European 

Respiratory Society / American Thoracic Society (ERS/ATS) in 2014 (Singh 2014). These same Societies 

also published an official Technical Standard on how the 6MWT should be performed in patients with 

chronic respiratory disease (Holland 2014).

The ERS/ATS systematic review concluded that the 6MWT is a valid, reliable, and “robust test of 

functional exercise capacity in adults with chronic respiratory disease.” The review also concluded that 

the relationship between 6MWD and either VO2peak or peak work on a progressive incremental 

Cardiopulmonary Exercise Testing (CPET) was moderate to strong and was consistent across patient 

groups with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). Seven out 

of eight studies of patients with COPD or ILD compared the VO2 peak as estimated by the 6MWT versus 

the CPET and found no significant differences between the two testing techniques. Review of 35 studies 

of people with chronic lung disease showed a consistent association between results of the 6MWT and 

mortality and hospitalization. 6MWT results are associated with oxygen desaturation in many patients, 

and several studies showed that it was more sensitive than CPET in detecting such exercise-associated 

desaturation. The authors conclude that “The 6MWT has historically been considered to be a test of 

submaximal exercise capacity, however, direct comparisons of the physiological demands of the 6MWT 

and CPET reveal that, in patients with chronic respiratory disease, measures of peak exercise 

performance are similar between the tests.” (Singh, 2014, p. 1469).

The 6MWT measures peak VO2, (VO2peak), which provides acceptable estimates of VO2max 

when VO2max is not clinically advisable or achievable. As for the CPET, the 6MWT would generally yield 

a VO2peak rather than a VO2max in most or all of these patients since individuals with significant lung 

disease can rarely achieve the maximal anaerobic level of exertion needed to generate a true VO2max. 
4

Dale and colleagues studied the 6MWT versus the incremental cycle test in 25 people with asbestosrelated pleural disease and found that 6MWD correlated with peak work rate (r=0.58, p=0.002). They 

concluded that “6MWT may be a useful surrogate measure of peak exercise capacity and physical 

activity levels in the absence of cardiopulmonary exercise testing” (Dale, 2013).

The 6MWT is a field test that is widely available, does not require specialized equipment, and 

can be performed safely in a typical medical office setting by most patients with pulmonary or cardiac 

compromise. The accuracy of estimation of VO2max provided by the VO2peak from the 6MWT is 

adequate for the determination of medical impairment. It is important to note that both the 6MWT and

the CPET reflect a number of different functional domains, including respiratory, cardiac, peripheral 

vascular, neurologic and musculoskeletal functionality. For this reason, determination of whether 

impairment is due to chronic respiratory disease versus other causes requires a clinical decision by the 

examining physician that impairment is not due to significant disease of other organ systems.

Eaton et al tested 30 people with pulmonary fibrosis with the 6MWT and incremental exercise 

treadmill testing and found an excellent and highly significant (“striking”) correlation (r=0.78, p<0.0001) 

between treadmill VO2max and results of the 6MWT (Eaton, 2005). Within-subject-reproducibility on 

repeat testing was far better for the 6MWT distance (r=0.98, SD/mean=0.042) than for the VO2max 

(r=0.88, SD/mean=.105). They concluded that the 6MWT is superior to maximal exercise testing based 

on the former’s higher reproducibility. 

The ERS/ATS Technical Standard published by Holland et al. (2014) provides standardized 

instructions and quality assurance procedures for 3 field walking tests in chronic respiratory diseases, 

the 6MWT, the Incremental Shuttle Walk Test (ISWT) and the Endurance Shuttle Walk test (ESWT). All 3 

tests produce results similar to those from the CPET; however, in the view of the Board, the 6MWT is 

more feasible to perform in typical medical settings than the other field walking tests reviewed. The 

ESWT requires the ISWT as a prerequisite and the ISWT requires much more detailed monitoring and 

technician training during the test than the 6MWT. As discussed in the next section, a reasonable 

equation is available to estimate VO2peak from the 6MWT but not from the ISWT or ESWT.

So, in the opinion of the Board, if the CPET is not available, affordable or suitable, the 6MWT as 

described in the ERS/ATS official technical standard (Holland, 2014) is a permissible testing methodology 

that a physician may use in assigning a VO2max for application in Table 5-12 of the Guides.

2. If the 6MWT is a valid methodology for assigning a VO2max for application in Table 5-12, should the 

evidence document that the test conforms with any particular medical standard in validating the test 

outcome? Also, what are acceptable methods for calculating the VO2max from a validated 6MWT 

result?

In the opinion of the Board, yes, the evidence should document that the 6MWT was performed 

according to the ERS/ATS official Technical Standard (Holland, 2014). The authors of that standard 

reported that the 6MWT demonstrates good construct validity as a test of functional exercise 

performance, has good test-retest reliability with evidence of a learning effect between first and second 

test, elicits a VO2peak that is similar to that produced by a CPET, and has similar precautions and

contraindications to the CPET. They note that the test is sensitive to variations in methodology including 

use of encouragement, provision of supplemental oxygen, changes in track layout and length, and use of 

wheeled walkers and recommended strict adherence to the recommended protocol for performing the 

6MWT. They also recommended that clinically significant heart disease and musculoskeletal limitations 
5

be factored into the results of the 6MWT for assessment of respiratory status. The recommendation to 

perform two 6MWT because of the learning effect is for use of the test in serial assessment of change 

over time, for example, to assess progress during a program of pulmonary rehabilitation. On p. 1431, 

Holland et al state, however, that, “Where the 6MWD is used as a one-off measure to stage disease or 

assess risk (e.g. likelihood of hospitalization or mortality), the magnitude of the learning effect may be 

less important and one test may be sufficient.” Performing the test twice would require sequential 

6MWT tests on different days and, given the statement in the Holland review, may not be necessary for 

a one time use of the 6MWT to assess impairment after maximal medical improvement.

To estimate VO2max from the 6MWT requires a statistical methodology derived from study of a 

large number of subjects. In the opinion of the Board, the best available method which is medically 

acceptable is to use the equation published by Ross et al in 2010 to estimate the VO2peak in an 

individual patient. This equation is stated in the article as:

 Peak VO2 (ml / kg /min) = 4.948 + 0.023*Mean 6MWD (meters)

This regression equation was derived from pooled data taken from 11 studies conducted 

between 1996 and 2006 including a total of 1,083 patients with diverse cardiopulmonary disorders. The

equation is presented to calculate the mean VO2peak in a group from the mean 6MWD in that group.

Although the structure of the equation is the same as would be used to calculate the VO2peak for an 

individual from that individual’s 6MWD, the authors reported that the Standard Error of the Estimate 

(SEE) for the individual calculation was 3.82 ml/kg/min and that is too large, i.e., would produce an 

estimate with wide confidence intervals for an individual. Examining the plots of the regression 

equations for the whole data set and several of the component sub-studies, we have not found evidence 

that using the equation for individual patients would systematically over- or under-estimate the 

VO2peak values calculated from the 6MWD values for those patients. So we do not expect that the point 

estimates of VO2peak produced by using this equation would be biased, just that the confidence 

intervals would be larger than we would like. This is the largest pooled dataset available to derive such a 

regression equation.

In contrast, the ACSM regression equation provided by DOL is not as good a candidate for use in 

this setting. That equation, intended for use in sports medicine, appears unchanged in the ACSM text 

from the 6th edition through the current 11th edition (issued this month). Its derivation has limited 

documentation but appears to be based on just two older studies of 3 and 10 young (<45 years old) 

athletic (VO2max 35-58 ml kg-1 min-1) subjects (Dill, 1965; Nagle, 1971). One of the 3 subjects in the first 

study was a world class marathon runner, the other 2 were healthy athletes. In contrast, the Ross study 

combined data points from a total of 1,083 subjects with pulmonary and cardiac disease in the 11 

studies to derive the equation given above. So in the opinion of the Board, if the 6MWT is used, the 

VO2peak should be calculated from the 6MWD using an equation derived from that in Ross et al:

VO2peak (ml per minute per kg) = 4.948 + 0.023 * 6MWD (meters)

Conclusion and Board recommendations

In conclusion, the preferred method of assigning VO2max to an individual claimant with 

pulmonary disease for application in Table 5-12 of the Guides is direct measurement of VO2max or, 

more likely, VO2peak using the CPET. If CPET is not available, the 6MWT is the next best method and is 

entirely acceptable. For this purpose, it is more reliable, less likely to generate indeterminate results, 
6

and more likely to accurately classify impairment than PFTs alone. It is important to confirm the 

respiratory disease diagnosis using PFTs and/or other clinical information. A clinical judgment will be 

required to rule out or properly apportion the contribution of cardiac, musculoskeletal or neurologic 

causes of impairment as determined with either the CPET or 6MWT. The valid methods of performing 

the 6MWT are those described in the ERS/ATS standard paper (Holland, 2014). The equation derived by 

Ross et al (Ross, 2010), although less precise for use in individual claimants than we would like, does not 

appear to systematically overstate or understate the level of impairment and is far better supported 

with research data than the ACSM equation for estimating the VO2max from the 6MWT in people with 

respiratory disease.

References

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3. Sietsema KE, Sue DY, Stringer WW, Ward SA. Wasserman and Whipp’s Principles of Exercise 

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4. Oren A, Sue DY, Hansen JE, Torrance DJ, Wasserman K. The role of exercise testing in 

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11. Cahalin L, Pappagianopoulos P, Prevost S, Wain J, Ginns L. The relationship of the 6-min walk test 

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11. Holland AE, Spruit MA, Troosters T, et al. An official European Respiratory Society/American 

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12. Dale M, McKeough Z, Munoz P, et al. Functional exercise capacity and health-related quality of 

life in people with asbestos related pleural disease: an observational study. BMC Pulmonary 

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13. Eaton T, Young P, Milne D, Wells A. Six-Minute Walk, Maximal Exercise Tests Reproducibility in 

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7

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