[Federal Register Volume 60, Number 145 (Friday, July 28, 1995)]
[Pages 38839-38844]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-18578]


[[Page 38840]]


Agency for Toxic Substances and Disease Registry

ATSDR's Final Criteria for Determining the Appropriateness of a 
Medical Monitoring Program Under CERCLA

AGENCY: Agency for Toxic Substances and Disease Registry (ATSDR), 
Public Health Service (PHS), Department of Health and Human Services 

ACTION: Notice.


SUMMARY: This notice announces the criteria for determining the 
appropriateness of a medical monitoring program under the Comprehensive 
Environmental Response, Compensation, and Liability Act (CERCLA). Draft 
criteria were published for public comment on September 9, 1994 (59 FR 
46648). The public comment period ended October 24, 1994. Comments were 
received from 15 individuals representing States, industry, activist 
groups, and environmental medicine clinics. This document reflects 
those comments received on the draft criteria.

ADDRESSES: Division of Health Studies, Agency for Toxic Substances and 
Disease Registry, 1600 Clifton Road, NE., Mailstop E-31, Atlanta, 
Georgia 30333, telephone (404) 639-6200.

FOR FURTHER INFORMATION CONTACT: Dr. Wendy E. Kaye, Chief, Epidemiology 
and Surveillance Branch, Division of Health Studies, ATSDR, telephone 
(404) 639-6203.

SUPPLEMENTARY INFORMATION: Section 104(i)(9) of the Comprehensive 
Environmental Response, Compensation, and Liability Act (CERCLA), as 
amended [42 U.S.C. 9604(i)(9)], provides for the Administrator of the 
Agency for Toxic Substances and Disease Registry (ATSDR) to initiate a 
health surveillance program for populations at significantly increased 
risk of adverse health effects as a result of exposure to hazardous 
substances released from a facility. A program included under health 
surveillance is referred to as ``Medical Monitoring or Screening'' by 
ATSDR and is defined in the legislation as ``the periodic medical 
testing to screen people at significant increased risk for disease.'' 
ATSDR has established criteria to determine when medical monitoring is 
an appropriate health activity and the requirements for establishing a 
medical monitoring program at a site. The legislation also states that 
a mechanism to refer people for treatment should be included in the 
program. Statutory language only allows ATSDR to provide medical care 
or treatment in cases of public health emergencies as declared by the 


    ATSDR is responsible for the public health-related activities of 
CERCLA. ATSDR's primary initial response at a hazardous waste site is 
the public health assessment, which is required for every site on the 
National Priorities List (NPL). A public health assessment can also be 
conducted in response to a petition from the public. Other important 
components of ATSDR's initial response at sites include health 
consultations and public health advisories. During the process of 
developing the public health assessments and health advisories, ATSDR 
invites the participation of communities through a variety of avenues 
such as public meetings, public availability sessions, and Community 
Assistance Panels (CAPs). The documents produced by ATSDR during the 
process are placed in a public repository to allow the public access to 
the documents. The public health assessments, health consultations, and 
public health advisories undergo review by ATSDR to determine if 
follow-up health-related activities are needed for populations at risk 
in the affected community.
    The types of follow-up health activities recommended for a site 
will depend on the amount of information on the possible exposures and 
their suspected pathways. In any case in which an association has not 
been established between an exposure and a specific adverse health 
outcome, several research and health education activities may be 
considered. Those activities could include health outcome studies, an 
exposure assessment at the site, epidemiologic studies, or professional 
    ATSDR's Division of Health Assessment and Consultation has 
established a program for the investigation of exposures in communities 
which enables a more timely response to questions on whether 
individuals in a community are being exposed. The program incorporates 
a variety of industrial hygiene techniques for measuring chemicals in 
the environment, as well as selected biological markers of exposure.
    The Division of Health Education provides a wide variety of 
services to educate health care professionals and communities on the 
effects of exposures to hazardous substances. Activities in a community 
around a hazardous waste site may include conducting grand rounds for 
health care providers on the effects of a specific chemical, providing 
fact sheets on chemicals, conducting workshops on clues to 
environmental disease, and producing case studies in environmental 
    The Division of Health Studies is responsible for conducting 
epidemiologic research, including several types of studies (cluster 
investigations, disease and symptom prevalence studies, analytic 
epidemiologic studies), surveillance programs, and exposure registries. 
Cluster investigations and disease and symptom prevalence studies 
investigate the occurrence of disease in populations. Analytic 
epidemiology studies are conducted to evaluate the causal nature of 
associations between exposure to hazardous substances and disease 
outcomes. The surveillance program focuses on exposures to substances 
at hazardous waste sites and includes systems that follow populations 
exposed to hazardous wastes because of where they live or their 
occupation. It also includes surveillance of emergency events in which 
hazardous substances are released into the environment. The National 
Exposure Registry maintains a listing of people exposed to hazardous 
substances. The Registry is composed of chemical specific 
subregistries. The chemicals are selected from the ATSDR/EPA priority 
list of hazardous substances.
    Medical monitoring is considered one of several follow-up health 
activity options under the site-specific work conducted by ATSDR. A 
medical monitoring program for the community around a site will be 
considered with other health follow-up activities when the information 
from ATSDR's initial response at the site is reviewed. In cases in 
which there is no known association between the exposure and specific 
adverse health effects (which could include health outcomes, illnesses, 
or markers of effect), medical monitoring is not an appropriate public 
health activity. In cases in which there is limited information on a 
specific health effect's relationship to an exposure, then options such 
as epidemiologic surveillance, a disease and symptom prevalence study, 
or an epidemiologic study are more appropriate. When adequate 
information exists that links exposure to a chemical with a specific 
adverse health effect, further consideration will be given to the 
appropriateness of medical monitoring in that population.

[[Page 38841]]

    Medical monitoring should be directed toward a target community 
identified as being at ``significant increased risk for disease'' on 
the basis of its exposure. Significant increased risk will vary for 
particular sites depending upon such factors as the underlying risk of 
the selected outcome, the risk attributable to the exposure, and the 
presence of sensitive subpopulations. These factors will be considered 
when evaluating the appropriateness of medical monitoring in a 
community. The CERCLA legislation also provides for a mechanism for 
referral for treatment of those who are screened positive for the 
selected health outcomes; therefore, a mechanism to refer people for 
diagnosis, interventions, or treatment should be in place prior to the 
initiation of a medical monitoring program.
    The primary purpose of a medical monitoring program is not 
considered to be a research activity that further investigates the 
cause-effect relationship between exposure and outcome. The purpose of 
a medical monitoring program is case-finding in order to refer 
individuals for further evaluation and, as appropriate, treatment. 
Within this framework, medical monitoring includes both testing for 
early biological effect and an assessment of exposure using biological 
specimens (for example, blood or urine), when appropriate. This is 
provided as a service to individuals in communities where there is 
believed to be an increased risk of disease from exposure to hazardous 
substances released into the environment.

Criteria for Considering Medical Monitoring

    The criteria outlined below will be used to determine the 
appropriateness of conducting medical monitoring in a community and 
will be applied in a phased approach. Phase I, conducted by ATSDR, 
consists of an evaluation of the exposure and outcome criteria. Phase 
II consists of an evaluation of the system criteria. Phase II will be 
conducted with the input of a panel consisting of community, State and 
local health officials, and ATSDR. At the end of Phase II, a detailed 
medical monitoring plan will be written at sites where a monitoring 
program is established. All of the criteria must be met at a site in 
order for a medical monitoring program to be established at that site. 
In addition, resources must be available to initiate and sustain the 

Phase I

Exposure Criteria

    A. There should be evidence of contaminant levels in environmental 
media that would suggest the high likelihood of environmental exposure 
to a hazardous substance and subsequent adverse health outcomes.
    The National Research Council (NRC) defines exposure as ``an event 
that occurs when there is contact at a boundary between a human and the 
environment at a specific contaminant concentration for a specified 
period of time; the units to express exposure are concentration 
multiplied by time'' (NRC, 1991). The specific contaminant 
concentration and period of time will vary for different chemicals and 
different media. The exposure must be to a hazardous substance as 
defined under CERCLA, and the result of a release from a CERCLA-covered 
facility. A release from a CERCLA-covered facility includes those 
events that establish an open pathway of exposure (i.e., an unfenced 
area with high soil contamination could be considered a ``release'') or 
allows contaminants to go off-site via air, surface water, ground 
water, or other pathway. The primary criteria for medical monitoring 
should be documented evidence of exposure of a population to a 
hazardous substance in the environment. An exposure will be considered 
to be at a sufficient level if there is documentation of an increased 
opportunity for exposure to a level that meets or exceeds some health-
based comparison value (such as Minimum Risk Levels (MRLs) or Reference 
Doses (RfDs)) or that meets or exceeds a level reported in the peer-
reviewed literature to result in some adverse health effect. 
Documentation is considered sufficient if it is from an exposure 
assessment, environmental exposure modeling, or sampling from a general 
area (for example, water samples from an aquifer or a town water 
supply). Documentation of individual levels of exposure is not 
required. In cases in which exposures are unknown or undocumented, 
environmental monitoring is a more appropriate initial activity.
    B. There should be a well-defined, identifiable target population 
of concern in which exposure to a hazardous substance at a sufficient 
level has occurred.
    Initially, the target population of concern will be defined 
geographically on the basis of exposure. In addition, all populations 
considered will be assessed for the presence of any sub-population at 
increased risk of the adverse health effects associated with the 
exposures. An example of a subpopulation at increased risk would be 
preschool children in an area with known lead exposures. The size of 
the target population of concern is not a factor in the decision for 
monitoring. In areas where biological markers of exposure have not been 
collected, environmental sampling can be used to estimate exposure 
levels. The target population of concern is the population in which 
there is documented exposure at a sufficient level to place the 
individuals in that population at significant increased risk for 
developing some specific adverse health effect.

Outcome Criteria

    A. There should be documented human health research that 
demonstrates a scientific basis for a reasonable association between an 
exposure to a hazardous substance and a specific adverse health effect 
(such as an illness or change in a biological marker of effect).
    Previous studies on human populations must demonstrate a reasonable 
association between a particular exposure and an adverse health effect. 
In order to make that inference, consideration should be given to the 
strength, specificity, and consistency of the association among the 
identified studies. The period of exposure (including the timing and 
duration of the exposure) and its relationship to the latency period 
for the disease or illness should also be examined if information is 
available. Consideration should be given to whether the association has 
demonstrated a dose-response relationship and whether the association 
is consistent with the existing body of knowledge. This information 
could include a variety of occupational, epidemiological, or other 
studies involving human populations.
    B. The monitoring should be directed at detecting adverse health 
effects that are consistent with the existing body of knowledge and 
amenable to prevention or intervention measures.
    The monitoring should be established for specific adverse health 
effects. The specific adverse health effect being monitored should be a 
result of the possible exposure consistent with the existing body of 
knowledge. An adverse health effect is consistent with the existing 
body of knowledge if it has been described in the literature as caused 
by that agent or by similar agents, taking into account structure-
activity relations.
    In addition, the adverse health effects (disease process, illness, 
or biomarkers of effect) should be such that early detection and 
treatment or intervention 

[[Page 38842]]
interrupts the progress to symptomatic disease, improves the prognosis 
of the disease, improves the quality of life of the individual, or is 
amenable to primary prevention. If the adverse health effects that are 
of concern in an individual or in a community are not easily detectable 
and not medically treatable, then medical monitoring would not be 
beneficial and would not be an appropriate public health activity. An 
easily detectable effect is one that can be found on clinical 
examination, or through the use of simple, diagnostic tests in an 
outpatient setting. Also, the test procedures must be acceptable to the 
patient and the community. The diagnostic tests must be 
nonexperimental, relatively noninvasive (such as the drawing of a tube 
of blood for laboratory tests), and simple to administer.

Monitoring for Evidence of Continuing Exposure

    At sites with exposure in the community, the monitoring program 
might include biological markers of continuing exposure. For example, 
the Bunker Hill Superfund site has had lead screening of children for 
many years. Those sites would be ones in which the exposure is known to 
have a variety of adverse health effects, but for which no tests are 
available to detect those effects at a time when intervention could 
affect the course of the disease process. In those instances, the 
primary intervention is to remove the individual from the exposure. 
This allows the medical monitoring system to recommend referral for 
intervention prior to the onset of detectable adverse health effects. A 
monitoring system that includes biomarkers of continuing exposure is 
similar to medical surveillance of hazardous waste workers where 
changes indicative of increasing or continued exposures occur 
sufficiently early that the exposure can be curtailed and the risk for 
disease reduced (Gochfeld 1990).

Phase II

General Information

    Phase II of the program is carried out by ATSDR with assistance 
from the community. When ATSDR has determined that exposure from a site 
has met the exposure and outcome criteria, a site panel will be formed 
based on recommendations from the community and the State and/or local 
health departments to review the system criteria and to assist in the 
development of a site-specific medical monitoring plan. The site panel 
will include representatives from ATSDR, the community, State or local 
health departments, local medical societies, and subject experts as 
necessary. The site panel will function in much the same manner as the 
Community Assistance Panels (CAPs) that are established at some sites 
during the public health assessment process. The site panel will follow 
the established procedures for those CAPs. The site panel will be 
responsible for assessing the available community health resources and 
determining the feasibility and extent of the screening program for the 
community. If the panel determines that a screening program is feasible 
in the community and ATSDR concurs with that decision, ATSDR will 
develop a site-specific monitoring plan. That plan will be presented to 
the site panel for review and concurrence. After the plan has been 
developed and has undergone peer review, it will be presented to the 
community at large for their input prior to establishing the program.

System Criteria

    A. The general requirements for a medical screening program should 
be satisfied.
    The monitoring aspect of a health surveillance program consists of 
the periodic medical testing to screen individuals who are at increased 
risk of disease. Monitoring serves to identify those individuals with 
an unrecognized adverse health effect. This is consistent with the 
definition of screening as ``the presumptive identification of 
unrecognized disease or defect by the application of tests, 
examinations, or other procedures which can be applied rapidly. 
Screening tests sort out apparently well persons who probably have a 
disease from those who probably do not. A screening test is not 
intended to be diagnostic. Persons with positive or suspicious findings 
must be referred to their physicians for diagnosis and necessary 
treatment.'' (Commission on Chronic Illness, 1957) In general, the 
ability to predict the presence or absence of disease from test results 
depends on the sensitivity and specificity of the test and the 
prevalence of the disease in the population being tested. The higher 
the prevalence, the more likely a positive test indicates disease 
(Mausner & Kramer, 1985). In order for a screening program to be of 
public health benefit, the population being screened should be at a 
significantly high risk for the undiagnosed disease (i.e., the disease 
should have a sufficiently high prevalence in the population).
    Given that definition, there are certain requirements for screening 
programs that should be considered when evaluating a possible medical 
monitoring program for a site (adopted from Mausner & Kramer, 1985). 
Those requirements are:
     The natural history of the disease process should be 
understood sufficiently for screening.
     The early detection through screening should be known to 
have an impact on the natural history of that disease process. For 
example, the detection of breast cancer while it is localized has been 
shown to increase the ten-year survival rate. For that reason, several 
groups have made recommendations for the early detection of breast 
cancer in asymptomatic women. Those recommendations include breast 
self-examination, breast physical examination, and mammography (Mettlin 
& Dodd, 1991; Kelsey & Gammon, 1991).
     There should be an accepted screening test that meets the 
requirements for validity, reliability, estimates of yield, 
sensitivity, specificity, and acceptable cost. The purpose of ATSDR-
sponsored medical monitoring is not to develop new screening tests. The 
medical monitoring program will use tests that have been recommended 
and used for screening in other settings.
    The U.S. Preventive Services Task Force has established criteria 
for determining the effectiveness of preventive strategies including 
screening tests. The criteria for effectiveness of a screening test 
include the efficacy of the screening test and the effectiveness of 
early detection. The Task Force used efficacy to mean accuracy and 
reliability. The accuracy is measured using four indices: sensitivity, 
specificity, positive predictive value, and negative predictive value 
(see table below for definitions). A test with poor sensitivity will 
result in a large proportion of persons with disease being told they 
are free of disease (false-negatives). A test with poor specificity 
will result in healthy persons being told they have the disease (false-
positives). There may be serious consequences in the use of screening 
tests with poor sensitivity and/or specificity. Persons with false 
negative results may have delays in diagnosis and treatment. False 
positive results can result in follow-up testing that is uncomfortable, 
expensive and potentially harmful. The evaluation and selection of a 
screening test must include a determination of the likelihood of 
producing false positive results (the positive predictive value (PPV)). 
The PPV changes in accordance with the prevalence of the condition in 
the screened population. PPV is unlike 

[[Page 38843]]
sensitivity and specificity in that it is not a constant characteristic 
of a screening test. If the condition is sufficiently rare in the 
screened population, even tests with excellent sensitivity and 
specificity can have low PPV, having more false positive results than 
true positive results.
    Another important aspect in determining the efficacy of a screening 
test is the reliability of the test. The reliability (reproducibility) 
is the ability of the test to give the same result when it is repeated. 
An accurate test with poor reliability can produce results that vary 
widely from the correct value, even though the average of the results 
approximates the true value. Poor reliability may be due to either 
interobserver variation or intraobserver variation (U.S. Preventive 
Services Task Force, 1989).

                           Definition of Terms                          
          Term                  Definition               Formula*       
Sensitivity............  Proportion of persons    a                     
                          with the condition who  a + c                 
                          test positive.                                
Specificity............  Proportion of persons    d                     
                          without the condition   b + d                 
                          who test negative.                            
Positive Predictive      Proportion of persons    a                     
 Value.                   with positive test who  a + b                 
                          have condition.                               
Negative Predictive      Proportion of persons    d                     
 Value.                   with negative test who  c + d                 
                          do not have the                               
*Explanation of Symbols                                                 
                             Condition absent        Condition present  
Positive Test..........             a                        b          
Negative Test..........             c                       d           
Legend: a=true +; b=false +; c=false -; d=true -.                       

     The screening program should be one that is feasible and 
acceptable to individuals and the community. Therefore, plans and 
possible screening tests for a medical monitoring program will be 
presented to the community for input prior to the initiation of any 
recommended program.
    B. An accepted treatment, intervention, or both, for the condition 
(outcome or marker of exposure) must exist and a referral system should 
be in place prior to the initiation of a medical monitoring program.
    There should be established criteria for determining who should 
receive referral for intervention or treatment. These criteria will be 
based on the selected effect being screened for and the screening test 
being used. Results will be evaluated by ATSDR longitudinally and 
cross-sectionally to identify changes in the system or screening tools 
that require follow-up (Gochfeld 1990). A referral mechanism should 
exist so that those who are eligible for the intervention can be 
referred to a qualified health care provider for further diagnosis, 
treatment, or intervention. The referral must be for treatment or 
intervention that is standard practice and not experimental in nature. 
The medical monitoring (screening) program is not responsible for the 
cost of the referral, the intervention, or the treatment of individuals 
participating in the program.
    C. The logistics of the system must be resolved before the program 
can be initiated.
    After medical monitoring has been determined to be appropriate for 
a site, the specifics of the monitoring system will be detailed in a 
site-specific medical monitoring plan. The site panel consisting of the 
community members, appropriate health officials, and subject experts as 
necessary will work with ATSDR to develop and review the site-specific 
medical monitoring plan. The specifics of the medical monitoring system 
recommended can vary for each site. The monitoring plan is the protocol 
for the specific program to be proposed in a community. The plan will 
outline the target community, the types of outcomes to be screened for, 
the participants in the referral system, and the program reports. The 
plan will include a review of the latency period for the outcomes being 
monitored and the duration of the exposure to define the period of time 
that the program will operate in a specific site population. The target 
population; the completeness with which the exposed population can be 
identified, contacted, and followed; the screening tests; and the 
selected health outcomes will all influence the specifics of the 
system. Existing medical facilities and personnel will be used when 
    The monitoring plan will be submitted for peer review prior to its 
implementation at a site. The plan for a site might require additional 
review by an expert panel (ethicists, NRC) to evaluate the screening 
tests recommended. ATSDR's Division of Health Studies will work closely 
with the Division of Health Education to provide professional health 
education when needed to enhance the medical monitoring program.
    Medical monitoring is one of ATSDR's service activities and is not 
considered to be a research tool. The monitoring activity at each site 
will be routinely evaluated for the effectiveness of the screening 
tests in place and the types of effects being detected. Due to 
confidentiality issues in dealing with small groups of people, the 
reporting from the system will consist of annual reports noting the 
number of individuals screened, the number of referrals made, and the 
number of conditions diagnosed in the referral system. ATSDR will 
develop a list that includes information on the types of exposures seen 
in the communities and the types of screening tests that were included 
in the monitoring. ATSDR can provide this information as available to 
the site panels to assist them in deciding on the types of screening 
tools based on what has been used in other areas.
    The referral system will consist of the review of the screening 
results and the referral to appropriate health care providers or 
referral physicians. The specific mechanisms for determining who needs 
referral and for selecting the health care providers in the referral 
pool must be in place prior to the initiation of the medical 
monitoring. Once the participant has been referred to the 

[[Page 38844]]
referral providers, those providers will be responsible for any 
subsequent diagnosis, treatment, or intervention.
Summary of Medical Monitoring

    Medical monitoring will be considered along with the other health 
follow-up activities to be recommended for populations around specific 
sites. The Division of Health Studies will make a determination on 
whether a site meets the exposure and outcome criteria for medical 
monitoring. If a site meets the previously discussed criteria and is 
selected for further consideration of a medical monitoring program, 
ATSDR will work with the community and other appropriate entities in 
designing the specific monitoring and referral system for that site's 
target population. ATSDR will notify, and where appropriate, work with 
the state health department to establish the program. The Division of 
Health Studies will monitor the program and be responsible for the 
oversight on the annual reports.


Commission on Chronic Illness. Chronic Illness in the United States, 
Vol. 1. Commonwealth Fund, Harvard University Press, Cambridge, 
1957, page 45.
Gochfeld M. Medical surveillance of hazardous waste workers. In 
Principles and Problems in Occupational Medicine State of the Art 
Reviews: Hazardous Waste Workers. Gochfeld M and EA Favata, editors. 
Philadelphia: Hanley & Belfus, Inc., 1990; 5(1):1-8.
Kelsey JL and MD Gammon. The epidemiology of breast cancer. CA-A 
Cancer Journal for Clinicians 1991; 41(3):146-165.
Mausner JS and S Kramer. Epidemiology--an introductory text. 
Philadelphia: W.B. Saunders, 1985, pages 220-230.
Mettlin C and GD Dodd. The American Cancer Society guidelines for 
the cancer-related checkup: An update. CA-A Cancer Journal for 
Clinicians 1991; 41(5):279-282.
NRC (National Research Council). Human Exposure Assessment for 
Airborne Pollutants: Advances and Opportunities. Washington, D.C.: 
National Academy Press, 1991, pages 17-37.
U.S. Preventive Services Task Force. Guide to Clinical Preventive 
Services: An Assessment of the Effectiveness of 169 Interventions. 
Baltimore: Williams & Wilkins, 1989, pages xxix-xxxvii.

    Dated: July 24, 1995.
Claire V. Broome,
Deputy Administrator, Agency for Toxic Substances and Disease Registry.
[FR Doc. 95-18578 Filed 7-27-95; 8:45 am]