The Information Content of Premanufacture

Notices

April 1983

NTIS order #PB83-241059
Library of Congress Catalog Card Number 83-600522

For sale by the Superintendent of Documents,

U.S. Government Printing Office, Washington, D.C. 20402
Preface

Some chemicals have been associated with deleterious effects on human health and

the environment. Responding to concerns that newly developed chemicals might pose

risks to health or the environment, Congress included provisions in the Toxic Substances

Control Act that require manufacturers and importers of new chemicals to notify the

Environmental Protection Agency (EPA) before new chemicals are introduced into commerce. The implementation of those provisions began in July 1979, and the EPA has

now received more than 1,500 Premanufacture Notices that describe new chemicals.

The Office of Technology Assessment (OTA) prepared this background paper, “Information Content of Premanufacture Notices,” in response to a request from the Subcommittee on Commerce, Transportation, and Tourism of the House Committee on

Energy and Commerce. OTA examined 740 Premanufacture Notices, and this study

reports the results of analyzing those notices for the presence or absence of the information specified by the Toxic Substances Control Act and for other items of physicalchemical and toxicity information that are useful for estimating potential health and

environmental effects. In addition, this study reports the regulatory and voluntary compliance actions that EPA has taken as a result of reviewing Premanufacture Notices.

The general finding of this study is that the amount of information contained in

Premanufacture Notices varied widely. Every notice contained most or all of the information items specified in the law, and many also reported nonspecified and useful information about the characteristics and toxicity of the chemical. At the same time, about

half of the notices did not contain any toxicity data. This absence is not surprising given

that the law does not require companies submitting Premanufacture Notices to carry

out toxicity studies, but only to notify EPA of toxicity data that they have available.

Certainly, the absence of toxicity data complicates EPA’s efforts to decide whether

a new chemical may present an unreasonable risk to health or the environment. But

the importance of toxicity data for making decisions about particular chemicals varies.

Those data are less important for chemicals that closely resemble others for which there

is much information and experience. They are critical for unusual chemicals or chemicals

for which there is limited information. An additional study would be necessary to evaluate

the EPA’s decisionmaking process and whether or not it was compromised by absent

data. The last chapter of this report outlines such a study.

OTA background papers are prepared by OTA staff and contractors, and drafts

of the papers are sent for review to interested organizations and individuals. This paper

was written by Michael Gough and Stedman Stevens; John Bell designed computer formats and programs. The 30 individual and organizational reviewers of the first draft

are listed in appendix C.

,.. Ill
Health Program Advisory Panel

Sidney S. Lee, Panel Chair

Michael Reese Hospital and Medical Center

Chicago, 111.

Stuart H. Altman

Florence Heller School

Brandeis University

Waltham, Mass.

Carroll L. Estes

School of Nursing

University of California

San Francisco, Calif.

Rashi Fein

Department of Social Medicine and

Health Policy

Harvard Medical School

Melvin A. Glasser

Health Security Action Council

Committee for National Health Insurance

Washington, D.C.

Patricia King

Georgetown Law Center

Washington, D.C.

Joyce C. Lashof

School of Public Health

University of California

Berkeley, Calif.

Margaret Mahoney

The Commonwealth Fund

New York, N.Y.

Frederick Mosteller

Department of Health Policy and Management

School of Public Health

Harvard University

Boston, Mass.

Mitchell Rabkin

Beth Israel Hospital

Boston, Mass.

Dorothy P. Rice

Department of Social and Behavioral Sciences

School of Nursing

University of California

San Francisco, Calif.

Richard K. Riegelman

School of Medicine

George Washington University

Washington, D.C.

Walter L. Robb

Medical Systems Operations

General Electric

Milwaukee, Wis.

Frederick C. Robbins

Institute of Medicine

Washington, D.C.

Rosemary Stevens

Department of History and Sociology of Science

University of Pennsylvania

Philadelphia, Pa.
OTA Information Content of Premanufacture Notices Staff

H. David Banta, Assistant Director, OTA

Health and Life Sciences Division

Clyde J. Behney, Health Program Manager

Michael Gough, Project Director

J. Stedman Stevens, Research Assistant

John Bell, Systems Analyst

Virginia Cwalina, Administrative Assistant

Pamela Simerly, Secretary

Mary E. Walls, Secretary

OTA Publishing Staff

John C. Holmes, Publishing Officer

John Bergling Kathie S. Boss Debra M. Datcher Joe Henson

Doreen Foster Linda Leahy Donna Young
Contents

Chapter Page

I. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

2. “New Chemicals” and the Toxic Substances

Control Act. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Regulation of New Chemicals . . . . . . . . . . . . . . . . . . 11

Actions Available to EPA Following PMN

Reviews . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Public Notice of New Chemicals Considered for

Manufacture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

PMN Reporting Requirements . . . . . . . . . . . . . . . . . . 14

EPA Management of PMN Review . . . . . . . . . . . . . 15

Proposed Exemptions to the PMN Reporting

Requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Structural Activity Relationship Analysis and

Its Use in PMN Review . . . . . . . . . . . . . . . . . . . . . 20

3. Methods Used in Study of Information Content

of Premanufacture Notices. . . . . . . . . . . . . . . . . . . 25

PMNs Examined by OTA . . . . . . . . . . . . . . . . . . . . . 25

Inspection of PMN Files . . . . . . . . . . . . . . . . . . . . . . . 26

Information Collected From PMNs . . . . . . . . . . . . . 27

Security Precautions To Protect Confidential

Business Information . . . . . . . . . . . . . . . . . . . . . . . . 29

EPA Cooperation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Analysis of the Data... . . . . . . . . . . . . . . . . . . . . . . . 30

Organization of the Presentation of the Analysis . 30

4. Frequency of Submission of TSCA-Specified

Data on Premanufacture Notices . . . . . . . . . . . . . 33

Numbers of PMNs Submitted to EPA . . . . . . . . . . . 33

Chemical Name and Production Volumes. ....,.. 34

Chemical Formulae and Structures . . . . . . . . . . . . . . 35

Byproducts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

Number of Workers Exposed and Disposal . . . . . . 37

Summary of Findings About Reporting of

TSCA-Specified Information . . . . . . . . . . . . . . . . . 38

5. Frequency of Submission of Physical-Chemical

Information on Premanufacture Notices ..,.... 41

How Many Physical-Chemical Data Were

Submitted on PMNs? . . . . . . . . . . . . . . . . . . . . . . . 41

Physical-Chemical Data Were Reported More

Frequently unmanufactured PMNs . . . . . . . . . . . 43

Submission of Physical-Chemical Data on

PMNs of Different Classes . . . . . . . . . . . . . . . . . . . 44

Summary of Findings About Submission of

Physical-Chemical Data . . . . . . . . . . . . . . . . . . . . . 45

6. Frequency of Submission of Toxicity

Information on Premanufacture Notices . . . . . . . 49

How Many Toxicologic Data Were Submitted

on Pans? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

Toxicity Data Were Reported More Frequently

on Manufactured PMNs . . . . . . . . . . . . . . . . . . . . . 52

Submission of Toxicity Data on PMNs

Describing Different Classes of Chemicals . . . . . 53

Page

7. Submission of Physical-Chemical and Toxicity

Information on Some Subgroups of

Premanufacture Notices . . . . . . . . . . . . . . . . . . . . 57

PMNs Submitted for Consumer Products . . . . . . . . 57

PMNs Submitted for Polymers . . . . . . . . . . . . . . . . . 58

PMNs Submitted for Site-Limited Chemicals . . . . . 59

PMNs Submitted for Low-Production-Volume

Chemicals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60

Comparison of Toxicity Data Submitted on

Consumer and Nonconsumer Substances,

Both Polymers and Nonpolymers, Scheduled

for Production indifferent Amounts . . . . . . . . . . 62

Magnitude of Scale-Up in Production of

Low-Volume Chemicals . . . . . . . . . . . . . . . . . . . . . 64

Are PMNs Submitted for Imported Chemicals

More Complete Than Those Submitted for

Other Chemicals?. . . . . . . . . . . . . . . . . . . . . . . . . . . 66

8. Actions Taken by the Environmental

Protection Agency as a Result of Reviewing

Premanufacture Notices . . . . . . . . . . . . . . . . . . . . . 69

9. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

Frequency of Reporting of Information on

Premanufacture Notices . . . . . . . . . . . . . . . . . . . . . 75

Data Submitted on PMNs That Described

Chemicals Intended for Consumer Use . . . . . . . . 75

Data Submitted on PMNs That Described

Chemicals Proposed for Exemption From

PMN Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76

Usefulness of Submitted Information for

EPA’s Risk Assessment Process . . . . . . . . . . . . . . . 77

Possible Further Evaluation of the PMN

Review Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78

Appendix A: Summary of Topics Considered at

Evaluation Meeting During Initial Screen of

Premanufacture Notices at the Environmental

Protection Agency . . . . . . . . . . . . . . . . . . . . . . . . . . 83

Appendix B: Copies of Face Sheets: EPA and

CMA PMN Forms . . . . . . . . . . . . . . . . . . . . . . . . . . 84

Appendix C: Acknowledgments . . . . . . . . . . . . . . . . . . 86

Appendix D: Acronyms and Glossary . . . . . . . . . . . . . 88

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

Tables

Table No. Page

1.

2.

3.

Proposed Low-Volume and Site-Limited

Intermediate Exemption Provisions . . . . . . . . . . . . 17

Proposed Polymer Exemption Provisions . . . . . . . 17

Completeness of PMNs for TSCA-Specified

Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

vii
Contents—Continued

Table No. Page

4. Number of Class 1, 2, and 3 PMNs That

Have Name, Structure, and Formula . . . . . . . . . . 35

5. Number of PMNs Describing Chemicals

Intended for Industrial, Commercial, and

Consumer Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

6. Items of Physical-Chemical Information

That Were Scored on PMNs. . . . . . . . . . . . . . . . . . 41

7. Number of Physical-Chemical Data Items

Submitted on PMNs. . . . . . . . . . . . . . . . . . . . . . . . . 42

8. Completeness of PMNs for PhysicalChemical Information as a Function of the

Time Between End of the Review Period

and the Commencement of Manufacture . . . . . . . 44

9. Physical-chemical Information on PMNs

Describing Class 1, Class 2, and Class 3

Chemicals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

10. Items of Toxicity Information That Were

Scored on PMNs. . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

11. Eight General Classes of Short-Term Tests

That Measure Mutagenicity or Other

Interactions With DNA . . . . . . . . . . . . . . . . . . . . . . 50

12. Number of Toxicologic Items Submitted on

PMNS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

13. Completeness of PMNs for Toxicity

Information as a Function of the Time

Between End of the Review Period and the

Commencement of Manufacture . . . . . . . . . . . . . . 52

14. Toxicity Information on PMNs Describing

Class l, Class 2, and Class 3 Chemicals . . . . . . . . 53

15. Completeness of PMNs Submitted for

Consumer-Use Products as Compared to

Other PMNs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

16. Physical-Chemical and Toxicity

Information Submitted for Site-Limited

Chemical PMNs and All Other PMNs . . . . . . . . . 59

17. Physical-chemical and Toxicity

Information Submitted on PMNs That

Project Initial Year Production Volumes of

1,000 Kilograms or Less, of Between 1,001

and l0,000 Kilograms, and All Others . . . . . . . . . 61

18. Number of Submissions of Toxicity Data

on Polymers and Nonpolymers To Be

Produced indifferent Amounts . . . . . . . . . . . . . . . 63

19. Number of Submissions of Toxicity Data on

PMNs Describing Consumer-Use Chemicals

and Polymers and Nonpolymers To Be

Produced in Different Amounts . . . . . . . . . . . . . . . 63

20. Number of Submissions of Toxicity Data

on PMNs Describing Nonconsumer-Use

Chemicals and Polymers and Nonpolymers

To Be Produced in Different Amounts . . . . . . . . . 64

Table No. Page

21. Estimated First Year Production Volumes,

and Increases Expected in the Third Year. . . . . . . 65

22. Physical-Chemical and Toxicity Information

Submitted for Import PMNs and All Other

PMNS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

23. EPA Summary of Informal Regulatory Actions

in Fiscal Years 1979, 1980, 1981, and First

Three Quarters of Fiscal Year 1982 . . . . . . . . . . . . 70

24. Estimated Costs of Tests That Might Be

Reported on PMNs . . . . . . . . . . . . . . . . . . . . . . . . . . 78

Figures

Figure No. Page

1. Letter of Request for This Background Paper . . . . 4

2. Disposition of PMNs Submitted From July 1979

and Including All Those That Completed the

90-Day Review Period by the End of September

1981 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

3. Form Used by OTA in Collection of Data

From PMNs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

4. Number of Valid PMNs Received Each Month:

April 1979 Through June 1982 . . . . . . . . . . . . . . . . . 34

5. Percentage of PMNs Containing the Three Most

Commonly Reported Toxicity Tests and the

Two Tests Related to Chronic Toxicity and

Ecotoxicity . . . . . . . . . . . . . . . . . . . . ... , . . . . . . . . . . 51

6. Percentage of Polymer and Nonpolymer PMNs

That Contained the Three Most Commonly

Reported Toxicity Tests and Tests Related to

Chronic Toxicity and Ecotoxicity. . . . . . . . . . . . . . . 54

7. Percentage of PMNs That Described ConsumerUse or Nonconsumer-Use Products and

Contained the Three Most Commonly Reported

Toxicity Tests and Tests Related to Chronic

Toxicity and Ecotoxicity . . . . . . . . . . . . . . . . . . . . . . 58

8. Percentage of PMNs That Describe Site-Limited

or Other Chemicals and Contained the Three

Most Commonly Reported Toxicity Tests and

Tests Related to Chronic Toxicity and Ecotoxicity . 60

9. Percentage of PMNs That Described Low-or

High-Production-Volume Chemicals and

Contained the Three Most Commonly Reported

Toxicity Tests and Tests Related to Chronic

Toxicity and Ecotoxicity . . . . . . . . . . . . . . . . . . . . . . 62
Summary
1 .

Summary

The Premanufacture Notice (PMN) Program is

the U.S. Government’s effort to identify toxic substances before they enter commerce, to impose

controls when necessary, and thereby to reduce

unreasonable risks to human health and the environment. The Toxic Substances Control Act

(TSCA) requires that a Premanufacture Notice be

submitted to the Environmental Protection Agency (EPA or the Agency) at least 90 days before

a new chemical is manufactured or imported into

the United States.

Using the information in the PMN and professional judgment, EPA reviews each PMN to determine if the chemical described in the notice presents or may present an unreasonable risk to human health or the environment. When EPA does

not conclude that an unreasonable risk may be

associated with the substance described in a PMN,

manufacture of the chemical can begin at the end

of the 90-day PMN review period.

In the event that EPA determines that the substance presents or will present an unreasonable

risk, the Agency can regulate its manufacture.

If EPA decides that the information presented

in the PMN is: 1) insufficient for the Agency to

make a reasoned evaluation of the health and environmental effects that might be associated with

the substance, and 2) that the substance may

either (a) present an unreasonable risk or (b) be

produced in quantities such that there will be

substantial environmental or human exposure, the

Agency can restrict or ban the manufacture of the

substance pending the submission of additional

appropriate data.

When exposure to the substance under the conditions of use described in the PMN is of no concern to EPA, but the Agency has concerns about

potential risks under other conditions of use, the

Agency can write an order requiring submission

of more data before the substance can be manufactured for a “significant new use.”

A PMN is to contain certain information about

the new chemical to enable EPA to make decisions necessary to protect human health and the

environment under the provisions of TSCA. Because TSCA does not allow EPA to require that

information be generated about a substance simply because the substance is new, it was expected

that the amount and type of information present

on PMNs would vary.

The PMN program differs significantly from a

premarket testing program that was adopted by

the European Economic Community (EEC) and

was considered for adoption by the Organization

for Economic Community and Development

(OECD) (3). The PMN program requires the submission of data within the possession of the submitting company, and TSCA forbids EPA from

ordering the generation of test data simply because

the chemical described on the PMN is new. In

practice, this means that data the company generates in its normal course of business are submitted to EPA.

The EEC program requires the submission of

specified test data, whether or not the submitting

company would have generated those data in its

normal course of business. In other words, the

EEC approach requires testing. Furthermore, as

production volumes increase, EEC requires the

submission of additional data. In contrast, once

a new chemical has completed PMN review, it is

no longer subject to regulation as a new chemical.

Both the PMN and the EEC programs may add

exemptions and make other alterations to their

general requirements. The General Accounting

Office is now preparing a report that compares

the OECD system to the PMN program; the report is expected to be completed in late 1983.

This OTA background paper responds to a request for a report that describes the nature and

extent of information reported on PMNs in general and on PMNs submitted for certain subgroups

of chemicals, such as those that have now entered

manufacture, and on EPA’s use of those data in

decisionmaking about new chemicals (fig. 1). It

reports the examination of all PMNs received by

EPA in the first 2 years of the program’s opera3
——

Figure 1 .—Letter of Request for This Background Paper

NINETY—SEVENTH CONGRESS

JAMES J. FLORIO, N.J. CHAIRMAN

JIM SANTINl, NEV. NORMAN F. LENT, N.Y.

BARBARA A. MIKULSKI, M. D. EDWARD R. MADIGAN. ILL.

JAMES H. SCHEUER. N.Y. GARY A. LEE, N.Y.

ANTHONY TOBY MOFFETT, CONN.

( u

OFFICIO)

WASHINGTON, D.C. 20519

June 7, 1982

Dr. John H. Gibbons

Office of Technology Assessment

600 Pennsylvania Avenue, S.E.

Washington, D. C. 20510

Dear Dr. Gibbons:

As you are aware, there has been considerable debate in

recent months regarding the effectiveness of the premanufacturing

notice (PMN) provisions of the Toxic Substances Control Act (TSCA).

Concerns regarding the impact of these provisions on innovation have

been addressed in numerous studies including the OTA’S just completed

assessment, “Technological Innovation and Health, Safety, and

Environmental Regulations”. However, little, if any, assessment has

taken place regarding (1) the extent to which current PMN submissions

either fulfill or compromise efforts to perform the preventive health

and environmental protection mandate of the Act, and (2) the expecte d

effects of EPA’s proposed exemptions from the PMN process.

Questions in this regard surfaced repeatedly during the

Subcommittee’s reauthorization hearings on TSCA, though few objective

answers could be rendered due to the scarcity of independent assessment of these questions. Given the substantial nature of these

outstanding concerns, and in light of the OTA’s assessment, “Technologies for Determining Cancer Risks from the Environment", which encompasses both toxic substances risk assessment and regulatory analysis,

the Subcommittee is requesting that OTA review TSCA’s PMN provisions

and submissions. The assessment should include the following

components:

(1) Characterization of the notices received t o

date regarding classes of chemicals and their

uses.

(2) Assessment of data that were submitted on (a )

different classes of chemicals, (b) substance s

that were subsequently placed on the market a s

compared to those that were not, and (c) sub -

stances that would be exempted from PMNs under

EPA’s currently proposed changes ;
Ch. 1—summary ● 5

Figure 1.—Letter of Request for This Background Paper—Continued

June 7, 1982

Page 2

(3) Analysis of the impact of the original data

submissions on subsequent EPA decisions under

the PMN section.

The Subcommittee anticipates that the OTA would use the

recommendations of the Organization for Economic Cooperation and

Development (OECD) and other appropriate organizations on premanufacturing testing policy in its assessment of the new chemical testing program

under TSCA. In addition, it is expected that the OTA would observe all

rules and procedures regarding the protection of

in the assessment.

confidential data used

JJF:rfl

tion (through June 1981) and those submitted in

June 1982. In addition, the data reported on PMNs

that describe chemicals of certain specified classes

were analyzed separately. For instance, PMNs

that describe chemicals that, according to EPA

records, are now being manufactured were arialyzed and compared to those that described chemicals that have not yet been manufactured.

EPA is considering exempting some classes of

chemicals from PMN reporting requirements.

PMNs submitted for the classes of chemicals likely

to be exempted—chemicals used and consumed

only at the site of manufacture, chemicals to be

manufactured in amounts of less than 10,000kilograms annually, and polymers-were also analyzed separately.

To collect the information reported in this background paper, 45 items for which data might be

submitted on PMNs were identified. The presence

or absence of each of the 45 items was recorded

and the frequency of submission of the items for

all PMNs and some subsets of PMNs was computed.

TSCA, by mandating the submission of available data, leaves to the submitting company decisions about which data are to be developed.

Therefore, the reported data reflect company decisions about what data are important. The absence

of data from PMNs makes EPA’s task of deciding

whether anew chemical may bean unreasonable

risk more difficult. On the other hand, the fact

that a submitting company does not have to submit data that it regards as unnecessary represents

a saving to the company, and if the chemical presents no risk, then both society andthe company

benefit.

If EPA decides that particular data are necessary

for the evaluation of a new chemical and that such
6 Ž The Information Content of Remanufacture Notices

data are absent from the PMN, the Agency can

make an informal request for the data, or it can

write an order requiring their submission. Whichever mechanism is used to ask for the data, the

burden is on EPA to show that the data are necessary. Requiring submission of more data, especially toxicity data, would reduce the number

of times that EPA makes decisions without such

data. It would also place the burden for developing data on the submitting companies.

In some cases, the absence of important information—of types that neither the company nor

EPA recognizes as essential-may compromise the

protection that the Agency affords to human

health and the environment. Requiring the submission of a list of test results would guard against

that happening, but at the same time, some of the

required data might be unnecessary-at least for

some chemicals. In those cases, the costs of

developing that information would not reduce

risks to human health or the environment.

In general, the frequency with which PMNs

contained the TSCA-specified and required information items about the identity of the chemical,

its expected production volumes, its likely uses,

the number of workers who might be exposed in

their places of employment, and methods for its

disposal was high. More than 90 percent of all

PMNs reported those items. One TSCA-specified

reporting requirement, that the PMN identify

byproducts associated with the manufacture or

processing of the chemical, was less frequently

met. Only 67 percent of PMNs reported byproduct information. Overall, 62 percent of PMNs

reported all TSCA-specified information; 86 percent reported all but byproduct information.

Additional physical and chemical information

beyond that which is specified in TSCA was

reported on 96 percent of all PMNs, and at least

one item about toxicity was reported on 53 percent. OTA looked at physical-chemical and toxicity information reported on some subgroups of

PMNs, and found more frequent reporting on

PMNs that describe substances that are more likely to be hazards. For instance, reporting of both

physical-chemical information and toxicity data

was more frequent on PMNs that described substances which, according to EPA records, subsequently began manufacture. Toxicity information

was more frequently reported on PMNs that described nonpolymeric substances. That seems

especially welcome, given that a near majority of

PMNs have no toxicity information, because hazard is more often associated with nonpolymeric

substances than with polymers (polymers are

chemicals composed of repeating subunits).

These generally positive observations must be

tempered by the fact that about half of PMNs

reported no toxicity information. Furthermore,

only 17 percent of PMNs have any test information about the likelihood of the substance’s causing cancer, birth defects or mutations-three biological effects that were singled out for special concern in TSCA.

The conclusions to be drawn from the results

of the analysis presented here must be limited to

generalizations about the frequency of submission

of information. The results show that more data

are reported for some classes of PMNs than for

others.

The following chapters present the results of

OTA’s analysis of the technical content of PMNs

and, where appropriate, related findings and conclusions. However, the interpretation of the results is not a matter of inherent validity or of one

interpretation’s being correct and others being

wrong. Instead, the interpretation to be placed on

the results will depend on the beliefs and outlook

of the reader.

If the reader is of the opinion that no premanufacture reporting should be required or that only

the information items specified in TSCA should

be submitted, the results may be interpreted to

show that the PMN program is resulting in too

much information being submitted. If, on the

other hand, the reader thinks that particular items

of information other than the TSCA-specified

items should be reported on every PMN, the results may be interpreted to show that too little

information is being reported.

Considering the results in more detail may lead

to a middle position. There is, as shown in this

paper, a tendency for information to be submitted

for substances likely to be more hazardous or to

result in more widespread exposures. For instance,
Ch. 1—Summary ● 7

toxicity data are submitted more frequently on

PMNs that describe nonpolymers, which as a

group are more likely to be hazardous, than on

PMNs that describe polymers; more data are submitted on PMNs that describe consumer-use products than on other PMNs. Those observations are

consistent with the idea that companies develop

and report appropriate data to EPA.

The data that lead to the satisfying conclusion

that more information is being reported about

more worrisome groups of chemicals also show

the frequency of toxicity data reporting. About

40 percent of nonpolymers scheduled for annual

production in excess of 10,000 kg did not report

any toxicity data. About 30 percent of PMNs describing nonpolymer, consumer use chemicals, to

be made in amounts greater than 10,000 kg annually, did not report any toxicity. Taking a middle position might lead to the conclusion that the

trends are encouraging, but attach reservations

to conclusions about whether the information

now reported is adequate for the review of all new

chemicals.

Regardless of how the information about the

frequency of submission of data is interpreted, immediate questions arise about whether the information available for a particular substance was

appropriate and sufficient. Answering those questions would require an examination of EPA’s decisionmaking process about at least some PMNs on

a case-by-case basis. That study would be different from the one reported here, and would involve

a process similar, in some regards, to that used

by EPA to review PMNs. A group of scientists

would review the data on the PMNs, supplement

that information with other information available

from the scientific literature and experts, decide

if EPA’s decision was appropriate, and ask whether additional information on the PMN might have

made a difference in the decision.

The next two chapters discuss the regulation of

new chemicals (ch. 2) and the methods used by

OTA in this study (ch. 3). Chapters 4 through 6

present the results of examining PMNs for the reporting of TSCA-specified data items (ch. 4), of

physical-chemical data (ch. 5), and of toxicity data

(ch. 6). Chapter 7 presents comparisons of toxicity data reported on certain subgroups of PMNs

(e.g. site-limited chemicals compared to all others

and consumer-use chemicals compared to all

others). Chapter 8 discusses actions taken by EPA

to regulate new chemicals, and chapter 9 is a general discussion of the the OTA findings.
2

"New Chemicals" and the

Toxic Substances Control Act
"New Chemicals" and the

Toxic Substances Control Act

After more than 5 years of consideration and

debate during three terms of Congress, the Toxic

Substances Control Act (TSCA) was passed by

Congress on September 28, 1976, and signed into

law by President Ford on October 11,1976. TSCA

states that it is Federal policy that: 1) chemical

manufacturers and processors are responsible for

developing data about health and environmental

effects of their products, 2) that there be adequate

statutory authority to regulate chemicals posing

an unreasonable risk to health or the environment, and 3) that regulatory efforts not unduly

impede innovation.

An important facet of TSCA (and the Resource

Conservation and Recovery Act, which provides

for the regulation of chemical disposal) is that the

law directs regulatory emphasis at hazardous substances wherever they may occur. Other environmental protection laws are directed at regulating

exposures through specific media, such as air and

water.

TSCA is generally directed at chemical substances (TSCA sec. 2), and section 3 defines a

“chemical substance” as any organic or inorganic

substance of a particular molecular identity including any substance which results in whole or

in part from a chemical reaction or that occurs

in nature as well as any element or uncombined

radical. [Note: Throughout this report the terms

“chemical” and “substance” are used interchangeably to mean “chemical substance.”]

Certain substances are excluded from regulation under TSCA:

REGULATION OF NEW CHEMICALS

●

●

●

●

●

●

mixtures;

pesticides, regulated under the Federal Insecticide, Fungicide and Rodenticide Act, when

they are used as pesticides;

tobacco and tobacco products;

nuclear materials, which are regulated under

the Atomic Energy Act;

food and food products which are regulated

under the Federal Food, Drug and Cosmetic

Act; and

pistols, firearms, revolvers, shells, and cartridges.

Section 5 of TSCA is directed at preventing human and environmental exposure to new substances that will present or may present an unreasonable risk to human health or the environment and requires that the Environmental Protection Agency (EPA) be notified before new

chemicals are introduced into commerce. The requirement for premanufacture notice (PMN) reflects the conclusion that human health and the

environment may be better protected at less cost

when a toxic chemical is regulated before it has

become established in commerce:

The most desirable time to determine health

and environmental effects of a substance, and to

take action to protect against any potential

adverse effects, occurs before commercial production begins. Not only is human and environmental harm avoided or alleviated, but the cost of any

regulatory actions in terms of loss of jobs and

capital investment is minimized. (TSCA Legislative History, p. 678, quoted in OTS, 1982).

Premanufacture notification allows EPA to istrator of EPA to compile an “Inventory of

make regulatory decisions about “new” chemicals. Chemical Substances” of all chemicals subject to

The category of new chemicals was established the provisions of TSCA that are manufactured or

by TSCA section 8(b), which directs the Admin- imported into the United States. The Inventory

11
12 ● The Information Content of Premanufacture Notices

was published on June 30, 1979, and all chemicals

that did not appear on that list and which are not

exempted from TSCA, are, by law, new.

Section 5 of TSCA stipulates that any person

who intends to manufacture a substance that is

not listed on the inventory and that is not excluded from TSCA must notify EPA of his or her

intention 90 days before manufacture is to begin.

Manufacture of small amounts of a chemical for

research and development purposes to determine

its usefulness and properties is, of course,

permitted.

To initiate the EPA review of the new chemical,

the company submits a PMN that is to contain

information about chemical identity, proposed

uses of the chemical, the expected production

volumes of the chemical for various uses, expected

byproducts, estimates of the numbers of people

likely to be exposed in manufacture of the chemical, and methods for disposal.

The notice . . . shall include—

(A) insofar as known to the person submitting

the notice or insofar as reasonably ascertainable,

the information described in subparagraphs (A),

(B), (C) (D), (F), and (G) of section 8(a)(2), and

(B) in such form and manner as the Administrator may prescribe, any test data in the possession or control of the person giving such notice

which are related to the effect of any manufacture, processing, distribution in commerce, use,

or disposal of such substance or any article containing such substance, or of any combination of

such activities, on health or the environment, and

(C) a description of any other data concerning

the environmental and health effects of such

substance, insofar as known to the person making the notice or insofar as reasonably ascertainable. (TSCA sec. 5(d)(1)(a))

The subparagraphs of section 8(a)(2) referred

to in section 5(d)(1)(a) read as follow:

(A) The common or trade name, the chemical

identity, and molecular structure of each chemical

substance or mixture for which such a report is

required.

(B) The categories or proposed categories of use

of each such substance or mixture.

(C) The total amount of each substance and

mixture manufactured or processed, reasonable

estimates of the total amount to be manufactured

or processed, the amount manufactured or processed for each of its categories of use, and reasonable estimates of the amount to be manufactured or processed for each of its categories of use

or proposed categories of use.

(D) A description of the byproducts resulting

from the manufacture, processing, use or disposal

of each such substance or mixture.

(F) The number of individuals exposed, and reasonable estimates of the number who will be exposed, to such substance or mixture in their places

of employment and the duration of such exposure.

(G) ., . the manner or method of its [such substance or mixture] disposal . . . (TSCA sec.

8(a)(2)).

ACTIONS AVAILABLE TO EPA FOLLOWING PMN REVIEWS

The Administrator of EPA is charged with reviewing the information in the PMN within 90

days after receipt of the notice, and the agency

can extend that review period for a maximum of

90 additional days (TSCA sec. 5(c)). The review

of a PMN can result in any one of at least four

actions by the agency.

(1) If the data in the PMN and expert opinion

within the agency do not lead to the conclusion

that an unreasonable risk is associated with the

substance, manufacture can begin without restriction. Importantly, if EPA takes no action and the

Agency is notified that manufacture of the substance described on the notice has begun, the

name of the substance is placed on the Inventory

of Chemical Substances. Unless the substance is

the subject of a Significant New Use Rule (SNUR),

this action transfers the substance from the “new”

category, subject to section 5 of TSCA, to the “existing” category. [A “SNURed” chemical (see (2)

immediately below) remains subject to section 5

requirements. ] The testing and regulation of existing chemicals are the subject of other sections
Ch. 2— “New Chemicals” and the Toxic Substances Control Act ● 13

of TSCA. Those sections are not discussed in this

report.

(2) If EPA decides that the manufacture and use

of the substance as described in the PMN are not

associated with unreasonable risk, but, that a

potential new use of the substance might be associated with unreasonable risk, EPA can commence a separate rulemaking to restrict the manufacture or distribution of the substance for uses

not specified in the PMN. Under such a rule, manufacture can commence for the particular uses

named in the PMN, but if the company that submitted the PMN or any other company decides

to manufacture the substance for a “significant

new use,” EPA must be informed. The Agency

then can require additional information about the

substance (TSCA, sec. 5(a)(1)(B)).

The use of this authority is illustrated by the

example of a chemical developed for use in commercial cleaning compounds. EPA was satisfied

that its use by professional cleaning people would

not be associated with an unreasonable risk, but

the Agency was concerned that its use by consumers might result in such a risk. EPA took no

action against the manufacture of the substance

for commercial uses but drafted a “consent 5(e)

order” (see (3) immediately below) that requires

the reporting of additional information about toxicity before the substance is manufactured for a

new use. The submitter consented to the order and

agreed not to contest it in court so that manufacture for commercial uses could begin. At the same

time, EPA announced that it would write a SNUR

that requires that the Agency be notified before

the substance is manufactured for use in consumer

products. Therefore, the name of the substance

is placed on the Inventory of Chemical Substances

but flagged so that any subsequent manufacturer

will know it is subject to pending regulation. According to EPA officials, future 5(e) orders of any

kind will generally be linked to SNURS unless the

submitter withdraws the PMN in the face of the

5(e) order.

(3) Section 5(e) of TSCA authorizes EPA to

issue an administrative order regulating a new

substance pending development of additional information by the submitter. To issue a 5(e) order,

EPA must make two findings: First, the information available to EPA is insufficient to permit the

evaluation of any risk that maybe associated with

the new substance, and, second, either the new

substance may present an unreasonable risk to

health and the environment or the new substance

will be produced in substantial quantities, resulting in significant exposure.

(1)(A) If the Administrator determines that

(i) the information available to the Administrator is insufficient to permit a reasoned

evaluation of the health and environmental effects

of a chemical substance with respect to which

notice [PMN] is required . . . ; and

(ii) (I) in the absence of sufficient information

to permit the Administrator to make such an evaluation, the manufacture, processing, distribution

in commerce, use, or disposal of such substance,

or any combination of such activities, may present an unreasonable risk of injury to health or

the environment, or

(11) such substance is or will be produced in substantial quantities, and such substance either

enters or may reasonably be anticipated to enter

the environment in substantial quantities or there

is or may be significant or substantial human exposure to the substance,

the Administrator may issue a proposed order

. . . to prohibit or limit the manufacture, processing, distribution in commerce, use, or disposal of

such substances or to prohibit or limit any combination of activities (TSCA, sec. 5(e)).

In practice, 5(e) orders require that the PMN

submitter develop specific items of information

to assuage EPA’s concern about the substance.

The order can either prohibit or restrict manufacture during the period required for the development of additional information.

(4) Finally, EPA may decide from examination

of the PMN that the manufacture, processing,

distribution, use, or disposal of the substance

“presents or will present an unreasonable risk of

injury to health or environment” (TSCA sec. 5(f)).

In those cases, EPA can regulate the substance.

Briefly, then, EPA can make any one of four

decisions after inspecting a PMN:

1. The substance described on the PMN can be

manufactured without restriction.
14 ● The Informatjon Content of Premanufacture Notices

2. The substance can be manufactured for the

uses described on the PMN, but the Agency

can require that it be notified if manufacture

for a significant new use is considered (TSCA 4,

sec. 5(a)(2)).

3. The manufacture, processing, distribution,

use, or disposal of the new substance can be

regulated pending the development of additional information about the substance

(TSCA sec. 5(e)). In these cases, the AdPUBLIC NOTICE OF NEW CHEMICALS

CONSIDERED FOR MANUFACTURE

TSCA section 5 (d)(2) provides that the Administrator is to publish a notice of receiving a PMN

in the Federal Register within 5 business days after

receipt of the notice. The published notice is to:

1) identify the chemical substance, 2) list the uses

or intended uses, and 3) describe the results of any

tests that were required by EPA rules under the

provisions of TSCA section 5(b). (To date, no

PMN containing EPA-required test results has

been submitted.)

PMN REPORTING REQUIREMENTS

As required by TSCA section 5 (d)(1) all PMNs

shall contain sufficient information to identify the

new chemical, and to describe its projected uses

and production volume, the number of workers

likely to be exposed to it, its byproducts, and

methods for its disposal. Those information items

are specifically identified in the Act. In addition,

TSCA section 5 lists some general classes of information that are to be reported on the PMN.

The general reporting requirements say that any

available information about the substance’s physical and chemical properties and effects on health

and the environment are to be included.

EPA has wrestled with the problems of specifying the form for PMNs and exactly what information should be submitted. In general, initial

plans favored the submission of more detailed information, and subsequent modifications have

pulled back to more general reporting requireministrator must conclude that a decision

about unreasonable risk cannot be made because of missing information.

The manufacture, processing, distribution,

use, or disposal of the new substance can be

regulated because it presents or will present

an unreasonable risk (TSCA sec. 5(f)). In

these cases, the Administrator decides that

the available information is sufficient to

decide that regulation is required.

To protect confidential business information

(CBI) from public disclosure, the submitter may

designate those information items in a PMN that,

were they to become public, would harm the submitter’s business. Frequently, submitters have

designated the chemical name as CBI. In those

cases, the submitter, as part of the PMN, can use

EPA guidelines and propose up to three “generic

names” for listing in the Federal Register.

ments (see 44 F.R. 2242, Jan. 10, 1979; 44 F.R.

28564, May 15, 1979; 44 F.R. 59764, Oct. 16,

1979; 45 F.R. 74378, Nov. 7, 1980)

Currently, the EPA Office of Toxic Substances

(OTS) is considering a proposal that PMNs will

be required to contain only the items of information—chemical identity, proposed categories of

use, estimates of production volumes, description

of byproducts, estimates of the number of individuals exposed in their places of employment,

and disposal methods—specified in TSCA section

5(d)(l)(a) and other “information that is essential

for the review of most PMN’s” (OTS, 1982). The

other essential information is not described in

Priorities for OTS Operation, but the point is

made that even without having asked for additional information on the PMN itself, EPA will

be able to telephone the submitter to ask for additional information as needed to review the
Ch. 2– “New Chemicals” and the Toxic Substances Control Act ● 15

PMN. EPA states that in most cases, submitters 1982). Currently, a PMN can be submitted on a

have been forthcoming with such information form proposed by EPA, or on a form prepared

when requested (OTS, 1982). by the Chemical Manufacturers Association, or

.

EPA also intends to require that all PMNs be on forms devised by individual companies.

submitted on a specified, simplified form (OTS,

EPA MANAGEMENT OF PMN REVIEW

Upon receipt of a PMN, EPA initiates a review

that, with some exceptions, must be completed

within 90 days. During the review period, EPA

examines the PMN, and may request additional

information from the submitter. If EPA does not

find that the new substance presents or may present an unreasonable risk, EPA takes no action

and the company submitting the PMN can begin

manufacture when the 90-day period is completed. The submitter can request that the “clock

be stopped” during the 90-day period if the company needs more time to develop information. If

EPA agrees to the request, the agency waits until

the company has obtained the desired information and then restarts the clock. Section 5(C) of

TSCA authorizes EPA to extend the review period

an additional 90 days for good cause.

PMN review is divided into 2 stages, an initial

“screening” review and a detailed review. During the initial screening period, employees of EPA

qualified by education and experience for the

tasks, review the PMN for:

1.

2.

3.

4.

5.

6.

If

completeness, i.e., having the specific information required by TSCA;

correctness of chemical identity;

possibilities of occupational, environmental,

and consumer exposures;

potential for human health effects;

potential for environmental effects; and

probable accuracy of projections of market

size, new markets, and production volumes.

an EPA reviewer thinks that the company

might have additional information or that additional information is essential for the review, EPA

can call the submitter. According to EPA officials

and to some chemical company officials who reviewed the first draft of this OTA background

paper, companies generally respond to such requests and supply the information.

When the requested information is unavailable

or the company does not produce it, EPA employees can take one of several actions. They can make

reasonable worst case estimates about the missing information, or they can negotiate with the

company and reach an agreement that the company will run tests and supply data to EPA. If the

company refuses to carry out necessary tests, EPA

can write an order, as described by TSCA section 5(e), limiting or prohibiting manufacture

pending development of appropriate data.

In general, each individual reviewer’s report is

reviewed by other, senior EPA scientists at a series

of meetings. These meetings discuss the chemical

described in the PMN, the information submitted,

what conjectures can reasonably be made based

on similarities to other chemicals, and appropriate

strategies to search the literature for information

about similar chemicals. Appendix A reproduces

the items that may be discussed at the Evaluation

Meeting which is held near the end of the initial

screening period. Information about these items

can be made available in the PMN or it can be

estimated by EPA. Test-generated data are more

reliable than estimates, but, there may be many

instances when estimates are necessary.

The process of PMN review changed in May

1982 (as is described below). However, for most

of the PMNs examined by OTA, the major decision was made at the “disposition meeting. ” These

meetings, held at day 45, considered the reviewers’

comments and the reports of the earlier meetings,

and discussed outstanding matters. The meetings

produced one of four decisions:

1. no further review was necessary,

2. the chemical was referred to another EPA office or to another agency for action because

OTS had identified an exposure that might
16 ● The Information Content of Premanufacture Notices

be of concern to another office or agency but

was not of concern to OTS, or

3. the PMN was referred for detailed review, or

4. the decision was made to initiate some follow-up action, such as the writing of an

SNUR.

If the first or second decision was reached, a final

disposition report was written, the submitter was

notified that manufacture could begin at the end

of the 90-day review period, and the PMN file

was closed out. If the third or fourth decision was

reached, the PMN was sent to other groups within

OTS for detailed review or other action.

Somewhat less than 10 percent of PMNs (7 percent of those examined by OTA) are sent to detailed review. Detailed review involves other individuals, frequently contractors to EPA, taking

longer, harder looks at PMNs. During the detailed

review, EPA can also telephone the submitter and

request additional information. The EPA’s PMN

Review Process Manual (OTS, 1981) describes the

review process in detail, and Arthur and Garrett

(1982) provide a useful diagram of the process.

The review process was characterized by several

EPA employees as reviews of reviews of reviews.

There was agreement that the available information was thoroughly analyzed and that reasonable

use was made of information about related chemicals. However, some EPA employees expressed

concern about the adequacy of the data received

on the PMNs and whether calls for additional information should have been made more often.

During the evolution of the PMN review process at EPA, some chemicals were identified as

members of chemical classes that cause no or little concern about health or environmental effects.

EPA scientists could, in the case of those chemicals, decide to drop them from further consideration at any time during the review period. In May

1982, the PMN review process was changed to

accommodate EPA’s conclusion that decisions

about some chemicals could be made earlier in

the review process. Since that time, a “focus

meeting” has been held at about 15 days after

PMN receipt. This meeting centers on identifying health and/or ecological concerns and assessing the accuracy of the estimates made of possible exposure to and release of the new chemical.

The result of the focus meeting maybe a decision

that the PMN describes a chemical of little or no

concern, and such substances are dropped from

further review.

OTA made no attempt to determine how the

new meeting affected PMN review. EPA staff reported, however, that the meeting has been beneficial, speeded up the process, and conserved

resources for the more difficult-to-review PMNs.

PROPOSED EXEMPTIONS TO THE PMN REPORTING REQUIREMENTS

TSCA section 5(h)(4) permits the Administrator On August 4, 1982, EPA proposed more genof EPA to exempt substances from the PMN re- eral exemptions directed at:

porting requirements. The first exemption was

granted on November 3, 1981, for chemicals used 1. site-limited intermediate chemicals,

in or for instant photographic film articles (40 F.R. 2. chemicals manufactured in quantities of

54585). A manufacturer of those chemicals had 10,000 kg (22,000 lb) or less annually, and

petitioned for the exemption because of industry 3. polymers.

desire to introduce chemicals quickly in order to The proposed exemptions for site-limited intercapitalize on newly opened-up markets. The

90-day PMN review period, according to the petimediates and low-volume substances were published in one notice (47 F.R. 33896), and the one

tion, would sometimes cause introduction of a for polymers was published separately (47 F.R.

new film to be delayed to the extent that a holiday market was missed. The exemption imposes

33924).

requirements on the manufacture and use of the EPA, in proposing these exemptions, responded

chemicals to restrict exposures. to industry petitions that were based on two dif-
Ch. 2—"New Chemicals" and the Toxic Substances Control Act ● 17

ferent lines of reasoning. Industry advanced the

ideas: 1) that low-volume chemicals and site-limited intermediates are “characterized by limited

exposure, ” and 2) that polymers “represent a class

of substances that have intrinsically low levels of

biological activity” (OTS, 1982).

Following some provisions of the industry petition, EPA proposed a policy that PMNs describing low-volume chemicals and site-limited intermediates that are not excluded from the exemption (see table 1) should be subject to an abbreviated EPA review. Agreeing with the idea that

some polymers have inherently low toxicity, EPA

decided that a finding of no unreasonable risk for

those polymers would not depend on conditions

of use, and that it would not be necessary for the

Agency to review the specific properties or uses

of certain polymers before they were manufactured (OTS, 1982). For certain other polymers,

the Agency proposes a short review period (see

table 2).

The proposed exemption for low-volume chemicals is divided into two parts. The first deals with

substances made in amounts of 1,000 kg or less

annually; the second with substances made in

amounts of 10,000 kg or less annually. Any

substance made in quantities of 1,000 kg or less

would be granted an exemption unless under the

conditions of use, the:

. . . substance or a reasonably anticipated metabolite or environmental transformation product

may cause . . . . serious chronic effects, including

carcinogenic and teratogenic effects . . . . serious

acute effects [lethal or sublethal] . . . . [or] . . . .

significant environmental effects . . . under

anticipated conditions of manufacture, processing, distribution in commerce, use, or disposal.

Table 1 .—Proposed Low-Volume and Site-Limited Intermediate Exemption Provisions

Other

manufacturers

Exemption Imports Qualified Exclusions (under Subsequent exemption

category a

eligible for

eligible? expert review? Exclusions (automatic) conditions of use) notice required exemption?

Low volume ( <1,000 kg) Yes No None Serious acute or chronic effects; Before use or site of No

significant environmental manufacture changes.

effects.

Low volume ( <10,000 kg) Yes Yes Carcinogenic or teratogenic effects. Serious acute or chronic effects; Before use or site of No

Acutely toxic effects. significant environmental manufacture changes.

effects.

Site-limited intermediates No Yes Carcinogenic or teratogenic effects. Serious acute or chronic effects; Before volume Yes

significant environmental increases or site of

effects. manufacture changes.

aSome new chemical substances may be eligible for more than one exemption, Manufacturers and importers may apply for any exemption for which they are eligible.

SOURCE: Environmental Protection Agency; 47 F.R. 33897.

Table 2.—Proposed Polymer Exemption Provisions

Polymers for which no review is required Polymers that qualify for a 14-day reveiw Polymers excluded from exemption

1. Polymers manufactured from 1. Polymers of greater than 1,000 1. Water soluble polymers.

monomers listed by EPA. molecular weight. 2. Polymers containing less than

2. Polymers of average molecular 32 percent carbon.

weights greater than 20,000. 3. Polymers containing more than

3. Polymers that have limited and specified percentages of certain

defined numbers of low molecular elements.

weight components. 4. Polymers produced by living or

once-living organisms or cells

(“biopolymers”).

5. Polymers containing halogens or

cyano groups.

6. Polymers containing chemically

reactive groups.

7. Polymers that are designed to

degrade, decompose, or

depolymerize.

SOURCE: Office of Technology Assessment from Environmental Protection Agency; 47 F.R. 33924.

98-826 0 - 83 - 4
Chemicals suspected to have carcinogenic or

teratogenic potential are to be automatically excluded from the proposed exemptions for sitelimited intermediates and substances to be made

in amounts between 1,000 and 10,000 kg annually. In addition, substances with potential acutely toxic effects are to be excluded from the 1,000

to 10,000 kg annually low-volume exemption. To

be excluded from both the two proposed low-volume exemptions and the proposed site-limited intermediate exemption are any substances which,

under conditions of use, potentially may cause

serious acute or chronic health effects or significant environmental effects (table 1).

The reporting requirements for substances made

in amounts between 1,000 and 10,000 kg annually

or for use as site-limited intermediates include a

stipulation that a “qualified expert” review all

available data about the substance. The qualified

expert, an employee of the submitting company

or a consultant hired by the company, after his

or her review, must conclude that the chemical

meets the terms of the exemption.

To allow EPA to make a determination about

the likelihood that a substance for which an exemption is requested will not cause an undesirable

human health or environmental effect, the manufacture must submit a notice to the Agency 14

days before commencement of manufacture that

states which exemption is being sought. In addition, for substances to be manufactured or imported in amounts of 1,000 kg or less annually,

the notice is to contain sufficient information to

identify the chemical and describe its use and site

of manufacture. EPA, on the basis of toxicity data

or by reason of structural analogies between the

substance proposed for exemption and known

toxic substances, could declare the chemical ineligible for exemption.

For substances to be made or imported at between 1,000 and 10,000 kg annually and for sitelimited intermediates, the notice is to contain information about chemical identity, description of

uses (for low-volume chemicals), production volume (for site-limited intermediates), and site of

manufacture. EPA can declare any substance ineligible for exemption if the notice fails to meet

the exemption requirements. Substances that are

granted exemptions are not eligible for listing on

the Inventory of Chemical Substances and remain

subject to PMN requirements.

As is shown in table 1, only the first company

to submit an exemption for low-volume production will be eligible for exemption. If, subsequently, another submission is made for a chemical that

has received a low-volume exemption, a complete

PMN and review will be required. A trade association that reviewed the first draft of this report

objected to this provision of the proposed exemption. They argue that any number of manufacturers should be eligible for low-volume exemption

from PMN reporting requirements on a chemical.

Any number of manufacturers can receive a sitelimited exemption to manufacture a substance.

The proposed polymer exemption distinguishes

between polymers for which no review is required, those for which a 14-day review is required, and those excluded from exemption. Table

2 displays some aspects of the polymer exemption.

Polymers exempted from any review will require only that EPA receive an exemption notice

at the time of the start of manufacture. Such

substances will not be entered on the Inventory

of Chemical Substances because they have not

undergone PMN review. The exempted polymers

will become subject to section 5 PMN requirements if manufactured outside the terms of the

exemption.

For polymers subject to 14--day review, a PMN

must be submitted to EPA that identifies the

manufacturer, the site of manufacture, and the

polymer, and provides information about the

molecular weight of the polymer and the amount

of low-molecular weight material in the polymer

preparation, projections of expected production

volumes and uses, and any test data. Furthermore,

the submitter must certify that the substance is

a polymer and that it meets the conditions for

exemption.

In the event that EPA does not notify the submitter otherwise, manufacture of the polymer can

begin at the end of the shortened review period.

Manufacturers are to notify EPA when manufacture commences, and, at that time, a polymer that

has completed the 14-day review and gone into
Ch. 2—"New Chemicals" and the Toxic Substances Control Act ● 19

production will be placed on the Inventory of

Chemical Substances.

Certain classes of polymers (table 2) are excluded from the proposed exemption rule. In general, EPA excluded those classes because the agency has not had sufficient experience with them to

accept that they are of low potential hazard.

The low-volume, site-limited intermediate, and

polymer exemptions are still in the proposed stage.

Objections to the proposed exemptions focus on

the undeniable fact that less information would

be received by EPA about the exempted substances and that EPA’s review period would be

shortened. EPA justified its decisions on the basis

that the proposal exemptions are sufficient to

guard against unreasonable risk. However, several

comments have been received arguing against the

exemptions because they are seen as weakening

the PMN process to the point that protection

RISK ASSESSMENT

Two factors are of importance in estimating the

risk that may be posed by a substance. The first

is to determine any deleterious effect that the

substance may cause to human health or the environment. In this background paper, the word

“hazard” will be used to describe such effects. The

second factor is “exposure.”

Exposure is a complicated factor; determining

it for risk assessments considering human health

involves estimating the number of people who

may come in contact with the substance, the duration of the contact, the route(s) of adsorption, the

amount of substance which may be encountered

by people, and, especially for workers, whether

or not they employ personal protection equipment

to reduce the contact. For environmental risk

assessments, exposure estimates must consider the

number and kinds of organisms that might come

into contact with the substance and the distribution of the substance in different parts of the environment. An additional complicating factor in

considering exposures is the persistence of the

substance, which may vary in different parts of

the environment.

against unreasonable risks is being lessened. On

the other hand, industry sees the proposed exemptions as having ample safeguards and argue that

the procedure should be further simplified to

minimize burdens.

Several reviewers of the first draft of this

background paper objected to the proposed exemptions. The exemption categories are seen as

being too broad. The absence of a requirement

that the qualified expert submit the data considered in reaching a decision to certify a substance as qualified for exemption is viewed as

preventing EPA from carrying out its duty to

review test data before a chemical is manufactured. Furthermore, some reviewers expressed

concern that polymer preparations may be contaminated with hazardous chemicals and that

EPA’s general decision that some polymers are inherently less hazardous is an unjustified overstatement.

Human risk is estimated from knowledge of the

health hazard of a substance and the number of

people who are likely to be exposed to it at particular exposure levels (9). Environmental risk is

estimated from knowledge of the environmental

hazard of a substance and the number of organisms or fraction of the environment expected to

come into contact with the substance at expected

exposure levels.

Low levels of either hazard or exposure reduce

the amount of concern expressed about a substance. For instance, a very hazardous toxic

substance might be used in manufacturing. Although its toxicity is well known, the chemical

is also contained in sealed reaction vessels and

there is little or no human or environmental exposure. While there is some lingering concern in

case an accident releases the chemical, safeguards

to contain the accidental release or inactivate the

chemical can reduce those worries also. Limited

exposure, then, reduces concern about risks.

At the other extreme are substances to which

exposure is widespread but which have extremely low toxicities. For instance, polyester fibers in
20 ● The Information Content of Premanufacture Notices

clothing, to which almost everyone is exposed, considered. This background paper reports the

cause no worry for the population in general be- frequency with which PMNs contained informacause of very low (if any) toxicity. tion useful in making risk assessments.

EPA, or any other risk assessor, needs infor- EPA has to estimate effects when toxicity data

mation about both hazard and exposure. If either are not included in the PMN. The technique for

hazard or exposure is very low, the need for the making those estimates and some difficulties with

other kind of information maybe reduced. How- it are described in the next section.

ever, always, both components of risk must be

STRUCTURAL ACTIVITY RELATIONSHIP ANALYSIS AND

ITS USE IN PMN REVIEW

Only about half of PMNs report any toxicity

data (see ch. 6), and although about 96 percent

report at least one physical-chemical datum in addition to those specified in TSCA, reporting of

such data is spotty (see ch. 5). EPA, in the absence

of those data, must estimate either toxicity or

physical-chemicals properties. A complex of activities—examining the chemical structure of the

new substance, deciding which parts of the structure may be important in biological systems, comparing the structure to related structures described

in the chemical literature, and making projections

about the toxicity or chemical behavior of the new

substance—is involved in making estimates when

data are lacking. All of these activities are grouped

under the rubric of Structural Activity Relationship (SAR) analysis.

The underpinnings of SAR analyses are many

observations that certain chemical structures and

subunits are associated with toxic properties and

other structures and subunits are not. At the same

time, it is well known that some substances which

are quite closely related differ significantly in toxicity. A well-known example is the comparison

of 2-acetylaminofluorine to 4-acetylaminofluorine.

These two substances differ in the location of a

small chemical sidechain; the first is a carcinogen;

the second is not. The very different toxic properties of these two similar chemicals points to the

difficulties of using SAR (9).

No one claims that SAR is developed or refined

to the point that no toxicity testing is necessary.

However, arguments do arise about when its use

is appropriate, when it leads or may lead to incorrect predictions about toxicity. Ideally, criteria

for when it is and is not appropriate would be

available, but they have not been developed. The

considerable amount of professional opinion and

considered judgment that are involved in the use

of SAR analysis is illustrated in EPA’s proposed

low-volume chemical and site-limited intermediate

exemptions.

Factors that will be considered in evaluating

structural similarity include the molecular size,

shape, charge distribution, and weight, and the

position, size, and chemical characteristics of

functional groups or other substituents. These factors are judged in terms of their effect on such

parameters as chemical reactivity, stemochemically governed interaction with enzymes, absorbability and distribution, metabolism, and excretion

from an organism. (Other factors and parameters

may be important in specific cases.) The greater

the number of such factors that are identical or

nearly identical between two substances, the

closer the structural similarity.

The absolute degree of structural similarity,

however, is not the important determinant of the

significance of structural similarity . . . . the

significance of structural similarity to a human or

animal carcinogen or teratogen would be judged

with reference to the probability of eliciting carcinogenic or teratogenic effects. Therefore, all

available information concerning possible mechanisms of action of a carcinogen or teratogen will

be relevant to an assessment of the significant [sic]

of structural similarities between that substance

and a new chemical substance. Moreover, information indicating that certain groups on the carcinogen or teratogen are or maybe critical for toxicologic activity has to be considered before determining whether the new molecule has significant
Ch. 2—"New Chemicals" and the Toxic Substances Control Act ● 21

structural similarity to a referent chemical. Structural similarities at toxicologically significant sites

or a molecule are of greater importance than similarities at other sites.

In a number of cases, neither the mechanism

of action nor structural requirements for activity

of a referent toxic substance is known, even

though its toxicity has been clearly established.

In such instances, attention is usually drawn to

chemically or biologically active groups as potential sites of action. Structural similarity at these

sites would reasonably be accorded higher significance than similarity at less reactive sites.

It follows from this summary statement that a

determination of significant structural similarity

is often dependent on the kinds and amount of

toxicological information available for the

referent chemical. Because this information will

vary for each new substance, the Agency is unable

to prescribe definitive criteria against which structural similarity can be measured. The determination whether there is significant structural similarity will be based primarily on whether there is an

identifiable or plausible mechansim [sic] of toxicity that can be shared by the referent chemical

and the new substance; or, lacking information

or hypotheses on mechanism, whether substructures known or expected to be required for activity of the referent chemical are present in the

new substance (47 F.R. 33900). (Emphasis added

in paragraphs 3 and 4).

An acknowledged shortcoming of SAR analyses is that it can say nothing about an entirely

“new” structure. However, EPA officials point out

that the vast majority of substances submitted on

PMNs are derivatives of known chemicals and

that SAR is useful and sufficient to make decisions about those.

It would be possible to compare PMNs that describe novel chemicals to those that describe “me

too” chemicals with an eye to determining if more

data, especially toxicity data, were submitted on

substances for which SAR is more likely inappropriate. Such an analysis was beyond the resources of the study described in this background

paper.

Questions can be asked about what criteria EPA

used to decide that SAR was sufficient for making estimates of toxicity. OTA did not attempt

to answer that question, but it is clear from data

presented in this paper that in many cases no toxicity data were presented on the PMNs. In those

cases, if EPA was concerned about toxicity, the

Agency would have to rely on SAR. It may be

that EPA was too willing to use SAR analysis

when what was desirable or actually necessary

was more information about the chemical. To

determine whether or not EPA received necessary

information about particular chemicals would require a study different from the one described here

(see ch. 9).
3 ■

Methods Used in Study of

Information Content of

Premanufacture Notices
Methods Used in Study of Information

Content of Premanufacture Notices

PMNS EXAMINED BY OTA

All premanufacture notices (PMNs) considered

by the Environmental Protection Agency (EPA)

to be valid and complete that were received by

EPA from the beginning of the program (July 1,

1979) through the end of June 1981 and which

either completed PMN review or were withdrawn

because of a 5(e) notice being planned or written

were examined. In addition, the PMNs submitted

in June 1982 were examined by OTA. The total

number of examined PMNs was 740; 670 of which

were received in the first 2 years of the program

and 70 of which were received in June 1982.

Figure 2, which is based on records obtained

from EPA, describes the disposition of the 701

PMNs that entered review through June 1981.

Twenty-nine of the PMNs were returned to the

submitters as invalid; some of these PMNs described chemicals already on the Inventory of

Chemical Substances, and no PMN was necessary

for them. Others of the invalid PMNs were judged

to be incomplete.

Of the 672 valid PMNs, 50 underwent detailed

review, indicating that additional review was

necessary to resolve some uncertainty about risk

that remained after the initial screen. Nine of the

fifty were associated with unreasonable risk during the detailed review, and 5(e) orders were written. In each of those nine cases, the submitters

abandoned their intent to manufacture or import

the new substance and withdrew the PMN rather

than perform testing. In the case of two other

PMNs that underwent detailed review, the manufacturers decided to withdraw the PMNs before

a 5(e) order was written. The remaining 39 PMNs

that underwent detailed review PMNs were either:

1) judged not to present an unreasonable risk or

2) judged not to present an unreasonable risk

because the submitters undertook voluntary actions to reduce hazard or exposure after EPA informed the submitters of agency concern.

Figure 2.—Disposition of PMNs Submitted From

July 1979 and Including All Those That Completed

the 90-Day Review Period by the End of

September 1981

‘1 ., ..i+ , ‘?, .,:

~

. .

~, * :..$ * “$ : & <* ‘

. *, .X.,,+ - ~~ ~f~~ ~ 1’ -. , .

?,”‘;;

. .

Valid and "complete"

661 Completed review

SOURCE: Office of Technology Assessment from data collected by the Environmental Protection Agency,

Mr. Florio’s letter (fig. 1) requesting this study

specifically asked that OTA compare PMNs describing marketed (manufactured) chemicals to

those that described chemicals that have not been

manufactured. OTA used EPA-compiled records

to separate the PMNs received through June 1981

into those that had been manufactured by August

1982 and those that had not.

Some EPA employees told OTA staff that there

is no legal requirement that a submitter report that

manufacture has begun and that separating the

PMNs between those that described chemicals that

25

98-826 0 - 83 - 5
have begun manufacture and those that have not

may be subject to significant error. However, EPA

encourages submission of a “notice of commencement” (NOC), and industry reviewers of the first

draft of this study firmly expressed their opinion

that NOCs were viewed as a required notice and

that they were submitted. OTA depended on

EPA’s classification of a chemical as being

manufactured or not, which in turn depended on

the Agency’s having or having not received an

NOC. There maybe some error in those classifications. EPA was in the process of sorting out its

NOC records when OTA was examining PMNs,

and three different lists of manufactured chemicals

were produced during that time. Some 40 chemicals listed as “manufactured” on EPA’s first list

were removed from subsequent lists because clerical or transcriptional errors at EPA had incorrectly classified them. OTA used the most recent

available information from EPA, which should

have the fewest errors in classification.

As is shown on figure 2, half of the PMNs that

were received by EPA through June 1981 were

classified as being manufacturered by August

1982. Therefore an examination of all the PMNs

received by that date provides a comparison between 331 chemicals that were reported to have

begun manufacture after EPA’s receiving a PMN

and 330 that had not.

The PMNs received through June 1981 that described the nine substances that did not proceed

INSPECTION OF PMN FILES

PMNs are submitted either on an EPA-provided

form (44 F.R. 59764 and see app. B), on a form

developed by the Chemical Manufacturers Association (CMA) (see app. B), or in other formats

including letters. Upon receipt, each PMN is

photocopied and distributed to the appropriate

review groups in EPA. One copy is maintained

in the document control room until the 90-day

(or, in exceptional circumstances, longer) review

period is completed, and a copy is then deposited

in an inactive document control room.

In most cases, each inactive PMN is stored in

a file folder along with additional information

to manufacture because of EPA writing 5(e) orders

were also inspected. In those nine cases, EPA

decided that it had insufficient information to

make a decision about unreasonable risk to

human health or the environment and required

that the submitters generate more data before

manufacture could begin. In each of those cases,

the submitters decided not to produce additional

data, review was suspended as incomplete, and

the substance did not begin manufacture.

In addition to the PMNs received through June

1981, the PMNs received in June 1982 were examined. Comparison of the PMNs received during the two time periods was expected to reveal

any differences in PMN content between the 1979

to mid-1981 period and June 1982.

A shorthand nomenclature has been adopted

to distinguish between and among the groups of

PMNs examined by OTA. Those PMNs that were

received through June 1981 and that described

chemicals that had begun manufacture before the

end of August 1982 are called “manufactured

PMNs.” Those that were received through June

1981 and that had not begun manufacture by

August 1981 are called “nonmanufactured

PMNs.” All PMNs received in June 1982 are called

“June 1982 PMNs.” The nine PMNs for which

EPA wrote 5(e) orders during the period 1979

through September 1981 are called “regulated

PMNs.”

produced and obtained during EPA’s review. During OTA’s examination of PMNs, 11 file folders

were empty. Because the original PMN documents

were being photographed at a location away from

EPA during the summer of 1982 when OTA was

carrying out its examination, no copy of those 11

PMNs was available to OTA. Unless those 11

PMNs are included in the 29 “invalid” PMNs

shown on figure 2, those PMNs are not included

in any tabulation of PMNs reported here.

An annoying filing habit hampered OTA’s inspection of some PMNs (and would hamper any

other inquiry as well). Frequently, manufacturers
Ch. 3—Methods Used in Study of Information Content of Premanufacture Notices ● 2 7

submit several PMNs at the same time. Sometimes

the PMNs submitted together are closely related;

for instance, two forms of an organic chemical

differing only in that one is a sodium salt and that

the other is a potassium salt. Other times, the

PMNs submitted together have nothing in common except that they are the products and intermediates in a series of reactions. For instance,

Chemical A+ Chemical B -> Chemical C. Putting such PMNs together in a single file results

in the PMN forms being intermixed, and although

separable by attention to numbers on the form,

information retrieval is slowed.

OTA staff examined each PMN file for the presence or absence of information (45 items) and

recorded findings on the form illustrated in figure

3. To a major extent, OTA’s investigation depended on recording whether or not an item of

information was present. Three reasons could account for OTA’s reporting that no information

had been submitted for an item:

1. The submitter had not presented the

information.

2. The submitter had presented the information, but the information was not present in

the file inspected by OTA.

3. OTA incorrectly recorded that no information was present.

There was no way to judge the frequency with

which a piece of information was lost from a file

(reason 2), but it was essentially impossible for

a single item or a few items of information that

were reported on a PMN to be lost. PMNs are

INFORMATION COLLECTED FROM

The OTA data collection form (see fig. 3) was

designed to facilitate recording of the presence or

absence of information required by TSCA (see

lower right hand comer of form) and the presence

or absence of some data items identified by the

Organization for Economic Cooperation and Development (OECD) as useful in reviewing the

properties of new chemicals. Those data items,

called the Minimum Pre-marketing Data (MPD)

set, were accepted by the European Economic

Community (EEC) as a common standard for the

stapled. Therefore, if any information reported

on the PMN was found about a substance, probably all the PMN-reported information was

found. However, some EPA staff mentioned to

OTA that records of telephone conversations with

submitters were sometimes lost from the files.

Therefore, some information that was reported

to EPA might have been lost from the files and

not recorded by OTA. In fact, the concern expressed about lost telephone records was so great

that even though the OTA data collection form

provided for the tabulation of data requested by

EPA subsequent to the PMN submission, those

data were not analyzed separately. Instead, the

presence of a datum was recorded whether it was

submitted on the PMN or secured by a phone call

during the review process.

OTA staff could have misreported the absence

of information (reason 3 for OTA reporting that

an item of information was not reported). Such

errors are bound to occur, especially in an effort

that includes collecting 45 pieces of information

about 740 PMNs (a total of 33,300 pieces of information). To estimate the frequency of such errors, the information collected by OTA about

whether each PMN described a Class 1, Class 2,

or Class 3 substance was rechecked. Each of the

740 PMNs was reexamined to determine how frequently the class of the chemical reported on the

notice was correctly recorded by OTA. That examination showed that 23 errors were made in

740 entries, or an error rate of 3 percent. (The data

presented in this background paper report the corrected counts about chemical classes. )

premarket review of many new chemicals and

were considered for adoption as a mandatory reporting system by OECD. However, in a December 1982 meeting, OECD decided that reporting

of the MPD data is only one way to provide information about the toxic effects of new chemicals. The United States, the only OECD member

that did so, objected to the MPD requirement

because it represented “inflexible, across-theboard, one-time notice requirements for all new

chemicals, ” and EPA, which represented the
28 ● The Information Content of Premanufacture Notices

Figure 3.—Form Used by OTA in Collection of Data From PMNs

PMN

CMA File # — OTHE R

EPA Date NOC Filed Time Difference Days

— — . —

Parent Subsidiary— Manufacturer Feedstock Source— Sole Customer—

Further Processor— Other—

Production Volume---Exemption Non-exemption

Import country Non-import

Polymer Low Volume Site-limited Intermediate Other —

Final Disposition:

Specify any additional information requested: YES OR NO

OECD

CHEMICAL ID

Chemical Name

Formula

CAS# —

Finger-print Spectra

Degree of Purity —

—

PRODUCTION

Estimated Production/year

Intended Uses— Ind. Corn Cons SL Inter

Disposal Methods 

Mode of Transportation

ACUTE TOXICITY

Acute Oral Toxicity

Acute Dermal Toxicity

Acute Inhalation Toxicity

Skin Irritation

Skin Sensitization

Eye Irritation —

—

REPEATED DOSE TOXICITY DATA

14-28 Days

MUTAGENICITY DATA

RECOMMENDED PRECAUTION AND ECOTOXICITY DATA

EMERGENCY MEASURES Fish LC50 -at least 96 hr exposure

Daphni a -reproduction 14 days

ANALYTICAL METHODS Alg a -growth inhibition 4 days

PHYSICAL DATA DEGRADATION/ACCUMULATION DATA

Melting Point Bio-degradation:

Boiling Poin t Bio-accumulation:

Density —

—

Vapor Pressure—

Water Volubility

Partition Coefficient

Hydrolysis—

EPA, TSCA section 5 requirements:

Chemical Name and Structure —

Intended Uses

Spectra — Estimated Production Volume

Adsorption-Desorption —

Byproducts

Dissociation Constant — #of Workers to be Exposed

Particle Size —

— Disposal Method—

Toxicity—

/=data present

XX=data absent —

SOURCE:Office of Technology Assessment.
Ch. 3—Methods Used in Study of Information Content of Premanufacture Notices ● 29

United States at the OECD meeting, prefers the

more flexible PMN reporting requirements that

have been developed under the Toxic Substances

Control Act (TSCA) (3). In some cases, other

items of information, neither specified by TSCA

nor identified by OECD, were submitted on a

PMN and those were noted by OTA on its forms.

The OTA form provided space to record the

type of form used for the PMN submission and

whether or not the substance had entered manufacture (NOC = “notice of commencement” of

manufacture). In addition, OTA recorded whether or not the substance might be exempted from

the usual PMN review under EPA’s proposed lowvolume, polymer, or site-limited intermediate exemption programs. These classifications on OTA’s

part were necessarily rough. If the PMN identified

the substance as being made in amounts of less

than 10,000 kg annually, or as a polymer, or as

a site-limited intermediate, that information was

recorded. Some of these chemicals might not fit

into an exemption category because of reasons not

reported on the PMN or recorded by OTA, and

in some cases the submitter might prefer to submit a regular PMN rather than an exemption notice even if the exemption program were in effect.

Nevertheless, the submitter-supplied information

about production volumes, site-limited and polymer attributes allows some analysis of the information content of PMNs that describe members

of classes being considered for exemption from

PMN reporting requirements by EPA.

The “final disposition” indicated whether or not

a 5(e) order was written for the substance. If there

was a record of EPA-requested additional information, that was also noted in the form.

Data were transferred from the OTA form to

a computer for analysis. The accuracy of the

transfer of data was checked visually and corrections made before the analysis began.

SECURITY PRECAUTIONS TO PROTECT CONFIDENTIAL

BUSINESS INFORMATION

EPA has to protect the confidential business information (CBI) that is included in PMNs. OTA

staff who were to have access to PMNs signed a

security agreement with EPA pledging not to

divulge any CBI from the PMNs. In addition,

OTA staff read the relevant parts of the EPA

security guide dealing with protecting CBI. OTA

made the suggestion that the first draft of this

report would be first circulated to the appropriate

security officials at EPA so that EPA could bring

to OTA’s attention any CBI that was included in

the background paper. This agreement was modified somewhat. EPA security officials inspected

all tabular data in the first draft for CBI. After

EPA COOPERATION

they agreed that no CBI was in the tables, the draft

was sent out for review. Furthermore, OTA staff

agreed not to remove any PMN file or its contents from the workroom that was provided for

OTA at EPA.

OTA’s legal counsel informed OTA staff that

none of these conditions was necessary for OTA

to obtain and examine CBI. However, in the interest of being cooperative and because the restrictions that OTA agreed to did not greatly hobble

OTA’s work, OTA staff entered into the agreements mentioned above.

EPA staff were courteous and helpful to OTA and interviews. Many, but probably not all, of

staff throughout this project. Helpfulness was ex- the EPA staff who aided this study are listed in

tended by EPA staff in day-to-day cooperation appendix C.
30 ● The /nformation Content of Premanufacture Notices

ANALYSIS OF THE DATA

A computer program written by John Bell was collected data and the program for analysis will

used to analyze the collected data. The OTA- be made available on request to OTA.

ORGANIZATION OF THE PRESENTATION OF THE ANALYSIS

TSCA contains both specific and general reporting requirements. The items specifically required are listed in TSCA section 5 (d)(1)(a)(A).

In brief, the submitter is required to name and

describe the chemical, make projections of the expected uses and production volumes, estimate the

number of workers who may be exposed to the

substance, describe byproducts of the chemical’s

manufacture, and present methods for disposal

of the chemical. The general reporting requirements (TSCA sec. 5 (d)(1)(a)(B) and (C)) state that

the notice shall include “any test data in the possession or control of the person giving such notice”

that bears on the effects of the manufacture, use,

and disposal of the substance and a description

of any data about health and environmental effects of the substance “insofar as known to the

person making the notice or insofar as reasonably

ascertainable. ”

EPA has defined the terms “possession or control” and “known to or reasonably ascertainable”

in the proposed PMN reporting rules (44 F.R.

2265):

“Known to or reasonably ascertainable” means

all information in a person’s possession or control, plus all information that a reasonable person similarly situated might be expected to possess, control, or know, or could obtain without

unreasonable burden or cost.

“Possession or control” means in possession or

control of the submitter, or of any subsidiary,

parent company, or any company which the parent company owns or controls if the subsidiary,

parent company, or other company is associated

with the submitter in the research, development,

test marketing, or commercial marketing of the

substance . . . . Information is included within

this definition if it is: (I) in the submitter’s own

files, (2) in commercially available data bases to

which the submitter has purchased access, or

(3) maintained in the files in the course of employment by employees or other agents of the submitter who are associated with research, development, test marketing, or commercial marketing

of the substance.

The general reporting requirements apply to

two kinds of information, those that describe the

new substance and those that describe results of

tests of the substance’s possible toxic effects. The

OTA data collection form (fig. 3) was used to collect data for this study.

OTA examined each PMN to determine how

completely:

1. the TSCA-specified data items were

reported,

2. what additional physical-chemical information, and

3. what toxicity information was reported.

Results of OTA’s inspection of PMNs are presented in four parts. Chapters 4, 5, and 6 describe

the amounts of the three types of information submitted. Chapter 7 discusses the amount of information present in subgroups of PMNs, including

those subgroups that are likely to be exempted

from PMN reporting requirements and those that

are of interest because of consumer use.
4

Frequency of Submission of

TSCA-Specified Data on

Premanufacture Notices
4 ●

Frequency of Submission of TSCASpecified Data on Premanufacture Notices

The Toxic Substances Control Act (TSCA)

specifies that a company that plans to manufacture or import a new chemical in the United States

submit a Premanufacture Notice (PMN) to the En- 2.

vironmental Protection Agency (EPA). The PMN

is to contain information that identifies the

chemical, projects the amount of the chemical to

be made for specified uses, estimates the number

of workers involved in manufacture, and de- 3.

scribes byproducts produced in the chemical’s

manufacture and methods for its disposal. The fre- 4.

quency with which TSCA-required information

was submitted was examined on PMNs that:

1. had been submitted before the end of June

1981, completed review by the end of September 1981 and the manufacture of which

had begun by the end of September 1982

(called here “manufactured PMNs”),

PMNs like those in 1 except that EPA had

not been informed about commencement of

manufacture through the end of September

1982 (called here “non-manufactured

PMNs”),

all PMNs submitted in June 1982 (called here

“June 1982 PMNs”), and

PMNs that have not completed review because EPA issued a “5(e) order” requiring

submission of more information (called here

“regulated PMNs”).

NUMBERS OF PMNs SUBMITTED

Figure 4 shows the numbers of PMNs received

by EPA since the program’s inception. As is readily apparent, the number of submitted PMNs was

small at first, but rapidly increased. A number

of factors might account for the increasing numbers of PMNs. It maybe that companies hastened

the development process for new chemicals immediately before the start of the PMN program

in order to list the chemicals on the Inventory of

Chemical Substances without having to experience the delay and uncertainty of the PMN review

process. That scheduling change could have contributed to a subsequent hiatus in the introduction of new chemicals. As a result of hurrying

development of chemicals closest to production,

the time necessary to complete development of

chemicals at earlier stages might have been lengthened. Also, companies might have found it necessary to use the time when few PMNs were submitted to develop methods to prepare and submit the notices. Finally, any PMN-imposed

TO EPA

additional burdens to develop and submit information might have caused a delay in submission

of PMNs.

Although there is some flattening out of the rate

of increase, the number of PMNs continues to increase. Since the beginning of 1982, EPA has

received more than 70 valid notices each month.

It is important to remember that PMNs are required only for new substances. Many chemical

products are formulations or mixtures of already

existing chemicals, and those are exempted from

the PMN reporting requirements by TSCA (see

ch. 2). The number of new formulations and mixtures introduced each year was not determined

by OTA, but it is certainly many times greater

than the 1,000 or so new chemicals which require

PMNs. Since the components of the mixtures and

formulations are listed on the Inventory, they are

subject to the provisions of TSCA that apply to

existing chemicals.

33

98-826 0 - 83 - 6
34 ● The Information Content of Premanufacture Notices

Figure 4.–Number of Valid PMNs Received Each Month: April 1979 Through June 1982

Year

SOURCE: Drawn from data collected by the Environmental Protection Agency.

CHEMICAL NAME AND PRODUCTION VOLUMES

Whatever is accepted about the usefulness and

applicability of Structural Activity Analysis

(SAR) (see ch. 2), it is clear that knowledge of the

chemical’s structure is central to the process of

estimating chemical and biological properties.

TSCA specifies that new chemicals be named and

that formulas and structures be provided for

chemicals when available. The reporting of these

items is essential to review of the PMN.

Chemicals are named according to standard

rules, and names, therefore, provide information

about the substance. The name is a critical element in learning about the structure of the chemical, and, in turn, knowledge of the chemical’s

structure underpins EPA’s review of the PMN. An

accurate name is also necessary for listing the

chemical on the EPA’s Inventory of Chemical

Substances at the end of the review period.

Essentially all PMNs report the chemical name

(table 3). OTA’s examination found 11 PMNs, a

little more than 1 percent, that did not report a

name. All of the PMNs that did not include names

described polymers (see table 4).

The amount of the substance to be manufactured is an important element in estimating exposures. As is shown on table 3, essentially all

PMNs report estimated production volumes. If

EPA implements the program it is considering to

exempt low-volume substances from PMN review, the estimates of production volume will take

on additional importance.
Ch. 4—Frequency of Submission of TSCA-Specified Data on Premanufacture Notices . 35

Table 3.—Completeness of PMNs for TSCA-Specified Information

NonManufactured manufactured June 1982 Regulated Totals

Number Percent Number Percent Number Percent Number Number Percent

PMNs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331

Number with:

Chemical name . . . . . . . . . . . . . . . . . . . 325

Chemical class . . . . . . . . . . . . . . . . . . . 331

Production volume . . . . . . . . . . . . . . . . 329

Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325

Byproducts . . . . . . . . . . . . . . . . . . . . . . . 233

Number of workers . . . . . . . . . . . . . . . . 315

Disposal . . . . . . . . . . . . . . . . . . . . . . . . . 313

All TSCA-specified information . . . . . . . 218

All TSCA-specified information except

by products . . . . . . . . . . . . . . . . . . . .“. . . 293

SOURCE: Office of Technology Assessment.

100 330 100 70 100 9

98

100

99

98

70

95

326 99

330 100

328 99

322 98

207 63

302 92

298 90

190 58

69 99

70 100

69 99

69 99

49 70

68 97

65

46

9

9

9

9

8

9

9

8

89 274 83 62 89 9

740 100

729 99

740 100

735 99

725 98

497 67

694 94

685 93

462 62

638 86

Table 4.—Number of Class 1, 2, and 3 PMNs That Have

Name, Structure, and Formula

Name Formula Structure Formula and structure

Class Total Number Percent Number Percent Number Percent Number Percent

1 293 293 100 273 93 264 90 256 87

2 73 73 100 35 48 39 53 28 38

3 374 363 97 134 36 70 19 46 12

SOURCE: Office of Technology Assessment.

CHEMICAL FORMULAE AND STRUCTURES

EPA has divided all substances subject to regulation under TSCA into three classes. Essentially:

• Class 1 substances have a single component

chemical and that chemical can be described

by a chemical formula;

● Class 2 substances are complex combinations

of chemicals, which cannot be described by

a chemical formula; and

● Class 3 substances are polymers.

The EPA’s proposed rule for PMN reporting (44

F.R. 59764) provides an example of a Class 1 substance. The name of the chemical in the example

is N-(4-bromophenyl) acetamide; its formula, a

listing of the atoms in the chemical, is C8H8ONBr;

its structure is represented by a drawing that

shows the arrangements and relationships of the

atoms in the chemical:

H

H O H

HC

I II H

H

Such precise representation is not possible for

a complex combination of chemicals (Class 2), but

knowledge of the components that go into the

combination can sometimes be represented by formulae and structures.

Chemical polymers (Class 3) are chains of

smaller chemicals. A linear homopolymer is a
36 ● The Information Content of Premanufacture Notices

chain of a single monomeric subunit. If the

monomer is chemical A, the linear homopolymer

is A-A-A-A-A-A . . . . Except for the fact that

chain lengths may vary, say 50 or 100 or 500 or

more As in different preparations, such a polymer

can be represented accurately by structures and

formulae.

Other polymers can have two or more different

monomers, say B, C, and D, and their order of

assembly may vary. For instance, a polymer made

from a mixture of B, C, and D might be any of

a great variety of polymers (. . . B-C-D . . ., or

. . . D-B-B-B-C ..., etc. ) that differ in composition and length. It is impossible to describe such

heteropolymers by structures or formulae although each of the monomers can, of course, be

so described.

Further adding to the complexity of polymers

is that some branch. For instance, monomers E,

F, and G might react to produce a backbone of

E and F (. . . E-E-F-E-F . . .) with the G monomer

being attached to all or some of the Es (. . .

E-E-F-E-F ..., or . . . E-E-F-E-F . . .).

Few chemical reactions go to completion, and

polymer preparations frequently have “unreacted”

or “free monomers” associated with them. Sometimes the monomers are known to be toxic, and

in those cases, knowing the percentage of free

monomers or short polymers that is present is

important.

As expected, given the relative ease of producing such information for Class 1 chemicals, 93 perBYPRODUCTS

The TSCA-specified item least frequently reported on PMNs is the identification of byproducts produced during the manufacture of the new

substance (table 3). Industry reviewers of the first

draft of this paper pointed out that some reactions produce essentially no byproducts, and that

the absence of information might reflect that no

byproducts were present. While that may be the

case, when a submitter reported that no byproducts were formed, that was recorded by OTA, and

it is represented in the counts reported on table 3.

cent of Class 1 PMNs presented chemical formulae, 90 percent presented structures, and 87

percent both (table 4). The absence of this information from PMNs that do not report it may

mean that the submitting company does not have

the data.

Reporting of formulae and structures was much

less frequent for Classes 2 and 3. As is shown on

table 4, about half of Class 2 substance PMNs included either formula or structure and 38 percent

included both. Industry and EPA reviewers of the

first draft of this paper pointed out that information about the chemicals that were used in the

reaction to produce a Class 2 substance frequently

provides important data about the composition

of such substances in lieu of formulae and structures. EPA reviewers further stated that the

observed low frequency of reporting of formulae

and structures for Class 2 substances produces a

distorted view of the information the Agency

receives on PMNs for those substances. The Agency reviewers expressed general satisfaction with

the information submitted for Class 2 substances.

Other reviewers expressed dismay about the absence of such information. And, again, a determination of what errors might have resulted from

the absences would require a study of particular

PMNs and the decisions made about them.

Of the PMNs for Class 3 substances, 36 percent included a formula, 19 percent a structure,

and 12 percent both. If the name of the polymer

is sufficient to indicate the identity of the

monomeric subunits and their relationships, no

further information may be necessary.

OTA examined the possibility that PMNs that

described site-limited chemicals might more frequently not report byproduct information, and

that excluding those from consideration might

have a significant impact on the percentage of

PMNs that report byproducts. However, 60 (52

percent) of the 115 PMNs that described sitelimited chemicals reported byproduct information. Therefore, although the percentage of sitelimited PMNs that reported byproduct information was less than for all PMNs considered
Ch. 4—Frequency of Submission of TSCA-Specified Data on Premanufacture Notices ● 37

together, excluding them from consideration of health effects, is a byproduct of several manuwould not materially affect the percentage of facturing processes. A byproduct that is toxic or

reporting of byproduct information. one about which little is known presents special

The importance of byproducts varies. If the problems. In any case, absence of reported bybyproduct is a common chemical with no toxici- product identity decreases EPA’s ability to evalty or if it is present in very low concentrations, uate any risk associated with the chemical’s production and its byproducts. it is of little or no concern. At the other extreme,

the “dioxin” that is now of such concern because

USES

Uses for new chemicals are divided into three

categories—consumer, commercial, and industrial-on the basis of information supplied by submitters on the PMNs. About three-fourths of all

PMNs specified that the substance was intended

for one or more of those classes of use. In addition, OTA counted those PMNs that described

site-limited or intermediate chemicals as industrial-use chemicals. Adding that number of PMNs

to the number that specified either consumer,

commercial, industrial, or some combination of

uses and to the 27 that described a general use

substance, such as a component of a paint, brings

the total of PMNs that reported uses to 725 (98

percent). (See table 3).

Exposure assessment depends on estimates of

the numbers of people who may be exposed to

a substance, on estimates of the amount of the

substance that exposed persons may encounter,

on estimated routes of exposure, and on estimates

of incidence and duration of exposure episodes.

Consumer-use products are most important in

terms of numbers of people who may be potentially exposed to a substance. More people use

them, and any restrictions placed on uses are more

likely to be ignored or misinterpreted as the

number of users increases. On the other hand, the

highest potential intensity of exposure is likely for

products used in industry for the fabrication of

other products. Commercial-use products probably fall between consumer- and industrial-use

products both in terms of number of people potentially exposed and in potential intensity of exposure. Table 5 shows that the most frequently

reported uses were industrial, followed in order

by commercial and consumer, and last, by general. Somewhat over 40 percent of all PMNs indicated that the chemical was expected to be used

in more than one class of use (table 5).

Table 5.—Number of PMNs Describing Chemicals

Intended for Industrial, Commercial,

and Consumer Uses

Number of PMNs

Classes of use reporting use

Industrial . . . . . . . . . . . . . . . . . . . . . . . . . . . 552

Commercial . . . . . . . . . . . . . . . . . . . . . . . . . 247

Consumer . . . . . . . . . . . . . . . . . . . . . . . . . . 105

Industrial, commercial . . . . . . . . . . . . . . . . 111

Industrial, consumer . . . . . . . . . . . . . . . . . 65

Commercial, consumer . . . . . . . . . . . . . . . 66

Industrial, commercial, consumer . . . . . . 57

General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

SOURCE: Off Ice of Technology Assessment.

NUMBER OF WORKERS EXPOSED AND DISPOSAL

Over 90 percent of all PMNs reported the num- make inquiries about the numbers of workers esbers of workers who might be exposed and meth- timated to be involved in the proposed manufacods for disposal (table 3). Notes in the PMN files ture of the substances described on the PMNs.

indicated that EPA had often called submitters to
38 ● The Information Content of Premanufacture Notic e

SUMMARY OF FINDINGS ABOUT REPORTING OF

TSCA-SPECIFIED INFORMATION

Overall, 62 percent of the 740 PMNs reported

all TSCA-required information. That low percentage of completeness is very much influenced by

the low frequency of reporting byproduct information. When that item is ignored, 86 percent of

PMNs reported all TSCA-specified information

(table 3). It must be remembered, however, that

byproduct reporting is TSCA-specified, and its

frequent absence is remarkable. Production volume, chemical class, chemical name, and proposed uses were reported on almost every PMN.

The number of workers potentially exposed to the

substance and disposal methods were reported on

over 90 percent of all PMNs.

The frequency with which TSCA-specified data

was submitted did not differ by more than a few

percent among the manufactured, nonmanufactured, and June 1982 PMNs. From OTA’s examination, there is no discernible correlation between

the likelihood of being manufactured and the completeness of submission of TSCA-specified information. Also there is no obvious change in completeness between the PMNs submitted through

June 1981 and those submitted in June 1982.

TSCA specifies that the formula (atomic composition) and structure (arrangement of atoms)

of a new chemical be reported when available.

In practice, reporting formula and structure

should be easiest for Class 1 substances. Class 2

substances, by definition, cannot be described by

formula and structure although such information

can be presented for components or reactants that

were used to produce the complex composition

substances of this class. Class 3 substances

(polymers) also present problems for submitters;

they may be of varying sizes and compositions.

As expected, reporting of formula and structure

was most frequent for Class 1 chemicals, 93 and

90 percent respectively. The same two items were

reported on 48 and 53 percent of Class 2 PMNs;

36 and 19 percent Class of 3 PMNs (table 4).

The absence of formula and structure information on Class 2 chemicals would appear to create

a weakness in PMN review, which often depends

on knowledge of the structure of the substance.

However, both industry reviewers and EPA reviewers of the first draft of this background paper

are convinced that adequate information for review of Class 2 substances is present despite the

absence of any formula or structure information

from about half of the PMNs reporting those substances.

The absence of exact formulae and structures

for polymers probably causes fewer problems.

Polymers, because of their large size, tend to be

inactive biologically. Concern may be attached

to the monomers that are used to build the polymers, and ideally the formula and structure of the

monomers should be included. Of course, concern about monomers decreases with decreasing

concentrations of free monomers and short

polymers in the polymer preparation. A more

detailed analysis than that undertaken here would

be necessary to determine if formulae and structures were submitted appropriately for polymers

with significant monomer contamination.

OTA’s finding that not all PMNs contain all

items of TSCA-specified information does not

square with EPA’s classifying them as complete.

In particular, information about byproducts was

missing from more than 30 percent of the PMNs.

It maybe that such information had been obtained

by EPA during the PMN review process and subsequently lost from the files. If that is not the case,

the absence of those data would necessarily complicate EPA’s review.
5 .

Frequency of Submission of

Physical-Chemical Information

on Premanufacture Notices
5.

Frequency of Submission of

Physical-Chemical Information

on Premanufacture Notices

Many different types of information can be

used to describe the physical and chemical properties of a substance. The most important for the

Environmental Protection Agency (EPA) are those

that describe or project the behavior of the chemical under normal environmental conditions. For

instance, a chemical that is soluble in water presents problems different from those of a waterinsoluble chemical.

OTA inspected premanufacture notices (PMNs)

for the presence or absence of nine items of physical and chemical information. Those nine are

listed in table 6 along with a short description of

the use of each item. Table 6 also lists two other

items that were checked by OTA. “Transportation” provides information about how the chemical is to be moved, and “emergency information”

means that the submitter has developed methods

to cleanup spills and decontaminate workers who

come in contact with the substance.

Inspection of appendix A shows that EPA evaluated many of these items of information in evaluating PMNs. When an item was missing from

the PMN file, and it was of value to the PMN

review, EPA scientists had to estimate it. The

items examined by OTA include seven (melting

point, boiling point, density, vapor pressure, volubility in water, partition coefficient, and infrared

spectra) identified by the Organization for EcoTable 6.—items of Physical-Chemical Information

That Were Scored on PMNs

Item/Usefulness in determining possible risks of chemicals

Purity. -Necessary to delineate final product composition

and to know how much new chemical will be manufactured.

Infrared spectra.-Provides a “fingerprint” for identifying the

chemical.

Analytical methods.—Provides information useful for identifying the chemical.

Melting point.- Provides information about the physical state

(liquid or solid) of the chemical during use.

Boiling point.-Provides information about the physical state

(liquid or gas) of the chemical during use and some information about volatility.

Density.—Provides information about whether the chemical

will float or sink in water.

Vapor pressure. —Provides key information about potential

for exposure through inhalation and escape of the substance into the atmosphere.

Water solubility.—Provides information about chemical

behavior in water and an indication of the likelihood of

chemical being taken up by animals and humans.

Partition coefficient.—This measurement reflects the relative

affinity of a chemical for an aqueous versus an organic environment. It is important for making predictions about a substance’s persistence in various environments.

Transportation. — Information about the method(s) used to

move the chemical from site to site,

Emergency Information.—Warning of possible hazards of the

chemical and methods to decontaminate people and areas.

SOURCE: In part from Mazza (1982); Office of Technology Assessment.

nomic Cooperation and Development as useful

in describing new chemicals, and, at one time,

recommended for inclusion in PMNs by EPA (46

F.R. 8986).

HOW MANY PHYSICAL-CHEMICAL DATA WERE SUBMlTTED ON PMNs?

Data about the nine physical-chemical items or at least highly desirable to characterize the

listed in table 6 are collected by companies in the chemical and manage its manufacture. None of

development and manufacture of at least some the items of physical-chemical data listed in table

chemicals because such information is necessary 6 is specified in the Toxic Substances Control Act

41

98-826 0 - 83 - 7
—

42 ● The Information Content of Premanufacture Notices

(TSCA), but reporting of such data in “the possession or control” of the submitter is provided for

by the general reporting requirements.

The data in table 7 show that none of the PMNs

examined by OTA reported all the items of physical-chemical data listed there. Also shown is the

fact that only 29 of the PMNs, 4 percent of the

total, reported none of the physical-chemical items

listed in the table.

There are, of course, several possible reasons

for physical-chemical data not being present in

the PMN. First, the submitter might not have the

data because they have no value in the development or manufacture of the chemical. Second, the

submitter might have some data, but, for one reason or another, not reported them. Third, data

may have been lost from the file.

There was general agreement among reviewers

of the first draft of this background paper that

it would be unusual for a submitter to develop

data about all items shown on table 6. For instance, knowledge of the melting point is useful

for a chemical that exists as a solid and a liquid

under the conditions of manufacture and use;

knowledge of the boiling point might be less important. Similarly, knowledge of the vapor pressure of a solid has little usefulness. Arguments like

these certainly can be advanced to explain why

none of the PMNs reported all the items and emphasize that submitters develop and collect data

that are important to them. Since EPA is most

interested in the properties of the chemicals under

normal exposure conditions, the data collected by

submitters should be useful to the Agency also.

One reviewer expressed the opinion that it is

impossible to develop a chemical for manufacture

without some physical-chemical data. The same

reviewer also suggested that some submitters

might elect not to report physical-chemical data

because those items are not specified in TSCA.

Other reviewers emphasized that a new chemical that represents only a small change from an

existing chemical may require few physical-chemical measurements to manage its development and

manufacture. As an example, a reviewer suggested

that a new polymer that differed from an existing

polymer only in being somewhat longer might be

produced without developing new physical-chemical data.

The physical-chemical datum most frequently

reported was purity, followed by information

about analytical methods. Those two items are

especially important to the manufacturer. Knowledge of purity is necessary to any estimates of how

much of the new chemical will be made, and analytical methods are necessary to locate and measure the substance.

The items that are most directly related to predicting the behavior of a chemical in the environment and its likelihood of being taken up by animals and humans—melting point, boiling point,

density, volubility in water, and partition coefficient—were reported less frequently. Of these, solTable 7.–Number of Physical-Chemical Data [terns Submitted on PMNs

Manufactured Nonmanufactured June 1982 Regulated Total

Number Percent Number Percent Number Percent Number Number Percent

PMNs . . . . . . . . . . . . . . . . . . 331 100 330 100 70 100 9 740 100

Infrared spectra . . . . . . . . . 8 4 6 0 86 12

Purity . . . . . . . . . . . . . . . . . . 67 49 70 3 543 73

Analytical methods . . . . . . 191 58 176 53 39 56 8 414 56

Melting point. . . . . . . . . . . . 83 25 78 24 11 16 7 179 24

Boiling point . . . . . . . . . . . . 92 28 97 29 23 33 7 219 30

Density. . . . . . . . . . . . . . . . . 61 18 63 19 9 13 7 140 19

Vapor pressure . . . . . . . . . . 83 25 73 22 18 26 6 180 24

Volubility (water). . . . . . . . . 149 45 129 39 27 39 3 308 42

Partition coefficient . . . . . . 15 5 11 3 0 — 27

Transportation . . . . . . . . . . 238 72 197 60 47 67 482

Emergency information . . . 107 32 111 34 31 44 6 255 34

—all . . . . . . . . . . . . . . . . . . . 0 0 — o — o 0 —

—none . . . . . . . . . . . . . . . . . 9 ‘ 3 19 6 1 1 0 29 4

SOURCE: Office of Technology Assessment.
Ch. 5—Frequency of Submission of Physical-Chemical Information on Premanufacture Notices ● 4 3

ubility in water was reported on 42 percent of all

PMNs and melting point and boiling point on 24

and 30 percent respectively. Vapor pressure was

reported on 24 percent and partition coefficient

on 4 percent.

A reviewer pointed out that measurements such

as melting points and boiling points are only

possible on relatively pure substances. Many commercial chemicals are not so pure and such measurements, even if they were made, according to

the reviewer, would be meaningless. Additionally,

EPA reported that the majority of PMNs describe

solid materials and that some measurements, especially vapor pressure, have little value for those

substances.

The partition coefficient, which measures the

relative affinity of a chemical for both aqueous

and organic environments, is gaining wide acceptance as being especially useful in making predictions about possible bioaccumulation of a chemical. Its usefulness is limited to substances that are

soluble in both octanol and water. Despite that

limitation, EPA staff reported that partition coefficients are very important in making estimates of

effects on the environment. It was often used in

PMN reviews, and when it was not supplied on

the PMN (it was absent from 96 percent), EPA

reviewers estimated the partition coefficient based

on knowledge of related chemicals.

An industry reviewer drew attention to an important piece of information that EPA often obtains on the PMN or subsequently requests. A

simple “block diagram” of the process by which

the chemical is to be made supplies much information about the temperatures and conditions of

manufacture that is useful in assessing worker exposure and learning about the properties of the

chemical. Another reviewer from an environmental organization also mentioned the block diagrams but characterized them as less valuable for

risk assessment than are more detailed descriptions of the manufacturing processes. Unfortunately, OTA did not collect data about the frequency with which process descriptions were reported.

PHYSICAL-CHEMICAL DATA WERE REPORTED MORE

FREQUENTLY ON MANUFACTURED PMNs

The data in table 7 show that PMNs that described manufactured chemicals were more complete in reporting physical-chemical data. An explanation for this observation could be that more

data have been accumulated on chemicals that are

closer to being manufactured. In other words, if

a submitter waits to file a PMN until he is more

nearly ready to produce the chemical, he may

have accumulated more information about the

chemical.

Table 8 reports an examination of the possibility that chemicals for which PMNs were submitted

closer to the time of manufacture reported more

information about physical-chemical properties

of the substance. Manufactured chemicals were

divided into eight groups-those for which notices

of commencement of manufacture were filed before the end of the 90-day review period and those

filed within 1 to 9 days, 10 to 29 days, 30 to 89

days, 90 to 119 days, 120 to 179 days, 180 to 365

days, and more than 1 year after the end of the

review period. Inspection of table 8 does not reveal any consistent pattern in completeness of

reporting and does not support the idea that the

amount of physical-chemical information submitted on PMNs depends on the length of time

between submission and manufacture.

The reason for more complete reporting on

manufactured chemicals is not known, and further analysis would be necessary to find it. In

absence of that knowledge, the apparent difference between manufactured and yet-to-be manufactured chemicals remain an interesting observation.
44 . The lnformation Confent of Premanufacture Notices

SUBMISSION OF PHYSICAL-CHEMICAL DATA

ON PMNs OF DIFFERENT CLASSES

In general, less concern is attached to polymers

(Class 3) substances than to other chemicals because their large size (high-molecular weight)

tends to make them biologically inactive. Table

9 describes the number of polymer PMNs that

contained physical-chemical data and compares

that information to the same information submitted about nonpolymers (Classes 1 and 2).

As can be seen, there are few pronounced differences in reporting physical-chemical data between nonpolymers and polymers (Class 3)

PMNs. For instance, the volubility of the chemical

in water was more frequently reported for Classes

1 and 2 PMNs, probably because many polymers

are water-insoluble. Although that could have

been reported, it might have been left out of the

submission as superfluous.

Class 2 submissions describe complex combinations of chemicals, and they less frequently report

structures and formulae (see table 4) than do Class

1 submissions. However, PMNs for both Classes

1 and 2 report physical-chemical data with about

the same frequencies. Therefore, despite the less

frequent reporting of structure and formula for

Table 9.–Physical-Chemical Information on PMNs Describing

Class 1, Class 2, and Class 3 Chemicals

Class 1 Class 2 Class 3 Class 1 and Class 2

Number Percent Number Percent Number Percent Number Percent

PMNs . . . . . . . . . . . . . . . . . . . . . 293 100 73 100 374 100 100

Infrared spectra . . . . . . . . . . . .

Purity . . . . . . . . . . . . . . . . . . . . .

Analytical methods . . . . . . . . . 148

Melting point . . . . . . . . . . . . . . 110

Boiling point . . . . . . . . . . . . . . . 69

Density. . . . . . . . . . . . . . . . . . . . 43

Vapor pressure . . . . . . . . . . . . . 61

Volubility (water) . . . . . . . . . . . 147

Partition coefficient. . . . . . . . . 17

Transportation . . . . . . . . . . . . . 155

Emergency information. . . . . . 87

11

80

50

36

24

15

21

50

6

53

30

12

59

33

17

31

14

22

39

3

45

29

16

81

45

23

42

53

40

42

253

234

52

119

82

97

122

7

283

140

44

292

181

127

100

57

63

166

20

200

116

SOURCE: Office of Technology Assessment.
Ch. 5—Frequency of Submission of Physical-Chemical Information on Premanufacture Notices ● 45

Class 2 and 3 chemicals, EPA receives physicalchemical data useful for its analysis about equally

for all classes of chemicals.

Transportation information was more frequently reported for polymers. The more frequent

transportation information is consistent with the

idea that polymers are end products of chemical

production lines and moved to another manufacturing site to be incorporated into a final product.

In contrast, Class 1 and 2 substances might more

frequently be intermediates in production and not

transported from the site of their manufacture.

The data in table 9 suggest that manufacturers

develop and submit essentially the same amount

of physical-chemical information about polymers

and nonpolymers. At least some of the exceptions

to this generalization are easily explainable given

differences between the two kinds of chemicals.

SUMMARY OF FINDINGS ABOUT SUBMISSION

OF PHYSICAL- CHEMICAL DATA

PMNs were inspected for the presence or absence of information about nine items concerning physical-chemical properties and whether or

not emergency information and information

about how the chemical was to be transported was

submitted. Those items are listed and briefly described in table 6.

None of the inspected PMNs reported all 11

items (table 7). Unlike the finding that TSCArequired information was reported equally frequently on manufactured and nonmanufactured

PMNs, physical-chemical data were more frequent on manufactured PMNs.

A method was devised to investigate the

possibility that manufacture of chemicals for

which PMNs were prepared later in the development cycle contained more data. The idea was

that a chemical that entered production very soon

after submission of the PMN was further along

in its development than a chemical that entered

production after a longer delay. However, no consistent patterns were seen between frequencies of

submission of physical-chemical data and the time

between PMN submission and commencement of

manufacture (table 8).

No other explanation for the dichotomy in

reporting physical-chemical data on manufactured

and nonmanufactured PMNs was investigated.

However, there is at least one other possible explanation for the observation. Some EPA employees emphasized that the Agency does not require

that the manufacturers notify the Agency of commencement of production of the chemical. Others

were confident that those notices were nearly

always submitted, and industry reviewers of the

first draft of this report said that they understood

submission of the commencement of manufacture

notice was mandatory. Nevertheless, it is possible that some percentage of those PMNs listed as

not manufactured do, in fact, describe chemicals

that are now being produced. If that is true, the

lower frequency of reporting physical-chemical

data would parallel a lower frequency of notifying EPA of commencement of manufacture. This

possibility was not examined, although calling

submitters of nonmanufactured PMNs would be

a way of exploring the possibility.
6

Frequency of Submission of

Toxicity Information on

Premanufacture Notices
Frequency of Submission of Toxicity

Information on Premanufacture Notices

The legislative history of the Toxic Substances

Control Act (TSCA) emphasizes that Congress

was interested in toxic substances being identified

before they enter commerce. And, of course, the

most direct and immediate way of learning about

toxicity is from toxicologic tests.

There are two reasons for toxicologic information appearing in a premanufacture notice (PMN)

file; it could have been submitted on the original

PMN, or it could have been requested by the Environmental Protection Agency (EPA). There are

two avenues for request: a formal 5(e) order under

TSCA, or an “informal” request with which the

submitter complies.

OTA inspected each PMN for 11 items about

toxicity that appear on the European Economic

Community (EEC) Minimum Premarketing Data

(MPD) set (46 F.R. 8986) of required premarket

testing information. Table 10 lists those items and

describes their uses in risk assessment. (One toxicity item listed by EEC, a determination of any

lethal effect of the substance on algal growth, was

not recorded by OTA). The summary of toxicity

concerns addressed in EPA’s initial review of

PMNs (app. A) lists many of the specific tests

scored by OTA. When a test result was not reported, and that test was of importance to EPA’s

risk assessment, EPA scientists would have had

to estimate the chemical’s toxic effects based on

Structural Activity Relationship (SAR) analysis.

The first three items listed on table 10, acute

toxicity tests, are similar in that they measure the

lethality of the substance in laboratory animals;

they differ in routes of exposure. Contact irritations and sensitizations, whether of the eye or the

skin, are common problems in the workplace and

in consumer uses. The two skin tests and one eye

test provide estimates of the effects from shortterm exposures of those organs. Repeated dose

toxicity tests employ repeated doses at a level not

Table 10.—ltems of Toxicity Information

That Were Scored on PMNs

Item/Usefulness in determining possible risks of chemicals

Acute oral toxicity.—Provides information from animal tests

about possible lethal or other serious effects from shortterm ingestion.

Acute dermal toxicity. —Provides information from animal

tests about possible lethal or other serious effects from

short-term exposures on the skin.

Acute inhalation toxicity.— Provides information from animal

tests about possible lethal or other serious effects of shortterm inhalation.

Skin irritation-Provides information from animal tests about

possible irritation resulting from contact with the skin.

Skin sensitization.—Provides information from animal tests

about possible changes in the skin resulting in increased

sensitivity to other substances.

Eye irritation. —Provides information from animal tests about

possible adverse effects from the substance reaching the

eye.

Repeated dose toxicity.—Provides information from animal

tests about effects of repeated exposures on major organ

systems.

Mutagenicity.– Provides information from tests on microorganisms, animals, or cells from various organisms about

the possible mutagenicity of the chemical.

Fish toxicity.—Provides information about possible adverse

effects on fish.

Daphnia toxicity.— Provides information about possible adverse effects on invertebrates.

Biological accumulation/degradation. —Provides information

about the tendency of the chemical to be accumulated or

to be degraded in biological systems.

Miscellaneous.—Some PMNs included additional information from other toxicity tests and other sources.

SOURCE: In part from Mazza (1982); OTA (1981); Office of Technology Assessment.

known to cause death and measure the effects on

organ systems.

Mutagenicity is the capacity to cause changes

in the genetic material, DNA. Most tests for mutagenicity are “short-term” or “in vitro tests,” which

require a few days to a few weeks for execution

and measure interactions between the chemical

and DNA (11). Table 11 is a description of eight

general types of short-term tests useful for measuring mutagenicity or other interactions with DNA.

49
50 Ž The Information Content of Premanufacture Notices

Table 11.—Eight General Classes of Short-Term Tests

That Measure Mutagenicity or Other interactions

With DNA

1. Mutagenesis in bacteria and bacterial viruses.

2. Mutagenesis in yeast.

3. Mutagenesis in cultured (laboratory-grown) mammalian

cells.

4. Mutagenesis affecting mouse hair color.

5. Mutagenesis in fruit fries (Drosophila melanogaster).

6. Effects on chromosomal mechanics in intact

mammals and in mammalian cells in culture.

7. Disruption of DNA synthesis and DNA repair

mechanisms in bacteria and other organisms.

8. in vitro transformation of cultured cells.

SOURCE: Off Ice of Technology Assessment (1981).

TSCA focused attention on three kinds of toxicities-carcinogenicity (the capacity to cause cancer), mutagenicity, and teratogenicity (the capacity to cause birth defects). Such “chronic toxic effects” can result from low dose exposures. Mutagenicity (certainly), carcinogenicity (generally),

and teratogenicity (perhaps) result from interactions between environmental agents and DNA.

Of the toxicity tests listed in table 10, only

HOW MANY TOXICOLOGIC DATA

The number of PMNs containing toxicity information is shown on table 12. Overall, 53 percent

of all PMNs inspected had some information

about toxicity. PMNs that described manufacmutagenicity tests measure interactions with DNA

and bear directly on questions of chronic toxic

effects. Other tests for chronic toxic effects, involving large numbers of experimental animals,

long periods of time, and high costs (9) are considered too expensive for new chemicals.

Fish and daphnia toxicity tests provide information about “ecotoxicity.” They are especially useful in making projections about the effect of the

chemical on aquatic organisms.

Biological accumulation and degradation tests

provide important information about the persistence of the chemical in organisms and biological methods for degradation. The value of

these tests is greatest for substances to be discharged into water, and industry reviewers of the

first draft of this report pointed out that such tests

are not necessary on substances that will not reach

a water source. OTA did not collect information

about whether or not it was planned to discharge

chemicals described on PMNs into water, and so

cannot comment on the appropriateness of ecotoxicity data submission.

ERE SUBMITTED ON PMNs?

tured chemicals had such information somewhat

more frequently; 59 percent reported some toxicologic information. As a group, the June 1982

PMNs reported toxicity data less frequently than

Table 12.-Number of Toxicologic items Submitted on PMNs

NonManufactured manufactured June 1982 Regulated Total

No. Percent No. Percent No, Percent No. No. Percent

PMNs . . . . . . . . . . . . . . . . . . . . .. 331 100 330 100 70 100 9 740 100

Acute oral toxicity . . . . . . . . . . . 165 50 126 38 25 36 1 317 43

Acute dermal toxicity . . . . . . . . 132 40 75 23 13 19 0 220 30

Acute inhalation toxicity . . . . . 33 10 28 8 4 6 0 65 9

Skin irritation . . . . . . . . . . . . . . . 124 37 101 31 21 30 1 247 33

Skin sensitization . . . . . . . . . . . 40 12 23 7 3 0 9

Eye irritation. . . . . . . . . . . . . . . . 137 41 115 35 20 1 37

Repeated dose toxicity. . . . . . . 56 17 28 8 0 — 1 85 11

Mutagenicity . . . . . . . . . . . . . . . . 58 18 55 17 11 16 2 126 17

Fish toxicity . . . . . . . . . . . . . . . . 35 11 26 8 1 1 2 64 9

Daphnia toxicity. . . . . . . . . . . . . 16 5 12 4 1 1 0 29 4

Biological accumulation or

biological degradation . . . . . 20 6 12 6 0 5

No toxicity information. . . . . . . 137 41 167 53 6 47

SOURCE: Office of Technology Assessment.
Ch. 6—Frequency of Submission of Toxicity /formation on Premanufacture Notices ● 5 1

did the manufactured or nonmanufactured

PMNs.

The most frequently reported toxicity tests were

acute oral toxicity tests that establish the lethality of the chemical when ingested by test animals.

Fifty percent of the manufactured PMN chemicals

and 43 percent of all PMNs contained that kind

of information. The second most frequently reported test was for eye irritation, followed closely by tests for acute dermal toxicity and skin irritations.

Mutagenicity tests, the only tests that bear on

chronic toxicity, were reported on less than onefifth (17 percent) of all PMNs. Data about ecotoxicity were reported even less frequently: fish

toxicity on 9 percent of PMNs; daphnia toxicity

on 4 percent; biological accumulation or degradation on 5 percent. Figure 5 is a comparison of the

frequency of submission of the three most commonly reported toxicity tests and mutagenicity

tests on manufactured, nonmanufactured, and

June 1982 PMNs.

TSCA is written to protect against unreasonable

risks to human health or the environment, and

PMNs contain limited data for EPA to consider

in making decisions about potential chronic toxicities or ecological toxicity. Several reviewers of

the first draft of this background paper pointed

to the absence of such data as a major concern.

EPA can use SAR analysis to make estimates of

toxicity when data are not available, but whether

EPA appropriately decides that SAR analysis is

sufficient can be questioned. At a more fundamental level, given the limited experience with SAR,

the appropriateness of the technique can also be

questioned. Unquestionably, however, it is employed.

The reduced toxicity submissions in June 1982

may be only a “blip,” an abnormally low month,

or it may reflect a downward trend over the periFigure 5.—Percentage of PMNs Containing the Three Most Commonly Reported Toxicity Tests and the

Two Tests Related to Chronic Toxicity and Ecotoxicity

70[

60 —

50 —

40 —

30 —

20 —

10 —

5 —

o —

Acute

oral

toxicity

—

Eye

irritation irritation

—

Skin

Manufactured PMNs N = 331

June 1982 PMNs N = 70

Mutagenicity

—

—

Daphnia

or fish

killing

SOURCE: Office of Technology Assessment.
52 ● The Information Content of Premanufacture Notices

od June 1981 to June 1982. The observed drop in

reporting of all toxicity information items was not

paralleled by a drop in physical-chemical data reporting. June 1982 PMNs were highest in the frequency with which 4 of the 11 physical-chemical

items were reported (see table 7).

A number of reviewers objected to drawing

even a tentative conclusion from comparing the

June 1982 data to earlier data. One group of industry reviewers inspected the publicly available

records for the June 1982 PMNs and provided its

appraisal of those for which no toxicity information was reported. According to the opinions of

those industry reviewers, the June 1982 PMNs that

contained no toxicity data described chemicals

that were not hazardous.

Another reviewer (not from an environmental

group), drew a very different conclusion from the

comparison of June 1982 data to earlier data. In

his opinion, if the decrease in toxicity data reporting is general and not confined to the single month

of June 1982, it reflects an industry perception that

EPA is no longer so serious about PMN reporting. In turn, that perception of decreased EPA

concern about new chemicals is being translated

into reduced industry attention being paid to

learning about potential toxicity.

TOXICITY DATA WERE MORE FREQUENTLY

REPORTED ON MANUFACTURED PMNs

Just as was found for physical-chemical data,

PMNs describing now-manufactured chemicals

contain more toxicity information than PMNs for

substances not yet manufactured. The same sort

of analysis described in table 8 was applied to toxicity data. As is shown on table 13, there is no

consistent relationship between time required for

commencement of manufacture and amount of

submitted toxicity information. Therefore, although more toxicity and physical chemical data

are reported for manufactured PMNs, the completeness of reporting does not appear to be a

function of how close to manufacture the substance was when the PMN was submitted. Instead, these observations may suggest that submitters’ analyses permit them to judge accurately

which substances are more likely to be manufactured and to produce more information about

them.

Table 13.—Completeness of PMNs for Toxicity Information as a Function

of the Time Between End of the Review Period and the Commencement of Manufacture

Time to notice of commencement

<1 1-9 10-29 30-89 90-119 120-179 160-365 >365

day days days days days days days days

No. No. Percent No. Percent No. Percent No. Percent No. Percent No. Percent No. Percent

PMNs . . . . . . . . . . . . . . . . . . . . . . . . . 10 45 100 41 100 87 100 23 100 41 100 58 100 25 100

Acute oral toxicity . . . . . . . . . . . . . . 3 29 44 17 41 50 57 10 43 20 99 26 45 19 76

Acute dermal toxicity . . . . . . . . . . . 3 19 42 12 29 38 44 10 43 13 30 24 41 13 42

Acute inhalation toxicity . . . . . . . . 0 5 11 7 17 10 11 1 4 3 7 4 7 3 12

Skin irritation . . . . . . . . . . . . . . . . . . 3 14 31 13 32 36 41 9 39 13 30 23 40 13 42

Skin sensitization . . . . . . . . . . . . . . 0 4 8 7 8 6 26 14 12

Eye irritation . . . . . . . . . . . . . . . . . . . 2 18 40 14

Repeated dose toxicity. . . . . . . . . . 0 3 6 5 12 12 14 5 22 8 20 12 21 11 44

Mutagenicity. . . . . . . . . . . . . . . . . . . 1 3 6 7 17 15 17 5 22 4 10 19 33 4 16

Fish toxicity . . . . . . . . . . . . . . . . . . . 1 4 8 3 7 9 10 4 17 3 7 12 4 16

Daphnia toxicity. . . . . . . . . . . . . . . . 1 0 – 2 5 2 2 3 13 1 7 3 12

Biological accumulation

or biological degradation . . . . . . 0 3 6 1 2 7 8 0 – 4 10 3 5 2 8

SOURCE: Office of Technology Assessment.
Ch. 6—Frequency of Submission of Toxicity Information on Premanufacture Notices ● 5 3

SUBMISSION OF TOXICITY DATA ON PMNs DESCRIBING

DIFFERENT CLASSES OF CHEMICALS

As a class, polymers are associated with less

hazard than some other chemicals, and some substances of this class are being proposed for exemption from PMN review by EPA (see table 2). In

many cases, the large size (high-molecular weight)

of polymers makes them biologically inactive because they cannot be taken up by most cells. For

that reason, EPA considers toxicity information

to be of less importance for Class 3 chemicals

(polymers) and of more importance for the Class

1 and 2 chemicals.

Table 14 shows the frequency, by class of chemical, with which toxicologic information was submitted on PMNs, and figure 6 shows the frequency of submission of the three most common toxicity items and mutagenicity and ecotoxicity. In

keeping with the inherently lower toxicity of polymers, less testing was reported for those substances.

More importantly, perhaps, removing Class 3

chemicals, polymers, from consideration allows

computation of the frequency with which toxicity

data for Classes 1 and 2 are submitted. Sixty-one

percent of nonpolymer PMNs reported acute oral

toxicity data, eye irritation was reported on 52

percent, and skin irritation on 49 percent. Mutagenicity data, important to making estimates of

chronic toxicity, were submitted on 27 percent of

Classes 1 and 2 PMNs and fish toxicity and daphnia toxicity on 13 and 5 percent respectively

(table 14).

If the proposition is accepted that toxicity data

are less likely to be needed for evaluating polymer

PMNs, the data in table 14 can be taken, with

some caveats, as a more accurate representation

of frequency of toxicity submission. However,

some monomers from which polymers are made

are toxic. If a polymer preparation is contaminated with a significant fraction of free monomers

or low-molecular weight polymers, toxicity information would be important. Polymer PMNs

sometimes report the percentage of monomers

present, but OTA did not attempt to correlate

percentages of monomeric and low-molecular

weight contamination with submitted toxicity

data. By the same token, some of the Class 3 polymers PMNs that submitted toxicity data reported

monomer toxicity, but OTA did not record those

details. In addition, reviewers of the first draft of

this report drew attention to the possible contamination of polymers with catalysts and other chemicals used in their manufacture.

Table 14.—Toxicity Information on PMNs Describing

Class 1, Class 2, and Class 3 Chemicals

Class 1 and

Class 1 Class 2 Class 3 Class 2

No. Percent No. Percent No. Percent No. Percent

PMNs . . . . . . . . . . . . . . . . . . . . .. 293 100 73 100 374

Acute oral toxicity. . . . . . . . . . . 178 61 44 60 96

Acute dermal toxicity . . . . . . . . 120 41 33 45 68

Acute inhalation toxicity . . . . . 34 12 8 11 24

Skin irritation . . . . . . . . . . . . . . . 147 50 32 44 69

Skin sensitization . . . . . . . . . . . 42 14 8 11 16

Eye irritation. . . . . . . . . . . . . . . . 153 52 36 49 85

Repeated dose toxicity. . . . . . . 52 18 10 14 24

Mutagenicity. . . . . . . . . . . . . . . . 82 28 16 22 28

Fish toxicity . . . . . . . . . . . . . . . . 43 15 5 7 16

Daphnia toxicity. . . . . . . . . . . . . 20 7 0 – 9

Biological accumulation

or biological degradation . . . 25 9 4 5 7

SOURCE: Office of Technology Assessment.

100 366 100

26 222 61

18 153 42

5 42 11

18 179 49

4 5 0 14

23 189 52

6 62 17

7 98 27

4 48 13

2 20 5

2 29 8
54 ● The Information Content of Premanufacture Notices

Figure 6.-Percentage of Polymer and Nonpolymer PMNs That Contained the Three Most Commonly

Reported-Toxicity-Tests and Tests Related to Chronic Toxicity and Ecotoxicity

All PMNs

Nonpolymer PMNs

Polymer PMNs

N = 740

‘ N = 366

N = 374

Acute

oral

toxicity

Eye

irritation

Skin

irritation

Mutage- Daphnia

nicity or fish

killing

SOURCE: Office of Technology Assessment.
7

Submission of Physical-Chemical

and Toxicity Information on

Some Subgroups of

Premanufacture Notices
7

Submission of Physical= Chemical and

Toxicity Information on Some

Subgroups of Premanufacture Notices

PMNs SUBMITTED FOR CONSUMER PRODUCTS

Risk assessment encompasses two elements:

1) estimates of hazard, a property that resides in

an object or substance or behavior; and 2) exposure that depends on estimates of the number of

people or organisms that may come in contact

with various amounts of the hazard for various

times through different media. The highest exposure, in terms of people likely to be exposed, are

associated with products intended for consumer

use. Therefore, knowledge of hazard is especially

important for these items.

Not only are there many consumers, but the

chances for misuse probably increase with the

number of users. Consumer-use items are purchased in retail outlets and may or may not be

used according to directions. Labels and instructions may be lost, washed off, ignored, or not

understood. A particularly striking example of

such an occurrence was the mistaken use of a lemon-scented dishwashing detergent to flavor tea

when samples of the product were mailed to consumers in 1982.

Table 15 presents the frequency with which

physical-chemical and toxicologic data were submitted for consumer-use premanufacture notices

(PMNs) and all other PMNs, and figure 7 shows

the frequency of submission of some toxicity data.

There were only small differences in the frequency of submission of physical-chemical data. Nine

of the eleven toxicologic data were more frequently reported on consumer products. The two exceptions are reporting of acute inhalation toxicity

and mutagenicity.

The overall more frequent submission of toxicity data fits with the idea that greater concern is

Table 15.—Completeness of PMNs Submitted for

Consumer-Use Products as Compared to Other PMNs

Consumer-use All other

PMNs PMNs

No. Percent No. Percent

Physical-chemical Information:

PMNs . . . . . . . . . . . . . . . . . . . . .. .105

Infrared spectra . . . . . . . . . . . . . . 18

Purity . . . . . . . . . . . . . . . . . . . . . . . 71

Analytical methods . . . . . . . . . . . 63

Melting point . . . . . . . . . . . . . . . . 23

Boiling point ... , . . . . . . . . . . . . . 25

Density. . . . . . . . . . . . . . . . . . . . . . 22

Vapor pressure . . . . . . . . . . . . . . . 27

Volubility water. . . . . . . . . . . . . . . 45

Partition coefficient. . . . . . . . . . . 4

Transportation . . . . . . . . . . . . . . . 79

Emergency information . . . . . . . . 31

100 635

17 68

68 472

60 351

22 156

24 194

21 118

26 153

42 263

4 23

75 403

30 224

Toxicology information:

Acute oral toxicity . . . . . . . . . . . . 50

Acute dermal toxicity . . . . . . . . . 39

Acute inhalation toxicity. . . . . . . 6

Skin irritation . . . . . . . . . . . . . . . . 39

Skin sensitization. . . . . . . . . . . . . 17

Eye irritation . . . . . . . . . . . . . . . . . 44

Repeated dose toxicity . . . . . . . . 20

Mutagenicity . . . . . . . . . . . . . . . . . 11

Fish toxicity . . . . . . . . . . . . . . . . . 14

Daphnia toxicity . . . . . . . . . . . . . . 10

Biological accumulation

or biological degradation . . . . 5

SOURCE: Office of Technology Assessment.

48 270

37 183

6 61

48 211

16 49

42 232

19 66

10 116

13 50

10 19

5 31

100

11

74

55

25

31

19

24

41

4

63

35

43

30

10

33

8

37

10

18

8

3

5

frequently attached to consumer-use products.

Because of the potentially great number of people exposed to these products, more information

about any hazard is desirable to make reasonable

decisions about risk. Despite the more frequent

reporting of toxicity information on the consumeruse PMNs, more than half of such PMNs reported

no toxicity data (see tables 18, 19, and 20).

57
58 ● The Information Content of Premanufacture Notices

70

60

50

Figure 7.-Percentage of PMNs That Described Consumer-Use or Nonconsumer-Use Products and

Contained the Three Most Commonly Reported Toxicity Tests and Tests Related to

Chronic Toxicity and Ecotoxicity

40

30

20

10

5

0

Consumer-use PMNs N = 105

Nonconsumer-use .,

PMNs

N = 635

Acute Eye Skin Mutage- Daphnia

oral irritation irritation nicity

toxicity

or fish

killing

SOURCE: Office of Technology Assessment.

PMNs SUBMITTED FOR POLYMERS

According to the Environmental Protection

Agency’s (EPA) proposed exemption of polymers

from PMN reporting requirements, polymers’

high molecular weights make them inactive in

most biological systems, and that property alone

is sufficient to reduce the need for information

about toxicity. OTA’s findings about the amounts

of information on polymer PMNs is presented in

tables 9 and 14. Consistent with the idea that polymers were less hazardous, toxicity data were less

frequently reported for those substances (table

14). The observation that physical-chemical data

items were reported about equally for both polymers and non-polymers reflects the usefulness or

necessity of such data in describing and identifying a chemical in the manufacturing plant.

EPA now receives fewer toxicity data about

polymers than other substances. The proposed

polymer exemption policy is expected to reduce

further the amount of toxicity data submitted

about those chemicals, but the tendency toward

less information is already established. An interesting question that could be addressed by examining polymer PMNs in detail is whether or not

toxicity information was more often submitted on

PMNs that describe substances to be excluded

from the exemption (see table 2).
Ch. 7—Submission of Physical-Chemical and Toxicity Information on Some Subgroups of Premanufacture Notices ● 59

PMNs SUBMITTED FOR SITE= LIMITED CHEMICALS

The number of people exposed to site-limited

intermediates is necessarily limited. EPA’s proposed exemption of these substances is based on

the idea that knowledge about the use of these

chemicals at their site of manufacture will be sufficient to make a decision between whether they

may or may not present an unreasonable risk. Although the number of people that might be exposed is limited to those at the production site,

exposure levels are potentially quite high. There

may be a special incentive for companies to test

site-limited intermediates because of concern

about high-exposure levels.

OTA used the information provided on the

PMNs to sort out the notices that described sitelimited chemicals (see table 16). The notices examined by OTA are not exactly comparable to the

group of chemicals proposed for exemption. EPA

proposes to exempt site-limited intermediates,

which are consumed or otherwise used only at the

site of manufacture. OTA examined a somewhat

larger universe, all those PMNs that described

site-limited chemicals. The distinction between the

two categories “site-limited intermediates” and

“site-limited chemicals” is not entirely clear, but

the first category is part of the second.

Table 16 shows a comparison of the amounts

of physical-chemical information and toxicity data

submitted for site-limited chemicals and all other

chemicals. Overall, physical-chemical information

was reported about equally on both groups of

PMNs, and toxicity information was reported

more frequently for site-limited chemicals. Over

half (52 percent) of the PMNs describing site-limited chemicals reported oral toxicity data; 42 percent of the others did.

The equal reporting of physical-chemical information is to be expected. In general, such information is necessary for the manufacturer regardless of whether or not the chemical is moved from

Table 16.—Physical-Chemical and Toxicity information

Submitted for Site-Limited Chemical PMNs

and All Other PMNs

Site- limited

chemical All other

PMNs PMNs

No. Percent No. Percent

Physical-chemical Information:

PMNs . . . . . . . . . . . . . . . . . .. ....115

Infrared spectra . . . . . . . . . . . . . . 17

Purity . . . . . . . . . . . . . . . . . . . . . . . 89

Analytical methods . . . . . . . . . . . 68

Melting point . . . . . . . . . . . . . . . . 31

Boiling point . . . . . . . . . . . . . . . . . 19

Density. . . . . . . . . . . . . . . . . . . . . . 14

Vapor pressure . . . . . . . . . . . . . . . 21

Volubility water. . . . . . . . . . . . . . . 51

Partition coefficient. . . . . . . . . . . 1

Transportation . . . . . . . . . . . . . . . 49

Emergency information . . . . . . . . 30

Toxicology Information:

Acute oral toxicity . . . . . . . . . . . . 60

Acute dermal toxicity . . . . . . . . . 46

Acute inhalation toxicity. . . . . . . 11

Skin irritation . . . . . . . . . . . . . . . . 50

Skin sensitization. . . . . . . . . . . . . 16

Eye irritation . . . . . . . . . . . . . . . . . 48

Repeated dose toxicity . . . . . . . . 14

Mutagenicity . . . . . . . . . . . . . . . . . 25

Fish toxicity . . . . . . . . . . . . . . . . . 12

Daphnia toxicity . . . . . . . . . . . . . . 2

Biological accumulation

or biological degradation . . . . 6

SOURCE: Off Ice of Technology Assessment.

100 625

15 69

77 454

59 346

27 148

17 200

12 126

18 159

44 259

<1 26

43 433

26 225

52 260

40 76

10 55

43 200

14 50

42 228

12 72

22 102

10 52

2 27

5 30

100

55

24

32

20

25

41

4

69

36

42

12

9

32

8

36

12

16

8

4

5

site to site. One item that is submitted less frequently on site-limited PMNs is information about

transportation, which is completely reasonable for

such chemicals.

As shown on table 16 and figure 8, toxicity information was reported more frequently for sitelimited chemicals than for all others. Since EPA

cannot require testing of new chemicals simply

because they are new, it can be assumed that the

development of toxicity information is done by

manufacturers for their own needs.
60 ● The Information Content of Premanufacture Notices

Figure 8.-Percentage of PMNs That Described Site= Limited or Other Chemicals and Contained the Three Most

Commonly-Reported Toxicity Tests and Tests Related to Chronic Toxicity and Ecotoxicity

Site-limited PMNs N = 115

Nonsite-limited PMNs N = 625

Acute Eye Skin Mutage- Daphnia

oral irritation irritation nicity

toxicity

or fish

killing

SOURCE: Office of Technology Assessment.

PMNs SUBMITTED FOR LOW-PRODUCTION-VOLUME CHEMICALS

The proposed low-volume exemptions argue

that limited production volumes reduce the amount

of information that EPA requires to make a judgment about any unreasonable risk that may be

associated with a new chemical. An important

caveat to any such generalization is that toxicity

varies over an extremely wide range, and a miniscule amount of a very potent toxic substance can

cause illness and death. However, most substances

are not extremely toxic, and, regardless of toxicity, reduced exposure limits risk.

In general, substances to be manufactured in

quantities less than 10,000 kg per year will be exempted from the usual PMN review unless they

may cause serious acute or chronic health effects

or significant environmental effects under conditions of use. The exemptions are discussed in ch.

2.

Some reviewers of the first draft of this report

commented that EPA had truncated the review

of some low-volume PMNs in the past. The shortened reviews were reported to have depended on

professional judgment that: 1) production volumes were limited, and 2) either potential toxicity

or exposure or both was low. Those reviewers

characterized the proposed low-volume exemptions as being an extreme position because they

depend so heavily on predicted production volumes.

For both low production volume exemptions,

EPA will inspect the notice to assure that the
Ch. 7—Submission of Physical-Chemical and Toxicity Information on Some Subgroups of Premanufacture Notices ● 61

chemical qualifies for exemption. No chemical

that receives a low-volume exemption will go on

the Inventory. Therefore, manufacture of those

substances by other companies will only be possible after submission of a PMN by the second

company.

When (or if) the production volume exceeds

10,000 kg per year, EPA intends to require that

the manufacturer submit a PMN for the substance. When PMN review is complete, the chemical will go on the Inventory. Part of the rationale

for the low-volume exemption is that manufacturers will be better able to bear the reporting costs

of the PMN review as production volume increases.

Table 17 reports and figure 9 abstracts some

of the information content of PMNs reviewed for

chemicals to be made in quantities of 1,000 kg or

less in the first year, those to be made in quantities of 1,000 to 10,000 kg in the first year and all

others. The frequency with which physical-chemical data are submitted fluctuates among the three

volume classes, but there appears to have been

more frequent reporting of toxicity information

for PMNs that describe low-volume chemicals.

The most striking differences in frequency of

reporting toxicity data are acute ingestion toxicity

and mutagenicity. Data from acute ingestion toxicity studies were reported on 59 percent of

chemicals slated for production in volumes less

than 1,000 kg; on 41 percent of those to be

manufactured in volumes between 1,001 and

10,000 kg; and on 37 percent of those to be made

in volumes greater than 10,000 kg. Mutagenicity

data were reported more often for the lower

volume chemicals; 31, 14, and 12 percent for the

less than 1,000, between 1,001 and 10,000, and

greater than 10,000 kg classes respectively.

Table 17.—Physical-Chemical and Toxicity Information Submitted on PMNs That

Project Initial Year Production Volumes of 1,000 Kilograms or less, of

Between 1,001 and 10,000 Kilograms, and All Others

Initial year production volume

<1,000 kg 1,001-10,000 kg >10,000 kg

No. Percent No. Percent No. Percent

Physical-chemical Information:

PMNs . . . . . . . . . . . . . . . . . . . . .. ....162

Infrared spectra . . . . . . . . . . . . . . . . . 14

Purity . . . . . . . . . . . . . . . . . . . . .. ....118

Analytical methods . . . . . . . . . . . . . . 73

Melting point . . . . . . . . . . . . . . . . . . . 61

Boiling point . . . . . . . . . . . . . . . . . . . . 38

Density. . . . . . . . . . . . . . . . . . . . . . . . . 19

Vapor pressure . . . . . . . . . . . . . . . . . . 36

Volubility water . . . . . . . . . . . . . . . . . 73

Partition coefficient. . . . . . . . . . . . . . 4

Transportation . . . . . . . . . . . . . . . . . . 84

Emergency information . . . . . . . . . . . 47

Toxicology information:

Acute oral toxicity . . . . . . . . . . . . . . . 98

Acute dermal toxicity . . . . . . . . . . . . 51

Acute inhalation toxicity. ... , . . . . . 11

Skin irritation ... , . . . . . . . . . . . . . . . 74

Skin sensitization. . . . . . . . . . . . . . . . 25

Eye irritation . . . . . . . . . . . . . . . . . . . . 76

Repeated dose toxicity . . . . . . . . . . . 29

Mutagenicity . . . . . . . . . . . . . . . . . . . . 51

Fish toxicity . . . . . . . . . . . . . . . . . . . . 19

Daphnia toxicity . . . . . . . . . . . . . . . . . 10

Biological accumulation

or biological degradation . . . . . . . 9

100

8

73

45

38

23

12

22

45

2

52

29

59

31

7

47

15

47

18

31

12

6

5

153

19

117

87

34

39

20

22

63

4

99

60

64

44

17

53

12

66

14

22

13

6

100 420

12 53

76 305

57 254

22 83

25 141

13 98

14 122

41 169

3 19

65 297

39 148

41 154

29 124

11 38

35 118

8 29

43 136

9 41

14 52

8 32

4 13

6 4 21

100

13

73

60

20

34

23

29

40

4

71

35

37

30

9

28

7

32

10

12

8

3

5

SOURCE: Office of Technology Assessment.
62 ● The Information Content of Premanufacture Notices

..

Figure 9.—Percentage of PMNs That Described Low- or High-Production-Volume Chemicals and Contained

the Three Most Commonly Reported Toxicity Tests and Tests Related to Chronic Toxicity and Ecotoxicity

70

60

50

40

30

20

10

5

0

—

—

Acute

oral

toxicity

SOURCE: Office of Technology Assessment.

Eye

irritation

Skin

irritation

Initial annual

production

<1,000 kg N = 162

>10,000 kg N = 420

Mutage- Daphnia

nicity or fish

killing

COMPARISON OF TOXICITY DATA SUBMITTED ON CONSUMER

AND NONCONSUMER SUBSTANCES, BOTH POLYMERS AND

NONPOLYMERS, SCHEDULED FOR PRODUCTION IN

DIFFERENT AMOUNTS

The finding that PMNs that described low-volume chemicals reported toxicity data more frequently might reflect a reluctance on the part of

manufacturers to test high-volume chemicals or

to report results. Given that the risk estimate for

high-volume chemicals is already elevated because

of high potential exposure, manufacturers might

think that any hint of toxicity may cause EPA to

require even more testing to allay fears. Furthermore a company that submits a PMN expects to

manufacture the chemical, and it is not interested

in expending more time and energy on additional

tests. Therefore there might be few incentives for

a company to test or to report test results on highvolume chemicals.

Alternatively, OTA considered that fewer toxicity data are reported for high-volume chemicals

because manufacturers have had a great deal of

experience with closely related substances and are

satisfied that the new chemicals are not hazardous. An obvious class of such chemicals is polymers.

The data presented in table 18 show the frequency of submission of toxicity data for polymers and nonpolymers at different projected pro-
. .

Ch. 7—Submission of Physical-Chemical and Toxicity Information on Some Subgroups of Premanufacture Notices ● 6 3

Table 18.—Number of Submissions of Toxicity Data on Polymers and Nonpolymers

To Be Produced in Different Amounts

<1,000 kg 1,001-10,000 kg >10,000 kg

Polymer Non polymer Polymer Non polymer Polymer Non polymer

No. Percent No. Percent No. Percent No. Percent No. Percent No. Percent

PMNs . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 100 127 100 56 100 100 100 291 100 143 100

Acute oral toxicity . . . . . . . . . . . . . . . . 16 43 80 63 14 25 50 50 65 22 89 62

Acute dermal toxicity . . . . . . . . . . . . . 6 16 45 35 14 36 36 53 18 71 50

Acute inhalation toxicity. . . . . . . . . . . 1 2 10 8 17 6 21 15

Skin irritation . . . . . . . . . . . . . . . . . . . . 11 30 63 50 16 29 37 37 42 14 76 53

Skin sensitization. . . . . . . . . . . . . . . . . 1 1 24 19 6 11 6 6 9 3 20 14

Eye irritation . . . . . . . . . . . . . . . . . . . . . 13 35 63 50 18 32 43 43 54 19 82 57

Repeated dose toxicity . . . . . . . . . . . . 4 11 25 20 4 7 10 10 15 5 26 18

Mutagenicity. . . . . . . . . . . . . . . . . . . . . 8 22 43 34 2 21 21 19 7 33 23

Fish toxicity . . . . . . . . . . . . . . . . . . . . . 4 11 15 12 10 3 22 15

Daphnia toxicity . . . . . . . . . . . . . . . . . . 2 5 8 6 1 2 5 5 6 2 7 5

Biological accumulation or

biological degradation . . . . . . . . . . 0 — 9 7 0 – 6 6 7 2 14 10

SOURCE: Office of Technology Assessment.

duction volumes. As can be seen, fewer data were icity data was more frequent than for PMNs as

submitted on polymers at all production volumes. a whole (compare table 12 with tables 19 and 20).

For nonpolymers, toxicity data submission was The frequency of submission of toxicity data for

more frequent on the PMNs that predicted higher nonpolymers was generally higher for substances

production volumes. intended for consumer use (tables 19 and 20).

The data relating polymers and production volumes were further broken down to examine sub- Another observation to be made from table 19

mission of toxicity data on consumer products is that over half (56 percent) of consumer-use

(tables 19 and 20). Toxicity data were more fre- PMNs described chemicals to be made in volumes

quently submitted on nonpolymers whether they greater than 10,000 kg annually. Therefore, less

described consumer- or nonconsumer-use chemi- than half (44 percent) of consumer-use chemicals,

cals. For nonpolymers to be made in greater than which are of special concern because of their ex10,000 kg volumes annually, the reporting of tox- posure characteristics, were slated for production

Table 19.-Number of Submissions of Toxicity Data on PMNs Describing Consumer-Use Chemicals and

Polymers and Nonpolymers To Be Produced in Different Amounts

>10,000 kg

<1,000 kg 1,001-10,000 kg Polymer Nonpolymer

No. polymer No. nonpolymer No. polymer No. nonpolymer No. Percent No. Percent

PMNs . . . . . . . . . . . . . . . . . . . . . 2 19 10 15 35 100 23 100

Acute oral toxicity . . . . . . . . . . 1 11 2 7 12 34 16 70

Acute dermal toxicity. . . . . . . . 7 1 6 12 34 12 52

Acute inhalation toxicity . . . . . 0 0 2 6 13

Skin irritation . . . . . . . . . . . . . . . 1 9 2 7

Skin sensitization . . . . . . . . . . . 0 6 1 3 3 9

Eye irritation . . . . . . . . . . . . . . . 7 2 6

Repeated dose toxicity . . . . . . 4 12 8 35

Mutagenicity . . . . . . . . . . . . . . . 0 4 12 4

Fish toxicity. . . . . . . . . . . . . . . . 1 2 1 1

Daphnia toxicity . . . . . . . . . . . . 1 2 0 1 3 9 3 13

Biological accumulation or

biological degradation . . . . . 0 0 0 1 1 3 3 13

SOURCE: Office of Technology Assessment.
64 ● The Information Content of Premanufacture Notices

Table 20.—Number of Submissions of Toxicity Data on PMNs Describing Nonconsumer-Use

Chemicals and Polymers and Nonpolymers To Be Produced in Different Amounts

<1,000 kg 1,001-10,000 kg >10,000 kg

Polymer Non polymer Polymer Non polymer Polymer Nonpolymer

No. Percent No. Percent No. Percent No. Percent No. Percent No, Percent

PMNs . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 100 108 100 46 100 85 100 256 100 120 100

Acute oral toxicity . . . . . . . . . . . . . . . . 15 43 70 65

Acute dermal toxicity . . . . . . . . . . . . . 5 14 38 35

Acute inhalation toxicity. . . . . . . . . . . 1 3 10 9

Skin irritation . . . . . . . . . . . . . . . . . . . . 10 29 55 51

Skin sensitization. . . . . . . . . . . . . . . . . 1 3 18 17

Eye irritation . . . . . . . . . . . . . . . . . . . . . 12 34 57 53

Repeated dose toxicity . . . . . . . . . . . . 4 11 20 18

Mutagenicity . . . . . . . . . . . . . . . . . . . . . 8 23 41 38

Fish toxicity . . . . . . . . . . . . . . . . . . . . . 3 9 13 9

Daphnia toxicity . . . . . . . . . . . . . . . . . . 1 3 6 6

Biological accumulation or

biological degradation . . . . . . . . . . 0 — 9 8

12 26 43 51

7 15 30 35

6 13 10 12

14 30 31 36

5

16

3 6 9 11

1 2 21 25

1 2 10 12

1 2 4 5

0 – 5 6

53 21 62

41 16

15 6 19 11

35 14 64 53

6 2 16 13

41 16 68 57

11 4 18 5

15 6 29 24

7 3 16 13

3 1 4 3

6 2 11 9

SOURCE: Office of Technology Assessment.

in volumes equal to or less than those proposed

for exemption by EPA.

The skewing of production volumes toward

higher values is most noticeable for polymers

being produced for nonconsumer uses (table 20).

Seventy-six percent of all nonconsumer-use polymers are slated for production in volumes greater

than 10,000 kg annually.

with increasing projected production volumes. An

easy-to-hand suggestion to explain that tendency

is that large production volume non-consumeruse substances are often “me too” chemicals. Manufacturers might be well acquainted with the properties of closely related substances and satisfied

with estimates of toxicity based on them. Apparently EPA is also satisfied with those estimates.

The frequency of submission of toxicity data

for nonconsumer-use polymers tends to decrease

MAGNITUDE OF SCALE-UP IN PRODUCTION

OF LOW-VOLUME CHEMICALS

Because of concerns about confidential business

information, OTA did not collect precise estimates

of first- and third-year production volumes. Instead, first year production was collected as:

1.1,000 kg or less,

2.1,001 kg to 10,000 kg, and

3. greater than 10,000 kg.

Third year production volume was recorded as

a multiple of the first year volume:

1. Less than a fivefold increase,

2. fivefold to tenfold increase,

3. twentyfold to fiftyfold increase,

4. fiftyfold to hundredfold increase,

5. hundredfold to two hundredfold increase,

and

6. greater than two hundredfold increase.

Table 21 shows the expected scale-up of production of chemicals from each of the initial year production volumes. Also shown are estimates of the

kilograms of each chemical to be expected in the

third year. These estimates are necessarily imprecise because exact production volumes were not

recorded. Instead, as is shown on the table, an

initial year production volume of 500 kg was assumed for the less than 1,000 kg class, 5,000 for

the 1,001 to 10,000 kg class, and 10,001 (rounded

down to 10,000) for the greater than 10,000 kg
.

Ch. 7—Submission of Physical-Chemical and Toxicity Information on Some Subgroups of Premanufacture Notices ● 65

1,001 kg to 10,000 kg

>10,000 kg

Table 21.—Estimated First Year Production Volumes, and

Increases Expected in the Third Year

Estimated a Estimated

Initial year first year third year

production Increase in product ion product ion

volume third year (kg) (kg)

<1,000 kg < 5-foldb

101 500-2,500

5- to lo-fold 23 500 2,500-5,000

10- to 20-fold 11 500 5,000-10,000

20- to 50-fold 10,000-25,000

50- to 100-fold 500 —

100- to 200-fold 4 5O,OOO-1OO,OOO

> 200-fold 11 500 >100,000

135

<5-fold 81 5,000 5,000-25,000

5- to 10-fold 41 5,000 25,000-50,000

10- to 20-fold 11 5,000 50,000-100,000

20- to 50-fold 9 5,000 100,000-250,000

50- to 100-fold 6 5,000 250,000-500,000

100- to 200-fold 2 5,000 500,000-1,000,000

> 200-fold o 5,000 —

150

c 5-fold 193 10,000 10,000-50,000

5- to 10-fold 50 10,000 50,000-100,000

10- to 20-fold 11 10,000 100,000-200,000

20- to 50-fold 3 10,000 200,000-500,000

50- to 100-fold 1 10,000 500,000-1,000,000

100- to 200-fold 7 10,000 1,000,000-2,000,000

> 200-fold o 10,000 —

265

a

See text.

b

For brevity the increases are written as 5- to 10-fold, 10- to 20-fold, etc. In practice, 5-to 10-fold means equal to or greater

than 5 and less than 10, 10- to 20-fold means equal to or greater than 10 and less than 20, etc.

SOURCE: Office of Technology Assessment.

class. The assumption of 500 for the first class and

5,000 for the second class may be either high or

low; the assumption of 10,000 for the third must

be low.

In all three classes, production of more than half

of all the chemicals increases less than fivefold.

At the other end of the production increase scale,

15 of the 155 less than 1,000 kg initial year production volume chemicals are expected to increase

by at least 50 times in the third year. The comparable fraction for the 1,001 to 10,000 kg class

is 8/150; for the more than 10,000 kg, 8/265.

EPA expects to require PMN review for lowvolume chemicals when their production increases

to at least 10,000 kg per year. It is impossible to

predict, from OTA’s collected data, what number

of PMNs report chemicals that will increase to

10,000 kg production volumes in the third year.

However, if all chemicals in the less than 1,000

kg per year class that increase by 20-fold or more

have an initial production of at least 500 kg, then

20 of the 155 chemicals of that class will require

PMN review in the third production year. For the

1,001 to 10,000 kg class, if all the chemicals that

increase in production at least fivefold have first

year production volumes of at least 5,000 kg, 69

of the I50 will require PMN review in the third

year. These estimates suggest that many chemicals

exempted from PMN review because of low production volume when they are first introduced

will be subject to review in their third year of

production.
———— ——

66 . The Information Content of Premanufacture Notices

ARE PMNs SUBMITTED FOR IMPORTED CHEMICALS MORE

COMPLETE THAN THOSE SUBMITTED FOR OTHER CHEMICALS?

The European Economic Community (EEC) has

adopted a base set of tests that are required before

a new substance can be marketed in member

countries. It is not an overstatement to contrast

the EEC and the Toxic Substances Control Act

(TSCA) requirements by saying that EEC demands that several kinds of test data be submitted

unless an exemption is granted; TSCA does not

authorize EPA to require generation of test data

unless EPA lacks information to make a determination about some unreasonable risk that the substance may present.

No impact of the EEC requirements would be

expected on the PMNs examined by OTA because

they were not in effect in 1979 and 1980. Nevertheless, the PMNs that described imports were examined separately. A comparison of import

PMNs to all other PMNs is shown in table 22.

The frequency with which chemical identification

data were submitted was essentially 100 percent

for both domestic and imported PMNs, but imports less frequently reported byproducts, numbers of workers, and disposal (data not shown).

Those smaller numbers may largely be explained

because byproducts, workers, and disposal methods in foreign countries are not a concern for the

United States EPA.

As is shown on table 22, neither physical-chemical nor toxicity data were consistently reported

more frequently on the import PMNs. Seven of

Table 22.—Physical-Chemical and Toxicity

Information Submitted for Import PMNs

and All Other PMNs

All other

Imports PMNs

No. Percent No. Percent

- Physical-chemical Information:

PMNs ., . . . . . . . . . . . . . . . . . . . . 63

Infrared spectra . . . . . . . . . . . . . . 4

Purity. . . . . . . . . . . . . . . . . . . . . . . 45

Analytical methods . . . . . . . . . . . 46

Melting point . . . . . . . . . . . . . . . . 24

Boiling point . . . . . . . . . . . . . . . . 12

Density . . . . . . . . . . . . . . . . . . . . . 10

Vapor pressure . . . . . . . . . . . . . . 9

Volubility (water) . . . . . . . . . . . . . 30

Partition coefficient . . . . . . . . . . 2

Transportation . . . . . . . . . . . . . . . 53

Emergency information . . . . . . . 21

Toxicology information:

Acute oral toxicity . . . . . . . . . . . 35

Acute dermal toxicity . . . . . . . . . 12

Acute inhalation toxicity . . . . . . 2

Skin irritation . . . . . . . . . . . . . . . . 23

Skin sensitization . . . . . . . . . . . . 3

Eye irritation . . . . . . . . . . . . . . . . 22

Repeated dose toxicity . . . . . . . 4

Mutagenicity . . . . . . . . . . . . . . . . 15

Fish toxicity . . . . . . . . . . . . . . . . . 13

Daphnia toxicity . . . . . . . . . . . . . 1

Biological accumulation

or biological degradation . . . . 9

100

6

71

73

38

19

16

14

48

3

84

33

55

19

5

35

6

24

21

2

14

677

82

498

368

155

207

130

171

278

25

429

234

285

210

65

227

63

254

82

112

51

28

27

100

12

74

54

23

31

19

25

41

35

42

31

10

34

9

38

12

17

8

4

4

SOURCE: Office of Technology Assessment.

the eleven physical-chemical items were more frequently present on domestic PMNs; 6 of the 11

toxicity items.
8

Actions Taken by the

Environmental Protection Agency

as a Result of Reviewing

Premanufacture Notices
8.

Actions Taken by the Environmental

Protection Agency as a Result of

Reviewing Premanufacture Notices

The heart of any questioning about the Premanufacture Notice (PMN) program is whether it has

protected human health and the environment

from unreasonable risks. A partial answer to that

question will become available in the years to

come as information is accumulated about the

health and environmental effects of substances

that passed through PMN review and then entered

commerce. In the meantime, a less satisfactory

answer to questions about the accomplishments

of the PMN program can be obtained by examining actions that the Environmental Protection

Agency (EPA) has taken to reduce exposures to

chemicals that may present unreasonable risks.

From among the PMNs examined by OTA,

nine described chemicals that did not begin

manufacture because of formal EPA actions. Six

of those described phthalates, which at the time

of review were especially suspect because of a

then-recently completed National Cancer Institute

test that showed some phthalates to be carcinogenic (9). Two of the remaining three were

benzidine dyes, which have long been associated

with human carcinogenicity. The fact that the

benzidine dyes were submitted shows that some

chemicals strongly associated with human toxicity

are considered for manufacture.

EPA’s insisting on more tests for those nine

chemicals prevented their being manufactured. In

those cases, when EPA issued a 5(e) order, the

submitter decided not to submit the requested information and withdrew the PMN. The reasoning behind the submitters’ decisions is not known

and may differ depending on the chemical and the

submitter. However, when EPA determined that

the new chemical might present an unreasonable

risk, the submitting company may have agreed

that the chemical was more likely than not to harbor some hazard, and that further testing might

confirm the hazard.

If a submitting company decided to execute the

EPA-requested tests, the tests might confirm that

the chemical is hazardous. In that case, the submitter cannot manufacture the chemical and is out

the money spent on developing test data. If the

test data are equivocal and neither confirm the

hazard nor dispel it, the submitter is also out the

cost of the test. He also faces another decision

about whether or not to produce more data at

more cost in the expectation that more data will

resolve EPA’s concern about the chemical. The

third possible outcome is that the EPA-requested

test data show that the chemical is not hazardous

and that production of the chemical can commence. In that case, for the cost of the test, the

submitter gains access to the market for those

chemicals.

Industry reviewers of the first draft of this

background paper expressed their conviction that

the cost of the required tests alone, with no consideration of the possible outcomes, was sufficient

to convince the submitting companies to withdraw the PMNs. Instead of spending the money

on the tests, it might be better spent on developing other chemicals.

Such activities are to be expected as a result of

TSCA and implementation of its provisions to

regulate new chemicals. The law provides that

chemicals that are suspected of being toxic are to

be identified before manufacture and prevented

from being manufactured unless sufficient data

are produced to show that the toxicity does not

present an unreasonable risk.

Three additional 5(e) orders have been written

(two in 1982; one in 1983). The two in 1982 were

“consent 5(e)’s, ” which represented an agreement

69
70 • The Information Content of Premanufacture Notices

between the submitter and EPA that manufacture

of the substances would be restricted and that the

company would not challenge the order in court.

In addition to the 5(e) orders, EPA had achieved

54 “voluntary regulatory” actions through the first

three quarters of 1982. In those cases, EPA requested that a submitter develop additional information or impose voluntary controls. Table

23 is from an EPA memo dated July 30, 1982 (6).

It shows results that EPA has obtained through

its “informal regulatory actions” from the beginning of the program through June 1982.

The memo (6) briefly describes each of the informal actions. Examples of each type of action

are discussed here:

●

●

Voluntary Testing (12 cases). -In one case,

EPA was concerned about the mutagenicity

of the chemical. The submitter performed a

bacterial mutagenicity test (see table 11 and

accompanying text for discussion, also (9))

and the results were positive. The company

complied with a request to affix warning

labels to containers of the chemical to alert

workers to a possible health hazard.

Voluntary Controls (26 cases) .-Most of the

actions involved developing an appropriate

warning label. For example, a PMN described a chemical for use by home hobbyists. EPA notified the submitter of its concerns about possible dermal absorption. The

submitter labeled the chemical bottles with

directions that rubber gloves be worn. In addition to such voluntary labeling actions,

some companies have agreed to reduce exposures during manufacture and, in one case,

●

●

●

not to manufacture a particular group of

chemicals.

Major Pending Negotiations Under Suspended Review Notice (13 cases).—In these

cases, EPA has negotiated with the submitter to produce additional toxicity information. The review period was suspended because the execution and analysis of tests

would extend beyond the 90-day review period. Upon completion of the tests and their

submission to EPA, the review “clock” can

be restarted from where it was stopped.

Withdrawal of PMN in Face of Likely 5(e)

Order (2 cases).— In one case, EPA decided

to write a 5(e) order because of large production volume and substantial potential exposure and release. The company, when notified of EPA’s intention to write a 5(e) order

to require testing, withdrew the PMN.

Withdrawl of PMN in Face of Likely 5(f)

Order (1 case). —A 5(f) order can be written

when EPA decides that a substance presents

or will present an unreasonable risk to health

or the environment. When the submitting

company learned that EPA was preparing to

regulate the substance under section 5(f), it

withdrew the PMN “stating that it did not

wish to be the target of EPA’s first TSCA section 5(f) order” (6).

These voluntary regulatory efforts have generated additional information, controlled exposures, and caused the withdrawal of PMNs that

described chemicals that caused EPA concern.

During the time the 54 voluntary actions occurred, EPA received a total of 1,499 PMNs. In

other words, voluntary regulatory actions accompanied about 3.6 percent of those PMN reviews.

Table 23.-EPA Summary of Informal Regulatory Actions in Fiscal Years 1979, 1980, 1981,

and First Three Quarters of Fiscal Year 1982

Fiscal year Fiscal year Fiscal year Fiscal year

1979 1980 1981 1982 Total

Informal action—voluntary testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 1 8 3 12

Informal action—voluntary controls . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 1 12 13 26

Major pending negotiations under suspended review period . . . . . . . 0 0 0 13 13

PMNs withdrawn in face of likely 5(e) order , . . . . . . . . . . . . . . . . . . . . o 1 1 0 2

PMNs withdrawn in face of likely 5(f) order. . . . . . . . . . . . . . . . . . . . . . 0 0 0

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3 21

SOURCE: Environmental Protection Agency (1982).
Ch. 8—Actions Taken by the Environmental Protection Agency as a Result of Reviewing Premanufacture Notices • 71

In summary, EPA has taken action on 66 PMNs

(12 formal 5(e) orders and 54 voluntary compliance). Whether that is an appropriate number

depends on the opinion of the observer. If the

observer considers most chemicals to be without

hazard, taking action on about 4.4 percent of all

PMNs may seem too high or just about right. On

the other hand, that percentage of actions may

seem too low to an observer who considers that

a larger fraction of chemicals are hazardous. Thus,

the implication of the percentage is a matter of

interpretation.

This paper focuses on the frequency with which

PMNs report various kinds of data to EPA. It

points to groups of PMNs for which EPA received

more or less information, but it has not delved

into how EPA used the submitted information and

other information in making decisions not to take

any action, in which case manufacture went ahead

unimpeded, or to take action to restrict manufacture or limit exposure. The last chapter of this

paper (ch. 9) outlines a possible method to investigate EPA’s decisionmaking process and its use

of the information submitted on PMNs.
—

9 m

Discussion
9

Discussion

FREQUENCY OF REPORTING OF INFORMATION ON

PREMANUFACTURE NOTICES

OTA inspected 740 premanufacture notice

(PMN) files to determine what items of information have been submitted to the Environmental

Protection Agency (EPA). The presence or absence of three kinds of information was recorded:

1. information specified by the Toxic Substances Control Act (TSCA) (seven items),

2. information that describes the physicalchemical properties of the chemical (11

items),

3. information about the toxicity of the chemical (11 items),

The results presented in this background paper

place limits on possible answers to questions about

how much information EPA has received on

PMNs. The reporting of TSCA-specified items is

high. Six of the seven specified items—chemical

identity, chemical class, production volumes, uses

for the chemical, numbers of workers likely to be

exposed in their places of employment, and disposal methods—were reported on more than 90

percent of all PMNs. The seventh specified item,

information about byproducts generated in the

manufacture of the chemical, was reported on

about two-thirds of all PMNs (table 3). Ninetysix percent of all PMNs reported at least one item

of non-TSCA specified physical-chemical information (table 7). Fifty-three percent reported at

least one toxicity test result (table 12). The other

side of the last observation is that 47 percent of

all PMNs, almost half, reported no toxicity data.

DATA SUBMITTED ON PMNs

CHEMICALS INTENDED FOR

The reporting of both physical-chemical and

toxicity data was more frequent on PMNs that

described chemicals that are known to be present

in commerce as compared to chemicals that, so

far as is known, have not actually entered commerce (tables 7 and 12). Those findings are important because exposure is certainly greater to

manufactured chemicals. Nevertheless, 41 percent

of PMNs that described manufactured chemicals

reported no toxicity data.

About 10 percent (70 of 740) of the PMNs examined here were submitted in June 1982. The frequency of reporting of toxicity data on those

PMNs was lower than the frequency on all PMNs,

both those that described manufactured and notyet-manufactured chemicals, received during the

1979 through June 1981 period. In contrast, 4 of

the 11 physical-chemical items examined by OTA

were reported most frequently on June 1982

PMNs.

The lower frequency of toxicity test reporting

in June 1982 might be considered an aberration

and not reflective of a downward trend. Alternatively, it might be taken as a harbinger of decreased toxicity testing. A decision can be made

between these two points of view by examining

PMNs received during other months. EPA’s establishing a program to monitor and report the information content of PMNs on an ongoing basis

might be the best way of tracking the frequency

of reporting of specific information on PMNs.

THAT DESCRIBED

CONSUMER USE

Consumer-use chemicals are of special interest by OTA, 105 (14 percent) were designated by the

because of their use by many people, which results submitting companies as being intended for conin widespread exposure. Of the PMNs examined sumer use.

75
76 ● The Information Content of Premanufacture Notices

OTA’s examination of consumer-use PMNs

concentrated on the frequency of reporting of toxicity data. Fifty-seven of the consumer-use PMNs

described nonpolymers, and 47 described polymers (table 19). Reporting of toxicity data on both

consumer use polymers and nonpolymers was

more frequent than for the corresponding nonconsumer-use chemicals (compare tables 19 and

20).

Acute oral toxicity was reported on 70 percent

of the PMNs that described consumer use, nonpolymer chemicals to be made in excess of 10,000

kg annually (table 19). That frequency is the highest reporting frequency of any type of toxicity information for any subgroup of PMNs examined

here. It suggests that these substances were singled out for special concern, perhaps because of

the high-exposure potential. Despite the high frequency of reporting of acute oral toxicity, mutagenicity data were reported on only 17 percent

of the high-volume, nonpolymer, consumer-use

chemicals. That frequency is the same as that

found for all PMNs taken together (table 12), and

it highlights the low frequency of reporting data

about chronic health effects.

DATA SUBMITTED ON PMNs THAT DESCRIBED CHEMICALS

PROPOSED FOR EXEMPTION FROM PMN REVIEW

EPA has proposed exempting some categories

of chemicals from PMN reporting: 1) some polymers, 2) site-limited intermediates, and 3) chemicals to be manufactured in low volumes. Not all

polymers, site-limited intermediates, or low-volume substances would qualify for exemption (see

ch. 2), but many would. OTA examined separately PMNs that had been identified by submitters

as polymers, site-limited chemicals, and low-volume chemicals.

The polymer exemption is premised on the idea

that those substances, in general, are less likely

than other chemicals to be toxic. Consistent with

that idea, PMN submitters reported and evidently

developed fewer toxicity data for polymers than

for other classes of chemicals (tables 14, 18, 19,

and 20).

The proposed exemptions for site-limited intermediates and low production volume substances

are based on the idea that limited exposures associated with those substances reduce risk. Therefore, EPA proposes that it needs less information

to make a decision about those substances.

OTA’s examination of PMNs shows that toxicity information was more commonly submitted

for site-limited chemicals than for all other

chemicals (table 16 and fig. 8). Although the

number of people who might be exposed to those

chemicals is limited, levels of exposure conceivably are quite high. Since EPA does not require the generation of test data, the submitting

companies apparently develop such information

for their own use. Whether or not toxicity data

would be developed for these substances with the

same frequency if the exemption becomes final is,

of course, unknown. Of course, the data would

no longer be submitted to EPA.

PMNs describing chemicals to be made in volumes of less than 1,000 kg per year reported toxicity data more frequently than did PMNs describing other chemicals (table 17 and fig. 9). More

detailed analysis showed that polymer PMNs

tended to project greater production volumes

(tables 18-20), and the reduced reporting of toxicity data for polymers at least partially accounted

for the more frequent reporting of toxicity data

on low-volume PMNs. Data about expected increases in production volume suggest that about

a one-third of the low-volume exemption substances will require a PMN review by their third

year of production due to their exceeding the

10,000 kg annual production mark (table 21).

The proposed polymer exemption, to some extent, acknowledges the present situation. Apparently because those substances are thought to

be less hazardous, fewer toxicity data are submitted about them.
Ch. 9—Discussion . 77

The site-limited intermediate and low-volume

exemptions are more complex. Toxicity data are

more frequently submitted on PMNs that describe

those chemicals. Whether those data would be

developed for the company’s own use with the

same frequency under an exemption policy is

unknown, although it appears likely. Additionally, more knowledge of the exact content of the

PMNs is necessary to know if the submitter-identified site-limited and low-volume chemicals

would qualify for the proposed exemptions.

In the absence of a substantial amount of additional information, OTA can come to no definite conclusions about either the proposed exemptions or the overall adequacy of EPA’s PMN

program. The results reported here do, however,

provide information about the number of data received by EPA.

If the reader generally believes that most chemicals chosen by companies for manufacture are

not hazardous under company-specified conditions of use and with appropriate safeguards,

then, certainly, the proposed exemptions will be

seen as desirable and efficient. If the reader does

not share that general viewpoint, then a critical

question can be asked about whether the companies will generate toxicity information under

the proposed exemptions, and a decrease in data

would be seen as harmful.

USEFULNESS OF SUBMITTED INFORMATION FOR EPA’s

RISK ASSESSMENT PROCESS

EPA’s list of items to be considered in evaluating a chemical’s risk (see app. A) shows that

every item of physical-chemical and toxicity information considered in this report can be of use

in reviewing PMNs. However, not every item is

necessarily required for the review of every PMN.

The critical question is whether the information

received for EPA review was sufficient, and the

analysis necessary to answer that question goes

beyond this OTA examination.

A related question stems from the absence of

toxicity data and EPA’s use of Structural Activity

Relationship (SAR) analysis (see ch. 2). Regulatory actions to remove pesticides from the market

have made it clear that tests on the exact product,

not closely related chemicals, are necessary to ban

or restrict production. Therefore, there seems to

be little dependence on SAR in those decisions.

Pesticides are, by nature, active in some biological

systems, and greater care is necessary for their use

than for chemicals in general. So, on the one side,

SAR is not sufficient to regulate closely related

chemicals of classes known to be biologically

active.

SAR is used to estimate the physical-chemical,

and toxic properties of substances when PMNs

contain no data. Few chemicals are toxic under

normal conditions of use and the presumption can

be made that most new chemicals present no or

minimal hazard. Therefore, the use of SAR, which

depends on using information about related chemicals to estimate the hazard of the new chemical,

may be more appropriate for new chemicals.

At the same time, it must be recognized that

SAR is in its infancy. Its current level of use in

the PMN program may be correct, too high, or

too low. In any case, careful attention to its use,

its successes and failures, is necessary to define

situations where its use is or is not appropriate.

Industry reviewers of the first draft of this

background paper stated that physical-chemical

and toxicity data are obtained to enable the submitting company to process and manage the new

chemical. Those data, collected by the company

and submitted to EPA, are seen by industry as

sufficient for EPA review of PMNs. It is not entirely clear that all such data are reported. For instance, only 38 percent of Class 1 substances

(chemicals that can be represented by a chemical

formula or structure) reported melting points; 24

percent reported boiling points (tables 6 and 9).

One or the other or both of these measurements

might be expected on every Class 1 chemical.

Information collected by EPA suggest that factors other than a company’s need for information
78 ● The Information Content of Premanufacture Notices

may influence the reporting of data on PMNs. In

particular, an EPA analysis (2) showed a clear

correlation between submission of more data and

larger company size, regardless of whether the

company was or was not primarily a chemical

manufacturer. In 1981, EPA estimated that running tests, collecting, and submitting the physicalchemical and toxicity data of the types that OTA

looked for would cost between $53,000 and

$67,850 (table 24) per chemical. (Earlier, EPA had

estimated that the costs of submitting a PMN,

which included collecting and organizing existing

data but not the costs of testing, would be in the

range of $1,555 to $15,325 (44 F.R. 59767, Oct.

16, 1979).)

Two tests of particular value are partition coefficient tests that measure the relative affinities of

a chemical for aqueous and organic environments

and mutagenicity tests that measure interactions

with DNA. These are not often reported on PMNs

(5 and 17 percent respectively, tables 9 and 12),

and they are not a major part of the costs associated with the full set of tests shown in table 24.

All of the physical chemical tests, including determination of the partition coefficient, are estimated

to cost $3,800, and mutagenicity tests are

estimated to cost $1,350 for the simple bacterial

tests (table 24).

In general, industry reviewers of the first draft

of this background paper were approving of the

PMN program. They see it as doing an adequate

job of protecting health and the environment, and

Table 24.—Estimated Costs of Tests

That Might Be Reported on PMNs

Type of data Estimated cost

Physical/chsmical data:

Data about 11 characteristics. . . . . . . . . . . . $3,600

Acute toxicity data:

Acute oral toxicity . . . . . . . . . . . . . . . . . . . . . 2,000

Acute dermal toxicity. . . . . . . . . . . . . . . . . . . 2,800

Acute inhalation toxicity . . . . . . . . . . . . . . . . 3,300

Skin irritation. . . . . . . . . . . . . . . . . . . . . . . . . . 700

Skin sensitization . . . . . . . . . . . . . . . . . . . . . . 3,200-6,700

Eye irritation (for chemicals showing

no skin irritation , . . . . . . . . . . . . . . . . . . . . 450

Repeated dose toxicity data:

14- to 28-day-repeated dose test(s) using

probable route(s) of human exposure . . . 10,200-12,800

Mutagenicity data:

Gene (point) mutation data. . . . . . . . . . . . . . 1,350

Chromosomal aberration data . . . . . . . . . . . 18,000

Ecotoxicity data:

Data about killing of three lower organisms 4,100

Degradation/accurnu/at/on data . . . . . . . . . . 3,100-11,850

SOURCE: Office of Technology Assessment, 1981.

they looked with favor on the proposed exemptions.

Environmental organization reviewers, however, equally emphatically stated that absence of

data, especially toxicity data, causes EPA to

“swallow uncertainty” too often and to fail to

discharge properly its duties under TSCA. They

urged that EPA insist on obtaining more toxicity

data, and some argued that EPA should require

submission of a base set of data, similar to that

required by the European Economic Community

(46 F.R. 8986).

POSSIBLE FURTHER EVALUATION OF THE PMN

Some industry reviewers of the first draft of this

background paper praised EPA for recruiting a

competent staff for the PMN review program.

They expressed satisfaction that many of the Office of Toxic Substances’ staff exercise what the

industry reviewers see as “proper professional

judgment” in their duties.

EPA employees who review PMNs speak of

“swallowing uncertainty” when they make decisions with insufficient data. No amount of inspecting records of the amount of data submitted on

REVIEW PROCESS

PMNs, as was done here, can reveal the frequency with which the data submitted on a PMN were

sufficient for adequate review.

There must be cases in which EPA exercised

“professional judgment” or “swallowed uncertainty” when data were limited among the PMNs examined by OTA. A surer base for conclusions

about the adequacy of PMN data submission and

use could be provided by an examination of:

1) the EPA’s use of the submitted data, 2) the

Agency’s decisions to ask or not to ask for more
Ch. 9—Discussion ● 7 9

information, and 3) the appropriateness of the

Agency’s deciding to use or not to use SAR analysis when data were not available. Such an examination would require evaluation of the suitability

of the PMN data and careful inspection of written records and interviews of EPA officials to describe the decisionmaking process.

Clearly, not all PMNs, not even many PMNs,

could be examined in that depth. A sample of

some of the PMNs that resulted in a regulatory

action or a voluntary restriction (see ch. 8) could

be examined to learn about the processes and decisions that resulted in an EPA action. Equally,

perhaps more, important, a selection of PMNs

that resulted in no EPA action would also have

to be examined. PMNs that described chemicals

of high potential concern-some to be made in

very large amounts and for consumer use (see

table 19), or polymers to be excluded from the

proposed exemption (see table 2), or chemical

classes known to be highly reactive or biologically

active—could be selected. The selection process

would be critical because a charge likely to be

leveled an any analysis is that the PMNs chosen

for study were not representative.

The study should include a careful look at the

quality of the submitted data, the steps that EPA

took to find additional data, and an effort to see

if other data were readily available. If SAR analysis was used by EPA, the study should examine

the bases for the decision to use that technique,

the appropriateness of EPA’s efforts to gather information on related chemicals, and the reasonableness of the decisions made by EPA.

An analysis of this sort, if not limited to a few

PMNs, could involve amounts of staff and resources rivaling those used for PMN review by

EPA. It would require various kinds of experts

and access to diverse sources of data. The cost

might be so high as to be prohibitive. At the same

time, such an analysis might be necessary to

decide if EPA’s decisions about unreasonable risks

were reasonable.
Appendixes
Appendix A.—Summary of Topics Considered at

Evaluation Meeting During Initial Screen of

Premanufacture Notices at the

Environmental Protection Agency

I. General Information for PMN Substances

A. Manufacturing Process and Chemistry

B. Physical-Chemical Properties

1. Composition

2, Physical form (solid, liquid, gel, etc. )

3. pKa ionization constant

4. Partition coefficient (affinity for aqueous

and organic solvents)

C. Use Function

1. Known and potential uses

2. Production capacity and potential growth

D. Regulatory Concerns

II. Assessments

A. Structural Activity Team Report

B. Health Hazards

1.

2.

3.

4.

Metabolism, uptake, excretion

Acute toxicity

a. LD50 (amount of chemical necessary to

kill 50 percent of test animals)

b. Other acute effects

Carcinogenicity, mutagenicity, teratogenicity

Other chronic effects

C. Ecological Hazards

1. Effects on microbes

2. Effects on invertebrates

3. Effects on plants

4. Effects on fish

5. Effects on mammals and birds

6. Effects on ecosystem process

D. Worker/Consumer Exposure

1. Worker exposure from manufacture

2. Worker exposure from processing

3. Consumer exposure

E. Environmental Release

1. Release from manufacture

2. Release from processing

3. Release from use

4. Release from disposal

F. Environmental Fate

1. Persistence

a. Degradation

b. breakdown products

G. Non-Risk Factors

1.

2.

3.

4.

5.

Company size and characteristics

Substitutes (for the new chemical and old

chemicals that the new chemical may substitute for)

Potential new uses

Financial effect of the PMN chemical on

company

Benefits to society

HI. Summary of Outstanding Problems of Scientific/

Technical Concerns

A, Most Serious Problem

1.

2.

3.

4.

5.

6.

IV.

Health hazard

Ecological hazard

Worker/consumer exposure

Environmental release

Environmental fate

Non-risk factor

A. Related Substances

B. Solvents (used in manufacture and processing)

C. Catalysts (used in manufacture and processing)

D. Byproducts (from manufacture and processing)

V. Priority Problem in Profile

83
Appendix B.—Copies of Face Sheets:

EPA and CMA PMN Forms

Tuesday

October 16, 1979

Part Ill

Environmental

Protection Agency

Reproposal of Toxic Substances Control

Act (RCA) Premanufacture Notice (PMN)

Forms and Provisions of Rules
App. B—Copies of Face Sheets EPA and CMA PMN Forms ● 85

APPENDIX A

PREMANUFACTURE NOTICE FORM

PROPOSED BY

MANUFACTURING CHEMISTS ASSOCIATION

NOTE: Copies of the compiete form can be obtained from the Chemicai Manufacturers Association,

2501 M St., NW, Washington, D.C., 20037.
—

Appendix C.—Acknowledgments

The individuals and organizations listed below assisted in the preparation and review of this background

paper. Their assistance is gratefully acknowledged.

Garrity Baker

Chemical Manufacturers Association

Ruth Bell

Environmental

Paul Bickart

Environmental

(reviewer)

Irving Baumel,

Environmental

Protection Agency

Protection Agency

Ph.D.

Protection Agency

Blake Biles, Esq.

Jones, Day, Reavis & Pogue

D. Christopher Cathcart

Chemical Manufacturers Association

Chemical Manufacturers Association

Washington, D.C.

(reviewer)

Chemical Specialties Manufacturers Association

Washington, D.C.

(reviewer)

Edwin H. Clark, Ph.D.

Conservation Foundation

Wendy Cleland-Hamnett

Environmental Protection Agency

Anna Coulakis

Environmental Protection Agency

Geraldine V. Cox, Ph. D.

Chemical Manufacturers Association

J. Clarence Davies, Ph. D.

Conservation Foundation

(reviewer)

Joseph DeSantis

Environmental Protection Agency

Denise Devoe

Environmental Protection Agency

Ralph Domenick

General Accounting Office

(reviewer)

George S. Dominguez

Springborn Management Consultants, Inc.

(reviewer)

David Dull

Environmental Protection Agency

Ralph Engel

Chemical Specialties Manufacturers

(reviewer)

86

Association

Howard Fribush

Environmental Protection

Samuel Gusman, Ph. D.

Conservation Foundation

Khristine L. Hall, Esq.

Agency

Environmental Defense Fund

(reviewer)

Gerald A. Hapka, Esq.

E. I. du Pent de Nemours & Co., Inc.

(reviewer)

Jim T. Hill, Ph. D.

Chemical Specialties Manufacturers Association

(reviewer)

Steven Jellinek

Jellinek & Associates

(reviewer)

David Klauder, Ph. D.

Environmental Protection Agency

Edward Klein

Environmental Protection Agency

(reviewer)

Timothy Knutson, Esq.

Environmental Protection Agency

James M. Kuszaj

Dow Chemical Co.

(reviewer)

L. M. Magner, Ph. D.

E. I. du Pent de Nemours & Co., Inc.

Carl Mazza, Ph. D.

Environmental Protection Agency

(reviewer)

Frank Mirer, Ph. D.

United Auto Workers

(reviewer)

J. Raymond Miyares, Esq.

Bracken and Baram

G. R. Munger

The Society of the Plastics Industry, Inc.

(reviewer)

Jim Nelson

Environmental Protection Agency

Office of Toxic Substances

Environmental Protection Agency

(reviewer)
App. C —Acknowledgments . 87

Ron Outen, Ph. D.

Government Research Corp.

(reviewer)

Frederica Perera, Ph. D.

Natural Resources Defense Council, Inc.

(reviewer)

Catherine T. Petito

Natural Resources Defense Council, Inc.

(reviewer)

Ted E. Potter

Shepherd Chemical Co.

(reviewer)

Justin Powell, Ph. D.

Environment] Protection Agency

(reviewer)

James Scott

Environmental Protection Agency

Michael Shapiro

Environmental Protection Agency

Ellen K. Silbergeld, Ph. D.

Environmental Defense Fund

(reviewer)

The Society of the Plastics Industry, Inc.

New York

(reviewer)

Margaret Stasikowsi

Environmental Protection Agency

(reviewer)

Robert M. Sussman

Covington & Burling

(reviewer)

Synthetic Organic chemical Manufacturers

Association, Inc.

Washington, D.C.

(reviewer)

Susan Vogt

Environmental Protection Agency

(reviewer)

Andrew B. Waldo

Synthetic Organic Chemical Manufacturers

Association, Inc.

(reviewer)

Marcia E. Williams

Environmental Protection Agency

(reviewer)
Appendix D.—Acronyms and Glossary

Acronyms and Glossary

5(e) order.—A formal regulatory order from EPA stating that a chemical may pose an “unreasonable risk,”

restricting its manufacture, use, or disposal, and

stipulating tests that have to be performed to satisfy

the Agency that the chemical does not pose such

risks.

carcinogen.-A substance or agent that causes cancer.

CBI.—Confidential Business Information.

Class I substance or chemical.-A chemical that can

be represented by a chemical formula and structure.

Class II substance or chemical. —A complex chemical

combination that cannot be represented by a chemical formula or structure.

Class 111 substance or chemical. —A polymer.

CMA.—Chemical Manufacturers Association.

daphnia. —Minute freshwater crustaceans.

ecotoxicity.-The property of causing harm to biota—

plants, animals, or microbes—in the environment.

EEC.—European Economic Community.

EPA.—Environmental Protection Agency.

Inventory of Chemical Substances. -An EPA-compiled list of all chemicals, subject to the provisions

of TSCA, that are present in U.S. commerce.

kg.–kilogram (about 2.2 pounds).

manufacture. —In this study, the manufacture or importation of a “new” chemical. This legally can take

place only after PMN review.

MPD.—Minimum Pre-Marketing Data set, a data set

required by the EEC before a chemical can be manufactured within those countries.

mutagen.—A substance or agent that interacts with

DNA, the genetic material, and produces heritable

changes.

“new” substance or chemical .-A substance or chemical not listed on the Inventory Chemical Substances.

NOC.—Notice of Commencement: a notice sent to

EPA to notify the Agency that manufacture of a

“new” chemical has begun.

OECD.—Organization for Economic Cooperation and

Development.

OTA.—Office of Technology Assessment.

OTS.—Office of Toxic Substances, EPA.

PMN.—Premanufacture Notice.

Manufactured PMN.—In this study, a PMN received by EPA before the end of June 1981 that completed review by the end of September 1981 and that

described a chemical which began manufacture before

the end of August 1981.

Nonmanufactured PMN.–In this study, a PMN

received by EPA before the end of June 1981 that completed review by the end of September 1981 and that

described a chemical which had not begun manufacture by the end of August 1981.

Regulated PMN.—In this study, a PMN that resulted in EPA writing and issuing a S(e) order requiring the PMN submitter to produce data about the

chemical.

June 1982 PMN.–In this study, any PMN received

by EPA in June 1982.

polymer.—A chemical that is composed of repeating,

simpler chemical subunits (and see ch. 4).

review period.—The 90 days after EPA receives a

PMN. If EPA does not find that the PMN describes

a chemical that may present an unreasonable risk,

manufacture may begin after 90 days.

SAR.-Structural Activity Relationship analysis, techniques for estimating chemical and biological activities of a chemical substance based on knowledge

of related chemicals.

teratogen.—A substance or agent that causes birth

defects.

TSCA.—Toxic Substances Control Act.

88

References

1.

2.

3.

4.

5.

6.

Arthur, J. L., and Garrett, R. L., “Exposure

Assessment of New Chemicals Under Section

5 of the Toxic Substances Control Act,” Toxic

Substances J. 4:80-103, 1982.

Bannerman, D. G., “Impact of TSCA on Market Introduction of New Chemicals, ” speech

delivered before the American Chemical Society, Las Vegas, Nev., Mar. 31, 1982.

Dickson, D., “U.S. Softens Toxic Chemicals

Accord,” Science 218:982, 1982.

Environmental Protection Agency, “Status of

Premanufacture Notices,” typed tables, Jan.

29, 1981.

Environmental Protection Agency, Monthly

Status Report for PMNs and TMEA's—]une

2982, memorandum, July 16, 1982.

Klein, E. A., “Summary of Informal Regulatory Actions—Quarterly Report, ” memo to

Don R. Clay, Director, Office of Toxic Substances, Environmental Protection Agency,

July 30, 1982.

7.

8.

9.

10.

11.

Mazza, C., “Perspectives on the MPD Review

Drawn From Experience in PMN Review,”

memo to Don R. Clay, Director, Office of

Toxic Substances, Environmental Protection

Agency, Jan. 6, 1982.

National Research Council, Identifying and

Estimating the Genetic Impact of Chemical

Mutagens (Washington, D. C.: National

Academy Press, 1983).

Office of Technology Assessment, U.S. Congress, Assessment of Technologies for Determining Cancer Risks From the Environment

(Washington, D. C.: U.S. Government Printing Office, OTA-H-138, June 1981).

Office of Toxic Substances, Environmental

Protection Agency, PMN Review Process

Manual (Washington, D. C.: EPA, 1981).

Office of Toxic Substances, Environmental

Protection Agency, Priorities for OTS Operation (Washington, D. C.: EPA, 1982).

91

U. S. GOVERNMENT PRINTING OFFICE : 1983 0 - 98-826