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Reproductive and Cancer Hazard Assessment Section
Office of Environmental Health Hazard Assessment
California Environmental Protection Agency
May 1997
1 BACKGROUND
The Safe Drinking Water and Toxic Enforcement Act (Proposition
65, California Health and Safety Code 25249.5 et seq.) requires
the Governor to publish lists of chemicals known to cause cancer
and reproductive toxicity. One of the mechanisms by which a chemical
is placed on this list is a finding by the "state's qualified
experts" that a chemical has been clearly shown through scientifically
valid testing according to generally accepted principles to cause
cancer or reproductive toxicity. As lead agency for the implementation
of Proposition 65, the Office of Environmental Health Hazard Assessment
(OEHHA) has formed two committees within its Science Advisory Board
(SAB) to serve as the state's qualified experts. These committees,
which are independent panels of scientists and health professionals,
are the Developmental and Reproductive Toxicant (DART) Identification
Committee, and the Carcinogen Identification Committee (CIC).
The purpose of this document is to describe the procedure used
by OEHHA to identify, prioritize, and select candidate chemicals
for evaluation by the SAB Identification Committees. The procedure
is designed to ensure that the efforts of the SAB are focused on
chemicals which pose the greatest hazard to Californians, and that
these chemicals are selected in an open, objective and predictable
manner. This procedure ensures that chemicals posing the highest
level of carcinogenic, reproductive or developmental hazard concern
are addressed first and forthwith by the SAB. At appropriate points
in the prioritization process, opportunity is provided for input
and review by state agencies and departments, individual SAB Identification
Committee members, the Committees as a whole if they so choose,
the scientific community, and the public. This process has been
the subject of extensive review and comment by the public, external
scientists, and by the SAB Identification Committees. This refined
prioritization process should ensure that chemicals posing the highest
degree of hazard are identified promptly and brought to the SAB
for their evaluation and finding within an estimated time frame
of 9 to 15 months.
2 SUMMARY OF KEY POINTS
This section outlines the key features of the prioritization process.
2.1 OEHHA Selection of Candidate Chemicals
OEHHA will perform all prioritization steps up to and including
the selection of chemicals for preparation of hazard identification
documents. OEHHA will randomly select chemicals from the tracking
database for further evaluation, develop draft data summaries, assign
draft priorities, circulate the draft data summaries and priorities
for public and SAB committee member review and comment, hold a public
workshop, and then, after review of oral and written comments, assign
final priorities.
Assigned priorities may change as new scientifically valid toxicological
information relevant to potential cancer, reproductive or developmental
effects becomes available. In such circumstances, notice will be
provided regarding a proposal to revise the prioritization, and
opportunity will be provided for public input.
2.2 Use "Tiered" Evaluation Process
To expedite the process and use resources efficiently, the level
of analysis employed during the course of assigning final priorities
will vary according to the complexity of the toxicological issues
to be addressed. Preparation of a data summary will provide sufficient
information for many chemicals, while for others, additional analysis
supplemental to the data summary may be necessary to resolve particular
scientific issues prior to the assignment of a final priority. For
example, a supplemental analysis may be beneficial by providing
a focused evaluation of a key toxicological issue germane to a specific
chemical, such as the design of a critical study, apparent inconsistency
in results in a given species, or by providing additional chemical-specific
information regarding mode of action, or apparent route- or species-specific
toxicity, or with respect to the relationship, if any, of developmental
toxicity and maternal toxicity. In general, an issue-specific supplemental
analysis will be performed, when warranted, only on chemicals which
appear to be of higher toxicological concern, i.e., those chemicals
assigned a draft priority of "high" or "medium high".
Although a supplemental analysis may address several issues, a chemical
will undergo, at most, only one supplemental analysis during the
course of prioritization.
2.3 Organization of the Tracking Database
Changes to the terminology and organization of the tracking database
have been made. The database is now organized into three mutually
exclusive groups. Category I includes all chemicals nominated or
otherwise identified for entry into the tracking database for which
some supporting information is available, but which have not been
assigned a final priority status. Category II includes those chemicals
in the tracking database which have been assigned a final priority
status other than high. If data are inadequate, the priority status
for the chemical is "inadequate data". The Candidate List
is composed of chemicals with a final priority status of high level
of carcinogenic, reproductive or developmental hazard concern.
2.4 Initial Work Focused on Chemicals with "High"
Hazard Level of Concern and Known or Potential Exposure in California
Prioritized chemicals with a final high level of carcinogenic,
reproductive or developmental hazard concern will be assigned to
the Candidate List, from which chemicals will be chosen for the
preparation of a hazard identification document. All other final
prioritized chemicals will be assigned to Category II.
Information on exposure will be taken into account in the selection
of chemicals from the Candidate List. Chemicals with the highest
level of exposure concern will be selected first from the Candidate
List to be brought before their respective Committee. Chemicals
on the Candidate List (those with "high" level of hazard
concern) for which there are lower exposure concerns in California
will, in general, be addressed subsequent to those chemicals determined
to have both a high level of hazard concern and a high level of
exposure concern.
Action is not anticipated for Category II chemicals until all chemicals
identified as posing a high hazard concern have been identified
from the tracking database, assigned to the Candidate List, and
have been brought before the Committees. At that point, with Committee
and public input, OEHHA will refine the existing process in order
to determine which of the Category II prioritized chemicals should
be brought forward for consideration by the CIC and the DART Identification
Committee.
3 SUMMARY OF PROCESS STEPS
The complete procedure for selecting chemicals for hazard identification
includes the following sequential steps:
-
Random selection of the numerical order for chemicals from
Category I to be assigned to groups for preparation of a draft
data summary, with notice of each group of chemicals selected
published in the California Regulatory Notice Register
on a regular (e.g. quarterly or biannual) basis.
-
Development of a draft data summary, followed by assignment
of a draft priority.
-
Identification by OEHHA of any chemicals for which there is
a key toxicological issue which may require a focused supplemental
analysis, beyond a data summary. In such cases OEHHA will perform
the supplemental analysis prior to assignment of a draft priority.
-
Solicitation of public comment on draft data summaries and
draft priorities during a 60-day comment period, and solicitation
of additional information on chemicals identified as requiring
a focused supplemental analysis. Opportunity for oral as well
as written comments will be provided by a public workshop held
during the 60-day period.
-
For those chemicals not identified as needing a focused supplemental
analysis:
Following review and consideration of public comments received,
OEHHA will assign the final prioritized chemicals to Category II
or the Candidate List. If public comment identifies a key toxicological
issue, such that a supplemental analysis is necessary before a final
priority can be assigned, OEHHA will solicit public comment on the
supplemental analysis as described in the following step.
OEHHA will conduct the supplemental analysis and then circulate
it for public and scientific review during a 60-day comment period.
Opportunity for oral as well as written comment will be provided
by a public workshop held during the 60-day period. Following review
and consideration of public comments received, OEHHA will assign
the final prioritized chemicals to Category II or the Candidate
List.
Under exceptional circumstances, the process may be abbreviated
to allow OEHHA to respond to specific public health needs. Following
consultation with the Committee Chair, the Director of OEHHA may
request that a chemical be placed on the agenda of the next scheduled
meeting. In all cases, the chemical will be noticed in the California
Regulatory Notice Register and appropriate notification periods
will be followed.
4 DETAILED PROCESS DESCRIPTION
The steps of the prioritization process, summarized above, are
described in more detail in the following sections. Figure 1 presents
a flow chart of the prioritization and listing process, showing
how a chemical is tracked, prioritized, may be placed on the Candidate
List, and ultimately may reach the Committee for consideration.
4.1 Database of Suggested Chemicals for Consideration (Tracking
Database)
A tracking database has been established to keep account of chemicals
entered into the system as they progress through different stages
of evaluation. The tracking database, updates of which are released
quarterly, includes all identified potential candidate chemicals.
These chemicals have been suggested by state agencies and other
sources or obtained from literature searches. To date, over 580
potential candidate carcinogens and over 320 potential candidate
developmental or reproductive toxicants (DARTs) have been entered
into the tracking database.
A chemical may enter the system by a number of mechanisms, including
the following:
(1) literature searches and reviews of databases by OEHHA, (2)
suggestions by members of the SAB Identification Committees, (3)
suggestions by other State agencies, (4) suggestions by the general
public, and (5) suggestions by the scientific community. The basis
for identifying a chemical as a potential candidate may be, for
example, positive cancer or reproductive toxicity bioassays, or
some evidence of very high production or use volume, particularly
in California, accompanied by some evidence of relevant toxicity
(birth defects, reproductive toxicity, or cancer).
Figure 1: Flowchart for consideration
of chemicals under proposition 65
The five primary sources of potential candidate chemicals are described
below:
1. Literature searches and other sources. Sources
of potential candidate chemicals include the following:
-
Current scientific literature
-
Chemical Carcinogenicity Research Information System (CCRIS)
-
Database from Gold et al. (1984, 1986, 1987, 1990)
-
Pesticide registrant data submitted to Cal/EPA
-
Publications on Darts (e.g., Schardein [1993])
-
Other databases
OEHHA periodically reviews the above sources. OEHHA and the Department
of Pesticide Regulation will work together to identify potential
candidate chemicals from pesticide registrant data.
2. Suggestions from the SAB Identification Committees.
The Identification Committees, as the state's qualified experts,
may bring candidates to the attention of OEHHA.
3. Suggestions from other State organizations. A
process is being developed to establish an ongoing mechanism for
soliciting candidate chemicals from other state organizations. The
proposed elements of this process include: (1) a mechanism to regularly
request suggestions of candidate chemicals from state organizations
and committees and (2) forms requesting summary information on the
chemicals.
4. Suggestions from the general public. Input from the public
will be solicited through the California Regulatory Notice Register.
Information supporting the suggestion of a chemical will also be
requested. Although such information is not specifically required,
OEHHA will use it or other supporting information to consider placement
of a chemical on the tracking list.
5. Suggestions from the scientific community. Periodically,
suggestions from the expert scientific community may be solicited
or volunteered.
Suggested chemicals are tracked using a computer database. In cases
where chemicals are suggested but no supporting data is received,
OEHHA will screen the chemicals to determine whether the chemicals
should be entered into Category I. The information categories for
the tracking system will include the source of the suggestion (e.g.,
literature source, general public); the date the chemical is entered
into the database, and other important dates such as assignment
to Category II or the Candidate List (if applicable) and subsequent
procedural steps; results of reviews by authoritative bodies; brief
comments on available epidemiological studies, animal bioassays,
and other studies relevant to an assessment of the carcinogenicity
or developmental and reproductive toxicity; data on use, occurrence,
and production, and other information relevant to an assessment
of exposure; other pertinent comments; and key references.
4.2 Category I
Category I of the tracking database will include all chemicals
nominated or otherwise identified for which some supporting information
is available, but which have not yet been assigned a final priority
status. OEHHA will search for information relevant to an assessment
of developmental or reproductive toxicity, or carcinogenicity, for
all chemicals in Category I. This information could be in the form
of epidemiological studies, animal studies, or other relevant data
indicating the potential developmental or reproductive toxicity
or carcinogenicity of the chemical. OEHHA will also search for information
on the occurrence, use, and level and extent of exposure for all
chemicals in Category I.
Chemicals will be randomly selected from Category I for
evaluation of the available toxicological and exposure data, development
of a draft data summary, assignment of a draft priority status,
and progression into Category II or the Candidate List. OEHHA
will publish in the California Regulatory Notice Register
on a quarterly basis notice of those chemicals selected from Category
I.
A draft data summary will be prepared based upon a review and evaluation,
in most instances of the secondary literature, resulting in an assignment
of a draft hazard priority level for developmental or reproductive
toxicity or carcinogenicity concern of "high", "medium
high", "medium", "low", "no identified
concern", or "inadequate data".
Chemicals will also be assigned a level of exposure concern of
"high", "medium", "low", "no
identified concern", or "inadequate data". Exposure
information will not be used in the assignment of hazard priorities
and placement of chemicals on the Candidate List, which is based
solely on the level of hazard concern. Rather, exposure information
will be considered in determining the order in which chemicals on
the Candidate List are selected for the preparation of hazard identification
documents. In addition, exposure information will be used as a basis
to identify and help fill data gaps for chemicals found to have
high potential for exposure, but insufficient or inadequate relevant
toxicity data. To the extent possible, OEHHA will inform other appropriate
agencies of this information. For example, if a high exposure chemical
is found to be inadequately tested for carcinogenicity, but there
is some evidence to suggest carcinogenic potential, OEHHA may recommend
the chemical to the National Toxicological Program for further testing.
4.3 Category II
A chemical progresses from Category I to Category II or the Candidate
List following preparation of a draft data summary, assignment of
a draft priority, public and external scientific review and comment,
review by OEHHA of comments, and assignment of a final priority.
Category II includes those chemicals which have been assigned a
final priority other than high level of carcinogenic, reproductive
or developmental hazard concern. Action is not anticipated for Category
II chemicals until all high priority chemicals have been identified
from the tracking database, assigned to the Candidate List, and
have been brought before the Committees.
4.3.1 Basis for Assignment of Priorities
The assignment of a hazard priority to a chemical is based on the
level of developmental/reproductive toxicity or carcinogenicity
concern. Evidence for prioritization will come from epidemiological
or animal toxicity studies or other relevant data indicating the
potential carcinogenicity or developmental/reproductive toxicity
of the chemical.
Epidemiological studies: The evidence considered will include
the study population, exposure situation, tumor type or developmental/reproductive
toxicity endpoint, nature of the dose-response curve, possible roles
of bias and confounding, and quality of studies. In judging the
epidemiological evidence, greater weight will be given to analytical
epidemiological studies and lower weight to descriptive studies
and case reports. Both positive and negative studies will be considered
in assessing the overall level of hazard concern.
Animal studies: The evidence considered will include the
number of experiments and species tested, route of administration,
frequency and duration of exposure, numbers of test animals, and
consideration of dose-response. Both positive and negative studies
will be considered in assessing the overall level of hazard concern.
Other relevant data: Evaluation of other relevant
data for use in prioritizing candidates will also be made. Such
data include information on mechanism of action, chemical structure,
maternal toxicity, metabolism, and genotoxic activity.
A qualitative appraisal of the potential for a chemical to cause
cancer or developmental/reproductive toxicity will be made on the
basis of a scientific evaluation of the available information. Chemicals
will then be assigned a hazard level of concern of "high",
"medium high", "medium", "low", "no
identified concern", or "inadequate data". This process
is not a final hazard evaluation, but rather a preliminary appraisal
for the purpose of prioritizing chemicals.
4.3.2 Level of Hazard Concern
Chemicals will be assigned a high level of hazard concern if this
preliminary evaluation indicates the existence of evidence that
is likely to demonstrate a strong and biologically plausible potential
to cause cancer or developmental/reproductive toxicity. Chemicals
which appear to have less evidence will be assigned lower levels
of hazard concern, which reflect OEHHA's preliminary evaluation
of the weight of the available information.
For developmental toxicants, chemicals are likely to be assigned
a high level of hazard concern if they appear, in animal or human
studies, to cause developmental toxicity which is not secondary
to concurrent maternal toxicity. In general, the nature and severity
of both the developmental effects and any reported maternal toxicity
will be taken into account in assigning levels of hazard concern.
Chemicals which appear to have less evidence will in general be
assigned lower levels of hazard concern, which reflect OEHHA's preliminary
evaluation of the weight of the available information.
For male and female reproductive toxicants, chemicals are likely
to be assigned a high level of hazard concern if they appear, in
animal or human studies, to cause reproductive toxicity which is
not secondary to concurrent systemic toxicity. In general, the nature
and severity of both the reproductive effects and any reported systemic
toxicity will be taken into account in assigning levels of concern.
Chemicals which appear to have less evidence will in general be
assigned lower levels of hazard concern, which reflect OEHHA's preliminary
evaluation of the weight of the available information.
At times, for particularly difficult scientific issues, the OEHHA
Director or designee may request assistance from outside experts
in assessing the level of carcinogenic or developmental/reproductive
toxicity concern.
4.3.3 Evaluation of Exposure Information
Direct or indirect evidence of exposure in California, including
information on level and extent of exposure, will be noted and included
in the data summary. In general, direct exposure data from monitoring
are not likely to be available, as most monitoring programs target
only those chemicals that are known hazards. Indirect information
may be more widely available. Quantitative information such as amounts
produced or used in California will be collected when possible,
although it is recognized that quantity of use does not necessarily
correspond directly to actual exposures. The tracking system will
record use and occurrence information such as whether the chemical
is used in California industries, is a byproduct of industries operating
in California, is a pesticide used on food crops grown or imported
into California, or is a component of consumer products or drugs
sold in California. Information on current restrictions on exposure
to the chemical will also be noted when readily available. In the
absence of information specific to California, evidence of exposure,
production or use in the U.S. will be assumed to reflect the experience
in California. A qualitative evaluation of the level of concern
in terms of exposure will be expressed as "high", "medium",
"low", "no identified concern", or "inadequate
data".
Exposure information will not be used in the assignment of hazard
priorities, but will be taken into account in the selection of chemicals
from the Candidate List for Committee consideration. Chemicals with
the highest level of exposure concern will be selected first from
the Candidate List to be brought before their respective Committee.
Chemicals on the Candidate List (those with "high" level
of hazard concern) for which there are lower exposure concerns in
California will, in general, be addressed subsequent to those chemicals
determined to have both a high level of hazard concern and a high
level of exposure concern.
4.3.4 Authoritative Body Evaluations
The reporting of priority status will also address evaluations
conducted by authoritative bodies. (If an authoritative body formally
identifies a chemical as a carcinogen or DART, and the nature of
the authoritative body action and the evidence for carcinogenicity
or reproductive toxicity meet the criteria outlined in Title 22
Section 12306, of the California Code of Regulations, then the chemical
is administratively added to the Proposition 65 list. The US Environmental
Protection Agency, the International Agency for Research on Cancer,
the National Toxicology Program, the National Institute for Occupational
Safety and Health, and the US Food and Drug Administration have
been designated by the state's qualified experts as authoritative
bodies under Proposition 65.)
Chemicals for which it is anticipated that evaluations by an authoritative
body will be released within a reasonable time (e.g., one
to three years) may be assigned a priority but will generally be
postponed from further consideration until completion of the review
by the authoritative body. Postponement will be noted in the tracking
database, and actions by the authoritative body tracked.
In addition, chemicals that have been recently reviewed by an authoritative
body and found to have insufficient, minimal or no evidence of carcinogenicity
or developmental/reproductive toxicity will likely be categorized
as "low" or "no identified concern". Exceptions
to these generalizations may occur. For example, if an authoritative
body has evaluated a chemical but failed to review all relevant
data, or compelling new data have become available since the evaluation,
the chemical may be categorized at a higher level of hazard concern.
4.3.5 Testing By, or On Behalf of, or for Use By Authoritative
Bodies
OEHHA also recognizes that on occasion it may be reasonable to
postpone prioritization, for a defined period of time, to allow
for the completion of a study undertaken by, on behalf of, or for
use by an authoritative body. OEHHA may, at its discretion, choose
to postpone prioritization when the study results would allow OEHHA
to prioritize a chemical for endpoints for which there otherwise
would be insufficient data, or when OEHHA determines that the study
is of sufficient significance so as to be relevant to the assignment
of a priority to the chemical. Prioritization of postponed chemicals
would proceed when the study results become available. Postponement
will be noted in the tracking database.
4.3.6 Data Gaps
In the process of reviewing the available data on chemicals in
the tracking database, data gaps will likely be identified. To the
extent possible, OEHHA will inform other appropriate agencies of
this information. For example, if a high exposure chemical is found
to be inadequately tested for carcinogenicity, but there is some
scientific evidence to suggest carcinogenic potential, OEHHA may
recommend the chemical to the National Toxicology Program for toxicological
testing.
4.3.7 Review of Priorities; Supplemental Analysis
Once draft priorities have been assigned, OEHHA will publish a
notice in the California Regulatory Notice Register, announcing
the release of draft priorities and draft data summaries on these
chemicals, the start of a 60-day public comment period, and the
date, time and place when a public workshop will be held to provide
opportunity for oral as well as written comments.
Occasionally, in the course of assigning draft priorities, OEHHA
may identify scientific issues germane to prioritization which could
not be adequately addressed in the data summary. In such instances,
OEHHA will notice the intent to address specific scientific issues
related to individual chemicals at the public workshop. For example,
a supplemental analysis may be beneficial by providing a focused
evaluation of a key toxicological issue germane to a specific chemical,
such as the design of a critical study, apparent inconsistency in
results in a given species, or by providing additional chemical-specific
information regarding mode of action, or apparent route- or species-specific
toxicity, or with respect to the relationship, if any, of developmental
toxicity and maternal toxicity.
Following review and consideration of the comments received, OEHHA
will assign final priorities to chemicals and update Category II
and the Candidate List. OEHHA will publish notice of this action
in the California Regulatory Notice Register. In some cases,
if a supplemental analysis has not already been performed, OEHHA
may determine that additional analysis and public comment are needed
in order to address scientific issues not adequately addressed in
the data summary. Once OEHHA has completed the necessary supplemental
analysis, this information will be released for public comment and
undergo the same comment and review process (i.e., public workshop,
60-day comment period) as that employed for the original data summary.
Although a supplemental analysis may address several issues, a chemical
will undergo, at most, only one supplemental analysis during the
course of prioritization.
4.4 Candidate List
The Candidate List will consist of those chemicals found by OEHHA
to have a final priority of high carcinogenic, developmental or
reproductive hazard concern. All other final prioritized chemicals
will be assigned to Category II. Action is not anticipated on Category
II chemicals until all high priority chemicals on the Candidate
List with known or potential exposure have been brought before the
Committees. At that point, with Committee and public input, OEHHA
will refine the existing process in order to determine which of
the Category II prioritized chemicals should be brought forward
for consideration by the CIC and the DART Identification Committee.
4.5 Chemicals Under Consideration for Listing
OEHHA will select chemicals from the Candidate List, publish notice
of initiation of hazard identification documents, solicit germane
scientific data, studies and analyses, and begin the preparation
of hazard identification documents for those chemicals. Information
on exposure will be taken into account in the selection of chemicals
from the Candidate List. Chemicals with the highest level of exposure
concern will be selected first from the Candidate List to be brought
before their respective Committee. Thus the end result of the process
is a form of triage, in which chemicals with the highest level of
hazard concern and with the highest level of exposure concern are
selected first and brought forward expeditiously for Committee consideration.
Chemicals on the Candidate List (those with "high" level
of hazard concern) for which there are lower exposure concerns in
California will, in general, be addressed subsequent to those chemicals
determined to have both a high level of hazard concern and a high
level of exposure concern.
The chemicals selected by OEHHA for the preparation of hazard identification
documents and Committee consideration will be published in the California
Regulatory Notice Register, and data concerning carcinogenicity
or developmental/reproductive toxicity will be requested.
Under exceptional circumstances, the process described in this
document may be abbreviated to allow OEHHA to respond to specific
public health needs. Following consultation with the Committee Chair,
the Director of OEHHA may request that a chemical be placed on the
agenda of the next scheduled meeting. In all cases, the chemical
will be noticed in the California Regulatory Notice Register
and appropriate notification periods will be followed.
5 FINAL STEPS IN THE CONSIDERATION OF CHEMICALS BY THE STATE'S
QUALIFIED EXPERTS
The final two steps of the process under which chemicals are considered
by the state's qualified experts, while not part of the prioritization
procedure, are described below.
5.1 Development and Publication of a Hazard Identification Document
OEHHA will gather and analyze the available data on the candidate
chemicals for consideration by the Committees. Comment from and
participation by scientists with the relevant expertise from other
state agencies and departments will be solicited. Public input and
comment will be solicited by issuing a notice in the California
Regulatory Notice Register requesting that relevant data on
the candidate chemical be submitted to OEHHA within 60 days. The
Director of OEHHA may hold a public workshop to provide for exchange
of information on a candidate chemical and dialogue with the community.
OEHHA and, if appropriate, scientists having relevant expertise
from other state agencies and departments, will develop a hazard
identification document utilizing information in the published scientific
literature, and that received from the public and other sources.
Internal scientific review of the predecisional draft document in
progress may be conducted by scientists from other state agencies
and departments, as appropriate. When the draft is complete, a notice
announcing the public availability of the hazard identification
document and commencement of a 60-day public comment period will
be placed in the California Regulatory Notice Register, and
the draft document will be submitted to the members of the relevant
SAB Identification Committee. At the close of the 60-day public
comment period, OEHHA will organize and index the comments received
and provide this information to the Committee at least two weeks
prior to the meeting at which the candidate chemical will be considered.
5.2 SAB Committee Meeting and Decision
The hazard identification document and the public comments received
during the 60-day comment period are considered by the appropriate
SAB Committee at a public meeting. The Committee chairperson will
facilitate the meeting, during which the public will have further
opportunity to comment. At the conclusion of the deliberations,
the Committee, as the state's qualified experts, may render an opinion
as to the developmental or reproductive toxicity or carcinogenicity
of a chemical, as appropriate. The Committee may render an opinion
that the chemical has been clearly shown to cause cancer or reproductive
toxicity, may fail to reach such a conclusion, or may defer the
decision to a later meeting. In those cases where the decision is
to defer, the Committee will prescribe an action plan that will
discuss further steps to be taken and indicate the timeline for
reconsideration of the chemical. For example, the action plan could
require reanalysis of data and revision of the hazard identification
document, with reconsideration of the chemical at a subsequent meeting.
The dates of Committee deliberations on specific chemicals will
be recorded in the tracking database. Following Committee deliberation,
the draft hazard identification document will be finalized by OEHHA.
5.3 The Proposition 65 List
Chemicals that the SAB Identification Committees find to have been
clearly shown, through scientifically valid testing according to
generally accepted principles, to cause cancer or reproductive toxicity
will be proposed for inclusion on the Proposition 65 list in accordance
with procedures specified in statute (California Health and Safety
Code 25249.5 et seq.). The Proposition 65 list is updated
at least annually.
6 START-UP
Originally, in implementing the prioritization procedure, for carcinogens
OEHHA has first considered chemicals previously selected by the
Carcinogen Identification Committee and other candidate chemicals
with readily available toxicological data. For Darts, OEHHA proposed
to consider previously identified candidate Darts prior to considering
new candidate Darts in the following order: 1) all chemicals in
the top five ranks of the Donald et al. list and all chemicals
identified through the Delphi process; 2) chemicals in the remaining
ranks of the Donald et al. list; 3) all chemicals published
in the California Regulatory Notice Register as candidates,
chemicals formally nominated by other state agencies, and chemicals
identified by the SAP Reproductive Toxicity Subpanel (the predecessor
to the current DART Identification Committee). Using these previous
groupings, OEHHA has completed evaluation of one group of candidates
for DART evaluation identified by means of the Donald et al.
and the OEHHA Delphi processes, and a second group is near completion.
OEHHA has also completed evaluation for one group of carcinogen
candidates.
Now, OEHHA has moved to the random selection process noted above.
This random selection approach will be used as a pilot program for
eighteen months, after which OEHHA will evaluate its experience
under the process and refine the process if warranted.
4 REFERENCES
Donald JM, Monserrat LE, Hooper K, Book SA, Chernoff GF (1992).
Prioritizing Candidate Reproductive/Developmental Toxicants for
Evaluation. Reproductive Toxicology 6:99-108.
Gold L, Sawyer C, Magaw R, Backman G, de Veciana M, Levinson R,
Hooper N, Havender W, Bernstein L, Peto R, Pike M, Ames B (1984).
A carcinogenic potency database of the standardized results of animal
bioassays. Environmental Health Perspectives 58:9-319.
Gold L, de Veciana M, Backman G, Magaw R, Lopipero P, Smith M,
Blumenthal M, Levinson R, Bernstein L, Ames B (1986). Chronological
supplement to the carcinogenic potency database: Standardized results
of animal bioassays published through December 1982. Environmental
Health Perspectives 67:161-200.
Gold L, Slone T, Backman G, Magaw R, Da Costa M, Ames B (1987).
Second chronological supplement to the carcinogenic potency database:
Standardized results of animal bioassays published through December
1984 and by the National Toxicology Program through May 1986. Environmental
Health Perspectives 74:237-329.
Gold L, Slone T, Backman G, Eisenberg S, Da Costa M, Wong M, Manley
N, Rohrbach L, Ames B (1990). Third chronological supplement to
the carcinogenic potency database: Standardized results of animal
bioassays published through December 1986 and by the National Toxicology
Program through June 1987. Environmental Health Perspectives
84:215-285.
National Cancer Institute (NCI). Survey of Compounds Which Have
Been Tested for Carcinogenic Activity. Prepared by Technical
Resources, Inc., Rockville MD. NIH Publication No. 91-3243 (formerly
Public Health Service Publication No. 149). NCI, US Department of
Health and Human Services, National Institutes of Health, NCI, Bethesda,
MD.
Office of Environmental Health Hazard Assessment (OEHHA, 1994).
Proposal for Compiling and Prioritizing Candidate Agents for
Consideration by the Carcinogen Identification Committee. OEHHA,
California Environmental Protection Agency, Sacramento, CA (January
28).
Office of Environmental Health Hazard Assessment (OEHHA, 1996a).
Procedure for Prioritizing Candidate Chemicals for Consideration
Under Proposition 65 by the "State's Qualified Experts".
OEHHA, California Environmental Protection Agency, Sacramento, CA
(May 17).
Office of Environmental Health Hazard Assessment (OEHHA, 1996b).
Procedure for Prioritizing Candidate Chemicals for Consideration
Under Proposition 65 by the "State's Qualified Experts".
OEHHA, California Environmental Protection Agency, Sacramento, CA
(October, 1996).
Schardein JL (1993). Chemically Induced Birth Defects, 2nd
ed., Marcel Dekker, Inc., New York.
Last Updated May 16, 1997
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