WEDNESDAY, OCTOBER 12, 1977

PART IV

=

COUNCIL ON

ENVIRONMENTAL

QUALITY

TSCA INTERAGENCY

TESTING COMMITTEE

Initial Report to the Administrator,

Environmental Protection Agency
55026

[3125-01]

COUNCIL ON ENVIRONMENTAL

QUALITY

TSCA INTERAGENCY TESTING -

COMMITTEE

Initial Report to the Administrator,

Environmental Protection Agency

As required by section 4(e) of the

Toxic Substances Control Act (TSCA), presented herein is the first official report of the Interagency Testing Committee. The Committee has the statutory responsibility to identify and recommend

to the Administrator of EPA chemical

substances which should be tested to determine their hazard to human health or

the environment.

This report reflects the consensus of

representatives from all eight member

agencies: ten substances and categories of substances are recommended as high priority for testing and designated for

consideration by EPA within twelve

months.

As required by the statute, the Committee will continue its review process, reporting to the EPA Administrator

within six months from the date of this

report such additional recommendations

NOTICES

as the Committee finds desirable during

that period.

Dated: October 5, 1977.

WARREN R. MUIR,

Chairman TSCA Interagency

Testing Committee.

EXECUTIVE OFFICE OF TEO PRESIDENT,

COUNCIL ON ENVIRONmIENTAL QUALiTYr,

Washington, D.C., October 4,1977.

Hon. DOUGLAS M. COSTLE,

Administrator,

Environmental Protection Agency,

Washington, D.C.

DEAR M . COSTLE: The enclosed document is the first official report submitted

to you by the Interagency Testing Committee pursuant to Section 4(e) of the

Toxic Substances Control Act (TSCA).

It reflects the consensus of representatives from all eight member agencies:

that the ten listed substances and categories of substances be recommended as high priority for testing under TSCA

and designated for consideration by EPA

within twelve months.

The report describes the process employed by the Committee in making its

recommendations and the rationale for

each designation. A supporting dossier

for each designation will be forwarded to

the Office of Toxic Substances In the

next few weeks.

Only a portion of the compounds Identified in the July preliminary report has

been considered to date. The first revision of our recommendations will be

based largely upon further review of

those chemicals previously identified.

Because this is a continuing process, we will, of course, Identify additional chemicals for such review as Information be- comes available to us.

The Committee has been hampered In its

deliberations by the lack of a readily available and consolidated source of data on the

many chemicals to which man and the on- vironment are ekposed. Other activities

under TSCA, e.g., development of coordinated data systems, inventory reporting, and

other information collection under Section

8, should be of considerable value in future

Committee efforts.,Thereforo, we expect that a number of additional substances will be

listed and integrated in our future reports,

We hope our ,analysis and recommendations will be helpful to EPA In its implementation of the Toxic Substances Control

Act.

Sincerely,

WARREN R. Mum, Ph.D.,

Chairman, TSCA Interagency Testing Committee.

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977
NOTICES

INITIAL REPORT OF THE TSCA INTERAGENCY TESTING COMMITTEE

TO TE I

ADMINISTRATOR, ENVIRONMENTAL PROTECTION AGENCY

October 1, 1977

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

55027
NOTICES

CONTENTS

Committee Membership i

Acknowledgments ii

SUMMARY iii

CHAPTER 1. INTRODUCTION

1.1 Background 1

1.2 Committee Establishment and Responsibilities 2

CHAPTER 2. DEVELOPMENT OF HE COMMITTEE'S INITIAL RECOMMENDATIONS

2.1 Selection of the Commi tee's Basic Approach 4

2.2 Establishment of the -xttial Listing -. 7

2.3 Reduction to the Maste= File 7

2.4 Selection of the Preliminary List 8

2.5 Public Comment on the Preliminary List 10

2.6 Selection of Substances for Detailed Review 11

2.7 Considerstion for Listing and Designation 14

2.8 Consideration of Availability of Testing Facilities

and Personnel 15

CHAPTER 3. RECOMMENDATIONS OF THE COMMITTEE

3.1 Substances and Categories of Substances Recommended

for Testing 17

3.2 Reasons for Recommending Tes.ting of the Substances

and Categories 19

3.2.A Alkyl Epoxides 19

3.2.B Alkyl Phthalates 20

-3.2.C Chlorinated Benzenes, Mono- and Di- 21

3.2.D Chlorinated Paraffins, 35-64Z Chlorine 22

3.2.E Chloromethane 23

3.2.F Cresols 24

3.2. G Re.xachloro-1 , 3-Butadiene 25

3.2.H Nitrobenzene 26

3.2.1 Toluene 27

3.2.J Xylenes- 28

APPENDICES

APPENDI A DATA SOURCES US=D FOR PREPARATION OF THE

INITIAL LIST 29

APPENDIX B -PRODUCTION, RELESE AND EXPOSURE SCORES 32

APPENDIX C ORDERING OF TE CHEMICALS BASED ON

'PRODUCTION, RELEASE, AND EXPOSURE 38

APPENDIX D BIOLOGICAL AND "NVIRONMENTAL SCORES 39

FEDERAL REGISTER, VOL. 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977
NOTICES

TSCA INTERAGENCY TESTING CONMITEE

Statutory Member Agencies

Council on Environmental Quality National Institute of Environmental

Health Sciences

Warren R. Muir, Member and

Committee Chairman Hans L. Falk, Member

Warren T. Piver, Alternate

Department of Commerce National Institute for Occupational

Safety and Health

Sidney R. Galler, Member

Norbert P. Page, Member

'Bernard Greifer, Alternate

Jean G. French, Alternate

Environmental Protection Agency National Cancer Institute

William M. Upholt, Member James M. Sontag, Member

James R. Beall, Alternate

National Science Foundation

Marvin E. Stephenson, Member

and Committee Vice Chairman

Carter Schuth, Alternate

Occupational Safety and Health

Administration

Grover C. Wrenn, Member

James M. Vail, Alternate

Liaison Agencies (non-Voting)

Department of Defense Department of Interior

Seymour L. Friess Charles R. Walker

Food. ani Drug Administration U.S. Consumer Product Safety

Commission

Allen H- Heim

Robert M. Hehir

Joseph McLaughlin

Committee Staff

Secretary: Phyllis D. Tucker

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

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FEDERAL REGISTER, VOL. 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

NOTICES

ACKNOWLEDGHENTS

The Committee wishes to acknowledge the important contributions

of the many individuals and groups who have significantly aided

us in our w6rk. These include:

- Clement Associates, Inc., technical support contractor;

- the National Science Foundation, for funding and managing

the technical support contract and the National Cancer

Institute and National Institute of Environmental Health

Scientes for assist~ng in that funding;

Z- government experts who assisted in the scoring of biological

activity and test needs, including Laurence Fishbein of the

National Center for Toxicological Research, Elizabeth Weisburger

of the National Cancer Institute, and a number. of experts from

the Department of Interior;

EPA staff members who assisted the Committee in a variety

of activities, and particularly:

Donald Barnes, Office of Toxic Substances

Joyce Dan, Interim Secretary to the Committee

John Lyon, Office of General Counsel

Joseph Merenda, staff support to EPA member

Lamar Miller, interim staff support to EPA member

Ralph Northrop, Jr.., Office of Toxic Substances

the numerous experts who prepared presentations and materials

for the Committee; and

the many individuals and organizations who submitted comments

on the Committee's Preliminary List.

io
NOTICES

SUMMARY

The Toxic Substances Control. Act (TSCA) established the TSCA

Interagency Testing Committee, giving it the continuing responsibility

to identify and recommend to the Administrator of the Environmental

Protection Agency chemical substances and mixtures which should be.

tested to determine their hazards to human health and the environment.

The Committee's initial recommendations are to be published in the

Federal Register and transmitted to the EPA Adminitrator within nine

months of the effective date of TSCA. The Committee is to consider

additions to its recommendations at least every six months.

In meet3=g its charge, the Committee has, with the assistance of a

technical support contractor, carried out a multi-step screening

procedure to identify for its detailed review a limited number of

substances and categories of substances likely to have priority for

testing to determine their effects on human health and the

environment. A number of substances and categories identified by this

process have been reviewed by the Committee, which has given careful

consideration to each of the eight factors specified in Section

4(e) (1)(A) of TSCA. The Committee has also considered such factors as

test programs currently in progress, the current status of regulatory

action with respect to a substance, and the need for test data on all

members of certain categories rather than on one or more individual

members of the category.

In July, 1977, the Committee published a Preliminary List of 330

substances and categories of substances along with a background

document describing the methods used by the Committee in making those

selections. The Preliminary List included substances and categories

selected primarily on the basis of potential for human exposure and

environmental release. Public comments received on the Preliminary

List were reviewed by the Committee and considered in the development

of the Committee's initial recommendations.

Subsequently, the chemicals on the Preliminary List and chemicals

added -a the Preliminary List based on the public comments were

furthe- screened by the Committee based primarily on their potential

for adverse human and/or environmental effects, but also continuing to

co-nidr their exposure potential. Available data on and potential

for carninogenic, mutagenic, teratogenic and chronic toxic effects, as

welL as their ability to bioaccumulate or cause deleterious

environmental effects were considered. A scoring system which took

into account both available information and the lack of it for these

factors was used in this process. Using these scoring results and its

scientific judgment, the Commmittee further narrowed the list under

consideration to about 80 substances and categories. Aided by

information dossiers prepared by its contractor, the Committee

reviewed about half of these compounds and has selected for inclusion

in its initial recommendations to the EPA Administrator four

individual substances and six categories of substances. Each is being

1;is

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

55031
I

NOTICES

designated by the Committee for consideration by EPA within the next

12 months. They are (arranged alphabetically):

Substance or Category

Alkyl Epoxides

Alkyl Phthalates

Chlorinated Benzenes,

Mono- and DiChlorinated Paraffins

I

Chloromethane

CresOls

Hexachloro-1, 3-

butadiene

Nitrobenzene

Toluene

Xylenes

Testing Recommended

Carcinogenicity, mutagenicity, teratogenicity,

other chronic effects, environmental effects,

and epidemiological study

Environmental effects

Carcinogenicity, mutagenicity, teratogenicity,

other chronic effects, environmental effects,

and epidemiological study

Carcinogenicity, mutagenicity, teratogenicity,

other chronic effects, and environmental

,effects

'Carcinogenicity, mutagenicity, teratogenicity,

and other chronic effects

Carcinogenicity, mutagenic.ty, teratogenicity,

other chronic effects, and environmental

effects

Environmental effects

Carcinogenicity, mutagenicity, and

environmental effects

Carcinogenicity, teratogenicity, other

chronic effects, and epidemiologioal study

Mutagenicity, teratogenicity, and

epidemiological study

The Committee's reasons for each recommendation and a more detailed

definition of each of the categories are presented in Section 3.2.

The Committee expects that the precise definition of each category

willbe. considered further- by EPA in the course of developing testing

rules. The Committee also recognizes that certain members of a

category may already have been adequately tested for one or more of

the effects for which testing of the category has been recommended.

In that case, no further testing for that combination of substance and

effect would be needed.

A dossier summarizing the information considered by the Committee in

selecting each substance or category will be forwarded to EPA in the

next few weeks. The Committee will continue its review of the

remaLning substances and categories already selected for detailed

review, and may identify and review others, in anticipation of its

next report.

'v

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

55032
NOTICES

INITIAL REPORT OF THE TSCA INTERAGENCY TESTING CO ffTTEE

TO THE

ADMINISTRATOR, ENVIRONMMETAL PROTECTION AGENCY

October 1, 1977

CHAPTER I. INTRODUCTION

1.1 BACKGROUND

Section 4(e) of the Toxic Substances Control Act (P.L. 94-469,

hereafter referred to as TSCA) established the TSCA Interagency

Testing Committee. That Committee has the continuing responsibility

to identify and recommend to the Administrator of the Environmental

Protection Agency chemical substances or miLtures which should be

tested to determine their hazard to human health or the environment.

The statute provides that the Committee shall make its initial

recommendations to EPA by October 1, 1977.

To carry out this responsibility, the Committee has developed and

executed a multi-step screening procedure to identify for its detailed

review a number of chemical substances and categories of chemical

substances expected to have a high priority for testing based on the

criteria set forth in Section 4(e)(1)(A) of TSCA. The Committee

received extensive technical support in this screening, and in the

gathering of data on substances and categories selected for detailed

review, from Clement Associates, Inc. under a contract with the

National Science Foundation. After reviewing the information

available to it on each candidate, including public comments submitted

in response to the Committee's July, 1977, publication of a

preliminary list of substances under consideration, the Committee has

selected the ten substances and categories being recommended to the

EPA Administrator in this report. As required by the statute, the

Commirree will continue its review process, reporting to the EPA

Adm+nstrator within six months from the date of this report such

aaddit-nna! recommendations as the Committee finds desirable during

-that period.

This report documents the procedures used by the Committee in

selecting those substances and categories now being recommended for

testing, and, as required by the statute, provides the Committee's

reasons for making each such recommendation. In addition to the

material contained in this report, the Committee is now finalizing a

series of dossiers developed by its technical support contractor which

will summarize all of the non-confidential information considered by

the Commttee in deciding to recommend each substance or category for

testing. These dossiers will be transmitted to the EPA in a few weeks.

1

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

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FEDERAL REGISTER, VOL. 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

NOTICES

1.2 COMMITTEE ESTABLISHMENT AND RESPONSIBILITIES

The Committee, as established by Section 4(e) of TSCA, has eight

members, appointed by the eight Federal agencies identified for

membership in Section-4(e)(2)(A) of the Act. In additioni a number of

alternates have been designated as permitted by Section 4(e) (2) (B) (i).

The Committee has adopted the name "TSCA Interagency Testing

Committee", which is frequently shoftiened in this report to

"Committee". As provided by Section 4(e) (2) (B) (iii), it has selected

a chairman from among its members. The Committee has also invited

several other Federal agencies with programs related to the control of

toxic substances, but which were not included in the statutory

membership of the Committee, to designate liaison representatives to

attend Committee meetings. Current Committee members, alternates, and

liaison representatives are identified in the frontispiece.

The Comm.ttee's testing priority recommendations are required by

Section 4(e) to be published in the Federal Register and transmitted

to the EPA Administrator within nine months of the January 1, 1977,

effective date of TSCA. At least every six months .thereafter, the

Committee is required to review its recommendations and make such

revisions as are necessary.

The Committee's recommendations are to be in the form of a list of

chemical substances or mixtures set forth, either indivLdually or in

groups, in the order in which the Committee determines the EPA

Administrator should consider taking action under Section 4(a) in

developing and promulgating testing regulations. The Committee is

authorized to designate up to 50 of these substances or groups for

which the EPA Administrator must within 12 months either initiate

rulemaking requiring their testing or publish reasons for not taking

such action.

In developing its recommendations, the Committee is directed by

Section 4(e)(1)(A) of TSCA to consider, along with all other relevant

factors: the production volume, environmental release, occupational

exposure, and non-occupational human exposure to the substance or

mixture; the similarity of the substance or mixture in question to

others 'known to present unreasonable risk of injury to health or the

environment; the extent of data on the effects of the substance or

mixture in question on health or the environment and the extent to

which additional testing of the substance or mixture may produce data

from which effects can reasonably be determined or predicted; and the

reasonably foreseeable availability of facilities and personnel for

performing the testing being recommended. The Committee is also

directed by Section.4(e) to give priority attention in establishing

its list of recommendations to substances or mixtures which are known

or suspected to cause or contribute to cancer, gene mutations, or

birth defects.

2
NOTICES

The Committee's specific reasons for including each substance or

mixture in its recommendations are required to be published in the

Federal Register and transmitted to the EPA Administrator along with

the priority list.

While Section 4(e) refers to the Committee's recommendations as a list

of "chemical substances and mixtures", Section 26(c)(1) authorizes the

EPA Administrator to take actions (including the promulgation of

Section 4(a) testing regulations) with respect to categories of

chemical substances or mixtures as well. A category is defined in

TSCA as a group whose members are similar in molecular structure; in

physical, chemical, or biological properties; in us ; in mode of

entrance ihto the human body or into the environment; or in any other

way, so long as the grquping is not based solely on its members being "new chemical substances" as defined in the Act. Since the EPA

Administrator is authorized to promulgate testing regulations for

categories of chemical substances or mixtures, the Committee has

concluded that its recommendations to the EPA Administrator may also

include categories (or groups) of chemical substances or mixtures, as

well as individual substances and mixtures. This conclusion is

consistent with Section 4(e) which states that the Committee's

recommendations for testing "shall be in the form of a list of

chemical substances and mixtbres which shall be set forth, either by

individual substance or mixture or by' groups of substances or

mixtures...."

In order to maintain consistency in this report and in keeping with

its meaning in TSCA, the term "category" will be used to reflect

groupings of substances. "Substance" will be used to refer to both

individual chemicals as well as mixtures.

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

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55036

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

NOTICES

CHAPTER 2. DEVELOPMENT OF THE COMMITTEE'S INITIAL RECOWMIMATIONS

2.1 SELECTION OF THE COMMITTEE'S BASIC APPROACH

Estimates of the number of chemical substances and mixtures subject to

TSCA range from tens of thousands to over 100)900;-the-number and

identities of these substances and mixtures will not be established

until after the completion of the chemical inventory under Section

8(b) of TSCA. Nevertheless, all of these substances and miJtures,

together with others which. may be manufactured in the future, are

subject to the promulgation of testing rules under Section 4(a) and are

thus within the puziviev of the Interagency Testing Committee.

At the same time, Section 4(e) of TSCA specifies a number of factors

which the Committee is to c6nsider in determining whether to recommend

a substance for testing. Careful consideration of these factors

requires the collection and review of a substantial amount of data

concerning the production, use, chemical and biological activity, and

previous testing of each substance or category of substances under

-consideration.

As a result, because of the lack of a comprehensive and readily

accessible data base on current chemica\Is, 'the large number of

potential candidates for the Committee's consideration, and the

statutory deadline for the Committee's initial recommendations to EPA,

the Committee has had to select for its detailed consideration only a

small subset of the possible candidates.

In considering alternative approaches to. selecting a limited number of

substances for detailed review, the Committee met with a number of

experts on chemical data systems and chemical characterization.

Several possible approaches were identified. One was a nomination

approach in which Committee members or other experts would nominate

specific chemicals for consideration. Another was to use

structure-activity relationships to identify for review substances

chemically similar to others of known hazard. Yet another approach

was to focus the Committee's attention on those substances known to

have high\ levels of production volume, environmental release, or human

exposur.e.

After considering these alternatives, the Committee decided to adopt a

combined strategy employing features of each. This resulted in a

multi-step screening process wherein a relatively large number of

substances were considered initially and at each subsequent step a

smaller subset was selected for collection of more data and more

intensive review.
NOTICES

T-e basic steps in the process adopted by the Committee, which are

illustrated in Figure 1 and are described in more detail in

subsequent sections; were as follows:

a. Establishment of an-INITIAL LISTIIIG of about 3,650

substances and categories of substances previously

identified as potential hazards to human health or

the environment,

b. Compilation of a smaller MASTER FILE (about 1,700

substances and categories) through elimination from

the INITIAL LISTING of substances not in commercial

production or used predominantly as pesticides, food

additives, or drugs,

c. Selection of a PRELIMINARY LIST of about 330 substances

and categories for further consideration based on

evaluation of the production volume, environmental

release, occupational exposure, and general human

exposure levels of the substances in the MASTER iLE,

d. Selection of about 80 substances and categories for

detailed review based on evaluation of the potential

biological activity and need for health and ecological

effects testing of substances appearing on the

PRELIMINARY LIST,

e. Selection of substances and categories recommended

for testing after review of preliminary dossiers

prepared by the Committee's contractor, public

comments on the PRELIMINARY LIST, and other pertinent

information available to the Committee from

various agencies,

f. Documentation of the Committee's reasons for including

each substance or category in its list of

recommendations and completion of a final dossier

summarizing the information considered by the Committee

in reaching its decision.

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

55037
55038 NOTICES

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Carrying out this multi-step process required the collection, review,

coding, and analysis of data on a large number of chemical substances,

as well as the application of scientific judgment in many areas where

adequate data were unavailable. The Committee was supported

extensively in these efforts by Clement Associates, Inc. under a

contract with the National Science Foundation (Contract No. NSF ENV77-

15417 with partial funding by the NIMRS and NCI. The contractor employed

expert consultants from a variety of disciplines in carrying out its tasks

under the contract. In addition, many U.S. Government agencies made

data and expertise of their employees available to the Committee for

these efforts.

Several of the steps of the Committee's procedure employed

quantitative scoring of the substances under consideration. Members

of the Committee used their professional expertise and judgment in

applying these scores to the decisions at each step.

2.2 ESTABLISHMENT OF THE INITIAL LISTING

In order to focus its initial attention on substances likely to

require health and/or ecological effects testing, and for which

sufficient preliminary data were likely to be available to permit more

detailed reviews at later steps, the Committee chose to limit its

initial consideration to substances or categories of substances which

had already been identified, in previous reviews as being of concern

because of potential adverse effects on human health or the

environment or as having large production volumes and a potential for

substantial human exposure or environmental release. Nineteen

separate source lists of this type were identified by the Committee

and pooled to produce the INITIAL LISTING of about 3,650 substances,

mixtures, and categories. The individual source lists are identified

and described briefly in Appendix A.

2.3 REDUCTION TO THE MASTER FILE

The INITIAL LISTING included a number of substances having pesticide,

food additive, or drug uses, all of which are regulated under other

Federal statutes and are exempted from regulation by TSCA. To

identify them, the INITIAL LISTING was compared with lists of

pesticides prepared by the EPA and lists of food additives and drugs

prepared by the Food and Drug Administration, using Chemical Abstracts

Service (CAS) Registry Numbers. This initial purge of substances

subject to other statutes was incomplete, since some entries on source

lists did not include CAS numbers. To compensate for this, a further

manual purging was required. Consideration was also given to the fact

that a substance used as a pesticide, food additive or drug may also

have other uses that are subject to the authority of TSCA. Since

pesticides, food additives, and drugs are generally produced in

limited volumes, substances identified as such but having annual

production over 10 million pounds were considered likely to have other

uses as well and were retained on the truncated list for further

review of their uses. Substances identified as pesticides, food

additives, or drugs but known to the Committee or its contractor to

have other uses within the jurisdiction of TSCA were also retained.

7

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

NOTICES 553039
The resulting file was reduced further by the elimination of chemicals

which were judged not likely to be in commercial production. This was

accomplished by comparing the file against EPA's Candidate List of

Chemical. Substances, prepared by the Office of Toxic Substances (dated

April 1977). Again, the basis of comparison for this purge was an

assigned CAS number. Consequently, this purge did not affect those

chemicals on source lists for which no CAS number was given. In an

attempt to eliminate-substances' which are not in commercial

production, the followifg rule was adopted: any substance not

identified by a CAS number which appeared on the NIOSH Registry

(Source List 13 of Appendix A) and on none of the other source lists

was judged not likely to be in commercial production. This decision

was based on the fact that the NIOSH Registry lists any substance for

which toxic effects have been reported, including research chemicals.

A scan of the substances eliminated by the application of this rule'

demonstrated its usefulness: few of the purged substances were

recognized to be in commercial production.

As a result of the purges described above, a MASTER FILE of

approximately 1700 substances emerged.

2.4 SELECTION OF THE PRELIMINARY LIST

Having developed a MASTER FILE of substances-to be considered for

possible recommendation to EPA for testing, the Committee began to

apply the eight factors explicitly identified for its consideration In

Section 4(e) (1) (A). While recognizing that there would be advantages

to applying all of the first seven factors* simultaneously in

evaluating the relative priorities for detailed review of the

substances under consideration, the Committee concluded that

assembling and evaluating the necessary data for all substances on the

MASTER FILE would not be feasible within the time schedule established

by statute, considering the limitations of current chemical

information systems and the number of professional judgments which

would have to be made. Evaluation of the fifth, sixth, and seventh

factors (relating to chemical similarity to substances of known

hazar&, existing health and environmental effects data, and need for

testing) was anticipated to require more independent review and

judgment and to be the more time-consuming portion of the task.

Hence, the Committee decided to further reduce the number of

substances under consideration before explicitly evaluating those

factors which had, to scme extent, already been reflected in the

choice of source lists.

* The eighth factor, the reasonably forseeable availability

of facilities and personnel for performing the needed

testing, was considered principally by the ComiIttee in

terms of the aggregate facilities and personnel needs for

carrying out all of the Committee's recommendations. See

Section 2.8 for further discussion of this factor.

8

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY,'OCTODER 12, 1977

55040 NOT'ICES
1NOTICES

_Ths_1reduction,_ which resulted in the selection of the Lf

LIST, was based principally on eva.uac.fotff- the first tour factors

identified for the Committee s consideration in Section 4(e)(1)(A) of

TSCA. These are:

i) quantity of the substance produced annually

(ii) amount of the substance released into the

environment

(iii) number of individuals occupationally

exposed and duration of their exposure

(xv) extent to which the general population

will be exposed.

Using a combination of published data and judgment, the Committee's

contractor made an attempt to score each substance in the IASTER FILE

for these four factors. Appendix B. describes in more detail how

scores were assigned to substances. Information on the use or uses of

a substance was critical to the assignment of scores for environmental

release and general population eaxposure, and scores for those factors

could not be assigned if use information could not be found by the

contractor. For about 1,000 of the 1,700 substances in the iASTER

FILE this was the case; as a result, for only about 700 of the

substances was it possible to assign scores. By combining the scores

for the four factors, as described in Appendix C, a rank-ordered list

of the scored substances was prepared for the Committee's

consideration.

In selecting the approximately 330 substances and categories included

on the PRELIIARY LIST, the Committee considered all of the scored

substances and eliminated from current consideration a number of them

which in the Committee's professional judgment were found to be:

a. Currently under stringent regulation or of lower

priority for the Committee's purposes

because their hazard is reasonably well

characterized (e.g., vinyl chloride and

mercury);

b. Essentially inert materials (e.g. certain

polymers) or substances reasonably well

characterized as having low toxicity (e.g.,

methane);

c. Covered by testing requirements under food,

drug and cosmetic or pesticide legislation

(e.g., citric acid); or

d. Certain natural products (e.g., asphalt)

whose consideration should be deferred pending

better characterizatibn for testing purposes.

Others of the scored substances were specifically selected by the

Committee for inclusion on the PRELIMINARY LIST based on judgment of

members that further review was needed. The remainder of the scored

substances were considered for inclusion on the PRELIMARY LIST based

on their relative ranking in the scoring process.

9

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55041
NOTICES

In addition to the scored substances, the Committee also considered in

selecting the PRELIMINARY LIST the unscored substances from the MASTER

FILE and a limited number of additional substances recommended by

Committee members or the Committee's contractor. A number of

substances from these sources were included on the PRELIMINARY LIST

based on the Committee's knowledge of the substance and its uses or

the Committee's professional judgment that the substance should be

further evaluated.

In reviewing substances for possible inclusion on the PRELIMINARY

LIST, the Committee also considered the desirability of grouping

substances nto categories. In several cases the Committee grouped

chemlcally-related substances from the MASTER FILE while in other

cases the Committee retained groups which had already appeared in one

of the source lists. About 15% of the entries on the PRELIMINARY LIST

were categories.

2.5 PUBLIC COMMENT ON I. PRELIMINARY LIST

The PRELIMINARY LIST, together with a background document describing

its development, was published by the Committee in July, 1977. Notice

was published by the Committee in the Federal Register (42 FR 30531

and 42 FR 40756) announcing the availability of the list and

background document and requesting public comment. Comments were

specifically requested on:

a. The methodology used by the Committee in

developing the PRELIMINARY LIST;

b. Substances not appearing on the PRELIMINARY

LIST which commentors might recommend for

consideration by the Committee and the

commentor's reasons for the recommendation;

c. Substances appearing on the PRELIMINARY LIST,

which commentors might recommend that the

Committee not consider further and the reasons

for that recommendation; and

d. -Comments on. the needs for and relative priority

of testing of the substances being considered by

the Committee.

As an additional aid to ccmmentors and others interested in the

Committee's activities, copies of the list of substances comprising

the MIASTER FILE and a tabulation of the scores for production volume,

environmental release, and occupational and general population

exposure considered by the Committee in selecting the PRELIMINARY LIST

were made available for public inspection at the headquarters and

regional offices of the Environmental Protection Agency.

Comments on the PRELIMINARY LIST were received from about 65

industrial firms, trade associations, environmental organizations,

government agencies, and individuals. About two-thirds of the

10

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

55042
commentors recommended deletion from the Committee's further

consideration of one or more substances or categories appearing on

the PREJ.7 AY LIST, while four commentors recomended additional

substances for the Committee's consideration. About one-fifth of the

commentors included comments on the methodology employed by the

Committee in developing the PREL1INAPy LIST and about one-third

included comments on other issues related to the Committee's

activities. Such issues were the use of categories in the Committee's

recommendations to EPA, documentation of the Committee's reasons for

its decisions with respect to specific substances, and provision of

opportunity for public comment on the Committee's actions.

Public comments on the PRELflfINARY LIST have been reviewed by the

Committee and considered in the development of the Committee's initial

recommelations. Four of the seven additional substances recommended

by commentors were added to the PRELIINARY LIST for consideration in

selecting substances and categories for detailed review. Because of

the large number of comments recommending deletions of substances from

the Committee's consideration and the limited time available under the

statutory deadline, pertinent comments were considered on a

substance-by-substance or category-by-category basis during the

Committee's review of preliminary dossiers and consideration of

reasons for and against recommending testing. Comments on the

Committee's methodology have been reviewed and will be considered in

subsequent activities of the Committee. In the Committee's judgment,

the recommended changes in methodology would not, if implemented,

alter its initial recommendations. Comments dealing with use of

categories, documentation of the Committee's reasons for actions, and

other more general issues were also reviewed and considered in the

development of the Committee's recommendations.

2.6 SELECTION OF SUBSTANCES FOR DETAILED REVIEW

This step of the Committee's procedure extended the scoring of the

substances under consideration to factors (v) through (vil) of Section

4 (e) (1) (A). These factors are:

(v) the extent to which the substance or

mixture is closely related to a chemical

substance or mixture which is known to

present an unreasonable risk of injury to

health or the environment;

(vi) the existence of data concerning the effects

of the substance or mixture on health or the

environment; and

(viLi) the extent to which testing of the substance

or mixture may result in the development of

data upon which the effects of the substance

or mixture on health or the environment can

reasonably be determined or predicted.

11

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NOTICES

To accomplish this, each substance on the PRELIMINARY LIST was scored

-for each of seven biological activity factors by a number of experts

available through the Committee's contract. The factors were:

carcinogenicity, mutagenicity, teratogenicity, acute toxicity, other

toxic effects such as reproductive effects or organ-specific toxicity,

bioaccumulation; and ecological effects. After reviewing a summary of

information on the biological activity of the substance developed by

the contractor based on the open literature, each of the contractor's

scorers assigned a score to the substance for the effect(s) for which

that scorer was responsible.

A total of nine scorers was used by the contractor, with two or three

scorers separately evaluating each effect in most cases. Each scorer

considered both the summary information provided by the contractor and

his personal knowledge of the substance and chemically-related

substances in assigning scores. Any substantial discrepancies among

individual scorers were identified, discussed among the scorers, and a

consensus reached; in the case of minor discrepancies in the scores

for any factor, the scores of the several scorers were averaged.

In addition, three of the effects (carcinogenicity, mutagenicity, and

ecological effects) were separately scored by government experts from

the National Cancer Institute, National Center for Toxicological

Research, and Department of Interior,. respectively. These scores were

averaged with those of the contractor's scorers.

Scores assigned for the various effects took the form of either a

numerical score (generally 0, 1, 2, or 3) or a letter score (generally

x, xx, or xxx). Assignment of a numerical score indicated a judgment

that further testing of the substance is not needed for the effect

under consideration, while the magnitude of the score indicated the

degree to which the effect had been confirmed or .the dose level at

which it had been found. Assignment of a letter score, on the other

hand, indicated a judgment that further testing should be carried out,

with the number of "x's" assigned reflecting a judgment as to the

level of numerical score that might be anticipated after testing. For

example, in scoring a substance for carcinogenicity a score of 3 meant

that the substance is well established as a carcinogen in humans or

expermmental animals, while a score of xxxmeant that the substance is

strongly suspected of carcinogenic activity but has not been

adequately tested. In averaging the scores assigned to a substance by

the several scorers for a given factor, no mixing of numerical and

letter scores was permitted. Any discrepancies between scorers in

chosing the numerical or letter scale were discussed among the scorers

and resolved. The criteria applied by the scorers in assigning scores

for the various factors are described in more detail in Appendix D.

Categories of substances appearing on the PRELIMINARY LIST were not

generally scored as entities, but rather, scores were assigned

separately for each of the example substances listed under the

category heading in the list.

12
.Using-these-scores, :the.-contractor .provided the Committee a series of

lists bf the substances appearing on the PRELIHINARY LIST ranked

according to various criteria. These included separate lists for each

factor- ranked by the average score a substance received for that

factor. (identifying those substances judged most in need for testing

for a single effect) and a list ranked by the sum of the letter scores

received by a substance for all factors (identifying substances

requiring testing for a number of effects). Also tabulated on each

list.was an exposure index for each substance which was derived from

the earlier scoring of production volume, environmental release, and

occupational and general population exposure. For the human health

effects factors and total letter score lists the exposure index used

was the sum of the production volume, occupational exposure, and

general population exposure scores, while for the bioaccumulation and

ecological effects factors, the exposure index was the sum of the

production volume and environmental release scores. The Committee

also received from its contractor a list of those substances evaluated

by the scorers which were known or might be anticipated to have

additional adverse health or environmental effects as a result of

contaminants appearing in the commercial product or degradation

products of the substance under consideration.

The Committee's selection of substances and categories from the

PRELIMINARY LIST to be carried forward for detailed review used the

various lists provided by its contractor as guides, but reflected the

independent judgments of the members of the Committee. First, the

scores themselves were reviewed, with any major discrepancies between

the contractor's scores and those of the government scorers or the

judgments of Individual tommittee members being considered. Then, the

Committee turned to the various ranked lists, reviewing in turn the

substances ranked most in need of testing on the sum-of-letter-scores

lst or the lists for the individual factors. Each

substance appearing in the top 75 to 100 positions on one or more of

these lists was considered by the Committee and a decision made

whether to select it for detailed review.

Particular attention was paid by the Committee to substances known or

suspected to be carcinogens, mutagens, or teratogens, Jn keeping with

the statutory guidance provided the Committee in Section 4(e)(1)(A) of

TSCA. This emphasis was reflected not only in the Committee's

consideratzon of individual substances and categories, but also in its

struc=nring of the review process, since these effects were scored

individually and, in effect, received greater attention than dLd other

effect:s scored 3n groups (e.g., other toxic effects or ecological effects).

Categories of substances appearing on the PRELfl12TARY LIST were also

revewed, in terms of the scoring of their example members and the

Commaztt's judgment as to retaining them. A number of decisions to

modify previous categories or define new categories were made by the

Commixt-ee during this review process.

In reviewing these lists, more than two-thirds of the individual

substances .scored by the contractor were explicitly considered by the

Committee. Approximately eighty substances and categories were

selected by the Committee for the drafting of preliminary dossiers and

further detailed review. Of these, about half were individual

substances and half categories.

13

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FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

NOTICES

2.7 CONSIDERATION FOR LISTING AND DESIGNATION

For each of the approximately eighty substances and categories

selected for detailed ieview., preliminary dossiers have been (or are

being) prepared by the Committee's contractor. Within the time period

allowed by the statute for development of the Committee's initial

recommendations, preliminary dossiers were drafted for about

one-half of the substances and categories for detailed review.

Consideration of these and other information resulted in the

initial recommendations transmitted by this report. Consideration of

the remaining substances and categories already selected for detailed

review, and others which may subsequently be selected, will continue

and will be reflected in subsequent recommendations to EPA by the

Committee.

The preliminary dossiers summarized information obtained from the open

literature relating to the identification, relevant chemical and

physical properties, production volume, uses, environmental release,

and exposure to the substance under consideration as well as

information on the nature and findings of previous studies of its

human health and environmental effects. Information on the biological

activity of other chemically similar substances was also included

where available. Preliminary dossiers for categories of substances

included these types Of information for specific members of the

category, generally the example members identified in the PRELIMARY

LIST.

Using the information summarized in the preliminary dossier, together

with information submitted 'n public comments on the PRELIMINARY LIST,

information available to the Committee from various Federal agencies,

and the members' individual knowledge, the Committee reviewed each

substance or category. Each of the factors specified in Section

4(e)(1)(A), as well as any other relevant factors identified by the

Committee on a case-by-case basis, was considered. In particular, in

considering factor (vi) of Section 4(e) (1) (A), the existence of data

concerning the effects of the substance on helath or the environment,

the Committee considered test programs currently in progress, as well

as data already generated. Another factor considered in certain

instances was the status of current regulatory action relative to the

suostance. In .each case where a category of substances was under

consideration the appropriate definition of the category and the need

for data on all members of the category were considered. Where relevant

to the particular type of testing under consideration for a substance or

category, factor (viii) of Section 4(e) (1) (A), the availability of

test facilities and personnel, was discussed on a case-by-case basis.

In general, however, this factor was considered in the aggregate after

the Committee's tentative recommendations for all substances and

categories had been identified. The Committee's consideration of this

factor is discussed further in section 2.8 of this report.

14
NOTICES

After reviewing and thoroughly discussing the information available to

the Committee on the substance or category under consideration, a

decision was made regarding whether to recommend the development of

test rules by EPA and, if so, for which effects. Subsequently, one or

more Committee members participated in the drafting of the supporting

reasons for each recommendation and these reasons were again reviewed

by the Committee. A final decision to recommend the substance or

category for testing represents a consensus by the Committee members

that sucli testing is needed to evaluate the effects of the substance

(or of each individual substance falling within the definition of a

category) on human health and the environment, and that priority

attention should be given by EPA to requiring the conduct of such

testing. The Committee recognized, of course, that some members of

recommended categories may have already been adequately tested for the

effects of concern and would not require further testing.

Several substances and categories reviewed by the Committee were

deferred for further consideration because of insufficient information

to adequately define the categories or to determine the needs for

testing.

Assignment of priority order to the substances and categories

recommended for testing was also considered. The Committee concluded

that all of the substances and categories being recommended at this

time should be given equal priority in EPA's development of test

rules. Factors contributing to this decision were the limited number

of recommendations being made, the Committee's decision to designate

all recommended substances and categories for consideration by EPA

within 12 months, and the Committee's understanding of EPA's plans to

develop its test rules for various effects, e.g., carcinogenicity,

rather than for individual substances or categories. The Committee

recommends that these substances and categories be included in the

first applicable "effects rule".

2.8 CONSIDERATION OF AVAILABILITY OF TESTIG FACILITIES AD PERSONNEL

One of the criteria listed in Section 4(e)(1)(A), that the Committee

was required to consider, is the reasonably foreseeable availability of

facil-rZties and personnel for performing the testing it recommends.

The Cmmttee reviewed the results of recent surveys of toxicology

testi:& capabilities conducted by the Society of Toxicology (SOT) and

the D E Commttee to Coordinate Toxicology and Related Programs

(CT=)- While the SOT surveyed general toxicology testing

capabifes, the COTEP specifically assessed inhalation test

caoab-i'7-4ties. The Committee also reviewed the capabilities and

plans ci the National Center for Toxicological Research (ITCTR), the

possibl impact of the FDA's Good Laboratory Practices, and the

logist-ic and practical considerations for carcinogenicity,

mutagenicity, and reproductive effects testing. It also was briefed

on ecological test capabilities and needs in that area.

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

55047
NOTICES

Based upon these reviews, the Committee has concluded that there are

sufficient toxicology testing capabilities in the U.S. to carry out

the health effects testing recommended by the Committee in this

report.

A more difficult area to assess was that of environmental or ecological

testing. Capabilities for acute studies are probably adequate, but

the National capability for conducting long-term tests of chemical

pollution on the envLronment will be less certain until the test

standards and protocols are defined through the rulemaking process.

The Committee feels, however, that the testLng burden likely to

result from recommendations in this report is reasonable.

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

55048
NOTICES

CHAPTER 3. REC01NENDATIONS OF THE C0I.MITTEE

3.1 SUBSTANCES AND CATEGORIES OF SUBSTANCES RECOMEMMDED FOR TESTMIG

As described in Chapter 2 of this report, the Committee has, with the

assistance of a technical support contractor, carried out a multI-step

screening procedure to identify for its detailed review a limited

number of substances and categories of substances likely to hav;

priority for testing to determine their effects on human health and

the environment. A number of substances and categories identified by

this process have been review'ed by the Committee, which has given

careful consideration to each of the eight factors specified in

Section 4(e)(1)(A) of TSCA. The Committee has also considered such

other factors as it judged relevant on a case-by-case basis. Such

additional factors have included test programs currently in progress,

the current status of regulatory action with respect to a substance,

and the need for test data on all members of certain categories rather

than on one or more individual members of the category.

The eighth factor specified in Section 4(e)(1)(A) for the Committee's

consideration, the reasonably foreseeable availability of facilities

and personnel for performing the recommended testing, has (as

described in Section 2.8 of this report) been considered by the

Committee with respect to the aggregate requirements of all of the

testing recommendations made here, as well as for each individual

testing recommendation. In the Committee's judgment there are, or can

be made available within the next few years, adequate facilities and'

personnel for conducting the testing now being recommended by the

Committee. Furthermore, any specific limitations of facilities or

personnel which cannot now be identified by the Committee would be

expected to be short-term in nature and can be taken into account by

EPA in establishing the time periods for submission of the test data

under Section 4(b)(1).

In selecting substances and categories for inclusion in its initial

recommendations, the Committee has also given priority attention to

substances known or suspected to cause cancer, gene mutations, or

birth defects.

Based o its consideration of the factors identified in Section

4(e)(1)(A) and all other relevant factors identified by the Committee,

and us-in all of the information available to it, including the

knowledge and professional judgment of its members, it is the

consensus of the TSCA Interagency Testing Committee that the ten

substances and categories of substances listed in the accompanying

table should be given priority consideration by the Administrator of

the Euvironmental Protection Agency for the promulgation of

regulations under Section 4(a) requiring the conduct of the types of

testing specified. Each of these substances and categories is

designated by the Committee for consideration by EPA within the next

12 months.

17

FEDERAL 'REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

55049
55050

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NOTICES

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In lstng and designatiug-these ten substances and categories, the

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in the development of test rules under Section 4(a) of TSCA. All are

of high priority and should be included in the first applicable

"effects rule" (e.g., carcinogenicity) developed by EPA.

In selecting categories of substances for inclusion in its

recommendations, the Committee recognizes that some members of a

category- may have already been adequately tested for one or more of

the effects listed; in such cases no additional testing would be

required. The Committee also recognizes that the precise definition

of each category will have to be considered and decided by EPA in

developing its test rules.

The Committee's reasons for including each substance or category of

substances on its list of recommendations, which are required by

Section 4(e)(1)(B) to be submitted with the Committee's

recommendations, are presented in the following section. In addition,

the Committee will forward to EPA in the next few weeks a dossier on -

each substance or category included on the Committee's list of

recommendations. These dossiers will summarize the information

pertaining to each substance or category which was considered by the

Committee in making its decision to recommend testing.

3.2 REASONS FOR RECOMMENDING TESTING OF THE SUBSTANCES Af41

CATEGORIES

The ten substances and categories which the Committee has designated

for consideration by the EPA Administrator for development of test

rules within twelve months are listed below with the Committee's

reasons for recommending them.

3.2.A ALKYL EPOXIDES

TESTING RECOMMENDATIONS:

Carcinogenicity

Matagenicity

Te-atogenicity

O=er Chronic Effects

n _r-vronmental Effects

Epidemiology

CATEC-O IDENTIFICATION: This category includes all noncyclic

aliphatic hydrocarbons with one or more epoxy functional groups.

REASONS FOR RECOMMENDATIONS:

Production, Release and Exposure: Although these compounds are

generally used as industrial intermediates, several alkyl epoxides are

produced in very large quantities (e.g., ethylene oxide at over 4

billion pounds per year). The vast amounts produced thus raise

concerns primarily with respect to workplace exposure. The reactivity

of these compounds is such that environmental persistence is not

anticipated; however, their reaction products may be of significance.

19

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NOTICES 55051
55052

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

NOTICES

EFFECTS OF CONCERN: The epoxy structure is a relatively reactive

functional group which is believed to be the source of the

carcinogenic and mutagenic activity which is well characterized for

several members reviewed (particularly the diepoxides). Thus, while

some members of the group appear to be relatively well characterized

as potential mutagens and/or carcinogens, these results and the

presence of the epoxy functional group raise the need for testing

other compounds in this group for these and other effects.

Carcinogenicity: Diepoxides are demonstrated carcinogens in animal

studies. Ethylene oxide proved inactive while propylene oxide showed

carcinogenic activity in mice. Other alkyl'epoxides are less well

tested. Because of the alkylating properties of these compounds it is

recommended that alkyl epoxides be tested for carcinogenic potential.

Mutagenicity of most members of this group tested provides further

concern for carcinogenic potential.

Mutagenicity: Because most mebbers of this group which have been

tested proved to be mutagenic; other members of this group should be

tested for this effect.

TeratogenicLty: In general, these compounds have not been adequately

tested for teratogenicity but should be, considering the reactivity of

the epoxy group toward biological materials.

Other Chronic Effects: Because of the reactivity of epoxides with

biological materials, they should be tested for specific chronic organ

effects and behavioral changes.

Environment Effects: While the persistence of these compounds as

epoxides is not great, concern is expressed for reaction products. In

view of this possibility, the fate of epoxides in the environment

should be determined through testing.

Epidemiology: Because of the large scale production of several

of these compounds, and because of the strong toxicological

evidence of possible carcinogenic and mutagenic effects,

the Ccmmittee recommends that retrospective epidemiologic studies be

required for two or three of the highest exposure compounds when

suitable cohorts can be identified.

3.2.B ALKYL P HTHXLATES

TESTING RECOMMNDATIONS:

Environmental Effects

CATEGORY IDENTIFICATION: This category consists of all high

production (e.g., 10 million lbs/yr or greater) alkyl esters of

1,2-benzene dicarboxylic acid (orthophthalic acid).

20
REASONS FOR RECOMMENDATIONS:

Production, Release, and Exposure: Many Of these compounds are

produced in large volume, some of them over one hundred million pounds

per year. Their use as plasticizers in, a wide variety of products

results in large volumes of alkyl phthalats reaching the aquatic

environment either as wastes from formulating plants or from use and

disposal of end products.

Effects of Concern:

Environmental Effects: Many of the alkyl phthalares are quite stable,

breaking down only slowly to monophthalates or phthalic acid.

There has been a great deal of information published on their

environmental fate and toxicity to aquatic organisms. Some are known

to have considerable toxicity to fresh water fish. In view of the

large volume in which they can be expected to reach the aquatic

environment and persist and accumulate in aquatic organisms, it is

important to have data on the toxicity to aquatic organisms of all

high production alkyl phthalates. Each such compound should be tested

for chronic toxicity to typical aquatic organisms, especially fish.

Effects on reproduction (or population) should be included in this

testing.

3.2.C CHLORINATED BENZENES, MONO- AND DITESTING RECOMMENDATIONS:

Carcinogenicity

Mutagenicity

Teratogenicity

Other Chronic Effects

Environmental Effects

Epidemiology

CATEGORY IDENTIFICATION: This category consists of four

close:ly-related chemical substances: monochlorobenzene (CAS No.

108-9G-7), and ortho-, meta-, and paradichlorobenzene (CAS Nos.

95-50-1, 541-73-1, and 106-46-7).

REASONS -OR RECOMMENDATIONS:

Product=on, Release and Exposure: The chlorobenzenes are produced in

large qantities, monochlorobenzene over 300 million pounds/year and

ortho- and pata-dichlorobenzene approximately 50 million pounds each.

These chemicals are widely used in industrial processes, as solvents,

and in many consumer products. Therefore, the exposure and potential

for hazard is great, particularly in light of their high release rate

and anticipated persistence in the environment.

21

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NOTICES 503
55054 -

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

NOTICES

Effects of Concern:

Carcinogenicity: One very limited animal study suggested the

induction of sarcomas following subcutaneous injections of

para-dichlorobenzene. A possible association of several cases of

leukemia with human exposure, to mixtures of ortho- and.

para-dichlorobenzenes has also been reported. These studies, as well

asother animal toxicity experiments, do not provide sufficient data

on which to assess thercarcinogenic potential of members of this

class.

Mutagenicity: While a study has demonstrated back mutations in yeast

exposed to ortho-dichlorobenzene, the data are inadequate to assess

the potential mutagenic hazard. Additional testing is needed in view

of the widespread release and exposure. The other chemicals inthis

class should also be tested for mutagenicity.

Teratogenicity: While teratogenic effects are suspected for certain

higher chlorobenzenes, the mono- and dichlorobenzenes have not been

adquately tested.

Other Chronic Effects: Liver, kidney, respiratory and neurological

effects have been observed with high level exposures. Effects at

lower levels cannot be characterized from existing data. Chronic

studies should be undertaken.

Environmental Effects: The environmental fate of these compounds

should be determined. Evidence exists for environmental pollution and

bioaccumulation in aquatic life. The effects are unknown. Studies

should be initiated to assess the impact of these chemicals on

terrestrial and aquatic systems.

Epidemiology: A possible link has been made between exposure to

ortho- and para-dichlorobenzene and leukemia. 'urther efforts to

evaluate chronic effects should be made by the identification and

evaluation of specific populations who are or have been exposed to

either ortho- or paradichlorobenzene.

3.2.D CHLORINATED PARAFFINS, 35-64% CHLORINE

TESTING RECOMMENDATIONSr

Carcinogenicity

Mutagenicity

Teratogenicity

Other Chronic Effects

Environmental Effects

CATEGORY IDENTIFICATION: This category is comprised of a series of

mixtures of chlorination products of materials known commercially as

paraffin oils or paraffin waxes; those-having a chlorine content of

35% through 64% by weight are included.

22
REASONS FOR. RECOMMENDATIONS:

Production, Release, and Exposure: The 1972 annual production of

chlorinated paraffins was about 80 million pounds. The use of these

materials in a wide variety of household and paint products, as well

as adhesives and flame retardants, results in an estimated release

rate of about 50 million pounds per year.

Effects of Concern:

Human Health Effects: A chronic study in mice showed evidence

of degenerative changes in the liver and spleen; no data are available

on the carcinogenicity, mutagenicity, teratogenicity, or other chronic

effects of these mixtures. The Committee recommends that commercial

products in this category be tested for such effects.

Environmental Effects: The occurrence of residues of chlorinated

paraffins in fish indicates the need for critical assessment of the

biological significance of this contamination of the aquatic

environment. The persistence, environmental fate, and chronic effects

on aquatic organisms of the chlorinated paraffins should be determined

by appropriate testing.

3.2.E CHLOROMETHANE

TESTING RECOMMENDATIONS:

Carcinogenicity

utagencity

Teratogenicity

Other Chronic Effects

SUBSTANCE IDENTIFICATION: CAS No. 74-87-3

PAONS FOR RECOMMENDATIONS:

Produrtion, Release, and Exposure: The 1974 U.S. production of

chlorcmethane was over 350 million pounds, most of this being used as

a syntaeitic intermediate. However, it is estimated that about 5Z of

the aal production (over 15 million pounds per year) is released

inta the environment. NIOSH estimates that the number of workers

exposea to chloromethane numbers about 31,000.

Effects- of Concern:

Carcinogenicity: To date, chloromethane has not been the subject of a

carcinogenicity study, although it is structurally related to

chloroform, carbon tetrachloride, and iodomethane, all of which have

been reported as being carcinogenic. Moreover, chloromethane has

recently been reported as exhibiting mutagenic properties in the

Salmonella mutagenic test with microsomal activation.

23

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

NOTICES 55055
NOTICES

Mutagenicity: The initial positive results in the Salmonella

mutagenic test with microsomal activation should be supplemented

with test data regarding chromosomal abberrations.

Teratogenicity: The absence of data in this area, coupled with known

toxic effects, calls for the initiation of studies to determine the

extent of the potential hazard to the reproductive system and the

fetus.

Other Chronic Effects: Exposure to dhloromethane has been implicated

in damage to the central nervous sytem, liver, kidneys, bone marrow

and cardiovascular systems. Effects on these systems should be

examined in chronic toxicity tests.

3.2.F CRESOLS

TESTING RECOMMENDATIONS:

Carcinogenicity

blutagenicity

Teratogenicity

Other Chronic Effects

Environmental Effects

CATEGORY IDENTIFICATION: This category consists of the three isomers

of methyl phenol: ortho-cresol (CAS No. 95-48-7), meta-cresol (CAS No.

108-39-4), and para-cresol (CAS No. 106-44-5).

REASONS FOR RECOMMENDATIONS:

Production, Release, and Exposure: Cresols are produced in large

quantities, having a combined U.S. production in 1975 of about 90

million pounds. An annual release rate of about 45 million pounds has

been estimated. Their wide use as industrial solyents leads to

substantial occupational exposure. NIOSH estimates that roughly two

million workers are exposed to cresols. In addition, cresols are used

in many consumer product s, resulting in a large general exposure.

Effects of Concern:

Carcinogenicity: Cresols have not been evaluated for carcinogenicity.

Because of widespread exposure and suggestive evidence of

mutager.ic effects in certain plants, cresols should be tested for

carcinogenicity.

Mutagenicity: There is some suggestion of the mutagenic potential of

cresols in certain plants, but its potential as a human mutagen has

not been assessed. It is, therefore, recommended that further

mutagenic studies be conducted.

24

FEDERAL REGISTER, VOL. 42,'NO. 197-WEDNESDAY, OCTOBER 12, 1977

55056
NOTICES

Teratogenicity: The teratogenicity of the cresols has not been

assessed, but such testing is needed in view of the evidence of

biological activity of cresols (see Other Chronic Effects, below) and

their widespread exposure.

Other Chronic Effects: Although toxic effects involving the central

nervous system, lungs, kidneys, liver, pancreas, and spleen have been

observed.following acute exposure to cresol-containing products,

adequate testing of cresols for chronic effects following

prolonged-exposure has not been reported and should be conducted.

Environmental Effects: There is evidence that creosote oils

containing cresols are acutely toxic to fish and taint fish flesh at

low concentrations. Because of their substantial release into the

aquatic environment, cresols should be tested for chronic effects on

fish and other aquatic organisms.

3.2.G HEXACHLORO-1,3-BUTADIENE

TESTING RECOMMENDATIONS:

Environmental Effects

SUBSTANCE IDENTIFICATION: CAS No..87-68-3

REASONS FOR RECOMMENDATIONS:

Production, Release, and Exposure: Although the most recent (1974)

data available indicate that this compound is no longer commercially

manufactured in the U.S., it continues to be produced as a waste

byproduct of various chlorination processes and is also imported into

the U.S. for industrial solvent use. The release of

hexachlorobutadiene into the environment has not been quantified, but

there is good evidence of widespread distribution in the aquatic

environment.

Effe-ts of Concern:

Environmental Effects: Hexachlorobutadiene's human health

effec = are being studied in depth. It is a stable substance

which-> -%dely distributed in the aquatic environment and has

been renorted to bioaccumulate in fish and other aquatic

organsms. These factors indicate that hexachlorobutadiene

should be tested to determine its fate in aquatic systems and

its ef-ects on invertebrates, fish, higher vertebrates, and

plant liFe in aquatic systems. Its appearance in some

Europe-n agricultural products suggests that its uptake by

plants and/or foraging species should also be studied.

25.

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

55057
3.2.H NITROBENZENE

TESTING RECOMMENDATIONS:

Carcinogenicity

Mutagenicity

Environmental Effects

-SUBSTANCE IDENTIFICATION: CAS No. 98-95-3

REASONS FOR RECONMENDATIONS:

Production, Release, and Exposure: U.S. production of nitrobenzene in

1975 was about 400 millidn pounds. Its release to the environment has

been estimated to be about 20 million pounds annually. Although its

predominant use (97 percent of-production) is in closed systems in

aniline manufacture, nitrobenzene is also an industrial sofvent and dye

intermediate. General population exposure can arise from environmental

release, and from dispersive uses such as perfume in soap; cleaner for

woodwork, wood flooring and paneling; ingredient of metal polishes and

shoe blacking. Nitrobenzene liquid and vapor penetrate intact skin

readily, and the efficiency of vapor absorption by Inhalation is high.

Effects of Concern:

Carcinogenicity: No information is available on the carcinogenicity

of nitrobenzene. Since it is biologically active, producing cellular

changes,

nitrobenzene should be tested for

carcinogenicity.

Mutagenicity: Although there is evidence of its biological activity,

no mutagenicity pesting has been reported for nitrobenzene.

Mutagenicity testing should be performed.

Environmental Effects: Nitrobenzene is a relatively persistent

substance in the environment. Its low volatility, stability to light,

and low water solubility indicate that bioaccumulation is possible.

Acute effects have been demonstrated in fish. Nitrobenzene inhibits

oxygen utilization and hydrogen sulfide production in sewage

microorganisms, inhibits growth in yeast, and is toxic to various soil

bacteria and microorganisms. Additional data are needed to adequately

characterize the persistence and fate of nitrobenzene and its

matabolites in the aquatic environment. Testing is needed for such

characteristics as well as to determine the effects of chronic exposure

to natrobenzene on fish, aquatic invertebrates, aquatic plant life, and

waterfowl.

26

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

55058 NOTICES
3.2.1 TOLUENE

TESTING RECOMMENDATIONS

Carcinogenicity

Teratogenicity

Other Chronic Effects

Epidemiology

SUBSTANCE. IDENTIFICATION: CAS No. 108-88-3

REASONS -OR RECOMMENDATIONS:

Production, Release and Exposure: Toluene is produced in large

quantities with an annual production rate in excess of 5 billion

pounds. Because of its widespread use as a solvent, as well as a

multiplicity of other uses, toluene has an unusually high occupational

exposure (over 1 million workers). Its presence in many

consumer products leads to a large general exposure. Toluene is currently

being substituted for many benzene-uses and has an annual release rate

exceeding 1 billion pounds.

Effects of Concern:

Carcinogenicity: Previous studies based solely on skin application

techniques in animals have demonstrated a carcinogenic potential for

toluene. Some of these studies were limited in design and prevented

an appropriate appraisal of the carcinogenic hazard of toluene. It

is, therefore, recommended that testing be conducted in long-term

animal experiments taking into consideration the appropriate route of

exposure.

Teratogenicity: Information is lacking on the teratogenic hazard of

this chemical, thus necessitating the initiation of studies to

determine if toluene is teratogenic.

Other Chronic Effects: Liver, central nervous system and

hematopoietic effects have been observed at high level exposures.

Efec-ts at lower levels cannot be characterized from existing data.

Chronic studies to evaluate the effects of prolonged exposures are

recommended.

Ep-d.e_±log : Occupational studies have been conducted predominantly

on the acute toxic effects of toluene. There is little information on

chronic effects in humans from exposure to low levels of toluene over

an ext-uded period of time. Because of its long-term use,

high human exposure, and demonstrated effects in animals,

epidemiological studies may be particularly important in assessing

the human health effects of toluene.

27

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

NOTICES 55059
NOTICES

3.2.J XYLENES

TESTING RECOMMENDATIONS:

Mutagenicity

Teratogenicity

Epidemiology

CATEGORY IDENTIFICATION: This category consists of the three isomers

of dimethyl benzene: ortho-xylene (CAS No. 95-47-6), meta-xylene (AS

No. 108-38-3), and para-xylene (CAS No. 106-42-3)

REASONS FOR RECOMMENDATIONS:

Production, Release, and Exposure: In the aggregate, approximately

8 billion pounds of xylenes are produced each year. Approximately 900

million pounds are released to the environment each year. Mixed

xylenes were ranked by NIOSH 13th out of approximately 7000 agents in

terms of the number of workers exposed. Xylenes are also used in a

wide variety of consumer products, resulting in general population

exposures.

Effects of Concern:

Mutagenicity: Mutagenesis tests have not been reported for any of the

xylenes, but should be conducted in view of widespread exposure and

evidence of toxic effects to several organ systems.

Teratogenicity: Xylenes cross the placental barrier and, according to

two Russian studies, are embryotoxic. Therefore, they should be

tested for teratogenicity.

Epidemiology: Because of their long-term use, high human exposure,

and demonstrated effects in animals, epidemiological studies may

be particularly important in assessing the human health effects

of xylenes and should be conducted.

28

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

55060
NOTICES

APPENDIX A

DATA SOURCES USED FOR PREPARATION OF THE INITIAL LIST

01 Toxic Poliutants in Point Source Water Effluent Discharge

This list of 120 chemicals and categories consists of Appendices A

and C of the settlement agreement dated 7 June 1976 between the

Environmental Defense Fund and EPA. It is a priority list of

toxic pollutants subject to regulations through point source

effluent limitations CSection 307Ca)) under the Federal Water

Pollution Control Act.

02 Scoring of Organic Air Compounds, June 1976, MITRE, MTR-6248

This list of 337 chemicals and categories was compiled and

documented by MITRE (September 1976) under contract to EPA. The

relevant factors in selecting chemicals for the list were: (1)

quantity produced, (2) potential for atmospheric release, and (3)

toxicological effects.

03 Final Report of NSF Workshop Panel to Select Organic Compounds

Hazardous to the Environment, April 1975

This list of 80 chemicals and categories was compiled and

documented by Stanford Research Institute under contract to the

National Science Foundation. The list consists of those chemicals

having the greatest potential for environmental release, selected

from the universe of manufactured organic chemicals with the

highest calculated release rates.

04 Potential Industrial Carcinogens and Mutagens

This list of 88 chemicals has been compiled by the National Center

for Toxicological Research. The list is made up of industrial

compounds which are potential carcinogens and/or mutagens, and.

-oich have been selected based upon available data concerning

activity, use, production, and population at risk.

05 Occupational Carcinogens for Potential Regulatory Action

T1 list of 116 chemicals and categories was compiled by OSH4A

fr suspected carcinogens. Selection was based primarily upon

data available through the NIOSH Registry (Source List 13).

07 Chemicals Tested or Scheduled for Testing at the Fish-Pesticide

Research Laboratory, Department of Interior

This list consists of 174 toxic chemicals which are suspected of

being hazardous to fish and wildlife.

08 Substances with Chronic Effects other than Mutagenicity,

Carcinogenicity, or Teratogen'icity; A Subfile of the NIOSH

Registry

-A subfile of the NIOSH Registry (Source List 13)

Z9

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

55061
55062

FEDERAL. REGISTER, VOL. 42, NO. 197-WEDNESDAY, OCTOBER' 12, 1977

NOTICES

09 Criteria Documents Prepared or Planned by NIOSH, February 24, 1977

This list of 127 chemicals and categories consists of substances

for which criteria documents have been or will be prepared and

delivered to the Department of Labor. In selecting these

chemicals NIOSH considered: a) the number of workers exposed, b)

known or suspected toxic effects, and c) physical and chemical

properties.

10 Suspected Carcinogens; A Subfile of the NIOSH Registry

This is a list of 1,900 chemicals and categories which have been

reported to have produced cancer in test animals. The list is

included in Source List 13.

11 Suspected Mutagens; A subfile of the NIOSH Registry

This is a list of approximately 100 chemicals and categories which

have been reported to have produced mutagenic effects in test

systems. This list is included in Source List 13.

13 NIOSH Registry of Toxic Effects of Chemical Substances, 1976

This list of 21,543 chemicals and categories was compiled and

documented in the NIOSH Registry. Only those substances which

were on Source Lists 8, 10, 11, or 12 were included in the INITIAL

I LISTING.

17 The'Ecological Impact of Synthetic Organic Compounds on Estuarine

Ecosystems, September, 1976, EPA-1600/3-76-075

This list of 9 chemicals was compiled as part of a study of the

impact of synthetic organic compounds on estuarine ecosystems.

The effects of the 9 chemicals and a number of pesticides were

analyzed and documented in the study.

18 Threshold Limit Values for Chemical Substances and Physical

Agents in the Workroom Environment with Intended Changes for 1976,

American Conference of Government Industrial Hygienists

This list of a pprox~mately 570 chemicals and categories was

compiled by the ACGR to give Threshold Limit Values for chemical

substances and physical agents in the workroom environment.

19 National Occupational Hazard Survey (1972-1974)

This list of over 7,000 chemicals and-other hazards has been

compiled by NIOSH. These hazards are ranked according to the

estimated number of workers exposed. Only the chemicals ranked

among the top 500 hazards were included in the INITIAL LISTING.

20 Chemicals Being Tested for Carcinogenicity by the Bioassay

Program, DCCP, National Cancer Institute, 1977

This list of 372 chemicals includes those which have been selected

for bioassay by the National Cancer Institute.

30
NOTICES

21 EPA/Office of Toxic Substances List of Priority Toxic

Chemicals, 1977

This list of 162 chemicals was compiled by EPA/OTS from the NIOSH

list of carcinogens (Source List 10).

22 A Study of Industrial Data on Candidate Chemicals for

Testing, EPA Contract # 68-014109, November, 1976

This list of 650 chemicals and categories was compiled by Stanford

Research Institute as part of the contracted effort to produce

Source List 03. Production and calculated release data are

included.

24 General List of Problem Substances, Environmental Contaminants

Committee, Ottawa, Ontario, Canada, 1977

This list of 160 chemicals and categories of environmental concern

was compiled by the Canadian government.

OTHER LISTS USED FOR REFERENCE BUT NOT USED AS SOURCE LISTS

FOR THE INITIAL LISTING:

06 Survey of Compounds which have been Tested for Carcinogenic

Activity (Index, 1970-1971), NIH/HEW

This list of 3,634 chemicals and categories is a cumulative index

by CAS number of PHS 149 volumes through 1970-1971.

14 Research Project to Gather and Analyze Data and Information on

Chemicals that Impact Man and the Environment

This list of 3,200 chemicals and categories was compiled and

documented by Stanford Research Institute under contract to the

National Cancer Institute. The documentation Includes total

production and calculated release data for each of the chemicals

in nine hazard categories: (1) over-the-counter drugs, (2)

-prescription drugs, (3) cosmetics, (4) trade-sales paints, (5)

water pollutants, (6) air pollutants, (7) soaps and detergents,

(82) pesticide residues in food, and (9) Intentional food

a&citves.

16 Other Potential Modifiers of the Stratosphere, 1975

T-s list of 41 chemicals was compiled by the National Institute

of Environmental Health Sciences from the universe of 275

manufactured chemicals ranked for release rate used by Stanford

Research Institute in preparing Source List 03. This list

identifies potential .modifiers of the stratosphere and provides

related information.

23 EPA/Office of Research and Development, Chemical Production

A set of production data compiled by EPA/ORD on approximately 140

chemicals.

31

FKDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

55063
55064

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

NOTICES

APPENDIX B

PRODUCTION, RELEASE, AND EXPOSURE SCORES

A. The production, environmental release, occupational

exposure, and general.population exposure factors described

in the text were scored in the following manner:

in the following manner:

Factor 1: Production

Annual production data were collected from a number

of sources:

a. Scoring of Organic Air Compounds (Source List

02 of Appendix A)

b. A Study of Industrial Data on Candidate

Chemicals for Testing (Source List 22 of

Appendix A)

c. EPA/OR&D Chemical Production (Source List 23

of Appendix A)

d. Synthetic Organic Chemicals, United States

Production and Sale, 1975, United States

International Trade Comnission

e. Chemical Economics Handbook, 1975 Stanford

Research Institute

f. Chemical and Engineering News: Vol. 52,

No. 51, dated 12/23/74; Vol. 55, No. 18,

dated 5/2/77; Vol. 55, No. 24, dated 6/13/77

The Factor 1 score assigned to a chemical was

the common logarithm of the highest annual production

value (in millions lbs/yr) found in any of the

above sources. If an annual production value was

not available for-a chemical in any of these sources,

a Factor 1 score of -0.5229 (corresponding to an

assumed annual production of 300,000 pounds) was

assigned.

32
NOTICES 55065

Factor 2: Quantity Released into the Environment

The quantity of chemical released into the environment

was scored on a scale from 0 to 3 as follows:

Release Rate

30 percent

Estimate Based on Uses

Mostly dispersive uses

3 to 30 percent Some dispersive uses

.3 to 3 percent

.3 percent

Few dispersive uses;

or primarily industrial

chemical with- propensity

for leaks

Well contained industrial

chemical

Estimates of release rates for a number of chemical's

are given in Source List 22 of Appendix A. For those

chemicals for which no release rates were given, an

estimate was made on the basis of the dispersive

nature of the chemical's uses as indicated in the

above table.

An estimate was also made of the chemical's persistence

according to the following table:

Score Lifetime Example

Infinite (years

or greater)

Order of 1 year

Order of a few

days

Hours or less

Compounds of metals, freons,

CC14, N20, SF6, many polymers

Tetrachloroethylene, flame

retardants, phthalate esters,

silicones

Reactive compounds

The sum of the scores of the two subfactors, release

quantity and persistence, was taken as an indication

of the environmental burden posed by the chemical.

Factor 3: Occupational Exposure

The source of data on occupational exposure to

chemicals was the National Occupational Hazard

Survey (NOHS) conducted by the National Institute for

33

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

Score
5506G

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

NOTICES

Occupational Safety and Health. In this survey,

the approximately 7000 most common hazards occurring

in the working place were rank ordered. To achieve

an occupational exposure score with a range and direction similar to those of the other factors, the

Factor 3 score assigned to a chemical was 3.8451

minus the common logarithm of its rank on the NOHS

list. (3.8451.is the logarithm of 7000.) Chemicals

which did not appear on the NOHS list were given a

score of zero, equivalent to having been ranked

number 7000 on the survey.

Factor 4: Extent to Which the General Population

is Exposed

Four individual subfactors were scored and then summed

to measure the general population exposure. The four

subfactors were scored as followA:

SUBFACTOR i Number of people exposed to the chemical

(exclusive of a workplace environment)

Score No. of People Example

3 20 X 10 Widely used household

products (e.g., wearing

apparel, shoe polish,

certain surface coatings, common paints and

their solvents, common

plastics and their additives, detergents,

furnishings and carpets,

wood cleaning products,

refrigerants, natural

gas, nonfood packaging

materials, flame

proofers)

General air, food and

water contaminants

Automotive products

(e.g., gasoline and

additives, rubber,

surface coatings,

plasticizers, flame

proofers)

Products used widely

in commercial buildings

(mostly same as household, including

commercial cleaners,

di6infectants)

34
NOTICES

No. of People Example

2-20 X 10

0.2-2 X 10

2 X 10

Less widely used household products (e.g.,

unco-mn paints,

specialty apparel such

as baby wear, hobby

uses, arts and crafts,

tools)

Regional air and water

pollutants, farm

chemicals (exclusive

of pesticides)

Specialty hobbies

(e.g., photography),

specialty products

Neighborhood air and

watet pollutants from

local industries

Chemical intermediates

rarely found outside

the workplace

SUBFACTOR 2

Score

Frequency of exposure (to the typical person

in ranking number of people exposed under Subfactor 1)

Frequency

Daily or more often

Weekly

Monthly

Yearly or less

frequently

35

Examoless

General air, food and

water contaminants,

household products in

regular use, material

used inside automobiles, clothing

Hobby crafts, household products used

intermittently (e.g.,

certain cleaners),

bleaches, gardening

products

Dry cleaning, certain

solvents, house maintenance (e.g., polishes,

certain cleaning agents),

automobile maintenance

Application of household paints, specialty products

FEDERAL REGISTER, VOL 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

Score

55067
55068

SUBFACTOR 3

Score

Exposure intensity. This is intended to

reflect the total amount of material that

comes into contact with the average or typical

person whose exposure has been scored under

subfactors 1 and 2. Scoring of this factor

considered the number of grams of the

material that makes contact with the average

person in the course of one exposure (daily,

weekly, monthly or yearly as scored in subfactor 2). Thus, for example, a trace pollutant

may lead to exposure of a typical person of the

order of micrograms per day every day; use of a

specialty solvent, might lead to exposure of a

typical person of the order of grams per day

once a year: these would be scored 3,0 and 0,3

respectively on subfactors 2 and 3.

Intensity Examples

High (10 or more

grams per exposure)

Medium (10 to

10 g per exposure)

Low (10 to 10

g per exposure)

Very- low (less

10 g per exposure

SUBFACTOR 4

Plastics, fabrics,

surface coatings,

volatile solvents in

closed spaces, liquids

contacting skin, high

concentration gases

Fabric additives,

solvents in open spaces

or outdoors, dusts,

solutes, transitory

exposures to vapors or

aerosols

Low level indoor exposure,

volatile substances from

home furnishings and

building materials (e.g.,

plasticizers, flame

proofers), low volatility

solvents, pigments

Environmental contaminants

(low level air, food, and

water contaminants),

monomers in polymers

Penetrability. This is a measure of the material

that comes into contact with a person (whether by

dermal, inhalation, or ingestion exposure) and that

is' expected to be absorbed into the body (even

transitorily) with potential for interaction with

cells.

FEDERAL REGISTER, VOL. 42, NO. 197-WEDNESDAY, OCTOBER 12, 1977

NOTICES
NOTICES

Penetrability Examples

High (10 to 100%

absorption)

Medium (I to 10%

absorption)

Low (0.01 to 1%

absorption)

Nealegible

(less than 0.01%

absorption)

Organic solvents iu liquid,

mist, or aerosol form,

vapors and gases if likely

to be soluble in body fluids,

respirable-sized particles,

surface active agents,

materials known to have

high dermal systemic

toxicity

Solvents with low volatility

and/or larger molecules,

organic materials in

water solution, waxes and

polishes, coarse dusts

Certain solids, dermal

exposure to most inorganic

materials in water solution

Polymers, metals

B. In making the judgments called for in scoring

Factors 2 and 4 above, knowledge of the

chemical's uses was necessary. Use information

was collected from the following sources:

1. Thd Condensed Chemical Dictionary,

Ninth Edition, Hawley, Van Nostrand

Reinhold Company, New York, 1977.

2. The Merck Index, Ninth Edition, Merck

and Company, Inc., Rahway, N.J., 1976.

3. Faith, Keyes, and Clark's Industrial

Chemicals, Lowenbeim and Moran, Fourth

Edition, J. Wiley and Sons, Inc., New

York, 1975.

4. Chemical Marketing Reporter, Schnell

Publishing Company, Inc., New York.

5. Encyclopedia of Chemical Technology,

Kirk-Othmer, Inter-Science Publishing

Company New York, 1972.

37

FEDERAL REGISTER, VOL 42, NO. 197-WEDNSDAY, OCTOBER 12, 1977

Score

55069
55070 NOTICES

APPENDI= C

ORDERING THE CHEMICALS BASED ON

PRODUCTION, RELEASE, AND EXPOSURE

A linear weighting scheme was used to rank order the

chemicals. The rank of the jth chemical, r was computed

by the formula:

4 fij

rj= wi -- ,

Si

where wi is the weight assigned to the ith factor,

f is the ith factor score of the jth chemical,

and si is a scaling factor chosen to normalize the assigned scores.

The four scaling factors employed were:

sI = log 20,850 - 4.3191; 20,850 million lb/yr

being the maximum of all Factor 1 chemical production

quantities.

s2 - 6; 6 being the maximum of all Factor 2

environmental release scores.

s3 - 3.8451 - log 3 = 3.3680; third being the

h-hest NOHS rank among the scored chemicals.

(Ranked first and second on the NOHS list were

continuous noise .and mineral oil, the former not

being a chemical hazard and the latter not being among

the scored chemicals.)

s4 = 12; 12 being the maximum of all Factor 4 general

population exposure scores. 1f

This choice of se, s., s3, s 4 , guaranteed that . ... !1

for all i and J, and furthermore, that for each i,

for at least one chemical J.

38

FEDERAL REGISTER, VOL. 42,-NO. 197--WEDNESDAY, OCTOBER 12, 1977
NOTICES

APPENDIX D

55071

BIOLOClCAL AND ENVIRONMENTAL SCORES

A. The. five human. health effect factors and two environmental effect

factors mentioned in the text were scored in the following

. manner:.

Factor. 1: Carcinogenicity

a.. Numerical Scores Assigned:

. ,

3 Established ca~cinogen in humans or in 2 animal

species, or in one animal species in well-replicated

experiments

2 ~stablished carcinogen in 1 animal species

I Insufficient or inadequate experimental data for

definite.conclusions, but either (a) no experimental

or. structural reason. for suspicion, or (b) good

negative mutagenicity tests, or (c) low.biological

activity. (Note: some inert.compounds - examples,-

argon, nitrogen - were given a score of zero en

this factor despite not having peen tested.

o Adequately tested in animals with negative results

in each of two.species

b. .Letter. Scores Assigned*:

xxx Needs testing, strongly suspect (close structural

,relationship. to known carcinogen,-positive result in

validated in vitro test, inconclusive but suspicious

.positive animal tes_t, etc.)

xx Needs testing, suspect, (structural resemblance to

known carcinogen, etc.)

x. Needs testing, some reason for suspicion (potent

organ-specific toxin, enzyme inducer, suspect cocarcinogen, etc.)

*Ch~rals presently undergoing testing for carcinogenicity in

the framework of th~ NCI bioassay program were'-scored as

suspect carcinogens. Their special status was documented for

the:~bers of the Committe~.

c., Criteria for Accepting.Positive Test Results (scores 2 or 3)

Validated. positive findings in animal studies consisted of

".any test.results which clearly indicated treatment-related.

carcinogenicity or tumorigenic effects. This was based on the

criteria set. out in.the report of the National Cancer Advisory

Board. Subcommittee' on Environmental Carcinogenicity, "General

Criteria. for Assessing the Ev~dence for Carcinogenicity of

Chemical Substances (1976)".

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I

NOTICES

d. Criteria for Accepting Negative Test. Results (including

zero scores)

In general. the protocol of the'test ~onformed to. or was'

'reasonably consistent with the currentNCI Guidelines (J.M.

Sontag'et al...Guidelin~sfor Carcinogen Bioassay in Small Rodents, DREW 76-801).. It was recognized that many older tests

do not conform to these guidelines. Therefore,. good scientific

judgment was applied to the evaluation of these tests in order

to determine whether differences 'in protocols significantly

weakened confidence in the reported negative results. In

assigning a zerQ score, the'guiding principle was the judgment that further testing was unnecessary.

Factor 2; Mutagenicity

'.

a.. Numerical Scores Assigned:

2 Mutagen in two or more test syst7ms*

1 . Mutagen in one test system

o Tested in more than one system with negative results

and no reason for suspicion (similar to inactive compounds. etc.)

*These and o~her scores were normalized to the 0-3 scale.or

x-xxx scale respectively for all factors involved.

b. Letter Scores Assigned:

xxx Needs testing. strong reason for suspicion (structural similarity to known mutagen, reported carcinogenicity. teratogenicity, or other. cellular toxicity)

xx Needs testing. some reason for suspicion (structural

similarity to known.~utagensand/or carcinogens) .

x. Needs testing. no. reason to assign high priority

c. Examples of Short-Term Test Systems Considered for Scoring

Were:

The Salmonella/mic=osometest. (Ames).E. coli WP2 uvr .

A. etc. test (Bridges. Witkin). B. subtilis M45 Rec-. etc.

test (Kada),.E. coli pol A+/pol A1- test (Rosenkranz). Yeast

test (Zimmerman). Neu~ospora test (de Serres) and'Drosophila

test (Vogel).. Mammalian cells in culture and in vitro transformations were also considered. .

40

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NOTICES

Factor 3: Teratogenicity

a. Numerical Scores Assigned:

3 Confirmed teratogen in humans or in two appropriate

animal ppecies

2 Confirmed teratogen in 1 animal species

1 Insufficient or inadequate experimental data for

definite conclusions, but either (a) no experimental

or structural reason for suspicion, or (b) low biological activity

0 Adequately tested n two suitable animal species with

negative findings for teratogenic activity

b. Letter Scores Assigned:

XXX Needs testing, strongly suspect (close structural

relationship to known teratogen, inconclusive but

suspicious positive animal tests, etc.)

zx Needs testing, suspect (equivocal result in anima

test, etc.)

x Needp testing, some reason for suspicion -

c. Criteria for Acceptance of Teratogenicity Tests

Accepted teratogenicity tests conformed reasonably to the

recommendations and principles outlined in' "Principles for

Evaluating Chemicals in the Environment," National Academy

of Sciences, pp. 173-182, 1975; and "The Testing of Chemicals for Carcinogenicity, Mutagenicity, Teratogenicity,"

Department of Health and Welfare, Canada, pp. 137-176,

March 1973.

Factor 4: Acute Toxicity

a. n-mnaerical Scores Assigned:

3 extremely toxic: < 50 mg/kg

2 very toxic: 50-500 mg/kg

1 moderately toxic: 0.5-5 g/kg

0 very slightly toxic: > 5 g/kg

41

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b. Letter Scores Assigned:*

xx not tested, but suspected to be in range 2-3

X not tested, but suspected to be in range 0-1

*See factor 2 for normalized scored.

c. Criteria for Quantitation of Acute Toxicity

Standard systems of toxicity rating based on probably lethal

dose in humans were used when available . Lowest lethal

doses and LD50 values in various animal systems were also

widely used.

Factor 5: Other Toxic Ef!ects

a. Numerical Scores Assigned:

3 Effects at low doses (Guidelines: < 1 mg/kg/day)

2 Effects at moderate doses (Guidelines: 1-10 mg/kg/day)

1 Effects at high doses (Guidelines: > 10 mg/kg/day)

O Very low or negligible biological activity (e.g.,

nitrogen, argon, etc.) 0

b. Letter Scores Assigned:

XXX Needs testing (structural similarity to another

chemical-which rates 2 or 3., questionable reports

of effects which need confirmation, etc.)

xx Needs testing, some reasons for suspicion

x Needs testing, inadequate information available

to give high pirority

c. Criteria for Scoring

This factor includes both reversible and irreversible

effects, delayed -or cumulative toxicity, organ-specific

effects, effects on reproduction, behavior, etc. The score

entered reflects the toxic effects-noted in animals (or in

humans if data were available) at the lowest dose-range. If

the chemical was reported or suspected to have more than

one toxic effect, xxx or xx for one type of toxic effect

superseded any numerical score for another. Also, x for one

type of toxic effect superseded 2 or 1 for another. In many

cases, reports of one type of effect at low doses engendered suspicion of the likelihood of others; in such

cases the chemical was scored with the appropriate number of

x's, unless thoroughly tested.

42
Factor 6: Bioaccumulation

a. Numerical Scores Assigned:

3 High Q104)*

2 Appreciable (102-104)

I Low (4102)

0 Experimental evidence for non-accumulation (<);

water soluble compounds

*The degree of bioaccumulation (more precisely, the tissuespecific. storage factor) is defined as the concentration of

the chemical in the tissues (at "steady state" or after prolonged exposure) divided by the concentration of the chemical

in the ambient medium.

b. Letter Scores Assigned.,

XXX Testing important, judged likely to be high

xx Testing.important, judged not likely to be high,

but likely to be appreciable

x Needs testing, little or no experimental data

c. Criteria for Scoring

Bioaccumulation is used here in its broad sense of the

accumulation of a chemical in one or more tissues of an animal

(or plant) to levels higher than those in the ambient medium.

For purposes of screening chemicals, it was considered significant primarily in cases in which the accumulation in tissues

represented an enhanced probability of effects, either on

the organ in which the cheilcal was concentrated, or on animals which feed on the organism which accumulated the

chemical. High degrees of bioaccumulation are usually found

only in aquatic organisms. For these organisms, bioaccumulation is known to be dependent primarily on water solubility

and- it is empirically predicted by the octanol/water

partition coefficient. Zero scores were assigned to

completely water soluble organic chemicals.

Substances which are easily metabolized will not be

bioaccumulated even if they have a high partition

coefficient (example, chloroform). Thus ease of

metabolism was a factor considered in evaluating the

potential for bioaccumulation.

43 4.

FEDERAL REGISTER, VOL 42, NO. 197-WDNESDAY, OCTOBER 12, 1977

NOTICES 55075
NOTICES

Factor 7: Ecological Effects

a. Numerical Scores Assigned:

3 Effects at low concentrations (10-9 or less in air or

water)*

2 Effects at moderate concentrations (10-7 - 10-9 in air

or water)

1 Effects at high concentrations (10-6 or greater in air

or water)

0 No reported effects that could justify priority for

testing

*In air for gases or vapors: I part of chemical per billion parts

air by volume (ppb). In water for liquids and solids: 10-9 gram

per cubic meter (ng/m3)

b. Letter Scores Assigned:*

xx Testing needed, possibility of major or widespread effects

x Testing needed, possibility of minor or local effects

*See factor 2 for normalized scores.

c. Criteria for Scoring:

Ecological effects considered included beside tonic effects

on non-human animals and plants, ecosystem effects, effects

on atmosphere and climate, ozone depletion, etc. Generally,

numerical scores (established hazard), were assigned only to

a limite number of. thoroughly tested chemicals (e.g., pesticides, some-metal containing compounds, or some specific

chemicals).. In other cases, the potential for ecological

effects was judged according to availability of data on

toxicity in particular, published information on specific

tests, structural similaritT to- compounds of better known

eco-toxicity,: published data on depletion potential for

stratospheric; ozone. Zero scores were assigned only to compounds with low biological activity (LD5O> 1 g/kg or AQTR >

100 ppm).

B. An extra, factor was scored if the presence of a contaminant in

a commercial product was the-major reason for concern, or if a

trace- degradation product was the major reason for concern (examples: dioxin, methyl mercury)....

44

FEDERAL REGISTER, VOL 42, NO. 19Z-WEDNESDAY, OCTOBER- 12i T977'

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NOTICES

Factor 8: Contaminants and Environmental Degradation or Conversion

Products

a.. Numerical or Letter Scores Assigned:

1 C6ntaminants, etc., known to be important

0 Contaminants, etc., not suspected, or known to be of

no importance.

X Contaminants, etc., suspect, needs testing

b. Criteria for Scoring:

The scores for this factor were not averaged. A letter

score took priority over a numerical score at any time; if

no letter score was assigned to a chemical, the numerical

score 1 was overriding. A zero score was assignedonly if

it was scored unanimously by all scorers. The score for this

factor was not added: (1) if the principal breakdown product

was the major problem and it was the basis for scores

on other criteria such as persistence and toxicity (examples:

DDE, PAN); (2) for in vivo metabolism of carcinogens to

active forms (e.g., arene oxides, activated nitrosamines, etc.

etc.).

C. It is of relevance for the scoring method to add that in order

to facilitate the inclusion of a zero score in a letter score

average, the zero score was changed into 0.1X. Also, in some

instances fractional numerical or letter scores were assigned

by scorers.

D. The following literature sources were extensively used by the

scorers:

References of general interest

1. NIOSH Registry of Toxic Effects of Chemical Substances (1976)

2. Zirk-Othmer Encyclopedia of Chemical Technology. Edited by

A. Standen, Interscience Publishers, New York (1963, 1972).

3. The Condensed Chemical Dictionary, 9th ed. Van Ilostrand

Reinhold Co., New York (1977).

4. The Merck Index, 9th ed. Merck & Co., Inc., Rahway, N.J.

(1976).

5. Chemical Consumer Hazard Information System. Consumer

Product Safety Commission, Washington, D.C. (1977).

6. A Study of Industrial Data on Candidate Chemicals for Testing. Stanford Research Institute, Palo Alto, California,

(1976).

45

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NOTICES

7. The Encyclopedia of Chemistry. Hanpel & Hawley, 3rd ed.

Van Nostrand Reinhold Co., New York (1973).

8. Brown, S.L., et al. Research Program on Hazard Priority

Ranking of Manufactured Chemicals, Phase II- Final Report

to National Science Foundation. Stanford Research Institute

Menlo Park, California (1975).

9. Dorigan, J., et al. Scoring of Organic Air Pollutants,

Chemistry, Production and Toxicity of Selected Synthetic

Organic Chemicals, MITRE, I4R-6248 (1976).

1. References on Carcinogenicity

Cl. Survey of Compounds Which Have Been Tested for Carcinogenic Activity Through 1972-1973 DHEW Publication No. NIH

73-453, National Cancer Institute, Bethesda, Maryland

C2K Suspected Carcinogens - A subfile of the NIOSH Toxic Substances List.

C3. IARC Monographs on the Evaluation of Carcinogenic Risk of

Chemicals to Man. Lyon, France. WHO, Internationdl Agency

for Research on Cancer.

C4. Chemicals Being Tested for Carcinogenicity by the Bioassay

Program, DCCP. National Cancer Institute (1977).

C5. Informa=ton- Bulletin on. the Survey of Chemicals Being Tested for Carcinogenicity, No. 6. WHO, Lyon, France (1976).

2,3. References on Mutagenicity and Teratogenicity I

MNi. Shepard, T.H. Catalog of Teratogenic Agents. Johns Hopkins

University Press, Baltimore (1973).

MTZ EMIC/Environmental utagenicity Information Center File,

National Laboratories, Oak Ridge, Tennessee.

4,5. References on Acute Toxicity and Other Toxic Effects

AOl Thienes, C.L. & Haley, T.J. Clinical Toxicology. Lea

& Febiger, Philadelphia (1972).

AOZ.. Gosselin, Hodge, Smith & Gleason. Clinical Toxicology

of Commercial Products, 4th ed. The Williams and WUiins

Company, Baltimore (1976).

A03. Casarett, L.J. & Doull, J. Toxicology, the Basic Science

of Poisons. McM:illan Publishing Co., Inc., New York.

A04. Debruin, A. Biochemical. Toxicology of Environmental Agents.

Elsevier/North Holland, Inc., New York (1976).

46
NOTICES

A05. Threshold Limit Values for Chemical Substances and Physical

Agents in the Workroom Environment with Intended Changes

for 1976. American Conference of Government Industrial

Hygienists.

A06. Criteria for a Recommended Standard - Occupational Eposure

to .... , prepared by NIOSH..

A07. Browning, E. Toxicity and Metabolism of Industrial Solvents.

Elsevier, Amsterdam (1969).

A08. Browning, E. Toxicity of Industrial Metals, 2nd ed.

Appleto=-Century-Crofts, New York (1969).

A09. Fairhall, L.T. Industrial Toxicology, 2nd. ed. Williams

& Wilkins Co., Baltimore, Maryland (1969).

AOIO. Sax, N.I. Dangerous Properties of Industrial Materials,

3rd ed. Reinhold Publishing Corp., New York (1975).

A011. Chemical-Safety Data Sheets. Manufacturing Chemists

Association, Washington, D.C.

A012. Industrial Safety Data Sheets. National Safety Council,

Chicago, Illinois.

6,7. References pn Bioaccumulation and Ecological Effects

BE1. Applegate, V.C., J.H. Howell, A.E. Hall, Jr. & N.A. Smith,

1957 Toxicity of 4.346 Chemicals to Larval Lampreys and

Fishes. U.S. Dept. Interior, Fish & Wildlife Se_-rice.

Special Scientific Report-Fisheries No. 207. Wash., D.C.

BE2. Battelle Columbus Laboratories 1971, Effects of Chemicals

on Aquatic Life: Selected Data from the Literature through

1968. Vol. 3 of Water Quality Criteria Data Book. U.S.

Environmental Protection Agency, Washington, D.C.

BE3_ Hahn, W., and P. Jensen, Water Quality Characteristics of

Hazardous Materials; Teatas A & 1. University, (1974) (Taken

ftom the NIOSH Registry of Toxic Effects of Chemical Substances (1976).

BZ&. Kemp, H.T., R.L. Little, V.L. Holoman, and R.L. Darby.

!973, Effects of Chemicals on Aquatic Life (Compilation

Dated 1968-1972). Water Quality Data Book - Vol. 5 U.S.

Environmental Protection Agency, Duluth, Linn.

BE5_ Leo, A., C. Hansch, & 1). Elkins, Partition Coefficients

and Their Uses. Chem. Rev. 71:525-616 (1971).

BE6. Lincer, J.L., UE. Haynes, and IUI.L. Elein, 1976. The

Ecological Impact of Synthetic Organic Compds. on Estuarine

Ecosystems. U.S. Environmental-Protection Agency,

Gulf Breeze, Florida, EPA-600/3-76-075.

q7

FEDERAL REGISTER, VO.. 42, NO. 197-EDNESDAY, OCTOBER 12, 1977

5560
NOTICES

BE7. Metcalf, R.L., P.Y. Lu, and I.2. Kapoor, 1973. Environmental

Distribution and Metabolic Fate of Key Industrial Pollutants

and Pesticides in a Model Ecosystem. Illinois University,

Water Resources Center, Research Report 69 , Urbana, Illinois.

BE8. Pimentel, D. 1971. Ecological Effects of Pesticides on

Non-target Species. Executive Office of the President,

Office of Science and Technology, Washington, D.C.

BE9. Sauter, S., K.S. Buxton, K.J. Malek, and S.R. Petrocelli,

1976. Effects of Exposure to Heave Metals on Selected Freshwater Fish. Toxicity of Copper, Cadmium, Chromium, and Lead

to Eggs of Seven Fish Species. Environmental Protection

Agency, Duluth, Minnesota. EPA-600/3-76-105.

BElO. National Academy of Sciences. 1973. Water Quality Criteria,

1972. U.S. Environmental Protection Agency, Ecological

Resaerch Series No. EPA-R3-73-033.

BEll. McKee, J.E., and HLW. Wolf (eds.) 1963. Water Quality

Criteria, 2nd Edition. State Water Quality Control Board,

Sacramento, California.

BE12. U.S. Environmental Protection Agency. 1976. Criteria Document

PCBs. Washington, D.C.

BE13 National Institute of Environmental Health Sciences, 1973.

Symposium on Phthalate Ester Plasticizers. Environmental

Health Perspectives, Experimental Line 3.

BE14 National Academy of Sciences 1975a. Principles for Evaluating Chemicals in the Environment. Washington D.C.

BE15' National Academy of Sciences 1975b. Assessing Potential

Ocean Pollutants. Washington D.C.

BEI& U.S. Environmental Protection Agency 1975. Quality Criteria

for Water (prelminary draft). Washington D.C.

BE17 National Academy of Sciences 1976. Halocarbons: Effects on

Stratospheric Ozone, Washington D.C.

48

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