Environmental Contaminants in Food

December 1979

NTIS order #PB80-153265
Library of Congress Catalog Card Number 79-600207

For sale by the Superintendent of Documents, U.S. Government Printing Office

Washington, D.C. 20402 Stock No. 052-003-00724-0
FOREWORD

This report presents the major findings of an OTA assessment of Federal and

State efforts to deal with the environmental contamination of food. Undertaken at

the request of the House Committee on Interstate and Foreign Commerce, the

study examines both regulatory approaches and monitoring strategies for coping

with contaminated food.

The assessment is concerned with chemical and radioactive contaminants

that inadvertently find their way into the human food supply. To bring the scope of

inquiry within manageable bounds, we excluded naturally occurring toxins such

as fungal and microbial toxins.

The Office of Technology Assessment was assisted by two advisory panels of

scientists and representatives of public interest groups, agriculture, the chemical

industry, fisheries, and State and foreign governments. The Food and Drug Administration, the Department of Agriculture, and the Environmental Protection

Agency each designated staff members to attend panel meetings, provide background information, and review draft reports, Background papers were commissioned concerning the scientific aspects of detecting and regulating environmental contaminants in food. The Congressional Research Service provided five

analyses of previous food contamination episodes, Reviews of the draft report

were provided by the advisory panels, Federal agencies, and a number of interested individuals not previously involved with the assessment.

Because this assessment addresses concerns of American citizens as well as

policy makers and scientists, the summary of the report is also being published as

a separate document. The summary provides the interested citizen with an informative and clear overview of this complex problem. Copies of the summary can

he obtained free of charge from the office of Technology Assessment, U.S. Congress, Washington, D.C. 20510.

JOHN H. GIBBONS

Director

///
Tolerance Advisory Panel

James Anderson

Manager for Material Safety

Allied Chemical Corporation

Louise Burke

Executive Director

Consumer Council of Virginia Foundation

Consumer Council of Virginia, Inc.

Kenneth Crump

Department of Mathematics and Statistics

Louisiana Tech University

Donald Epp

Department of Agricultural Economics and

Rural Sociology

Pennsylvania Stale [University

Frederick Halbert

Dairy Farmer

Delton, Mich.

Joseph Highland

Chairman

Toxic Chemicals Program

Environmental Defense Fund

Monitoring Advisory Panel

Raymond Allred

Director

Environmental Conservation Research

Continental Oil Company

Richard Anderson

Chairman

Statistics Department

University of Kentucky

John Bourke

Director

Analytical Division

Food Science Department

Cornell University

Vaughan Bowen

Woods Hole Oceanographic Institute

Shirley Briggs

Executive Director

Rachel Carson Trust for the Living

Environment, Inc.

Leon Chesnin

Department of Agronomy

University of Nebraska

Robert Jackson

Assistant State Health Commissioner

Director, Office of Health Protection and

Environmental Management

Virginia State Health Department

Kazuo K, Kimura

School of Medicine

Wright State University

Marvin Legator

Director

Division of Environmental Toxicology

Deportment of Preventive Medicine and

Community Health

University of Texas Medical Branch

David Lindsay

Technical Secretary

Steering Group on Food Surveillance

Ministry of Agriculture, Fisheries, and

Food

United Kingdom

Roy Mart in

Director

Science and Technology

National Fisheries Institute, Inc.

William Cooper

Professor

Department of Zoology

College of Natural Science

Michigan State University

John Davies

Chairman

Department of Epidemiology and Public

Health

School of Medicine

Universitv of Miami

Blake Early

Environmental Action, Inc.

Edward Elkins

Director

Chemistry Division

Washington Research Laboratory

National Food Processors’ Association

Ronald J. Hingle

Administrator

Food and Drug Control Unit

Bureau of Environmental Services

Louisiana Office of Health Services and

Environmental Quality

Richard Merrill

School of Law

University of Virginia

Joseph Rosen

Department of Food Science

Rutgers University

John Rust

Professor Emeritus

Pharmacology/Radiology

University of Chicago

Gary Van Gelder

College of Veterinary Medicine

University of Missouri

John Van Ryzin

RAND Corporation

George Whitehead

Deputy Director

Office for Consumer Affairs

Michigan Department of Agriculture

S. Roy Koirtyohann

Environmental Trace Substances Center

University of Missouri

Charles Krister

Retired Manager

Biochemicals Department

E. I. DuPont de Nemours and Company

John Laseter

Director

Center for Bio-Organic Studies

University of New or leans

John Martin

Moss Landing Marine Laboratories

Rebecca Sharitz

Savannah River Ecology Laboratories

University of Georgia

Gerald Ward

Department of Animal Science

Colorado State University

Iv
Food and Renewable Resources Program Staff

Joyce C. Lashof, Assistant Director

Health and Life Sciences Division

J. B. Cordaro, Program Manager*

Walter Parham, Program Manager

Catherine Woteki, Project Director

Robert Smith, Research Assistant

Chris Elf ring, OTA Congressional Fellow

Administrative Staff

Phyllis Balan Elizabeth Galloway Ogechee Koffler

Contractors

Lloyd W. Hazleton, Technical Advisor to Tolerance Panel

Robert Huggett, Technical

Samuel

OTA Publishing Staff

Advisor to Monitoring Panel

Iker, Editor

John C. Holmes,

Kathie S. Boss

Food Advisory Committee

Martin E. Abel, Chairmen Lorne Greene

Publishing Officer

Joanne Heming

Robert 0. Nesheim

Senior Vice President Chairman of the Board Vice President, Science and

Schnittker Associates

Johanna Dwyer, Co-Chairman

Director

Frances Stern Nutrition Center

David Call

Dean, College of Agricultural

and Life Sciences

Cornell University

Cy Carpenter

President

Minnesota Farmers Union

Eliot Coleman

Director

Coolidge Center for the

Study of Agriculture

Almeta Edwards Fleming

Social Program Coordinator

Florence County, S.C.

American Freedom From

Hunger Foundation

Richard L. Hall

Vice President, Science and

Technology

McCormick & Company, Inc.

Laura Heuser

Member, Board of Directors

Agricultural Council of America

Arnold Mayer

Legislative Representative

Amalgamated Meat Cutters and

Butcher Workmen of North

America

Max Milner

Executive Director

American Institute of Nutrition

Technology

The Quaker oats Company

Kathleen O’Reilly

Director

Consumer Federation of America

R. Dennis Rouse

Dean, School of Agriculture

Auburn University

Lauren Seth

Agricultural Consultant

Thomas Sporleder

Professor of Agricultural

Economics

Texas A&M University

Sylvan Wittwer

Director and Assistant Dean

College of Agriculture and

Natural Resources

Michigan State University

*Resigned June 16, 1979, and continued to serve under contract to assessment completion.
Contents

Chapter Page

I. Summary . . . . . . . . . . . . . . . . . . . `“ “ “ “ ● ● ● “ ● 00 G o “ ● “ o ● ● o ● o ● “ o ● 00 “ ● “ o “ “ “ Health Impacts of Environmental Contamination. . . . . . . . . . . . . . . . . . . . . . .

Economic Impacts of Contamination. . . . . . . . . . . . . . . . . . . ““ .“ . ““. ““. “ .“

Major Problems in Identifying Environmental Contaminants . . . . . . . . . . . . .

Problems of Regulating Environmental Contaminants. . . . . . . . . . . . . . . . . . .

Findings and Conclusions . . . . . . . . . . . . . . . . . “ “ “ “ . “ “ “ . m “ “ “ o “ o “ . “ . “ “ “ “ Congressional Options. . . . . . . . . . . . . . . ..” . . “ “ “ “ .0. “ o ‘. “ c o “ o “ “ o “ “ “ ““

Option l.--Maintain the Present System . ..........”””’ . . . .. .”.”””.

Option2.—Amend the Food, Drug, and Cosmetic Act . . . . . . . . . . . . . . . . .

Option 3 .—Establish an Investigatory Monitoring System. . . . . . . . . . . . . .

Option 4.—Improve Federal Response to New Contamination Incidents . .

II. Environmental Contamination of Food.”~””.”. .“””.’””ooooQo ● +00 ”00”0

How Food Becomes Contaminated . .........””””” ....”””..”.... .“””

Magnitude of the problem . . . . . . . . . . . . . . . . . . . . .“.”””””.”..”.“...”

Evidence of Human Illness Resulting From Consumption of

Contaminated Food. . . . . . . . . . . . . . . . . . ...””””””.””.” “o” ”””..

Polychlorinated Biphenyls. . . . . . . . . . . . . . . . . . “ ~ . “ “ m “ “ ~ 0. ~ 0. “ “ o ~ .

Polybrominated Biphenyls . ..........”””” ..”””.””” .“.”.”.”””.”

Mercury and Methylmercury . . . . . . . . . . . . . . . . . “ . “ “ ~ ~ .“ “ “ ~ “ . “ “ 0.

Radioactivity . . . . . . . . . . . . . . . . . . . . “ “ “O 00 “ ““ ~ s o “ ~ 000 s Q “ o “ “ s “ o “ Number of Food Contamination Incidents. . . . . . . . . . . . . . . . “ . ““” ~ “ “ “.”

Economic Impact . . . . . . . . . . . . . . . . ..””””.”” “0”””00.0””””. ““s”””

Costs of Food Condemned. . . . . . . . . . . . . . ...”.”. “. ““””.””””.””

Health Costs... . . . . . . . . .....,..””””.” 0“0.o’0”””””00 ““”””””..

Distributional Effects and Costs . . . . . . . . . . . . . . . “ ““ “ . “ . “ “ “ “ “ .0 “ ““

Potential Food Contamination problems. . . . . . . . . . . . . . . .“ .“ “ . “. ‘“” ““ “ “ Conclusions and Issues . . . . . . . . . . . . . . . “ . “ “ ~ “ . ~ ~ . ~ “ ~ . “ “ “ “ o “ “ o ~ o “ s “ “ Chapter II References . . . . . . . . . . . . . . . . . . . “ “ “ ~ “ . . . “ 0.0. s o “ 0000. s “ “ .

111. Federal Laws, Regulations, and Programs” . . . . . . . . . . “ “ “ “ “ 00 ● o “ o “ ● 0000

Federal Laws. . . . . . . . . . . . . . . . . “ “ .“” “ “ ““ “O . “ “ “ 000 “ “.” ~ o ‘ . “ 00 “ .- e o

Action Levels and Tolerances. . . . . . . . . . . . . . “ ‘ “ “ “ “ “ ~ “ “ ~ “ “ “ ~ o “ o “ “ o “ “ ~ Criteria forgetting Action Levels and Tolerances . . . . . . . . . . . . . . . . . . . .

Determining Action Levels and Tolerances . . . . . . . . . . . . . . “ . . “ . “ “ “ “ . .

Evaluation of the Scientific Data. . . . . . . . . . . . . . . . .“” . ““ “ ““ ~ ““” “ “ “ Evaluation of Decisionmaking Approach . . . . . . . . . . . . . . ““ . .“ “.” . “ “ Federal Monitoring programs. . . . . . . . . . . . . . . . . “ . “ “ . “ “ 000 “ “ s m “ . “ “ “ “ ~

Food and Drug Administration . . . . . . . . . . . . . . . “ “ . “ “ “ “ “ “ “ “ .0 “ o ‘ “ “ “ .

U.S. Department of Agriculture . . . . . . . . . . . . . . . “ . “ “ ‘ “ “ “ “ “ “ “ o “ “ 0.00

Environmental Protection Agency . . . . . . . . .......”..”.”.o““” ”s”s.”s

Critique of Federal Monitoring programs. . . . . . . . . . . . . . . . . . . . “ . . . “ . “ Chapter III References . . . . . . . . . . . . . . ““” ““”” ~ “ “ “ .’. o “ .0 “ . .“ s . “ o .“ “

V. Methods for Assessing Health Risks.....”“”””OCO””OOOO 0“00”00”0

Possible Toxic Effects . . . . . . . . . . . . . . . . . . ..””.”””.””””.” .“”..”””””.

Human Epidemiology. . . . . . . . . . . . . . . . ....”.”.o.o’s ““0”””””.”.”00

Animal Tests and Other Methods for Toxicological Testing . . . . . . . . . . . . . .

The Carcinogen Bioassay. . . . . . . . . . . . . . . “ . ““ “ “ “ “ .0 “ “ 000. c “ .0.....

Short-Term Tests for Mutagenesis and Potential Carcinogenesis. . . . . . . .

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vii
Contents--continued

Chapter

Interactions of Two or More Substances . . . . . . . . . . . . . . . . . . . . . . . . . . .

Extrapolating From High Doses to Low Doses. . . . . . . . . . . . . . . . . . . . . . . .

Chapter Preferences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

VI.

VII.

VIII.

Ix.

Methods of Estimating and Applying Costs to Regulatory Decisionmaking . .

Cost Effectiveness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Cost-Benefit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Application of Methods for Regulation, . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Chapter VI References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Monitoring Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Strategies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Regulatory Monitoring. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Investigatory Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..., , . . . . . .

Monitoring for Suspected Environmental Contaminants . . . . . . . . . . . . .

Monitoring for Uncharacterized Environmental Contaminants . . . . . . . .

Specimen Banking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Sampling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 . . . . . . . . . . . . . . .

Quality Assurance. ,... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Chapter VII References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Monitoring Instrumentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Organic Environmental Contaminants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis ., ..., . . . . . . . . . . . . . . . . , . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Application to Investigatory Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Detecting and Quantifying Trace Metal Contaminants . . . . . . . . . . . . . . . . . .

Analysis ....., . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Application to Investigatory Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Speciation of Trace Metals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis of Foods for Radioactivity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Applications to Investigatory Monitoring. . . . . . . . . . . , . . . . . . . . . . . . . . .

Estimated Cost to Equip a Laboratory to Conduct Investigatory Monitoring. .

Chapter VIII References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Congressional Options. .. .. .. .. .. .. .. ... ... ... ....$ . . . . . . . . . . . . . . .

Option 1—Maintain the Present System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Option 2—Amend the Food, Drug, and Cosmetic Act. . . . . . . . . . . . . . . . . . . .

Option 2A--Simplify Administrative Procedures. . . . . . . . . . . . . . . . . . . . .

Option 2B-Requiret reestablishment of Tolerances . . . . . . . . . . . . . . . . .

Option 2C-Clarify the Role of Economic Criteria . . . . . . . . . . . . . . . . . . . .

Option 2D-Establish Regional Tolerances . . . . . . . . . . . . . . . . . . . . . . . . .

 Option 3-Establish an Investigatory Monitoring System . . . . . . . . . . . . . . . .

Option 3A-Establisha National Monitoring System for Suspected

Environmental Contaminants. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Option 3B-Establisha National Monitoring System for Uncharacterized

Environmental Contaminants. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Option 4—Improve Federal Response to New Contamination Incidents . . . . .

Option 4A-Designate a Lead Agency . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Option 4B-Establish a Center to Collect and Analyze Toxic Substances

Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Appendixes

A. Substances Whose Production or Environmental Release Are Likely to Increase

in the Next Ten Years . . . . , . . , . . . . . . . . . . , , . . . , . , . . , , . . . . . , . . . , . , . . . . . .

B. FDA Derivation of PCB Tolerance—Federal Register. . ., , . . . . . . . . . . . . . . . . . . .

Page

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125

.,.

Vlll
Contents--continued

Appendix Page

C. Methods for Toxicologic Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137

D. Review and Evaluation of Methods of Determining Risks From Chronic Low-Level

Carcinogenic Insult . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154

E. Measuring Benefits and Costs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166

F. Priority Setting of Toxic Substances for Guiding Monitoring Programs . . . . . . . . . . 177

G. Approaches to Monitoring Organic Environmental Contaminants in Food . . . . . . . 187

H. Analytical Systems for the Determination of Metals in Food and Water Supplies . 195

I. Analysis of Foods for Radioactivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215

J. Commissioned Papers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228

K. Executive Agency Observers at Advisory Panel Meetings. . . . . . . . . . . . . . . . . . . . `229

LIST OF TABLES

Table No. Page

1.

2.

3.

4.

5.

6.

7,

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

l9.

20.

21,

A-].

D-1.

G-1.

G-2.

G-3.

H-1.

H-2.

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17

17

18

22

26

36

50

51

51

51

52

66

68

69

74

83

95

98

101

104

123

164

188

192

199

201
Contents--continued

Table No. Page

H-3,

H-4.

H-5.

H-6,

I-1.

Multielement Atomic Emission Determination Limits for Two Common Plasma

Excitation Systems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204

Determination Limits for X-Ray Fluorescence Techniques. . . . . . . . . . . . . . . . . . 205

List of Sample Preparation Facilities Required . . . . . . . . . . . . . . . . . . . . . . . . . . 209

Summary of Cost-Productivity Estimates for Various Analytical Techniques . . . 210

Costs for Space, Furnishings, Equipment, and Supplies .,,..............,.. 225

LIST Of FIGURES

Figure No. Page

l. Distribution of PCB Contamination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

2. Distribution of States Responding to Questionnaire . . . . . . . . . . . . . . . . . . . . . . . 24

3. State Food Laws. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

4. Scope of Investigation: Distribution of Materials . . . . . . . . . . . . . . . . . . . . . . . . . 53

5. Steps in the Ames Spot Test. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65

6. A General Scheme for the Qualitative and Quantitative Analysis of the

Organic EPA Priority Pollutants in Semisolid Foods . . . . . . . . . . . . . . . . . . . . . . . 94

7. Comparison of the Gas Chromatographic Analysis of a Standard Mixture of

Polychlorinated Biphenyls on Two Types of Gas Chromatographic Columns . . . 96

D-I, Illustration of Why the Dose-Response Curve Should Be Linear at Low Dose in

the Presence of Background Carcinogenesis ... , ... , ., . . . . . . . . . . . . . . .

D-2. Typical Fit of Mantel-Bryan Curve to Experimental Data , . . . . . . . . . . . . . .

D-3. Comparisons of “Safe” Doses Computed From the Mantel-Bryan Procedure

and From a Procedure Based on the Multistage Model . . . . . . . . . . . . . , . . .

D-4a, Example of Data Exhibiting Downward Curvature . . . . . . . . . . . . . . . . . . . .

D-4b, Example of Data Exhibiting Upward Curvature. . . . . . . . . . . . . . . ., , . . . . .

E-1 .

G-I .

G-2.

G-3.

H-1 .

1-1.

Analysis of a Shift in Supply .-. , . . . . . . . . . . . ... , . . . . . . ... , ., , ., . . . . .

A Simplified Diagram for the Qualitative and Quantitative Analysis of the

Organic EPA Priority Pollutants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... , .

A General Scheme for the Qualitative and Quantitative Analysis of the EPA

Organic Pollutants in Semisolid Foods . . . ... , . . . . . . . . . . . . . . . . . . . , . . .

, .. 156

. . . 158

. , , 161

. . . 162

. , . 162

.0. 170

. , . 189

, . , 189

General Analytical Scheme To Detect and Monitor New Trace Organics and

Priority Pollutants in Food and Water Samples . . . . . . . . . . . . . . . . . . . . . . . . . . 192

Flow Diagram of the General Operational Protocol of a Monitoring Laboratory 197

Comparison of Gamma Spectra Taken With a Sodium Iodide Detector and a

Germanium Diode Detector.........,..,.. . . . . . . . . . . . . . . . . . . . . . . . . . . . 222
\

Summary

I
.

Chapter 1

Summary

The environmental contamination of food is a nationwide problem. A

number of recent incidents dramatically illustrate the potential health hazards and economic harm that can be caused by such contamination-animal

feeds in Michigan contaminated by polybrominated biphenyls (PBBs), the

Hudson River contaminated by polychlorinated biphenyls (PCBs), and Virginia's James River contaminated by kepone.

These are some of the more serious of the 243 food contamination incidents identified in an OTA survey of the 50 States and 10 Federal agencies.

These incidents have occurred in every region of the country. They have involved all categories of food. While the OTA survey clearly shows the national

character of such contamination, the true extent of the problem is still

unknown.

The latest major food contamination incident—one not included in the

OTA survey-graphically points up the ominous dimensions of the problem.

PCBs from a damaged transformer contaminated animal fats at a packing

plant in Billings, Mont. The plant used the adulterated fats to produce meat

and bone meal that were sold both to feed manufacturers and directly to

farmers. The contaminated feed spread through at least 10 States—polluting

poultry, eggs, pork products, and a variety of processed foods (including

strawberry cake). The result: contaminated food found in 17 States, and hum

dreds of thousands of pounds of food products seized or destroyed.

This assessment, undertaken at the request of the House Committee on

Interstate and Foreign Commerce, examines the adequacy of current Federal

and State efforts to deal with the environmental contamination of food. In

particular, the study evaluates the effectiveness of 1) Federal and State

monitoring systems in detecting contamination episodes before they reach

crisis proportions, and 2) Federal efforts to regulate contaminations. The

study explores alternative approaches to the problem and presents policy options for Congress.

Environmental contaminants in food fall

into three categories—synthetic or natural

organic chemicals, metals or their organic

and inorganic derivatives, and natural or synthetic radioactive substances. Such contaminants are regulated under the Federal Food,

Drug, and Cosmetic Act. To regulate them under the law, the Food and Drug Administration (FDA) defines environmental contaminants as “added, poisonous, or deleterious”

substances that cannot be avoided by good

manufacturing practices, and that may make

food injurious to health.

Unlike food additives, environmental contaminants inadvertently find their way into

the human food supply (including sports fish

and game). They can enter food directly or indirectly as a result of such human activities

as agriculture, mining, industrial operations,

or energy production. In no instance is their

presence in food ever intended.

3
Four factors determine whether and how

seriously the environmental contamination of

food will affect human health: the toxicity of

the contaminant, the amount of the substance

in the food, the amount of the contaminated

food eaten and the physiological vulnerability of the individual or individuals consuming

the food.

Based on other countries’ experiences,

there is considerable evidence of human illness caused by the consumption of food containing various organic chemicals and

metals. In such cases, the level of the contaminant in food exceeded the levels usually

found in the U.S. food supply. The effects of

mercury poisoning are well-documented. The

best known case involved the consumption of

mercury-contaminated fish from Japan’s Minamata Bay. Some of the offspring of exposed

mothers were born with birth defects, and

many victims suffered central nervous system damage.

Another incident in Japan stemmed from

the inadvertent contamination of rice oil by

PCBs. The consumption of food cooked with

this oil resulted in 1,291 cases of so-called

“Yusho disease”—a condition marked by

chloracne (a severe form of acne), eye discharges, skin discoloration, headaches, fatigue, abdominal pains, and liver and menstrual disturbances,

No such mass-poisoning episodes have occurred in the United States. But there are

studies indicating that present levels of some

environmental contaminants may cause physiological changes. For example, the accidental contamination of animal feed in 1973 exposed most of the population of Michigan to

PBB in dairy products and other foods. Evidence on what impact this exposure has had

on human health is conflicting, although some

disparities in white blood cell function have

been noted in farm families, The long-term

significance of these physiological changes is

not yet known.

The clinically obvious harmful health effects of radiation are usually associated with

massive, high-level exposures. Past cases of

radioactive contaminated foods have involved relatively small amounts of radioactive substances with low dose rates. Generally, the young are most sensitive to radiation

exposure. However, since any amount of radiation is potentially harmful, prudent public

policy must assume that any unnecessary exposure to high-energy radiation should be

avoided.

The economic impacts of a contamination

incident have traditionally been stated in

terms of the estimated dollar value of the resulting food loss. Only limited data on such

costs are available. Dollar value estimates for

condemned food were available for less than

30 percent of the contamination episodes

noted in the OTA survey. Thus, the real cost

of environmental contamination of food during the 1968-78 decade is at least several

times the $282 million reported to OTA.

The loss of food only partially reflects the

total economic impact of environmental contamination, Health and “distributional” costs

are also involved. The health costs include

medical expenses and lost workdays from illness resulting from food contamination incidents. Since the health effects may not immediately be evident, the expected illnesses

or deaths from an episode are usually estimated on the basis of available toxicity data

for a particular contaminant. In other words,

estimated health costs are more likely to be

projections than actual figures based on

known cases of illness or death.

The “distributional” costs of environmental contamination disclose the expenses or

losses incurred by affected businesses, individuals, and government bodies. These might

include farmers, fishermen, food processors,
Ch. l—Summary ● 5

animal feed suppliers, chemical companies, fied, their actual dollar losses are not known.

consumers, and local, State, and Federal To understand who is bearing the major ecoagencies. Although the individual organiza- nomic brunt of a contamination episode, actions suffering such losses are usually identi- tual cost data are required.

MAJOR PROBLEMS IN IDENTIFYING

ENVIRONMENTAL CONTAMINANTS

To determine whether an environmental

contamination incident has occurred, it is

necessary to establish the presence of the

contaminant in food. In some instances, people or animals have become ill before the responsible contaminant was identified. No one

knew or even suspected that the particular

substance was present in food. This has been

the pattern in many major contamination incidents—those involving PBBs, PCBs, and

mercury.

Our regulatory monitoring system has

failed to detect such environmental contaminants as they entered the food supply. Thus,

this assessment identifies and evaluates

other approaches for monitoring either food

or the environment for toxic substances that

may harm human health. The ultimate objective of monitoring is to prevent or minimize

human exposure to environmental contaminants in food.

The only sure way to prevent this kind of

contamination is to make certain that toxic

substances are not released into the environment. There are various Federal environmental laws that are designed to limit such releases. But the laws and regulations are not

likely to prevent the deliberate or accidental

misuse or disposal of the thousands of toxic

substances manufactured in the United

States.

The problem is compounded by disposal

and handling practices that was accepted in

the past but are now recognized as posing

serious environmental hazards—hazards

that will persist for many years to come. The

toxic chemical waste dump at the Love Canal

near Niagara Falls, N. Y., clearly illustrates

the threat. According to Environmental Protection Agency (EPA) estimates, there are

1,200 to 2,OOO of these abandoned chemical

and radioactive waste sites in the United

States that pose an imminent danger to human health and will cost as much as $50 billion to clean up. As long as these substances

remain in the environment, the potential for

food contamination exists.

Once an environmental contaminant is

found in food, limits are established to control

and restrict its presence. Such regulations

are set up and enforced by FDA for food

traded in interstate commerce, and by State

agencies for food produced and sold within a

State. In either case, the aim is to limit the

public’s exposure to a particular contaminant.

Key factors involved in such regulation are

time and information. After a contaminant is

identified. authorities must have information

on its toxicity, the amount present in the food,

and how much and what kinds of food are

contaminated. By monitoring the food supply

for the contaminant, regulators can determine the level and extent of the contamination. With this information and necessary

toxicity data, they can establish regulatory

limits for the contaminant in food.

However, this kind of information generally takes time to generate—usually longer

than the public is willing to wait in the event

of a food contamination incident. As a result,
authorities are often pressed to set regulatory limits before they have enough time to

develop information on the nature and extent

of the contamination.

This assessment has focused on two central problems: regulating environmental contaminants and identifying environmental contaminants. Following are major findings and

conclusions growing out of this assessment.

● FDA relies on action levels rather than tolerances to regulate environmental contaminants in food.

Under the Food, Drug, and Cosmetic Act,

FDA is given authority to set tolerances for

the amount of an unavoidable contaminant

permissible in food. However, the procedures

required to set a tolerance are complex, cumbersome, and time-consuming. Therefore,

FDA relies on action levels, informal judgments about the level of a food contaminant to

which consumers may safely be exposed.

Action levels are administrative guidelines

that can be developed and promulgated more

easily and quickly than tolerances. Action

levels are used when scientific data are incomplete. Public input is not required. They

are used when new information is likely to be

forthcoming that might alter the level. FDA is

under no constraints to review action levels

or to replace action levels with formal tolerances. FDA has sometimes lowered or raised

action levels as new data became available.

FDA is now in the process of lowering the

PCB tolerance.

● No policy exists defining the relative

weights to be given to the evidence when

setting an action level or tolerance.

In setting an action level or tolerance, FDA

takes into account short- and long-term toxicological data, available information on the

levels of the contaminant in food, the amount

of contaminated food consumed by various

population groups, the level that can be measured, and the potential impact of various action levels or tolerances on the national food

supply. Generally, the more information

about a particular factor, the greater its influence. Because the amount and quality of

information available when FDA encounters

an environmental food contamination problem are inevitably unpredictable, it does not

predetermine the weighting of various factors. However, FDA maintains that the public

health factor outweighs all others in its considerations.

The Food, Drug, and Cosmetic Act does not

specify the role that the costs of a regulatory

decision should play in setting a tolerance or

action level. The Act does require that FDA

take into account the extent to which a substance cannot be avoided in food production.

FDA interprets this requirement as justification for weighing the costs of food condemned

against the health benefits derived from a tolerance.

● To assess human risk from exposure to

chemicals, FDA and EPA rely on alreadyexisting animal studies and epidemiological evidence derived from previous human exposures,

When a new environmental contaminant is

discovered in food, regulatory agencies are

under intense pressure to act to protect the

public. FDA and EPA (if the contaminant is a

pesticide) review the available literature on

the contaminant and calculate an action level

based on that evidence. Rarely are new

studies commissioned—even when the data

are inadequate.

New human epidemiological studies and

conventional 2-year animal studies are of little immediate help because so much time is

required to generate results. However, toxicologists have developed a variety of tests

that can evaluate a substance’s possible toxic

effects in 90 days or less. Some of these shortterm tests measure the potential of a substance to produce mutations and possible

cancer,
Ch. I—Summary ● 7

Short-term tests could be used more widely

in screening environmental contaminants to

determine whether they are mutagens or potential carcinogens. Although the results of

such tests do not provide the data needed to

set an action level or tolerance, they still can

alert regulators to latent dangers that require further investigation.

Conventional 2-year animal studies (which

usually entail an additional year for data

analysis) would continue to serve an important role in the setting of tolerances. If data

from a carcinogen bioassay are available at

the time an environmental contaminant is discovered in food, the information can prove

crucial in reaching a regulatory decision. If

data were nonexistent or inadequate, a newly

commissioned carcinogen bioassay could be

used to revise an initial action level.

Epidemiological studies would remain useful for confirming suspected chronic effects

of a toxic substance to which a population

has unknowingly been exposed over a period

of time. They can also confirm retrospectively

or refute the adequacy of regulatory actions.

No currently available toxicological testing

methods or statistical interpretation techniques are adequate for evaluating the combined effects of low-level exposure to toxic

substances. Indeed, there are no satisfactory

techniques for testing the interactions of

more than two substances.

● Current monitoring at both Federal and

State levels is regulatory, designed to ensure that substances in food do not exceed

prescribed limits. Little effort is made to

detect and identify substances in the food

supply for which no action levels or tolerances exist.

Technology now exists that would make

possible a national investigatory monitoring

system to detect unregulated chemicals as

they enter the food chain. Such advanced

technology is available in some Federal regulatory monitoring laboratories and in a limited number of State labs. It is not routinely

employed in Federal or State regulatory monitoring.

The goal of food monitoring is to protect

consumers by determining short- and longterm trends in the levels of various chemicals

in food and the environment. Investigatory

monitoring could be designed to complement

already-existing regulatory monitoring. Each

of these approaches could be complemented

by specimen banking-the regular collection

and storage of samples that could be later

analyzed if a new contaminant is found in

food. EPA and the National Bureau of Standards are now working towards developing

such a specimen-banking program.

However, food sampling may not be the

best approach to investigatory monitoring. To

discover a substance as it enters the environment and before it gets into the human food

supply, it is necessary to monitor water, soil,

air, river sediments, and nonfood organisms.

● Management of food contamination incidents is hindered by the complexity of the

food system, the rapidity with which food

is moved through the system, and failures

by State and Federal agencies to coordinate their information-gathering activities.

Many food contamination incidents initially fall under State jurisdiction. Technically,

the Federal Government does not become involved unless requested by a State or until

contaminated food enters interstate commerce. This country’s food marketing system

is complex. Most food produced or processed

within a particular State is distributed for

consumption in other States. Thus, most environmental contamination incidents are likely

to become interstate problems. Figure 1 illustrates the extent of food contamination that

can occur from a single source of contamination, in this case PCB-contaminated animal

feed from a meatpacking plant in Billings,

Mont.

The number of State and Federal agencies

involved complicates the generation and dissemination of scientific information on the

51+-515 ~ - 79 _ 2

Ch. /—Summary ● 9

toxicological and chemical properties of the

contaminant, the amount and type of food

contaminated, and the concentration of the

substance in food. At least three Federal

agencies (EPA, FDA, and the U.S. Department

of Agriculture (USDA)), each with different

responsibilities, may provide technical assistance. At the State level, departments of

health, agriculture, and the environment may

share accountability for regulating environmental contaminants in food.

tential exists for breakdowns in communication. This was the case in the recent PCB contamination of animal feeds in 10 Western

States. The Idaho Department of Agriculture

did not inform the Idaho Department of

Health and Welfare of the PCB contamination. USDA would report the results of its investigations only to the Idaho Department of

Agriculture. EPA attempted to determine the

source of the PCBs by analyzing air and water samples, but failed to report its negative

In the absence of a clear authority to coor- results to the State.

dinate activities of various agencies, the poCONGRESSIONAL OPTIONS

There are four basic options for Congress

to consider regarding the Federal response to

the environmental contamination of food.

Each is discussed in greater detail in chapter

IX. Congress can:

1. Allow the present system to continue by

taking no action. The present system

consists of regulatory monitoring and

the establishment of action levels (and

occasionally tolerances) for environmental contaminants in food.

2. Amend the Food, Drug, and Cosmetic

Act to specifically address the unique

problems posed by environmental contamination of food.

3. Establish a national investigatory monitoring system.

4. Improve the Federal response to new

contamination problems by designating

a lead agency or establishing a center to

orchestrate the delivery of Federal assistance to affected States.

Option 1

Maintain the present System

Pros: There are two principal advantages

in maintaining this system. No additional appropriations or legislation are required. No

changes in existing regulations are necessary.

Cons: The time needed to identify an environmental contaminant in food and- take corrective action would not be shortened if the

current system were retained. Moreover, action levels and tolerances permit a certain

level of contaminant to be present in food. If

tolerances or action levels are not reduced,

little effort will be made to eliminate the contaminant. There is no requirement for review

of an action level once it is established. Thus,

FDA is under no pressure to actively seek out

new data to verify the appropriateness of an

existing action level. Finally, States have no

clearly defined authority to turn to when they

suspect environmental contamination of food.

Option 2

Amend the Food, Drug,

and Cosmetic Act

An amendment to the Food, Drug, and Cosmetic Act could contain one or more of the

following changes. Each change is discussed

in greater detail in chapter IX.

● Congress could amend the Food, Drug,

and Cosmetic Act to simplify the administrative procedure for setting tolerances. The change could be modeled

after section 553 of the Administrative

Procedures Act. This would encourage

FDA to move from action levels to toler-
●

●

●

ances, thus bringing more public participation into the process,

Congress could amend the Food, Drug,

and Cosmetic Act to require the establishment of a tolerance within a specified time after the setting of an action

level. This would encourage the FDA to

gather additional information on a contaminant’s toxicity and the public’s exposure. It would result in a definitive tolerance that FDA could enforce with less

concern over legal challenge.

Congress could clarify to what extent

economic criteria can be used in setting

tolerances for environmental contaminants in food,

FDA could be granted authority to set regional tolerances. This would provide

FDA with flexibility to set different

levels for different regions based on expected levels of exposure, regional levels

of contamination, and local eating patterns.

Pros: Since its passage in 1938, the Food,

Drug, and Cosmetic Act has been amended

several times to deal with new problems of

food regulation. Congress has never directly

addressed the environmental contamination

of food. There are several unique characteristics of this problem that could be clarified

through an amendment dealing specifically

with the environmental contamination of

food.

Cons: Even though the Food, Drug, and Cosmetic Act does not contain provisions on environmental contaminants, FDA has been able

to regulate them through interpretation of

sections 402 and 406.

Option 3

Establish an Investigatory

Monitoring System

Congress could establish a national investigatory monitoring system based on monitoring for either suspected or uncharacterized

environmental contaminants. Some chemicals are not regulated by action levels or tolerances but are suspected to be dangerous to

humans if consumed in food. Uncharacterized environmental contaminants are substances that may have entered the food sup

ply, but are not regulated or suspected food

contaminants. A system that combines elements of both approaches could also be set

up. Because any of these monitoring approaches would require some research and

development before going into full operation,

Congress could choose to establish a pilot program. Such a program would spur research

and development and assess the feasibility

and cost effectiveness of the various approaches.

Pros: Investigatory monitoring would increase the probability of detecting unregulated substances in food. Present food-monitoring efforts are not designed to detect

unregulated environmental contaminants in

food. The limited amount of investigatory

monitoring that does exist is primarily concerned with trace metals. To identify new

contaminants as they enter the food supply,

more of this type of monitoring is needed.

Cons: The costs of setting up an investigatory monitoring program could be large, and

there is no certainty that the sampling plan

would identify all environmental contaminants before they enter the food chain. Furthermore, investigatory monitoring relies on

sophisticated instrumentation that is generally not found in Federal or State monitoring

laboratories,

Option 4

improve Federai Response to

New Contamination Incidents

The Federal response to new contamination problems has been hampered by the multiplicity of agencies with regulatory or monitoring responsibilities for the environment

and for food. Congress could designate a lead

agency or establish a center to orchestrate

delivery of Federal assistance to affected

States.

Pros: With a clearly delineated agency or

center, States suspecting contamination of
Ch. /—Summary ● 11

food would have one reliable Federal source

for generating, evaluating, and disseminating

technical information. Response time might

be shortened, duplication of effort reduced,

and effective management of the incident enhanced.

Cons: Better coordination among FDA,

USDA, and EPA could accomplish the same

goals without the expense of establishing a

new research center. Historically, the major

impediment to timely Federal response to

chemical contamination of food was lack of

awareness that food contamination had taken

place. When contamination became apparent

and one or more Federal agencies were

alerted, response was rapid. Furthermore,

establishment of a lead agency or a new center would not ensure that information would

be generated more quickly than is now the

case.

* * *

Options 2 through 4 are not mutually exclusive. If Congress wishes to put greater emphasis on protecting consumers from contaminated food, one or more could be chosen. For

example, Congress could decide to simplify

the administrative procedures for setting

tolerances (Option 2), require the setting of a

tolerance at some specified time after an action level is set (Option 2), establish a pilot

program of investigatory monitoring for organic chemicals (Option 3), and designate

FDA the lead agency to deal with new contamination problems (Option 4).
Environmental Contamination

of Food
Chapter II

Environmental Contamination of Food

Maintaining an adequate, safe food supply has been a major goal of the Federal Government since 1906, when the first Federal food and drug law was signed

into law. Historically, chemicals such as salt, sugar, and wood smoke have been

used to preserve foods. Modern food technology relies extensively on the use of

chemicals not only for preservation but also to produce appealing colors, flavors,

aromas, and textures.

Most developed countries now have food laws designed to permit the use of

such chemicals in food under conditions judged to be safe. These chemicals are

not considered adulterants or contaminants and are classed as intentional additives. Other chemicals may enter food as a result of their use in food production,

handling, or processing. Such substances maybe legally permitted if they are unavoidable under good manufacturing practices and if the amounts involved are

considered safe. These chemicals are classed as incidental additives. The presence of both these classes of chemicals in food is controlled by regulation.

Environmental contaminants include substances from natural sources or from industry and agriculture. Many of the naturally occurring contaminants in food are of microbiological origin and consist of harmful bacteria,

bacterial toxins, and fungal toxins. (Aflatoxin, a contaminant of peanuts and grains, is an

example of a fungal toxin or mycotoxin. ) The

second category of environmental contaminants includes organic chemicals, metals and

their complexes, and radionuclides. Only

those environmental contaminants introduced into food as a result of human activities

such as agriculture, mining, and industry are

considered in this assessment.

The environmental contamination of food is

a result of our modern, high-technology society. We produce and consume large volumes

of a wide variety of substances, some of

which are toxic. It is estimated that 70,000

chemicals may currently be in commercial

production in the United States and that 50 of

these chemicals are manufactured in quantities greater than 1.3 billion lbs per year.

Seven percent of this country’s gross national

product (GNP), $113 billion per year, is generated by the manufacture and distribution of

chemicals (l). During the production, use, and

disposal of these substances, there are opportunities for losses into the environment. For

example, the Environmental Protection Agency (EPA) estimates that there are more than

30,000 chemical and radioactive waste disposal sites. Of these, 1,200 to 2,000 are considered threats to human health (2).

Environmental contamination of food takes

two forms: long-term, low-level contamination

resulting from gradual diffusion of persistent

chemicals through the environment, and relatively shorter term, higher level contamination stemming from industrial accidents and

waste disposal.

An example of low-level contamination is

polychlorinated biphenyls (PCBs). This group

of substances was widely used in transformers and capacitors, as heat-transfer fluids,

and as an additive in dyes, carbon paper, pesticides, and plastics (3). Although production

was halted in 1977, PCBs remain an ubiquitous, low-level contaminant of many foods, especially freshwater fish.

An example of the second type of contamination is polybrominated biphenyls (PBBs) in

15
16 . Environmental Contaminants in Food

dairy products and meat. PBBs, a fire retard- level contaminant in Michigan because they

ant, were accidentally mixed into animal are very stable and resistant to decay. Anifeed. Dairy cattle that were fed the contami- mals raised on farms affected by the original

nated feed produced contaminated milk. The feed contamination are now contaminated by

distinctions between the two types of food the PBB residues remaining in the pastures

contamination are not exclusive. For exam- and farm buildings.

pie, PBBs have now become a long-term, lowHOW FOOD BECOMES CONTAMINATED

gated railroad cars, trucks, ships, or storage

buildings used for transport or storage of

human food and animal feed are also sources

of environmental contamination. The interiors are sprayed or fumigated with pesticides,

and if not sufficiently aired, contamination of

the food or feed occurs.

The manufacture of organic chemicals produces sludges, gases, and liquid effluents of

varying chemical complexities. The usual

waste disposal methods (sewage systems, incineration, landfill) are unable to prevent organic residues from entering the environment

in spite of Federal laws and corresponding

regulations governing disposal. The routes include the atmosphere, soil, and surface or

ground water.

Chemicals contaminate foods through different routes depending on the chemical and

its physical properties, its use, and the source

or mechanism of contamination.

Organic substances that have contaminated food have been either industrial or

agricultural chemicals. Pesticides are the

only agricultural chemicals known to be environmental contaminants in food (see tables

1-3). A pesticide becomes an environmental

contaminant when it is present in foods for

which the application or use of the substance

has not been approved. Livestock, poultry,

and fish can be contaminated when application or manufacturing of pesticides occurs in

the vicinity or when residues are transported

through the environment. Improperly fumii

1

,

Table 1.— Reported Incidents of Food Contamination, 1968-78, by State and Class of Contaminant

Stat e Pesticide Mercury PCB PBB Other Total

New York . . . . . . . • ., .

Idaho. . . . . . . . . . . .

South Carolina. . . . . . . . . . . . .

Minnesota . . . . . . . . . . . . . . .

Louisiana . . . . . . . . . . . . . .

Colorado. . . . . . . . . . . . . . .

Georgia. . . . . . . . . . . .

Maryland. . . . . . . . .

Texas . . . . . . . . . . . . . . .

New Jersey. . . . . . . . . . . . . . . .

1

1

1

2

—

1

5

1

1 — — 3

3

1

1

17

2

15

3

1

4

—

1-biphenyl —

8

1

15

—

4 —

—

— — —

1 2-petroleum

1

1

— —

— —

2 1-ß-methoxy napthalene

and tetraline

—

Kansas . . .

Missouri . . . . . . . . . . . . . . . .

New Mexico. . .

Alaska. . . . . . . . . . .

California .

Indiana .,

— (I)*

—

1—

3

—

— (l)*

4

(:)*

4

9

—

4 —

—

— —

— — —

(l)*

1 — — —

— — —

3 well-documented 1 — —

5 other incidents

13

1

Michigan .

Virginia, ., .. .

1

—

19

2

—

1 — 17 — — 1

Totals ... . . . 56 1 4 88

“Several conservatively estimated as one

SOURCE Of fLce of Technology Assessment

8
Ch. //— Environmental Contamination of Food ● 17

Table 2.— Reported Incidents of Food Contamination, 1968-78, by State and Food

Fruit/ Game/meat/

State Dairy Eggs Vegetable Fish/shellfish Grain poultry

3

1 —

1

9—

—

3

1

2—

—

—

2

—

4—

1

27

—

—

1 —

1—

—

—

—

—

1—

—

—

—

—

—

3

—

1

—

—

—

1

1

1

4

8

Table 3.— Number of Incidents of Environmental Contaminants of Food Reported by Federal Agencies, 1968-78

Agency Pesticides Mercury PCB’s Other Food affected

USDA/FSQS 39 — — — Chickens, turkeys. ducks. cattle, swine, lambs

— 1 — — Swine

— — 6 — Poultry

— — — 1 (Phenol) Cattle

FDA .. . 21 — — —

— 84 — —

— — 3 —

Total. . . . 60 85 9 1

SOURCE Off Ice of Technology Assessment

Metals can be released into the environment in several ways. The mining and refining processes produce dust and gases which

enter the atmosphere. Metallic salts formed

during recovery and refining processes can

escape as waste products into surface and

ground water. Sewage sludge used as fertilizer on agricultural land also poses a potential

food contamination problem. Trace metals

present in the sludge can be taken up by

crops grown on treated soil. Cadmium is the

trace metal in sludge that currently generates the greatest concern.

Radioactivity in food stems from three

sources: natural radioactivity. releases from

Fish. cheese, pasta

Fish

Fish, eggs, bakery products

operation of nuclear reactors and processing

plants, and fallout from nuclear weapons

tests. The primary route by which food becomes contaminated is the deposition of airborne material on vegetation or soil. The subsequent fate of the radionuclide is determined by its chemical and physical nature

and whether it is absorbed and metabolized

by plants or animals. Natural radioactivity

may become a concern when ores containing

radioactive substances are mined and processed. The products or wastes may concentrate the radionuclides. Examples of this are

uranium tailings, phosphate rock waste, or

slags from phosphorus production. Radium

may enter the food chain when it dissolves in
18 . Environmental Contaminants in Food

ground water and is taken up through plant

roots.

Nuclear reactors normally release radioactive noble gases that do not contaminate

foods. Reactors do contain large inventories

of fission products, transuranics, and other

activation products. Accidental releases can

contaminate vegetation by deposition of particles on leaves and soil, or through water. Gaseous releases would most likely involve the

volatile elements such as iodine and tritium,

or those with volatile precursors, such as

strontium-90 and cesium-137. Aqueous releases would follow failure of the onsite ion

exchange cleanup system. Any of the watersoluble elements could be involved. Table 4

summarizes the radionuclide contaminants of

significance for foods.

Nuclear waste-processing plants could

also have either gaseous or aqueous releases.

In this case, the fission products are aged

before processing, and iodine and the gaseous precursor radionuclides are not released. Tritium and carbon-14 are the major

airborne products, while the waterborne radionuclides are the same as for reactors.

Atmospheric nuclear weapons tests distribute their fission products globally. Local

deposition depends on the size of the weapon

and the conditions of firing (high altitude, surface, or underground).

Table 4.— Radionuclide Contaminants of Significance for Foods

Normally present in small amounts, Significant only when

enhanced

Normally present in small amounts

Member of uranium series. Normally present, metabolized

somewhat Iike calcium

As radium-226, only a member of thorium series

Members of uranium series

Normally present

Product of nuclear reactions

Product of 24’ Pu decay

Low energy, usually in form of water or organic

compounds

Low energy, usually in form of organic compounds

Short half-life, so important only for fresh foods, e.g., milk

and leafy vegetables

Follows calcium somewhat in metabolism

Follows potassium somewhat in metabolism

Most important are isotopes of zirconium, cerium, barium,

rubidium, rhodium. Mostly surface contaminants

Follow stable elements in metabolism
Ch. //— Environmental Contain/nation of Food ● 19

MAGNITUDE OF THE PROBLEM

There is little information available on the

number of food contamination incidents, the

amount and costs of food lost through regulatory actions, or the effects of consumption of

contaminated food on health. To obtain information on the extent of the problem, OTA reviewed the literature and sought information

from the States and Federal agencies.

Evidence of Human Illness

Resulting From Consumption of

Contaminated Food

In evaluating the significance of environmental contaminants in food the key question

is whether consumption of contaminated

foods poses a health risk. Measurable health

effects depend on the toxicity of the substance, the level at which it is present in food,

the quantity of food consumed, and the vulnerability of the individual or population. In

Japan, foods contaminated with substances

such as PCBs, mercury, and cadmium have

produced human illness and death. No such

mass poisonings have occurred in the United

States. However, in cases such as PBBs

where a large populace has been exposed,

some physiological changes have been noted.

But no conclusions can as yet be drawn on the

ultimate health effects.

It is known from limited surveys that the

U.S. population is exposed to a wide variety

of chemical contaminants through food, air,

and water. The long-term health effects and

the implications of possible interactions

among these residues are unknown. A recent

literature review of over 600 published

studies (4) found that nonoccupationally exposed U.S. residents carry measurable residues of 94 chemical contaminants. Twentysix of these are organic substances, including

twenty pesticides and pesticide metabolizes.

The remainder are inorganic substances.

Americans also have been exposed to low

levels of PCBs, PBBs, mercury, and ionizing

radiation through their food. The following

sections briefly summarize current knowledge and the extent of uncertainties on the

health effects of these environmental contaminants.

Polychlorinated Biphenyls

PCBs occur in food as the result of environmental contamination leading to accumulation in the food chain, direct contact with

food or animal feeds, or contact with foodpackaging materials made from recycled paper containing PCBs (5). Several comprehensive literature reviews have been published

in the last 5 years detailing the acute and

chronic toxic effects of PCBs in animals and

humans (5-1 1).

Human illness has been caused by exposures to PCBs at much higher levels than

those that occur in the United States. In the

early part of 1968 the accidental contamination of edible rice-bran oil led to a poisoning

epidemic among the Japanese families who

consumed the oil. The disease became known

as Yusho or rice-oil disease. Its chief symptoms were chloracne (a severe form of acne)

and eye discharge; other symptoms included

skin discoloration, headaches, fatigue, abdominal pain, menstrual changes, and liver

disturbances. Babies born to mothers who

consumed the rice oil were abnormally small

and had temporary skin discoloration. The

first symptoms of Yusho disease were registered on June 7, 1968, and 1,291 cases had

been reported as of May 1975 (9).

Since the rice oil was also contaminated

with polychlorinated dibenzofuran (PCDF), it

is difficult to determine from the Yusho data

exactly what effect(s) exposure to PCBs alone

could have on humans. It has been calculated

that the PCDF made the rice oil 2 to 3.5 times

more toxic than would have been expected

from its PCB content alone (1 1). Careful records of the 1,291 Yusho patients have been

kept to determine possible long-term effects.

At least 9 of 29 deaths that occurred as of

May 1975 were attributed to cancer (malignant neoplasm), but a causal relationship be-
20 ● Environmental Contaminants in Food

tween PCBs and cancer cannot necessarily

be inferred because of the high concentration

of PCDF in the oil. The Yusho study, nevertheless, had two important results: first, the information established that PCBs can be transferred from mother to fetus and from mother

to child through breast feeding, and second

highly chlorinated PCB compounds are excreted more slowly from the body than less

chlorinated ones (9).

More recent experiments in animals have

demonstrated a variety of toxic effects.

Cancers have been produced in mice and rats

fed PCBs (6, 12). Monkeys fed levels of PCBs

equivalent to the amounts consumed by Yusho patients developed similar reproductive

disorders (13-16). Young monkeys nursing on

mothers consuming feed containing PCB developed toxic effects and behavioral abnormalities (15-1 7)0

Polybrominated Biphenyls

Practically every Michigan resident has

been exposed to PBB-contaminated food products. It is estimated that some 2,000 farm

families who consumed products from their

own PBB-contaminated farms have received

the heaviest exposure (18).

Fries (19) studied the kinetics of PBB absorption in dairy cattle and its elimination in

milk, If intake of contaminated milk alone is

considered, those Michigan residents most

severely exposed consumed from 5 to 15

grams of PBB over the initial 230 days of the

exposure. Those residents that coincidentally

consumed contaminated meat and/or eggs

may have received higher total doses of PBB,

but the number of such cases is probably

small,

Geographically the residents of the lower

peninsula, where the original accident occurred, were found to have the greatest levels

of exposure. In 1976, the Michigan Department of Public Health conducted a study on

PBB concentrations in breast milk. It was

found that 96 percent of the 53 women

selected from the lower peninsula and 43 percent of the 42 women selected from the upper

peninsula excreted PBB in their breast milk

(20).

Low concentrations of PBBs also have been

detected in animal feed in Indiana and Illinois. Unconfirmed surveys of food throughout

the country found extremely low levels below

the Food and Drug Administration (FDA) action level in the following States (21):

State Food

Alabama. ., . . . . . . . . . . . Chicken

Indiana. . . . . . . . . . . . . . . Turkey

Iowa , ... , . . . . . . . . . . . . Beef

Mississippi. . . . . . . . . . . . Chicken

New York . . . . . ... , . . . . Chicken

Texas . . . . . . . . . . . . . . . . Chicken

Wisconsin . . . . . . . . . . . . Duck

Wolff, et al. (22) reported that serum PBB

was higher for males than females. It was

suggested that the greater proportional body

fat in women may account for this difference,

but exposure may also be important. Males

may consume more contaminated food or

have more direct contact with PBB than

females.

The same study found no consistent trends

with respect to age. It was observed, however, that young males had greater concentrations of serum PBB than young females.

Young females had greater concentrations

than older males, and older males had

greater concentrations than older females. It

was also found that very young children and

individuals who had lived on farms less than

1 year had lower serum PBB levels than other

groups (22)0

Serum PBB concentration is related to the

intensity of exposure. Most studies indicate

that consumers and residents of nonquarantined farms had significantly lower PBB levels than residents of quarantined farms; however, families on quarantined farms stopped

consuming meat and milk from their own animals (20)0

In late 1974, the Michigan Department of

Public Health conducted a survey to determine if any adverse effects could be correlated with PBB levels in the body, A sample of

165 exposed persons (quarantined farms)
Ch. Il—Environmental Contamination of Food ● 21

and 133 nonexposed (nonquarantined farms)

was studied. Medical history interviews and

physical examinations were performed on

each subject and blood specimens were

taken, Blood PBB levels as high as 2.26 parts

per million (ppm) were found in the exposed

individuals; about half exhibited levels

greater than 0.02 ppm. Of the nonexposed individuals, only two showed blood PBB levels

greater than 0.02 ppm; 70 percent of the

adults and 97 percent of the children exhibited levels of 0.0002 to 0.019 ppm. Comparison of a list of selected conditions and complaints revealed no significant differences in

the frequency of illness between the two

groups. Physical examinations and clinical

laboratory tests disclosed no effects attributable to “chronic” PBB exposure (24).

The effect of PBB exposure on white blood

cell (lymphocyte) function of Michigan dairy

farmers who consumed contaminated farm

products was examined by Bekesi, et al. (25).

Forty-five members of Michigan farm families who had eaten PBB-contaminated food

for periods of 3 months up to 4 years after the

original accident were compared for immunological function to 46 Wisconsin farmers and

79 New York residents. All of the exposed individuals showed reduced lymphocyte function, and 40 percent showed abnormal production of lymphocytes. There were also significant increases in lymphocytes with no detectable surface markers (“null” cells). However, the short- and long-term health implications of these differences are not now known.

Lillis (20) examined Michigan farmers and

consumers of dairy products and found that

the effect of PBB on humans was mainly neurological in nature. He found marked fatigue,

hypersomnia, and decreased capacity for

physical or mental work. Other symptoms included headache: dizziness: irritability; and

swelling of the joints with deformity, pain,

and limitation of movement. Less severe gastrointestinal and dermatological complaints

were also encountered.

Mercury and Methylmercury

Foods are the major source of human exposure to mercury. The mercury concentration

in food is dependent on the type of food, the

environmental level of mercury in the area

where the food is produced, and the use of

mercury-containing compounds in the agricultural and industrial production of the food.

All living organisms have the ability to concentrate mercury, Therefore, all animal and

vegetable tissues contain at least trace

amounts (26). Several recent reviews have examined the health effects associated with

consumption of mercury (26-28). The results

of these reviews indicate that the effects of

methylmercury poisoning become detectable

in the most sensitive adults at blood levels of

mercury of 20 to 50 μg/100 ml, hair levels

from 50 to 120 mg/kg, and body burdens between 0.5 and 0.8 mg/kg body weight (26).

Since the Minamata Bay tragedy in Japan,

the effects of chronic exposure to methylmercury have been well-documented. Mercury

readily accumulates within the central nervous system (29-3 1), and clearance of mercury

back into the bloodstream is slow (32). Consequently, the central nervous system is considered to be the critical target in chronic mercury exposure. The clinical symptoms of central nervous system involvement include

headache, vertigo, vasomotor disturbance,

ataxia, and pain and numbness in the extremities (30). The most prominent structural

changes of the central nervous system resulting from chronic mercury exposure are diffuse cellular degeneration (30).

In evaluating the teratogenic hazards of

mercury exposure to man, the placental

transfer of mercury is particularly significant. Levels that are not toxic to pregnant

women are sufficient to produce birth defects

in their offspring (33-35). Transfer of methylmercury across the human placenta results

in slightly higher blood levels in the infant at

birth than in the mother (36). Table 5 compares fetal and maternal blood concentra-
22 ● Environmental Contaminants in Food

Table 5. — Methylmercury Concentrations in

Normally Exposed Populations —

Concentration (μg Hg/g)

Location Maternal blood Placenta Fetal blood

Japan ...- – ‘

- 0.017 0.072 0.020

Sweden . . . . . . 0.006 — 0.008

Tennessee. . . 0.009 0.021 0.011

lowa. . . . . 0.001 0.002 0.001

SOURCE Adapted from B J Koos and L D Longo ” Mercury To; IcIty In the

Pregnant W’oman, Fetus, and Newborn Infant “ A rner(can ,/ourrra/ of

Obstetrms and Gynecology 126(3) 390, 1976

tions in normally exposed populations in

Japan, Sweden, and the United States,

In humans, the most widely reported fetal

risk associated with maternal exposure to

mercury is brain damage. The placental

transfer of mercury and its effects on the

human fetus were first recognized in the

1950’s with the well-known outbreak of congenital Minamata disease in the towns of

Minamata and Niigata, Japan. By 1959, 23 infants suffering from mental retardation and

motor disturbances had been born to mothers

exposed to methylmercury during their pregnancies. The clinical symptoms of the infants

resembled those of severe cerebral palsy or

cerebral dysfunction syndrome. They included disturbance of coordination, speech,

and hearing; constriction of visual field; impairment of chewing and swallowing; enhanced tendon reflex; pathological reflexes;

involuntary movement; primitive reflexes; superficial sensation; salivation; and forced

laughing (30). Only 1 of the 23 mothers exhibited any symptoms of mercury poisoning (32).

Radioactivity

Ionizing radiation (X-rays, gamma rays, or

beta particles with sufficient energy to strip

electrons from molecules and produce ions)

can produce birth defects, mutations, and

cancers (37). These adverse health effects

are usually associated with high dose levels

delivered at high dose rates.

Such a combination is not ordinarily encountered in food. Previous radioactive contamination of foods has involved relatively

small quantities of radioactive elements

which have delivered low dose rates (38).

In these situations, the effects of the radiation exposure on health are extremely difficult to evaluate. High dose rates (100 million

to 1 billion times background) are estimated

to produce 2,600 ionization events per second

in cells. Background radiation levels are estimated to produce less than one ionization in

the cell nucleus per day (37). Because cells

have the capacity to repair damage to their

genetic material, repair of ionization damage

may occur at low radiation exposure. Higher

exposures may overwhelm the cells’ repair

capacity. Whether any effects are observed

in such cases depends on several factors.

These include the dose delivered to the tissues, the nature of the emissions, and the metabolism of the cell. The following examples

illustrate these points:

Strontium-90 in food arouses most concern not only because of its long half-life

but also because it behaves in the body

in a manner somewhat similar to calcium. The replacement of bone calcium

with strontium-go exposes tissues and

cells covering the bone to radiation, In

addition, bone marrow is subject to the

ionizing radiation from the strontium-go.

Thus, cancer of the bone-forming and

bone-covering tissue as well as leukemias of the bone marrow blood-forming

cells can possibly result.

Iodine is concentrated by the thyroid

gland. Radioiodines produced in atmospheric nuclear detonations or released

from nuclear power stations are also

taken up and concentrated by the thyroid, increasing the risk of thyroid

cancer.

Tritium, or radioactive hydrogen, combines chemically with oxygen to form

water. Tritium derived from food would

be widely distributed throughout the

body exposing all tissues to radiation.

The uncertainties surrounding the repair

capacities of cells and the irreversible nature

of the possible health effects have led to the

adoption in the United States of a prudent

policy toward low-level ionizing radiation.

Since any amount of radiation is potentially

harmful, unnecessary exposure should be

avoided.
Ch. //—Environmental Contamination 01 Food ● 23

Number of Food Contamination

Incidents

Questionnaires were mailed to the commissioners of health in each of the 50 States and

the District of Columbia as well as to Federal

agencies. For the 10-year period 1968-78,

each was asked to report on the number of incidents of environmental contamination of

food that resulted in regulatory action. This

survey has limitations. Some States did not

answer all questions. The questions were

subject to interpretation and misunderstanding. The accuracy and completeness of the

answers were dependent on the respondent.

The results presented are therefore preliminary and do not necessarily represent complete and comprehensive information on all

States responding. Nonetheless, these data

are the first to be developed on the extent of

environmental contamination of food.

Responses were received from 32 States.

Seven of the top ten agricultural States and

six of the top ten manufacturing States responded to the questionnaire, The agricultural States in the top 10 were California, Texas,

Minnesota, Nebraska, Kansas, Indiana, and

Missouri. The manufacturing States in the

top 10 were California, New York, Michigan,

New Jersey, Texas, and Indiana. Three of

these States—California, Texas, and Indiana—are in the top ten for both agricultural

and manufacturing production. A fairly representative distribution of States responded

from each region of the United States (figure

2).

In the following discussions, an incident is

defined as a case in which a Federal or State

agency has taken regulatory action against

contaminated food, The Michigan PBB episode is reported as one incident because the

contamination stemmed from one source and

was limited to one State. Mercury contamination is reported as separate incidents because the sources differed (environmental

mercury v. industrial waste), the States involved are widely separated, and regulatory

actions were taken at different times, Eighteen States reported at least one environmental contaminant incident since 1968 for a

total of 88 incidents. All food categories were

involved and a variety of substances were implicated (see tables 1-3).

The data provided by States are complemented by the Federal responses. The two

Federal agencies responsible for regulating

the Nation’s food supply reported the number

of environmental contamination incidents

that they had identified since 1968. FDA had

108 reported incidents, and the Food Safety

and Quality Service of the U.S. Department of

Agriculture (USDA) had 47 reported incidents (see table 3). The combined Federal and

State total number of incidents comes to 243.

Neither State nor Federal responses indicated any significant radionuclide contamination episodes during the 1968-78 period.

Extensive Government programs for monitoring radionuclides in food exist. Thus far, radionuclide contamination of food has not been

found to exceed the exposure limits recommended in the Federal Radiation Council Protective Action Guides. In most cases, the

amount of food contamination in the continental United States has never even approached these limits (39), While atmospheric

nuclear testing is less a threat today than

before the signing of the 1963 Test Ban Treaty, radionuclide contamination of food is still

a concern of both Federal and State governments.

The number of food contamination incidents reported to OTA does not represent the

total number that has occurred in the United

States, only those in which the Federal Government and 18 State governments have taken regulatory action. Many incidents never

come to the attention of State or Federal

authorities. This is because local government

officials can and do handle environmental

contaminant incidents by warning offenders

or by condemning contaminated products

without informing the appropriate State officials. Also, the farmer whose livestock or

poultry has been environmentally contaminated may negotiate directly with the firm responsible for the contamination for financial
24 . Environmental Contaminants in Food

u)
Ch. //— Environmental Contamination of Food ● 25

reimbursement without reporting the contamination to Federal or State officials (40).

Economic Impact

The economic impact of an incident involving the environmental contamination of food

includes the cost of condemned food, health

costs, and the corresponding distributional

effects and costs. The magnitude of the economic impact is determined by:

the amount of food contaminated,

the concentration of the contaminant in

food,

the chemical and toxicological characteristics of the contaminant, and

the corresponding regulatory action

taken on the contaminated food.

The initial regulatory action taken by Federal and State authorities may be the issuance of a warning or the establishment of

either an action level or a tolerance. A more

detailed discussion of this regulatory action is

presented in chapter III. Action levels and tolerances establish a permissible level for the

contaminant in food. Any food found to contain concentrations of the substances above

this level is condemned and either destroyed

or restricted from being marketed.

Costs of Food Condemned

In addition to the four factors listed above,

the cost of condemned food is also affected by

its position in the food production and marketing process at the time of condemnation,

An action level or tolerance for a contaminant is the most important of the five factors.

If no action level or tolerance is set, no food

would be condemned and thus there would be

no costs incurred. The impact of such a regulation will depend on the exact level of a

substance that is allowed to be present in

food,

The chemical properties of a contaminant

are also important because of the potential

for long-term effects on the amount of food affected. Since many contaminants biologically

and chemically degrade slowly, their presence in the environment can mean food contamination above the action level or tolerance

for many years after the source of the pollution has been stopped. The James River in Virginia, for example, is still closed to commercial fishing several years after kepone discharges into the river have been eliminated.

The relative influence for each of these factors on the final cost will vary in each contamination incident.

Estimates of the cost of food condemned

through regulatory action are most often expressed in dollars. Consequently, this cost is

usually (and incorrectly) cited as representative of the total economic impact. Such costs

were collected in OTA’s State and Federal

surveys. The data, however, only partially reflect the total economic impact for environmental contamination of food in the United

States. This is because the cost of condemned

food is only one component of the total economic impact of an incident. In addition, few

of the incidents reported to OTA included

data on the cost of food condemned. OTA estimates from the available data that the total

cost of condemned food as a result of environmental contamination in the United States

since 1968 is over $282 million (table 6). T he

only cost estimates used were those clearly

stated for an incident by the reporting States

or Federal agencies.

State Estimates. —Of the 18 States reporting contamination incidents, only 6 provided

data on the economic impact in dollar terms.

Of those six, Michigan represents 99 percent

of the total cost ($255 million) while reporting

only 19 percent of the number of incidents in

the 18 States. Indeed, Michigan accounts for

90 percent of the total costs reported in the

United States while reporting only 7 percent

of the incidents that occurred during the

1968-78 period. It must be recognized, however, that 84 percent of Michigan’s costs are

attributed to the PBB incident. Many incidents reported by State and Federal agencies

are considerably smaller than the PBB episode. Thus, the PBB episode is an indication

of how severe a contamination incident can

be.
26 . Environmental Contaminants in Food

Table 6.—Economic Impact of Food Contamination

—————— ————— —

Reported incidents Total estimated cost ($)

State

Idaho. . . Dieldrin

PCP

Colorado. . . . Dieldrin

Maryland,

Texas. . .

Indiana .

Michigan.

Federal

Mercury

Mercury

Mercury

Dieldrin

Dieldrin

Mercury

PCB

PCNB

PBB

Picloram

Chlordane

DDT

Toxaphene

Parathion

Diazinon

Pentachlorophenol

PCB

Dieldrin

USDA/FSQS Pesticides

Mercury

PCB

Phenol

$ 100,000

3,000

100

3,700

23,000

85,000

25,027

250,000

10,000,000

30,000,000

100,000

215,000,000

12,000

2,500

2,000

2,000

328

13,700

28,468

150,000

12,500

$255,813,323--

18,900,000

63,000

7,450,000

— 

350 ——

26,413,350

Total United States ... . . . . . . . . . .

SOURCE Off Ice of Tec;n810gy Assessment

$282,226,673

Some States reported the amount of food

destroyed without estimating the cost. Kentucky, for example, reported the destruction

of 400,000 lbs of milk since 1968 because of

pesticide contamination. While such information can be converted into dollars, data on

market position and price of product at time

of confiscation are not readily available.

Many States were unable to provide any estimates on either the cost or the amount of food

condemned as a result of reported contamination incidents. New York (with PCBs) and

Virginia (with kepone) are two States that

could not provide cost estimates for food condemned as a result of environmental contamination. Virginia, however, has initiated a

study to determine the economic impact of the

kepone incident.

Federal Estimates.—Of the two Federal

agencies reporting information to OTA on environmental contaminant incidents, USDA’s

Food Safety and Quality Service (FSQS) reported food condemnation cost estimates.

These estimates, however, only cover livestock and poultry—the food products over

which FSQS has regulatory authority. FDA,

which has regulatory authority over the remaining food commodities, did not estimate

costs for reported environmental contamination incidents (70 percent of the Federal

total). Thus, a significant proportion of the

total costs for environmental contamination

incidents requiring Federal action is unknown. Comparison of the two agency responses with the State responses reveals little duplication in the reporting of incidents.

FSQS cost estimates were determined by

the number of animals or pounds destroyed

multiplied by the market value at the time of

confiscation. Since most of these animals

were taken at the farm or wholesale level, the

market value was the farm or wholesale

price. Most of the losses resulting from FDA

actions would be based on a wholesale or retail price because the seized products had advanced further in the marketing system.

Therefore, their estimated costs would be

greater than if they were seized at the production level (generally the case with FSQS

seizures).

Summing up, the available data on the cost

of condemned food is limited; consequently

OTA’s $282 million condemned-food estimate

is likely to be a gross underestimation of the

actual costs. The true cost would be impossible to estimate from this limited sample.

Health Costs

Health costs are also an important component of economic impact. These costs are incurred by the consumer whose health has or

potentially can be affected adversely by a

contaminant present in food. These adverse

effects can cause illness and death, and the

range of effects will vary depending on the

toxicity of the contaminant, the concentration

of the contaminant in food, and the amount of

food consumed.
Ch II—Environmental Contamination of Food s 27

In this country, the concentration of contaminants has been at levels that have not

produced immediate measurable and conclusive effects in exposed populations. Estimates

are therefore made for the potential longterm effects on exposed populations from

various contaminants in food.

Health costs can be estimated from such

projected health effects. Costs would include

health care costs for treating illness and

burial expenses associated with death. Additional costs would include estimated value of

productive days or years lost from work due

to the projected illness or death associated

with the contaminant in food. All of these

health-related costs, however, do not and

cannot include the emotional and psychological impacts on those afflicted and their

friends and families.

Health costs are not available for previous U.S. food contamination incidents. Approaches and techniques for estimating

health costs are discussed in chapter VI.

Distributional Effects and Costs

Distributional effects and costs involve the

various people, groups, and organizations

who are economically affected by an environmental contamination incident. Information

on the extent and distribution of such effects

and costs provides a clearer picture of the

total economic impact on society. This information is usually couched in descriptive

terms. Those who are economically affected

are identified but the extent of the impact is

seldom estimated in dollars. The exact distribution of costs from an incident through society is affected by the same five factors that

influence the cost of condemned food.

Many of the distributional effects and

costs for various types of environmental contaminant incidents are discussed in the following sections. The purpose of this discussion is not to identify all the distributional

costs but rather to demonstrate the variety of

effects and costs that can result from an incident.

Producers.— Food producers are affected

economically in different ways by contamination episodes. But all are affected directly

when the food they produce is condemned.

For example, food found contaminated at the

farm level is confiscated and destroyed. This

was the case for over 500 Michigan farmers

whose dairy herds were partially or entirely

destroyed (41). In such cases, farmers either

replace their livestock, plant a new crop, or

go out of business.

Farmers can be faced with severe economic hardship, since they are not always reimbursed financially for the animals or commodities confiscated. While insurance programs such as the Federal Crop Insurance

Corporation are available to cover natural

hazards which might destroy crops or livestock, such Federal assistance is not available to farmers for losses from environmental

contamination. An injured farmer can obtain

a loan at commercial rates or sue the responsible firm for compensation. But the loan and

the interest add to a farmer’s financial difficulties, and suing for compensation can take

time that the farmer may not have.

The commercial fisher is faced with a different situation. If a river, lake, or species of

fish is restricted because of environmental

contamination, the fisher whose source of income depends on this species or waterway

may have few employment alternatives. The

alternatives depend to some degree on the extent of the contamination. If the only waterway available in a section of a State or a

whole State is closed to commercial fishing

because of the contamination, the fisher’s

source of employment is eliminated until the

restriction is ended. Since the restriction can

last for years (depending on the chemical stability of the contaminant), the fisher either

will have to move to other commercial fishing

areas or seek other employment.

Food producers economically affected by

the condemnation of contaminated food are

likely to incur health costs. This is because

many of the producers and their families regularly eat the food that they produce or har-
28 . Environmental Contaminants in Food

vest. Consequently they are exposed to the

contaminated food at greater concentrations

than the average consumer. This was the

case for several farm families in Michigan.

Firms Held Accountable for Environmental Contamination.—In most instances blame

for a contamination incident can be established. Those accountable are subject to fines

and lawsuits. Firms admitting responsibility

often try to settle with producers out of court

if possible. Most of the compensation is for

the economic damages stemming from the destruction of food or loss of employment. Compensation for people whose health has been

impaired as a result of eating contaminated

food would be sought through civil litigation.

Such litigation, however, is rare in this country, since the level of contamination in food is

so low that demonstrating the necessary

cause and effect is difficult.

Fines or compensation paid by the firms

held accountable for the contamination are,

in fact, poor indicators of the true costs incurred by the producers. This is because the

settlement costs which are frequently negotiated or imposed bear little relationship to the

actual costs incurred.

For example, compensation has been provided by Michigan Chemical Corporation and

Farm Bureau Services, Inc., to many of the

farmers whose livestock and poultry were destroyed following PBB contamination. Michigan Chemical and Farm Bureau Services

have together paid more than $40 million in

compensation from a jointly established insurance pool (42). In another case involving

PCB-contaminated fish meal sold to poultry

producers, Ralston Purina Company negotiated compensation for the 400,000 chickens

destroyed. The cost of the compensation has

not been disclosed (43).

Governments.— Federal, State, and local

governments also incur costs from an environmental contamination incident. Although

the Federal Government and most State governments have agencies with programs to

regulate or control food safety problems,

these programs usually are not funded to

handle the kind of long-term problems created by a PBB or kepone incident. The Michigan Department of Agriculture, for example,

estimates it will spend $40 million to $60 million within the next 5 years to monitor and

test for PBBs in animals and animal byproducts (44). This is money that could have been

saved or spent for other programs if PBB contamination had not occurred. In order to recover its expenses from the PBB incident, the

State of Michigan filed a lawsuit against both

the Michigan Chemical Corporation and

Farm Bureau Services, Inc., claiming more

than $100 million in damage (45).

Federal involvement is limited unless the

contaminated food is part of interstate commerce, Many of these incidents are not considered by the Federal Government to involve

interstate commerce, FDA may provide technical assistance at the request of the State

government when a contamination incident is

regarded to be a local problem (43). These

technical facilities and experts are available

to all States through the Federal and regional

offices. Additional expenditures by the Federal Government for contamination incidents

are limited. Additional State expenditures,

however, can be substantial. Federal expenditures are made when Federal regulations

are developed and promulgated for particular contaminants in food such as PCB.

Consumers.—Consumers can incur costs

from an environmental contaminant incident

in several ways. The removal of food from

commerce could increase prices for that food

product or other food products being sold.

Thus, the consumer could pay more for food

as a result of an environmental contamination incident. In order for this price increase

in food to occur, however, a significant

amount of a food product or food products

would have to be taken off the market. Such

prices of food might vary by State or region

and affect certain socioeconomic classes differently.

Health costs could increase as a result of

the consumption of contaminated food. This

would not affect all consumers but rather

those who received the most exposure and/or
Ch. II—Environmental Contamination of Food ● 29

those most susceptible to a contaminant, such

as children or senior citizens. While these

costs would already be included in estimated

total health costs, the distributional effects

could indicate those consumers most likely to

be affected.

Indirect Costs. —Most of the costs mentioned directly stem from an environmental

contamination incident. However, indirect or

secondary costs can and do occur. For example, a bait and tackle store on a lake that is

closed to commercial and sport fishing because of an environmental contamination is

likely to suffer economic hardship, Food processors whose normal supply of food has been

condemned because of environmental contamination will also suffer economically unless they find new sources of supply. These

are just two examples of the many indirect

costs which might occur.

Because a limited number of substances

posing health problems already have been

identified in food, concern exists that other

toxic substances are likely to contaminate

food in the future. This concern arises from

the number of substances presently being

manufactured, used, and disposed of in the

United States, and the difficulties in preventing them from entering the environment. New

substances developed to meet new needs or to

replace known toxic substances may create

unexpected environmental problems if not

properly controlled. Byproducts of new technologies such as synthetic fuels are also potential environmental contaminants. These

are described in appendix A.

There are two methods of objectively assessing possible future contaminants: 1 ) by

sampling the food supply for chemical contaminants and ranking them according to potential hazard and 2) by surveying the universe of industrial chemicals and ranking

them according to their potential for entering

the food supply in toxic amounts. These methods are discussed in more detail in chapter

VII, “Monitoring Strategies. ”

Of the three categories of environmental

contaminants considered in this report, organic chemicals probably pose the greatest

potential environmental and food contamination problems. This conclusion is based on the

number, volume, and toxicity of the organics

manufactured and used in this country (40).

Both trace metals and radioactive substances

continue to warrant concern, but not as great

a concern as organic substances. The extent

of food contamination from these substances

depends on our success in preventing them

from entering the environment.

CONCLUSIONS AND ISSUES

Data presented here indicate that environmental contamination of food is a nationwide

problem of unknown magnitude. Long-term,

low-level exposure to toxic substances in food

poses health risks that are difficult to

evaluate given present techniques. Incidents

of high-level contamination of food that cause

human illness have not occurred in the United

States, However, regulatory actions have

been taken to restrict consumption of contaminated food in cases where the potential

health risks were considered unacceptable.

These episodes have resulted in economic

losses when contaminated food was removed

from the market,

The following chapters analyze several

issues related to the regulation of environmental contaminants in food. These are:

Q Is our present regulatory system protecting the public health? (Chapters 111 and

IV)
30 . Environmental Contaminants in Food

● Are methods used by the regulatory

agencies for estimating health impacts

the most appropriate ones? (Chapters III

and V)

● Should economic impacts be an explicit

part of regulatory decisionmaking? If so,

how should economic impacts be evaluated? (Chapters III and VI)

c Should regulatory monitoring be capable

of detecting substances as they enter the

food chain? (Chapters VII and VIII)

CHAPTER II REFERENCES

1. Storclz, William J. “C&EN’s Top Fifty Chemical Products and Producers, Chemical and

Engineering News 56(18):33, 1978,

2. Murray, Chris, “Chemical Waste Disposal A Costly Problem, ” Chemica~ and Engineering News, p. 12, Mar, 12, 1979.

3. National Academy of Sciences, National Research Council, Commission on Natural Resources, Environmental Studies Board, Committee on the Assessment of Polychlorinated

Biphenyls in the Environment. Polychlorinatea’Biphenyls (ISBN O-309-02885-X), 1979,

4. Hammons, A. “Levels of Chemical Contaminants in Nonoccupationally Exposed U.S.

Residents,” draft manuscript prepared for

Health Effects Research Laboratory, Environmental Protection Agency, 1978.

5. U.S. Food and Drug Administration. “Poly -

chlorinated Biphenyls (PCBS), Federal Register 42(63):17487, 1977,

6. Kimbrough, R, D. “The Toxicity of Polychlorinated Polycyclic Compounds and Related

Chemicals, ” CRC Critical Reviews in Toxicology 2:445, 1974,

7, Fishbein, L, “Toxicity of Chlorinated Biphenyls, ” Ann. Rev. Pharmacol, 14:139, 1974.

8. Peakall, D. B. “PCBS and Their Environmental Effects, CRC Critical Reviews on Environmental Contaminants 5:469, 1975.

9. National Institute of Occupational Safety and

Health. Criteria for a Recommended Stanciard. Occupational Exposure to Polychlorinated Biphenyls (PCBS), 1977 (DHEW Publ.

No, 77-225).

10. Kimbrough, R, D., et al. “Animal Toxicity, ”

Environ, Health Persp. 24:173, 1978.

11, Cordle, F., et al. “Human Exposure to Polychlorinated Biphenyls and Polybrominated

Biphenyls, ” Environ. Health Persp. 24:157,

1978.

12. Kimbrough, R. D,, and R. E. Linder. “Induction of Adenofibrosis and Hepatomas of the

Liver in BALB/oJ Mice by Polychlorinated Bi13,

14,

15.

16,

17.

18.

19.

20,

21.

Toxic Substances, Special “Act;ons Group.

“Assessment of the Hazards of Polybrominated Biphenyls(PBBs)” (draft), 1977.

22. Wolff, M. S., B. Aubrey, F. Camper, and N.

Hames. “Relation of DDE and PBB Serum Levels in Farm Residents, Consumers, and Michiphenyls (Aroclor 1254), ” ]ournal of The National Cancer Institute 53:547, 1974.

Allen, J. R., et al. “Residual Effects of

Short-Term, Low-Level Exposure of Non-Human Primates to Polychlorinated Biphenyls, ”

Toxicology and Applied Pharmacolog y

30:440, 1974.

McNulty, W. P. “Primate Study, ” National Conference on Polychlorinated Biphenyls,

Chicago, 1975.

Barsotti, D. A., et al. “Reproductive Dysfunction in Rhesus Monkeys Exposed to Low Levels of Polychlorinated 13iphenyls (Aroclor

1248), ” Food and Cosmetics Toxicology 14:99,

1976.

Allen, J. R., and D. A. Barsotti. “The Effects of Transplacental and Mammary Movement of PCBS on Infant Rhesus Monkey s,”

Toxicology 6:331, 1976.

Allen, J. R. “Response of the Non-Human Primate to Polychlorinated Biphenyl Exposure, ”

Federation Proceedings 34:1675, 1975.

Meester, W. D. and D. J. McCoy, Sr. “Human

Toxicology of Polybrominated Biphenyls, ”

Clinical Toxicology 1o(4):474, 1977.

Fries, G. F., G. S, Marrow, and R. M. Cook.

“Distribution and Kinetics of PBB Residues in

Cattle, ” Environmental Health Perspectives

23:43, 1978.

Lillis, R., H. A. Anderson, J. A. Valcinkas, S.

Freedman, and I. J. Selikoff. “Comparison of

Findings Among Residents of Michigan Dairy

Farms and Consumers of Produce Purchased

From These Farms,” Environmental Health

Perspectives 23:105, 1978.

Environmental Protection Agencv, Office of
Ch. //— Environmental Contamination of Food ● 31

gan Chemical Corporation Employ ees, ” Environment] Health Perspectives 23: 177, 1978.

23. Cook, H. D., R. Helland, B. H, Vander Weele,

and R. J, DeJong, “Histotoxic Effects of Polybrominated Biphenyls in Michigan Dairy Cattle,”’ Environmental Research 15:82, 1978.

24. Kay, K. “Polybrominated Biphenyls (PBB) Environmental Contaminants in Michigan, 1973-

1976, ” Environmental Research 13:74, 1977.

25, Bekesi, J. G., J. F. Holland, H. A. Anderson, A.

S. Fischbein, W, Rem, M. S. Wolff, and I. J.

Selikoff. “Lymphocyte Function of Michigan

Dairy Farmers Exposed to Polybrominated Biphenyls, ” Science 199:1207, 1978.

26, United Nations Environment Program and the

World Health organization. Environmental

l-iec~lth Criteriu 1: Mercury, Geneva, p. 23,

1976,

27. National Academy of Sciences, National Research Council, An Assessment of Mercury in

the Environment, Washington, D, C., 1978.

28. U.S. Environmental Protection Agency, Ambien t Water Quulity Criteria: Mercury, 1979.

29. Lu, F. C. “’Mercury as a Food Contaminant, ”

WHO ChronicJe 28:8, 1974.

30, D’Itri, F, M. “The Environmental Mercury

Problem, ” CRC Press, p. 73, 1972.

31. Friberg, L., and J, Vestal. “Mercury in the Environment, ” Cl? Caress, 1972.

32. Gerstner, H, B,, and J. E. Huff. ‘*Clinical Toxicology of Mercury, ” Journal of Toxicology

and Environmental Health 2:49 1, 1977.

33. Olson, F. C,, and E. J, Massaro. “Pharmacody -

namics and Tera tologic Effects of Transplacentally Transported Methyl Mercury in the

Nlouse, ’” Jnternationul Conference on Heuvy

Met(lis in the Environment, pp. 32 and 184,

1972.

34. Weiss, B., and R. H, Doherty. “Methylmercur~ Poisoning, “’ Teratology 12(3):311, 1976.

35. Rizzo, A. M., and A. Furst. “Mercury Teratogenesis in the Rat, ” Proceedings of the Western Pharmacology Society 15:52, 1972.

36. Evans, H. L., R. H. Garman, and B. Weiss.

“Methylmercury: Exposure Duration and Regional Distribution as Determinants of

Neurotoxicity in Nonhuman Primates, ” Toxicology and Applied Pharmacology 41: 15,

1977.

37. National Academy of Sciences, ‘ Advisory

Committee on the Biological Effects of Ionizing Radiations. Effects on Populations of Exposure to Low Levels of Ionizing Radiation,

Washington, D. C., 1972.

38. National Academy of Sciences, Food Protection Committee. 13adionuclides in Foods,

Washington, D. C., 1973.

39. Dodge, Chris. “Contamination of Food by Radioactive Nuclides, ” Congressional Research

Service, OTA Working Paper, August 1978.

40. Monitoring Advisory Panel, Sept. 21, 1978.

41. Michigan Department of Agriculture, Infor42

43.

mation and Education Division. “A Brief

Chronology of the PBB Incident” (no date).

Anonymous. “Two Firms Fined $4,000 Each

for PBB Contamination of Cattle Feed in

Michigan, ” Toxic Material News, p, 144, May

24, 1978,

Jaroslovsky, Rich. “Contamination of Fishmeal with PCBS Sparks FDA Study of Mishap

at a Ralston Purina Plant, ” The Wall Street

Journal, p. 46, July 12, 1978.

44. Whitehead, George, Deputy Director for Con45

sumer Affairs, Michigan Department of Agriculture, Jan. 16, 1978.

McNally, JoAnn. “Polybrominated Biphenyls:

Environmental Contamination of Food, ” Congressional Research Service, OTA Working

Paper, Sept. 21, 1978.
Chapter III

Federal Laws, Regulations,

and Programs
Chapter III

Federal Laws, Regulations,

and Programs

FEDERAL LAWS

Congress has enacted several laws that not only regulate but also attempt to

limit or restrict the introduction of toxic substances into the environment. Table 7

summarizes the Federal laws affecting toxic substances control.

Some of these laws give Federal agencies authority to prevent unsafe food

from reaching consumers. Most important in terms of this assessment is the

Federal Food, Drug, and Cosmetic (FD&C) Act (l). Broadly speaking, this statute

prohibits the introduction of adulterated food into interstate commerce. The

FD&C Act allows the Food and Drug Administration (FDA) to establish tolerances

for toxic substances whose occurrence in food cannot be avoided. The Poultry and

Poultry Products Inspection Act (2) and the Federal Meat Inspection Act (3) give

the U.S. Department of Agriculture (USDA) authority to inspect meat, poultry, and

their byproducts. The adulteration provisions of these Acts govern all environmental contaminants except for pesticides that may occur in meat and poultry.

Under these laws, section 408 of the FD&C Act applies to such pesticide contamination. In practice, USDA uses the tolerances established under the FD&C Act

and consults with FDA and the Environmental Protection Agency (EPA) to determine an action level when no tolerance exists.

Following is a brief summary of the pertinent provisions of the FD&C Act:

Section 402(a)(l) declares that any food

that “bears or contains any poisonous or

deleterious substance which may render it injurious to health” is adulterated. The single

exception is if the substance is not, in the

language of the Act, “added” to the food. In

such cases, the presence of the substance

does not imply that the food is adulterated

unless it is present in sufficient quantity to

“ordinarily render it injurious to health. ”

The FD&C Act recognizes that certain

“added” toxic substances in foods require

special attention, Section 406 empowers FDA

to establish tolerances for “added’” poisonous

substances whose occurrence in food cannot

be avoided or whose use is “necessary” to

produce the food. Thus, Congress authorized

FDA to “license” the presence of certain

potentially toxic substances in food, seemingly because of their economic utility or the inability of existing, commonly used production

methods to eliminate them. The legislative

history of section 406 is skimpy. But Congress’ principal objective apparently was to

permit continued use of pesticides on raw

agricultural commodities while giving FDA an

effective means of control—the power to declare illegal any food that contained any

amount of an added substance that exceeds

FDA tolerance. Congress left the distinction

between “added”’ and other constituents undefined, and did not attempt to clarify the

concepts of “necessary” or “unavoidable”’ in

section 406(4).

Amendments to the 1938 FD&C Act deal

with specific categories within the broad

class of substances “added”’ to foods including pesticides, food additives, vitamins

and minerals, and animal drugs. Each amendment in effect establishes a system under

35
36 ● Environmental Contaminants in Food

Table 7.— Federal Laws and Agencies Affecting Toxic Substances Control

Statute Year enacted Responsible agency Sources covered

Toxic Substances Control Act . .....1976 EPA

Clean Air Act. . . . . . . . . . . . . . . . . . 1970, amended 1977 EPA

Federal Water Pollution Control Act

(now Clean Water Act) . ..........1972, amended 1977 EPA

Safe Drinking Water Act . ..........1974, amended 1977 EPA

Federal Insecticide, Fungicide, and 1947, amended 1972, 1975, EPA

Rodenticide Act . . . . . . . . . . . . . . . . 1978

Act of July 22, 1954, (codified as

Section 346(a) of the Food, Drug, 1954, amended 1972

and Cosmetic Act) .

Resource Conservation and

Recovery Act . .................1976

Marine Protection, Research, and

Sanctuaries Act . . . . ..........1972

Food, Drug, and Cosmetic Act . .....1938

Food additives amendment . .....1958

Color additives amendments ... 1960

New drug amendments . . . . . . . . . . 1962

New animal drug amendments. .. .1968

Medical device amendments .. 1976

Federal Meat Inspection Act. . ......1967

Poultry Products Inspection Act .. ..1957

Egg Products Inspection Act . ......1970

Fair Packaging and Labeling Act .. ..1976

Public Health Service Act ... . .....1944

Occupational Safety and Health Act .1970

Federal Hazardous Substances Act. 1960

Consumer Product Safety Act 1972

Poison Prevention Packaging Act .. 1970

Lead-Based Paint Poisoning 1973, amended 1976

Prevention Act .,

Hazardous Materials Transportation 1975, amended 1976

Act .,

Federal Railroad Safety Act . . . . . 1970

Ports and Waterways Safety Act 1972

Dangerous Cargo Act .. ...195 2

Federal Mine Safety and Health Act. .1977

CPSC = Consumer Product Safety Commlsslon

DOT = Department of Transportation

EPA = Environmental Protection Agency

FDA = Food and Drug Admlnlstratlon

HEW = Health Educatton and Welfare

EPA

EPA

EPA

FDA

FDA

FDA

FDA

FDA

FDA

USDA

USDA

USDA

FDA

FDA

OSHA, NIOSH

CPSC

CPSC

CPSC

CPSC, HEW, HUD

DOT (Materials

Transportation

Bureau)

DOT (Federal

Railroad Admin.)

DOT (Coast Guard)

Labor (Mine Safety

All new chemicals (other than food

additives, drugs, pesticides, alcohol,

and tobacco) and existing chemicals

not covered by other toxic

substances control laws

Hazardous air pollutants

Toxic water pollutants

Drinking water contaminants

Pesticides

Tolerances for pesticide residues in

food

Hazardous wastes

Ocean dumping

Basic coverage of food. drugs,

and cosmetics

Food additives

Color additives

Drugs

Animal drugs and feed additives

Medical devices

Food, feed, and color additives;

pest icicle residues in meat and

poultry products

Packaging and labeling of food and

drugs for man or animals, cosmetics, and medical devices

Sections relating to biological

products

Workplace toxic chemicals

Hazardous (including toxic)

household products (equivalent in

many instances to consumer

products)

Hazardous consumer products

Packaging of hazardous household

products

Use of lead paint: on toys or furniture,

on cooking, drinking, and eating

utensils, in federally assisted

housing

Transportation of toxic substances

generally

Railroad safety

Shipment of toxic materials by water

Toxic substances and other harmful

and Health Admin.), physical agents in coal or other

NIOSH mines

HUD = Housing and Urban Development

NIOSH = National Institute for Occupational Safety and Health

OSHA = Occupational Safety and Health Administration

USDA = United States Department of Agriculture

SOURCE Environmental Law Institute, An Andlys(s 01 ~asl federal Efforts To Contro/ Tox)c .Subslances Washington D C 1978
Ch. Ill—Federal Laws. Regulations, and Programs ● 37

which FDA is empowered to license, and

thereby limit, the use (or in the case of

pesticide residues, the occurrence) of potentially toxic substances in or on food.

The Pesticide Chemicals Amendment of

1954, now section 408 of the FD&C Act, provides that a raw agricultural commodity shall

be deemed to be adulterated if it bears or contains any residue of a pesticide that does not

conform to a tolerance established under section 408, Pesticides that are unintentionally

present on commodities are usually considered environmental contaminants by FDA,

and are regulated under section 406.

At no point, in 1938 or subsequently, has

Congress specifically addressed the problem

of environmental contaminants in food. FDA

could have regulated them all under the “may

render injurious” language of section 402(a)

(1). But this provision would not have given

FDA authority to determine administratively

what levels of a contaminant could be tolerated. FDA would have been required to prove

its claim of hazard each time it seized a contaminated product.

Accordingly, since the early 1970’s FDA

has classified environmental contaminants as

“added poisonous or deleterious substances’

whose occurrence cannot entirely b e

avoided, thus avoiding the less rigorous “ordinarily injurious” standard of section 402(a)

(l). The tolerance-setting authority of section

406 can then be applied to environmental

contaminants in food.

Relying on section 406, FDA prescribes the

level of a contaminant that, under section

402(a)(2)(A), will render a food adulterated.

Before FDA can ascertain this level, sufficient scientific data must be accumulated to

answer several questions implicitly posed by

sections 402 and 406. FDA must be able to

determine that the environmental contaminant in question is:

1.

2.

3.

4.

added,

poisonous or deleterious,

a substance unavoidable by good manufacturing practice, and

one which may make the food injurious

to health. -

Furthermore, an analytical method that can

reliably detect, measure, and confirm the

identity of the contaminant in the food under

scrutiny must be available (5).

To determine whether these requirements

can be met, FDA scientists explore and review the scientific literature, consult F D A

files, and draw on information available in

other agencies, in academia, or in private industry. Then, based on the best scientific

data available (which are often incomplete),

FDA will prescribe what level of contamination will trigger enforcement action (5).

Regulatory procedures employed to control

environmental contaminants in food include

the establishment of action levels or tolerances. A formal tolerance is a regulation having the force of law. Tolerances are adopted

through formal rulemaking procedures and

specify the level of a contaminant that will

render a food adulterated. If supported by

substantial evidence in the rulemaking record, FDA’s tolerance cannot be questioned by

any court. An action level is an in.formed judgment about the level of a food contaminant to

which consumers may safely be exposed. It is

a statement of FDA’s professional judgment

and represents a commitment to initiate regulatory enforcement action against any lots of

food discovered containing excess levels. Essentially the same criteria are considered in

establishing tolerances and setting action levels. The principal differences between the

two approaches lie in the procedures for

their adoption, the strength of the scientific

data supporting them, and the differing

weight they carry in court (4).
38 . Environmental Contaminants in Food

FDA will set a tolerance when the following conditions exist:

1. The substance cannot be avoided by

good manufacturing practice.

2. The tolerance established is sufficient

for the protection of the public health,

taking into account the extent to which

the presence of the substance cannot be

avoided and the other ways in which

the consumer may be affected by the

same or related poisonous or deleterious substances.

3. No technological or other changes are

foreseeable in the near future that

might affect the appropriateness of the

tolerance established (6).

To establish a tolerance, FDA first publishes a proposal, accepts comments, and

issues a “final’* regulation, Formal objections

can be raised to this “final” tolerance. Such

objections can, if they raise material issues of

fact, require a lengthy trial-type hearing

before an FDA administrative law judge, who

then issues an initial decision based on the

formal hearing record. That decision, in turn,

can be appealed to the FDA Commissioner

(who issued the original “final” tolerance).

The Commissioner’s ultimate decision is subject to review in a court of appeals (l).

Because the tolerance-setting procedure is

cumbersome and time-consuming, FDA initially relies on an action level when it regulates an environmental contaminant. An action level is an administrative guideline and

the functional, though not legal, equivalent of

a section 406 tolerance. It is established

when “technological or other changes that

might affect the appropriateness of the tolerance are foreseeable in the near future” (6).

To set an action level, FDA simply announces in the Federal Register that it is

establishing an action level for a contaminant, and states that the data supporting the

designated level are available for public inspection. This announcement may briefly discuss the pertinent factors that went into the

decision, but any discussion is not likely to be

(nor is required to be) extensive. While the

announcement also notes that public comments will be accepted, FDA makes no commitment to respond to any comments or, indeed, to reconsider the action level within

any specified period (6). The process does not

require a detailed public discussion of the

selected levels, nor does it trigger a public

debate about the correctness of FDA’s premises or its balancing of relevant factors.

Finally, the Commissioner of FDA may exempt from regulatory action any contaminated food if he determines “based upon all

available scientific evidence, that the food is

safe for consumption and that destruction or

diversion of the food involved would result in

a substantial adverse impact on the national

food supply” (6). This has only happened

once, and the action did not involve human

food,

If the environmental contaminant is a pesticide for which no tolerance has been established by EPA, FDA relies on EPA to recommend an action level (as it did in the case of

kepone). In other respects, the procedures

and criteria for regulating pesticides as environmental contaminants are the same as for

other contaminants.

Criteria for Setting Action Levels

and Tolerances

For the setting of action levels or tolerances, neither the law nor regulations require FDA or EPA to follow a standardized

set of toxicologic protocols to evaluate risk.

No policy exists defining the relative weight

to be given to evidence. The burden of proving

there is a health hazard lies with FDA. When

setting an action level or tolerance, FDA considers the following types of data:

1.

2.

available acute and chronic toxicological data, including information on the

biological half-life of the substance and

its metabolic fate;

available data on the levels and incidence of the contaminant in the overall

food supply and specifically in the food

commodity or commodities that are

being considered for an action level or

tolerance;
Ch. IIl—Federal Laws, Regulations, and Programs ● 39

3.

4.

5.

6.

7.

In

normal serving sizes of the concerned

food(s) and frequency of ingestion;

susceptibility of certain population

groups, such as infants and the aged, to

adverse effects from anticipated dietary

exposure to the contaminant:

the level at which available analytical

techniques can detect, measure, and

confirm the identity of the contaminant;

capability of manufacturers to monitor

their food production to ensure that the

products comply with the action level or

tolerance; and

the anticipated impact of various possible levels of regulation on the national

food supply.

response to questions on how FDA evaluates these data, Commissioner Donald Kennedy wrote:

Each factor is assessed individually (assuming information on each is available) and

then collectively brought into balance by a

composite analysis in terms of the estimated

risk to the public health versus both the extent to which the substance is unavoidable

and the quantity of food that would be unlawful under levels being considered (5),

FDA has not fixed the weight to be given to

each of the above factors. Each will, to some

degree, influence the final decision; generally, the more information about a particular

factor, the greater its influence, This is one

reason that FDA offers for not prescribing a

predetermined quantifiable set of criteria for

each factor. The amount and quality of information available when FDA encounters an

environmental food contamination problem

are inevitably unpredictable, FDA maintains

that because of this uncertainty, it is impractical to state in advance the precise weight of

each factor in the final determination. However, FDA maintains that the public health

factor outweighs all others in its considerations (5).

Determining Action Levels

and Tolerances

In general, EPA and FDA follow similar

procedures when evaluating the health risk

associated with consumption of a toxic substance in food, Both agencies consider three

areas when evaluating the scientific information: 1) existing animal toxicity data, 2) existing human toxicity data, and 3) exposure

data based on the level of the contaminant in

food and the average consumption of that

food. Both agencies also consider what effect

an action level or tolerance will have on the

availability of food.

Evaluation of the Scientific Data

When a food contaminant is identified, the

first step in establishing an action level or

tolerance is to assemble and evaluate all

available information on its toxicity. This information comes from articles published in

the scientific literature, information provided

by private industry, and data from other Government agencies. From animal toxicity data

and whatever human toxicity data may be

available, a no observed effect level (NOEL) is

calculated and expressed in milligrams per

kilogram of body weight per day. NOEL is the

level at which the substance had no observed

effects.

An acceptable daily intake (ADI) is then

calculated by dividing the NOEL by a safety

factor. The term “acceptable” does not imply

absolute safety for all people in all cases, and

the term “safety factor” implies more than it

seems. The safety factor reflects the uncertainty of translating animal data to humans,

the variability of the human population, the

insufficiency of the data available, and the

severity and reversibility of toxic effects.

When 2-year chronic toxicity studies in

animals are available, the safety factor used

is 100. When threshold levels have been observed in humans, the safety factor employed

is 10. If long-term studies are available and

show no irreversible effects, a much smaller

safety factor might be selected. If evaluation

of available toxicological data indicates that

no threshold exists, a very large safety factor

(on the order of 1,000 or more) maybe used.

F. ‘I’. Arnold, chairman of the Kepone Action

Level Hearings, stated that “the determination of an appropriate safety factor is an art
40 . Environmental Contaminants in Food

rather than a science and is dictated by the

chemical in question, its toxicological properties and surrounding circumstances” (7).

The next step is to calculate the maximum

permissible intake. The maximum permissible intake is the product of ADI and the

average weight of an adult (this figure varies

from 60 to 70 kg). This figure is then compared to the maximum potential exposure

through consumption of contaminated food.

Tolerances are set so that the amount of the

contaminant consumed in food is less than or

equal to the ADI. Mathematically, this can be

expressed as:

ADI x Average body weight

Tolerance = of consumer

Food factor x 1.5 k g

Where ADI = the NOEL divided by an appropriate

safety factor

Average body

weight of

consumer = 60 kg for EPA calculations, and 70 kg for

FDA calculations

Food factor = percentage of the average daily diet

made up by the food in question

1.5 kg = the average weight of food consumed in

a day

Appendix B provides a detailed example of

how these concepts were applied by FDA in

the development of tolerances for polychlorinated biphenyls (PCBs) in food,

These procedures have several limitations.

The data on toxicity of an environmental contaminant for humans and animals may often

be inadequate for setting a tolerance. Because of time constraints and the necessity to

make a regulatory decision, action levels for

environmental contaminants in food may be

based on incomplete, scanty toxicological information. Once a level is set, however, no

law requires FDA to collect new evidence on

the toxicity of the substance in question even

though that issue may well continue to be of

critical importance to the population receiving the highest exposure and to food producers.

Because of the nature of the problem presented by environmental contaminants in

food and because so little data are usually

available, EPA and FDA cannot have formal

requirements for toxicity data. Moreover, in

most instances there are no petitioners or

sponsors of commercial uses of the material

to which FDA can look for the necessary additional tests. Available industry data are frequently used because of the lack of published

or publicly available information on the substance. While known toxic effects of metabolic products of the substance in question are

considered, unknown metabolizes cannot be.

Finally, additive and synergistic effects between the contaminant and other toxic substances in food are not considered in the tolerance-setting procedures.

Questions are frequently raised about

safety factors and the extrapolation from animal data to humans. Comparisons between

animals and humans are based on milligrams

of the toxic substance per kilogram of body

weight, although many maintain that milligram of toxic substance per square centimeter of body surface area is a more appropriate comparison,

Little scientific evidence exists to support

safety factors. Historically, a factor of 10 in

extrapolating from animals to man and a factor of 10 in extrapolating from the least-sensitive human to the most-sensitive have been

used although they have little theoretical or

factual basis. Many believe that the use of

different safety factors for different toxicological effects (a greater safety factor for irreversible effects, a smaller factor for reversible effects) or the use of mathematical models to extrapolate from animal to human risk

would be more appropriate. Finally, the safety factor approach may not make allowances

for vulnerable groups such as infants, except

in those instances in which infants are considered the primary population at risk. Individuals with predisposing conditions or previous exposure may not be adequately covered

by safety factors. In truth, it may be impossible to protect every individual with allergies

or predisposing physiological conditions.

The methods used for estimating dietary

exposure to toxic substances are limited by

lack of sound data. FDA bases some tolerance

decisions on their Total Diet Studies, Because
Ch. III— Federal Laws, Regulations, and Programs ● 41

these are based on the diet of a teenage male,

they do not reflect the dietary patterns of

vulnerable groups, nor do they reflect ethnic

and regional preferences or vegetarian diets.

EPA and FDA rely on USDA’s Food Consumption Survey, which was completed in 1965-66.

It is believed that some shifts have occurred

in consumption patterns since then, and

USDA is now conducting a new Food Consumption Survey.

Evaluation of Decisionmaking Approach

As discussed earlier, FDA regulates environmental contaminants in food under section 406 of the FD&C Act. This section does

not specifically address environmental contaminants, but authorizes FDA to regulate

food for potentially toxic substances that are

“added” and “unavoidable’” in the production of food. When setting an action level or

tolerance, FDA considers the impacts on the

national food supply or, stated in another

manner, the impacts on the availability of

food to the American consumer. In quantifying this criterion, FDA estimates the

amount of food that would be banned from

commerce because of the action level or tolerance.

The final rule reducing PCB tolerances (8)

illustrates FDA’s interpretation of section

406 of the FD&C Act for environmental contaminants in food. FDA clearly states that for

PCBs “(i)t has had to decide, in effect, where

the proper balance lies between providing an

adequate degree of public health protection

and avoiding excessive losses of food to

American consumers. ”

FDA later goes on to state that:

(I)n establishing a tolerance for PCBs in

fish, FDA must take into account the amount

of fish a given tolerance would remove from

commerce. Sect ion 406 of the Act, however,

neither requires nor authorizes FDA to

weigh secondary economic impacts when it

considers the level at which a tolerance

should he set. Consideration of such impacts

would be inconsistent with the paramount

concern of section 406, which is protection of

the public health, and would complicate the

decisionmaking process under section 406 in

a way Congress did not intend. Obviously,

consideration of the amount of food loss

caused by a tolerance helps to ensure that

the direct economic consequences of the

tolerance (in this case, decreased sales and

employment in the commercial fishing industry) will not be disproportionate to the increased degree of public health protection

accomplished by the tolerance: but FDA considers secondary economic consequences,

such as potential impact on the recreational

fishing industry, totally beyond the scope of

section 406 (8).

The decisionmaking process used by FDA

is a form of cost-effectiveness analysis—a

procedure to compare the change of health

effects in biological terms with the change of

the cost in dollars (a further analysis of this

procedure appears in chapter VI). In the PCB

decision, FDA compared change in human

risk data for 5 parts per million (ppm), 2 ppm,

and 1 ppm levels in fish with the estimated

amount of food that would be condemned in

order to arrive at a 2-ppm tolerance level. In

FDA’s judgment, a 2-ppm tolerance was a

proper balance between “providing an adequate degree of public health and avoiding

excessive losses of food to American consumers. ” While other factors were considered by FDA in its decision, the estimated

human risk data and loss of food are the two

principal factors weighed in the decision.

The language of section 406 provides FDA

with the flexibility to interpret the unavoidability requirement as it sees fit. FDA

recognizes that its regulatory decision will

have an economic impact, but FDA considers

only a component of the total economic impact in its decision-i. e.. food condemned.

FDA also realizes that the amount of food

condemned will have an effect on employment and commercial sales associated with

the contaminated food product. It must be

recognized that even for such a widespread

contaminant as PCBs, an action level for an

environmental contaminant is likely to have a

more severe impact on local employment and

commercial sales than on the amount of food

available to the American consumer.
42 . Environmental Contaminants in Food

In addition, FDA’s attempt to measure the

impacts on availability of food by estimating

cost of food condemned has several flaws.

First, FDA estimates the amount of food expected to be condemned for one year from a

proposed action level or tolerance. For

substances such as PCBs in freshwater fish,

estimates for the amount of food expected to

be condemned should be for more than one

year. This is because PCBs are ubiquitous in

the environment and degrade very slowly. It

is highly likely that freshwater fish will be

contaminated with PCBs at levels above 2

ppm and consequently restricted from commerce for several years.

Second, estimating the cost of food banned

by the tolerance does not necessarily reflect

the impact on the availability of food. While

this might occur for small amounts of food

condemned—a herd of cattle or a few hundred gallons of milk—this would not be the

case for incidents that condemn significant

amounts of food. A more accurate estimate of

the impact on the availability of food would

be to consider the percentage or amount of a

food product condemned out of the total

amount of that particular product that is produced in this country, Then an estimate of the

relative importance of the affected food product to the American diet would need to be

made, FDA does not do this second step. This

type of analysis would also attempt to estimate

the impact such a tolerance would have on

the supply and price of other foods available

to and consumed by the American consumer.

While the latter analysis may be theoretically sound, given the time constraints for setting an action level for a newly discovered

contaminant, it may not be practical for an

initial regulatory decision. The more thorough analysis is more applicable to tolerancesetting.

FEDERAL MONITORING PROGRAMS

On the Federal level, the responsibility of

monitoring foods for environmental contaminants falls mainly on two agencies, FDA and

USDA. USDA limits its monitoring activities

to meat and poultry products, while FDA analyzes samples of animal feeds, fruits, vegetables, grain, eggs, milk, processed dairy

products, and seafood. Most monitoring activities of these two agencies could be classified

as regulatory monitoring-analysis of food

samples for known environmental contaminants and for some suspected environmental

contaminants for enforcement purposes.

Food and Drug Administration

FDA collects approximately 8,000 food and

feed samples a year and analyzes them for a

variety of chemical residues, mainly pesticides. Domestic food commodities comprise

about 70 percent of this total, imported commodities make up around 30 percent. In addition, approximately 1,300 seafood samples

are collected for analysis annually. Most food

and feed samples are collected at their point

of origin or processing, and attempts are

made to collect the seafoods as close to the

point of origin as possible (9).

Some agricultural products are analyzed

for the presence of trace metals—lead, zinc,

and cadmium—as well as for synthetic organic chemicals. All fish samples collected

for determination of chlorinated pesticides

and PCBs are also analyzed for mercury.

Some canned-tuna samples are analyzed for

lead, cadmium, arsenic, selenium, and mercury. Because some containers have leadsoldered joints that may contaminate the

food, an unspecified number of canned-food

samples are analyzed to determine lead content (9).

FDA also determines the total dietary intake and exposure trends of some known and

suspected environmental contaminants in its

Total Diet Studies. The contaminants included in this program include some pesticides, PCBs, mercury, lead, cadmium, arsenic, selenium, and zinc, Other organics and

metals are excluded (9). Because it involves
Ch. Ill—Federal Laws, Regulations, and Programs ● 43

not the analysis of individual raw food products but rather combinations of prepared

cooked foods which approximate a total

dietary intake, this program differs from the

regulatory monitoring activities of FDA.

Monitoring for known environmental contaminants is carried out through the use of

specified “accepted” methods for extraction,

cleanup, and identification. The procedures,

when applied to samples in which regulated

synthetic organic chemicals such as pesticides are to be determined, will often indicate

the presence of other compounds that are

chemically similar to those under analysis.

The FDA Compliance Program Guidance

Manual (10) specifies that if, during the

regulatory monitoring analyses, unidentified

analytical responses appear (thus indicating

an uncharacterized chemical) with “significant” intensity, data from the sample collection and analysis should be transmitted to the

Bureau of Foods Laboratory in Washington,

D. C., which presumably will identify the uncharacterized chemicals.

FDA may select a chemical for further

study based on production volume, toxic byproducts, environmental stability, volubility,

behavior, toxicity, uses, and methods of disposal. After an analytical method is developed, samples that have the highest probability of being contaminated with the particular

(selected) compound are collected. These

samples are often fish, since rivers, lakes,

and estuaries receive chemicals not only from

direct discharges from municipalities and industry but also from erosion and runoff. Further research and monitoring activities on a

given chemical depend on the results of these

initial analyses (9).

The present radionuclide-monitoring program is a joint undertaking by FDA, EPA, and

the States, This program monitors: 1) foods

grown near eight selected nuclear power facilities for tritium, gamma emitters, and

strontium-90; 2) food samples from the total

diet studies; 3) specified imported foods; and

4) milk, fruit, vegetables, and water collected

near phosphate mines in Florida (11).

EPA monitors milk, air, water, and soil for

radioactivity. The milk-monitoring program is

a joint effort with State and local agencies,

FDA advises and monitors the milk-sampling

program, which is carried out by 63 State and

local health agencies. Milk from each area is

sampled once a month by the State and/or

local inspectors and submitted for analysis to

the EPA laboratory in Montgomery, Ala.

U.S. Department of Agriculture

USDA is responsible for evaluating the

quality of meat and poultry products and providing the consumer with products that meet

the criteria spelled out in the Meat and

Poultry Inspection Acts. These criteria include monitoring for environmental contaminants. The majority of compounds evaluated

are those that are approved for use in agriculture, either administered directly to food

animals (such as growth promoters), or applied to agricultural crops to which food animals may eventually be exposed (such as pesticides).

Testing of meat and poultry products for

residues by USDA falls into broad monitoring

and surveillance categories. The monitoring

activity, called the National Residue Monitoring Program, is designed to determine the

frequency at which tolerance-exceeding

amounts of monitored compounds are occurring in the national meat supply. In effect, the

monitoring program is designed to evaluate

how effectively users and/or manufacturers

of the compounds are complying with the

laws or use restrictions (12).

Under the monitoring program, animal tissues are collected from slaughterhouses under Federal inspection throughout the United

States at a rate that will detect violations if

they are occurring in at least 1 percent of the

animal population [13). Based on statistical

calculations, 300 samples per compound per

species have to be collected annually to determine a l-percent incidence with 95-percent

assurance. In effect this means that the same

sample of tissues may be analyzed for more

than one compound. This level of testing re-
44 ● Environmental Contaminants in Food

quires sampling approximately 1 in 8,000

head of livestock and 1 in 700,000 poultry.

These collections are stratified according to

geographic areas, with more samples being

collected from areas where meat or poultry

are slaughtered.

USDA does not monitor all compounds for

which tolerances have been established.

There are no suitable methods to analyze

some of them within existing regulatory

monitoring laboratory capabilities. Available

resources may also limit the number and

variety of compounds tested, The selection of

which compounds to monitor is based on factors such as frequency and patterns of use,

toxicity, previous testing results, and public

concern. Major groups of compounds in the

monitoring program include synthetic organic

chemicals (mainly chlorinated hydrocarbon

insecticides), trace metals, antibiotics, sulfonamides, and certain hormones and drugs

used for growth promotion and disease control. Organophosphate pesticides were monitored for several years but this monitoring

was discontinued because residues of the

parent compound were not found in animal

tissue and suitable routine methods for detecting the metabolizes were not practical

(12),

In 1978, about 150,000 tests were completed on approximately 20,000 domestic

samples collected under the national residue

monitoring program. An additional 2,000

samples were collected from imported products (12). Many of these samples are analyzed

for potential contaminants other than trace

metals and synthetic organics. In 1977, for instance, around 2,300 out of 22,000 samples

were analyzed for chlorinated hydrocarbon

pesticides and 1,300 for trace metals. The remainder were analyzed for antibiotics, hormones, and drugs (13). Data generated by this

program are used not only for regulatory

functions but also to help pinpoint problems,

assist in trend analysis, and indicate areas

that need more intensive sampling.

Surveillance samples are those collected to

evaluate a problem. The area of sampling

may be as small as a single farm or as large

as a State or region, depending on the circumstances. Indications of problems come

from many sources: the National Residue

Monitoring Program, activities of USDA inspectors, information from State or other

Federal officials, or from public news

sources. Because these samples are biased

(i.e., collected in response to a given need),

they do not reflect the overall condition of the

national meat supply. In most cases the samples are used to determine either the extent

of a problem or to evaluate the acceptability

of a herd or product. Any product found to be

in violation may not be released into commerce until subsequent samples show that it

is in compliance. These followup samples are

considered surveillance samples,

Analyses of samples collected in USDA

programs are performed in a manner similar

to those in the FDA program—prescribed

analytical methods are used. USDA, like FDA,

may try to identify an “uncharacterized” substance when “unknown” peaks appear in the

analysis of a sample. Depending on the identity of the compound, further investigation and

sampling may be carried out,

Environmental Protection Agency

EPA has no mandate to regularly analyze

food commodities for chemical contamination. Some of its programs designed to determine the ecological impact of pollutants may

include certain types of foods for analysis.

This is particularly true in the case of

seafood. Samples from aquatic food chains

are often selected for analysis to ascertain

whether a pollutant is concentrated as it

moves up the food chain.

In addition, the mobilization, degradation,

and transfer of pollutants is often studied by

EPA. For example, under the auspices of

EPA’s Chesapeake Bay program, trace metals

and synthetic organic chemicals are being

studied in water, living organisms, and sediments of the Chesapeake Bay by various State

agencies and academic institutions. The results of this and similar studies are not designed to protect the public from consuming

contaminated food and are seldom used as
Ch. Ill—Federal Laws, Regu/at/ens, and Programs ● 45

such. Rather, the results are used in protecting the environment from chemical insults

and helping EPA better regulate the introduction of toxic substances into the environment.

Some data transfer between EPA and other

Federal agencies exists. For example, in the

EPA-funded kepone studies in the Chesapeake Bay region, kepone concentrations in

edible fish, shellfish, and crabs are obtained

which assist the Commonwealth of Virginia

and FDA in their efforts to keep contaminated

sea food off the market. This is true even

though the study is not designed specifically

for this purpose.

Another program administered by the EPA

is the Mussel Watch (14). It is designed to

analyze shellfish collected from strategic

locations in the marine coastal zone of the

United States for selected organic chemicals,

trace metals, and radionuclides. This program was started in 1976 and now involves

the collection of oysters and/or mussels from

29 stations on the west coast, 34 stations on

the east coast, and 26 stations on the gulf

coast, Collections from these stations make

up a total of 107 samples,

The trace metals for which samples are

analyzed in this program include lead, cadmium, silver, zinc, copper, and nickel. The radionuclides measured in the samples include

plutonium-238 and -239, americum-241, cesium-137, curium-242 and -244, and lead-210.

The synthetic organic chemicals included in

the analysis are the halogenated hydrocarbons p,p’-DDE and p,p’-DDD—two of the principal breakdown products of the pesticide

DDT—and PCBs. Samples are analyzed for

these synthetic organic chemicals as well as

petroleum hydrocarbons, whose presenc e

may indicate oil pollution. Recently, a number

of uncharacterized substances have bee n

found by Mussel Watch scientists. They are

now designing the program to encompass

systems to track and identify them (15).

Critique of Federal Monitoring

Programs

A chemical substance found in food becomes the subject of Federal regulatory monitoring if it has caused a problem at some time

in the past. In other words, a compound may

enter the food supply and be undetected for

years but categorized as a known contaminant when discovered. An example would be

kepone in seafood of the James River in Virginia (16). This compound is an insecticide

that had been entering the aquatic food chain

for at least 7 years before discovery. Its presence in seafood was determined after workers in the facility that manufactured it became ill from industrial exposure to this toxicant (17)0

As soon as the sick workers were discovered, samples of fish and oysters from the adjacent river were analyzed and shown to contain kepone. Within a few months, action

levels were established for kepone in seafood.

Because existing monitoring programs analyze for known regulated environmental contaminants, the compound was not discovered

because it was not sought. It is unlikely that

the presence of kepone would be known and

regulated today had the workers not become

ill. In this case, kepone was placed in the

known-environmental-contaminants category

as a result of the illness of production

workers, not chemical monitoring.

Another example of a toxic compound entering the food supply and going undetected is

the fire-retardant polybrominated biphenyls

(PBBs), PBBs entered the food supply in Michigan in the late spring or early summer of

1973 (18,19), Bags of a fire retardant containing these compounds were shipped to farmers’ cooperative units in Michigan in place of

the intended livestock feed supplement, The

fire retardant was unknowingly mixed with

cattle feed and fed to herds throughout the

southern part of the State. Even though farmers soon noted the symptoms of poisoning in

the cattle and reported the problem to State

and Federal officials, it was almost a year

before the causative agents, PBBs, were identified. During this year dairy products and

beef contaminated with these compounds

were consumed by the citizens of Michigan.

Soon after the compound was identified in

food products, action levels were established

to protect the consumer. In this case the trig-
46 . Environmental Contaminants in Food

ger for designation of PBBs as known environ- check for known environmental contaminants

mental contaminants was sick cattle, not are insufficient to detect toxicants in food for

chemical monitoring. which there have been no action or tolerance

From these two case studies it appears levels established.

that monitoring programs designed mainly to

CHAPTER III REFERENCES

1. Federal Food, Drug and Cosmetic Act, 21

U.S.C. 321 et seq.

2. Poultry and Poultry Products Inspection Act,

21 U.S.C$ 451 et seq.

3, Federal Meat Inspection Act, 21 U.S.C. 601 et

seq.

4. Merrill, R, A, FDA Re,gu~ation of Food Safety,

unpublished manuscript, 1978.

5. Kennedy, D., Commissioner, Food and Drug

Administration, to J. B. Cordaro, Jan. 22,

1979,

6.21 CFR 109.

7. Arnold, F. T. Kepone Action Levels—Review,

Analysis and Recommendations, Office of

Special Pesticide Reviews, Environmental

Protection Agency, Mar. 9, 1977.

8. “Polychlorinated Biphenyls(PCBS), Reduction

of Tolerances, ” Federal Register 44(127):

38330, 1979.

9. Food and Drug Administration. Report in Response to the Office of Technology Assessment letter of June 5, 1978—’’Request for Information on Federal Capabilities for Environmental Mcmitoring and Toxicity Testing, ”

1978.

10. Food and Drug Administration. Compliance

Program Guidance Manual, Compliance Program 7305.007 -’’Pesticide and Metals in

Fish Programs” (FY ‘78), Oct. 1, 1977.

11. Food and Drug Administration, Compliance

Program Guidance Manual, Compliance Program 7305.006-’” Radionuclides in Foods”

(FY “78), Oct. 1, 1977.

12. Clark, G. U.S. Department of Agriculture,

1979.

13. U.S. Department of Agriculture. The National

Residue Program, USDA-Food Safety and

Quality Service, May 1978.

14. Goldberg, E, D., V. T. Barrington, J. W. Harvey, G. H. Martin, J, H. Parker, P. L. Risebrough, R. W. Robertson, W. Schneider, E. S.

and E. Gamble. “The Mussel Watch, ” Environmental Conservation, vol. 2, Summer

1978,

15. Risebrough, R. W. Bodega Marine Laboratory, University of California, Bodega Bay,

Calif., personal communication, 1978.

16. Huggett, R. J., M. M. Nichols $ and M. E.

Binder. “Kepone Contamination of the James

River Estuary, ” Proceedings of Symposium on

Contaminants and Sediments: Fate and

Transport, R, A. Baker (cd.), Honolulu,

Hawaii, April 1979 (in press),

17. Food and Drug Administration. Compliance

Program Evaluation (FY ‘77), Kepone and

Mirex Contamination (7320.79A).

18. McNally, J. M, “Pol~brominated Biphenvls:

19

Environ-mental Conta-mination of Food, ” special paper for OTA, Library of Congress, Congressional Research Service, 1978.

Michigan Department of Agriculture, Information and Education Division. “A Brief

Chronology of the PBB Incident” (no date).
Chapter IV

State Laws, Regulations,

and Programs

. .

,=-
Chapter IV

State Laws, Regulations,

and Programs

STATE LAWS

State food and drug laws, and the organizations that administer them, vary

widely. Basic State food and drug statutes are based on the Federal food laws;

however, not all States have adopted the model uniform State food, drug, and cosmetic bill of the Association of Food and Drug Officials. As shown in figure 3, 42

States have adopted the model statute, which is almost identical to the 1938 Federal Food Drug and Cosmetic Act. Consequently, these 42 States have the same

legislative authority for regulating food contaminants within their borders as the

Federal Government does for food in interstate commerce. The 1906 Act, still retained by eight States, does not contain the tolerance-setting provisions of the

1938 Act under which environmental contaminants are regulated (l).

Authority for regulating environmental

contaminants in food rests with two or more

agencies in most States. Usually the Department of Agriculture and the Department of

Health share responsibilities for food regulation. In some States a variety of other agencies and bodies are also involved in regulatory or research activities: departments dealing with commerce, fish and game, consumer

protection, environmental improvement, public administration, conservation, along with

university divisions, independent laboratory

agencies, and various independent boards

and commissions (2).

The Food and Drug Administration (FDA)

believes that this variability in laws and regulatory organizations makes it more difficult

for the States to accomplish their goals:

The variability of organizational structure

complicates the problems of many of the individual State agencies in accomplishing

their program goals because of overlapping

responsibilities and the lack of a clear delineation of responsibilities. For example, it is

not uncommon to find authority granted to

two agencies for some divided program segments of a single program category (e.g.,

Figure 3.— State Food Laws

50 r 42

40 —

30 —

Inu

%

z

20 —

10 —

o —

f

8 —

4

FD&C Act 1906

25

Food

Uniform FD&C Act Additives

20

2L

34

fEnrichment

I

Pest Req

Amendment

(Food ) Color

Additives

SOURCE Food and Drug AdmtnlstratlonState Programs and Serwces m Food

and Drug Control, 1978

49
milk, shellfish). Frequently, two or more in- stances, the State agency has an unclear role

dependent agencies of relatively equal rank as an advisor or consultant to the local govare charged with enforcement of portions of ernment. However, the local agency may not

the same general food and drug law. In still be legally bound to follow the advice and/or

other States, there is no central State control direction that may be suggested by the State

over the food and drug program. In these in- agency (1).

STATE Monitoring PROGRAMS

Non-Federal monitoring is limited almost

exclusively to programs originated and carried out by individual States. In some cases

there is close coordination between State and

Federal activities. Federal agencies may decrease their monitoring in a given area if

State monitoring is considered sufficient. For

example, FDA does not monitor seafood for

kepone (3) even though the concentrations in

finfish, crabs, or shellfish remain essentially

unchanged since its discovery in 1975 (4).

FDA feels that the ongoing monitoring programs in Virginia are sufficient to protect the

consumer.

Analysis of the OTA State survey reveals

that State food-monitoring laboratories are

equipped to analyze for those substances that

are regulated in foods through action levels

or tolerances. For instance, most had instrumentation (atomic absorption spectrophotometers and gas chromatography) to analyze for

mercury and chlorinated hydrocarbon pesticides.

FDA published a study entitled “State Programs and Services in Food and Drug Control” in September 1978 (l). The publication

provides a compilation of States’ analytical

capabilities during the years 1975 and 1976,

listing numbers and educational levels of

chemical analysts, types of analytical equipment, and expenditures for food inspection.

In 1974 and 1975, the States spent annually about $64.9 million for food inspection and

analytical activities. This amounted to 72 percent of their total inspection and analytical

expenditures (l). Table 8 shows program

areas and expenditures for States. These

Table 8.—Program Areas and Expenditures for

States

Expenditures

Millions of Percent of total

Program dollars (food and drug)

Food ‘. . . . . . . . . . . . . . . . . . $64.9 72.3

Drugs, devices, cosmetics . . . 9.7 11.0

Feed . . . . . . . . . . . . . . . . . . . . 6.4 7.0

Weights and measures (food) . 5.5 6.0

Pesticides ... , ... , . . . . . . . 3.3 3.7

Total . . . . . . . $89.8 100.0

SOURCE Food and Drug AdmlnlstratlonS/ate Progrdms and Serv/ces /rJ food

and Drug Contro/, 1978

figures do not include the estimated $75 million expended by local governments.

The educational levels of the chief chemist,

supervisory chemist, and chemist and laboratory technicians are presented in table 9 (l).

The salary ranges for the chemical personnel

are shown in table 10 (l). Only 1 percent of

the chemists working in State food and drug

programs earned more than $20,000 per year

in 1975 and 1976. Approximately 64 percent

of them had annual salary ranges of $8,000 to

$15,000.

The available analytical equipment and

physical facilities are listed in table 11 (l).

These data confirm the OTA survey findings,

since gas chromatography and atomic absorption spectrophotometers rank first and

third, respectively, in numbers. A breakdown

of food commodities analyzed, samples collected, and analyses performed is given in

table 12 (l). The FDA document urges caution

in interpreting these data because “. . . some

States do not maintain comprehensive analytical records on food analyses especially if

food is not the major laboratory workload.”
Ch. IV—State Laws, Regulations, and Programs ● 51

Table 9 .—Number of Employees by Category and Education Level in Various State Food and Drug Programs

Personnel ‘- Number of employees Advanced degree College degree Some college No college

Chief chemist. . . . . . . . . . 109 68 ‘

-

4 0

- -

1 0

Supervisory chemis t 232 62 167 3 0

Chemist. . . . . ... . . . . . 633 66 561 6 0

Laboratory technicians . . 833 0 127 375 332

SOURCE Food-and-Drug Adminlstratlon Slate Programs and Serv/ces (n food and Drug Conlro/ 1978

Table 10.—Salary Ranges of Various Chemical Personnel in State Food and Drug Programs

Salary-range s

$ 6,000- 9,000- 

. . . . . . . . . . . . . . .

$ 7,000-10,000 . . . . . . . . . . . . . . . .

$ 8,000-12,000 . . . . . . . . . . . .

$ 8.000-14,000 . . . . . . . . . . . . . .

$10,000-15,000 . . . . . . . . . . . .

$12,000 -18000. . . . . . . . . . . . . . . . .

$16,000-20,000 . . . . . . . . . . ... . .

over $20,000 . . . . . . . . . . . . . . . .

Number of chief chemists

o

0

0

2

2

17

71

8

N u m ber of s u pervisory chemists

3

0

0

17

143

53

7

0

SOURCE Food and Drug Admlnlstratlon- Sfate Programs and Sew/ces In Food arrd Drug Cor?tro/ 1978 -

Table 11 .—Physical Facilities and Key Equipment in

114a State Food and Drug Laboratories

Number of key

Key equipment items equipment itemsb

Spectrophotometers . . . . . . . . . . . . . -

269

Flame photometers . . . . . . . 90

Atomic absorption spectrophotometers . . 125

Spectrofluorimeters . 88

Gas chromatography . . . . 348

Polarographs. ... . 42

Polarimeters . . . . . 54

Mass spectrometer. ., . . 19

Electrophoresis. . . . . ., . . 86

Auto analyzers. ., ... . . . . . . . . . . 120

Liquid chromatography . . . . . . ., . . . . . 18

Physical facilities

Average floor space (ft.2

) . . . . . 10,245

Average bench space (tin, ft.). . . . . . . . . 845

Average storage (ft. z) 1,150

a

Two States not reporting lab equipment or space

bshows only total number of equipment Items reported by the s!ate a9encles

Does not show those labs that do not have one or more of the equipment items

listed

SOURCF Food and Drug AdmlnistratlonStale Programs and Services In Food

and Drug Con Ire/ 1978

Number of chemists

o

26

70

153

139

5

0

0

This probably accounts for the extensive analytical activity reported in the “other food”

category, rather than in the categorical program areas”’ (l). Even so, it is evident that

milk and milk products are the most commonly sampled and analyzed food commodities.

The large number of samples and analyses

indicate that the States perform extensive

monitoring for regulated contaminants in

food, But the low salary ranges, the lack of sophisticated analytical equipment such as

mass spectrometers, the time spent per analysis, and the sample-type distribution indicate that State monitoring programs are as

inadequate as Federal programs in detecting

environmental contaminants in food for

which no action or tolerance levels have been

established,
52 ● Environmental Contaminants in Food

Table 12.—Total Number of Samples, Sample Determinations, and Man-Hours by Food Commodity Categories

With Number and Percentage of States Reporting Analytical Activity

Number of States

Food commodity reporting analytical

categories activities

Bakery products. ., . . . . . 35

Soft drinks . . . . . . . . . . . . . 35

Candy . . . . . . . . . . . 29

Grade A milk (raw) . . . . . . 50

Other milk products. 47

Canned foods. . . 35

Frozen foods . . . . . . . 27

Seafood. . . . . . . . . . 34

Shellfish . . . . . . . . . . . . 24

Raw agricultural products 29

Other foods. . . . . . 40

Total s

Number of samples

Percent of States (thousands)

70 11.5

70 18.7

58 7.0

100 342.0

94 200,7

70 21.3

54 7.3

68 6.6

48 37.6

58 40,1

80 103,0

7958

Number of

determinations

(thousands)

23.3

64.6

18.1

1,157,1

546.8

870

27.6

34.4

106.3

89.6

326.3

2,481,1

Number of manhours (thousands)

31.5

17,5

13.6

319.0

185.6

48.5

19.3

33.2

67.6

112,7

220.1

1,068.6

SOURCE Food and Drug Adnllnistrallon S/ate Programs and Serv/ces In Food and Drug Control 1978

FEDERAL/STATE LIAISON

Many environmental contamination incidents are initially State problems. Theoretically, the Federal Government does not become involved until a contamination incident

is determined to be an interstate problem.

Given the complexity of this country’s foodmarketing system, most food produced or

processed within a particular State is distributed for consumption in other States. Thus,

most environmental contamination incidents

are likely to become interstate concerns.

Figure 4 reveals the extent of food contamination that can occur from a single source of

contamination, in this instance polychlorinated biphenyls (PCBs) contaminated animal

feed from a meatpacking plant in Billings,

Mont. (5). This widespread contamination of

food occurred during an estimated time period of 2 to 5 months.

The States and the Federal Government establish liaison when contamination crosses

State lines. Liaison is also established at the

request of States. States often require Federal assistance in investigating a contamination incident. The objective is to generate scientific information on the nature and extent

of the contamination. This information would

include the toxicological and chemical properties of the contaminating substance, the

amount and type of food contaminated, and

the concentration of the substances in food.

Such information is used by State and Federal authorities to: 1) determine the appropriate Government response for protecting the

public health and 2) inform the general public

about the incident and explain the Government response. To contain an incident, scientific information needs to be accurate and immediately available. This is as true for an episode involving a substance that has previously contaminated food (1979 PCB contamination of animal feed in Billings, Mont. ) as for

a substance which has not (1973 polybrominated biphenyl (PBB) contamination of animal

feed in Michigan).

The generation and dissemination of scientific information on an incident is hindered by

the number of State and Federal agencies involved. As already noted, three Federal agencies (the Environmental Protection Agency

(EPA), FDA, and the U.S. Department of Agriculture (USDA)), each with different responsibilities, can be involved along with various

State agencies. The PBB incident in Michigan

and the PCB incident in Montana reflect this

particular problem.

Generating Information

Before the needed scientific information

for developing regulations is generated, the
Ch. IV—State Laws, Regulations and Programs ● 53

4

I

.L_-
.54 . Environmental Contaminants in Food

contaminating substance in food must be

identified. This identification process may require lengthy investigative work which could

be hindered by a multiplicity of involved Federal and State agencies. The PBB incident

provides an example of the extensive investigations sometimes necessary.

The Michigan Department of Agriculture

(MDA) initially analyzed blood and feed samples from a herd owned by Mr. Frederic Halbert (at his urging). These samples proved to

be negative because MDA was not analyzing

for PBB. Additional samples were analyzed

by the USDA’s National Animal Disease

Center in Ames, Iowa. While the Disease

Center detected an unusually high peak of an

unidentified substance, it did not determine

its identity. The substance was eventually

identified by Dr. George Fries of USDA’s

Agriculture Research Center at Beltsville,

Md., who had previous experience in chemical analysis of PBB (6). The discovery came

nearly 8 months after adverse symptoms occurred in the herd at the Halbert farm.

The laboratories and agencies involved in

identifying PBB are part of the agriculture

system in the United States. They were the

obvious institutions to which Mr. Halbert

would go for assistance. If he had initially

contacted the Michigan Department of Public

Health (MDPH), it is likely that different

Federal laboratories and agencies would

have analyzed the samples. There was and

still is no systematic procedure at the Federal

level for assisting States in identifying a

potential food contamination problem like

PBB. Were it not for the perseverance of Mr.

Halbert and the experience of Dr. Fries, the

identity of PBB might have taken longer and

the people of Michigan would have been exposed to PBB-contaminated food even longer.

Once a contaminant has been identified in

food, the necessary scientific information can

be generated for either regulating or controlling the contamination. In the PBB incident,

FDA helped to develop and evaluate this information and worked with MDA in controlling the incident. FDA’s involvement was

based on the fact that it has the Federal

authority for regulating contaminants present in food. Examples of actions taken by

State and Federal authorities in such instances include removing food from the market, setting action levels or tolerances for the

contaminant in food, and disposing of the contaminated food. Because little scientific information on PBBs was available, it took time

to generate the information and establish

final permissible levels (although contaminated herds and food were identified as

quickly as possible and removed from the

market). The PBB incident involved FDA,

USDA, MDA, and MDPH. Even more State

and Federal agencies were involved in the

PCB contamination episode in the Western

United States.

The PCB contamination began in Montana

with animal feed and quickly spread to 16

other States. Idaho was particularly affected

by the contamination of poultry and eggs.

This incident involved all three relevant Federal agencies—FDA, EPA, and USDA—as

well as the Idaho Departments of Agriculture

and Health and Welfare, and district health

departments. USDA made the initial analysis

of poultry samples which proved positive for

PCB; FDA was involved with the removal of

PCB-contaminated food from the market; and

EPA with the proper disposal of the contaminated food. At least 5 days elapsed from the

time USDA was confident it had a PCB contamination incident to the time it notified FDA

of its findings. It took FDA an additional 5

days to begin its investigation of the contamination incident (7). Such delays would be

unlikely if only one Federal agency were involved or communications between the two

agencies were better.

PCB is a substance whose chemical and

toxicological properties are fairly well

understood. It has contaminated food in the

past. Nevertheless, there was confusion

among the State agencies in Idaho as to the

proper response to the contamination. The

confusion resulted from two conditions. First,

some of the State officials involved were not

familiar with the chemical and toxicological

properties of PCB. PCB was a new food con-
Ch. IV—State Laws, Regulations. and Programs ● 55

taminant in Idaho, and the appropriate officials had little experience with this type of

problem. Second, the involvement of three different Federal agencies obstructed efficient

communication between the State agencies

and the Federal Government.

While the Federal agencies had the most

expertise on PCBs, the sharing of that experience was hindered by the fact that it was

available in and distributed by three sources

instead of one. Consequently, State agencies

had to go to different Federal sources, depending on what information they needed. In

addition, the Federal agencies did not always

communicate with the various State agencies.

EPA, for example, took air and water samples

in the area surrounding Ritewood Farms to

determine whether PCBs that contaminated

Ritewood’s eggs and poultry came from either

of these two sources. This was before the

PCB-contaminated animal feed was identified. EPA, however. did not report their negative findings to the State. In another instance,

USDA initially would report its results only to

the Idaho Department of Agriculture, the

State agency with which USDA has had a

long-standing association. The Idaho Department of Health and Welfare, which is concerned with protecting the public health, at

first was not informed by either USDA or the

State Department of Agriculture of the PCB

contamination. Communication broke down

at two levels, between the State and Federal

Governments and within the State government (8). The fact that there are several different Federal and State agencies involved

with different aspects of controlling and

regulating a contamination incident further

complicates an already complicated problem.

The major environmental contamination incidents that occurred in Idaho and Michigan

continue to be major issues of concern among

the residents of these States--a result of

their fears over a potential health threat that

cannot be seen, smelled. or tasted. In Michigan, for instance, the PBB episode remains a

live and controversial political issue. Consequently, it becomes imperative that the information generated by the State and/or Federal Government on an incident is accurate

and appropriately applied. This objective is

hindered by the variety of State and Federal

agencies that become involved.

CHAPTER IV REFERENCES

1.

2.

3.

4.

5.

U.S. Department of Health. Education, and

Welfare, Food and Drug Administration.

State Programs and Services in Food and

Drug ~ontrol, 1978.

OTA Survey of 31 States, 1978.

Food and Drug Administration. Compliance

Program Evaluation (FY ‘77), Kepone and

hlirex Contamination ( 7320. 79A).

Huggett, R. J., hi. hf. Nichols, and M. E.

Binder. “Kepone Contamination of the James

River Estuary, ” Proceedings of Symposium on

Con tc~minan ts and Sediments: Fete and

Transport. R. A. Baker (cd.), Honolulu, Hawaii. April 1979 (in press).

Gardner, Sherwin, Acting Commissioner of

Food and Drug Administration. Testimony be6.

7.

8.

fore Subcommittee on Oversight and Investigation, House Committee on Interstate and

Foreign Commerce, Sept. 28, 1979.

Michigan Department of Agriculture, Information and Education Division. ‘‘A Brief

Chronology oft he PBB Incident ,“ (no dat e).

Foreman, Carol Tucker, Assistant Secretary

for Food and Consumer Services, U.S. Department of Agriculture. Testimony before the

Subcommittee on Oversight and Investigation, House Committee on Interstate and Foreign Commerce, Sept. 28, 1979.

Gallagher, Ed, State Health Officer, Idaho Department of Health and Welfare, personal

communication, Oct. 10, 1979.
Chapter V

Methods for Assessing

HeaIth Risks
Chapter V

Methods for Assessing Health Risks

The availability and quality of data on the toxicity of contaminants in large

part determine the Food and Drug Administration’s (FDA) ability to protect public

health. Chapter III reviewed the strengths and weaknesses of FDA’s procedures

for setting action levels and tolerances. This chapter addresses four issues related to the methods used for assessing health risks:

●

●

●

●

What is the role of human epidemiology in the setting of action levels and

tolerances?

What are the roles of animal and other toxicological tests?

Are current testing procedures adequate for the assessment of interactions of toxic substances?

Are methods for quantitative risk assessment sufficiently developed for

application to environmental contaminants in food?

POSSIBLE TOXIC EFFECTS

The possible toxic effects of an environmental contaminant depend on its chemical

nature, its concentration in food, and the type

of toxic action involved. If the substance is

highly toxic and/or is consumed in large quantity, acute toxic effects may occur and the

onset of the symptoms would be rapid and

severe. If a small amount of a highly toxic

substance is consumed, or if the substance is

of low toxicity, the health effects may not be

seen for many months or years (or may not be

observed at all). Potential effects of toxic environmental contaminants in food include systemic toxicity, mutations, cancer, birth defects, and reproductive disorders.

Systemic toxicity involves changes in the

structure and function of organs and organ

systems: weight change, structural alterations, and changes in organ system or whole

animal function. Functional effects may include changes in the lungs, liver, and kidneys,

in cardiovascular function, in brain and nervous system activity and behavior, and in resistance to disease (1). Systemic toxicity is

studied in whole animal tests.

Some environmental contaminants have

been shown in experiments to cause point mutations (which generally affect a single gene)

or more extensive effects such as gross

changes in chromosome structure or changes

in chromosome number. Such genetic effects

in humans often cannot be immediately detected. Indeed, damage to the human gene

pool may not become apparent for many generations if the deleterious effect is due to a recessive gene (2). However, a chemical’s mutagenic potential can be evaluated indirectly

from various biological tests involving microorganisms, mammalian cell cultures, insects,

and whole mammals (l).

Some environmental contaminants in food

may cause cancer. Direct cause-and-effect

associations between exposure to a specific

chemical and human cancer are difficult to

establish because of the complex nature of

cancer and the vast number of potential carcinogens to which humans are exposed. In

some cases, exposure to one toxic agent may

trigger a sequence of events leading to

cancer. In others, carcinogenesis may depend

on interactions of several factors, combinations of noxious agents, co-factors, and

natural or acquired metabolic peculiarities

(2). The cancer-causing potential of a sub59
stance is evaluated through animal tests and

a variety of short-term tests employing bacteria, insects, or cell cultures (1).

Environmental contaminants may produce

birth defects other than inherited mutations.

These are called “teratogenic effects. ” Malformations may include gross, histological,

molecular, and sometimes behavioral anomalies. Human sensitivity to a teratogenic agent

during pregnancy is determined by: 1) the

time at which the insult is received during

gestation, 2) the dose of the compound,

3) transfer of the teratogen to the developing

fetus, 4) uterine factors, and 5) dietary factors. The teratogen may work its effect by

producing mutations or chromosomal aberrations, interfering with cell division, altering

nucleic acid synthesis, inhibiting specific

enzymes, or altering membrane characteristics. A seemingly small change may have far-

-reaching effects, since the fetus is undergoing

rapid biochemical, structural, and physiological growth and change (1).

Environmental contaminants can have

other effects on the reproductive process in

both males and females. Toxic effects may include reduced or altered sperm formation, inhibition of ovulation, increased spontaneous

abortion, fetal resorption, and increased

numbers of stillborn infants, Teratogenic and

reproductive effects are evaluated through

animal tests (l).

Given the range of possible adverse health

impacts, it is clear that newly discovered environmental contaminants must be subjected

to the best available toxicological testing

techniques so that any harmful effects can be

uncovered. Furthermore, regulators must

have information on the possible toxic effects

of ingesting small amounts of a substance in

food over an extended period of time, perhaps over a lifetime. It would also be desirable to know what effects other toxic substances already present in our air, water,

and food may have on the metabolism and

toxicity of a new contaminant,

HUMAN EPIDEMIOLOGY

The science of epidemiology seeks to determine the distribution and causes of diseases

and injury in humans, It focuses on groups

rather than individuals (3).

There are several types of epidemiological

studies. Each provides different levels of information on environmentally related disease

or injury. The cohort-study method is the best

way to develop information on potential toxic

effects in a population exposed to an environmental contaminant in food. In a cohort

study, individuals are classified into groups

according to the levels of exposure, including

a control group with no previous exposure to

the suspect substance. The groups are then

followed over a period of time and studied for

differences in disease incidence (3). Such epidemiological studies have an advantage over

animal tests. There are some agents known to

cause disease in humans that do not produce

similar adverse effects in animals (benzene,

for example) (4). Human epidemiological data

can also be used to directly estimate human

risk, thus eliminating the need for extrapolating from animal experiments.

Epidemiological evidence has sometimes

weighed heavily in the setting of tolerances or

action levels. This was the case in FDA’s decisions on mercury and polychlorinated biphenyls (PCBs). However, if epidemiological data

are lacking when an environmental contaminant is discovered in food, the usefulness of

further epidemiological studies is restricted

by inherent limitations of the science.

Beyond the obvious ethical considerations,

such studies are of little use when a rapid

regulatory decision must be made. At the low

levels that environmental contaminants usually occur in food, pathological effects may

not occur for many years, Most cancers, for

example, have a latency period of at least 5 to

10 years, As much as 40 years may elapse between the onset of exposure and the development of the disease, Thus epidemiological
Ch. V—Methods for Assessing Health Risks ● 61

methods can only be used retrospectively to

evaluate the health status of individuals who

have been through this 5- to 40-year period.

The findings are compared to the health histories of “control” individuals who presumably have not experienced comparable exposures.

Such retrospective studies are vulnerable

to scientific criticism: a) it is very hard to find

an adequate control group (unlike animals

whose entire lives can be in a “controlled”

environment) because of the variability in

human susceptibility and personal behavior

patterns, b) it is impossible to define potential

synergisms and/or inhibitions by other substances to which the target group may have

been exposed, and c) it is difficult to quantify

previous levels of exposure (5).

Retrospective studies suffer other handicaps, They are extremely expensive, difficult,

and time-consuming to carry out, A given type

of cancer, for example, may occur in the

“normal” population at a rate of 1 case for

each 100,000 people. An exposure to a toxic

substance that increases by a factor of 100

the likelihood of that cancer occurring would

raise the incidence to 1 case for each 1,000

people. To ascertain in a statistically satisfactory and compelling way that such an increase had occurred, one would have to do

comprehensive medical studies on at least

3,000 people. Assuming an average cost of

$200 for each person studied (which is a low

estimate considering the costs of physicians”

time, laboratory analysis, and the technological assessments necessary to show a person

free of a given tumor or disease), the expense

for such a study would be $600,000. It would

be necessary under most circumstances to

find more than one new case of a disease to

convince a nonstatistician and even most

statisticians. This would double or triple the

costs (5). Furthermore, demonstrating that

the incidence had increased would still leave

the vexing problem of correlating the increase with the exposure to the specific

suspect substance.

Such limitations make cohort epidemiology

studies inappropriate for determining the toxic potential of a given contaminant. Moreover, in a regulatory scheme designed to prevent serious illness from developing in humans, the time required to generate epidemiological data would preclude its use in initial

regulatory decisions. The prospects for developing a human epidemiological method that

would meet such regulatory demands are

presently hard to imagine.

One area, however, where human epidemiological studies have and will continue to

be useful is in the confirmation of suspected

chronic-effect data when a population that

has inadvertently been exposed to a substance or a hazard (such as radiation) over a

long period of time can be identified. In this

instance, carefully designed studies can

be the “clincher’” which finally provides

thorough documentation of the suspected toxicity. Such studies can confirm or refute the

adequacy of regulatory actions (in retrospect)

(5), Again, however, these kinds of studies are

extremely expensive and consume limited resources which might be better spent supporting other types of evaluations using other

techniques.

People who fail to understand these limitations criticize reliance on animal tests when

epidemiological information is negative or

lacking. This fundamental misunderstanding

may delay health-related regulatory action

and dilute its effectiveness in preventing

illness.
62 . Environmental Contaminants in Food

ANIMAL TESTS AND OTHER METHODS FOR

TOXICOLOGICAL TESTING

Toxicologists have developed a number of

techniques to assess the toxicity of a compound. Some tests can be conducted in 90

days or less. These include simple tests such

as 2-hour “range finding” to determine the

dose of a substance that is lethal to 50 percent of the animals (LD50). More complex

tests include 90-day continuous exposure or

paired feeding studies, and short-term tests

for mutagenesis and potential carcinogenesis. Tests requiring more than 90 days, such

as lifetime exposure studies, are generally

considered long-term. In addition to the time

necessary for exposure and data-gathering,

analysis of the results may take up to an additional year, depending on the complexity of

the experiment, the number of animals used,

and the amount of data collected (l).

Testing methods can be categorized by

‘‘endpoint” as well as duration. Some experiments are based on expected results such

as functional changes, birth defects, or cancer, By the use of an appropriate experimental design, several such endpoints can be

assessed in the same experimental period (l).

Appendix C describes the range of toxicological tests available for assessing the health

risks associated with consumption of contaminated food. Each section describes the tests

for assessing a given endpoint, and includes a

discussion of available long- and short-term

tests,

Animal tests provide valuable information

for the setting of action levels and tolerances.

The animals serve as proxies for humans in

cases where data are lacking on the human

health effects of a contaminant and experiments involving humans would be unethical,

Because of shorter animal lifespans, the effects on several generations can be studied.

Furthermore, animals can be raised in controlled environments, thus eliminating many

of the factors that complicate human epidemiological studies, In many cases, animal

experiments are the only means by which

needed information can be obtained. Using a

carefully selected battery of 90-day tests,

considerable data can be generated on a contaminant’s potential toxic effects including its

potential for causing mutations and cancer.

Despite widespread scientific agreement

on the usefulness of animal tests, several controversies exist. These include the appropriateness of the carcinogen bioassay techniques, the potential of short-term tests for

evaluating mutagenesis and carcinogenesis,

the lack of emphasis on testing for potential

toxic interactions, and the usefulness of

methods for extrapolating from high-dose animal test results to low doses in humans.

The Carcinogen Bioassay

The carcinogen bioassay (6) is a chronic

toxicity study requiring 2 years’ exposure to

the test substance and usually a third year

for evaluation of the results. The carcinogen

bioassay is used to determine the cancercausing potential of a compound in males and

females of two mammalian species, usually

the rat and mouse. The test animals are exposed to the test substance throughout their

entire lifespan.

Different groups are exposed to different

levels of the substance up to the maximum

tolerated dose (MTD). The MTD is the highest

dose given during a chronic study that predictively will not alter the animals’ normal

longevity from effects other than cancer. In

practice, the MTD is considered to be the

highest dose that causes no more than a 10-

percent loss in weight compared to control

animals. Throughout the study, animals are

examined weekly for signs of toxicity. Animals may be killed at prearranged times and

their tissues examined for signs of cancer. At

the completion of the study, all remaining

animals are killed and detailed examinations

are made of their tissues.

Animal tests for carcinogenicity have been

questioned because the results are generalized to humans while the animals are fed
Ch. V—Methods for Assessing Health Risks ● 63

much larger doses of the suspected substance

than would be consumed by people. However,

an earlier OTA report entitled Cancer Testing Technology and Saccharin (7) found that

“animal tests are the best current methods

for predicting the carcinogenic effect of substances in humans. All substances demonstrated to be carcinogenic in animals are regarded as potential human carcinogens; no

clear distinctions exist between those that

cause cancer in laboratory animals and those

that cause it in humans. The empirical evidence overwhelmingly support s this

hypothesis. ”

The report also found that the rationale for

feeding high doses was sound.

The rationale for feeding large doses of a

substance in animal tests is as follows. As

the dose of a substance that causes cancer is

increased, the number of exposed animals

that develop cancer also increases. To conduct a valid experiment at high dose levels,

only a small number of animals (perhaps several hundred) is required. However, to conduct a valid experiment at low dose levels, a

very large number of animals is required.

(The smallest incidence rate detectable with

10 animals is 10 percent or 1 animal. To

detect a l-percent incidence rate, several

hundred animals would be required.) Another important variable is the strength of

the carcinogen. The stronger the carcinogen,

the greater will be the number of animals

getting cancer at a particular dose (7).

If data from a carcinogen bioassay are

available at the time an environmental contaminant is discovered in food, the results

provide crucial information to guide the

regulatory decision. However, if no data or inadequate data exist, a newly commissioned

carcinogen bioassay would require 2 to 3

years for completion. In this case, the carcinogen bioassay could be used to revise an

initial action level.

Short-Term Tests for Mutagenesis

and potential Carcinogenesis

Chemicals are evaluated for mutagenicity

not only to detect potential carcinogens but

also to detect the serious hazard posed by mutagens. In the long run, chemical compounds

causing mutations and teratogenic effects

may create a greater burden on society by increasing the incidence of genetic disease and

birth defects than by causing cancer (2,11).

A number of short-term tests and batteries

of tests have been developed to assay chemicals for mutagenicity (1,2). Many of the same

tests are also viewed as screens for carcinogens on the assumption that cancer arises

following damage to the genetic material of

cells (2). The ability of these tests to detect

carcinogens is currently undergoing validation (8). The Environmental Protection Agency (EPA) currently uses some of these tests to

identify mutagens (9, 10). Presently there is no

universal agreement on a “best” set of tests.

Environmental contaminants in food are

screened to identify those capable of causing

genetic damage, to determine the types of

damage they cause, and to evaluate the risks

they pose to the general population and certain subpopulations.

The major difficulty in designing tests to

detect mutagens and potential carcinogens is

the need to reflect the metabolic capabilities

of man as nearly as possible while remaining

economically realistic. Whole animal tests

more nearly reflect responses of man and are

therefore useful in estimating risk to humans.

Tests using lower organisms are less directly

applicable to humans, but they are simpler

and more economical to perform. As a consequence they are more popular for use in mutagen screening than animal tests. Risk estimates based on tests in lower organisms have

been proposed (12) but are not accepted as

sufficient evidence for setting action levels

and tolerances.

Many chemicals are not directly mutagenic, but once ingested or absorbed are converted into mutagenically active derivatives.

Activation therefore poses important practical and conceptual problems that must be

dealt with in evaluating the mutagenic potential of environmental agents. The practical

problem is one of designing tests to identify
64 ● Environmental Contaminants in Food

mutagens that adequately mimic the metabolic capabilities of an intact animal. The conceptual problems focus on the fact that evidence of an agent’s mutagenicity is not sufficient to evaluate the actual risk posed to an

individual or a population by exposure to the

agent (2).

The ability of an agent to cause genetic

damage in an intact animal depends not only

on the mutagenic potential of the agent or its

metabolizes but on a number of other factors

as well. The fate of any chemical substance

entering the body is determined by a dynamic

process involving its absorption, distribution,

biochemical alteration, and excretion. Many

mutagenic agents are formed by the action of

intestinal bacteria. Consequently, the route of

exposure to an agent can play a significant

role in determining its activity. Enzymatic

processes in the body inactivate as well as

create mutagens. Many active mutagens may

exist in the body as intermediates in the

metabolic pathways that process the parent

compounds. As a result, the active mutagen

may have a short lifespan and be distributed

only in those tissues that possess high levels

of activating enzymes (2).

There are four major factors determining

the ability of an environmental agent to produce a genetically adverse effect in an organism, The first is the metabolic response of

the organism to the agent. This response will

determine the distribution, lifespan, and fate

of the mutagen in the body tissue. The second

is whether the mutagen damages the genetic

material in cells. The third is the response to

the genetic damage by the DNA repair machinery in the cell. Fourth is the type of lesion

the agent is capable of producing in the genetic material.

Short-term tests for detection of mutagenesis and potential carcinogenesis fall into

four categories:

●

●

●

Q.

procedures that can be carried out directly in human populations,

intact animal tests,

tests employing cultured mammalian

cells, and

tests employing micro-organisms.

Several procedures that can be carried out

directly in exposed human populations have

been found to be indicators of the presence of

mutagenic agents. These procedures include

analysis of white blood cells for chromosome

aberrations (cytogenetic analysis) (13), analysis of blood and/or urine of the presence of

mutagenic agents (14), analysis of semen for

abnormal sperm (15), and the detection of extra chromosomes in sperm (16).

Intact animal tests usually use as test

animals either mice or fruit flies [Drosophila

melanogaster). The dominant lethal test detects lethal damage resulting primarily from

chromosomal aberrations by treating male

mice with test agents and mating them. The

uteri of the pregnant females are examined

for fetal death and resorption. Because the

endpoint is detected in the offspring of the

treated animal, mutation in the germinal cells

(the sperm) is detected by this method. The

specific locus test involves the crossing of two

genetically distinct strains of mice with visible markers, such as spotted coats. Mutations

are detected by the appearance of recessive

traits in the offspring. The utility of this testis

restricted because of the number of animals

needed. Cytogenetic screening of white blood

cells or bone marrow cells from treated

animals detects damage to chromosomes.

The micronucleus test detects chromosome

breaks in bone marrow cells of treated animals (17).

The use of cultured mammalian cells for

mutagenesis testing is a great simplification

over the use of intact animals. At the same

time, the cells retain much of the mammalian metabolism and genetic characteristics.

Moreover, human cell cultures can be used

where exposure of people to toxic agents

could not be allowed. The major weakness of

cultured mammalian cells as test systems is

that they are isolated from the metabolic activity of the intact animal (2).

Several strategies have been developed to

try to approximate the metabolic capabilities

of the intact animal in mammalian cells, The

simplest and most widely used activation system employs homogenates of mammalian
Ch. V—Methods for Assessing Health Risks ● 65

liver. Either the liver homogenate is incubated with the test substance before it is applied to the cell culture, or the test substance

and the homogenate are included in the test

plates. A major difficulty with the liver microsome activation system is that it cannot be

prepared with reproducible enzyme levels

from one batch to the next. Storage conditions also alter the activities of the preparations, Furthermore, not all the activation

mechanisms present in the intact animal are

represented in the liver homogenate. The

greatest advantage of the liver homogenate

method is that it preserves the simplicity of in

vitro testing (18).

Methods for mutagen screening have been

developed using many micro-organisms, including fungi, bacteria, and viruses present

in bacteria. The most widely known system is

the “Ames test” which employs specially

bred strains of Salmonella bacteria. Figure 5

illustrates the steps in the Ames spot test. The

Ames plate test allows quantitative comparisons to be made of mutagenic potential (19).

Numerous other tests have been devised

which are in varying stages of validation (20).

Some of these are described in appendix C.

The great appeal of these techniques is that

they are rapid, simple, and inexpensive. No

animal colony is required, and the necessary

technical skills are those required for conventional bacteriology.

These tests have been criticized because

the cell structure of bacteria is very different

from the cell structure of mammals. Validation studies now underway are attempting to

evaluate 30 mutagenicity assay systems for

their ability to predict chemical carcinogenicity (8).

Bacteria also lack the enzyme systems that

are the principal mammalian mutagen-activating enzymes. This criticism is partially

overcome by the use of liver homogenates described above. Finally, each test is sensitive

to one particular type of genetic damage.

Therefore, the best approach is to use a battery of short-term tests designed to test for

the different types of genetic damage.

Interactions of Two

or More Substances

Tests designed to detect effects from interactions of two or more substances are of limFigure 5. —Steps in the Ames Spot Test

Suspected carcinogen

on filter paper

Rat-liver Tester

extract bacteria

2

MUTAGENESIS is detected in the Ames test by mixing an assay” a dose of the chemical to be tested is placed on a

extract of rat liver (which supplies mammalian metabolic disk of filter paper on the tester bacteria. After 2 days most

functions) with tester bacteria (which cannot grow because of the his- bacteria have died for lack of histidine (2), but

a mutation makes them unable to manufacture histidine, a DNA damage caused by the chemical diffusing out from

necessary nutrient) and plating the mixture on an agar the disk has given rise to mutations, some of which result

medium so that a thin layer of bacteria covers the medium in reversion of the his- mutation. The histidine-making

evenly, as is shown on a microscopic scale (1). In this “spot revertant bacteria proliferate, forming visible colonies (3).

SOURCE Redraw n v, II h perm[sslon Devoret R Bacterldl Tests for Polen!lal Carcinogens Scfentlffc Arner/can 241 (2} 40 August 1979
ited use for regulatory actions. This does not

mean that such information is not important.

It rather reflects the rudimentary nature of

our present understanding of interactions,

the complexities of the tests, and the difficulties in interpreting the results in a fashion

meaningful to regulators.

Six different types of interactions may occur when two or more chemicals interact in a

biological system. The effects produced may

differ in magnitude from those caused by any

one of the chemicals alone.

●

●

●

●

●

●

If the interaction of two substances produces an effect equal to the sum of the

individual effects, the response is called

summation or addition.

If the interaction of two substances produces an effect greater than would be

anticipated from the sum of the individual effects, the response is known as potentiation or synergism.

If the effect is less than the sum of the

two would predict, the response is antagonism.

When an inert substance, having no

observed effect at a given dose, enhances the effect of another simultaneously administered chemically, the effect is usually referred to as activation.

If an inert substance decreases the effect of another chemical administered simultaneously, the effect is called inhibition.

Finally, there may be no interaction and

each chemical would exert its own effect

independently of the other (2 1).

Once ingested, a chemical may exert an action locally in or on the stomach or intestines.

While such effects possibly could be produced by environmental contaminants, they

are not likely to be observed at the low levels

normally encountered in food. The more serious concern is the systemic effects that may

occur after absorption from the gastrointestinal tract.

Following absorption from the gastrointestinal tract, additive chemicals may produce

their effect by acting on a target organ, by

acting on different target organs or systems,

or by acting differently on different organs to

produce the same effect. Most of the interactions are at the biochemical level and the

mechanisms are still being studied.

The key consideration is whether present

testing technologies are adequate to provide

data that are useful in making regulatory

decisions. Techniques have been developed to

study the interactions of drugs, other chemicals, and physical agents such as radiation.

Such techniques should be applicable to the

study of the effects of environmental contaminants. However, their scope is usually limited to the study of two component interactions because of the large number of test animals required and the difficulties in interpreting the results. For example, a relatively

simple test involving two agents in a factorial

design would require about 100 animals. A

more recent study (22) of the combined effects of cadmium, mercury, and lead used 50

to 60 animals in each of 15 different treatment groups. The results indicated that a particular combination of the three metals could

be synergistic, antagonistic, or additive, depending on the relative doses employed (table

13).
Ch. V— Methods for Assessing Health Risks ● 67

The testing for interactions among toxic

substances is further complicated by the necessity to limit the number of substances

studied, Because of the large number of animals required, and the difficulties in interpreting results, the number of substances

tested are confined to those that may be most

important, Deciding what is ‘‘important” to

study out of the vast number of toxic substances to which we are exposed is a difficult

problem, Perhaps a reasonable approach

would be to focus on those to which people

are known to be exposed (see chapter VII).

The choice could also be based on structureactivity relationship or known mechanism of

action, Chemical selection for testing is being

reviewed and evaluated in an ongoing OTA

study entitled “Assessment of Technologies

for Determining the Carcinogenic Risk from

the Environ merit.”

The study of the interactions of two or

more substances is an area in which far more

basic research is required before meaningful

information can be generated for regulatory

decisions. At the present time, no satisfactory

methods exist for testing the interactions of

more than two chemicals.

Extrapolating From High Doses

tO Low Doses

Quantitative risk assessment. based on

mathematical models, is often proposed as an

alternative to the current use of safety factors (chapter 111) (24,25). This approach is

now most extensively employed in assessing

carcinogenic risks (26). The technique is also

being investigated as a means to evaluate

other types of irreversible toxic effects (23).

The following discussion of mathematical extrapolation of risk involves only its uses in determining risks from chronic low-level carcinogenic insults.

Mathematical models can be used to estimate the number of extra cancers that are

likely to be caused by the presence of a carcinogen in the food supply. Models may be

used to estimate a tolerance based on calculations of a “safe dose’” for human consumption. They can also forecast the likely change

in the number of extra cancers that would accompany some projected increase or decrease in the level of human exposure occurring either as a result of regulatory action or

inaction, The technique is therefore used to

calculate benefits to be derived from reducing human exposure to a substance.

The typical carcinogen bioassay use s

around 100 animals at each experimental

dose. If a particular experimental dose produces evidence of a lifetime increase in

cancer of 1 in 10, this increase can be measured using 100 animals. But if the increased

cancer risk is less than 1 in 100, this increase

will often not be detected even with a 100-

animal feeding experiment. The extra human

risk resulting from environmental exposure is

usually much smaller than 1 in 100 (perhaps

on the order of 1 in 100,000) for any given

chemical over a lifetime exposure. It would

not be practical to conduct an experiment

with enough animals to directly measure this

small an increase in risk (30).

For these reasons, carcinogen bioassays

use (in addition to a control dose of zero)

several doses at which the projected extra

cancer incidence may be 1 in 10 or larger.

These high-dose data are then used to estimate the extra risk at a very low dose where

the extra risk may be no larger than 1 in

1,000,000. These problems are often referred

to collectively as the “low close extrapolation

problem” (30).

A low-dose extrapolation involves the

choice of a mathematical function to model

the dose-response relationship and the choice

of statistical procedures to apply to the mathematical function (24-29). The choice of mathematical function is crucial to the outcome of

a low-dose risk estimate. If the assumed relationship between tumor occurrence and dose

does not apply in the low-dose regions to

which the extrapolation is being made, a serious overestimate or underestimate of the

“safe dose’” may result. Even though different

dose-response models may agree in the observable response range, they could differ by

many orders of magnitude at low-dose levels.

Furthermore, there is no experimental way to
68 . Environmental Contaminants in Food

predict the shape of the dose-response curve

at very low doses,

Because of the possible disparity of doseresponse functions when extrapolated to low

doses, the dose-response function must be selected not only on the basis of how well it can

be made to fit experimental data but also on

the basis of known (or at least plausible) information on the biological mechanisms

through which a chemical induces or promotes cancer. This is a major source of uncertainty in extrapolation procedures, since

the exact biological mechanisms through

which carcinogenesis may occur are unknown (30).

Several theories on the nature of the process by which cancer develops serve as the

bases for different low-dose extrapolation

models. Some “linear” models project that

the relationship between the dose received

and the cancer risk is a straight line at low

doses and that there is no threshold. Other

models level off at low doses and therefore

predict that a threshold dose exists below

which the agent has no carcinogenic effect

(24-30).

Newer models take into account the effects

of metabolic activation and detoxification

upon carcinogenic dose response (26), These

“kinetic” models encompass free toxic substances, metabolizes, deactivators, and the

possible interactions of these substances,

Only a “steady-state” situation is studied in

that the variation over time of the concentrations of these agents is not considered. If

deactivation of the carcinogen is 100-percent

efficient, the model predicts a threshold dose

below which there is no carcinogenic risk.

However, in a naturally occurring process, it

is likely that deactivation would be less than

100-percent effective. A number of modifications to the model allow for imperfect deactivation. These situations rule out a threshold

and would lead directly to a model for which

carcinogenic response varies linearly with

dose at low dose,

The mechanisms through which most carcinogens produce cancer are not sufficiently

understood so that the shape of the doseresponse curve can be predicted with certainty, As pointed out earlier, experiments of

sufficient size to permit direct experimental

investigations of the dose-response curve at

low dose cannot be conducted. There are

plausible arguments that the dose-response

curve is linear at low dose for many carcinogens, On the other hand, no mechanism that

would lead to a more cautious dose-response

relationship has been seriously proposed except for some dose-response relations in

radiation-induced carcinogenesis.

In view of these uncertainties, it would

seem reasonable to base estimates of added

cancer risk on a mathematical model that encompasses low-dose linearity until the mechanisms through which the carcinogen operates

are understood sufficiently to conclusively

rule out low-dose linearity,

Caution must be used in interpreting the

results of low-dose extrapolations, particularly when they are applied to humans,

Table 14 demonstrates that different models

applied to the same data sets yield differing

estimates of virtually safe doses. Virtually

safe doses based on the multistage model are

identical with those based on the one-hit

model when there is only one experimental

dose. This is illustrated with Data Sets I and

Table 14.—Virtually Safe Doses Computed

From Three Different Data Sets and

Three Different Models

Virtually safe doses (lower

Dose- 95-percent confidence bounds

Data response for dose) in ppb corresponding

set model to extra risk of 1/1 ,000,000

la ... Probit 14.2

SOURCE Adapted from K S Crurnp and M D Masterman Assessment of Car

c Inoqenlc R(sk From PC Bs In Food OTA Working Paper 1979
Ch. V—Methods for Assessing Health Risks ● 69

II. The multistage model also yields virtually

the same value as the one-hit model for Data

Set III. However, as explained in appendix D,

the multistage model can yield higher values

for the virtually safe dose than the one-hit

model whenever the data exhibit upward curvature and are inconsistent with the one-hit

model (30).

Caution also must be exercised when comparing calculations of extra lifetime risks.

Table 15 summarizes the results of an FDA

risk assessment of PCBs (31) with a similar

risk assessment commissioned by OTA (30).

Differences can arise in such calculations

when different methods are used to extrapolate from animals to man. The extrapolation

can be performed on the basis of milligrams

per kilogram of body weight per day, parts

per million of substance in the diet, milligrams of substance per square centimeter of

body surface area per day, or milligrams of

substance per kilogram of body weight per

lifetime.

Table 15. — Extra Lifetime Risks of Cancer

Associated With Consumption of PCBs in Food

Extra lifetime Upper limit of new

Dose (g/day) risk/100,000 cancers/year

FDA’

9 2’ 4 4 21

14 9 ’ 72 34

201 [ 9 8 47

OTAb

3 3(! 013 4

035 11

127f 5

‘]BaCI,j r,n NC I birldssd 7 io j tc. td mallqn,+n Ifs fr,! mdlf,: .in{j f[malfs

: Ba+fI! ,rl K !mh rrju qh ~ 1 q 751 S(I jff Y and hppa tor~lrular care {ncm]ds

‘ Ba\Ifj c, n h [q h f~ f [ or SII MC rs ?f!lh ~If rc c r] t I If) of f I sh ~ per I(,S con tam I n ,itr?{j

* I t h PC. F3< I f trd(. rar> r c I,> I dt I I ~ h~, t j ,it 1 2 r r ~ [~ [ r.)

[j Ba>e(j , ,r, FDA T r,ld I D IPt St (1 j Y 1 q ?(J

~’ Ba\P j ‘n F E! A T 01+ I D I( t 5 I hIj ~ 1 Q 75

fBa~{, cj ,, ~1 ~+(.r~qf In tak ~ c f rf’flrlf ‘r n., II m IrTq mr)re than 24 I hs t par Lak c

MlchiQan fish

1.

2,

3.

CHAPTER V

SRI International. “Assessment of h4ethods

for Regulatin~ ‘Unavoidable” Contaminants in

the E’ood Supply, ” OTA Working Paper, 1978.

Legator, hf. S. “Short ‘1’erm Procedures fo r

Determining Nlut:ig~;niclCar cinogenic Activist},’” OTA ~lrorking Paper, 1979.

Llachfahon, B., and T. F. Pugh. Epidemiolog}r

Principles (]nfl Mcthmls, Little, Brow-n and

Differences also arise when varying animal data serve as the basis for the risk assessment, And, of course, the choice of the

model also affects the final outcome. In this

case, both extrapolations were based on milligrams of PCB per kilogram of body weight

per day. Both FDA and OTA applied a linear

model: however, different assumptions were

made on the amount of PCBs that would be ingested and on the size of the exposed population. FDA’s risk assessment therefore applies

to the 15 percent of the total U.S. population

expected to consume the fish species known

to be most highly contaminated with PCBs.

The OTA calculations are based on the average daily intake of PCBs based on FDA's total

estimates of the PCB intake

consumed more than 24 lbs of

sport fish per year.

Although many different

models exist and can be used for low-dose

risk assessment, it appears prudent at this

time to use a model that does not arbitrarily

rule out low-dose linearity. Models are still

being developed and when” appropriate could

be used to guide regulatory decisions. Doseresponse models for low-dose risk assessment

provide a useful technique for assessing the

possible added risk attributable to environmental contaminants. Such models also might

well be used in place of safety factors in

future procedures adopted for food contaminant regulations. The major impediment to

the widespread use of the models in environmental food contamination considerations is

the lack of data on which to perform the analysis.

REFERENCES

4.

5.

Company, Boston, Mass., 1970.

Ray, V. “Are Benzene Effects Limited to the

Chromosomal Level?, ” Banbury Report 1—

Assessing Chemical A4utqgens: The Risk t~~

Humans, Cold Spring Harbor Laboratory,

1979.

]ackson, R, S. “The Limitations of Applying

Iluman Epidemiology to the Regulator Pro-
70 ● Environmental Contaminants in Food

6.

7,

80

9.

10.

11,

12.

13.

14.

15.

16.

17.

18.

cess for Toxic Substances, Particularly Carcinogens,” OTA Working Paper, 1979.

Sontag, J. M., N. P. Page, and U. Saffiotti.

Guide~ines for Carcinogen Bioassay in Sma~l

Rodents, DHEW Publication No. (NIH) 76-801,

Government Printing Office, Washington,

D. C., 1976.

Office of Technology Assessment. Cancer

Testing Technology and Saccharin, Government Printing Office, stock no. 052-003 -

00471-2, Washington, D. C., 1977.

U.S. Department of Health, Education, and

Welfare. National Toxicology Program Annual Plan Fiscal Year 1979,

U.S. Environmental Protection Agency. FIFRA

Testing Guidelines, 1978.

U.S. Environmental Protection Agency. TSCA

Test Standards, 1979.

Neel, J. V. “Mutation and Disease in Humans, ” Banbury Report l—Assessing Chemical Mutagens: The Risk to Humans, Cold

Spring Harbor Laboratory, 1979.

Committee 17, Council of the Environmental

Mutagen Society, “Environmental Mutagen

Hazards,” Science 187:503, 1975.

Kilian, D. J., and D. Picciano. “Cytogenetic

Surveillance of Industrial Populations, ”

Chemical Mutagens, Principles and Methods

for Their Detection, Vol. IV, A. Hollaender

(cd.), Plenum Press, New York, 1976.

Legator, M, S., L. Troung, and T. H, Connor.

“Analysis of Body Fluid Including Alyklation

of Macromolecules for Detection of Mutagenic Agents, ” Chemical Mutagens, Principles and Methods for Their Detection, Vol. V,

A, Hollaender and J, DeSerres [eds.), Plenum

Press, New York, 1978.

Heddle, J. A., and W. R. Bruce. “On the Use of

Multiple Assays for Mutagenicity, Especially

the Micronucleus, Salmonella, and Sperm

Abnormality, Assays in Progress, ” Genetic

Toxicology, P. Scott, B. A, Bridges, and F. H.

Sobels (eds.), 1977.

Kapp, R. A. Mutation Research, in press,

1979.

Kilbey, B. J., M. Legator, W. Nichols, and C.

Ramel. Handbook of Mutagenicity Test Procedures. Elsevier, Amsterdam, 1977.

Ames, B. N., W. E. Durston, E. Yamasaki, and

F. O. Lee. “Carcinogens and Mutagens: A

Simple Test Combining Liver Homogenates

for Activation and Bacteria for Detection, ”

Proceedings of the National Academy of

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

31.

Sciences 70:2281, 1973.

Ames, B. N. “A Bacterial System for Detecting Mutagens and Carcinogens, ” Mutagenic

Effects of Environmental Contaminants, H. E.

Sutton and V. I. Harris (eds. ), Academic

Press, New York, 1972.

Devoret, R. “Bacterial Tests for Potential

Carcinogens, ” Scientific American 241(2):40,

1979.

Fingl, E., and D. M. Woodbury. “General Principles, ” The Ph~lrmacological Basis of Therapeutics, L. S. Goodman and A. Gilman (eds. ),

5th edition, MacMillan Publishing Co., Inc.,

New York, 1975.

Schubert, J., E. J. Riley, and S. A. Tyler.

“Combined Effects in Toxicology—A Rapid

Systematic Testing Procedure: Cadmium,

Mercury, and Lead, ” Journal of Toxicology

and Environmental Health 4:763, 1978.

Van Ryzin, J., personal communication, 1979.

Interagency Regulatory Liaison Group, Work

Group on Risk Assessment. “The Scientific

Bases for Identification of Potential Carcinogens and Estimation of Risks,”’ Journal

National Cancer Institute 63:241, 1979.

Scientific Committee of the Food Safety Council. “A Proposed System for Food Safety Assessment ,“ Food and Cosmet. Toxicol. 16,

Supplement 2, 1978.

Cornfield, J. “Carcinogenic Risk Assessmerit, ” Science 198:693, 1977.

Crump, K. S., D. G. Heel, C. H. Langley, and R.

Pete. “Fundamental Carcinogenic Processes

and Their Implications for Low-Dose Risk Assessment, ” Cancer Research 36: 2973, 1976.

Guess, H. A., K. S. Crump, and R. Pete. “Uncertainty Estimates for Low-Dose-Rate Extrapolations of Animal Carcinogenicity

Data, ” Cancer Research 37: 3475, 1977,

Rai, K., and J. Van Ryzin. “Risk Assessment of

Toxic Environmental Substances Using a

Generalized Multi-Hit Dose Response Model, ” Energy and Hecdth, N. Breslow and A.

Whittemore (eds, ) SIAM Press, Philadelphia,

Pa., p. 94, 1979.

Crump, K. S., and M. D. Masterman. “Assessment of Carcinogenic Risk from PCBS in

Food, ” OTA Working Paper, 1979.

U.S. Food and Drug Administration. An Assessment of Risk Associated with the Human

Consumption of Some Species of Fish Contaminated With Polych~orinated Biphenyls

(PCB’S), 1979.
Chapter VI

Methods of Estimating

and Applying Costs to

Regulatory Decisionmaking

*

54-515 0 - 79 - 6
Chapter VI

Methods of Estimating and Applying

Costs to Regulatory Decisionmaking

In the previous chapter, various testing methods for assessing health risks

were evaluated for their usefulness in regulating environmental contaminants—

i.e., setting an action level or tolerance. The primary issue involved in assessing

health risks is not whether the potential risks from an environmental contaminant

should be evaluated for purposes of regulation but rather what testing methods

are most appropriate for assessing potential risks?

The situation is reversed, however, when the associated costs of an action

level or tolerance for an environmental contaminant are assessed. The primary

issue is whether the costs should be taken into account in the setting of a

tolerance or action level. This is a policy issue which is addressed in chapter IX,

“Congressional Captions. ” In this chapter, the various approaches and techniques

for estimating the costs and benefits of a proposed tolerance or action level are

assessed, along with two common methods for applying cost and human risk data

in the regulation of environmental contaminants. A more detailed discussion of

the approaches and techniques for estimating the costs and benefits is provided in

appendix E.

Two methods, the cost-effectiveness method and the cost-benefit method, are

analyzed for their strengths and weaknesses as regulatory decision-assisting

tools. This analysis provides a basis for the discussion in chapter IX on the role of

economics in regulating environmental contaminants in food.

Cost-effectiveness is a regulatory decisionassisting tool that compares the estimated net

costs of the proposed regulation in dollar

terms with estimated reduction of human risk

expressed in scientific terms. In the regulation of environmental contaminants, the costeffectiveness method would compare the estimated change in costs of a proposed action

level or tolerance for a contaminant in food

with the associated reduction in human

health risk—i.e., the benefits of the proposed

tolerance or action level. The comparison of

net costs and risk reduction is performed for

several alternative levels in order to select a

tolerance or action level. The principal cost

of regulatory action is the cost of food held off

the market because it exceeds the proposed

action level or tolerance. There would also be

a reduction in medical costs as a result in the

reduction of human risk. These costs would

need to be subtracted from the cost of restricted food.

The cost in lost food would also have associated distributional effects which would

need to be identified to fully weigh the impact

of a regulation. These effects would include

identifying the consequences for producers,

change in the cost of food to consumers, and

indirect impacts on such businesses as food

processors, animal feed manufacturers, or

bait and tackle shops,

The cost of food losses and related effects

would be compared with the estimated reduction of human risk for the contaminant at the

proposed action level or tolerance. The hu73
74 ● Environmental Contaminants in Food

man risk data could include such information

as the reduction in the estimated number of

new cancer cases, the potential mutagenic

and teratogenic effects, and other toxicological effects described in chapters II and V.

The toxicological effects vary by substance

and are stated in scientific terms. The estimated net cost and reduced human risk at

various proposed action levels or tolerances

are estimated and compared. The cost-effectiveness method then requires the regulatory

agency to make its own judgment on what is

the proper balance of net cost and reduced

human risk when setting a tolerance or action

level.

The Food and Drug Administration (FDA),

for example, followed a similar procedure in

its decision to reduce the tolerance for polychlorinated biphenyls (PCBs). In deciding on a

2 parts per million (ppm) tolerance for fish,

FDA compared for 5 ppm, 2 ppm, and 1 ppm

in fish the estimated reduction of human risk

with the estimated increase in the amount

and cost of food expected to be taken off the

market. Table 16 shows the human risk from

cancer and cost data on commercial fish for

each of the three levels and the net changes

in risk and cost for moving to a 2-ppm and 1-

ppm tolerance. It is these net changes that

are evaluated in the cost-effectiveness method, Though FDA reviewed other available

toxicological data, it was FDA’s judgment

that the reduction in risk (13.3 cancers) for a

l-ppm tolerance did not offset the increased

cost ($10, 3 million) and that a proper balance

for the net changes

Tolerance

5 parts per million (ppm)

2 ppm ,

1 ppm

was established at 2 ppm.

Thus, FDA has placed an implicit dollar value

on life. A more thorough application of the

cost-effectiveness method would attempt to

identify all the net changes in the benefits

(the reduction of all known risks) and all

known costs,

Judgment is an important aspect to the

cost-effectiveness method. It allows the decisionmaking body, in this case FDA, flexibility

in interpreting health data and evaluating the

implications of that data on the setting of a

tolerance or action level. This flexibility can

be particularly important in the assessment

of insufficient or variable toxicological data.

While an agency’s interpretation of toxicological data might differ from others and generate disagreement about the final decision, the

cost-effectiveness method does allow the complexity and shades of gray to be factored into

the decisionmaking process,

The health data used in the cost-effectiveness calculations are generated by the toxicological and epidemiological procedures reviewed in the previous chapter. There are

also various approaches and techniques used

to estimate the costs of food likely to be taken

off or restricted from the market as a result

of a proposed tolerance or action level. The

cost estimates will vary depending on the approaches or techniques employed. All these

approaches require chemical analysis of a

statistically significant number of food products known or thought to be contaminated,

With such data, the amount of contaminated

food that exceeds the proposed action level or

tolerance can be estimated,

Table 16.— Impact of PCB Tolerance

Lifetime risk of cancer for Reduction

heavy consumers of fish in human risk

9.8 per 100,000 or 46.8 new cancers

per year

Starting level

7.2 per 100,000 or 343 new cancers

per year

125 new cancers

4.4 per 100,000 or 21 new cancers per

year

13,3 new cancers

One year cost (1974

dollars) of commercial

fish (land value)

$ 06 million

$ 57 million

$16 million

Increasing

costs

Starting level

$51 million

$10.3 million

SOURCE Federa/ Reg/ster VOI 44 No 127 June 29 1979 p 38333
Ch. VI—Methods of Estimating and Apply/rig Costs to Regulatory Decisionmaking ● 75

FDA multiplies the estimated amount of

food removed from commerce by the appropriate price (production, wholesale, retail,

etc. ) per unit (pound, bushel, ton, or animal,

etc.). This method of estimating food costs is

not the most accurate way of estimating costs

and does not attempt to measure the indirect

costs or distributional effects that result from

an action level or tolerance.

There are two other approaches for estimating the costs from the reduction of the

food supply: the alternative-cost approach

and the opportunity-cost approach. The alternative-cost approach estimates the cost of the

next best alternative method or methods, if

available, for replacing food removed from

the market.

For example, assume that 164,000 lbs of

lake trout in Lake Superior were restricted

from commerce because of the 2-ppm tolerance for PCBs. The alternative-cost approach

would require cost estimates of each available method as well as various combinations

of methods for producing (and thus replacing)

the entire 164,000 lbs of lake trout, the

amount condemned by the tolerance. In establishing the replacement cost, this approach does not consider price or supply

shifts in the restricted food product nor shifts

in the supply of other food products. Such

shifts are likely to occur when large amounts

of food in relation to the total supply are

taken off the market. Consequently, this approach can lead in some instances to an overstatement of costs.

The opportunity-cost approach does include shifts in supply. But what information is

included in the analysis depends on which

techniques are used. The budgeting technique only includes shifts in supply for the

contaminated commodity. This technique

uses data on the production of the contaminated product to calculate the costs of producing and consequently replacing a particular amount of that food product that has been

restricted from commerce. It is assumed that

other commodities will be produced in the

same amounts and at the same price that prevailed before the establishment of the tolerance or action level.

The modeling technique, however, includes

not only supply shifts but also resulting price

shifts in both contaminated food and other

food products. With this technique, mathematical models of the relevant portion of the

economy are employed to trace shifts in supply, changes in the amount and price of various commodities, and other factors affected

by the restriction on the use of a contaminated product.

These models can, if properly programed,

project changes in the production location of

particular crops as well as changes in the use

of various production factors in each region

of the country. Thus modeling can more realistically describe likely reactions in food production to the change created by a tolerance

level. The result is a better estimate of the potential cost of lost or restricted food.

In attempting to project replacement costs,

the opportunity-cost approach (using either

budgeting or modeling techniques) more accurately estimates the true costs of a tolerance or action level then either the alternative-cost or the FDA approach.

The distributional effects of a tolerance or

action level can be incorporated in the costeffectiveness method. But the opportunitycost approach can better generate these distributional effects. With either method these

effects are most easily identified when the

data are initially being collected. The information is important in determining who will

bear the brunt of the costs, both directly and

indirectly. The distributional effects flowing

from human health risks can also be identified. The available risk data can be assembled to determine who bears most of the potential and actual risks. Thus the distributional effects of the net cost and the reduction

of risk from a tolerance or action level can be

compared (l).
76 . Environmental Contaminants in Food

COST-BENEFIT

The cost-benefit method compares the estimated dollar costs of a proposed regulation

with the estimated dollar benefits of reducing

human health risks. The cost-benefit method

of setting tolerance or action levels also requires the evaluation of several alternative

levels. The differences in benefits and costs

as one moves from one proposed regulatory

level to the next are then compared. The tolerance or action level would be lowered until

the costs (impact from food condemned) are

greater than the benefits (reduction of human

risks). When this level is reached, the economically efficient tolerance or action level

will be the next higher level at which the benefits exceed the costs.

By representing the costs and benefits for

a proposed action level or tolerance in dollars, cost-benefit analysis attempts to make

the two sides of the ratio more comparable.

This method recognizes, as does cost-effectiveness, that any proposed action level or

tolerance will incur costs in terms of food

taken off the market and benefits reflected in

the reduction of either actual or potential

health risks. As the level is lowered, costs increase and human health risks decrease.

Techniques of estimating costs are similar

in the cost-benefit and cost-effectiveness

methods with the exception that the reduced

medical costs are included with the benefits.

There are some ways of valuing benefits,

though, which are unique to the cost-benefit

method.

Though both methods rely on the available

toxicological data, cost-benefit requires the

conversion of all data into dollar values. This

economic conversion is best accomplished

when the data are expressed as the number

of premature deaths per year avoided, the

number of person-days lost to illness avoided,

or the probability that some percentage of the

exposed population would die prematurely or

would lose a specified number of days from

normal activity due to illness.

Two approaches are available for converting the risks into dollars: forgone earnings

and willingness to pay. In the forgone-earnings approach the analyst places an explicit

economic value on life in attempting to estimate the productivity lost as a result of illness

or premature death caused by a contaminant

in food. This approach, however, does not include associated health costs such as medical

expenses incurred from illness. Including

such costs is required in order to more accurately represent the total reduction of

health costs—i.e., the benefits. The willingness-to-pay approach allows people affected

by the regulation (rather than the analyst) to

estimate how much they would be willing to

pay to avoid a risk.

The forgone-earnings approach attempts to

estimate the lost earnings of those individuals

who are estimated to become ill or die prematurely because of the contaminated food (l).

The estimated dollar value of the benefit will

be determined by various techniques chosen

or assumptions made by the analyst in converting the risk data to a dollar value. Discounting and earnings are two areas in which

the analyst can influence the value of the

benefit.

Since many of the benefits of a tolerance

are not likely to be realized until 10, 20, or 30

years later, discounting is used to convert

future dollar benefits into present dollars.

Discounting is also used for estimating future

costs. Discounting is required even if the future dollars are adjusted for the rate of inflation because a dollar spent now can be invested productively to yield a larger number

of real dollars—i.e., inflation adjusted—in

the future, For example, $100 invested at 5-

percent interest becomes $105 in one year.

Discounting is the reverse: $105 next year

has a present value of $100 when the discount rate is 5 percent. This means that

$10,000 worth of benefits that will occur 10

years from now would actually have a present value of $6,135 if a 7-percent discount

rate is used,
Ch. VI—Methods of Estimating and Applying Costs to Regulatory Decisionmaking ● 77

While most economists agree that future

costs or benefits need to be discounted, they

do not agree on the value of the discount rate.

The rate can vary from I percent to as high

as 15 percent (z). The rate, however, has to

remain constant for both the costs and the

benefits. Obviously, the value of the rate will

affect the estimate of benefits or costs, The

lower the discount rate, the greater the dollar

estimate in present dollars. Consequently,

more weight would be given to the benefits

and costs accrued in the future.

The estimate of the benefits also depends

on whether gross or net earnings are used.

Gross earning estimates include an individual’s or a group’s total wages or salaries. Net

earnings consist of total wages or salaries

minus the individual’s or group’s consumption. Obviously the gross earnings estimate

will be greater than the net earnings estimate.

The willingness-to-pay approach is conceptually a more correct approach in that it asks

the individual to place a dollar value on the

reduction of associated risks from an environmental contaminant. This value is then used

for placing a value on life itself. While conceptually correct, this approach does have

some inherent problems, such as: 1) the capability of the questioned person to accurately

understand the ramifications of the risk and

2) the individual’s economic position. For example, an economically disadvantaged person might place a small value on risk not because the person feels the risk is of little or no

concern but because that person cannot afford an increase in food prices. This approach is affected by the assumptions made

by the public being surveyed.

APPLICATION OF METHODS FOR REGULATION

The use of the cost-benefit and cost-effectiveness methods for regulatory purposes is

affected by the following factors: 1) FDA’s interpretation of the Food, Drug, and Cosmetic

Act, 2) the approaches and techniques for estimating the economic value of the costs and

benefits, and 3) the inherent difference between the two methods.

As noted earlier, FDA interprets the Act as

requiring it to weigh only the impact of the

cost and the amount of food removed from

commerce in the setting of the proposed tolerance or action level. FDA’s approach for

estimating this cost can be applied in either

the cost-effectiveness or the cost-benefit

method, but both of these methods can rely on

alternative-cost or opportunity-cost techniques which more accurately estimate the

cost incurred from condemned food. These

other techniques also more accurately estimate the tolerance or action level’s impact on

availability y of food than the approach used by

FDA.

Whichever technique is employed to estimate the costs, adequate information is

needed on the amount of food likely to be contaminated. Such information was available

for PCBs in fish, but it is not available for

PCBs in milk, poultry, and eggs. This is because contamination of milk, poultry, and

eggs is likely to occur as a result of industrial

accidents. Such accidents are sporadic and

therefore difficult to predict (e.g., the July

1979 PCB contamination of poultry and eggs

in Idaho) (3). Consequently, the estimates for

costs incurred because of food removed from

commerce cannot be determined for such

contamination incidents, and thus neither

method can be employed. Both methods could

be used to set a tolerance or action level for

mercury and kepone in fish.

The approach and techniques used by the

cost-effectiveness methods for generating

necessary data can take considerable resources and time, 2 months to over a year to

gather the data just for the costs alone. The

amount of time needed depends on the approaches and techniques used. The more accurate the information being generated, the

more time and resources are required.
78 . Environmental Contaminants in Food

FDA, however, often has to make an initial

decision in the form of an action level in 2

months or less for a newly identified environmental contaminant. A sufficient amount of

time is usually available for utilization of the

various approaches or techniques if a followup decision is involved. For- example, 6 years

expired from the time an initial PCB action

level was proposed until a final tolerance for

PCB was proposed this year. Either method is

more likely to be used in setting a formal

tolerance than an initial action level for an

environmental contaminant.

The substantive difference between the

cost-benefit method and the cost-effectiveness method is that the cost-benefit method

places an explicit value on life by converting

the health data to dollars while the cost-effectiveness method places an implicit value on

life by weighing the health data in its scientific form with the costs. As a result, a significant amount of judgment is exercised by the

analyst using the cost-benefit method when

selecting the different approaches and techniques for estimating the benefits. As discussed earlier, the selection of these approaches and techniques has a strong bearing on the outcome of the ratio and consequently the tolerance established by this

method.

The cost-effectiveness method places a

greater judgment burden on the agency and

less on the analyst. While the analyst does affect the outcome, judgment is primarily exercised by the agency in weighing the net cost

with the reduction in human risk (benefits).

The agency exercises less judgment in the

1.

2.

CHAPTER VI

Epp, Donald J. “Economic Analysis of Alternative Action Levels in the Regulation of Environmental Contaminants of Food, ” OTA

Working Paper, April 197’9.

Weinstein, Milton C., and William B. Stason.

“Foundations of Cost-Effectiveness Analysis

for Health and Medical Practices, ” New

England Journal of A4edicine, Mar. 31, 1977.

cost-benefit method, which only requires a

comparison of the numbers for each side of

the ratio to establish the appropriate tolerance.

The cost-effectiveness method has the potential to reveal more of an agency’s thinking

in the decision than cost-benefit does. This

was demonstrated with the earlier discussion

of FDA’s setting of a 2-ppm tolerance for

PCBs in fish. In addition, because it recognizes the uncertainties inherent in the estimates of the health risks, the cost-effectiveness method allows FDA the flexibility to adjust the weight given to the benefits or the

costs in its decision. For these reasons, the

cost-effectiveness method is the more appropriate method at this time for weighing the

costs in the setting of a tolerance.

Neither method can evaluate all the information required by FDA in setting a tolerance. For example, FDA requires for enforcement purposes analytical methodologies that

can detect, measure, and confirm the identity

of the contaminant at the level being proposed in food. This means that the tolerance

cannot be set at a level below the available

analytical capabilities for detecting the contaminant in food. While the analytical capability is an important factor in setting a tolerance, it cannot be evaluated within the decisionmaking framework by either method.

Consequently, these two methods should be

viewed as decision-assisting aids that allow

the regulator the means to weigh many of the

relevant costs and benefits in the setting of a

tolerance.

REFERENCES

3. Foreman, Carol Tucker, Assistant Secretary

for Food and Consumer Services, U.S. Department of Agriculture. Testimony before the

Subcommittee on Oversight and Investigations, House Interstate and Foreign Commerce Committee, Sept. 28, 1979.
\ Chapter VII

Monitoring Strategies
Chapter Vll

Monitoring Strategies

Monitoring involves the systematic collection and chemical analysis of food

samples or other samples from the environment. The aim is to protect consumers

by determining short- and long-term trends in the levels of various chemicals in

food and the environment.

STRATEGIES

Monitoring

achieve either

identify food

strategies can be shaped to

of two objectives. The first is to

lots that violate established

tolerances and action levels. The second is to

identify new environmental contaminants as

they enter the human food chain.

The first objective is met by regulatory

monitoring: the second through investigatory

monitoring. Each of these strategies could be

complemented by specimen banking. Neither

is incompatible or mutually exclusive.

Regulatory Monitoring

The Federal agencies responsible for limiting consumer exposure to contaminated food

now conduct regulatory monitoring. Food

samples are collected and analyzed for environmental contaminants for which action

levels and tolerances have been established.

Based on available information or agreements with States, not all samples are analyzed for all regulated substances. Regulatory

monitoring employs standardized, accepted

analytica1 techniques. Because the procedures are standard and can be verified by

other laboratories, they generate data that

can be presented in courts of law with little

probability of being successfully contested.

Chapter III reviewed Federal monitoring

programs and chapter IV reviewed State

monitoring programs. It is unlikely that these

monitoring programs will detect new environmental contaminants, since both are restricted to searching for regulated chemicals.

Therefore, investigatory monitoring approaches are vital.

Investigatory Monitoring

Investigatory monitoring attempts to detect

unregulated chemicals as they enter the food

chain. This strategy involves the collection

and analysis of samples which may or may

not be foods, The analytical techniques employed for the detection of unregulated chemicals may or may not be accepted as standard

methods comparable to those used for regulatory monitoring.

Analytical methods for investigatory monitoring include broad-spectrum determinations that may sacrifice some quantitative information (i. e., exactly how much of a given

substance is present in a sample) for more

qualitative information (i. e., better assessment of what or how many foreign substances are in the sample). These analytical

methods are not necessarily designed for use

in litigation, They are designed primarily to

indicate the presence of a potentially hazardous substance. If one is found, an accepted

analytical method to detect the substance

would have to be developed—a method compatible with instrumentation existing in regulatory-monitoring laboratories.

Investigatory monitoring includes two discrete types of monitoring: monitoring for suspected environmental contaminants, and

monitoring for uncharacterized environmental contaminants. Each of these (as well as
regulatory monitoring) can be complemented

by specimen banking.

Monitoring for Suspected Environmental

Contaminants

Some chemicals that are not regulated by

action levels or tolerances are suspected to

be dangerous to humans if consumed in foods.

This group includes chemicals that may be

present in food because of their use, toxicity,

production volume, and persistence. Examples of these chemicals can be found on the

Environmental Protection Agency (EPA)/

Natural Resources Defense Council (NRDC)

priority pollutant list established in June

1977. These substances may be called “suspected” or “potential” environmental contaminants.

Monitoring for suspected environmental

contaminants involves a different strategy

than the one used in monitoring for regulated

contaminants. Under the latter strategy,

foods are analyzed for compounds with specified action levels and tolerances to provide information for regulatory enforcement. This is

not required for investigator y monitoring.

Thus, the monitoring program for suspected

environmental contaminants is generally not

as intensive (see chapter 111), Furthermore,

the analytical methods for detecting suspected environmental contaminants may not

be as prescribed as those for regulated contaminants.

Suspected environmental contaminants

could be identified by surveying the universe

of industrial chemicals and ranking them according to their potential for entering the food

supply in toxic amounts (l). Such an approach has been recommended to FDA by an

internal study group established by former

Commissioner Donald Kennedy (7),

This method has been employed by the

Food and Drug Administration (FDA) to develop a list of chemical contaminants in food,

The criteria used in selecting the chemicals

included: occurrence in food, volume of production, associated impurities or byproducts,

predicted environmental stability, pattern of

use, oil/water partition coefficients, bioaccumulation potential, known toxicity, and

means of disposal. The FDA list of chemical

contaminants in foods is shown in table 17.

This approach is limited by available

analytical methods. Most of the chemicals

recognized as food contaminants are those

that are relatively easy to detect by gas

chromatography or atomic absorption spectrometry. Chemicals that cannot be easily

detected by these methods may, of course, remain unidentified and unrecognized as food

contaminants (l).

The factors used to identify a chemical’s

potential for entering the food supply are

based on knowledge of the properties and environmental behavior of other chemicals

already known to be in food. This knowledge,

in turn, is based on our information about the

extent of contamination information that

depends on our analytical capabilities. Thus,

there is an inherent tendency to identify as

potential food contaminants those chemicals

that are similar to chemicals already identified in food. Such a tendency can only be offset by the use of good scientific judgment or

the development of new data. This bias illustrates a general weakness in all systems for

setting priorities: chemicals on which there is

no information will automatically be given

low priority unless some room is left for largely intuitive judgments (1). The scientific criteria and methods used in determining what

priority various toxic substances receive in

monitoring programs are discussed in more

detail in appendix F.

Although these exercises in setting priorities suffer from many limitations (including

lack of data, poor choices of criteria on which

to set ranks, deficiencies in the scoring and

ranking systems, and deficiencies in scientific judgment), they still can serve a valuable

function in guiding monitoring systems. Setting priorities is a prescreening exercise in

which a compromise is struck between the effort expended in preparing a priority list and

the effort that would be wasted in identifying

and quantifying all the chemicals present in a

sample,
Ch VII— Monitoring Strategies ● 8 3

Table 17. —Chemical Contaminants in Foodsa

up to 1

up to 1 1

up to 1

up to 1 )

01-10

0.1-10

0.02-008

002-0.04

1.4

tr-6 7

03-2.0

t r-O. 1

0.2-0.8

unknown

unknown 1

unknown

unknown

unknown

unknown }

0.03-162

0.03-162

0.03 -16.2

Niagara River. N Y
84 . Environmental Contaminants in Food

Table 17.—Chemical Contaminants in Foodsa—(cont.)

Chemical contaminant Range in ppm Locations

White Lake, Mich

Ohio River, Ohio

Pine River. Mich

Houston Channel

Houston Channel

By applying appropriate criteria to the

universe of industrial chemicals, it may be

possible to detect potential environmental

contaminants in food that have not been identified as significant by other methods. Although there is no truly independent way to

verify the reliability y of priority lists, such lists

could be generated for a pilot program designed to evaluate this approach vis-a-vis uncharacterized monitoring.

Monitoring for Uncharacterized

Environmental Contaminants

Uncharacterized environmental contaminants are substances that may have entered

the food supply but which have not been

classified as regulated environmental contaminants or suspected environmental contaminants. Compounds may fall into this category because they are not known or suspected to occur in food. Because of a lack of

toxicity data on compounds, they may not be

recognized as threats to human health. This

class of substances is similar to suspected environmental contaminants in that there are

no stipulated analytical methods to detect

them and no monitoring is mandated. Uncharacterized environmental contaminants are

different from suspected contaminants in

that none have been placed on lists of potentially harmful substances.

Although validated analytical methods for

identifying uncharacterized environmental

contaminants may be lacking, data on their

presence or absence can be generated. Chemical analyses that are designed to show only

the presence or absence of a compound in a

sample are called qualitative analyses. In

many cases an accepted analytical method

for one class of compound will yield quantitative results for those compounds and qualitative results for others, Therefore, the pres-
Ch. VII—— Monitoring Strategies ● 85

ence or absence of some suspected or uncharacterized environmental contaminants may

be determined even though the chemist is not

specifically looking for them.

In setting up a system of monitoring for uncharacterized environmental contaminants,

some preliminary judgments would be made

about the chemical nature of the target substances. Classes of compounds to be monitored would be selected on the basis of their

structural characteristics, their use, and

their suspected toxicity. Trace metals, halogenated hydrocarbons, or radioactive substances are examples of such classes. The

class of compound determines the type of extraction required to separate the substance

from other constituents of food, as well as the

instrumentation needed to detect the presence of the substance.

The available analytical methods best

suited for the class or classes of compounds

under consideration would be selected. The

question of whether analytical techniques

are sufficiently advanced to support uncharacterized monitoring is explored in chapter

VIII.

The establishment of an uncharacterized

monitoring program would require the development of appropriate sampling and samplehandling guidelines. It would also be necessary to modify currently used analytical procedures. For example, a typical program for

organic contaminants would involve preliminary screening to establish baseline levels of

contamination in samples of food and water

or selected indicator species over a given

period of time. This information would then

be used to develop an appropriate sampling

plan to determine changes or trends over

time. An increase in levels of an uncharacterized substance indicates its entry into food

and water. This finding would trigger additional analytical efforts to characterize the

new compound. Preliminary information on

the substance’s structure would be transmitted to toxicologists for evaluation and

comparison with available information on

known toxic compounds. If alarming trends

or changes were observed, corrective regulatory actions could be taken.

Specimen Banking

It is difficult to detect environmental contaminants unless one is specifically looking

for them, Monitoring methods for identifying

suspected and uncharacterized environmental contaminants promise to partially alleviate the problems. Yet, even as new analytical

instrumentation is developed and scientific

knowledge expands, there will be new classes

of compounds discovered in foods that have

been present for years but were undetectable

with then-existing instrumentation. Information on how long the compounds have been in

food, what kinds of foods are affected, and

from what areas the foods were derived

would be of great help to epidemiologists and

public health officials who must decide

whether or not the chemicals have had (or

will have) an adverse impact on the public.

One approach to this problem is the collection and storage of samples on a regular basis

and in a manner that will protect their chemical integrity. In the future, when new instrumentation is developed or a toxic compound is

discovered in foods, samples can be withdrawn from storage and analyzed. This in effect would be retrospective analysis. Investigators could go back in time, reconstruct

events leading to a current situation, and estimate human exposures from the consumed

foods.

There are examples of this kind of retrospective detective work. When high concentrations of mercury were discovered in tuna

and swordfish, pollution was widely held

responsible, But analysis of museum specimens that had been stored for decades indicated that the mercury levels were probably as high a century ago as now. Therefore,

the mercury in fish may be from natural

sources and may have always been so. This

does not mean that the metal is not a potential

health threat but rather that the potential exposure from eating the fish has not changed

much over the years.
86 ● Environmental Contaminants in Food

There is a problem in utilizing most existing collections for retrospective chemical

analysis. Since samples were not collected

for use in chemical testing; they were not

stored in a manner to maintain their chemical

integrity. A 1975 survey of environmental

specimen collections in the United States by

Oak Ridge National Laboratories concluded

that few of the existing collections were suitable for retrospective chemical analyses (2).

Therefore, a need exists for a national program to collect, store, and maintain environmental samples (including food) to allow retrospective investigations,

EPA and the National Bureau of Standards

are now working towards developing such a

program by testing various methods of preserving samples for long periods of time without either adding unwanted chemicals or losing ones that are already in the sample. A

number of scientists are encouraging this

program and similar efforts (3-5). If continued

funding is made available for specimen banking of environmental samples (including

foods), future investigators will have an easier job of assessing what impact environmental contaminants in foods may have.

SAMPLING

Sampling involves the systematic collection

of information from a portion of the environment. Sampling is done in such a way that the

collected samples represent the whole in

terms of the information desired. In regulatory monitoring the samples must be food

commodities because the intent of the program is to determine the levels of regulated

substances in the food supply. This information is the basis for enforcement actions.

Food samples may not be the best indicators if the monitoring is meant to serve as

an early warning system—in other words, to

detect a substance soon after it enters the environment and before it gets into foods. It may

be better to analyze nonfood samples such as

river sediments, water, or uneaten organs

from food animals (the organs may concentrate the substance to analytically detectable

levels before it can be seen in the flesh). The

finding of an environmental contaminant in

nonfood samples would trigger the examination of foods.

The following discussion outlines the primary considerations in selecting samples for

investigatory monitoring systems. Constructing a sampling plan for such systems involves

a number of decisions based on preliminary

information about the nature and extent of

environmental contamination. Such decisions

include the number, sites, frequency, and

types of samples.

The number of samples to be taken depends on how much risk of being wrong we

are willing to accept. In other words, to what

degree of certainty do we want to know that

our food is free from environmental contaminants? One-hundred percent certainty would

require analysis of every food item. Acceptance of a lesser degree of certainty allows the

use of less costly sampling approaches.

Before preliminary data are collected,

there is no way to calculate the exact number

of samples needed to yield an answer of

specified certainty. The most difficult factor

to estimate is the variation specific to each

contaminant and how it changes over time

and space. This kind of information would

have to be collected in pilot programs for

suspected and uncharacterized monitoring

before a national sampling plan could be

developed. The number of samples taken will

probably be constrained by the money, manpower, and available laboratory resources.

The density and location of sampling sites

depend on the socially acceptable level of

uncertainty, whether the contaminant stems

from a point or nonpoint source, and how it is

transported in the ecosystem.

If one is dealing with widely distributed

nonpoint source environmental contaminants

that are transported through water, the ideal

sampling locations would be rivermouths that
Ch. VII—Monitoring Strategies ● 8 7

are discharge points of major watersheds.

one could very effectively monitor the industrial portion of Michigan by sampling

shellfish or fish from some two dozen major

rivers just as they enter the Great Lakes.

Baseline levels in these foods could be determined, but the origins of the contaminants

would be difficult to determine (6).

The other extreme is to monitor food products on a production, site-specific basis. If the

aim were to inventory all industries (including agriculture) that utilize and/or discharge

a toxic substance, one could then routinely

monitor food products, fish, and game at each

identified site. Theoretically, the kepone and

polybrominated biphenyls (PBB) situations

would have been detected much earlier with

such a system. The number of operation s

(large and small) that would need to be monitored is unknown, but the total appears to be

so large that the costs would preclude consideration of this alternative (6).

A reasonable compromise approach is to

use information generated under the Toxic

Substances Control Act on the types of chemicals manufactured at various locations to

guide in the development of a sampling plan

for use in investigatory monitoring systems.

The sampling plan would focus on some food

organisms and some nonfood items. The data

derived from analyses of such samples would

yield the greatest information about environmental contamination trends in the region

from which the samples were drawn.

The frequency of sampling depends on the

rates a t which the contaminant move s

through, accumulates in, and decomposes out

of the food production system being monitored, Different food production systems have

different genetic and environmental characteristics that determine the rates of material

dynamics or transfer. For a beef feedlot, a

range of 50 to 180 days would include the

period involving a single-batch process. For

an apple crop, a single sample per year would

suffice. The frequency of sampling may b e

different for each type of production process.

Once the species and the characteristics of

the production systems have been identified,

the appropriate sampling frequency can be

determined (6),

The selection of the types of samples to be

collected is also critical in identifying environmental contaminants as they enter the

food chain. Although biological samples offer

many advantages in monitoring systems, nonliving samples may be preferable in some instances. An example might be bottom sediments from rivers, lakes, or estuaries. Bottom

sediments are derived, for the most part,

from erosion of land and often bring with

them to the aquatic environment substances

that are used on land such as herbicides or

pesticides. Moreover, once they are in the

aqueous environment, they can “sorb” o r

concentrate many substances found in industrial discharges. The contaminated sediments

then serve as a mechanism to expose the

plants and animals that live in the waters to a

particular chemical. Contaminated sediments

may also be used to pinpoint the source of a

chemical once it has entered the river, lake,

or estuary (6).

Other types of nonliving samples might include air, river water, drinking water, or

rain. All have certain advantages and disadvantages. For instance, the concentrations of

many environmental contaminants in air and

water are very low, causing problems for the

analytical chemist. When a substance is

found in air or water, it is sometimes difficult

to determine where it entered the system.

However, because we breathe the air and

drink the water as well as eat the food from

these environments, air and water cannot be

eliminated as potential samples (6).

The most appropriate biological samples in

an investigatory monitoring system should

reflect key elements in the human food chain.

Samples may include not only traditional

agriculture products but also fish, game,

shellfish, crustaceans, and wild fruits and

nuts, Many of these wild foods also accumulate both point and nonpoint source environmental contaminants. Criteria for selection of

1– , 4—
88 ● Environmental Contaminants in Food

the exact organisms should include the following characteristics:

position in the food chain,

lifespan,

feeding behavior,

understanding of the organism’s physiology and biochemistry,

body fat content,

mobility,

availability for sampling, and

utility to humans (6).

Once a sampling plan is developed and

samples collected and analyzed, the dat a

must be presented in a form useful to the

regulator. The data analysis should be rapid

and provide information on trends as well as

specific concentrations without significant

distortion or deletion. Even with the bestdesigned computer retrieval system, the necessary data bank would become extremely

large, complex, and expensive.

The supply of data must also be timely. If

one wishes to regulate the level of an environmental contaminant in food when concentrations vary weekly, a monitoring system that

reports data with a 6-month delay is not

workable.

Finally, to develop information on exposure

trends and determine the effectiveness of

regulatory monitoring and enforcement, human tissues, blood, and urine can be analyzed

for the presence of environmental contaminants. Human monitoring can be performed

for either regulated, suspected, or uncharacterized substances. A sampling plan to detect

trends in exposure among different population groups could be developed, but data generated from human monitoring would be unable in most cases to identify the source of exposure. At the present time, EPA houses the

principal human monitoring program. This

program is primarily concerned with pesticide residues.

QUALITY ASSURANCE

To ensure that data generated by any monitoring strategy are as accurate as possible,

schemes have been developed to pinpoint errors. These schemes are called quality assurance programs. Such programs are mandatory in analytical laboratories because the

possibility y of errors always exist.

Errors arise from a number of sources. For

instance, impure chemical reagents, dirty

glassware, or sample containers can impart

contaminants to the sample that may interfere with the analysis and result in false

readings. Instruments are not always stable

and may give false readings. Some samples

may contain substances that interfere with

analyses, or a substance may be bound in a

sample in such a way that normal extraction

met hods will not extract it. Another factor is

the potential for human error in the laboratory. These factors, singly or in combination,

can lead to reported concentrations that are

in error. Since commodities that violate

standards could be marketed and consumed

if the results were erroneously low, human

health might be affected. If the results are

erroneously high, undue economic hardship

may be imposed on the food producer.

The Federal agencies that monitor foods

for environmental contaminants are aware of

these problems. Thus they use standardized

analytical methods that have been tested and

therefore offer some assurance that the results will be acceptable in court. When a violative sample is found, the product or batch is

reanalyzed whenever possible to assure that

results are valid.

These two practices are part of a quality

assurance program. There are others as well.

When a new chemical extraction or analysis

technique is tested, it is important to analyze

a sample w i t h known composition t o check

the validity of the technique. Also, during

routine determinations samples of known

composition should be analyzed to check on

the other types of potential errors. The

samples of known composition are called

“reference material" and may come from
Ch. VII—Monitoring Strategies ● 89

various source s including the Nationa l

Bureau of Standards and EPA,

Available reference materials do not

always satisfy the needs of current chemical

monitoring programs, since such materials do

not contain many known environmental contaminants. Moreover, the contaminants may

not be stable under the storage method used.

This is particularly true for synthetic organic

chemicals. Another problem is that the type

of reference material-i.e., beef liver—may

not be similar enough to the food samples to

be analyzed-–i.e., fish—to be very helpful.

This points up an important gap in our

ability to analyze accurately for environmental contaminants in foods. The variety of

reference materials and the variety of compounds of known concentration in these materials are insufficient to satisfy the needs of

the analysts. More effort must be expende d

to correct this problem.

Collaborative studies that involve more

than one laboratory or group analyzing the

same sample by the same or different methods are part of a quality assurance program.

If all results are similar within acceptable

limits there is some assurance that the method(s) are precise and perhaps accurate,

Often, more than one method can be used

to measure a given contaminant. Confidence

in accuracy can be increased if the methods

agree. This is one of the reasons that a monitoring laboratory should have several methods available.

All of these aspects are important to

assure that the proper answers are generated by a monitoring laboratory. All are timeconsuming and expensive. Therefore, any

chemical monitoring program must allocate

as much as 10 t o 20 percent of its time for this

increased workload.

CHAPTER VII REFERENCES
Chapter VIII

Monitoring Instrumentation

.
Chapter VIII

Monitoring Instrumentation

Various instruments have been designed to detect and quantify organic

chemicals, trace metals, and radioactivity in foods. This chapter focuses on not

only the technological state of this analytical art but also how such instrumentation could be applied in an investigatory monitoring program.

ORGANIC ENVIRONMENTAL CONTAMINANTS

Analysis

The vast number and wide diversity of natural and synthetic organic chemicals pose

difficult analytical problems. Many methods

and instruments have been developed to detect and quantify specific environmental contaminants in foods. There are generally three

steps required for each type of analysis: extraction, cleanup, and detection and quantification. Figure 6 is a flow chart depicting how

these steps would be applied to the analysis

of the Environmental Protection Agency priority pollutants in food.

Extraction usually involves mixing the food

sample with a selected solvent. In this step,

the chemical is removed from the food and

dissolved in the solvent. The time required for

this step depends on the physical and chemical characteristics of the food sample and the

substances. In some cases, the process may

take 24 hours or more. The initial extract contains not only the substance of interest but

possibly other organic compounds of similar

volubility that must be removed befor e

analysis.

The second step is known as the cleanup or

isolation stage. The complexity and time required for this procedure depends on the food

sample and the number of substances to be

removed. In many cases multiple cleanup

steps are necessary. The end products of

cleanup procedures are fractions containing

different classes of organic compounds.

The final step, detection and quantification, requires the use of highly sophisticated

instruments and techniques. Among the most

frequently used methods are mass spectrometry, gas chromatography, and liquid chromatography. Table 18 summarizes the techniques available for qualitative and quantitative organic analysis. More information can

be found in appendix G .

The gas chromatography is an instrument

designed to separate, identify, and quantify

organic compounds. In simplified terms it

consists of four components: an injection

port, a column, a detector, and a recorder.

There are many types of injection chambers,

columns, and detectors, but the principles of

operation are similar.

Gas chromatography involves vaporization

of the sample to be analyzed. The gaseous

sample then passes through a long tube or

column packed with a solid matrix which is

coated with an organic compound. This is

called the “liquid phase. ” The rate at which

various organic compounds in the sample

pass through this column is a function of

various chemical and physical properties,

notably molecular weight. polarity, and geometric structure. The time of passage through

the column is called the “retention time. ”

Each compound has a characteristic retention time in the column.

To determine when and how much of each

substance leaves the column, a detector is

placed at the end of the column. The retention

time can be used to identify each compound,

while the strength of the electrical signal

from the detector indicates the quantity. The

93
94 Q Environmental Contaminants in Food

Figure 6.— A General Scheme for the Qualitative and Quantitative Analysis of the Organic EPA Priority

Pollutants in Semisolid Foods

I

Extraction procedure Alternate

suitable for particular *

methods

food sample type ● w

t I

I

I

I

Initial cleanup

b

J

I

of extract - -0 ------ -

I

I

Initial interpretation

and quantification I

a Identification is based on the presence of characteristic ion fragments and associated chromatographic retention time

data. Absolute identification would require a detailed interpretation of the complete mass spectrum of the organic compound of interest.

SOURCE John L Ldseter Approaches to Monitoring Environmental Contaminants [n Food OTA Working Paper 1978

identity of the compound is confirmed by com- gerprint” are compared to a standard “finparing its retention time to that of a series of gerprint” to determine how much of each

standard solutions (of known composition) in- substance is present in the sample, If a peak

jected into the gas chromatography under the in the sample fingerprint, for example, has

same conditions. The areas under th e the same retention time but twice the area as

graphed peaks of a sample readout or “fin- one in the standard fingerprint, it is assumed
Ch. VIII— Monitoring Instrumentation ● 95

Table 18.—Techniques Available for Qualitative and Quantitative Organic Analysis

Approximate

Method detection limit, gm Specificity or common uses

Gas chromatography

Retention Indices. . ,

Electron captur e

Flame photometer .

Nitrogen/phosphoru s

Chemical methods

Pyrolysis ... ... . . .

Chemical reagents. . ,

Electrolytic systems .

Instrumentation

infrared-gratin g

Infrared-interferometer

Ultraviolet ... . . . . . . . .

Proton magnetic resonance

Mass spectrometer

Batch inlet .

GC-MS mode . . . . . . . .

Multiple-ion detection . . . .

Detects most compounds

Halides, conjugated carbonyls, nit riles, di- and

trisulfides

Phosphorus, sulfur

Nitrogen, phosphorus

Compound-type determinant ion

Classical-functionality determination

Sulfur, nitrogen, halogens

Compound-category-type identification

Compound-category-type identification

Aromatics conjugated carbonyls

Excellent for function, some molecular weight

data.

Best for complete identification,

molecuIar weight structure, and

function. Confirm any compound.

SOURCES Adapted f;om W McFadden Techniques of Comb!ned Gas Chromatography/Mass Spectrometry Wlleylntersc{

ence New York N Y 1973, p 4, and “Trace Orqanlc Analysls ‘ Enwronmental Science and Technology 12757

(1978)

that the identity of the sample peak is the

same as that of the known standard but that

twice as much is present.

Recent developments in analytical organic

chemistry promise new, more sensitive techniques for monitoring of synthetic organic

chemicals in foods. These developments include high-resolution glass capillary columns

for gas chromatography, and the linking of

gas chromatography to mass spectrometers.

The glass capillary column is much more

efficient in separating compounds than the

older “packed” columns (figure 7). The gas

chromatograph’s packed column separates

the individual components so that they exit

the column and enter the detector one at a

time. Some of the early data on the pesticide

family DDT-DDE-DDD were incorrect because polychlorinated biphenyls (PCBs) had

similar retention times in packed columns. As

a result, reported concentrations of DDT,

DDE, and DDD were often too high because

the peak areas were really reflecting a combination of pesticides plus PCBs (l). Because

of their superior resolution power, glass capillary columns avoid some of these problems.

Also because less cleanup is required, their

use reduces the possibility that an important

environmental contaminant may be removed

in the process of preparing a sample for analysis.

Although the capillary column offers a

number of advantages, it is more expensive

and difficult to use than the standard packed

column. More highly trained personnel are

required to operate capillary columns and interpret results. However, many chemists feel

that the advantages far outweigh any difficulties. Glass capillary columns are not now

widely used for monitoring synthetic organics

in foods. Packed columns continue to play an

important role in the organic chemistry monitoring laboratory, but their future use may be

restricted to more specific analyses.

Gas chromatography are currently the

primary means by which laboratories monitor for organic chemicals. Some chemists,

though, prefer mass spectrometers because

of their high sensitivity and flexibility (z). The

coupling of a gas chromatography to a mass

spectrometer introduces a new dimension

that allows a chemist to identify compounds
96 . Environmental Contaminants in Food

Figure 7. —Comparison of the Gas Chromatographic

Analysis of a Standard Mixture of Polychlorinated

Biphenyls (Aroclor 1254) on Two Types of Gas

Chromatographic Columns

A: Analysis Using a Conventional Packed Column

r I I 1 I 1 I I 1 1

0 6 12 18 24 3

Time (Minutes)

B: Analysis Using a High-Resolution Glass

Capillary Column

I 1 1 1 I I I 1

0 10 20 30 40

Time (Minutes)

SOURCE John L Laset II Approaches to Monltorlng Environmental Contaml

nants Ir Foc)i OTA i’dork(ng Pdper 1978

classed as uncharacterized (3). Moreover, results from a mass spectrometer can confirm

the identity of known chemicals whose presence (as indicated by gas chromatography

alone) is in doubt because of sample contamination or other factors. Mass spectrometers

are expensive and in addition require computerized data management systems.

Because of their physical and chemical

characteristics. many organic compounds

cannot be analyzed by gas chromatography.

Therefore, instruments such as infrared

spectrophotometers and high-pressure liquid

chromatography are necessary. These instruments add many thousands of dollars to the

costs of setting up and equipping an up-todate organic chemical-monitoring laboratory.

Application to Investigatory

Monitoring

Although the instrumentation described

above has been available for several years, it

has only recently been utilized for investigatory monitoring. Experimental projects incorporating computer analyses are now under

study in at least three research facilities: the

Bodega Marine Laboratory, the University of

New Orleans, and the Virginia Institute of

Marine Science, These projects employ highresolution glass capillary gas chromatographs coupled to mass spectrometers and

sophisticated computer analyses, The resulting “fingerprints” or readouts from a sample

extract are highly complex and show the

presence of not only known or suspected environmental contaminants but also many organic compounds that must be classified as

uncharacterized.

The three research groups are now testing

an approach to determine which compounds

deserve further testing. The gas chromatographic fingerprints are computerized so that

information on retention times and peak intensities are stored. Subsequent samples are

collected and analyzed and the data are computerized in the same manner. By comparing

results from the same location over time (or

with samples taken from other locations), one

can determine whether peaks are increasing

or decreasing, whether new peaks have appeared or old ones have disappeared, or

whether some peaks occur only in some locations.

With appropriate computer programs or

‘‘soft ware, ” the data bank could be asked if

there is a peak that occurs in samples from

only one area or location. If so, the investigator can assume that the compound is anthropogenic, or man-induced, The compound

could then be identified and its source con-
Ch. VIII— Monitoring Instrumentation ● 97

trolled before the concentration increased to

the point that a major contamination episode

occurred. This type of monitoring could have

detected kepone in the James River, Va., long

before thousands of pounds of the pesticide

entered the river.

Another question which could he asked of

the data bank is whether there is a peak that

is increasing with time. In other words, does

sampling over time indicate that a compound

is becoming more concentrated? Such a finding would flag the compound as one which

merits attention, Had this type of monitoring

program been in effect and this question been

asked earlier, widespread pollutants such as

PCBs could have been detected long before

they were,

Other information from the chemical labora tory car-r draw attention to an uncharacterized substance deserving attention. For example, gas chromatographic detectors exist

that respond mainly to organic compounds

containing halogens such as chlorine or bromine. Because naturally occurring halogencontaining organic chemicals are rare and

are far outnumbered by manmade ones, an

uncharacterized peak from a halogen-specific detector may represent a manmade compound, Historically, halogen-containing organics such as DDT, PCBs, polybrominated

biphenyls (PBBs), and kepone have caused

major pollution crises. Therefore, such information may be sufficient to focus attention on

a given peak from a halogen-specific detector.

Uncharacterized substances may or may

not be dangerous to human health if consumed. But no assessment of toxicity can be

made until the compounds are identified. To

perform the chemical and physical tests necessary to identify even one uncharacterized

peak may cost from $10,000 to $100,000, and

in some cases even more.

DETECTING AND QUANTIFYING TRACE METAL CONTAMINANTS

Trace metals pose many of the same problems that plague the analyst monitoring for

organic chemicals. However, the number of

trace metals is much smaller. If only the total

concentration of a metal is sought, more rigorous extraction procedures can be employed. But some metals, such as mercury,

form organic complexes--for instance, methylmercury--which give rise to a subset called

metallo-organics. These metallo-organics are

not stable under harsh conditions and are

often changed during rigorous extraction procedures.

Analysi s

Analysis for trace metals usually requires

extraction and cleanup before the quantitative analysis can be performed. Extraction

often involves destruction of the sample’s organic structure to release the metals from the

solid or liquid food. There are a few analytical instruments such as X-ray emission spectrographs that can accept solid or liquid samples, thus eliminating the extraction step (4).

But these instruments cannot detect all metals at environmental concentrations.

Depending on what instrumentation is used

in the final analysis, some cleanup of the extract may be required. The cleanup step is

not nearly as frequent with trace metals,

however, as with organic chemicals except if

a metal lo-organic complex is sought. For

metallo-organic compounds cleanup and separation procedures may be similar to those

for organic compounds. After extraction and

possibly cleanup, the sample is ready to be

analyzed by an instrument to determine

which metals, and how much, are present.

There are a variety of instruments available

for the determinations.

Probably the most commonly used instrument is the atomic absorption spectrophotometer (AA). The cost of this instrument is nominal ($ 15,000 to $25,000), and i t can be operated by a well-trained, motivated technician
98 . Environmental Contaminants in Food

with a high school chemistry and physics

background working under the supervision of

a chemist. One drawback of this instrument

is that only one metal can be analyzed at a

time.

In contrast, more sophisticated instrumentation such as X-ray emission, proton-induced

X-ray emission, or plasma emission spectrometers can cost in excess of $100,000. With

these instruments, 20 to 60 elements can be

determined simultaneously. These more sophisticated instruments require more highly

trained personnel to operate and maintain.

Table 19 summarizes the techniques available for qualitative and quantitative analysis

of trace metals. More information can be

found in appendix H.

Application to Investigatory

Monitoring

It is important to note that most AA units

can detect only the specific element (metal)

that they are set up to analyze. By contrast,

the gas chromatography may sometimes detect

the presence of organics other than those

being sought. As a result, metals are more

likely than synthetic organics to escape detection simply because they are not programed

for analysis.

With the rapid development of lower cost

techniques for detecting more than one element at a time, it would be possible to obtain

data on trace metals in foods that were previously not sought and therefore not obtained.

This is analogous to uncharacterized organic

monitoring where many unsought compounds

can be found in the analysis of a food extract.

Given the proper data systems, these “other”

metals can be tracked, and perhaps pollution

crises can be averted by detecting anomalous

concentrations early enough.

Speciation of Trace Metals

Often the active or functioning forms of elements must be identified and measured. The

need for the development of analytical methodology to identify and quantify the chemical

form of metals found in the environment—

i.e., chemical speciation—is pointed up by the

following examples.

●

●

Although arsenic is toxic, the plus three

oxidation state, As (III), is more toxic

than the plus five state, As (V). The compound arsine, AsH3

, is perhaps the most

toxic chemical form of arsenic.

Alkyl (organic) mercury compounds pose

greater propensities for bioaccumulation and the associated health effects

than do the more common inorganic

forms of mercury (but these also can

vary greatly in toxicity).

Chemical forms or states are an important

determinant of a trace metal’s toxicity in biological systems. The selection of elemental

analysis techniques capable of specifically

measuring those chemical forms most important from a biological-effects viewpoint

Table 19.—Techniques Available for Qualitative and Quantitative

Trace Metal Analysis
Ch. Vlll—Monitoring Instrumentation ● 9 9

should be a primary objective of any environmental monitoring program.

The status of the present analytical technology is inadequate for this purpose in most

routine monitoring programs. As a result, the

functioning forms of most elements cannot be

adequately studied. Thus the determination

ANALYSIS OF FOODS

Analysis

Measuring radioactivity in foods is a physical process. It is most efficient when the

radioactivity from a relatively large sample

can be placed close to a detector. This means

that direct measurements of radioactivity in

bulk samples are only useful when levels of

contamination are relatively high. Most measurements are preceded by preparation and

possibly chemical separation to reduce the

bulk of the material and to improve the efficiency of the measurement.

Foods generally have a high water content.

The primary method of reducing bulk is

freeze-drying or drying at room or at elevated

temperatures. Most of the radionuclides of interest are not volatile under these conditions.

Only elements such as tritium or iodine may

experience losses. The dried materials can be

reduced further by ashing at elevated temperatures, by cold-ashing with oxygen, or by

wet-ashing with oxidizing acids. Dry-ashing is

the simplest process, but it is most likely to

lead to loss of volatile elements. With care

even cesium, polonium, or lead can be retained. The other processes should not result

in losses of elements of interest, except for

iodine, tritium, and carbon.

Another way to reduce bulk is to treat

either the original sample or the dried or

ashed material with acids or other solvents

and thus remove the desired elements from

the bulk of the sample. This requires considerable testing beforehand to be certain that

the process operates in the desired manner.

The radionuclides of interest in ashed foods

should be soluble in strong acids if ashing

of the important (threshold) concentration

levels for various elements typically has been

rather crude. The most important current research need related to trace metal monitoring

is the development of methods to measure the

species rather than the total amount of trace

metals.

temperatures have not been excessive. If

there is concern that insoluble particulate

may be present, it is necessary to use more

drastic methods such as fusion to bring the

entire sample into solution.

In addition to bulk reduction, radiochemical separations are required to isolate the

desired radionuclide both from the remaining

bulk constituents and from other radionuclides that would interfere in the measurement. It is also necessary to convert the final

product to a form suitable for presentation to

the counter. This may involve electrodeposition, precipitation, or other processes.

The actual mass of radionuclide that is

measured is almost always extremely small.

As a result, many of the normal chemical reactions used in analytical chemistry to isolate

an element are not appropriate. For instance,

precipitates may not form. Therefore, it is

common to add a few milligrams of a carrier

material, preferably the inert form of the

same element. When such an inert form does

not exist, it is frequently possible to use similar elements as a carrier (for example, substituting barium for radium). The inert form

then follows normal chemistry, carrying the

radionuclide with it. It is also worth noting

that even when the separation technique does

not depend on the mass of element present, a

carrier may still be useful in preventing unwanted coprecipitation or absorption on

glassware.

In the chemical separations there is considerable use of classical analytical chemistry

based on precipitation. In most cases, precipitation will be the final collection step in
100 “ Environmental Contaminants in Food

preparing the desired radionuclide for counting. In other cases the techniques of ion exchange, liquid extraction, distillation, and

electrolysis may be required to prepare the

sample for counting.

In certain cases, the total amount of a sample may be limited, and analysis for several

radionuclides may be required. Procedures

should be available for the sequential analysis of single samples, even though separate

samples are used for routine work.

The measurement method used depends on

the type of radiation, the form of the sample,

and (to some extent) the amount of radioactivity. The selected analytical procedure

should be designed so that the sample is

brought to a suitable form for the equipment

and conditions that exist.

The major emitted radiations are generally

grouped as alpha, beta, and gamma. Alpha

radiation is characteristic of the natural and

artificial radionuclides of high atomic weight

and consists of energetic particles with very

low penetrating power. Its hazard is significant only within the body, where alpha-emitting nuclides can irradiate specific sensitive

tissues. Beta radiation appears in both natural and manmade radionuclides, and consists

of electrons possessing kinetic energy and

modest penetrating power. Gamma radiation

is pure electromagnetic radiation and is extremely penetrating. Thus, it is hazardous externally as well as when it is present in the

body. Gamma radiation can be directly measured in foodstuffs, while alpha and beta emitters generally must be separated from the

bulk constituents of the sample before they

can be measured.

It is possible to measure the total gamma,

total beta, or even the total alpha activity in a

sample of food. Unfortunately, such data are

valueless in estimating human exposure. The

accuracy of such estimates is very poor because natural potassium usually interferes,

and the chemical and radiation characteristics needed to evaluate possible hazards are

not known.

It is possible, however, to set a particular

total activity level as a screening level for a

specific food, If the measured value is below

the screening level, no analyses for individual

radionuclides are performed. In such a case,

the measurements should be considered internal data and the numerical results should

not be published, Any report should merely

list the samples as having activities below the

stated screening level. Table 20 summarizes

the typical limits of detection for radionuclide

measurement.

Alpha Emitters.—The measurement of

alpha activity is best carried out on a very

thin sample to avoid self-absorption of the

alpha particles. Most metals are electro-deposited onto small smooth discs of stainless

steel, nickel, or platinum. Evaporation of pure

solutions is used in some cases. The measurement of the total alpha activity can be conducted either in thin-window counters or by

scintillation counting with zinc sulfide phosphor. Both techniques are highly efficient, but

the scintillation method can give a considerably lower background with a consequently

lower limit of detection.

A somewhat less-sensitive technique is the

liquid scintillation spectrometer described in

the next section.

Alpha spectroscopy provides two other alternatives: the Frisch grid ionization chamber

or the silicon diode solid-state detector. The

Frisch grid unit can handle large area samples but is slightly poorer in resolving closely

separated energies. On the other hand, the

silicon diodes available are all quite small

and can only count samples of about 1-cm diameter with high efficiency.

Beta Emitters.—Beta counting is a little

more flexible in the mass of material that can

be present at the time of counting. This is true

for higher energy beta emitters but carbon-14

and tritium present a problem. Since each individual beta emitter gives off particles with

a range of energies from zero to a characteristic maximum, beta spectrometry is not possible for food samples.
Ch. VIII—Monitoring Instrumentation c 101

Table 20.—Typical Limits of Detection for Radionuclide Measurement

Counter

Nuclide efficiency %

Amerlclum.241 25

Ceslum-144 22

Cesium-137 30

2

Cobalt-60, other

activated

product s 1

Tritium 30

Iodine- 131 25

4

Phosphorus-32 45

Plutonium-239. -240 25

Radium-226 56

40

Strontium-90 45

Thor! urn-230, -232 25

U-Isotopic 25

Counter

background cpm

0.001

0 4

0 4

006

005

5

0.4

0 3

0 3

0005

0 2

0.001

0.3

0001

0.005

Chemical

yield %

60

75

75

75

—

75

80

80

60

85

90

85

80

70

75

10 min

0 3

6

4

30

100

15

5

25

3

0 6

1

1

2

0.3

0.7

SOURCE N H Harley Analysts of Foods for Radloactlvlty OTA Work Ing Paper 1979

LLD (dpm) per sample for various counting times

40 mln

015

3

2

14

50

6

2

13

1.5

0.3

0.6

0.5

1

0.1

0.3

400 mln

0.05

0 9

0 6

4 5

15

2

0.7

4

0.5

0.09

0.2

0.15

0,4

0.04

0.1

1,000 mln

003

0 6

0 4

3

10

1.5

0.5

2 5

0.3

0.06

0.1

0.1

0.2

0.03

0.07

The available counting equipment for

quantitative measurement includes geiger

counters, proportional counters, and scintillation counters. The geiger counter is relatively inexpensive and requires only simple

electronics but is not popular and is generally

not available as a counting system. The thinwindow proportional counter is used widely

and has both reasonably high efficiency and

low background. For low-level samples the

background can be further reduced by anticoincidence techniques. These add to the

complexity and cost of the system but are

sometimes necessary.

Scintillation counting can be performed in

two ways. Solid scintillators can be used for

counting chemical precipitates collected on

filter papers, and liquid scintillators can be

used whenever the sample can be made miscible with the scintillating solution itself. This

can even be done with solids by suspending

them in a scintillating gel. The advantage of

liquid scintillators is their high efficiency,

even for the low-energy emitters carbon-14

and tritium. Scintillation systems for counting

precipitates are not commercially available

at present. There are, however, many liquid

scintillation systems on the market, most of

them with automatic sample changers. These

use high levels of activity and short counting

times. The better systems also have a provision for rather crude spectrometry. They can

distinguish qualitatively and quantitatively

among carbon-14, tritium, alpha emitters,

and higher energy beta emitters.

Gamma Emitters.—Gamma rays are so

penetrating that the detector must have a
102 ● Environmental Contaminants in Food

considerable mass to absorb enough energy

to produce a response. Since energy absorption is required for spectrometry, solid detectors are most useful, Sodium iodide is a popular detector because crystals can be fabricated in large sizes and are transparent to

the scintillations produced by radiation. Sodium iodide has high efficiency but poor energy resolution and is now applied to samples

where some separation has taken place. The

advantages are that samples of food can

often be counted directly without chemical

preparation. Milk is a good natural example,

as the metabolism of the cow removes most

gamma emitters other than isotopes of cesium, iodine, and naturally radioactive

potassium.

More complex spectra can be resolved

with the solid-state germanium diode detector. Interferences from radionuclide impurities are greatly reduced compared to spectra

from sodium iodide detectors. The efficiency

of the diode is low and, for many analyses, a

spectrometer can only be used for one measurement a day, Another disadvantage is that

the detector must be kept at liquid nitrogen

temperature to maintain its detection capability.

Diode spectrometers may also be used to

measure the low-energy gamma-rays that accompany alpha emission. This allows direct

measurement in some environmental samples, but the levels in foods have not been

high enough for this technique.

General Requirements.—The choice of a

counting procedure depends on the precision

required. The relative precision of a quantitative counting measurement, in turn, is inversely proportional to the square root of the

number of counts obtained. Thus any improvement in precision must be obtained by

increasing the number of counts. This can be

done by using larger samples, by counting for

longer times, or by using counters with higher

efficiency, A secondary improvement is possible for low-activity samples by decreasing the

background, Each of these improvements has

some drawback, and selection of the optimum

balance requires a weighing of cost, manpower, and quality.

Applications to lnvestigatory

Monitoring

The monitoring of foods for radioactivity

should not be considered a primary defense

against human exposure. The first indication

of hazards should always come from information on releases or from measurements of radioactivity in air or water. Once the existence

of contamination has been established, foods

can be analyzed to evaluate the potential hazard to man.

Knowledge of the source of radioactive

contamination gives a good indication of the

nuclides that can be expected in the sample.

This information helps in planning the analysis, since requesting a complete analysis for

all radionuclides or even for all types of

radioactivity in a single sample would lead to

a lengthy and expensive operation. Indeed,

monitoring for suspected contaminants is

more applicable than the uncharacterized

monitoring.

The general groups of nuclides that maybe

encountered include those that occur naturally such as radioactive potassium and members of the uranium and thorium series, artificial fission products such as transuranic

elements, and other activation products that

result from nuclear weapon explosions and

nuclear reactor operations.

Fission products are a very complex mixture when they are formed, but the shortlived radionuclides die out rapidly and the

mixture becomes simpler within a few days.

The transuranics (plutonium, americium, etc.

formed by activation of the basic fissionable

material) are of some interest because of

their high toxicity when incorporated into the

body. Present evidence, however, indicates

that their uptake through the gut is relatively

small and that dietary intake is not a significant problem. The other activation products

are frequently elements that make up steel or

other metal containers or structural ele-
Ch. VIII—Monitoring Instrumentation ● 103

ments. Radioactive manganese, chromium,

cobalt, zinc, and iron are particularly common and result from interactions of the materials with neutrons released in the nuclear

reaction, Contamination of foodstuffs with

single nuclides is extremely unlikely, and

more than one member of any group will

probably be present in any sample.

In contrast to most other pollutants, the effects of radiation are considered to have a

linear response regardless of the level, Thus

there is no threshold and no absolutely safe

limit. The analytical significance of this is

that the lower limits of detection for radioactive substances have been brought down to

very low levels. The simple yes-or-no testing

for acceptability that satisfies regulators for

many other pollutants in foods cannot be

used.

ESTIMATED COST TO EQUIP A

INVESTIGATORY

Table 21 illustrates estimated costs, required space, and estimated downtime for a

laboratory designed to conduct investigatory

monitoring. In addition, the number of samples the system would be able to analyze in a

year are estimated.

These figures do not reflect the total costs

for establishing a national system of investigatory monitoring. Such a cost estimate

would require information on the total numAlmost all radionuclides of interest in

cases of contaminating events now exist in

foods in small but measurable quantities.

Short-lived nuclides are the exception and the

transuranic elements are only present at

levels that require considerable effort in

analysis. Since most of the radionuclides are

already present in foods, measurements

made for background information should produce a numerical answer, not merely an indication that the amount is less than some

pre-set value. This accumulation of background data provides a valuable baseline for

evaluating hazardous levels following a contaminating event. The natural activity data

are equally valuable, since the amount of information on food concentrations is presently

insufficient for valid comparisons with manmade radioactivity.

LABORATORY

MONITORING

ber of samples to be collected and analyzed.

Information of this sort could be obtained

through a pilot project to investigate the

feasibility of the two investigatory monitoring

approaches. This would determine the number of laboratories, the number of people and

their salaries, and costs of equipment maintenance, supplies, and training. Once the system is setup and running, some savings might

be realized through automation.

54.5>5 0 - 79 - B
104 ● Environmental Contaminants in Food

Table 21 .—Estimated Costs to Equip a Laboratory to Conduct Uncharacterized Monitoring

Approximate

Estimated

down

Analytical instrumentation Required space Samples per year time

Synthetic organics

1. Small, high throughput, GC-MSdata system with automated liquid

Injection device.

2. Electron impact/chemical

Ionlzatlon-equipped highresolution mass spectrometer

data system with automated

injection devic e

3. Gas chromotographic flame

ionization detector, electron

capture detectors (additional

chromotographic systems may be

required) .

4 Liquid chromotograph interfaced

to mass spectrometer system

5. Central data management system

6. Cold storage and processing

facilitie s

Synthetic organics subtotal

capital cost

5,000-6,000 ft. ’ 200-300 for 20- 50%

laboratory supporting uncharacterized environmental

facilities and equipment contaminants as welI as known

are required, environmental contaminants

$100,000

$200,000-

$300.000

20- 50%

$15,000 20-50 %

$20,000 20- 50%

$75,000- 20- 50%

$1,000,000

$500! 000

$1,585,000-

$1,935,000

Trace metals

1. Inductively coupled plasma $100,000 Approximately 2,500 ft.’

of laboratory equipped

with supporting facilities

and equipment are

required for items 1-4

3,000-5,000 3-15% 

Multielement atomic emission

syste m

2. Flame and furnace atomic

absorption spectrophotometer

(single element mode )

3. Electrochemical instrumentation

4. Central data management system.

Trace metals subtotal.

$25.000 3- 15°/0

3-15% 

3-15% 

Radionuclides

1. Four position alpha spectrometer

and detectors, multichannel

analyzer and outpu t

$21,000 Approximately 1,500 ft. ’ 1,000-4,000

laboratories equipped

with supporting

facilities and equipment

are required

2. Germanium diode gamma 5 %

spectrometer wit h detector,

shield, electronics, PDP-11

computer and outpu t

3. Four general purpose proportional

counters ,

4. Liquid scintillation spectrometer,

automatic sample. or alphacounting capabilities

Radionuclides subtotal

Total. . . . . . . . . . . . . . . . . . . . . . . .

$100,000

$10,000

$18.000

5 %

5%

$149,000

$1,934,000.

$2,309,000

SOURCES Adapted from J L Laseter Approaches to Monltonng Environmental Contaminants In Food OTA Work!ng Paper 1978 R K Skogerboe Analytical Sys

terns for the Determ!natlon of Metals {n Food an(j Water Supplles OTA Working Paper 1978 and N H Harley Analysls of Foods for Radloactlvlty OTA

Work!ng Paper 1979
Ch. Vlll—Monitoring Instrumentation ● 105

1. Butler, P. A. Environmental Protection Agen- vironmental Contaminants in Food, OTA

~~[)rking paper, 1978. cy, Gulf Breeze Environrnen tal Research Laboratory, personal communication, 1978. 4, Sko,gerboe, R, K, “Analytical System for the

2. Anonlrnous. “Trace Organic Analysis,”” En- Determination of Lletals in Food and Water

vironment~]f Science anci 7’ec~nology, 12(7) : Supplies, ” OTA Working Paper, 1978.

757, 1978. 5, Harley, N. Ii. “Analysis of Foods for Radio3. Laseter, J. L. “Approaches to Monitoring In- activity,”’ OTA W’orking Paper. 1979.
Chapter IX

Options

.
Chapter IX

4

Congressional Options

The present system of controlling environmental contaminants in food consists of two parts: regulatory procedures to set and enforce limits for environmental contaminants, and monitoring procedures to detect lots of food in violation of

established limits. Each State has authority for regulating food grown and consumed within its boundaries. The Federal Government is responsible for regulating food in interstate commerce.

Congress can choose to maintain this system. But if it wishes to put greater

emphasis on protecting consumers from contaminated food, one or more of the options discussed below could be adopted. None of these options (except for the

first) are mutually exclusive.

The current regulatory approach to controlling environmental contaminants in food

involves the setting of action levels (and occasionally tolerances), coupled with regulatory

monitoring for known [and a few suspected)

contaminants. Food containing an amount of

a contaminant that exceeds the action level

or tolerance can be identified through such

monitoring. This food is then removed from

the marketplace. Public exposure is thus

theoretically limited to those foods containing

quantities of contaminants that fall under

prescribed action levels or tolerances.

Pros: There are two principal advantages

to maintaining this system. No additional appropriations or legislation are required. No

changes in existing regulations are necessary.

Cons: There are a number of disadvantages in retaining the current system. The

time needed to identify an environmental contaminant in food and take corrective action

would not be shortened, The people would

people against exposure, In other words, action levels and tolerances permit a certain

level of contaminant to be present in food. Unless action levels or tolerances are reduced,

little effort will be made to eliminate the contaminant, The threshold concept on which action levels and tolerances are based—that

there are exposure levels to toxic substances

below which there are no effects on health

—is being increasingly challenged (especially

when carcinogens are involved).

If high action levels or tolerances are established, exposure is not reduced. Lowered

action levels and tolerances may reduce public exposure. But even low limits are set on

the basis (among other things) of nationwide

per capita consumption of a particular food.

Contamination problems, however, may be localized and further influenced by regional

food consumption patterns. Thus, a local population may be highly exposed to a toxic substance although the tolerance, based on national consumption, may be low.

continue to be exposed until a contaminant Moreover, there is no requirement for re- was detected and identified, and an action

level put into effect, view once an action level has been established. An agency is under no pressure to acMoreover, a c t ion levels and tolerances tively seek out new data that might alter a

tend to institutionalize rather than protect prescribed level,

109
110 ● Environmental Contaminants in Food

.

Tolerances and action levels have other

weaknesses. They are often not easily applied

when the environmental contaminant involved is a suspected carcinogen (such as

polychlorinated biphenyls (PCBs)). Furthermore, the time required to perform a complete chemical analysis for contaminants in

nonprocessed foods such as fish makes its difficult to prevent some shipments from reaching the marketplace.

Finally, there are procedural problems in

the present system. States have no clearly defined authority to which they can turn when

they suspect environmental contamination of

food.

OPTION 2-AMEND THE FOOD, DRUG, AND COSMETIC ACT

The Food, Drug, and Cosmetic Act has been

amended several times since its passage in

1938 to deal with new food regulatory problems. Environmental contamination of food is

now a national problem which Congress has

never directly addressed through legislation.

Thus, Congress could choose to give regulatory agencies more guidance by clarifying its

position on environmental contaminants in

food.

An amendment to the Food, Drug, and Cosmetic Act could include one or all of the following points. None are mutually exclusive.

Option 2A-Simplify

Administrative Procedures

Under current law and regulations, the

Food and Drug Administration (FDA) sets an

action level for a contaminant soon after an

interstate shipment of contaminated food is

discovered. FDA will then presumably launch

the elaborate rulemaking proceedings that

culminate in the establishment of a tolerance

(under section 701(e) of the Food, Drug, and

Cosmetic Act). In reality, the costs and delays

involved in the complex rulemaking procedures now required for the adoption of tolerances have discouraged FDA from moving

from the first (action level) to the second (tolerance) state of the process.

Congress could amend the Food, Drug, and

Cosmetic Act to simplify the administrative

procedure through which tolerances are set.

The changes could be modeled after section

553 of the Administrative Procedures Act.

This process involves publication of a tolerance proposal in the Federal Register, along

with (as required by recent court rulings) the

rationale and factual data underlying the

proposal. The public can then respond to the

proposal with written comments. FDA may

also hold legislative-style public hearings to

allow presentation of oral arguments and

evidence.

After considering all of the comments, FDA

publishes a final rule (in this case, a tolerance). This final rule includes explanation of

any changes from the original proposal and

responses to factual points raised by the public. Most agencies now use this model for

rulemaking. It is a process that can be carried out expeditiously with modest investment

of an agency’s resources.

Pros: Adoption of this streamlined rulemaking procedure would reduce the time and

expense now involved in setting a formal tolerance. It may encourage FDA to move from

action levels to tolerances, thus bringing

more public participation into the process.

Cons: Because action levels are administrative guidelines, they can easily be changed

when new scientific information becomes

available. Even if FDA comes to use a simplified procedure to set tolerances, it may still

be slow to revise them in the light of new

data.

Option 2B--Require the

Establishment of Tolerances

Congress could amend the Food, Drug, and

Cosmetic Act to require the establishment of
Ch. IX—Congressional Options ● 111

a tolerance within a specific time after the

setting of an action level.

Pros: This change would encourage FDA to

gather additional information on a contaminant’s toxicity and the public’s exposure. It

would speed up a process. that now operates

under no deadlines. And it would result in definitive tolerances that FDA could enforce

with less concern about judicial questioning.

Cons: This option, however, would substantially increase FDA’s workload unless tolerance-setting procedures were simplified. Indeed, it has been the costs and delays of the

current rulemaking process that have deterred FDA from moving from action levels to

tolerances. Thus, tolerances should not be required without also simplifying present rulemaking procedures,

Option 2C--Clarify the Role of

Economic Criteria

Congress could amend the Food, Drug, and

Cosmetic Act to clarify to what extent economic criteria can be used in setting tolerances. The Act does not specify that costs

(the adverse economic effects) of a proposed

tolerance be considered when setting a tolerance. FDA, in practice, does weigh the cost of

food lost when establishing a tolerance.

The Food, Drug, and Cosmetic Act could be

amended to prohibit FDA from considering

costs when setting a tolerance. Prohibiting

any economic assessment would ensure that

public health would be the first priority in setting a tolerance.

Conversely, the Act could be amended to

require FDA to weigh the costs against the

benefits of a proposed tolerance. Requiring

FDA to evaluate the economic consequences

of a tolerance would give FDA clear authority

to weigh such estimated effects together with

the potential health risks when establishing a

tolerance. Congress could require FDA to

gauge only the primary costs (as is now done

with food lost) or all associated costs (food

lost, employment impacts, distributional and

indirect effects) for a proposed tolerance.

The techniques available for estimating costs

require up to a year for generating the necessary data. Thus, weighing the costs is best

suited for setting tolerances. not action

levels.

The advantage in including costs in tolerance-setting decisions is that adverse economic impacts are likely to be reduced. The

disadvantage is that tolerance levels are likely to be higher than would be the case if costs

were not considered.

Pros: By clearly defining to what extent

costs can enter into tolerance-setting decisions for environmental contaminants in food,

Congress would eliminate ambiguities of interpretation and provide clear guidance to

FDA.

Cons: FDA has interpreted the Food, Drug,

and Cosmetic Act as allowing cost considerations, Legislation requiring economic assessment could limit FDA’s discretion to weigh

the costs of food lost if it judges the situation

warrants such a treatment.

Option 2D--EstabIish Regional

Tolerances

This option would give FDA the flexibility

to set different action levels or tolerances for

different regions, based on expected levels of

exposure, regional levels of contamination,

and eating patterns.

Pros: Action levels and tolerances may not

be set low enough to protect those populations that are most highly exposed, previously

exposed, or most vulnerable. States may not

exercise their authority to set tolerances

which are more restrictive than the Federal

tolerance because of budget limitations, inadequate information, or political pressures.

FDA can provide guidance to States and suggest more restrictive tolerances or warnings

to the public, but FDA has no authority to intervene if the contaminated food does not

enter into interstate commerce.

Cons: Regional tolerances would complicate monitoring and enforcement programs.

Regional tolerances might also be viewed as

Federal infringement on State authority.
112 ● Environmental Contaminants in Food

OPTION 3-ESTABLISH AN INVESTIGATORY

MONITORING SYSTEM

Environmental contaminants could be detected earlier in the food chain by improving

present environmental monitoring capabilities —establishing an investigatory monitoring system while maintaining current regulatory monitoring programs.

Congress could set up a national investigatory monitoring system that monitors for

either suspected or uncharacterized environmental contaminants. A system combining

elements of both approaches could also be established. Since any of these monitoring approaches would require some research and

development before a fully operational system could be devised, Congress could choose

to create a pilot program. Such a program

would spur research and development and

assess the feasibility and cost-effectiveness

of the various approaches.

The investigatory monitoring systems discussed in this assessment would call for different sampling and quality control procedures. The development of these procedures

is as important as the development of monitoring technology (some of it still in the experimental stage). Indeed, there is no comprehensive investigatory monitoring system

for toxic substances in food and the environment at any level of government.

Consequently, Congress might opt for a

pilot project to assess the capabilities and resource requirements of various national monitoring systems instead of mandating a particular monitoring approach. Such a pilot

project would focus on the monitoring of organic chemicals, inorganic, and radioactive

substances. It would determine the technology, sampling, and quality control needs for

monitoring these three toxic substance categories in food, air, water, and soil. The broader purpose of the project would be to develop

a comprehensive monitoring program tha t

would meet the Government’s regulator y

needs, provide data to make cost-effectiveness assessments of the alternative strategies, and reduce public exposures to environmental contaminants as much as possible.

Option 3A-Establish a National

Monitoring System for Suspected

Environmental Contaminants

Suspected environmental contaminants

are substances that are most likely to enter

the food supply and pose potential health

hazards, Lists of such substances could be

drawn up for organic chemicals, trace metals, and radioactive substances in order that

they be monitored in the food, Various criteria such as toxicity, volume of production,

occurrence in the environment, persistence,

and biodegradability could be used in putting

together the lists.

Pros: Present food monitoring efforts are

not designed to detect new environmental

contaminants in food. The limited amount of

monitoring for suspected contaminants that

does exist is primarily concerned with trace

metals. But far more of this type of monitoring

is needed to anticipate new contaminants in

food.

Cons: To draw up such lists successfully,

considerable information is needed. Substances for which there is little or no data

would automatically be given low priority. In

large part, the makeup of the lists would depend on scientific judgments. However, scientific judgments often vary (or even conflict).

Thus, the reliability of the lists may be in

question,

Priority lists of trace metals and radioactive substances, which are limited in number

and already well-investigated, would be more

reliable than a list of organic compounds.

There are thousands of such organic agents

manufactured, And there is little toxicological or environmental information available on

a great many of them.

If such lists were developed, the number of

substances monitored would necessarily be
Ch. IX—Congressional Options c 113

limited. Standards would be set up for determining which substances would get priority.

Of course, there would be no certainty that

unlisted substances might not get into the

food supply and threaten human health. The

cost of such a monitoring system would depend on how many substances were being

traced as well as the expenses of equipping

and staffing laboratories.

Option 3B--Establish a National

Monitoring System for

Uncharacterized Environmental

Contaminants

Uncharacterized monitoring would be designed to detect substances that are: lacking

toxicity data for potential human risk, not

known to be present in food, and not even

known to exist in the environment. This kind

of monitoring is most needed for synthetic

organic chemicals. The purpose is to detect

changes in the levels of various synthetic

organics in environmental or food samples

over time,

Scientists would not necessarily know the

identity of individual substances they were

monitoring. But if the concentration of a particular compound substantially increased,

they could analyze it further to establish its

identity, The literature would be reviewed on

the substances toxicological properties. Or

perhaps the substance would undergo toxicological testing. Depending on what information is developed, regulatory agencies could

then take appropriate action.

This approach tries to create a mechanism

for quantitatively measuring uncharacterized substances in food. Proper guidelines are

necessary since the cost of quantitatively

identifying one substance can range from

$10,000 to $100,000. Moreover, this monitoring approach requires sophisticated equipment for analyzing food samples. Also, the information generated by the analyses has to

be computerized. Computer technology makes

it possible to correlate and interpret chemical

data to provide a continuous surveillance of

the levels in food.

Pros: The uncharacterized monitoring approach is in the research stage at several laboratories in the country. If it is successfully

developed, this type of monitoring would reduce the time during which the public is exposed to high concentrations of uncharacterized environmental contaminants in food. Kepone, for example, was polluting the James

River, and people were eating kepone-contaminated fish for several years before the

chemicals presence was discovered. With an

uncharacterized monitoring system, kepone

may have been detected years earlier.

Cons: This combination of sophisticated instruments, dependence on computers, and

highly trained personnel is expensive. And

the “hardware” needed is generally not

found in Federal or State monitoring laboratories.

OPTION 4--IMPR0VE FEDERAL RESPONSE TO

NEW CONTAMINATION INCIDENTS

All of the major food contamination inci- ance, Congress could choose to designate a

dents have been marked by confusion. This lead agency or establish a center for the colstems from the involvement of three Federal lection and analysis of data.

agencies—FDA, the U.S. Department of Agriculture (USDA), and the Environmental Pro- Option 4A-Designate a Lead Agency

tection Agency (EPA)—in the monitoring and

regulation of environmental contaminants in The problem of conflicting Federal assistfood. To cut down on confusion and to im- ance efforts was dramatized by several reprove delivery of Federal technical assist- cent incidents including the most recent PCB
114 ● Environmental Contaminants in Food *

contamination. This sort of situation is not

unique, Official reactions following the polybrominated biphenyl (PBB) episode in Michigan and the kepone incident in Virginia were

similar.

The lead agency would serve as a clearinghouse for all information coming from and going to States. FDA would be the most likely

candidate for lead agency when food contamination is suspected.

Pros: With a clearly delineated lead agency, States suspecting contamination of food

would have one reliable source of technical

assistance. Conflicts of opinion would be settled internally, and public statements and

technical assistance provided with less ambiguity.

Cons: Designation of a lead agency might

decrease the amount of technical expertise

made available to the States. It would require

the lead agency to develop new agreements

with the other two agencies, During a food

contamination crisis the lead agency would

need to coordinate responses from the other

agencies.

Option 4B--Establish a Center to

Collect and Analyze Toxic

Substances Data

Major delays in protecting the public from

environmental contaminants in food now result from the time-consuming process of generating sufficient data on a substance’s toxicity and dispersal in the food supply. Congress

could overcome this problem by setting up a

new technical center.

Such a center would be able to rapidly assemble technical teams skilled in the identification and analysis of organic, inorganic, and

radioactive substances. A team would consist

of a multidisciplinary group of experts, including chemists, toxicologists, food and animal scientists, epidemiologists, biochemists,

biostatisticians, medical doctors, and others.

Its mission would be to identify the cause of

an actual or potential contamination incident,

and assess the possible environmental and

human health impacts. It would have no regulatory function.

The group would be able to mobilize within

24 hours. It would be the lead Federal organization that affected States could initially contact. In the wake of an episode, the team

could be responsible for followup scientific

research that would lay the groundwork for

epidemiological studies of the exposed population. It would also be able to conduct a

range of short-term toxicological tests to determine the mutagenicity and potential carcinogenicity of uncharacterized substances.

It would be able to examine an exposed population for any adverse health effects from ingesting a particular contaminant in food.

The new technical center, in essence,

would be similar to the Center for Disease

Control (CDC). It would have the same capabilities in chemical epidemiology as CDC has

in infectious disease. The new center could

be given responsibility for investigating all

toxic substance problems in the United

States, not just those limited to food. If it were

placed under CDC, it could build on work now

underway in that organization’s Environmental Hazards Unit. Furthermore, the center would be able to capitalize on the longstanding relationships between CDC and the

States. Since the center’s sole mission would

be the development of information on environmental contaminants, it would not be linked

to regulatory decisions.

As an alternative, the center might be located within FDA’s National Center for Toxicological Research or another Federal laboratory with existing analytical capabilities. It

could then use the laboratory’s equipment

and trained personnel for investigative analytical chemistry and toxicology.

It would be better not to locate the center

and the investigation teams in a regulatory

agency with direct responsibilities for food.

This would ensure that there is no possible

conflict of interest between its job of factfinding and the agency’s responsibility for regulating, By distancing itself from the regulatory process, the new center team would
Ch. IX—Congressional Options ● 115

strengthen its credibility with the media and

the public.

Pros: Accurate scientific information on

the nature and extent of food contamination

has to be generated quickly when an incident

occurs. Individual States often lack the scientific expertise to develop such data. The Federal Government does have the necessary capabilities, but the resources are scattered in

several agencies with differing areas of authority. Such a dispersal of expertise hinders

the gathering of urgently needed information

following a contamination episode. Jurisdictional problems crop up, and States find they

have to deal with more than one agency. The

resulting delays slow the making of necessary

health, environmental, and regulatory decisions.

Reaction time would be shortened and duplication of effort reduced by a technical or

toxic substances investigation team which

could react quickly in emergencies.

Cons: There is no assurance that a special

team could generate information more quickly than is now the case. If the center were not

part of a regulatory agency, it might not only

grow out of touch with the needs but also

could duplicate the investigatory work of the

agency. Furthermore, the potential for an

adversary relationship exists.

It could be argued that better coordination

among FDA, USDA, and EPA would accomplish the same goals without the expense of

establishing a new research center.
Appendixes
Appendix A

Substances Whose Production or

Environmental Release Are Likely

to Increase in the Next 10 Years*

by Clement Associates, Inc.

OTA requested Clement Associates to develop a list identifying new chemical substances likely to be manufactured in the near future and known chemicals likely to pose

an increased burden to the environment because of increased production, new applications, or new technological developments, including new energy technology. For these

projections, several factors were considered, including market trends, Federal regulatory activity, available substitutes for recently banned or restricted chemical substances,

and consumer needs.

During the development of the approach to this phase of the project, certain problems and limitations became apparent. The nature of chemical substances under research and development but not yet introduced to the market is usually closely guarded

proprietary information and therefore not available. In addition, there are no data systems which bring together chemical information to facilitate the retrieval of necessary

data. An approach was developed to obtain a maximum amount of information in a limited amount of time.

Sources, including personal contacts, were identified for information on new chemicals or chemicals whose production, use, and release to the environment -

- 

-

crease sharply because of future needs. These sources of information

reference list.

Following are

were selected.

the list of chemicals and a brief indication of why

LIKELY TO HAVE SIGNIFICANTLY

were likely to inare listed in the

these chemicals

CHEMICALS

ENVIRONMENTAL RELEASE IN THE NEAR FUTURE

Chemicals Whose Production and Use

Are Likely to Increase Sharply

Because of Future Needs

SoIuble Polymers

Soluble polymer “completing” agents are

being developed to remove toxic metals from

waste waters or remove radioactive metals from

nuclear waste fluids. Polyethylene glycol and its

*Excerpt from OTA Working Paper entitled “Priority Setting

of Toxic Substances for Guiding Monitoring Programs. ” A complete copy of the paper can be obtained through the National

Technical Information Service. (See app. 1.)

derivatives are the most versatile of the soluble

polymers. Others are polyethyleneimine, polyvinyl sulfonic acid, polyacrylic acid with such chelating groups as thiourea, 8-hydroxyquinoline,

iminodiacetic acid and hydroxyciniline, and polymers based on acrylic acid. (C&EN, Mar. 27, 1978,

p. 24)

The principal organic flocculants are polyacrylamides, polyamides, and polyepichlorohydrins.

Stiffening waste treatment regulations to reduce

sludge are making flocculants more attractive.

The chemicals make up a $100 million per year

119
120 c Environmental Contaminants in Food

market that may double within the next 5 years.

These polymers may also be used for enhanced oil

recovery if the price of oil would rise to make

enhanced recovery economical. (C&EN, Jan. 23,

1978, p. 9)

Multifunctional Acryiates

The use of radiation curing (ultraviolet or electron beam) is rapidly increasing. Radiation curing

contributes significantly to critical energy savings and pollution abatement. Demand for the following multifunctional acrylates used for ultraviolet inks and coatings is expected to increase:

pentaerythritol triacrylate, 1,6-hexanedioldiacrylate, trimethylolpropane triacrylate, and tetraethylene glycol. (C&En, Jan. 23, 1978, p. 12, Celanese

Chemical Co. Advertisement)

Polyester Resin

Concern about energy will augment the growth

of lightweight polyester resin in the United States

through the 1980’s. The need for lighter weight

materials in the automotive market, as well as the

demand for corrosion-resistant products in many

areas, will increase the demand for polyester

resin at an average of 9.2 percent a year through

1987. Polybutylene terephthalate (PBT) and polyethylene terephthalate (PET) will be among the

fastest growing polyester resins. PBT and PET are

expected to grow from a combined demand of 38

million lbs in 1977 to 322 million lbs by 1987—an

average annual growth rate of 24 percent. PBT is

currently the most widely used thermoplastic polyester resin. However, it is expected that PET production will increase more rapidly, overtaking

PBT production. The total polyester resin market

is expected to rise 140 percent in the next 10

years. other uses and average annual projected

production increases from 1977 to 1987 include

unsaturated reinforced polyester (9. 1 percent),

thermoset surface coatings (5 percent), cultured

marble and other unsaturated thermoses (4.0

percent), strapping (mostly scrap, 28 percent),

and fibers (4.0 percent). (C&EN Jan. 30, 1978, p.

11)

Zeolites

Zeolites (aluminosilicates) hold promise as detergent builders, A 25-million-lb market in 1977

has a prospect of a possible 400-million-lb market

in 1982. Zeolites containing detergents perform

“equivalent or roughly equivalent” to the phosphate-silicate formulations that now command 75

percent of the current heavy-duty powder market.

Environmental problems will continue to push

phosphate out of the heavy-duty home laundry

market. Zeolite 4A is a cubic crystalline sodium

aluminosilicate with the formula

Textile Chemicals

The market for textile chemicals is expected to

top the billion-dollar market by 1980. Examples

are:

Chemical Use

Biphenyl . . . . . . . . . . . . . . . . . . . . . . . . . . . . Dye bath

o-phenylphenol. . , . , . . . . . . . . . . . . . . additives

1,2,4-trichlorobenzene. . . . . . . . . . . . . . .

Methyl naphthalene. . . . . . . . . . . . . . . . . . . .

Perchloroethylene ., , . . . . . . . . . . . . . . . . . .

Alkyl aryl sulfonic acids . . . . . . . . . . . . . . . .

Ethoxylated alcohols , , , ., ., ., . . . . . . . . . .

Quaternary ammonium compounds . . . . . . .

Ethoxylated nonyl phenol, . . . . . . . . . . . . . . .

Alcohols of alkyl aryl sulfonic acid . . . . . . . .

Esters of phosphoric acid. . . . . . . . . . . . . . . .

Acrylic latex , . . . . . . . . . . . . . . . . . . . . . . . Finishing agents

Styrene-butadiene rubber latex . . . . . . . . . .

Polyvinyl alcohol , ... , . . . . . . . . . . . . . . . . .

Polyvinyl acetate , ., ., . . . . . . . . . . . . . . . . .

Melamine formaldehyde . . . . . . . . . . . . . . . .

Starches. . . . . . . . . . . . . . . . . . . . . . . . . . . .

Polyvinylchloride . . . ., ... , ., . . . . . . . . . .

Fluorochemicals . . . . . . . . . . . . . . . . . . . . . .

Glyoxal (dimethylol, dihydroxyethylene urea)

Carbamate (isobutyl, 2-methoxyethyl). . . . . .

Tetrakis phosphonium sulfate ‘ammonia . .

Cyclic phosphonates . . . . . . . . . . . . , .

Maleic anhydride. . . . . . . . . . . . . . . . . . . . . . Printing

Polyacrylic acids . . . . . . . . . . . . . . . . . . . . chemicals

Acrylates . . . . . . . . . . . . . . . . . . . . . . . . .

Butadiene acrylonitrile . . . . . . . . . . . . . . . . .

Hexamethylol melamine formaldehyde. . .

Dioctyl sulfosuccinates . . . . . . . . . . . . . . .

Ethoxylates . . . . . .

Pentachlorophenon . . . . . . Bacteriocides

o-phenylphenol. . . , . . . . . . . . . . . . . . .

Low (L and aromatic distillates. . . . . . . . . . .

Urea . . . . . . . . . . . . . . . . . . . . . . . . . . .

Ethoxylated alkyl phenols . . . . . . . . [dispersing

Sodium lauryl sulfate. . . . . . . . . . . . agents/mulsifiers

((;&EN, May 29, 1978, p. 12)

Pumice

Pumice has many similarities with asbestos.

They are both mineral oxides, low in density, heat

resistant, nonflammable, chemically inert, and

low in cost, Rhodes (Division of Beatrice Foods

Co., Des Plains, Ill.) claims pumice may be the safe

and economical alternative to asbestos (C&EN,

May 22, 1978, p. 9). The manufacturer suggests

that pumice be used in paints; chemicals (filtration media and chemical carrier); leather buffing:

compounders (powdered hand soaps and glass

cleaners); metal and plastic finishing; and ap-
Append/x A—Substances Whose Production or Environmental Release Are Likely to Increase in the Next 10 Years ● 121

placations in the dental, rubber, glass, furniture,

electronics, and pottery industries.

Polyvinylacetates

Acrylic and acetate resins compete in the market as textile and binder emulsions for nonwoven

fabrics. Currently, acrylics dominate both of

these markets by two-thirds of the total, Polyvinylacetates make up only 14 percent of the market,

with the remainder going to other resins. New

technical developments may change the status

quo. By 1987, acetates could surpass acrylics in

many quality paint and textile markets. (C&EN,

Mar, 20, 1978, p. 11)

Hydrazine and Its Derivatives

Originally used in rocket fuels, today hydrazine

and its derivatives are commercially used in herbicides, pesticides, blowing agents for plastics,

and water treatments. Its consumption is growing

by 15 percent per year according to Olin Chemicals’ advertisement in C&EN.

Olefinic Thermoplastic Elastomers

Olefinic thermoplastic elastomers are also

called TPO rubbers and were introduced in 1973,

having a market volume of 1.5 million lbs. It is anticipated that the demand for TPO rubber will

reach 44 million lbs by 1980 and that uses in automobiles will account for more than half of it.

Mechanical goods and wire and cable uses account for 12.7 and 18,2 percent of TPO demand,

respectively. Olefinic thermoplastic elastomers

are also used by carmakers in electrostatically

paintable body filler panels, air deflectors, and

stone shields. Recently they have been used as

sound deadening material on diesel-powered vehicles, jacketing and insulating material for wire

and cable coating, and many custom-molded and

extruded mechanical goods. (C&EN, Oct. 23, 1978,

p. 9)

Silicones

New markets for silicones as PCB replacements

in electrical transformers, in brake fluids, and as

elastomers are developing. Methylchloride is

used as an intermediate in the production of silicones, Other methylating agents could be used to

replace methyl chloride in most applications, but

the potential substitutes (e.g., dimethyl sulfate,

methyl bromide, methyl iodide) are much more expensive and have toxicity and handling problems

which make them less desirable.

Chlorobromination

Bromine chloride has been shown to be more effective as a disinfectant than chlorine in field trials. It is a heavy red liquid and 12 times more soluble in water than chlorine. Its vapor pressure is

one-third as great. Bromine chloride completely

hydrolyzes almost immediately to hypobromous

acid and reacts with ammonia in sewage to form

bromoamines. It is believed that chlorobromination is the best alternative to current chlorination

practices.

Polyethyleneterephthalate

DuPont is continuing a vigorous effort to develop a market for molded plastics made from conventional forms of thermoplastic polyethylene terephthalate. (See also Polyester resin, ) This resin

has a multibillion-pound demand as polyester

fibers and films and is finding a large market in

plastic beverage bottles. DuPont’s trade name for

PET is Rynite. Rynite’s prime targets will be

metals replacement, especially in automobiles.

Chemicals Produced or Released Due

to Energy Development Technology

Coal Liquefication and

Gasification Program

The conversion of coal to liquid to gaseous hydrocarbons for fuel technologies will result in the

release of many chemicals to the environment.

The contaminants may enter the environment via

two pathways: 1) emission into the atmosphere

with the consequent potential for long-range

transport and 2) direct discharge via runoff and

leaching into the aquatic and terrestrial domain

where impact might be expected to be more localized. Contaminants from coal combustion can be

classified into three groups: 1) organic chemicals,

2) inorganic chemicals, and 3) radionuclides.

Organic Contaminants

Organic contaminants from coal-derived procinto several categories as
122 ● Environmental Contaminants in Food

Hetrocyclics . . . . . . . . . . .

Simple aromatic

hydrocarbons ., ., . . . .

Phenols. . . . . . . . . . . . . . .

Polycyclic aromatic

hydrocarbons . .

Sulfur compounds

Organometallics. ,

Naphthyl cyanides

. . . . . .

. . . . . .

., ...,

,. ...,

Trapped organic

Pyridines

Quinolines

Benzene

Toluene

Xylenes

Phenols

Cresols

Xylanols

Benzo(a)pyrene

Dibenzofluorene

Dibenzoanthracene

Benzoanthracenes

Benzo(a)anthrone

Dimethylbenzoanthracene

Chrysene

Methylchrysenes

Benzocarbozoles

Idenopyrenes

Carbozoles

Pyrenes

Biphenyl

Acenapthalene

Acenapthalyne

Fluorene

Alkylanthracenes

Alkylphenanthracenes

Anthracene

Perylene

Benzoperylene

Coronene

Thiophenes

Mercaptans

Carbon disulfide

Methyl thiphene

Nickel carbonyl

Tetraethyl lead

Napthyl cyanide

Ammonium thiocyanate

compounds and aromatic

units in coals that were isolated, separated, and

identified by gas chromatography and mass spectrometry are shown in table A-1.

Inorganic ChemicaIs

Category

Acids . . . . . . . . . .

Chromium salts . .

Sulfur compounds

Trace elements. . .

.. .,,,

. . . . . .

. . . . . .

,, . . ! .

Examples

Sulfuric acid

Nitric acid

Hydrochloric acid

Chromium chloride

Chromium sulfide

Hydrogen sulfide

Carbon disulfide

Antimony Manganese

Arsenic Mercury

Barium Molybdenum

Beryllium Nickel

Bismuth Selenium

Cadmium Silver

Chromium Tellurium

Cobalt Thallium

Copper Tin

Fluorine Uranium

Gallium Vanadium

Lead Zinc

Fine particulate , . . . . . .

Gasses . . . . . . . . . . . . . . .

Radionuciides

Emissions from a

Sulfur particulate

Respirable coal dusts

Tar

soots

Carbon monoxide

Sulfur dioxide

Sulfur trioxide

Sulfur tetraoxide

Nitrous oxide

100-MW electricity generation powerplant that burns coal at a rate of approximately 100 tons per hour are estimated to

contain 1 ppm of uranium and 2 ppm of thorium, A

plant of this size is expected to release 1 percent

of its fly ash to the atmosphere. Under these conditions thorium-228 and -232, radium-224, and

lead-212 each contribute approximately 5 x 10-’

Ci per year; uranium-234 and -238, thorium-230

and -234, radium-226, lead-210, polonium-210,

and bismuth-2 10 each contribute approximately 8

x 10-:~ Ci per year; uranium-235 and praseodymium-231 both contribute approximately 3.5 x

10-4 Ci per year; and radon-220 and -222 together

account for approximately 1.2 Ci per year. (ERDA

report 77-64, August 1976)

Radioactive emissions of bituminous coals have

a high uranium content (75 ppm).

Solar Heating and Cooling

of Buildings

Water contamination can occur in solar-heated

domestic hot water systems at heat exchanger interfaces. Serious health consequences could be

expected if the contaminated water is ingested.

Water contamination could result from the heat

exchange fluids themselves, or in water-based

systems from such additives as:

Corrosion inhibitors—Chromates, berates, nitrates, nitrites, sulfates, sulfites, arsenates, benzoate salts, various triazoles, silicates, and phosphate compounds.

Freeze protestants—Glycols.

Heat transfer fluids—Paraffins, aromatic and

other synthetic hydrocarbons.

Bacteriacides— Chlorinated phenols.

Solar collectors used in heating and cooling

systems utilize organic chemical compounds as insulators that can emit highly toxic substances

under overheat or fire conditions. Fumes usually

consist of simple starches and phenolic compounds: ammonia, hydrochloric acid, hydrofluoric

acid, toluene diisocyanate (TOI), and hydrogen

cyanide.
Appendix A—Substances Whose Production or Environmental Release Are Likely to Increase in the Next 10 Years ● 123

Table A-1 .—Trapped Organic Compounds and Aromatic Units in Coal

45

46

47

48

49

50

51

52.

53

54

55

56

57

58

59

60

61.

62

63

64

65

66

67

68

69

70

71

72

73

74

75

76

77

78

79

80

81

82

B = branched T = identlflcatlon tentative ~ = identlflcatlon uncertain

Fuels From Biomass

Thermochemical biomass conversion can produce gases, tars, oils, and unconverted residue

(char) and ash, depending on the particular conversion process. Thermochemical reactions generated sulfur-containing (H2S, COS, CS2

, SOX) and

nitrogen-containing (HCN, NOX, NH3

) gases.

83

84

85

86

87

88

89

90

91

92

93

94

95

96

97

98

99.

100

101

102

103

104

105

106

107

108

Water can be affected by the residuals produced

from thermochemical conversion. Low-molecular

weight oils, phenols, leachates from char and ash

residues, and scrubber solution runoff may enter

water bodies by direct discharge or by percolation to subsurface waters from evaporation

points.
124 “ Environmental Contaminants in Food

REFERENCE LIST FOR SUBSTANCES WHOSE PRODUCTION OR

ENVIRONMENTAL RELEASE ARE LIKELY TO INCREASE

IN THE NEXT

Chemical Marketing and Economics Abstracts.

The Division of Chemical Marketing and Economics of the American Chemical Society (ACS) presents papers at ACS national meetings on subjects related to the responses of the chemical industry to economic changes as well as responses

of the financial community to changes in the

chemical industry. Abstracts of these papers are

published by ACS.

A Study of Industrial Data on Candidates for

Testing. This document, published by the U.S.

Environmental Protection Agency, Office of Toxic

Substances (EPA Contract No. 68-01-4109, November 1976) contains market forecasts for 10

major classes of chemicals (109 individual chemicals) with an annual production greater than or

equal to 1 million lbs. Chemicals that are used exclusively as drugs or pesticides are not included.

The market forecasts include: 1) a discussion of

production and trade statistics, 2) consumption

patterns, whenever possible, 3) growth trends, 4)

a brief summary of current uses as well as potential new applications, and 5) growth trends in endmarket consumption. A discussion of possible substitutes for some of the chemicals is also included.

Environmental Development Plans. The Environmental Development Plans (EDPs) published by

the U.S. Department of Energy (March 1978) were

conceived and prepared as basic documents to

assist in planning and managing environmental

programs of energy technology development. Approximately 30 EDPs covering major developing

energy technologies were prepared.

A Review of Current Information on Some Ecological and Health-Related Aspects to the Release

of Trace Metals Into the Environment Associated

With the Combustion of Coal. This document by

Merrill Heit is a technical report (HASL-320) from

10 YEARS

the Health and Safety Laboratory, Energy Research and Development Administration, New

York, N.Y. 10014, reviewing the literature on one

class of pollutants. Information on the environmental levels, ecological effects, and potential

toxicity to man of 35 elements that may be released into the environment by coal combustion or

gasification is presented.

Fossil Energy Update. This monthly journal

compiled by the Department of Energy lists abstracts of current scientific and technical reports,

journal articles, conference proceedings, theses,

and monographs on all aspects of fossil energy, including factors involving the environment, health,

and safety.

Chemical Engineering News. The Chemical Engineering News is a weekly publication of the

American Chemical Society that contains relevant information in such sections as “Chemical

World, “ “This Week,” “ Business Concentrates, ”

and “Science/Technology,” and in profiles on

selected chemicals.

Chemical Marketing Reporter. This weekly,

published by Schnell Publishing Company, Inc.,

contains information on chemical market reports

and profiles on selected chemicals.

Trapped Organic Compounds and Aromatic

Units in Coal. This article, published by Tyoichi

Hayatsu et al. in Fuel 57:541 (1978), contains a

detailed analysis of the organic constituents of

three coals: a lignite, a bituminous, and an anthracite. Organic compounds trapped in the coal

matrix, residuals, and products of the original

coalification process were described.

Personal Communications With Several Organizations, Including the Chemical Development

Association and Chemical Marketing Research

Association.
Appendix B

Friday

June 29, 1979

Part XII

Department of

Health, Education,

and Welfare

Food and Drug Administration

Polychlorinated Biphenyls (PCB’s);

Reduction of Tolerances

125
126 ● Environmental Contaminants in Food

30330 Federal Register / Vol. 44, No. 127 / Friday, June 29, 1979 / Rules and Regulations

DEPARTMENT OF HEALTH,

EDUCATION, AND WELFARE

Food and Drug Administration

21 CFR Part 109

[Docket No. 77N-0080]

Polychlorinated Biphenyls (PCB’s);

Reduction of Tolerances

AGENCY: Food and Drug Administration.

ACTION: Final Rule.

SUMMARY : The Food and Drug

Administration [FDA) is reducing the

tolerances for unavoidable residues of

the industrial chemicals polychlorinated

biphenyls (PCB’s) in several classes of

food. Specifically, the agency is reducing

the tolerances in milk and dairy

products from 2.5 parts per million (ppm)

to 1.5 ppm (fat basis), in poultry from 5

ppm to 3 ppm (fat basis), in eggs from 0.5

ppm to 0.3 ppm, and in fish and shellfish

from 5 ppm to 2 ppm.

DATES: Effective August 28, 1979;

objections on or before July 30, 1979.

ADDRESS: Written objections to the

Hearing Clerk (HFA-305), Food and

Drug Administration, Rm. 4-85, 5000

Fishers Lane, Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT:

Howard N. Pippin, Bureau of Foods

(HFF-312), Food and Drug

Administration, Department of Health,

Education, and Welfare, 200 C St. SW.,

Washington, DC 20204,202-24$3092.

SUPPLEMENTARY INFORMATION : In the

Federal Register of April 1,1977 [42 FR

17487), FDA proposed to reduce the

temporary tolerances for unavoidable

residues of PCB’s in several classes of

food. The agency received over 100

comments on the proposal from

interested individuals, consumer groups,

businesses, trade associations, State

government agencies, and others. The

agency has considered these comments

and is now issuing a final order reducing

the PCB tolerances as originally

proposed. Following a brief discussion

of the background, this document will

respond to the comments the agency

received and explain the agency’s

reasons for adopting the reduced

tolerance levels.

I. Background

PCB’s are a class of toxic industrial

chemicals that have become persistent

and ubiquitous environmental

contaminants as a result of past

widespread, uncontrolled industrial use,

As explained in the preamble to FDA’s

proposal initiating this rulemaking

proceeding (see 42 FR 17489), one result

of PCB contamination of the

environment has been contamination of

certain foods. In the Federal Register of

July 6,1973 (38 FR 18098), FDA issued

regulations to deal with the problem of

PCB contamination of food. Among

those regulations was one establishing

temporary tolerances for unavoidable

PCB residues in various categories of

food. Those original tolerances are now

codified in $109.30 (21 CFR 109,30). The

order FDA is issuing in this document

reduces certain of those tolerances.

FDA’s authority to issue tolerances for

unavoidable food contaminants is

derived from sections 402(a)(2)(A) and

408 of the Federal Food, Drug, and

Cosmetic Act (the act) (21 U.S.C.

342(a)(2)(A) and 346). Section

402(a)(2)(A) deems food adulterated,

and thus prohibited from interstate

commerce, if it contains “any added

poisonous or added deleterious

substance” that is unsafe within the

meaning of section 4080 Section 408

deems any added poisonous or

deleterious substance to be unsafe

unless its presence in the food is

required in the production thereof or

cannot be avoided by good

manufacturing practice. Section 408 also

authorizes the agency to promulgate

regulations limiting the quantity of such

a required or unavoidable substance

that can be present legally in food. Such

limits, called tolerances, are to be set by

FDA at the level found necessary to

protect the public health, taking into

account the extent to which the .

substance is required or unavoidable

and the other ways the consumer may

be affected by the same or other

poisonous or deleterious substances,

Once a regulation establishing a

tolerance has been promulgated for a

particular poisonous or deleterious

substance, food containing that

substance in an amount exceeding the

tolerance is deemed adulterated under

section 402(a) (2)( A].

One of the primary purposes of

section 408 of the act is to enable FDA

to deal effectively with environmental

contaminants such as PCB’s, These

substances often enter food as a result

of events beyond the reasonable control

of the food manufacturer or processor

and, once in the food, usually cannot be

removed by good manufacturing

practice. For example, in the case of

PCB’s, some species of fish have become

contaminated to varying degrees as a

result of the dumping of PCB-containing

industrial waste into the nation’s waters

(see the Federal Register of March 18,

1972 (37 FR 5705)]. Once the

contamination occurs, there is little that

can be done to remove the PCB’s from

the water or from the fish; their presence

is, in that sense, unavoidable. Because

the initial contamination of fish with

PCB’s cannot be avoided (nor the PCB’s

processed out), the only way to avoid

PCB’s in fish is to remove fish from

commerce if it contains PCB’s above a

given tolerance level. The degree of

avoidance accomplished by this method

is, of course, a function of the level at

which the tolerance is set, In this way, it

is theoretically possible to avoid PCB’s

in fish absolutely by removing from

commerce all fish that contain any

amount of PCB’s.

Section 408 of the act authorizes FDA

to make a practical judgment in dealing

with such environmental contaminants:

Based on an assessment of the degree to

which the contaminant poses a threat to

consumers, the agency can decide to

tolerate the contaminant’s presence in

food up to a level the agency considers

appropriate to protect the public health,

taking into account, among other factors,

the extent to which the presence of the

contaminant is unavoidable, In making

this judgment, the agency’s paramount

concern is protection of the public

health: The tolerance cannot be set

above the level. the agency finds

necessary to protect the public health

adequately. But in determining what

tolerance level provides an adequate

degree of public health protection, FDA

is required by section A08 to consider

the extent of unavoidability—in the case

of PCB contamination of fish, the

amount of PCB-contaminated fish that

must be disposed of to reduce human

exposure to PCB’s to a tolerable level,

As a practical matter, of course, a

tolerance, if it is to be enforceable,

cannot be set below the level at which

the contaminant can be reliably

measured for enforcement purposes by

available analytical methods.

The toxicological data available on

PCB's make it clear that, in an ideal

situation, it would be preferable not to

have PCB’s in food at any level. As

discussed more fully below, the data do

not permit the identification of any level

of PCB exposure that can be said to

provide an absolute assurance of safety,

It is equally clear, however, that the

reduction of PCB exposure from food

sources to zero, or to a level

approaching zero, would require

elimination of large amounts of food,

especially fish. Hence, in deciding the

appropriate levels for PCB tolerances

under section 408, FDA has had to make

some extraordinarily difficult judgments.

It has had to decide, in effect, where the

proper balance lies between providing

an adequate degree of public health
Append/x B— FDA Derivation of PCB Tolerances— Federal Register ● 127

Federal Register / Vol. 44, No. 127 / Friday, June 29, 1979 / Rules and Regulations 38331

protection and avoiding excessive losses

of food to American consumers.

The comments received on the

proposal reveal that by far the most

controversial aspect of this rulemaking

proceeding is the balancing judgment

FDA made in proposing to reduce the

PCB tolerance in fish from 5 to 2 ppm.

Some comments argued that the

proposed reduction would cause an

excessive loss of food and significant

adverse economic impact without

providing any significant increase in

public health protection. Other

comments argued the converse, i.e., that

the proposed reduction to 2 ppm would

not adequately protect the public health

and that the tolerance should be

reduced to 1 ppm (the lowest level at

which PCB residues in fish can be

reliably measured fop enforcement

purposes), despite the additional losses

of food that a reduction to 1 ppm would

cause. In each case, the comments

bolstered their arguments by contending

that FDA has either overestimated or

underestimated the toxicity of PCB’s and

the impact of the proposed reduction of

the tolerance in terms of food loss and

adverse economic consequences.

The comments criticizing the proposed

reduction of the fish tolerance highlight

the difficulty of the judgment FDA must

sometimes make in establishing

tolerances. Not only must FDA make a

qualitative judgment about the proper

balance between adequate public health

protection and excessive loss of food, it

also must often make that judgment on

the basis of data that are incomplete, or

even in dispute, and that can easily lead

reasonable people to differing

conclusions. As the comments illustrate,

it is nearly always possible to conduct

additional studies and investigations to

refine further the knowledge of a

substance’s toxicological profile, the

incidence and-degree of human

exposure to it, and the impact a given

tolerance reduction will have on the

food supply. As an agency whose first

responsibility is to protect the public

health, however, FDA must act on the

basis of the information available to it,

even when the information is

incomplete. Neither the agency nor the

public can afford to wait until every

uncertainty is resolved. See Ethyl Corp.

v. Environmental Protection Agency, 541

F. 2d 1, 24-29 (D.C, Cir,) (en hmc), cert.

denied, 426 U.S. 941 (1976].

In the case of PCB’s, even though

there are obvious shortcomings in the

available data, which are discussed

below, FDA considers the data to

provide a more than adequate basis for

the exercise of its judgment in reducing

the PCB tolerances. There would be no

advantage in delaying this action

because it will take years to resolve

certain of the shortcomings in the data

on PCB’s, if they can be resolved at all.

For example, no chronic toxicity studies

have been performed on the specific,

chemically distinct composition of PCB’s

found in fish residues. Even if such

studies were begun immediately, it

would be 3 to 4 years before results

could be available. That plainly is too

long to wait to take action necessary for

the protection of the public health.

Because of the emphasis the

comments placed on the proposed

reduction of the fish tolerance, this

document reviews the basis on which

the reduction was proposed and

explains why, after considering the

comments, the agency has decided to

promulgate the reduction as proposed.

After discussing the fish tolerance and

the major points raised about it in the

comments, this document responds to

the remaining comments received on

other aspects of the proposal.

11. The Tolerance for Fish and Shellfish

In the preamble to the April 1, 1977

proposal, the agency discussed new

toxicity data that had become available

after the original PCB tolerances were

promulgated in 1973 [42 FR 17488-9). In

contrast to the data underlying the

original tolerances, which consisted

primarily of data from retrospective

studies of humans in Japan who were

exposed to high doses of PCB’s and

showed acute toxic effects from the

exposure (42’FR 17487+), the new

toxicity data consist primarily of animal

studies showing an association between

PCB exposure and serious subchronic

and chronic toxicities, including adverse

reproductive effects, tumor production,

and, possibly, carcinogenicity, as well

as effects on numerous biochemical

systems [42 FR 17488-9). Although the

data do not fully resolve such important

questions as the carcinogenicity of

PCB’s, they lead to the conclusion that

neither “no effect” nor “allowable daily

intake” levels for PCB’s can be

established with any confidence and

that, from a toxicological point of view,

human exposure to PCB’s should be

reduced.

The preamble to the proposal also

discussed data FDA had gathered on

human exposure to PCB’s, especially

from dietary sources (42 FR 17489-90),

These data show that the current

incidence of PCB contamination of food

has declined significantly in comparison

to that on which the original PCB

tolerances were based (see 37 FR 5705),

Indeed, the new data show that fish are

the only food group in which detectable

levels of PCB contamination are now

routinely found.

Based on the declining incidence of

PCB contamination, which means that

PCB’s are avoidable in food to a greater

degree now than they were earlier, as

well as the new toxicity data suggesting

chronic toxic effects, FDA decided the

PCB tolerances should be reduced.

In the preamble to the proposal, the

agency analyzed the new toxicity and

exposure data as they bore specifically

on the tolerance for PCB’s in fish (42 FR

17492-3). The agency concluded that

reduction of the tolerance from 5 to 2

ppm was necessary to protect the public

health adequately, even though that

reduction would result in the estimated

loss of a minor percentage of marine fish

(approximately 0.2 percent) and up to 25

percent of freshwater fish shipped

interstate (the loss of marine and

freshwater fish having a combined

landed value of approximately $8

million per year). The agency concluded

that the increment of public health

protection afforded at least theoretically

by a further reduction of the tolerance to

1 ppm did not justify such a reduction in

light of the substantially greater loss of

food that would result (a combined

landed value, marine and freshwater. of

approximately $18 million per year).

As noted, a large majority of the

comments on the proposal dealt with

some aspect of the agency’s proposal to

reduce the fish tolerance to 2 ppm. Some

of the comments agreed that the

proposal struck a proper balance

between the need to protect the public

health and the need to avoid excessive

loss of food. Other comments argued

that the tolerance should be reduced to 1

ppm in light of the new toxicity data on

PCB’s, despite any additional loss of

food that might result.

Most of the comments on the fish

tolerance, however, were submitted by

members of the fishing industry, by

trade associations, and by agencies of

State governments involved in

commercial fishing matters, who argued

that reduction of the tolerance to 2 ppm

is not justified. Some of these comments

contended that the health hazard

presented by occasional consumption of

fish containing 5 ppm PCB’s is not

significant and that any reduction in risk

to consumers accomplished by reducing

the tolerance to 2 ppm would be minor.

These comments also argued that any

such risk reduction would be

outweighed by the resulting adverse

economic consequences, which some

argued would be far in excess of those

cited by the agency in its proposal. In

support of the latter argument, some of

these comments estimated the impact a
128 ● Environmental Contaminants in Food

38332 Federal Register / Vol. 44, No. 127 / Friday, June 29, 1979 / Rules and Regulations

2 ppm tolerance would have not only on

the commercial fish catch, but also on

employment and income in the fishing

and related industries and on

recreational fishing. Arguing that the

States would curtail recreational fishing

in certain areas if the tolerance were 

reduced to 2 ppm, the comments

projected large losses of sales among

those supplying boats, licenses, tackle,

and bait to sport fishers.

Due to the large volume of comments

challenging the proposed reduction of

the fish tolerance, the agency has

carefully reassessed the justification for

lowering the tolerance from 5 to 2 ppm.

It has reviewed the toxicological data

and has attempted to estimate in

quantitative terms the degree to which

lowering the tolerance would reduce

risk to consumers. In addition, it has reexamined the question of how much

additional loss of fish would occur as a

result of the proposed reduction. Based

on its reassessment, the agency

concludes that reduction of the

tolerance for PCB’s in fish to 2 ppm

strikes the proper balance between the

need to protect the public health and the

need to avoid unnecessary loss of food.

Hence, the reduced tolerance is being

promulgated as proposed.

A. Risk Reduction

As noted earlier in this preamble, the

proposal to reduce the fish tolerance

was based in part on new toxicity data

showing a relation between PCB

exposure and an increased incidence of

various subchronic and chronic toxic

effects, including adverse reproductive

effects, tumor production, and, possibly,

carcinogenicity (42 FR 17487-9). The

proposal itself noted certain factors that

complicate the evaluation of PCB

toxicity (e.g., varying degrees of toxicity

among the several forms of PCB’s, the

presence of toxic impurities such as

chlorinated dibenzofurans in

commercial preparations of PCB’s, the

differences in chemical composition

between commercial PCB’s and PCB

residues in fish, and varying

susceptibilities of different animal

species to the toxic effects of PCB’s);

these complicating factors were also

pointed out in some of the comments

received on the proposal,

Notwithstanding these factors,

however, there is little genuine dispute

over the fact that exposure to PCB’s

must be considered to pose a risk of

serious, chronic toxic effects in humans.

The toxicological judgment that flows

from this fact—i.e., that a reduction in

human exposure to PCB’s will reduce

this risk-was an important part of the

agency’s rationale for proposing to

reduce the fish tolerance. Nothing in the

comments and nothing discovered

during FDA’s reassessment of the

toxicity data alters the validity of that

fundamental judgment. The agency

therefore concludes that it is important

as a matter of public health protection to

minimize human exposure to PCB's.

The real question raised by the

comments is whether the degree of risk

reduction accomplished by lowering the

fish tolerance to 2 ppm is sufficient to

justify the increased loss of food that the

lower tolerance will cause. This is an

extremely difficult question because it is

not now possible for toxicologists to

quantify precisely, on the basis of

toxicity data derived from animal

studies, the risks posed to humans.

Using classical toxicological methods,

the most that can be done reliably is to

make qualitative judgments about risks:

A statistically significant increased

incidence of adverse effects in animals

is good evidence of a risk to humans,

and, generally, the greater the incidence

of effects in animals, the greater the risk

to humans (Ref. 43). Having identified

the risk of a chronic toxic effect from

exposure to a substance, classical

toxicological principles lead to the

conclusion that reduction in exposure

will reduce the risk (Ref. 44). Again,

there is no evidence that these

principles do not apply to PCB’s.

Scientists have recently developed

methods, incorporating mathematical

extrapolation models, for making

quantitative estimates of risks to

humans based on toxicity data from

animal studies. These risk assessment

methods do not purport to quantify

precisely the expected human risk, but

rather attempt to estimate in

quantitative terms an upper limit on the

risk to humans that can be expected

from a given level of exposure to a toxic

substance, assuming humans are no

more susceptible to the effects of the

substance than are the most susceptible

members of the animal species for

which toxicity data are available. These

risk assessments can be useful as a

means of comparing risks at various

exposure levels and illustrating the

toxicological judgment that a reduction

in exposure will reduce risk. Because of

all the problems inherent in

extrapolating from animal data to the

expected human experience, however,

the numbers produced by a risk

assessment must be interpreted

cautiously: They are estimates of upper

limits on risk and, though potentially

useful for comparative purposes, cannot

be said to quantify actual human risk

precisely. These assessments attempt to

avoid underestimating human risk, but

even that cannot be guaranteed. The

Work Group on Risk Assessment of the

Interagency Regulatory Liaison Group

(IRLG) has recently prepared a report

that discussers many of the principles

involved in risk assessment.

As part of its review of the

toxicological justification for reducing

the fish tolerance, the agency has

performed a risk assessment aimed at

comparing the estimated risks

associated with PCB exposure at the

various levels of exposure that would

result from different tolerance levels

The written report on this risk

assessment has been made a part of the

record of this proceeding as Reference

45.

As explained in that report, the risk

assessment involved the use of the most

recent available data on the incidence of

PCB contamination of fish to calculate

the level of exposure to PCB’s that could

be expected to result from tolerance

levels of 5,2, and 1 ppm (Table 4, Ref.

45). These calculations were based on

the assumption that under a given

tolerance level, no fish containing PCB’s

in an amount above that level would be

consumed, It is true, of course, that an

FDA tolerance level directly affects only

fish shipped in interstate commerce, but

States often adopt FDA’s tolerance

levels for application to intrastate and

recreational fishing. Thus, even if the

exposure calculations used in the risk

assessment (Table 4, Ref. 45) do

somewhat overstate the absolute

amounts of exposure reduction, they

nevertheless demonstrate that a

reduction of the PCB tolerance for fish

would result in a significant reduction of

PCB exposure [e.g., for heavy consumers

of the affected species, reduction of the

fish tolerance from 5 to 2 ppm reduces

exposure from an estimated 20.1

micrograms (μg) per day to an estimated

14.9 μg per day). Such significant

reductions in PCB exposure from fish

are especially important in terms of risk

reduction because fish are the only food

group in which detectable levels of

PCB’s are still regularly found.

Based on the calculations of exposure

at various tolerance levels and toxicity

data from animal studies, the agency

used a linear extrapolation method to

estimate the upper limits on certain risks

posed by exposure to PCB’s, This

analysis resulted in estimates of

significant potential risk to humans who

consume PCB-contaminated fish on a

continuing basis, especially fish

contaminated at or above the 5 ppm

level (Tables 6 and 7, Ref. 45). For

example, using the total malignancy

data from the National Cancer Institute

(NCI] Bioassay (Ref. 19), it is estimated
Appendix 6— FDA Derivation of PCB Tolerances—Federal Register . 1 2 9

Federal Register / Vol. 44, No. 127 / Friday, June 29, 1979 / Rules and Regulations 38333

that the upper limit on the lifetime risk

of cancer for heavy consumers of fish

most affected by the tolerances is 9.8

incidence of cancer per 100,000 of the

population, assuming the tolerance is 5

ppm; 7.2 per 100,000, assuming the

tolerance is 2 ppm; and 4.4 per 100,000,

assuming the tolerance is 1 ppm (Table

6, Ref. 45). Stated another way, it is

estimated that the upper limit on the

number of new cancers per year among

heavy consumers of fish most affected

by the tolerances is 46,8, assuming a

tolerance of 5 ppm; 34.3, assuming a

tolerance of 2 ppm; and 21, assuming a

tolerance of 1 ppm (Table 7, Ref. 45).

As explained in the report (Ref. 45),

the utility of this risk assessment for

evaluating actual risk to humans from

exposure to PCB’s is extremely limited.

This is due both to difficulties inherent

in making such extrapolations from

animals to humans and, perhaps more

importantly in this instance, to gaps and

uncertainties in the data available for

this particular risk assessment. For

example, the toxicity studies on which

the risk assessment is based used

commercial preparations of PCB’s,

which are chemically different from the

PCB residues found in fish and which

contain small amounts of highly toxic

impurities (e.g., dibenzofurans) not

known to be present in fish residues,

Also, in making the exposure estimates

required for the risk assessment, it was

necessary to use existing data on the

numerical distribution of PCB levels in

fish and rely on the assumption that the

effect of a given tolerance level is to

remove from commerce all fish

containing PCB’s exceeding the

tolerances. It is possible that neither the

assumption nor the data precisely reflect

what actually occurs.

For these reasons and others

discussed in the report (Ref. 45), the risk

assessment does not provide a basis for

precise quantification of the amount of

risk reduction accomplished by reducing

the fish tolerance, Despite the

limitations inherent in the risk

assessment, however, the agency

regards it as illustrative of the basic

validity of the toxicological rationale for

reducing the tolerance for PCB’s in fish:

Reduction of the tolerance will result in

a significant reduction in risk among

those who consume PCB-contaminated

fish. FDA considers this risk reduction

to be of significant public health value,

even though it cannot be precisely

quantified.

B. Loss Of Food

In the preamble to the proposal, the

agency estimated that the loss of food

from commercial channels resulting

from a 2 ppm tolerance for PCB’s in fish

would be approximately $8 million in

landed value, compared to

approximately $1 million for the 5 ppm

tolerance and $18 million for a 1 ppm

tolerance, The estimated $8 million loss

resulting from a 2 ppm tolerance

encompassed a negligible percentage of

the marine-fish catch (about 0.2 percent)

and about 25 percent of the freshwater

catch (42 FR 17492),

The agency arrived at these figures by

assuming that all fish containing PCB’s

above the tolerance would be removed

from both interstate and intrastate

commerce (“Economic Impact

Assessment for Proposed Reduction of

Temporary Tolerances for

Polychlorinated Biphenyls in Food,” Ref.

39). There are several difficulties

inherent in this assumption. On the one

hand, it may tend to overstate the loss

because (a) some states may not apply

FDA’s reduced tolerance to intrastate

fish, (b) some violative fish will be part

of nonviolative lots, and (c) some

violative lots may enter commerce

undetected. On the other hand, it may

tend to understate the loss because once

the violative percentage of a given

species reaches a certain level,

commercial fishers may stop fishing that

species altogether. Some of the

comments cited these difficulties in

support of arguments that FDA had

either overestimated or underestimated

the amount of fish that would be lost as

a result of a 2 ppm tolerance. Despite its

acknowledged limitations, adoption of

the assumption is a necessary and

reasonable method for dealing with the

uncertainties inherent in predicting the

impact of a tolerance reduction. None of

the comments suggested an alternative

method for estimating the amount of fish

that would be removed from commerce

as a result of the proposed tolerance

reduction.

Because of the comments it received

questioning the justification for the

proposed reduction in the fish tolerance,

the agency has re-examined its

projections of the food loss expected to

result from such a reduction. The

projections made in the preamble to the

proposal were based on data obtained

in 1974 on the levels of PCB’s in

commercial fish, primarily from the

Great Lakes (Ref. 39), In making those

original projections, the agency was

forced to rely on the assumption that

PCB levels in freshwater fish nationwide

were as high as those found in the Great

Lakes. FDA now has more recent and

more representative data on PCB levels

in commercial fish, which it obtained

through a nationwide sampling program

conducted in 1978 and 1979, Based on

these more recent data, the value of the

fish projected to be lost at tolerance

levels of 5 ppm and 2 ppm is

substantially less than was projected in

the proposal. The loss projected under a

1 ppm tolerance would remain about the

same (Table B, “Regulatory Analysis for

Final Regulation for Reduction of

Temporary Tolerances for

Polychlorinated Biphenyls in Food,” Ref.

46). Specifically, the amount of

commercial fish now projected to be lost

as a result of a 2 ppm tolerance is about

$5.7 million (expressed in 1974 dollars)

compared to the previously estimated $8

million; the current estimated loss of fish

under a 5 ppm tolerance is about $0.6

million (compared to the previously

estimated $1.1 million). Under a 1 ppm

tolerance, however, the projected fish

loss, using the new sampling data on

PCB levels, is about $16 million

(compared to the previously estimated

$18 million). The percentage of the

freshwater fish catch now estimated to

be lost under a 2 ppm tolerance is 14

percent (compared to the 25 percent that

had been estimated from the 1974 data);

under a 1 ppm tolerance, the currently

estimated loss of freshwater fish is 35

percent (compared to the previously

estimated 43 percent) (Ref. 46),

As noted earlier in this preamble,

many of the comments argued that the

impact of the proposed tolerance

reduction must be measured not only by

the amount of the resulting fish loss but

also by other economic impacts, such as

potential unemployment and loss of

income in the fishing industry and

postulated disruption of the recreational

fishing industry (e.g., reductions in boat,

tackle, and bait sales]. The comments

provided figures ranging into the

hundreds of millions of dollars on the

total economic value of these industries

and, without offering any further

analysis, contended that the impact on

them would be “severe” or “major.” The

predicted impact on recreational fishing

was premised on the possibility that

State governments would severely

curtail recreational fishing if the

tolerance were reduced to 2 ppm.

In establishing a tolerance for PCB’s

in fish, FDA must take into account the

amount of fish a given tolerance would

remove from commerce. Section 406 of

the act, however, neither requires nor

authorizes FDA to weigh secondary

economic impacts when it considers the

level at which a tolerance should be set.

Consideration of such impacts would be

inconsistent with the paramount

concern of section 406, which is

protection of the public health, and

would complicate the decisionmaking

process under section 406 in a way
130 “ Environmental Contaminants in Food

Federal Register / Vol. 44, No. 127 / Friday, June 29, 1979 / Rules and Regulations.

Congress did not intend. Obviously,

consideration of the amount of food loss

caused by a tolerance helps to ensure

that the direct economic consequences

of the tolerance (in this case, decreased

sales and employment in the commercial

fishing industry) will not be

disproportionate to the increased degree

of public health protection accomplished

by the tolerance; but the agency

considers secondary economic

consequences, such as potential impact

on the recreational fishing industry,

totally beyond the scope of section 408.

None of this should suggest that the

agency is unaware of, or unconcerned

about, the economic consequences of its

actions. It is keenly aware that actions it

takes to protect the public health can

have adverse economic consequences,

both direct and indirect, and that these

consequences can sometimes be felt

with particular severity in certain

narrow segments of the economy. For

example, some of the comments on the

proposal argue that the impact of a 2

ppm PCB tolerance for fish will be

especially severe for small-scale,

freshwater fishers who specialize in

certain species that happen to be

heavily contaminated. The agency

acknowledged this possibility in the

preamble to the proposal (42 FR 17492).

in the present case, however, the

agency has reason to believe that the

claims of adverse economic impact are

exaggerated. Based on the 1078/1979

data on PCB levels in freshwater fish, a

2 ppm tolerance will remove from

commerce about $5.7 million worth of

commercial fish. Although it is possible

that fishing for certain heavily

contaminated freshwater species may

cease entirely in locations where PCB

contamination is concentrated, at least

some affected fishers-both commercial

and sport-can be expected to adjust to

the reduced tolerance by increasing

their catch of other species or

transferring their activities to other, less

contaminated locations within their

current area of operation.

In evaluating claims of economic

impact, it is theoretically and

pragmatically sound to take into account

the motives and opportunities for

adaptive behavior by affected

individuals and fins. If the public

demand for commercially caught fish

remains stable or increases, and if the

attractions of sport fishing remain

strong, it can be expected that some

fishing activity will shift to species that

are not contaminated above the

tolerance. Over time, the shifts will

become easier as the levels of PCB

contamination decline because more

and more species will have average PCB

levels well below 2 ppm. Over the long

term, the adjustments will help to

minimize the net economic impact of the

tolerance reduction on both individual

fishers and the overall commercial

freshwater fishing industry.

None of the comments attempted to

quantify in dollar terms the impact of

the tolerance reduction on the

recreational fishing industry, but several

postulated a “severe” or “major” impact

premised on voluntary decisions by

individuals not to fish and mandatory

curtailments of recreational fishing by

State authorities. FDA is in no better

position than were those submitting the

comments to make precise predictions

about the future behavior of individuals

and State agencies. However, the

agency considers the premises

underlying the projections of “major” or

“severe” impact to be somewhat

speculative and of questionable validity.

AS noted to the extent that the behavior

of individual recreational fishers is

affected by the tolerance reduction at

all, they, as much as commercial fishers,

can be expected to adjust to the

tolerance by shifting their activities to

the less contaminated species and

locations. Also, even if State agencies

decide that some curtailment of

recreational fishing is necessary in light

of the reduced tolerance, it is reasonable

to expect that their actions will be

tailored by species and location. In the

past, the most common response of

State agencies to FDA’s PCB tolerance

for fish has not been the mandatory

curtailment of recreational fishing.

Instead, they have issued warnings

concerning particular species and

locations and made suggestions

regarding both limitations on

consumption of particular species and

methods of preparing and cooking fish

that minimize the amount of PCB’s

actually consumed from contaminated

fish. Thus, there is little reason to

believe that a 2 ppm tolerance will lead

to widespread, mandatory curtailment

of recreational fishing and the resulting

drastic economic impact the comments

postulate.

C. Conclusion

Based on the data now before it, the

agency concludes that a reduction of the

fish tolerance from 5 to 2 ppm will result

in a meaningful decrease in the risk

experienced by consumers from

exposure to PCB’s. Some reduction of

the tolerance is clearly in order because

the toxic effects associated with

exposure to PCB’s are serious and

irreversible; and, due to declining levels

of PCB contamination the current 5 ppm

tolerance permits contamination that

can fairly be termed “avoidable’’ -even

among the-more highly contaminated

commercial species most likely to be

affected by a reduced tolerance, only a

minor percentage (about 1.5 percent)

contain PCB’s at levels as high as 5 ppm

(Table A, Ref. 46). The agency’s

judgment is that the balance between

public health protection and loss of food

is properly struck by a 2 ppm tolerance.

As noted, as 2 ppm tolerance effects a

meaningful decrease in risk to

consumers while still excluding from

commerce only a relatively small

amount of food (about $5.7 million

landed value in 1974 dollars).

Several comments argued that an

adequate degree of public health

protection can be provided only by

lowering the fish tolerance to 1 ppm, the

lowest level at which PCB’s can be

reliably measured in fish for

enforcement purposes. Indeed, as one

would expect, the risk assessment

performed by the agency, and discussed

above, indicates that the estimated risks

that might be experienced by consumers

of contaminated fish would be reduced

even further by a reduction of the

tolerance to 1 ppm (Tables 6 and 7, Ref.

45). Based on the evidence now before

it, however, the agency does not

consider a reduction to 1 ppm necessary

or appropriate in light of the policy of

section 408 of the act.

The risk assessment the agency made

incorporated several conservative

assumptions that were designed to

avoid understatement of the human risk.

Thus, it is expected that the actual risk

experienced by consumers of the 12

more heavily contaminated species

covered by the risk assessment is less

than that estimated. Moreover, the

average consumer, who eats fish from a

variety of freshwater and marine

sources, will actually experience a far

lower level of PCB exposure and a

correspondingly lower degree of risk

than those whose fish consumption is

concentrated among the more heavily

contaminated (predominantly

freshwater) species. For these reasons,

notwithstanding the quantified risk

estimates produced by the risk

assessment, the agency reaffirms the

conclusion it expressed in the preamble

to the proposal: The 2 ppm tolerance

provides an adequate degree of

protection for all but those who

consume above-average amounts of

freshwater fish taken from

contaminated waters (42 FR 17493).

In the agency’s judgment, the

additional increment of public health

protection that might be provided by

reducing the tolerance to 1 ppm does not

justify the additional loss of food that
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Federal Register / Vol. 44, No. 127 / Friday, June 29, 1979 / Rules and Regulations 38335

would resuIt. First, as discussed above,

the agency estimates that under a

tolerance of 1 ppm, approximately $16

million worth of the commercial fish

catch would be vioIative and thus,

presumably, removed from commerce.

This is nearly triple the $5.7 milIion

worth estimated to be violative under a

2 ppm tolerance. It is far more likely

under a 1 ppm tolerance than under a 2

ppm tolerance that the more heavily

contaminated species of freshwater fish

would be violative in percentages high

enough to put an end to their

commercial exploitation and, possibly,

force some segments of the freshwater

fishing industry to cease operations

completely. Thus, the actual loss of food

resulting from the 1 ppm tolerance could

greatly exceed even the $16 million

landed value (1974 dollars) estimated

above.

Second, for the average consumer,

current exposure to PCB’s in fish is at a

tolerably low level, when considered in

light of the criteria of section 406 of the

act, without a 1 ppm tolerance, The

average consumer eats a modest amount

of fish from a variety of sources, both

freshwater and marine, most of which

yield fish with PCB levels below 1 ppm.

Because their exposure is thus low to

begin with, they are adequately

protected by a 2 ppm tolerance, which

ensures that they will not be exposed to

the unusually high levels of PCB’s found

in some species of fish. The slight

additional protection these average

consumers might gain from a 1 ppm

tolerance does not justify the

significantly greater impact such a

tolerance would have on the availability

of food. On the other hand, atypical

heavy consumers (e.g., the Great Lakes

sport fisher who catches and consumes

large quantities of the contaminated

species) would likely not be adequately

protected by even a 1 ppm tolerance

because of the amount of fish they eat

and because those fish are seldom

affected by FDA tolerances (either

because they are sport fish or are from

intrastate commercial channels and, in

either case, are outside FDA’s

jurisdiction). Protection of these

consumers depends on actions by State

authorities.

Finally, though the new toxicity data

on PCB's clearly support the need to

reduce exposure to this contaminant, the

uncertainties in the data (discussed

above) cast some doubt on the degree to

which consumers are at risk from

extremely low levels of PCB exposure,

and therefore weigh against lowering

the tolerance to 1 ppm. If, for example,

more definitive and incriminating data

on the reproductive risks posed by

PCB’s are forthcoming, the agency might

consider establishing a 1 ppm tolerance

despite the effect that would have on the

availability of food.

For these reasons, the agency

concludes that at this time a 1 ppm

tolerance would not strike the proper

balance between protection of the

public health and the need to avoid

excessive loss of food.

Though FDA considers 2 ppm to be

the appropriate tolerance level for PCB’s

in fish under the criteria imposed by

section 406 of the act, the agency is

concerned about the health of certain

groups that may not be adequately

protected by a 2 ppm, or even a 1 ppm,

tolerance. As noted, sport fishers and

others who consume abnormally large

amounts of the more highly

contaminated species may be at risk

from PCB’s regardless of any tolerance

FDA establishes. (The agency’s risk

assessment, using data from a study of

Lake Michigan sport fish eaters,

estimated that the upper limit on the

lifetime risk of cancer for heavy eaters

of sport fish from Lake Michigan is

about 12 to 14 times greater than the

corresponding risk for heavy eaters of

those commercial fish most affected by

a PCB tolerance, even assuming the

tolerance remained at 5 ppm (Table 6,

Ref. 45).] Those individuals, whose high

exposures to PCB’s tend to result from

localized conditions and fishing

practices beyond the control of FDA,

should take steps to reduce their

exposure to PCB’s. FDA urges State and

local health officials to evaluate the

situation in their own localities and

determine what steps, if any, they can

take to address these special situations.

In the past, some State and local

agencies have made FDA’s tolerance

level for PCB’ s applicable to fish in

intrastate commerce and have issued

advisories to sport fishers warning that

consumption of certain species of fish

should be minimized and suggesting

other ways in which PCB exposure

could be reduced. These agencies should

review their past actions in light of the

current state of knowledge about PCB’s

and make the changes or take the

additional steps that may now be

appropriate, FDA will cooperate with

these agencies, as it has in the past, by

providing technical advice and

assistance. FDA is sending letters to the

governors of States most affected by

PCB’s in fish, discussing the agency's

concerns about aspects of the PCB

problem that may require an up-to-date

review in their States.

The agency is advising that State

health departments be particularly

concerned about women of childbearing

age, especially pregnant and lactating

women, who may have consumed, or are

consuming, higher than normal amounts

of PCB-contaminated fish. Data that

were discussed in the preamble to the

proposal (42 FR 17468-9) suggest an

association between PCB exposure and

reproductive disjunction in rats and

monkeys. They also show acute toxic

effects in the nursing offspring of

maternal monkeys that had been

exposed to toxic levels of PCB’s. Data

gathered by FDA since it issued the

proposal in 1977, and discussed in the

report on FDA’s risk assessment on

PCB’s (Ref. 45), establish more clearly

the link between PCB exposure and

adverse reproductive effects in the

rhesus monkey. They also confirm the

earlier data showing acute toxic effects

in the nursing offspring of PCB-exposed

maternal monkeys. As explained in the

risk assessment report (Ref. 45), it is not

possible at this time to determine with

confidence the significance of these data

in terms of human risk. There have been

no reports of human reproductive

abnormalities or overt toxic effects in

nursing human infants that can be

attributed to PCB’s. That fact is of only

limited significance, however, because

epidemiological studies adequate to

detect such adverse effects in humans

have not been conducted.

An additional reason for concern in

this area is that PCB’s ingested by

human mothers are found, and to some

extent are concentrated, in human

breast milk [see the discussions in the

preamble to the proposal and in the risk

assessment report (Ref. 45)). In a recent

nationwide survey, consisting of 1,038

samples of human breast milk collected

in 44 States, the mean concentration of

PCB’s was estimated to be in the range

of 1.00 to 1.10 ppm (on a fat basis) (Ref.

45). Though the data are scanty, it is

reasonable to assume that among

women who consume above-average

amounts of PCB-contaminated fish, or

who are exposed to PCB's from other

sources, the levels of PCB’s in breast

milk are significantly higher, As noted it

is not now possible to determine the

significance of these facts in terms of

increased risk to the nursing infant.

In sum, although the agency concludes

that a 2 ppm tolerance for PCB’s

adequately protects most consumers,

women of childbearing age, especially

pregnant and lactating women, are

among those who should be careful to

avoid abnormally high exposure to

PCB’s in fish, They can avoid such

exposure by minimizing consumption of

both commercial and noncommercial

fish from waters known to be

contaminated with PCB's and avoiding
132 “ Environmental Contaminants in Food

38336 Federal Register / Vol. 44, No. 127 / Friday, June 29, 1979 / Rules and Regulations

entirely those species of sport fish

known to contain high levels of PCB’s

(e.g., coho and chinook salmon from the

Great Lakes, and freshwater trout,

striped bass, and catfish from some

locations). State and local governments

have the important role of advising

consumers about conditions in

particular localities.

The agency is aware that its decision

to set the fish tolerance for PCB’s at 2

ppm, rather than leaving it at 5 ppm or

reducing it further to 1 ppm, is inherently

judgmental in character. Section 406 of

the act provides no formula for

balancing public health protection

against loss of food, and, hence, there is

no way for the agency’s decisions under

section 400 to be arrived at

mechanically or quantitatively or to

appear clear-cut in every case. In this

case, for example, forceful arguments

have been made in the comments in

support of both a 5 ppm and a 1 ppm

tolerance, but those arguments all reflect

the subjective” judgments of those who

made them. In the end, the agency has

been mandated by the Congress to make

its own informed judgment about what

is necessary to protect the public health.

It has done that herein setting the fish

tolerance at 2 ppm.

The statute provides an opportunity

for a public hearing on the agency’s

order lowering the PCB tolerance for

fish. Such a hearing would provide

persons adversely affected by the order

an opportunity to present any additional

evidence they may have bearing on the

matters that influenced the agency’s

judgment. As always, the agency is

prepared to reevaluate its position in

light of evidence adduced at a hearing.

D. Other Comments on the Fish and

Shellfish Tolerance

In addition to the points addressed

above, the comments raised several

other points relating to the tolerance for

fish and shellfish:

1. One comment recommended that

FDA review its entire mechanism for

handling recurrent problems of

environmental contaminants in fish. The

comment stated that the PCB tolerance

should remain at 5 ppm for marine fish

because the levels in those fish are low

enough that a reduction to 2 ppm would

have no increased protective effect, but

would result in economic problems that

are unnecessary for species with only

occasional high PCB levels. The

comment stated further that tolerances

should be set for freshwater fish based

on their individual place in the market—

their tonnage, distribution patterns, and

consumption patterns. When such

factors combine to present a risk, it was

argued, the tolerance should be applied

selectively to both the species and the

body of water.

The individualized approach to

establishing and enforcing tolerances for

environmental contaminants suggested

by this comment is not feasible because

the necessary species-by-species,

location-by-location data on PCB

occurrence do not exist. Furthermore,

many lots of fish, as currently packaged

and shipped, do not bear the water-oforigin information required for the

recommended regulatory approach.

These limitations make it necessary for

the agency to establish tolerances for

fish on a generic basis. The result is a

uniform regulatory approach for all

species, which provides clear and fair

rules for all segments of the fishing

industry and is necessary to ensure that

uncertainties and limitations in data will

not result in increasing human exposure

to PCB’s. To the extent that certain

species only occasionally have PCB

levels above 2 ppm, the economic

impact of the reduced tolerance will be

slight.

2. One comment stated that any FDA

regulatory action regarding PCB’s in fish

should apply to sport fish as well as

commercial fish.

FDA’s regulatory authority extends

only to foods shipped in interstate

commerce and clearly does not extend

to fish caught and consumed by

individual sport fishers. FDA cooperates

with the State agencies who have

authority over sport fishing by sharing

data and views regarding toxicological,

analytical, and compliance matters, but

FDA has no direct control over the

regulatory approaches adopted by the

States. As noted, however, the agency

urges State and local health officials to

look closely at the PCB problem in their

areas and take whatever steps they find

necessary to address those aspects of

the PCB problem, such as the exposure

of sport fishers, that are beyond FDA’s

authority.

3. One comment requested

reconsideration of the proposal to

reduce the fish tolerance on the ground

that overall ingestion of PCB’s is

reportedly declining. Because levels in

other foods have already decreased

considerably, it was argued, there is less

need to lower the fish tolerance,

The agency is aware that PCB levels

in foods other than fish have declined

and that overall PCB intake is lower

than it was in 1973, when the original

temporary tolerances were established.

However, as discussed in the preamble

to the proposal and in section II of this

preamble, toxicological considerations

now make it desirable to reduce dietary

exposure to PCB’s even further.

Reduction of the tolerance for PCB’s in

fish will bean especially effective step

toward accomplishing that goal, because

fish are the one remaining significant

source of dietary exposure to PCB’s.

4. One comment contended that fish

products are being subjected to an

entirely different regulatory standard

than are poultry products, with no

reasonable basis for the different

treatment. The comment stated that the

emphasis in establishing 2 ppm as the

tolerance for fish appears to have been

safety to the consumer despite a

considerable economic impact. Yet, it

argued, the higher level of 3 ppm for

poultry is based on economic

considerations relating to feed

contamination, apparently without

public health considerations. The

comment went on to state that the

average per capita consumption of fish

is 19 grams (g) per day compared to 63 g

per day for poultry products. According

to the comment, this means that under

the proposed tolerances, and assuming

maximum permissible levels in all foods,

the average person will receive five

times as much PCB’s from poultry as

from fish.

The agency does not agree with the

comment’s contention that the

considerations involved in establishing

the tolerances for poultry and fish result

in different or conflicting regulatory

approaches for these products, First, the

3 ppm tolerance for poultry is based on

PCB residues in the fat of the bird, not in

all the edible tissue as it is for fish,

Poultry generally averages about 10

percent fat; hence, the 3 ppm tolerance

is comparable to a level of about 0.3

ppm for the entire edible portion. Thus,

even taking into account the higher

average level of chicken consumption

and assuming all foods contain

maximum permissible amounts of PCB’s,

poultry will actually be regulated at a

level that will result in a substantially

lower intake of PCB’s from poultry than

from fish. Second, data show that

detectable PCB residues occur so

infrequently in poultry that exposure to

PCB’s from that source is already at an

insignificant level. Hence, further

reduction of that tolerance would not

significantly reduce dietary exposure to

PCB’s and would not enhance protection

of the public health, Fish data, on the

other hand, show frequent occurrence of

PCB residues at significant levels, so

that reduction of the tolerance will

result in increased protection for

consumers of fish.

As explained in the preamble to the

proposal (42 FR 17491-2), the agency

selected 3 ppm (fat basis) as the
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Federal Register / Vol. 44, No. 127 / Friday, June 29, 1979 / Rules and Regulations 30337

tolerance for PCB’s in poultry to allow

for the regular use of poultry feed

contaminated up to, but not exceeding,

the 0.2 ppm tolerance for PCB’s in

poultry feed. (0.2 ppm is the lowest

feasible tolerance for PCB’s in poultry

feed because of limitations on analytical

cap ability.) The 3 ppm level took into

account the biomagnification of PCB’s in

poultry that results from regular feeding

with poultry feed contaminated up to,

but not above, 0.2 ppm. The agency

reasoned that it would be inconsistent

to set tolerances on two products at

levels such that the use of one product

that complies with the applicable

tolerance causes the second product to

be illegal and, thus, that it would be

inappropriate to do so in the absence of

other overriding considerations [e.g.,

safety). For the reasons stated in the

preceding paragraph, the 3 ppm

tolerance for poultry adequately

protects the public health and is thus

consistent as a matter of public health

protection with FDA’s other tolerances

for PCB’s.

5. One comment stated that any

decision to lower the fish tolerance

made in reliance on the regulation of

point source discharges and

manufacture of PCB’s should not fail to

consider the fact that PCB levels in

contaminated waters are not expected

to decline for many years.

The agency is aware that, despite

Environmental Protection Agency

(EPA) antipollution activities and the

resulting gradual decline in PCB levels

in at least some contaminated waters,

there will continue to be a significant

occurrence of PCB’s in fish for at least

the next several years because of the

stability and persistence of the PCB’s

now contaminating the environment.

That fact was taken into account in

deciding to reduce the tolerances.

6. One comment stated that, because

pollution of water with PCB’s is

expected to continue, PCB levels in fish

will continue to rise, and susceptible

fish should be harvested now before the

increased contamination makes them all

inedible.

Although the levels of PCB’s in waters

currently contaminated may not

decrease substantially in the near

future, the agency does not expect those

levels to increase, nor does it expect the

levels of PCB’s in fish to increase. Better

control of PCB levels should result from

efforts by the EPA and industry to

control discharge of additional PCB’s

into the environment. Hence, even if it

were possible to harvest whole species

of fish now, that step would not have

the effect of preventing increased future

exposure to PCB’s. Finally, FDA has no

authority to regulate the pace at which

particular species of fish are exploited

commercially.

7. Several comments stated that the

decision to reduce the tolerance for fish

should be reconsidered and the current

5 ppm level reaffirmed because PCB’s

are being steadily eliminated from the

environment and may be expected to

disappear as a significant problem

within the next decade.

The agency does not agree that PCB’s

can be expected to be an insignificant

problem within 10 years. Although

EPA’s continuing activities have

resulted in a significant decrease in the

amount of PCB’s being introduced into

the environment especially into water,

the stability and persistence of these

chemicals and the likelihood that some

amount of additional contamination will

continue to occur from waste disposal

sites ensures that PCB contamination

will remain a problem for the

foreseeable future. Moreover, that PCB

levels are declining (i.e., that PCB’s are

becoming more avoidable) is a reason to

consider lowering the tolerance. not a

justification for leaving it unchanged.

8. One comment argued that the

decision to reduce the fish tolerance

should be reconsidered because by

lowering the fish tolerance, thereby

preventing consumption of

contaminated fish, some might be led to

believe that the problem of exposure to

PCB’s had been solved. This

misconception could in turn reduce the

pressure to attack the real problem—

pollution, However, the comment

argued, if the environmental

contamination itself is viewed as the

“real” PCB problem of importance,

changing the fish tolerance is almost

irrelevant, given the small quantity of

PCB’s affected.

PCB contamination of the

environment is itself an important part

of the PCB problem because, as

discussed in the preamble to the

proposal (42 FR 17469-90), some human

exposure to PCB’s comes from the air

and water, though the amount is

probably minimal. EPA is addressing

that part of the problem. However, FDA

disagrees with the view that exposure to

PCB’s from dietary sources is

insignificant in comparison to the

amount of exposure from the air and

water. The agency has based the

proposed tolerance reductions on its

conclusion that dietary exposures to

PCB’s pose significant risks to

consumers, which can be reduced by

reducing exposure. That there is some

exposure to PCB’s from other sources is

not a good reason for withholding action

that can significantly reduce dietary

exposure.

9. Two comments requested FDA to

hold a public hearing before finalizing

reduction of the fish tolerance.

The agency does not consider a public

hearing on the fish tolerance to be

necessary or appropriate at this time.

Tolerances are established under

section 406 of the act under the formal

rulemaking procedures set forth in

section 701(e) of the act (21 U.S.C.

a71(e]]. Under those procedures, any

person adversely affected by this order

may file objection within 30 days and

request an evidentiary hearing on the

issues raised by those objections. The

opportunity for a hearing ensures that

all genuine, material issues relating to

the PCB tolerances will be fully aired.

Holding a hearing before issuing this

order would only duplicate the

opportunity for a public hearing already

available in formal rulemaking and

unnecessarily delay the proceedings.

10. One comment stated that the 5

ppm tolerance for PCB’s in fish should

be retained but requested that FDA

provide guidance to State agencies

regarding use or implementation of the 2

ppm tolerance if it is adopted.

As noted, FDA provides data and

views to the States on a range of matters

related to implementation of tolerances

for PCB’s in food and will continue to do

so.

11. One comment asked whether

procedures other than reducing the fish

tolerance have been evaluated as

alternative means of reducing intake of

PCB-contaminated fish.

The agency has considered the use of

general public warnings and/or labeling

as ways to limit consumption of

contaminated fish. Such approaches

have been rejected, except as they apply

to certain heavy consumers of

contaminated sport fish (discussed

above]. A public warning about fish

generally, or even about particular

species of fish, would not be effective in

protecting the general public from

commercial fish because, assuming no

changes are made in labeling,

consumers have no way to determine

the species or waters of origin of most

commercially prepared fish products. In

addition, general public warnings might

unduly discourage consumption of fish,

most of which is safe to eat and

nutritious. Similarly, the requirement of

warning labels on fish products in lieu of

a tolerance, even on a species-specific

basis, is not a sufficiently precise

regulatory approach because not all fish

from even the most heavily

contaminated species contain levels of

PCB’s above the 2 ppm tolerance level.
134 “ Environmental Contaminants in Food

38338 Federal Register / Vol. 44, No. 127 / Friday, June 29, 1979 / Rules and Regulations

Thus, as with general public warnings,

warning statements on labels are likely

to discourage consumption of safe fish.

12. Some comments contended that

most Americans would probably prefer

to be warned of the potential danger

from PCB residues and retain the option

of eating freshwater fish, rather than be

deprived of any choice in the matter by

having the fish removed from the

market.

The agency acknowledges that some

people would probably prefer to be left

with the choice of whether to consume

fish contaminated with PCB’s above the

2 ppm level. As noted, however, the

consumer of commercially marketed fish

generally lacks the information on

water-of-origin, size, and sometimes

even species that is needed to control

his or her intake of PCB’s. Under these

circumstances, there is no genuine

opportunity to exercise informed choice.

Moreover, the agency believes that as a

general matter it is obligated under

section 408 of the act to exercise its

scientific judgment and determine what

level of exposure, and thus what

tolerance level, will provide an

adequate degree of public health

protection,

13. One comment referred to the

agency’s decision not to reduce the

temporary tolerances for infant and

junior foods and for animal feeds on the

ground that the current tolerances are

“at the lowest level at which PCB’s can

be reliably determined for enforcement

purposes” and argued that lowering the

tolerance for fish would probably create

much greater economic hardship than

would developing and using more

sensitive analytical methods so that

other tolerances could be lowered,

The agency acknowledges that the

fish losses resulting from a 2 ppm fish

tolerance would probably be greater

than the costs of developing and using

the more sensitive enforcement analyses

that would be necessary for a reduction

of the other tolerances. The occurrence

of PCB residues in infant and junior

foods and animal feeds is now so

infrequent, however, that those foods do

not contribute significantly to dietary

exposure to PCB’s. Thus, spending the

resources to develop more sensitive

methodology and thereafter reducing the

tolerances for these foods would not

significantly increase the protection of

consumers, and it still would be

necessary to reduce the fish tolerance,

Because PCB’s do occur consistently at

significant levels in some fish, the

reduction of the fish tolerance can

provide increased protection for

consumers.

14. Some comments included requests

for compensation for commercial fishers

and processors whose livelihoods are

destroyed by reduction of the fish

tolerance. One comment asked, in effect,

that the effective date of the tolerance

reduction be delayed for 10 years so

fishers would have time to adjust

economically.

For reasons discussed earlier in this

document, the agency considers it

unlikely that the reduction of the fish

tolerance to 2 ppm will have the dire

consequences on which these comments

are premised. Moreover, FDA has

neither the authority nor the resources

to provide compensation for economic

losses that might be suffered as a result

of regulatory actions it takes. The

proposed 10-year postponement of the

effective date would be inconsistent

with the agency’s conclusion that a

reduction of the tolerance is necessary to

protect the public health.

15. A number of comments were

concerned that if the 2 ppm tolerance for

fish is adopted, FDA will close certain

waters to fishing or prohibit fishing of

certain affected species in certain

waters. They requested that more

studies be carried out before

determining whether such steps should

be taken.

The concern underlying these

comments is misdirected, FDA does not

have authority either to close waters to

fishing or to prohibit harvesting or

possession of fish. Any actions to close

waters to fishing would have to be

instituted by State agencies.

16. One comment suggested that if the

2 ppm tolerance is adopted, the counties

affected should be allowed to conduct

more comprehensive testing of residue

levels in the fish before any ban or

impoundment of fish in interstate

commerce is imposed.

In enforcing the fish tolerance, FDA

will sample and analyze individual lots

of fish in interstate commerce and take

regulatory action against lots, or the

shippers of lots, that exceed the

tolerance, There is nothing to prohibit

any interested party, including local and

State authorities, from conducting

comprehensive testing of fish before

shipment in interstate commerce and

from withholding from commerce fish

that exceed the tolerance.

17, One comment suggested that the

proposed 2 ppm tolerance for PCB’s in

fish is inadequate for protection of

public health, The comment stated that

the tolerance levels must be based on

the “no-effect” level observed in-the

most sensitive animal species for which

toxicological data are available, and it

suggested that the rhesus monkey is

more sensitive to PCB’s than the dog or

rat.

This comment is based on an

apparent misunderstanding of the

toxicological rationale underlying the 2

ppm fish tolerance. In evaluating the

safety of substances in food, FDA

ordinarily attempts to determine the

“no-effect” level for the substance, i.e.,

the highest level of exposure at which

no adverse effect is observed in

appropriate animal studies, It then uses

appropriate safety factors to extrapolate

the results of the animal studies to the

human situation and determine safe

levels of human exposure. In this case,

however, the reduction of the fish

tolerance is not based on any “noaffect” level, It is based instead on a

body of data that associate PCB

exposure with several serious chronic

effects but that do not permit the

establishment of “no-effect” levels for

those effects, Thus, the comment’s

argument that one species is more

sensitive to PCB's than another and that

the tolerance should be based on the

“no-effect” level observed in the most

sensitive animal species is not relevant

to the toxicological rationale the agency

relies on for reducing the PCB tolerance

to 2 ppm.

18. One comment disagreed with the

proposal to establish a 2 ppm tolerance

for fish instead of a 1 ppm tolerance.

One ppm is the lowest level of PCB

residues in fish for which there is

analytical methodology suitable for

enforcement purposes. The comment

stated that toxicological information,

especially that suggesting the

carcinogenicity if PCB’s coupled with

the presence of PCB residues in human

milk, requires the lowest possible

tolerance.

With respect to the carcinogenic

potential of PCB’s, NCI has concluded

that PCB’s (specifically, Aroclor 1254,

the commercial PCB most similar

chemically to the PCB residues in fish)

are not carcinogenic in Fischer 344 rats

under the conditions of the bioassay

(Ref. 47). After thoroughly reviewing

NCI’s report, the Data Evaluation/Risk

Assessment Subgroup of the

Clearinghouse on Environmental

Carcinogens accepted the report’s

conclusion that PCB’s were not

demonstrated to be carcinogenic in that

study, but suggested that PCB’s might

act as a tumor promoter. For the reasons

discussed in the preamble to the

proposal (42 FR 17489), FDA considers

the question of the carcinogenicity of the

PCB’s unresolved. For the purposes of its

risk assessment on PCB’s (Ref. 44),

however, the agency treated the various

PCB’s as though they were carcinogenic,
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Federal Register / Vol. 44, No. 127 / Friday, June 29, 1979 / Rules and Regulations 38339

and it considers the carcinogenicity of

PCB’s to be a matter worthy of further

serious inquiry.

The agency has long been concerned

with the exposure of nursing infants to

PCB’s in human breast milk. This, too, is

an area in which more must be learned

before definitive statements can be

made about the incremental risks posed

by this particular avenue of exposure.

For reasons discussed earlier in this

document, however, the agency

considers a 2 ppm tolerance adequate to

protect all but those who consume

above-average amounts of the more

heavily contaminated species.

111. Response to Comments on Other

Aspects of PCB’s

Following are the agency’s responses

to the comments that did not specifically

address the reduction of the fish

tolerance:

1. Some comments recommended that

the government regulate PCB’s only in

the environment rather than in food

products. Another comment suggested

that the limits on PCB’s in foods not be

reduced until PCB levels have been

reduced in the environment, where the

foods are produced.

EPA has the authority to control

environmental pollution and has already

taken important steps to prevent further

pollution by PCB’s. Some environmental

contamination with PCB’s already

exists, however, and will undoubtedly

persist for some years. FDA would be

failing in its duty to protect the public

health if it withheld the actions

necessary to minimize human exposure

to PCB’s from dietary sources until the

long-term problem of environmental

contamination has been solved.

2. One comment asserted that the

primary toxicological basis upon which

FDA established the temporary

tolerances for PCB’s in 1973 (38 FR

18096) consisted of two long-terms

feeding studies in rats and dogs that

were performed by the same testing

laboratory and that demonstrated a “noeffect” level for PCB’s at 10 ppm. This

comment also suggested that these same

two studies serve as the primary basis

for the current proposal to reduce those

original temporary tolerances: The

comment stated that discrepancies and

inconsistencies have recently been

found in these two feeding studies, as

well as in other unrelated studies from

the same testing laboratory, which

would indicate that toxic effects might

actually have been produced in both

rats and dogs, at dietary levels as low as

1 ppm. The comment requests that FDA

extend its audit of the testing laboratory

in question to include a review of the

data obtained in the two toxicity tests of

PCB’s in rats and dogs. The comment

suggested that FDA reconsider the

proposed temporary tolerances on the

basis of a reevaluation of the data from

the two long-term studies and, if judged

necessary, propose new tolerances or

reopen the matter for public comment.

Though the data from the two longterm toxicity studies of PCB’s in rats and

dogs referred to in the comment were

considered, the human toxicological

data formed the primary basis for

developing the original temporary

tolerances for PCB’s. This fact was

stated in the July 6, 1973 document

establishing the tolerances and in the

preamble to the April 1,1977 proposal to

reduce some of the tolerances.

The agency is aware that doubt has

been cast on the validity of the two

long-term toxicity tests of PCB’s in rats

and dogs referred to in the comment, as

well as on the validity of numerous

unrelated toxicity tests performed by the

laboratory facility in question (Ref. 48).

Therefore, the results from these two

tests are no longer considered worthy of

reliance and, as explained earlier in this

document, these studies played no part

in the agency’s decision to lower the

PCB tolerances.

3. One comment asserted that the

agency’s statement in the preamble to

the proposal that it was unaware of any

consumers who had suffered deleterious

effects caused by PCB ingestion (42 FR

17491) is misleading, in that the

statement actually reflects a lack of

knowledge rather than awareness of the

results of properly designed

epidemiological studies.

In making this statement the agency

relied on, the results of an

epidemiological study carried out with

sport fishers in Michigan that failed to

establish a correlation in humans

between the ingestion of PCB’s and the

occurrence of deleterious effects (Ref.

40). The study is discussed in the

preamble to the proposal (42 FR 17492-

3). The only purpose of the statement

was to cite an instance in which

relatively high exposure to PCB’s in fish

had not resulted in overt, acute toxic

effects, such as occurred in the Yusho

incident in Japan (42 FR 17488). The

Michigan example was intended to

illustrate the observation the agency

made in the preamble to the proposal

that the amount of PCB’s in

environmental samples required to

cause Yusho-type effects is not known.

This study has no direct bearing on the

agency’s conclusion that the chronic

effects of PCB’s require a reduction of

the tolerances,

4. One comment opposed reduction of

the temporary tolerance for PCB’s in

eggs on the ground that there are no

substantial data that suggest that the

current temporary tolerance is not

sufficient to protect consumers of eggs.

The comment contends that lacking such

evidence, there is not justification for

reducing the tolerance.

The agency acknowledges that the

data indicate that eggs do not contribute

measurably to dietary PCB exposure

and that reduction of the egg tolerance

will not significantly affect PCB intakes.

However, tolerances established under

section 408 of the act are intended to

permit only those residues that are

unavoidable. Because the available data

indicate that residues above the

analytical limits in eggs are avoidable

and because no evidence was presented

to the contrary, it is appropriate to

reduce the temporary tolerance for

PCB’s in eggs as proposed.

5. One comment requested that the

temporary tolerances for PCB’s in

animal feed be reduced, but it did not

present a rationale to justify reduction.

The presence of PCB’s in animal feed

is of concern because PCB’s transfer and

accumulate in human food products

derived from animals that consume

contaminated feed. The tolerance for

finished animal feed is currently set at

0.2 ppm—the lowest level at which

available analytical methodology can

measure PCB’s in animal feed for

enforcement purposes. It would serve no

useful purpose to reduce the tolerance

below this level in the absence of

analytical methodology for enforcing a

reduced tolerance. Moreover, in light of

the rare occurrence of PCB’s in animal

feeds, the agency considers the 0.2 ppm

level to provide an adequate degree of

public health protection, For these

reasons, the agency declines to reduce

the tolerance for PCB’s in finished

animal feed.

IV. “Temporary” Status of the

Tolerances

As currently codified in S 109.30, the

tolerances for PCB’s are designated as

“temporary,” The term “temporary” was

used to reflect the fact that the

tolerances are subject to revision as

new data become available. In the

preamble to the proposal for reducing

the tolerances, the agency stated that it

would retain the “temporary”

designation because of the possibility

that further downward revisions of the

tolerances might be necessary (42 FR

17493). The agency has now

reconsidered this use of the term

“temporary” and has decided to

abandon it. The term has never had any
136 . Environmental Contaminants in Food

30340 Federal Register / Vol. 44, No. 127 / Friday, June 29, 1979 / Rules and Regulations

legal significance as applied to

tolerances established under section 406

of the act, and its use is not provided for

in FDA’s procedural regulations

governing tolerance setting in Part 109

(21 CFR Part 109). When circumstances

are changing so rapidly that a particular

tolerance level is likely to be rendered

inappropriate in the near future, the

agency establishes an action level rather

than a tolerance (see $ 109.6(c) (21 CFR

109.6(c))). In the case of PCB’s, however,

the agency has concluded that formal

tolerances are appropriate. The term

“temporary” is being abandoned to

avoid the suggestion that the legal status

of the PCB tolerances is something other

than that of a formal section 406

tolerance.

Any FDA tolerance, just like any other

regulation, is “temporary” in the sense

that it is subject to reevaluation and, if

necessary, revision as new data become

available. The agency will continue to

monitor the PCB problem and, if

appropriate in light of changing

circumstances or new data, will propose

revisions in the PCB tolerances.

V. Analytical Methodology

Section 109.30(b) has been revised to

refer to FDA’s updated compilation of

analytical methodology for PCB’s

“Analytical Methodology for

Polychlorinated Biphenyls, June 1979.”

There have been improvements in the

analytical methodology for measuring

PCB residues since 1973, and most of the

revised procedures have now been

published in scientific journals. A copy

of each procedure or a reference to the

appropriate journal is provided in the

updated compilation. As stated in

3 109.30(b), the compilation is available

from the Hearing Clerk, Food and Drug

Administration, Room 4-65, 5600 Fishers

Lane, Rockville, MD 20857.

VI. References

The preamble to the proposal cited 42

references the agency relied on in

developing the proposal and stated that

those reference documents had been

placed on file with the Hearing Clerk,

FDA (42 FR 17493-4). The following

additional references, which are cited in

the foregoing preamble, have also been

placed on file with the Hearing Clerk,

FDA, Rm. 4-85, 5800 Fishers Lane,

Rockville, MD 20857, and may be seen

between 9 a.m. and 4 p.m., Monday

through Friday.

43. DuBois, K. P. and E. M. K. Ceiling,

“Textbook of Toxicology,” Oxford

University Press, 1959, pp. 24-28.

44. Ariens, E. J., A, M. Simonis, and J.

Offermeier, ‘*Introduction to General

Toxicology,” Academic Press, 1976, pp.

124-31.

45. An Assessment of Risk Associated with

the Human Consumption of Some Species

of Fish Contaminated with Polychlorinated

Biphenyls (PCB’S), 1979, FDA document.

46. Regulatory Analysis for Final Regulation

for Reduction of Temporary Tolerances for

Polychlorinated Biphenyls in Food, 1979,

FDA document,

47. National Cancer Institute Carcinogenesis

Technical Report Series No. 38, 1978.

48. Letter from Donald Kennedy,

Commissioner of Food and Drugs, to

various clients of Industrial Bio-Test

Laboratories, Inc., June 1977.

Therefore, under the Federal Food,

Drug, and Cosmetic Act (sees. 306,

402[a), 406, 701[a), 701[e), 52 Stat. 1045-

1046 as amended, 1049 as amended,

1055, 70 Stat. 919 as amended (21 U,S,C.

336, 342(a], 346, 371(a], 371[e))) and

under authority delegated to the

Commissioner of Food and Drugs (21

CFR 5,1), Part 109 is amended in $109,30

by revising the section heading and

paragraphs (a)(l), (2), (3), (4), and (7] and

(b) to read as follows:

$109.30 Toterences for polychlorinated

biphenyls (PCS’S).

(a) ● ● ●

(1) 1.5 parts per million in milk (fat

basis).

(2) 1.5 parts per million in

manufactured dairy products [fat basis).

(3) 3 parts per million in poultry (fat

basis).

(4) 0.3 part per million in eggs.

● *** *

(7) 2 parts per million in fish and

shellfish (edible portion), The edible

portion of fish excludes head, scales,

viscera; and inedible bones.

●

(b) For determining compliance with

the tolerances established in this

section, a compilation entitled

“Analytical Methodology for

Polychlorinated Biphenyls, June 1979" is

available from the Hearing Clerk, Food

and Drug Administration, Department of

Health, Education, and Welfare, Room

20857,

● *** *

Any person who will be adversely

affected by the foregoing regulation may

at any time on or before July 30, 1979,

submit to the Hearing Clerk (HFA-305),

Food and Drug Administration, Rm. 4-

65, 5600 Fishers Lane, Rockville, MD

20857, written objections thereto and

may make a written request for a public

hearing on the stated objections. Each

objection shall be separately numbered

and each numbered objection shall

specify with particularity the provision

of the regulation to which objection is

made. Each numbered objection on

which a hearing is requested shall

specifically so state; failure to request a

hearing for any particular objection

shall constitute a waiver of the right to a

hearing on that objection. Each

numbered objection for which a hearing

is requested shall include a detailed

description and analysis of the specific

factual information intended to be

presented in support of the objection in

the event that a hearing is held; failure

to include such a description and

analysis for any particular objection

shall constitute a waiver of the right to a

hearing on the objection. Four copies of

all documents shall be submitted and

shall be identified with the Hearing

Clerk docket number found in brackets

in the heading of this regulation,

Received objections may be seen in the

above office between the hours of 9 a.m.

and 4 p.m., Monday through Friday.

Effective date. This regulation will

become effective for foods initially

introduced into interstate commerce

after August 28, 1979 except as to any

provisions that may be stayed by the

filing of proper objections. Notice of the

filing of objections or lack thereof will

be announced in the Federal Register,

[Sees. 306, 402(a), 408, 701(a), 701(e), 52 Stall

1045-1046 as amended, 1049 as amended,

1055, 70 Stat. 919 (21 U.S.C. 336, 342(a), 346,

371(a], 371(e)])

Dated: June 26, 1979.

Donald Kennedy,

Commissioner of Food and Drugs.

[FS Dec. 79-z4wM Fded %2s-7s s.45 am]

BILLINQ COI)E 411 O-O3-M
Appendix C

Methods for Toxicologic Testing *

by SRI International

METHODS FOR TOXICOLOGIC TESTING

137
138 ● Environmental Contaminants in Food

scheme, experiments are designed and data are

collected based on expected results such as functional systemic changes, teratogenicity, or carcinogenicity. By the use of an appropriate experimental design, several endpoints can be assessed

in the same experimental period such as is done

in FDA’s three-generation studies (2).

For ease of presentation, this appendix has

been subdivided by endpoint into sections on Systemic Toxicity, Carcinogenicity, Mutagenicity,

Teratology and Effects on Reproduction, Metabolism, and Structure-Activity Relationships. This

appendix is not intended as an exhaustive survey

of all testing methods used, but is meant to give an

overview of those methods most commonly used

today by toxicologists.

LocaI and Systemic Toxicity

Some of the fastest and simplest methods for

determining the toxicities of substances involve

the observation of changes in the structure and

function of organs and organ systems. These

methods generally involve absolute and relative

weight changes, gross and microscopic structural

alterations, and primary and secondary tests for

organ, system, or whole animal function. With advances in the chemical, physiological, and behavioral sciences, modifications for testing systemic

toxicity have been proposed that make these procedures more sophisticated and relatively complicated. Several good texts are available which review systemic toxicity [3,4).

Range Finding

The classic determinations of toxicity involve

percent lethal or effective dose, concentration, or

time. These tests may employ any route of exposure, the ones chosen usually being based on factors such as chemical and physical properties of

the agent and potential routes of exposure from

the environment. The results obtained from these

determinations are usually specific for the species, sex, age, and condition of the organism, and

for the route of exposure and environmental conditions before, during, and after exposure. The

endpoints of these tests may be either structural

or functional changes, but they are usually limited to gross effects such as death or narcosis.

These tests are primarily used to determine relative toxicities of various agents and for range

finding for maximum tolerated dosage preliminary to beginning a subacute study. They are not

usually used to directly evaluate the hazard.

In general, these tests will employ young adult

rats and another mammalian nonrodent species.

Selection of this other species " . . should consider such factors as comparative metabolism of

the chemical and species sensitivity to the toxic

effects of the test substance . . . . “(l) The route of

administration chosen is that most nearly identical to the potential human exposure. Doses are

usually chosen to give results in the 20- to 80-

percent lethal or effective range and are usually

separated by 0.5 log units (5). Many modifications

of this basic procedure are accepted.

Irritation

The irritation potential of substances is tested

by observation of the reflex behavior of the animal and by direct observation of the site of contact with the agent, Attempts to quantitate reflex

behavioral responses, i.e., eye rubbing, regurgitation, or shallow breathing, have met with little

success. The simplest protocols for evaluating irritation involve the skin and eyes. Semiquantitative systems for scoring skin and eye irritation

have been proposed by several authors (6-12) and

involve placing the suspected irritant in contact

with the skin or eye of New Zealand White rabbits. Protocols for skin irritation involve contact

with both intact and abraded skin to differentiate

the agent’s ability to penetrate the skin barrier,

and occlusion of the contact site to maximize the

response. The severity of erythema and edema is

scored as the endpoint. Eye irritation studies are

carried out without washing and with washing at

various intervals to determine the effectiveness of

removal of the agent to reducing the adverse effect, Opacity, area affected, iris reaction to light,

hemorrhage, swelling, and discharge are scored.

Results from these tests can vary greatly depending on the method of application of the substance,

whether dry or premoistened, etc.

Other potential sites of irritation such as the

sensory nerves, respiratory system, urinary system, and gastrointestinal tract are usually evaluated secondarily or through necropsy. Secondary

effects include shallow breathing, regurgitation,

agitation on urination, and eye rubbing, which

are broadly categorized as reflex behavior, and

blood in feces, urine, and sputum, or nasal discharge, which are more indicative of the primary

irritant effect. These results are not quantifiable

by present methodologies. Primary evaluation

through necropsy is also a qualitative procedure

and has not undergone the extent of standardization and validation that the skin and eye tests

have. Other methods for testing irritation such as

resistance/compliance tests of the pulmonary system, direct observation by scope of the esophagus
Appendix C—Methods for Toxicologic Testing ● 739

and gastrointestinal tract, and roentgenographic

examination with and without radio-opaque dyes,

have not received wide use as testing techniques

for Government regulatory purposes.

Sensitization

Some substances, although not necessarily primary irritants, elicit an irritant-type response

after repeated contact with the organism. Tests

for this sensitization potential involve exposing

the animal to an agent at doses below those necessary to produce signs of primary irritation, waiting an appropriate interval, and then challenging

the animal with the substance again at a different

site (11). If the response on retest is substantially

higher than the initial response, the agent can be

classified as a sensitizer. Various test methods

and modifications have been proposed for testing

sensitizing potential (11, 13-21). Perhaps the most

common direct test for sensitization is the guinea

pig maximization test. In this test, the agent is

presented in Freund’s complete adjuvant which

increases the response. Studies on the mechanism

of sensitization have shown that the agent or a

metabolize of it (antigen) may induce the lymphocytes of the body to form a complex molecule

(antibody) which reacts with the antigen to form

an antigen-antibody complex. This reaction may

be with circulating free antibody or with lymphocyte-bound antibody, The formation of th e

antigen-antibody complex induces the production

and release of histamine and other compounds

which cause the erythema and edema at the site

of antigen attack, or may cause anaphylaxis if the

antigen reaches the blood stream (22,23). The

problem with testing methods based on this

mechanism, such as immunoelectrophoresis,

radioimmunoassay, ring test, hemagglutination

tests, or microphage migration, is that they do not

measure the actual adverse effect [dermatitis or

shock) but measure an indicator response. The

methods are valuable, however, in demonstrating

the presence of antibody capable of producing

these health effects. Several comparative tests

have demonstrated that these in vitro techniques

are often more sensitive indicators of the hazard

than the classic in vivo ones (22,23).

Structural Effects

The basic determination of structural effects

on organs and systems begins with the determination of absolute and relative weight changes.

Decreases in absolute body weight or rates of

weight gain for a test with a substance incorporated into the food or water may show either that

the agent is unpalatable or that it is interfering

with the energy balance, the central nervous system (CNS) regulation of food or water consumption, or the motivation of the animal. Although

substances administered by other routes of exposure may also interfere with palatability of food,

through direct or indirect effects on the sensory

nerves, this is less common. Increases in weight

may be caused by a proliferating tumor mass. The

evaluations of structural changes can be obtained

from animals exposed during subacute experiments.

In general, subchronic or subacute experiments are designed to last approximately 10 percent of the animals’ lifespan (90 days for rats). Immediately preceding and during the experimental

period, observations on animals should include

rate of growth, food and water consumption, demeanor, and reflex behavior; blood, urine, and

feces should be collected. During the experimental period, tissue biopsies may be taken for observation of structural changes. These techniques

may be unreliable, however, if a structural

change is localized and not included in the biopsy

material, and such manipulation is often not

allowed by regulatory testing guidelines. If biopsies are done, additional animals are required to

maintain the statistical validity of the experiment.

At the end of the experimental period, the animals

are sacrificed and the organs are inspected for

gross changes, removed and weighed, and preserved for histologic treatment and microscopic

examination (5). The specific organs and tissues

removed and examined will depend somewhat on

the expected action of the agent administered

(usually perceived from preliminary testing) but

should include at least the brain, liver, kidneys,

spleen, heart, testes (and epididymis) or ovaries

(and uterus), thyroid, and adrenals.

Changes in organ weights may signal a functional change in this organ or in other organs; for

example, an increase in heart weight could be due

to a decrease in oxygen diffusion from the lungs,

an increase in adrenal weight could signal a

blockage of steroid synthesis within it, etc. The

weights of organs can be directly compared with

those from control animals; however, this often introduces an artifact since experimental and control body weights are usually different. It is common practice therefore to determine the relative

weights of the organs in relation to the total body

weight of the animal. Recently it has been proposed that the relative weights should be taken as

a function of the animal’s brain weight, the postulation being that the brain’s growth curve devi-
140 ● Environmental Contaminants in Food

ates the least of any tissue in the body. While normalization based on this procedure would tend to

emphasize changes more than other techniques

currently in use, it is not yet widely accepted.

Tissue dry weight, after desiccation or ashing,

has also been used as a tool for determining

mechanisms of growth and metabolic balances

(24). This method has a major drawback, however, because it removes the organ from further

studies such as microscopic examination.

After gross observation and weighing, the

organs and tissues are preserved for histological

preparation and microscopic examination. The

most common methods for the preparation and

staining of individual tissues involve fixing with

10-percent buffered formalin solution, embedding

in parafin, and staining with hemotoxylin/eosin,

Many pathologists prefer other fixing and embedding media, and certain tissues require different

procedures. There are also special stains for

highlighting different cellular components. There

is no one best method for preparation and observation of the tissues. The most valuable procedure

from the pathologists’ viewpoint is to prepare the

tissues in a number of ways, which allows comparison of various aspects such as specific cellular components, nuclei, cell membranes, etc.

(25-27).

Special consideration can also be given to techniques in histochemistry and electron microscopy. These methods are not used routinely in

toxicological evaluation and depend on a knowledge of the mode of action of the toxic agent. They

can, however, indicate changes in cellular metabolism or structure before those changes become

manifest by the conventional histological procedures, and therefore they may be more suitable

for observing changes from agents whose toxicities are low or develop slowly. The equipment

necessary for these techniques is generally more

expensive than that needed for the more conventional microtechnique methods. They are also

more time consuming and less standardized than

conventional methods. The histochemical methods, although they might be more appropriately

classified as tests of organ function, are becoming

more widely accepted with investigators studying

mechanisms of toxic: action.

Functional Effects

Frequently, changes in organ or system function are observable before any change in structure becomes apparent. The test methods discussed below have generally been adapted from

human to animal use, and results are ordinarily

compared with animal control values and are not

necessarily comparable between species, Methods for evaluation of pulmonary function (28), cardiovascular function (29), and brain and neural

activity (30) have been modified for human and

animal use. These methods include testing ventilator flow, resistance, compliance, and gas diffusion capacity for the pulmonary system; electrical activity of the heart, and blood flow and

pressure for the cardiovascular system; electrical

activity of the brain (field and single unit) and

muscles; perception threshold, reflexes, and

chronaxy for neural function. The significance of

changes in brain activity as a determinant of toxicity is under question at present, however.

Generally, in these evaluations, each animal

serves as its own control. Baseline data for each

procedure is determined prior to administration

of the agent, and any changes in function are

noted during and after administration, since it is

important to determine whether the agent causes

reversible or irreversible changes in function.

Various other methods of testing for organ or

system function rely on both primary and secondary parameters. For example, liver function may

be assessed by dye clearance studies (primary) or

by analysis of serum enzyme concentrations (secondary). Most of the secondary procedures are

now automated and available through various

clinical laboratories at a reasonable cost, Many

investigators, however, still prefer to perform the

tests manually, and standard procedures are

well-defined and available in several texts

(31-33). Various modifications of these tests for

specific animal systems have been developed and

published, Tests usually considered appropriate

include total and differential blood counts, serum

enzyme and ion analysis, urinalysis (especially for

metabolizes of the agent), and liver and kidney

function tests (dye clearance). The value of these

tests is that abnormal results will often precede

obvious structural damage of the organ system in

question and will be apparent at lower dose

levels.

The study of hematologic effects encompasses

changes in the bone marrow as well as those in

the cells of the circulating blood. Observations

are made of the cells and of their absolute and

relative numbers. Specific tests such as dye dilution for blood volume, specific gravity, sedimentation rates, osmotic fragility, hematocrits, or clotting time, are not routinely performed but may be

indicated. Serial bone marrow biopsies may also

be performed for hematologic effects; the results
Appendix C—Methods for Toxicologic Test/rig ● 141

give both structural and functional information,

but these techniques are also not widely used.

The functions of the liver may be tested for

biliary obstruction (icterus index, alkaline phosphatase), liver damage (thymol turbidity, plasma

protein ratios, cholesterol ratio, glucose level,

transaminase level, and cholinesterase level), excretory function (bromsulphalein clearance, bilirubin tolerance), and metabolic function (glucose

tolerance, galactose clearance), The most common tests used in toxicology are the serum alkaline phosphatase and serum transaminases, and

in some cases a dye clearance (bromsulphalein) or

glucose tolerance.

The kidneys are responsible for excretion of

certain substances, e.g., urea, and for concentration and dilution of urine. Tests for excretion involve dyes like phenolsulphonphthalein and also

measure such substances as urea and creatinine,

Concentration and dilution tests involve measurement of urine specific gravity after fasting for

various periods. These tests are generally not

used in toxicology screening studies unless there

is reason to believe the toxicant acts on the

kidneys.

The evaluation of these tests may proceed with

or without modification of the tissue metabolism.

That is, promotors and inhibitors of enzyme systems, e.g., SKF-525A for mixed function oxidase,

may be used to enhance the susceptibility of a

particular organ or system to damage from a toxicant. This in effect maximizes the response so

that the toxic action can be more readily observed.

Many other specific tests are available for

evaluating various organs and systems such as

sperm motility, specific gravity of cerebrospinal

fluid. calcium-phosphorus ratios for the skeletal

system along with tensile strength and compaction, epinephrine sensitivity of heart muscle,

acetylcholine test of lungs, metabolism of excised

tissue, work and strain measurements of the various muscle systems, etc.

Behavioral Effects

A recent addition to the field of toxicology has

been behavioral testing. Testing methods have

been devised for everything from simple perception to complex tasks involving perception, learning, judgment, motivation, and motor activity. The

value of the behavioral methods lies in the ability

of the nervous system to respond to toxic agents

a t doses much lower than those necessary to produce “classic” signs of toxicity in the organism.

Therefore, these methods are a potential sensitive

indicator of hazard and can be used as an “early

warning system. ” Several good reviews of behavioral toxicology are available (34-37).

Some of these methods rely on newer methods

of analysis such as contingent negative variation

(CNV). Some are really an application of preexisting principles such as dorsal evoked potentials

and neuromuscular transmission time that have

been widely used by experimenters in the field of

neurophysiology. Most of these techniques have

only recently been turned to the evaluation of toxicity.

At the present time, standardization and validation of behavioral techniques has not been accomplished. The question often raised by regulatory agencies is how do you relate an observed behavioral decrement to an adverse health effect,

especially if there is no concurrent structural

change apparent in the nervous system. Because

of these factors, behavioral studies are often derogated by these agencies when setting exposure

limits for toxicants. Current research is being

conducted, however, under Government contracts to answer some of these questions.

Comparison of Short- and Long-Term

Methods for Systemic Toxicity

Most of the procedures noted in this section are

equally applicable to short- and long-term testing,

obvious exceptions being irritation and sensitization tests. The value of long-term testing for systemic toxicity lies in the ability to use low doses

that do not produce detectable adverse effects in

a short time period to see whether bioaccumulation and cumulative effects occur. Predictions of

the effect of bioaccumulation can be made knowing the effects of short-term high doses, but final

evaluation of the toxicity depends on the longterm effects observed, As will be pointed out in

the metabolism section, toxicants can be potentiated or inhibited by the metabolism and relative

accumulation of the toxic moiety. Without definitely knowing the various metabolic reactions,

rates, and probabilities, it is impossible to accurately predict toxic effects. High short-term

doses may induce a toxic reaction, such as death

from pulmonary edema, that might mask longterm, low-level exposure effects such as liver

cancer, The differences in short-term and longterm tests for systemic toxicity include the number of interim measurements allowed, the ability

to ascertain the types of effects which might

develop only over a long period and the progression or time course of toxic manifestations, and
142 w Environmental Contaminants in Food

the ability to evaluate mechanisms of bioaccumulation or adaptation in the organism.

Mutagenicity

Rapid identification of a food contaminant as a

possible mutagen is necessary to reduce the potential genetic risk to humans who might contact

the contaminant. Mutagenic effects on humans

often cannot be directly detected, and deleterious

effects on the human gene pool may not become

apparent for many generations if, for instance,

the deleterious effect is due to a recessive gene.

Heritable genetic damage in humans may result

from any of several types of effects on the genetic

material, The two major classes of effects are

point mutations, which generally affect a single

gene or part of a gene, and more extensive chromosomal effects such as gross changes in structure or changes in number.

Only a few tests are available that directly

evaluate genetic effects of exposure of mammals

to chemicals: however, the potential of a chemical

to produce heritable genetic alterations in man

can be evaluated indirectly from its effects on genetic material in various biologic test systems, including micro-organisms, mammalian cell cultures, insects, and intact mammals.

For substances that cannot feasibly be eliminated from the human environment, it is not sufficient to identify the existence of a genetic hazard;

quantitative assessment of the risk involved is

necessary for appropriate regulatory activity,

such as establishing action levels or tolerances

for food contaminants.

Mutagenicity testing is also used to prescreen

chemicals as an indicator of carcinogenic potential and, less frequently, other toxic effects such

as teratogenicity. This application is based on empirical demonstration or correlation between mutagenicity and carcinogenicity of chemicals (38)

and does not depend on the assumption that the

same mechanism is involved in both types of effect.

Approaches to Testing

As in all toxicological tests, mutagenicity tests

may produce false negatives (a negative result

when the substance is actually mutagenic) and

false positives (a positive result when it is not

mutagenic), and correlation between the results

from two test systems may be poor. Ideally, a mutagenicity test system should be sensitive enough

to detect any chemical that may cause heritable

genetic damage and its results should be reproducible. Finally, the test results should be quantitatively applicable to mutagenesis in humans.

Since no single test can fulfill these requirements

and none is reliable enough to stand alone as an

indicator of mutagenic potential, mutagenicity

‘testing should include a variety of systems selected to show whether the test substance or its

metabolize produce any of a range of genetic effects. The test battery approach includes systems

that will detect several types of gene mutations,

chromosomal aberrations, and DNA repair; thus,

this approach offers the greatest reliability for

determining mutagenic potential, Tests that evaluate effects in intact mammals are essential for

predicting mutagenicity in humans.

Since screening large numbers of chemicals by

the test battery approach (39,40) may be prohibitively costly, a hierarchical approach to mutagenicity testing, known as tier testing (41), has been

suggested. Tier 1 consists of relatively inexpensive short-term prescreening tests. These use

micro-organisms or other in vitro systems to determine priorities for indepth testing. Substances

that produce positive results in these tests, as

well as those that are negative but are structurally similar to known mutagens or to which there

is a substantial risk of exposure for humans during or preceding their reproductive years, should

continue into Tier 2.

Tier 2 tests are usually designed to detect substances that are not mutagenic in vitro but are

metabolized to an active form in the intact mammal. Tests used at this level may include the dominant lethal test, in vivo cytogenetic tests, the hostmediated assay, and body-fluid analysis. Substances that are negative in Tiers 1 and 2 are generally considered safe for use and are given very

low priority for further testing.

Only substances for which it is important to assess risk are subjected to Tier 3 testing, designed

to permit quantitative evaluation of mutagenic potential. Tests used at this level include multigeneration mammalian studies, such as the heritable

translocation test, X chromosome loss test, and

specific loci test in mice.

Tier testing may represent an efficient use of

resources in large-scale mutagenicity testing, but

the use of prescreening tests carries serious disadvantages in determining mutagenic potential, If

test chemicals are prescreened by a single microbial test, the proportion of false negatives may be

unacceptably high, and potentially hazardous or

useful substances may escape further testing.

The use of two or three tests at this level, including both micro-organisms and mammalian
Appendix C—Methods for Toxicologic Testing . 143

. . . , . . . . . .—- >--

cell cultures with and without activation by mammalian enzyme systems, may substantially increase the reliability of prescreening (96). Nevertheless, such cell systems may not approximate

metabolic events in the intact mammal closely

enough to reveal the mutagenic action of some

substances that are potential human mutagens.

Whatever the testing approach and test systems selected, mutagenicity tests should include a

positive control as well as negative (untreated

and solvent) controls. The positive control substance, a known mutagen in animal systems that

is selected for its structural similarity to the test

chemical, serves to demonstrate the sensitivity of

the test organism and the efficacy of the metabolic activation system used.

Current Test Systems

Chromosomal effects of many substances have

been demonstrated in plants such as Vicia faba

and Tradescantia (42), and the latter organism

has also been used in detection of somatic mutation (43). While the genetic events involved (alterations in DNA) are the same as those in mammalian cells, their relevance to human mutagenesis

has been questioned because of the major phylogenetic and physiologic differences between

plants and animals; thus, a negative result in

plants does not indicate that a substance is not a

mutagen in mammalian systems.

Of the many bacterial species that have been

used to detect point mutations, the most extensively employed are the Salmonella typhimurium

mutants developed by Ames (44,45). The Ames

test uses a series of histidine-requiring mutant

strains that revert to histidine-independence by

specific mechanisms, either base-pair substitutions or frameshift mutations, The original strains

have undergone several further modifications

that increase their sensitivity to mutagens by interfering with DNA repair or modifying the cell

wall to enhance the penetration of chemicals into

the cell. Bacteria treated with the test chemical

are plated on selective media or cultured in liquid

suspension to determine the number of revertants. A reproducible mutation rate twice the

spontaneous (control) rate is usually considered

evidence of mutagenic activity.

Because microbial cell systems do not possess

the metabolic capabilities of mammals, they will

not detect chemicals that exert a mutagenic effect

through metabolic intermediates, Several activating systems have been developed for use with in

vitro test systems to duplicate the effects of mammalian metabolism. The most extensively used

means of metabolic activation is the addition of

microsomal mixed-function oxidase enzymes, typically from rodent liver homogenates, to metabolize the test chemical in vitro, This activating system is added to the culture medium as part of the

Ames testing procedure with S. typhimurium, and

it has provided evidence for the mutagenicity of

many substances that have no direct mutagenic

effect on these bacteria (51). Microsomal enzyme

activation is also used with other microbial test

systems (46-48). The major drawbacks of this system are that it would not detect chemicals metabolized to mutagenic intermediates by mechanisms

other than liver microsomal enzymes, e.g., substances metabolized by the intestinal flora, and it

is possible that the in vitro metabolism of the

substance does not adequately mimic its metabolism in the intact organism because of competing

reactions. Another drawback is that a standardized in vitro activation system has not been devised to date.

Another widely used bacterial system is the

multipurpose strain of Escherichia coli developed

by Mohn and coworkers (49). This strain can be

used to measure reverse mutations restoring the

ability of the bacteria to synthesize the nutrients

arginine and niacin. Forward mutation rates in

two genes controlling galactose metabolism can

also be scored in this strain of E. coli. Use of this

test organism permits the detection of several

types of mutation in a single experiment.

Eukaryotic micro-organisms that are used to

detect the ability of chemicals to produce point

mutations include haploid strains of the yeasts

Saccharomyces cerevisiae and Schizosaccharomyces pombe (47,5o) and of the ascomycete Neurospora crassa (51). A diploid strain of S. cerevisiae permits detection of chromosomal damage

expressed as mitotic recombination that produces

phenotypic color changes (52).

Whole-animal activation mechanisms can circumvent this problem but they are generally much

less sensitive than tests using in vitro activation.

In these systems, rodents are exposed to the test

chemical by an appropriate route, and the effect

of rodent metabolizes on microbial genetic markers is determined by either body-fluid analysis or

host-mediated assay procedures,

In the body-fluid analysis (53-56), the microorganisms are treated with the urine, blood, or

homogenized tissues of the exposed animals. Caution is necessary in interpreting negative results

of these studies, in the absence of supplementary

pharmacologic data, since even if the chemical is

metabolized to a mutagen, other factors such as
144 ● Environmental Contaminants in Food

tissue-specific activation and detoxification

mechanisms and the half-life of the compound and

its metabolizes may affect test results. In the hostmediated assay (57,58), the micro-organisms are

exposed to mammalian metabolic products of the

test substance by being introduced into the peritoneal cavity, circulatory system, or testes of the

host mammal. The host is treated with the test

substance, and after an appropriate incubation

period, the indicator organism is removed and examined for mutations.

Genetic damage in micro-organisms can also be

assessed indirectly through the use of DNA repair-deficient strains of bacteria (44,59). These

tests organisms and otherwise identical strains

that have normal ability to repair DNA are

treated with the test substance. Toxic action of

the test substance produces zones in which bacterial growth is inhibited, and the difference in

size between the inhibition zones in repair-deficient and normal strains indicates the extent to

which this toxicity is due to damage to the DNA.

A number of mammalian cell systems in culture

have been developed for detecting point mutations, including cell lines derived from mouse lymphomas, Chinese hamster ovaries and embryos,

and human fibroblasts and lymphoblasts (60-63).

In addition, gross chromosomal changes such as

breaks, gaps, and rearrangements can be microscopically observed in these cells. Stable rearrangements, such as translocations and inversions, are considered evidence of heritable

changes. The induction of only gaps and breaks is

not regarded as evidence of mutagenicity, because these aberrations often occur as a result of

general cytotoxicity and thus may be present only

in moribund cells. Like microbial systems, in vitro

mammalian cell tests can be used in conjunction

with activation by mammalian enzymes or with

whole-animal activation to permit detection of

mutagenic effects by metabolic products of a test

substance.

Mammalian cells, including human white blood

cells, are also used to detect chemical damage to

DNA by measuring unscheduled DNA synthesis

(63). This indirect indicator of genetic damage is

evaluated by measuring the uptake of radioactive

thymidine for repair of damaged DNA during

those stages of cell growth when DNA synthesis

does not normally occur. A similar test with

mouse spermatocytes exposed in vitro or in vivo

demonstrates effects on DNA in germinal cells

(64),

Sister chromatid exchange, a reciprocal exchange of segments at homologous loci. measured

by autoradiographic methods, has also been used

to examine a variety of chemicals (65,66). Sister

chromatid exchange in various cell systems has

been demonstrated following exposure to known

mutagens, but additional work is needed to define

the extent to which results are correlated with

more traditional mutagenicity tests,

The fruit fly Drosophila melanogaster is used in

a comprehensive and extensively characterized

mutagenicity test system which can detect all

types of mutagenic activity at a fraction of the

time and cost of in vivo mammalian testing (67).

The large number of genetic markers and known

chromosomal aberrations make it possible to

assay a chemical for many types of mutagenic activity in a single test. The sex-linked recessive

lethal test (68) in Drosophila is a very efficient

mutagenicity assay, since about 20 percent of the

insect’s genetic material is located in the X

chromosome. Recessive lethal changes caused by

point or chromosomal mutation can be mapped

and in most cases the nature of the change causing the mutation can be determined. This test also

permits a quantitative assessment of mutagenic

activity. Because of the large size of Drosophila

chromosomes, this organism can also be used

readily to assess meiotic and mitotic recombination, dominant lethality, translocations, and deletions. Some indirect mutagens that required metabolic activation have been shown to be mutagenic

in Drosophila, indicating that these insects have a

microsomal mixed-function oxidase system (69).

However, to determine whether Drosophila test

results are useful for risk assessment, more information is needed on how their metabolism of

foreign chemicals compares to that in humans. A

few other species of insects have also proven useful in mutagenicity testing, including ‘several

species of the parasitic wasp, Habrobracon (70).

Clearly the most accurate predictions of mutagenic potential in humans can be drawn from

tests that determine direct genotypic and phenotypic effects in mammals exposed to the test

chemical by routes relevant to human exposures,

Several direct mammalian tests exist, but these

have the disadvantage of detecting only a few of

the possible types of genetic damage. Chromosomal damage occurring in vivo can be detected

in several different cell types, such as bone marrow cells and circulating lymphocytes, and the

presence of micronuclei in red blood cells (7 I).

Cytogenetic tests using mammalian lymphocytes

and the micronucleus test offer the advantage of

permitting direct comparison with effects on humans resulting from accidental exposures; how-
Appendix C—Methods for Toxicologic Testing ● 145

ever, these tests demonstrate only effects on somatic cells and do not provide direct evidence of

heritability.

Cytogenetic changes in mammals can also be

evaluated in germinal tissue from the testes. In

the direct spermatocyte test (72), male mice are

exposed to the test substance. After sufficient

time for the treated spermatogonia to reach the

spermatocyte stage, they are examined for cytogenetic abnormalities. This test allows for the actual observation of induced cytologic changes in

premeiotic male germ cells, but it does not permit

detection of effects in postmeiotic cells or their

transmission to the offspring.

Effects on offspring can be evaluated in mice by

the heritable translocation test (73) and the X

chromosome loss test (74). In the heritable translocation test, F, male offspring of treated mice are

mated to determine sterility, and indication o

possible translocation heterozygosity. Chromosomal effects are then confirmed by cytogenetic

analysis of the germinal cells of the male of offspring. The X chromosome loss test permits the

detection of chromosome loss resulting from nondisjunction in the female, since, unlike somatic

chromosome aneuploids, animals of XO genotype

are usually viable, Aneuploidy for the X chromosome can be detected by genetic markers and confirmed by cytologic observations.

The dominant lethal assay, usually performed

in the rat or mouse, uses fetal loss as an indicator

of induced chromosomal mutations in male germinal cells (75). The death of the zygote is assumed to result from chromosomal abnormalities in

the sperm of male mice exposed to the test chemical. This test is relatively easy to perform and its

results have been positively correlated with mutagenicity in other animal systems. Preimplantation

loss alone is not used as an indication of mutagenicity since it has been found to occur for reasons other than chromosomal changes in the

sperm. Disadvantages of this test are its relative

insensitivity and difficulty in clearly distinguishing weakly positive results.

Only one test is available at present that can

detect heritable gene mutations induced in mammalian germ cells. In the specific locus assay in

mice, forward mutations at seven loci, affecting

characteristics such as coat and eye color are

mated with mice homozygous for recessive alleles

at these loci (75). Because such a small number of

loci are involved, this test required the scoring of

20,000 to 30,000 offspring at each dose level to

produce reliable results and is therefore very

costly and time consuming.

Carcinogenicity

In the event of massive or long-term environmental contamination of food destined for human

consumption, one of the decisions to be made is

whether the contaminant appears to pose a significant carcinogenic risk. With this in mind FDA

submits the candidate compound to the Chemical

Selection Working Group at the National Cancer

Institute for consideration under the carcinogen

bioassay screening program (76,77).

Prerequisites for a Carcinogenicity

Study

Once the compound has been selected, it is

screened using a chronic or lifetime exposure

regimen (76,78,79). However, before the long-term

study is undertaken, specific toxicologic profiles

must be obtained. Young healthy adult animals of

each sex and strain to be used in the long-term

studies should be used in the preliminary studies.

The animals should be of uniform age and weight

and should be tested using the same formulation

and route of exposure to be used in the long-term

studies. The first is an acute study designed to

gain additional information on the acute toxicity,

assuming there is a paucity of data on this aspect

of toxicity, and to determine the lethality of the

test compound. The duration of this test should

not exceed 24 hours and should include at least

three dose levels determined by a geometric progression. one of the dose levels selected should

represent the highest dose to be used in subsequent studies. Throughout the investigation, all

relevant clinical signs should be recorded. Necropsies should be performed on a random selection of animals of each sex and strain, and any abnormal histopathologic changes should be noted.

After the 24-hour study, a 14-day investigation

should be initiated in an effort to ascertain the

doses necessary for the subchronic study, the

next prerequisite investigation for the chronic

study. This toxicologic study requires five dose

levels, with the highest one, estimated from the

24-hour acute study, producing no more than 10-

percent lethality. The other dose levels should

represent geometric decrements of the highest

dose. Animals should be treated with the test

substance for no more than 14 days, held another

24 hours, and then sacrificed for necropsy.

Throughout the study, the animals should be observed for clinical signs of toxicity. Other toxicity

data, such as those derived from organ function

tests and metabolism studies, are also necessary.
146 ● Environmental Contaminants in Food

The next toxicity study involves the administration of the test substance for 90 days and is used

as a predictor of the maximum tolerated dose

(MTD). This can be defined as the highest dose

given during a chronic study that can be predicted to not alter the animals’ normal longevity

from effects other than carcinogenicity, In practice, MTD is considered to be the highest dose that

causes no more than a 10-percent decrement in

weight compared to controls. Five dose levels are

required in this study, with a minimum of 10 animals of each sex and strain in each dose group.

The highest dose level used should be the lowest

concentration that produced any detectable untoward toxic effects in the 14-day study. The remaining dose levels should be determined as in

the 14-day study, If the selected dose levels do not

produce a discernible no-effect level, the study

should be repeated with lower doses.

Carcinogenic Bioassay

The chronic study (76,78,79) represents the

essence of the carcinogenicity bioassay. It is used

to determine the carcinogenicity of a compound in

males and females of two mammalian species,

usually the rat and mouse. The species selected

are tested throughout their entire lifespan. Each

test group should consist of a statistically representative number of animals. The highest selected

dose should represent MTD and the remaining

dose levels should be adjusted accordingly. There

should be at least one control group, in which the

animals receive only the vehicle used for administration of the test material, If no vehicle is used,

this control group should be untreated but identical in every way to the experimental groups. In

addition to the concurrent control group, a colony

or historical group should be used for the comparison of longevity, spontaneous diseases, and

spontaneous tumor incidence. The historical control may also be used for statistical comparisons.

In some studies, a positive control group that has

been treated with a compound structurally similar to the test compound and known to be carcinogenic in the test species may be indicated. However, because of the added risk of handling a

known carcinogen, a positive control group is seldom used.

Throughout the study, animals must be observed for signs of toxicity. Every animal should

be examined carefully each week, Animals should

be weighed and food consumption measured. In

some cases, it is desirable to evaluate tissue

distribution and concentration of the substance

or its metabolizes.

The animals in any one test group should be

sacrificed at an adjusted or prearranged date.

However, a group can be terminated earlier if

there has been high cumulative mortality. Moribund animals should be sacrificed immediately

upon discovery to lessen the likelihood of unobserved deaths and subsequent autolysis or cannibalism. Control groups should be sacrificed according to the original or adjusted sacrifice date;

the later date is preferred. Because of the strong

dependency on histopathologic results and to

avoid possible criticisms of the study, necropsies

and histopathologic examinations should follow

standard procedures required by regulatory

guidelines.

The major drawback to the carcinogenic bioassay procedure is the time and cost required to

complete and analyze such a study. If the study is

done properly, however, the results should be

conclusive and for the most part indisputable, although there still remains the question of extrapolation of results to the human population.

Short-Term Testing as a Prediction of

Carcinogenicity

Evaluation of carcinogenicity has generally relied on the results of long-term animal studies, To

use this kind of testing approach for every substance suspected of being carcinogenic would be

cost-prohibitive and certainly impractical in

terms of the overall time required to test all suspected chemicals. Therefore, short-term tests are

being developed to identify carcinogenic substances. There has been much criticism concerning the comparison of short-term testing results

from different laboratories because of the varying conditions and refinements in techniques

practiced among testing facilities. The protocols

for these short-term tests, especially those involving mammalian enzyme activation systems, have

not been standardized or validated through interlaboratory comparative testing procedures; thus,

comparisons of the data from one laboratory to

the next have often produced conflicting conclusions. In this light, a study conducted in one laboratory that compares several short-term testing

systems has added importance in clarifying the

relative usefulness of the compared systems,

In a recent study by Dr. Ian Purchase (80), 120

organic chemicals (50 known carcinogens and 62

noncarcinogens, based on published experimental data) were evaluated for activity in six shortterm test systems. These systems included: 1) mutation of Salmonella typhimurium (45), 2) cell

transformation (81), 3) degranulation of endoplas-
Appendix C—Methods for Toxicologic Testing ● 147

.—

mic reticulum (82), 4) sebaceous gland suppression (83), 5) tetrazolium reduction (84), and 6) lesion formation after subcutaneous implant (85).

Four additional tests used in a preliminary study

were found to be insufficiently accurate or sensitive to justify a full evaluation. The tests rejected were transplacental blastomagenesis (86),

piperidine alkylation (87], iodine test (88), and the

acridine test (89).

Although there were considerable variations

between tests in their ability to predict carcinogenicity, two tests were quite accurate in

distinguishing between the known carcinogens

and the noncarcinogens. These were the cell

transformation test and the bacterial mutation

test, which had accuracies of 94 and 93 percent,

respectively. The use of cell transformation and

bacterial mutation together provided an advantage over the use of either alone, predicting 99.19

percent of carcinogens. Not surprisingly, the inclusion of the other four tests in a screening battery with these two resulted in an improved ability to detect carcinogens (99.97 percent), but

greatly decreased the accuracy and discriminatory value of the battery. It is important to note

that all tests generated both false positives and

false negatives: the percentages for both can be

readily calculated by subtracting the positive

predictability values from 100 percent.

A description of each of the tests, with comparative percent accuracies for predicting carcinogenicity as determined by Purchase et al. (80) is

as follows:

● Bacterial mutation. The procedures used

were those of Ames, in which four strains of

S. typhimurium (TA 1535, TA 1538, TA 98, TA

100) were tested with each compound in an

assay medium containing a metabolic activation system composed of rat liver postmitochondrial supernatant (S-9 fraction) and cofactors. The overall accuracy of the test in

predicting the carcinogenicity of the compounds in this study (80) was 91 percent for

carcinogens and 94 percent for noncarcinogens. These figures agree with the previously

published value of 90 percent by McCann et

al. (90) but are considerably higher than

those published by Heddle and Bruce (91)

who found 65 and 81 percent, respectively.

● Cell transformation. The procedures used

were those of Styles (81) and involved three

types of mammalian cells—human diploid

lung fibroblasts (WI-38), human liverderived cells (Chang), and baby Syrian

hamster kidney cells (BHK 21/cl 13). In all

●

●

●

●

assays, the cells were used with and without

metabolic activation with S-9 fraction as

described previously. Without activation,

very few carcinogens transformed hamster

or human cells in the period of study. With

activation, all cell lines detected carcinogens

with an accuracy of 88 percent or better.

Furthermore, by the use of both the hamster

cells and either of the human cells, the

overall accuracy was improved to 94 percent

(91 percent for carcinogens and 97 percent

for noncarcinogens).

Degranulation. The procedure used is that of

Williams and Rabin (82) and the test is commonly called the Rabin test. The test measures the loss of ribosomes (degranulation]

from isolated rat liver endoplasmic reticulum following incubation with the test compound. The overall predictive value was 71

percent for both carcinogens and noncarcinogens.

Sebaceous gland test. The procedures used

were those of Bock and Mund (83) where test

chemicals were applied directly to the skin of

mice and a depression in the ratio of sebaceous gland to hair follicles indicates a positive response. The overall predictive value of

the test was 65 percent (67 percent for carcinogens and 64 percent for noncarcinogens).

Tetrazolium reduction. The procedures used

were based on those described by Iversen

and Evensen (84). Test solutions were applied directly to the skin of mice and the skin

samples were incubated in tetrazolium red

solution. An increase in the in situ biologic

reduction of the colorless tetrazolium to a

colored formazan compound indicates a positive response. The overall predictive value of

this test was 57 percent (40 percent for carcinogens and 71 percent for noncarcinogens).

Subcutaneous implant. The procedures used

were essentially- those of- Longstaff an d

Westwood (85] and involved the subcutaneous implantation of a filter disc overlaid with

a gelatinous suspension of the test c o m

-

pounds into mice. After 3 months, the surrounding tissues were scored for lesions. The

overall predictive value for this test was 68

percent (37 percent for carcinogens and 95

percent for noncarcinogens).

While the work of Purchase and associates (80)

does present a very salient assessment of the

more pertinent in vitro assays, it also points out
148 ● Environmental Contaminants in Food

the shortcomings of this type of approach. Shortterm tests do not use the induction of cancer as an

endpoint, but each has a parameter, such as induction of a point mutation, that varies with the

carcinogenicity or noncarcinogenicity of the test

substance. Accordingly, the authors feel that

these test parameters should not be given a

greater weight than that of any other arbitrary

response, regardless of how biologically significant any of these tests might appear to be with

respect to the theories of the chemical induction

of cancer. Also, however much generalized data

might be generated to support the predictive accuracy of the given test, this accuracy should not

be assumed to apply uniformly to compounds of

every chemical class,

Teratology and Effects on

Reproduction

An investigation of a teratogenic agent involves

the study of congenital malformations other than

those that are inherited. Teratogens themselves

act as triggers for malformation induction. Malformations may include gross, histological, molecular, and behavioral anomalies,

The sensitivity of an animal to a teratogen is determined by: 1 ) the period in which the insult is received during the gestation period (this includes

before germ layer formation and during embryogenesis or organogenesis); 2) the dose and the

route of administration of the compound; 3) placental transfer of the suspect teratogen, including

its lipid volubility, protein binding ability, and

metabolism: and 4) uterine and dietary factors.

A toxicologic profile of a suspect teratogen requires an evaluation of potential hazards to reproduction and, particularly, to developmental

processes that respond to environmental insult

through mutation, chromosomal aberrations, mitotic interference, altered nucleic acid synthesis,

enzyme inhibition, and altered membrane characteristics. This is particularly important in the conceptus, embryo, and the neonate where the biochemical, morphologic, and physiologic properties change rapidly. Thus risk assessment must

not only address the teratogenicity of a contaminant but also its effect on reproduction.

Classical Approach

For an adequate teratologic assessment (79,92,

93), exposure to the toxicant should parallel as

closely as possible that expected in the human

population. The pharmacologic activity of the

compound as well as its acute and chronic toxicity is also a consideration. For teratogenic studies,

the toxicant is usually administered daily on the

specific days of gestation representing the period

of greatest sensitivity. Administration of the test

substance should begin at or before implantation

and should continue throughout the period of major organogenesis.

The selection of an animal species for evaluation of teratogenicity is an important consideration. Test protocols currently in use recommend

at least two mammalian species, the first being a

rodent (e. g., mouse. rat, hamster) and a nonrodent

mammalian species (e.g., rabbit). One species

should be the same as that used in the test for

reproductive effects.

In conducting the teratogenic investigation, at

least three dose levels should be used, along with

concurrent control groups. These control groups

should consist of untreated animals, animals

treated with the vehicle of administration only,

and, possibly, animals treated with an agent that

is known to cause the effect that is being investigated. The use of historical or colony controls may also be helpful in evaluating the data.

Both test and control animals must be young,

mature, prima gravida females of uniform age,

size, and parity. The control groups should be

handled and maintained like the test groups. The

highest dose level to be considered should produce signs of embryo or fetotoxicity as suggested

by fetal growth retardation and more significantly by maternal or fetal mortalit y: however, maternal mortality should not exceed about 10 percent.

The other dose levels can be obtained in a decreasing logarithmic fashion to a suspected no-observable-adverse-effect level. In the classical

teratology study, treatment may be by gavage so

that the administered dose is accurately known. It

has been shown, however, that use of this route of

administration may induce anomalies in progeny

that are a consequence not of the test compound

but of the stress of dose administration (94).

Prior to initiating the study, it is important to

determine whether sires and dams have successfully mated, This includes examinations for the

presence of plugs or evidence of sperm in vaginal

smears. Throughout the study, females should be

observed for behavioral changes, food and water

consumption, body weight, vaginal bleeding indicating possible abortion, and spontaneous

deaths. Females showing signs of aborting or delivering prematurely should be sacrificed.

Fetuses should be obtained 24 hours before anticipated parturition by cesarian section, Dams

should be sacrificed and a complete necropsy per-
Appendix C—Methods for Toxicologic Testing ● 149

test material for at least 120 days. At this point

they are bred to produce the F, generation.

The types of data to be collected include

growth and time of delivery for each weanling as

well as overt signs of toxicity, the general

behavior and condition of the mothers, measurements of spermatogenesis in all Ff generation

males used to produce the F: generation, litter

size, number of stillborn/live births, and any physical or behavioral anomalies.

A statistically valid number of animals (males

and females) obtained from the F, generation and

used to produce the F~ generation should be sacrificed and examined at the appropriate time, with

special emphasis on the histopathologic state of

the reproductive system. In addition, an adequate

number of weanlings of each sex from each dose

level, including controls, should also be sacrificed

and used for histopathologic analyses.

Data derived from the above should be evaluated for the existence of a relationship between

exposure and the incidence and severity of effects on reproduction and behavior, tumors, and

mortality. The no-observable-adverse-effect level

should also be determined.

Compared to a teratology investigation, which

requires about 3 months to complete the exposure

and to analyze the results, a three-generation

reproduction study represents a considerably

longer expenditure of time, approaching 1.5 years

between the initiation of the study and the completion of the analysis of the gathered data. However, an elementary profile on teratogenicity and

reproductive performance can be obtained within

a period of a year or less as a part of a continuing

long-term toxicity study by adding the appropriate number of animals at the beginning of th e

long-term study (2).

Metabolism

Metabolic assessment studies are not directly

used for the assignment of risks, tolerances, or action levels, These studies are used to determine

parameters, such as absorption, distribution,

storage, and excretion, that may affect the performance of materials in biologic systems, thus

enabling the researcher to design testing protocols that measure the overall effect of exposure to

the material rather than just measuring a part of

the biologic response. These protocols can then

take into account such factors as tissue concentration, length of time in contact with specific

organs or tissues, ease of reactivity, and the production of significant (or nonsignificant) changes
150 ● Environmental Contaminants in Food

in overall body concentrations that may alter the

outcome of a specific testing regimen.

Metabolic study systems are usually centered

around the concept that the circulatory system is

the major means of transportation of the material,

regardless of the route of exposure, Although specific materials may be readily metabolized at or

near the site of entry into the body (e.g., the lungs,

skin, and intestines), the majority of materials are

transported unchanged to the liver and then distributed via the circulatory system to other tissues and organs. At the same time, some of the

material may be excreted unchanged in the urine,

feces, and air or converted to various metabolizes

that are excreted or bound in the tissues. The proportions of the metabolic products that are excreted or bound depends on the chemical nature

of the original compound, the dose, route of administration, species, strain, sex, diet, and environmental factors.

The objective of the metabolic study is to mathematically evaluate the rates and relative importance of these processes in limiting the concentration of materials in the tissues of the body.

For this purpose, the body is usually visualized as

a group of pharmacokinetic compartments, a simplistic view that surprisingly approximates fairly

accurately the complex, interdependent processes that actually occur in the body (95). These

compartmental models allow the researcher to

use measurements of blood concentration as indirect estimates of tissue concentrations and to

determine the length of time the material remains

unaltered (i. e., the biologic half-life). Rates of absorption from one compartment to another can

also be readily measured, thus giving the researcher information on the rate constants of diffusion into tissues and on the rates of distribution

from the blood to various tissues. Clearance or

elimination rates can also be determined for the

excretion of the material from the body via the

kidneys, gastrointestinal tract, lungs, saliva, and

perspiration.

The rate of metabolism of materials depends on

many factors, among the most important of which

are the physiochemical characteristics of the

molecule itself. Polar compounds are usually excreted very rapidly from biologic systems largely

unchanged because of the chemical activity of

these compounds, whereas nonpolar compounds

such as lipids usually remain in the body longer

because they must be metabolized to polar compounds before excretion occurs.

Another important factor in the metabolism of

a compound is its structural resemblance to naturally occurring substances in the body. Foreign

compounds that closely resemble normal body

constituents are frequently metabolized by the

same specific enzyme systems that metabolize

their normally occurring analogues. Most foreign

compounds, however, have no endogenous counterpart and must be metabolized by relatively

nonspecific enzyme systems. These nonspecific

enzymes catalyze many different types of reactions leading to a diversity of metabolic products.

In general, the nonspecific enzyme reactions can

be categorized into two types, The first includes

the conversion of one functional group into

another (oxidation of alcohol to aldehyde), the

splitting of neutral compounds to fragments having polar groups (hydrolysis of esters and amides),

or the introduction of polar groups into nonpolar

compounds (hydroxylation). The second type includes the conjugation of the created polar group

with glucuronate, sulfate, glutathione, or methyl

groups to form a soluble, excretable product. The

product formed in the first reaction may be either

more or less toxic than the parent compound or

may possess a different type of toxicity. Often, it

is this product that actually causes the toxic effects, including cancer, mutations, cellular necrosis, hypersensitivity, fetotoxicity, and blood dyscrasias. A portion of the chemically reactive

metabolize formed becomes bound to tissue macromolecules, such as cellular proteins, DNA,

RNA, glycogens, or lipids. In this way, it disrupts

the normal function of the macromolecule, causing adverse biologic effects. In contrast, the majority of the second type of reaction products are

usually either nontoxic or considerably less toxic

than the parent compound,

The metabolism of a foreign material is controlled by enzymes, and any factor which affects

these enzymes also affects the metabolism of the

compound and consequently its toxicity. The metabolism of a compound may be inhibited or stimulated by the presence of competing substrates.

Pretreatment with drugs, steroids, food additives,

pesticides, polycyclic hydrocarbons, polycyclic

amines, and normal constituents of food can result in an increase in the activity of enzymes that

metabolize foreign compounds. This increase in

enzyme activity differs according to the inducing

chemical, but is mediated through an increased

rate of synthesis of enzyme protein, a decreased

rate of turnover of enzyme, or an activation of enzyme, possibly by changes of structure or conformation. Because of this phenomenon, chronic

administration of a foreign material may enhance
Appendix C—Methods for Toxicologic Testing ● 151

the activity of the enzymes that catalyze its

metabolism.

Several types of biologic phenomena are readily studied using a metabolic test system. These include activation, antagonism, synergism, and potentiation. Activation has been briefly touched on

above with the description of the process of toxification: it involves the rendering of an inactive

molecule into an active molecule, usually through

the removal or substitution of a neutralizing factor attached to the molecule, but it may also involve the direct addition of a constituent to the

molecule. One of the most common examples of

activation, the conversion of a precarcinogen to a

carcinogen, is the addition of oxygen molecules to

polycyclic aromatic hydrocarbons via the microsomal NADPH-dependent cytochrome P-450

mixed function oxidase enzyme system. This conversion to the oxide produces a carcinogenic

agent of considerable potency, whereas the parent material does not possess a direct carcinoAPPENDIX

1.

2.

3,

4.

5.

6.

7.

8.

9.

10.

11,

12.

13.

14.

15.

16.

41 CI+’R 51206 (1976).

Food and Drug Administration Advisory Commi[-

tee on Protocols for Safety Evaluations: Panel on

Reproduction Report on Reproduction Studies in

the Safety Evaluation of F’ood Adciit ives and Pest iicicle Residues ( 1970). Tox, App). Pharm. 16:264.

A40dern Trends in Toxic~Jlogy ( 1968). E. Eloyiand

and R. Coulding, ecis,, But terworths, London.

Methods in ‘1’oxicolog}’ ( 1970). G, E. Pagett, cd.,

Davis, Philadelphia.

Frawlev, J. P. ( 1 955). Fooff Drug Cosmetic L(IW J.

1 o: 703.

Sm}th, 1{. I+’,, Jr,, an(i (;. P. Carpenter (1944). J.

Jnd. Hyg. (Jnd Toxicd. 26:269.

Friedenwt~ld, J. S., W. l“, Hughes, Jr., and H. Hermann ( 1944). Arch. of Oph th. 31 :279.

Carpenter, C. P., and H. F, Smyth, Jr, (1946). A m .

J. Ophth. 29: 1363.

Draize, J. H., G. Woodard, and H. O. Calvery

[ 1944),]. Phc~rm. find Expt. “rherc~peu. 82:377.

I)raizc, J. 11., and E. A. Kelly ( 1952). Proc. of the

Sci. Sec. of Toilet G(MN]S Assoc. 17:1.

Ilraize, J. H. ( 1955). Foo{j Drug Cosmetics Low ].

10:722.

Draize, J. 11. ( 1965). Assoc. of Food and Drug

Of ficicds ~)f the U. S., Topeka. Kans., 46.

Lansteiner, K., and J. Jacobs (1935). ]. Exp. Med.

61: 643.

Lansteiner, K,, and J. Jacobs (1936). ]. Exp. Meal,

64:625.

Buehler, E. V. (1!365). Arch. Derm, 91 :171.

Baer, R. L., S. Rosenthal, and C, J. Sims [1956). J.

Invest. Derm. 27:249.

genie potential per se. The determination of metabolic activation can permit the experienced researcher to predict the kind of adverse effect that

is likely to be elicited from the parent molecule,

thus enabling the researcher to better design experiments to observe these effects.

From a properly designed and well-carried-out

metabolic study, the researcher can gain valuable

insight into the potential toxic actions and biologic effects to be expected from a foreign compound. If a compound is not absorbed or if the

compound is destroyed or rapidly eliminated from

the body there is little likelihood of pronounced

toxic effects. If the principle metabolic products

are polar, conjugation (and thus elimination)

rapidly occurs and again there is little potential

for pronounced toxicity. On the other hand, if metabolism produces an activation product, toxicity

is enhanced and biologic effects may be pronounced.

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Review and Evaluation

Appendix D

Methods of

Determining Risks From Chronic LowLevel Carcinogenic Insult *

by Kenny S. Crump and Marjory D. Masterman

BASIC PRINCIPLES AND CONSIDERATIONS

To aid in determining a proper regulatory action regarding a carcinogen that is present in

man’s environment, whether it be a feed additive,

industrial pollutant, or otherwise, it is helpful to

have some knowledge about the number of extra

cancers that are likely to be caused by the presence of the carcinogen in the environment. It is

also helpful to have some knowledge of the likely

change in number of extra cancers that would accompany some projected increase or decrease in

the level of human exposure occurring either as a

result of regulatory action or inaction. This kind

of information is usually impossible to obtain directly from human data. For this reason it is often

necessary to use data from animal feeding experiments to estimate human risk. This procedure involves two difficult steps: 1) relating the animal

risk at high doses to doses very near to zero and 2)

relating the animal risk to risk in humans.

Typically, animal experiments use on the order

of 100 animals at each experimental dose. If a

particular experimental dose causes a lifetime increase in cancer risk of 1/10, this increase can be

measured with a small degree of accuracy using

100 animals. But if the increased cancer risk is

less than 1/100 this increase will often not even be

detectable by an animal feeding experiment. For

example, if the true risk is 1/100 it would require

that over 400 animals be tested at that dose in

order to be 99-percent sure of detecting any carcinogenic response at all (i. e., for there to be a

probability of 0.99 that at least one animal gets

cancer). If background or spontaneous carcinogenesis is present even larger numbers of animals

will be required, On the other hand, the extra human risk that we may want to estimate resulting

from environmental exposure is usually (and

hopefully) smaller than 1/100 for any given chemical, perhaps on the order of 1/1,000,000. It is

clear that it would not be practical to conduct an

experiment with enough animals to measure directly an increase in risk this small.

For these reasons the procedure has been developed of conducting lifetime animal feeding experiments using, in addition to a control dose of

zero, several doses at which the projected extra

cancer risk may be 1/10 or larger, These highdose data are then used to estimate the extra risk

at a dose where the extra risk may be no larger

than, say, 1/1,000,000. An equally important variant to this problem is the calculation of the socalled “safe” dose, that is, a dose for which there

is some measure of statistical assurance that

the extra risk at that dose is no more than, say,

1/1,000,000 These problems are often referred to

collectively in the literature as the ‘‘low-dose extrapolation problem. ”

Performing a low-dose extrapolation involves the choice of statistical procedures to apply to the

the choice of a mathematical function to model mathematical function. The choice for this mathethe dose-carcinogenic response relationship and matical function turns out to be extremely crucial

to the outcome of low-dose risk estimation. If the

*Excerpt from OTA Working Paper entitled “Assessment of

Carcinogenic Risks From PCBS in Food.”’ A complete copy of assumed relationship between tumor occurrence

the paper can be obtained from the National Technical Infor- and dose does not apply in the regions to which

mation Service. (See app. J.) the extrapolation is being made, a serious over154
Appendix D—Review and Evaluation of Methods of Determining Risks From Chronic Low-Level Carcinogenic Insult ● 155

estimate of the “safe” dose may result (Mantel

and Bryan, 1961, p. 458). Chand and Heel (1974)

compared five standard dose-response models

and observed that they could differ by many

orders of magnitude at low dose levels for which

extra risks are on the order of 1/100,000,000.

It might be supposed that it should be possible

to discriminate among the various potential doseresponse functions on the basis of experimental

data but, unfortunately, two different dose-response functions can often fit experimental data

equally well but still differ by several orders of

magnitude at very low doses. Moreover, even if a

particular dose-response function were to give a

significantly better fit to data than several others

this would still not furnish assurance that this

function would necessarily correlate in any way

with the true dose response at very low doses

where it is not feasible to measure the true extra

risk directly. As a consequence of the great disparity of dose-response functions at low doses it is

imperative that the dose-response function be selected, neither arbitrarily nor solely on the basis

of how well it can be made to fit experimental

data, but, insofar as is possible, it should reflect

known or at least plausible information regarding

the biological mechanisms through which a chemical induces or promotes cancer.

WHAT SHAPE SHOULD BE EXPECTED FOR THE DOSE-RESPONSE

CURVE AT LOW DOSES?

Tumors of so many different types arise in such

a diversity of different tissues, their etiology is so

little understood, and the agents that cause

tumors affect a subject in such diverse ways, that

it might seem that no general conclusions can be

drawn. However, for a certain broad class of “directly acting” chemical carcinogens the range of

uncertainty associated with the shape of the doseresponse curve at low doses can be greatly narrowed. As used in this paper, the term “directly

acting carcinogen” encompasses (Guess, Crump,

and Pete, 1977) carcinogenic agents for which

either the agent itself or a metabolize acts directly

at the cellular level and produces a heritable

change that eventually leads to the formation of a

tumor. Carcinogens that are carcinogenic by reason of their mutagenicity should fall into the category of “directly acting carcinogens. ” Accordingly, carcinogens that test positively using the Ames

mutagenicity screening test for carcinogenicity

are very likely to be directly acting (see McCann

and Ames, 1976). In a recent study (McCann,

Choi, Yamasaki, and Ames, 1975) in which about

300 carcinogens and noncarcinogens were tested

using the Ames test, 90 percent (157 out of 175) of

the carcinogens were mutagenic including almost

all of the known human carcinogens. This indicates that the class of directly acting carcinogens

may encompass most of the known carcinogens,

A partial solution to the low-dose extrapolation

problem for the case of directly acting chemical

carcinogens has been given in Peto (1977), Crump,

Heel, Langley and Peto (1976), and Guess, et al.

(1977). The key result is that, at least as long as

background carcinogenesis is present, we should

expect the dose-response curve not to be absolutely flat at zero dose. What this means is simply that

when risk is plotted against dose response on ordinary linear scales, the tangent line to the doseresponse curve at zero dose should have a positive slope. When a dose-response function has

this property we will say it is linear at low dose.

This simple property can have far-reaching consequences on low-dose extrapolation. For example, consider the two potential dose-response

functions:

Both of the curves give a risk of 1/10 at a dose of d

= 1 and are practically indistinguishable at

higher doses. However, at a dose of d = 1/1,000:

1) predicts a risk of 1/100,000 and 2) predicts a

risk of 1/10,000,000, a difference of two orders of

magnitude. We note also that 1 ) has a tangent line

with a positive slope at d = O whereas 2) does not.

One explanation of why the dose-response

function should be linear at low dose when background is present may be found in Crump, et al.

(1976) and Peto (1977) and will be briefly outlined

here. When background carcinogenesis is present, the cellular mechanism through which the

test agent produces cancer should already be operative in producing background tumors. When

this is true the effect of the test agent is to add to

an already ongoing process. The result of this

additive effect is illustrated in figure D-1. The

dose-response curve is for all tumors produced

through the mechanism through which the test

agent acts. Background carcinogenesis is allowed

for in the figure by an effective background dose

do. We see that, in this case, the added risk

caused by a dose d of the test agent should be ex-
156 ● Environmental Contaminants in Food

pected to increase approximately linearly near d

= O (i.e., the tangent line at d = O will have a positive slope). Implicitly assumed by the way figure

D-1 is drawn is the fact that an added dose of a

carcinogen acting through this mechanism does

not produce a smaller risk, If background carcinogenesis is allowed for as in figure D-1 by positing

an effective background dose do that is estimated

from the data, then the wide range of risks obtained using different models effectively disappears (Pete, 1977). We note that the existence of a

tangent line with a positive slope at zero dose

does not, in itself, imply any lower bound for extra

risk at low doses since the slope of the tangent

line could possibly be very small.

The evidence given above for a positive slope to

the dose-response function at zero dose applies

particularly to the case in which background carcinogenesis is operative. This does not imply that

we expect the dose-response curve not to be linear at low dose in the absence of background carcinogenesis. For example, the multistage models

of cancer (Armitage and Doll, 1961) are a fairly

broad class of models in which it is assumed that

Figure D-1 .—Illustration of Why the Dose” Response

Curve Should Be Linear at Low Dose in the Presence

of Background Carcinogenesis. dO Is the Effective

Background Dose and d Is the Dose of the

Carcinogen of Interest

at d =0

a number of events are required to occur at the

cellular level to initiate cancer. Although all models in this class are linear at low dose provided

background carcinogenesis is present, a sizable

subclass of them are linear at low dose in the

absence of background carcinogenesis (Crump, et

al., 1976).

Watson (1977) has recently proposed a more

specialized model for cancer induction and promotion based on reversible epigenetic cellular

changes. Watson concludes that his model supports the low-dose-linearity hypothesis and states

“as suggested by a different argument of Crump,

et al. . . . it is reasonable to assess the risk due to

an additional carcinogen at low constant dosage

by a linear relation. ”

The evidence for low-dose linearity given above

applies mainly to directly acting carcinogens. An

indirectly acting carcinogen might be one that

causes some gross physiological change such as

suppression of ovulation that could predispose

the subject to cancer. For such carcinogens the

shape of the dose-response curve at low dose is

highly speculative. There could possibly be a

threshold dose below which the agent has no carcinogenic effect at all on an individual, However

even if a threshold mechanism is operative, there

is likely to be considerable variation in individual

thresholds in a large population. Consequently the

dose-response curve for the entire population

could still exhibit a linear trend at risks as low as

1/1,000,000 or lower.

The effects of metabolic activation and detoxification on carcinogenic dose response have been

recently considered by Cornfield (1977) through a

kinetic model that encompasses free toxic substance, metabolize, deactivator, and the interactions of these substances. Only a steady-state situation is studied in that variation over time of the

concentrations of these agents is not considered.

The model predicts a threshold dose below which

there is no carcinogenic risk under the assumption that the deactivator is 100-percent efficient

in deactivating the carcinogen. However, in a naturally occurring process it is likely that deactivation would not be perfect and would be less than 

100-percent effective in always combining with

100 percent of the carcinogen before an amount

of the active metabolize reaches a cancer target

site, Any of a number of modifications to the

model to allow for nonperfect deactivation would

rule out a threshold and would lead directly to a

model for which carcinogenic response varies

linearly with dose at low doses, Cornfield’s own

modification of perfect deactivation, that of al-
Appendix D—Review and Evaluation of Methods of Determining Risks From Chronic Low-Level Carcinogenic Insult ● 157

lowing the deactivating reaction to be reversible,

leads, as Cornfield points out, to a model which is

linear at low dose. This occurs regardless of how

slowly the reverse reaction takes place, as long as

the possibility is not eliminated entirely. Furthermore, even in the extremely unlikely case of

perfect deactivation, an otherwise realistic model

should still imply low-dose linearity since the

theoretical time required for perfect deactivation

would not be zero and would likely be infinite.

For most, perhaps all, carcinogens, the mechanisms through which cancer is produced are not

sufficiently understood so that the shape of the

carcinogenic-response curve can be theoretically

predicted with certainty. As pointed out earlier,

neither can experiments of sufficient size be conducted that would permit direct experimental investigation of the dose-response curve at low

dose. We have noted that there are plausible arguments that the dose-response curve is linear at

low dose for many carcinogens. On the other

hand, this author knows of no serious proposal of

a mechanism that would lead to a more conservative dose-response relationship such as the risk

varying approximately as the square root of dose

at low dose. In view of these uncertainties it

would seem reasonable to base estimates of

added risk of cancer on a mathematical model

that encompasses low-dose linearity unless, of

course, the mechanism through which the carcinogen operates is sufficiently understood so

that low-dose linearity can be conclusively ruled

out. Once the principle of low-dose linearity is accepted the problem of estimation of risks at low

dose is nearly solved. This is because the disagreement between the upper statistical confidence bounds on risk at low doses based on a

model that incorporates low-dose linearity and

one that does not is typically several orders of

magnitude whereas the corresponding disagreement between two reasonable models both of

which incorporate low-dose linearity is usually

much less than this.

Mantel= Bryan

The Mantel-Bryan procedure as originally proposed (Mantel and Bryan, 1961) and “improved”

(Mantel, Bohidar, Brown, Ciminera, and Tukey,

1975) is for the purpose of conservatively choosing a “safe” dose of a carcinogen, a “safe” dose

being defined as one for which it can be expected

that, with a given level of statistical assurance

(e.g., 99 percent), the true dose producing a preassigned “safe” level (e. g., 1/1,000,000) of risk

will lie above the “safe” dose. In the MantelBryan procedure the mathematical model used

for the dose-response model is the probit function:

where d represents the dose of the carcinogen

and P(d) represents the probability of a cancerous

response in an animal subjected to a dose d. The

parameters in the model are an intercept parameter a, a probit slope parameter b, and C, which

represents the probability of a response in untreated animals. The parameter b is not estimated

from the data but rather is arbitrarily set equal to

1. This choice is stated as being conservative

(Mantel and Bryan, 1961), the argument for this

being that typical dose data exhibit a probit slope

in the experimentally observable region above 1 -

percent incidence that is greater than one, In

Mantel and Schneiderman (1975) it was observed

that a set of DES data (Gass, Coats, and Graham,

1964, C3H females) exhibited a probit slope of

one-half, but the general use of a probit slope of b

= 1 was still suggested.

With the probit slope parameter fixed at b = 1

the remaining parameters, a and C, are estimated

from the data and then adjusted so as to produce

a higher level of risk at a given dose that corresponds to an upper 99-percent statistical limit on

the true risk at a given dose. The safe dose is then

determined to be the one producing a given low

risk (e. g., 1/1,000,000) based on the adjusted values of a and C.

As pointed out in Mantel, et al. (1975), the

Mantel-Bryan procedure rewards larger and better experiments in that the more evidence there is

of safety, the higher the calculated safe dose will

be. However this advantage should be shared by

any extrapolation method that uses reasonable

statistical procedures.

Some have considered the Mantel-Bryan procedure to be too conservative (Federal Register, vol.

42, 1977, p. 10419) in that it involves three conservative choices (99-percent statistical assurance, lifetime risk of 1/1,000,000, and probit slope

set equal to 1) and that any one of these assumptions alone could provide adequate protection to

the public. The first two of these choices are regulatory decisions that would have to be made with

any extrapolation procedure. However, the arbi-
158 ● Environmental Contaminants in Food

trary selection for the slope parameter seems to . response relationship does not apply at the low

be peculiar to the Mantel-Bryan procedure. To investigate its effect upon the extrapolation procedure a typical fit is presented in figure D-2 (from

Crump, 1977b) of the Mantel-Bryan probit curve

(equation 1) to experimental carcinogenicity data

when the probit slope parameter is fixed at b = 1.

As can be readily seen the probit curve typically

provides a very poor fit, curving downward even

when the trend of the data is toward an increasingly upward curvature. This typically bad fit to

data of the probit curve raises serious questions

regarding the validity of statistical procedures associated with the Mantel-Bryan method (see Salsburg, 1977; and Crump, 1977b).

On the other hand, the Mantel-Bryan procedure utilizing the choice b = 1 was put forth as

conservative procedure and it gives that appearance in figure D-1 since the probit curve appears

to lie far above the trend of the data at the lowest

doses. However as mentioned earlier and also

pointed out by Mantel (Mantel and Bryan, 1961, p.

458) a procedure may, while appearing conservative at experimental dose levels, at the same time

seriously overestimate the “safe” dose (i. e., be

seriously anticonservative) if the assumed doseFigure D-2.—Typical Fit of Mantel” Bryan Curve

to Experimental Data (From Crump, 1977b)

—

o

o

0

Mantel Bryan

maximum likelihood

curve

\

“safe” dose curve

2

Dose

4 6

risk levels to which extrapolation- is ‘being made.

Thus, before the degree of conservation can be

evaluated for any procedure, the properties of the

dose-response curve at very low doses must be

evaluated,

As described earlier, there are strong arguments that indicate the dose-response curve

should be “linear at low dose” particularly for

directly acting carcinogens in the presence of

background carcinogenesis. This has led Peto

(1974) to recommend extrapolation procedures

using only dose-response functions from a class

containing only dose-response functions that are

linear at low dose, At the very least, however, it

would seem prudent not to go to the opposite extreme and use a dose-response function that rules

out linearity at low dose by assumption, However,

the Mantel-Bryan procedure, through its use of

the probit curve (equation 1) rules out linearity at

low dose in favor of a “flatness property” (see

Hartley and Sielken, 1977; Mantel, 1977; and

Crump, 1977b) at low dose which is anticonservative to the extreme. This property implies that

mathematical derivatives of all orders of the

probit curve approach zero (through positive values) as the dose approaches zero. This unusual

property is more often discussed within the context of mathematical oddities rather than in connection with a scientific investigation. It implies

that if the true dose-response curve comes from

an extremely broad class of functions known as

analytic functions and which pervade scientific

applications of mathematics, then the probit

curve will eventually underestimate the true risk

at low doses. Furthermore, at low enough doses,

the degree to which the risk will be underestimated will be arbitrarily large (i.e., the ratio of

the true risk to the probit estimate will grow arbitrarily large).

It was emphasized earlier that it is important

when extrapolating to low doses for the assumed

dose-response function to incorporate known or

at least plausible facts about the mechanisms of

carcinogenesis. In neither the original paper

(Mantel and Bryan, 1961) nor in the paper outlining the improved version is biological justification

given for the selection of a curve having the above

described “flatness property.” It should be mentioned at this point that the incorporation of background carcinogenesis into the Mantel-Bryan

probit model (equation 1) using the parameter C

implies that the mechanism through which the

test carcinogen produces cancer is independent

of the mechanisms through which all of the back-
Appendix D—Review and Evaluation of Methods of Determining Risks From Chronic Low-Level Carcinogenic Insult ● 159

ground cancers are produced (Crump, et al.,

1976). In keeping with the discussion in the last

section it would seem more proper to incorporate

background into the probit model by positing an

effective background dose do which adds to the

dose d of the test carcinogen. If background is incorporated in this way the probit curve no longer

has the “flatness property” and becomes linear

at low dose (Guess, et al., 1977). In fact. with

background incorporated in this way, the probit

curve assumes a shape similar to the one-hit model, sometimes referred to as the most conservative

of all procedures (e.g., Mantel, 1977).

Even though the “flatness property” implies

the probit curve should at suitably low doses be

anticonservative to the extreme, the “flatness”

property holds only for doses approaching zero

and the feature of arbitrarily fixing the probit

slope at 1 mitigates the anticonservativeness implied by the “flatness” property at any given low

dose (although the property itself will hold for all

choices of the parameters a, b, C), The cancer

risks that are typically extrapolated to are in the

risk ranges 1/10,000 to 1/100,000,000. We will examine the outcome of Mantel-Bryan extrapolations to these risk levels in a later section when

we compare them with extrapolations based on

the multistage model.

Linear Extrapolation

The technique for linear extrapolation was

recommended by Heel, Gaylor, Kirschstein, Safiotti, and Schneiderman (1975) for use on an interim basis until better procedures could be developed. The procedure is straightforward and is

based on an assumed linear relationship between

dose and response at low dose. The procedure

utilizes only the data for the group of control

animals and a single other dose group, usually

either the highest dose that elicits no response or

else the lowest dose that elicits some response. In

the case there are no cancers in the control animals the “safe” dose, based on a maximum risk of

1/1,000,000 and 99-percent statistical assurance,

is calculated as follows: An upper 99-percent confidence bound is calculated for the cancer risk in

the dose group of animals. From this risk and dose

one extrapolates back toward zero dose and zero

risk using a straight line relationship. The dose

corresponding to a risk of 1/1,000,000 on this

straight line is taken to be the “safe” dose. If

there are cancers in the control animals this procedure is modified to allow for the statistical

treatment of the response in the control group

while retaining the straight line relationship.

When data at other experimental doses are available this method of linear extrapolation has the

obvious shortcoming of not fully utilizing the

available data.

A linear dose-response curve is linear at low

dose but the converse is not necessarily true. A

curve can be linear at low dose and still have a

high degree of nonlinearity at higher doses.

Linear extrapolation is viewed by some as a

very conservative procedure. For example, comments were made during the decision on which

extrapolation procedure to incorporate into the

SOM document to the effect that linear extrapolation is the most conservative of all procedures.

Crump, et al. (1976) examined the extent of the

conservatism of a linear dose-response function

when compared with a multistage dose-response

model (Armitage and Doll, 1961). The multistage

model assumes that a cell must go through a number of different stages before cancer is initiated

in that cell and the model can encompass a high

degree of nonlinearity. It was determined that the

maximum possible degree of conservatism of a

linear model relative to a multistage model depended rather heavily on the incidence at the experimental dose relative to the background incidence. (This is consistent with the general relationship between background carcinogenesis and

linearity at low dose as discussed earlier. ) For example, when the incidence at the experimental

dose is four times the incidence at zero dose the

extra incidence at low dose derived from the linear dose response differs from the incidence derived from the multistage model by, at most, less

than a factor of 2.5 regardless of the number of

stages in the multistage process. Thus, when

background carcinogenesis is present, the linear

dose-response curve is not overly conservative

relative to the multistage dose-response curve. In

fact the linear dose-response curve is anticonservative when compared to the one-stage or onehit models.

Linear extrapolation has long been proposed

for use in radiation carcinogenesis (see Brown,

1976, for a review of the relevant reports). The

BIER (1972) report on radiation risks from the National Academy of Science recommended linear

extrapolation as a “best estimate” approach as

opposed to a conservative approach. Brown reviewed arguments both for and against linearity

and concluded that “linear extrapolation of

human data from high dose of low LET radiation

cannot be said to overestimate the risk at low
160 ● Environmental Contaminants in Food

doses. In fact, there is some doubt as to whether

the risk is not underestimated. ”

Certainly much remains to be learned about

both radiation and chemical carcinogenesis. However, if both radiation and chemicals cause cancer through similar mechanisms then it should be

expected that there would also be similarities between the respective carcinogenesis dose-response functions. Direct damage to DNA by the

carcinogenic agent has been implicated as one

cancer-initiating mechanism for both radiation

and chemicals (Brown, 1976; and McCann and

Ames, 1976). Thus, the findings related to the

potential linearity of the dose-response function

for radiation has implications for chemical carcinogens as well, particularly for “directly acting” carcinogens.

Extrapolation Methods Based

on the Multistage Model

Two methods of low-dose extrapolation which

are alternatives to the Mantel-Bryan or linear

procedures have recently been proposed independently by Guess, Crump, and Deal (Guess and

Crump, 1976, 1978; and Crump, Guess, and Deal,

1977) and Hartley and Sielkin (1977). Both of

these methods utilize a multistage dose response

function of the form:

where q~, ql, . . ., q~ are all non-negative parameters to be estimated from the data. This dose-response function is general enough to yield a considerably wide range of responses at low dose. On

the one hand, if q, >0 and q,= O for i~ 2 the doseresponse function (equation 2) becomes the onestage model which yields risks at low doses comparable to what would be obtained with linear extrapolation, On the other hand, the model can produce risks even as low as the probit curve (equation 1) down to any fixed positive low dose. Thus

this model is capable of fitting both highly linear

and highly nonlinear dose-response relations.

Since the model has the property of “linear at low

dose” if q,> O and does not have this property if

ql = O, use of this model does away with having to

make the arbitrary but crucial decision of having

to either assume linear at low dose as in linear extrapolation. Thus “safe” doses computed using

this model should provide a more realistic measure of the true uncertainty of low-dose extrapolation than would “safe” doses based on either an

assumed linear curve shape or an assumed highly

nonlinear curve shape.

The dose-response relation (equation 2) contains all of the Armitage and Doll (1961) multistage dose-response models as special cases but

also contains curves that are much flatter at low

dose than any of the multistage curves.

The two extrapolation procedures based on

equation 2 have some features that are different.

When computing “most likely” estimates the procedure of Guess, Crump, and Deal uses an infinite

dimensional maximization procedure so that it is

not necessary to specify a value of k, the degree of

the polynomial in equation 2. However the two

methods differ chiefly in the way the statistical

confidence intervals are computed. There have

not yet been sufficient comparative calculations

made to determine how safe doses may differ

using the two approaches, Mantel (1977) has

made a critical review of the statistical procedure

used by Hartley and Sielkin for calculating the

“safe’ dose.

Both the Hartley and Sielkin and the Guess,

Crump, and Deal (as extended by Daffer et al.,

1979) procedures can utilize times at which

cancer is detected in the experimental animals

rather than just the dichotomous information of

whether or not an animal contracted cancer before it died of some other cause or before the termination of the experiment, The utilization of time

data in low-dose extrapolation is important for at

least two reasons: 1) the age at which cancers occur should be important in assessing the magnitude of the harmful effect of a carcinogen on man

(e.g., cancers that occur early in life should be

viewed as more serious than those that occur in

extreme old age); and 2) in many animal carcinogenicity experiments the response data at the

highest doses lies below the trend of the lower

dose data, This sometimes appears to be due to

the fact that at the highest doses some of the animals are being poisoned by the chemical before

they have a chance to develop cancer, When this

occurs the high-dose data is often just deleted

from the analysis. However if the times at which

the animals die are properly used the high-dose

data might not appear anomalous. More research

needs to be done on the proper utilization of animal time of death data to assess the harmful effects of chemicals to man.

Comparisons Between Mantel-Bryan

and Multistage Extrapolations

To compare low-dose extrapolations using the

Mantel-Bryan probit model (equation 1) with
Appendix D—Review and Evaluation of Methods of Determining Risks From Chronic Low-Level Carcinogenic Insult ● 161

those using the multistage model (equation 2) we

present figure D-3 based on the same data as

figure D-2. In this figure, the Mantel-Bryan “safe”

dose is plotted on a log-log scale as well as both

the multistage “most likely” curve and the “safe”

dose based on (equation 2) and computed as outlined in Crump, et al. (1977). A 99-percent statistical assurance was used for both “safe” dose

curves. We note that the Mantel-Bryan “safe”

dose lies above the multistage safe dose curve at

values of added risk below 5 x 10-4, The MantelBryan “safe” dose curve lies above the multistage

“safe” dose curve by a factor greater than 20 for

an added risk of 10~ and by a factor greater than

300 for an added risk of 10~. Because of the

“flatness” property of the Mantel-Bryan probit

function (equation 1) described earlier, the

Mantel-Bryan “safe”’ dose curve will lie above the

multistage safe dose curve by arbitrarily large

factors at extreme low doses. Guess, et al. (1977)

have compared the Mantel-Bryan “safe” dose

curves to the multistage “safe” dose curves and

found this to be a typical situation. Thus it is clear

that if the true dose-response curve could be

similar to the multistage dose-response function

(equation 1) then the Mantel-Bryan procedure

could not be justifiably called conservative (see

Figure D-3.—Comparisons of “Safe” Doses

Computed From the Mantel” Bryan Procedure

and From a Procedure Based On the Multistage

Model (From Crump, 1977b)

r

Added Risk

also Crump, 1977 for further discussion of this

point.) On the other hand, we have seen that there

are quite plausible arguments for the true doseresponse curve to have the same shape at low

dose (linear) as the estimated multistage curve.

We note that both the multistage “safe” dose

curve and “most likely” curve have a slope 1 in

figure D-3 as plotted on the log-log scales which is

equivalent to the curves being linear at low dose.

The fact that the “most likely” curve has slope 1

is due to the fact that with this particular data set

the linear coefficient q, in equation 2 will always

be linear at low dose regardless of whether or not

the linear coefficient q, is estimated to be positive.

This property should be shared by any valid statistical procedure based on a dose-response function that does not rule out linearity at low dose by

assumption as Mantel-Bryan does. Just as it is not

possible to prove statistically the existence of a

threshold, it is likewise not possible to rule out the

possibility that the true dose-response curve is

linear at low dose on the basis of statistical

analysis. (See Guess, et al. (1977) for a thorough

discussion of this important point.) The MantelBryan obtains “safe’” dose estimates which are

considerably higher than those obtained using the

multistage model because it assumes away linearity at low dose, an assumption that we have seen

is probably unwarranted for that majority of carcinogens which are classified as ‘‘directly acting”

carcinogens.

Since extrapolation based on a model such as

the multistage model (equation 2) must always be

linear at low dose, the question arises as to how

different the result will be from simple linear extrapolation. For some data the difference will be

minimal. For example, for the data upon which

figure D-2 is based, “safe doses” computed using

the multistage model are almost identical with

*’safe’” doses based on linear extrapolation. For

some data sets, however, the difference could be

considerable. For example, with the Gass, et al.

(1964) DES using the C3H female mice, the “safe”

dose based upon linear extrapolation is lower

than the “safe” dose based on the multistage

model by a factor of about five and there are

other data sets where this difference is greater

than an order of magnitude.

The Gamma Multihit Carcinogenesis

Dose-Response Model

Rai and Van Ryzin (1978) have proposed basing

risk estimation on the gamma multihit model:
162 ● Environmental Contaminants in Food

where P(d) is the lifetime probability of cancer in

a tissue when subjected to a constant dose rate, d,

of the carcinogen. This model is obtained by assuming that cancer due to the carcinogen occurs

randomly according to a Poisson distribution. The

manner in which background carcinogenesis is incorporated into the model is equivalent to assuming that the event “cancer occurs due to the action of the carcinogen” is independent of the

event “cancer occurs spontaneously, ” This assumption would not apply, for example, to processes in which the effect of the carcinogen is to

speed up the rate at which the “spontaneous”

events occur which lead to the background cancers. At low dose rates, the response is approximately given by:

Consequently, this dose response model is linear

at low dose rates when and only when k = 1. Rai

and Van Ryzin calculate confidence intervals for

added risk at a given dose and for the dose producing a fixed added risk using asymptotic maximum likelihood theory. Although in the theoretical development k must be an integer, in the applications k is allowed to assume any positive value.

Lower statistical confidence limits on the dose

producing a given low amount of extra risk (“virtually safe dose” or “VSD”) computed using this

procedure can be compared with those computed

from the multistage model (equation 2) by considering two general classes of data.

If the data exhibit a general downward curvature as illustrated in figure D-4a, lower confidence limits on a VSD computed from the gamma

multihit model (equation 3) should generally be

less than or equal to corresponding lower confidence limits computed from the multistage

model (equation 2). In certain instances the gamma multihit lower limits could be much less than

the corresponding multistage lower limits. This

could occur when the data is consistent with k <1

in the gamma multihit model (presumably corresponding to a fraction of a hit).

On the other hand, if the data exhibit a general

upward curvature as illustrated in figure D-4b the

reverse situation will hold; gamma multihit lower

confidence limits on VSDs will generally be

greater than or equal to corresponding multistage

limits, Gamma multihit limits will not in general

share the low-dose linearity of multistage limits

by orders of magnitude at low doses. The reason

these large differences can occur is as follows.

The multistage family of models contains members which are simultaneously linear at low dose

and exhibit upward curvature at moderate doses.

For example, the particular multistage model:

is linear at low dose since q, >0 and still can exhibit upward curvature at moderate doses since

qz >0. This means there are dose-response curves

in the multistage class which are both linear at

low dose and can adequately describe data of the

type exemplified by figure D-4b. On the other

hand, this will generally not be true of gamma

multihit models. All dose-response curves in the

Figure D-4a.— Example of Data Exhibiting

Downward Curvature

%

x

Dose

Figure D-4b.—Example of Data Exhibiting

Upward Curvature
Appendix D—Review and Evaluation of Methods of Determining Risks From Chronic Low-Level Carcinogenic Insult ● 163

gamma multihit class that are linear at low dose

must exhibit downward curvature and consequently would generally not be consistent with

the data in figure D-4b. When this is true gamma

multihit lower confidence limits on VSDs will be

sublinear (e.g., quadratic) at low dose and consequently much larger than the multistage confidence limits.

Confidence limits based on the gamma multihit

model will be approximately correct whenever

this model is the correct model, A similar statement could be made for the probit model, multistage model, or any other model to which reasonable statistical methods are applied. However,

there may be considerable uncertainty as to what

the true model may be in a particular situation.

The multistage model not only reflects some reasonable assumptions regarding the carcinogenic

process which dovetail nicely with epidemiological data for many cancers (Pete, 1977 b), but it

also reflects some of the uncertainty with regard

to the true model by virtue of encompassing a

relatively large class of dose-response functions,

For example, as noted earlier, the multistage

class contains dose-response functions which are

linear at low dose and also exhibit upward curvature at moderate doses. On the other hand, the

gamma multihit class is more restrictive at this

point in that it does not permit such behavior. Is

this extra restrictiveness of the gamma multihit

model justified? To help answer this question,

consider the following modification to this model.

Suppose that the hits (phenomenological events

which are required to occur in a tissue in order

that a cancer appear) can possibly occur spontaneously in the absence of the carcinogen. Part of

the effect of the carcinogen could then be to speed

up the rates at which the spontaneous hits are occurring. For example, if one of the “hits” is in incorrect base substitution in DNA during mitosis,

the carcinogen could speed up the rate at which

these “hits” are occurring in individual cells by

providing more aberrant bases for use in such an

incorrect substitution. With this modification to

the model, the gamma multihit lower confidence

limits on VSDs will no longer be sublinear at low

dose and should be at least as small as corresponding limits calculated from the multistage

model (equation 2). Thus, in order to obtain

sublinear lower confidence limits on VSDs with

the gamma multihit model a modification such as

the one described above must be ruled out, not on

the basis of data, but by assumption.

By way of summary, confidence limits based on

the multistage model will always be linear at low

dose. Confidence limits based upon the gamma

multihit model may be either “super linear” (corresponding to k < 1) or “sublinear” (corresponding to k > 1). Superlinearity is achieved by making

the model too broad in that a fraction of a hit is

allowed which has no biological basis. On the

other hand, sublinearity is achieved by making

the model possibly too restrictive in that models

which are reasonable from a biological viewpoint

are ruled out by assumption.

In addition to questions as to the appropriateness of the gamma model, there is also a very significant difficulty with the statistical procedure

applied to the model in the Food Safety Council

(1978) report. This difficulty is illustrated in table

D-1. Here are listed lower confidence limits for

VSDs for the gamma multihit model which were

taken from table D-1 in Food Safety Council

(1978). For each of the 14 data sets a goodness-offit test was conducted for compatibility of the

data to the subclass of gamma models for which

k =1. As indicated by table D-1, the subclass of

models with k = 1 provided an adequate fit in 10

out of the 14 data sets. For these 10 data sets are

listed the VSD predicted by the best fitting gamma

model with k = 1. The significant point is that in 8

of these 10 cases, the lower confidence limit on

the VSD is greater than the VSD from the model

with k = 1, greater in some cases by enormous factors, e.g., a factor of 3,600 for aflatoxin B,, a factor of 1,000 for diethyl-nitrosamine, and a factor

of 18,000 for sodium saccharin. Put another way,

in the case of the sodium saccharin data, there is

a member in the gamma multihit class which fits

the data quite adequately and for which the VSD

is less by a factor of 18,000 than the lower confidence limit for the VSD reported in Food Safety

Council (1978). This obviously implies there is a

serious problem with the computation of the

lower confidence limits for the VSD. These lower

confidence limits are much too large, even based

on assuming the gamma multihit model is the correct model, for these 8 data sets. This problem

also exists for the 4 data sets which could not be

fit adequately by a model with k =1. This is wellillustrated by the graph in Food Safety Council

(1978) for the NTA data. In this graph, the lower

97.5-percent confidence limit for the VSD corresponding to a risk of 1O-G falls almost directly on

top of a data point for which the measured risk is

1/91. Put another way, even though the measured

risk at this dose is 1/91, the statistical procedure

used indicates, with 97.5-percent assurance, that

the risk is no greater than 1/1,000,000.

These difficulties can be overcome by using a

different statistical procedure. However, when

this is done, the lower confidence limits will be
164 ● Environmental Contaminants in Food

Table D-1.—Comparison of Lower 97.5-Percent Confidence Limits on Virtually Safe Doses From Gamma

Multihit Model Given in to Virtually Safe Doses From Best Fitting Gamma Multihit Model With k = 1

—— —— —. — -—

No. of

experimental

No. Substance ——— dose levels—.

1 ‘“ ‘- ‘ -- ‘“

2

3

4

5

6

7

8

9

10

11

12

13

14

.0013

.035

.000029

.0120

.011

.76

25.3

p <.005(9 d.f .)

.000032

.020

.00020

significant lack of fit

.00016

.000042

significant lack of fit

many times smaller than those reported in Food

Safety Council (1978). For data sets such as the 10

referred to in table D-1 which are compatible with

k= 1, lower confidence limits for VSDs must

essentially be calculated from a model with k <1

and consequently be smaller than those calculated from the one-hit model. This will lead, in

many cases, to super-small confidence limits, as

illustrated by the lower confidence limit for vinyl

chloride, For those data sets, such as botulinum

toxin-type A, which are incompatible with k = 1

because of their strong upward curvature, a

lower confidence limit for the VSD would still be

larger than one computed from the one-hit model.

However, the theoretical objections raised earlier

to the mathematical form of the gamma model

would still apply.

It may not be generally realized that it is uncommon to find data sets which are incompatible

with k = 1 by reason of strong upward curvature.

The four data sets in table D-1 which fall into this

category all involved a large number of animals

and a number of different experimental dose

levels. These four data sets contained from 330

animals distributed over 11 dose levels to 720

animals distributed over 6 dose levels. Most carcinogenicity bioassays are smaller than these, For

example, the standard bioassay for a given sex

and strain in the National Cancer Institute program seems to be 200 animals distributed over 4

dose levels. For experiments of this size it is more

difficult to rule out k= 1. Consequently it would

seem that, for most of the data sets that are likely

to result from a large screening program, appropriate statistical procedures applied to the gamma multihit model would yield lower confidence

limits for VSDs which are even smaller than those

calculated from the one-hit model.
Append/x D—Review and Evaluation of Methods of Determining Risks From Chronic Low-Level Carcinogenic Insult “ 165

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

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and Environmental Health 1:1 33-151, 1975.

Mantel, N. and W. R. Bryan. Safety testing of carcinogenic agents. J. Nat]. Cancer Inst. 27:455-470,

1961.

Mantel, N., and M. Schneiderman. Estimating

“safe” levels, a hazardous undertaking. Cancer

Research 35:1379-1386, 1975.

Mantel, N., N, R. Bahidar, C. C. Brown, J. L. Ciminera, and J. W. Tukey. An improved Mantel-Bryan

procedure for the “safety” testing of carcinogens.

Cancer Research 35:865-872, 1975.

Mantel, N. Aspects of the Hartley-Sielken approach for setting “safe doses’” of carcinogens. In

origins of Human Cancer Book C, Human Risk Assessment, H. H, Hiatt, J. D. Watson, and J. A.

Winsten (eds. ) (Cold Springs Harbor, N. Y.: Cold

Springs Harbor Laboratory, 1977), pp. 1397-1401.

McCann, J., E. Choi, E. Yamasaki, and B. N. Ames.

Detection of carcinogens as mutagens in the Salmonella/microsome test. Assay of 300 chemicals.

Proc. Nat. Acad. Sci. USA 72:5135-5139, 1975.

McCann, J., and B. N. Ames. Detection of

carcinogens as mutagens in the Sa]monella/microsome test. Assay of 300 chemicals: Discussion.

Proc. Nat. A cad. Sci. USA 73:950-954,1976.

Pete, R. Paper delivered at the NIEHS Wrightsville

Beach conference on Low-Dose Risk Estimation,

1974.

Pete, R. The carcinogenic effects of chronic

exposure to very low levels of toxic substances.

Presented at an NIEHS conference on cancer risk

estimation, Pinehurst, N. C., Mar. 10-12, 1976. Environment tal Health Perspectives, 1977.

Pete, R. Epidemiology, multistage models, and

short-term mutagenicity y tests. In Origins o.f Human

Cancer, Book C, Human Risk Assessment, H. H.

Hiatt, J. D. Watson, and J. A. Winsten (eds. ) (Cold

Springs Harbor, N. Y.: Cold Springs Harbor Laboratory, 1977 b), pp. 1397-1401.

Rai, K. and J. Van Ryzin. Risk assessment of toxic

substances based on a generalized multihit dose

response model. Proceedings of SIMS Conference,

Alta, Utah, June 26-30, 1978.

Salsburg, D. S. Open query: Theoretical problems

in the modified Mantel-Bryan procedure. Biometrics 33:4 19-421, 1977.

Watson, G. S. Age incidence curves for cancer.

Proc. Nat. Acad. Sci. USA 74:1341-1342, 1977.
Appendix

Measuring Benefits and Costs

by Donald S. Epp

tolerance level

The benefits to be evaluated are defined as the

reduction in hazards to human health. This definition follows directly from the concern of the Food,

Drug, and Cosmetic Act and the activities of FDA.

Any effects on the health of animals or plants, except as they become food and thus affect the

health of humans, is not considered in this report.

This is not to say that economic analysis is incapable of considering other values associated with

animal and plant life. Rather, it is to limit discussion to those aspects most germane to the decision

under consideration.

The measurement of human health and the determination of a relationship between a particular contaminant in food and subsequent human

health impairment must be made in biological,

medical, and physical science terms. For example, the conclusion that daily consumption of food

containing x parts per million (ppm) of a given

*Excerpt from OTA WoPi ing Paper entitled “Priority Setting

of Toxic Substances for Guiding Monitoring Programs. A complete copy of the paper can be obtained from the National

Technical Information Service. (See app. J.)

substance over a period of 3 years or longer will

result in a 50-percent loss of function of the arms

and hands is a medical and biological science conclusion. Until a determination of the health consequences is made, very little can be done toward

comparing benefits and costs of regulation,

Health hazards from exposure to food contaminants may be stated in various ways depending

on the health effects of the substance and on the

state of knowledge about those effects. The hazard from a substance that increases mortality in

the exposed population could be stated as the

number of premature deaths per year. If illness

requiring time-off from regular activity results

from a certain exposure level, the hazard to the

population might be stated as the number of person-days lost to illness per year. When it is not

certain that exposure will cause a particular consequence, but that the likelihood is increased,

probabilities may be attached to the outcomes.

The hazard from exposure would then be stated

that some percentage of the exposed population

would die prematurely or would lose a specified

number of days from normal activity due to illness, This method of stating hazard is encountered with cancer risks due to smoking tobacco.

166
Appendix E—Measuring Benefits and Costs ● 167

In many instances the substance in question

may not have been studied for health effects or it

may have been developed so recently that longterm effects of chronic exposure are uncertain. It

may, therefore, be impossible to calculate probabilities, let alone specify the numbers of people affected, This does not mean the matter is of no concern. Based on the chemical structure of the substance, scientists may believe that the long-run

consequences may be very serious. In such cases

a precise probability cannot be attached to a specific event occurring, It cannot even be said with

certainty that a health hazard exists. What can

be said is that a serious health risk may be present and the consequences of that risk are so grave

that society may wish to avoid whatever risk may

result. While this type of statement of the health

hazard is more difficult to use in a benefit-cost

analysis, it is not impossible.

No matter how the hazard is stated, the first

task in economic analysis is to convert the hazard

statement into units of measurement that are comparable with the statements of costs to be developed later. Many (although not all) of the costs associated with those decisions are measured in

monetary units—dollars. Likewise, at least some

of the most important benefits to be achieved from

restricting exposure to health risks are also measured in dollars. The most fruitful way to proceed,

then, is to assemble the appropriate monetary

measures and make conversion into monetary

terms wherever possible for those effects not so

measured.

Cash Cost Approach

One of the simplest ways to measure the cost of

illness and at least part of the cost of premature

death is to add up the expenditures made for

treatment or burial and other out-of-pocket costs,

These costs can be obtained in a straightforward

manner and summed for the number of individuals that will be affected at the tolerance level

being evaluated,

Even though the procedure does not involve

complex calculation, this approach does involve

decisions and judgments about the appropriate

costs to us. Medical service costs vary greatly between procedures and between locations, It

would be advisable, therefore, to obtain medical

costs for the specific types of procedures required and for the part of the countr y where affected individuals would likely reside, In some

cases where the contaminated food would likely

be consumed nationwide, a weighted average cost

of the appropriate medical service could suffice. . .

Where the contaminated food is consumed in particular regions of the country, e.g., catfish, the

health effects would likely be concentrated in

those regions also and the appropriate treatment

costs should relate to the same regions.

While the cash cost approach is relatively simple to calculate, it ignores some of the true costs

to society from an untimely death or an illness.

One of the most obvious omissions is the failure to

account for an individual’s contribution to economic output, had sickness or early death not intervened. This weakness is corrected with the forgone-earnings approach.

Forgone-Earnings Approach

Generally, the forgone-earnings approach uses

the discounted value of the future stream of earnings as the appropriate estimate for the cost of an

untimely death, and thus, the appropriate estimate of the value of a life saved from a premature

death. While it is clear that if an individual had

not died or become ill in a particular year he

would have continued to be productive for a number of years, it is not immediately obvious

whether the correct measure to use is gross earnings or net earnings.

Those who support the use of gross earnings

argue that what is of interest to society is lost production, and an individual’s contribution to that

production is measured by his or her earnings

stream. Thus, the loss to society is the discounted

present value of the stream of annual earnings

weighted by the probability that the individual

will be alive and well enough to earn that year’s

income. This approach is best suited to the analysis of illness rather than death and has been

used to study the loss to society from mental illness, syphilis, and illness of all kinds collectively,

Those who prefer to use net earnings argue

that, in the case of death, society may lose the production of the decedent, but it also no longer has

to supply goods for the decedent’s consumption.

Death releases resources to the rest of society for

their use. Thus, the appropriate measure of loss

to society is the discounted present value to the

stream of differences between an individual’s expected income in each year and that individual’s

consumption during the same period. Each annual

net earnings would be weighted by the probability

of the individual surviving to that year. With this

method of calculating, the cost to society of a

death could be negative (or a benefit) if the individual consumes more than he or she produces.

5U-515 o - 79 - 12
168 ● Environmental Contaminants in Food

Retired and unemployed individuals are likely to

have such negative life valuations.

The possibility of a negative value for a life has

led to several criticisms of the approach. Some

individuals produce products that are not marketed, but are none-the-less, real and valuable,

The largest single example is the output of housewives. Other objections have been raised to the

conclusion that the unemployed and retired are of

no value. It must be admitted, however, that these

latter objections appear to confuse the economic

value of an individual with an ethical value of a

human life, It is clear that the forgone-earnings

approach examines only one portion of an individual’s contribution to society—the contribution to

those things measured in the net national product

(NNP). If the goal of society is the maximization of

NNP, then assessing the costs or benefits of a

health-impacting project according to the forgone-earnings approach can be rationalized. If society holds other goals as well, then the use of

forgone earnings is merely an expedient approximation.

Willingness-to-Pay Approach

The most telling argument against the previously discussed evaluation techniques is that they

are conceptually incorrect for use in benefit-cost

analysis. They are directed to find the answers to

questions like “What is my life worth to other people like my heirs and society in general?” The conceptually correct question to ask is “How much

would I pay to avoid a small probability of my

death or illness?” Approaches that answer this

question are consistent with other measures of societal welfare since they estimate the aggregate

consumer surplus involved in the reduction in

mortality or morbidity rates.

What has come to be known as the “willingness-t o-pa y’” approach has received extensive

treatment in recent economic literature. A review

of much of the theoretical literature and the discussion of some technical points related to a person’s willingness to pay for small changes in mortality rate may be found in Epp, et al. (ch. 4), That

review will not be repeated here, but rather, the

remainder of this section will be addressed to reviewing techniques for determining an individual’s willingness to pay. Two approaches have

theoretical validity: compensation for risk-taking

and questionnaires of willingness to pay.

Compensation for risk-taking as a technique for

estimating the loss in consumer surplus due to increased risk of death, illness, or injury, has the

advantage of being observable to the marketplace. If an individual agrees to undertake a hazardous occupation which increases his probability of death in exchange for a given sum of money,

that sum can be used as an estimate of his willingness to pay for safety, Thaler and Rosen used

data that measures the relative riskiness of jobs

to estimate the tradeoff between wages and risk.

Thirty-seven broadly defined job classifications

shown to be actuarially riskier than the average

occupation were matched against a cross-sectional earnings survey. The results showed that individuals in the risky occupations received increased compensation of about $200 per year

(1967 dollars) for jobs where the risk of death was

1 in 1,000 greater than the average.

This estimate may be conservative when applied to the general population. The occupations

surveyed in the Thaler and Rosen study are approximately five times riskier than the average

U.S. occupation. People who take these jobs have

different reservation prices for risk than individuals who pick less risky jobs. The derived estimate of compensation required to offset greater

risk is, therefore, an extremely conservative approximation of aggregate willingness to be compensated. A further rationale for believing this estimate to be conservative is that the riskiness of

these jobs can in some measure be affected by the

individual employee. He or she is to some degree

in control of the personal risk level within the context of the risk level of the occupation. If the individual is not able to affect his or her personal

risk exposure, it is quite likely that they would

need to be compensated to a greater extent to

undertake the unwanted risk.

The other technique for assessing willingness

to pay is the questionnaire method. A representative sample of individuals are asked how much

they would be willing to pay to achieve a specified

change in a particular condition. For the problem

of environmental contamination of food, the question would most likely be directed toward the willingness to pay for a reduction in the probability of

suffering specific health effects, such as speech

impairment and nerve sensations from exposure

to methylmercury. Questionnaire design ranges

from direct questions about dollar amounts for a

specific risk change to a series of questions about

items related to the specific risk change of interest from which the analyst can infer an answer to

the “what would you pay?” question,

While the willingness-to-pa y approach is asking the conceptually correct question, it has seri-
Appendix E—Measuring Benefits and Costs ● 169

ous difficulties in application, because the items

of interest are going to be consumed in equal

amounts by everyone and no one can be excluded

from consuming the item if it is provided for anyone. For example, a reduction in the risk of lung

disorders due to reduced sulfur dioxide levels in

the air will be available to everyone in the area

regardless of their preferences or payment, If it is

provided for one person, it is impossible to exclude others. The communal consumption aspect

of this large class of similar goods and services

provides an incentive for people to misrepresent

their true preferences when asked, For instance,

if a person believes he will be required to pay

some amount in proportion to his answer yet there

is a high probability the good will be provided

whether or not he contributes and if it is provided,

he will be able to enjoy it, then it is rational for

him to respond that he is unwilling to pay anything for it, even if he knows he really would pay

some amount, if necessary. On the other hand, if

an individual knows that someone else will pay

for the good if it is found to be valued highly will

find it rational to grossly overstate its value to

him. Thus, the incentive to be a free rider makes it

difficult to accurately measure the value to society of an improvement in food safety.

In spite of the difficulties associated with empirical measurement of willingness to pay, several studies have been done and have reported some

success with various methods of presenting the

question to the respondents. Randall, et al. (1974)

used pictures of the powerplant at Fruitland, N.

Mex., at various levels of smoke emission to elicit

responses from residents and tourists as to the

amount they would pay (in the form of a sales tax

increase) to move from a less preferred view to

the respondent’s preferred view. The technique

was used in a similar fashion to examine questions about a powerplant location in southern

Utah (Brookshire, et al. ) and about reclamation of

stripmined land in Kentucky (Randall, et al.,

1978). A modification of the technique was used

by Mann, et al. to determine willingness to pay for

small changes in human mortality. Their study

found that people are able to comprehend risk

changes of the order of IO-6. Although the risk premiums stated in the Mann, et al. study were substantially different from those’ found by Thaler

and Rosen, the study indicated that individuals

were able to answer the type of question posed,

and that with improvements in the survey instrument, the willingness-to-pay questionnaire may be

a workable approach.

COSTS

The costs associated with establishing a particular tolerance level are the loss of social welfare

resulting from the reduction in supply because

some otherwise useful food products can no

longer be sold for consumption. The reductions in

consumer and producer surplus, which are discussed in detail in this section, account for the

economic value of resources, such as labor and

production capital, which may no longer be employed in producing the food product being considered, It is possible, however, that some resources may not have any alternative employment, In such case the tolerance level may cause

these resources to be unemployed. While this lack

of alternative employment is not strictly an economic cost, it is clearly a consequence that a decisionmaker may wish to consider. Therefore, other

effects (some might wish to call them costs) of the

decision are examined in the following section entitled “Distributional Effects. ”

The starting point for assessing the costs of

moving to a particular tolerance level is the physical product that will be affected. The results of

the monitoring program and various special test

procedures can tell what proportion of various

food products from any specified area will not

meet the tolerance level. The task of the economic

analysis is to evaluate the impact of such a reduction in the supply of that food product.

When analyzing the effects of a tolerance level

that removes some food products from the market,

there are two major alternative methods. These

two are what have been called the alternative

cost method and the opportunity cost method.

Either of these methods may employ models of the

affected industry, but as will be shown in the following sections, the opportunity cost method requires more sophisticated models and delivers a

more comprehensive description of likely effects.

Alternative Cost Approach

With the alternative cost method, the analyst

examines the additional cost necessary to achieve

a given objective using the next best alternative

method to the one under study. Applying this to

the PCB contamination of lake trout in Lake Superior, for example, would require that the analyst
170 ● Environmental Contaminants in Food

examine the next best method for producing

164,000 lbs of lake trout that did not exceed 2

ppm of PCB to replace that amount from Lake Superior which does exceed 2 ppm of PCB. This approach requires that there be some alternative

method available which will achieve the same

level of output in order that the costs of the two

alternative ways of producing the output can be

compared.

If there are several alternative methods available for producing a “replacement” amount of

production, the alternative cost approach requires not only that the cost of total replacement

with each method be examined, but that combinations of methods be considered also. To properly

evaluate the alternative cost figure, the analyst

must know the costs of various amounts of product from each alternative method. To continue

with the PCB contamination of lake trout example,

the analyst must consider not only the cost of

164,000 additional lbs of lake trout with less than

2 ppm of PCB from each of the other Great Lakes

(and any other large sources), but the costs of

various increments of production, such as 10,000

lbs. from each source. The least cost combination

of increments would be found by starting with the

least costly way of obtaining 10,000 additional lbs

and adding to that the next least costly way of getting 10,000 more lbs until a total of 164,000 lbs

are accounted for.

Opportunity COSt Approach

With the opportunity cost method the analyst

examines the additional cost necessary to achieve

a new market equilibrium amount of a food product which reflects the likely higher price and,

therefore, lower consumption of consumers. Since

restricting the supply of a food product from previous sources means a shift to higher cost alternative sources, we can use our knowledge of markets and people’s preferences for the food product to estimate their adjustment to the restriction,

This gives a different estimate of costs due to restriction than does the alternative cost method

which assumes no change in the amount of the

food product consumed.

A simplified partial analysis of the difference

between the alternative cost method and the opportunity cost method is presented with the use of

figure E-1. The decision to establish a tolerance

level such that some portion of the product currently offered for sale may no longer be sold is

shown by the shift in the supply curve. Curve So

represents the industry supply curve prior to the

change in tolerance level, while curve Sl represents supply under the higher cost next best alternative method of production which does not violate the new tolerance level. The alternative cost

method examines the increase in cost of obtaining

the initial equilibrium quantity, Q,. This increase

in cost is represented by the area ABP,PO. The opportunity cost method, on the other hand, recognizes that a new equilibrium price and quantity

will emerge after the shift in supply. Quantity will

shift to QI and price to Pz. Comparing the new

equilibrium with the old, the analyst using the opportunity cost method observes that the consumer

surplus has been reduced by an amount equal to

area ACPZPO in figure E-1. This reduction in wellbeing is clearly less than the one calculated with

the alternative cost method. Because the opportunity cost method recognizes changes in production and consumption, it is the preferred method.

The alternative cost method tends to overstate the

cost of more restrictive tolerance levels.

Figure E-1 .—Analysis of a Shift in Supply

I I

o! i 1

Q1 Qo

The above diagrammatic analysis presents the

essential features of the budgeting approach to

the opportunity cost method. This is discussed in

more detail below. Another approach, modeling,

carries the above analysis further to show

changes in the market for factors of production as

well as other product markets, While this method

cannot employ graphic analysis due to the complexity of relationships, the mathematical modeling techniques described below permit a much

more comprehensive analysis of likely effects of a

change in tolerance level.
Appendix E—Measuring Benefits and Costs ● 171

As was noted above, the opportunity cost approach measures effects of a change in tolerance

level as the change in consumer surplus in the

economy. There is abundant literature discussing

the problems of estimating consumer surplus;

some authors even question the value of the concept in many empirical contexts. For this exercise, however, it seems appropriate that consumer surplus be used. The ultimate consumer of the

contaminated food products should provide the

basis for evaluation. This becomes particularly

crucial where ramifications of the production

shift may include a variety of products, not just

the contaminated product. Consumer surplus becomes the common denominator allowing comparison among a variety of production effects. In

practice, the opportunity cost approach may employ either of two methods: budgeting or modeling.

Budgeting

With budgeting the analyst acknowledges that

production shifts are likely for the contaminated

product. This technique uses data on inputs used

in the production of a product to calculate the

costs of producing a particular amount of that

product, assuming that other commodities will be

produced in the same amounts and at the same

prices as with the status quo. The budgeting approach is a more limited and restricted approach

than the modeling one, but for some circumstances may prove advantageous.

Modeling

The second and more complete method of applying the opportunity cost approach is through

the use of production models. With this method,

mathematical models of the relevant portion of

the economy are employed to trace the shifts in

supply curves and the changes in the amount and

price of various commodities and factors which

result from the restriction on the use of a contaminated product. If these models are specified to include geographic areas and the various alternative production activities which take place in

each of these areas, they are able to project

changes in the location of production of particular crops and changes in the use of various production factors in each region of the country. This

more realistically describes the likely reactions to

the change in tolerance level and permits the calculation of a more accurate estimate of the

change in consumer welfare resulting from the

action level decision.

Comparison of Approaches

The alternative cost and opportunity cost approaches are not equally adapted to handling all

problems—each has several advantages and disadvantages. The alternative cost approach has

the advantage of using data that is more easily obtained and not requiring extensive development

of mathematical models prior to the analysis.

Since the alternative cost approach compares the

status quo with the next best alternative, subject

to the change in tolerance level, the only additional data needed beyond present production

techniques is an estimate of how the same amount

of product could be produced under the best alternative available with the new tolerance level.

This data can frequently be obtained from experts in the production of the food under consideration.

The major disadvantage of the alternative cost

approach is that it is conceptually erroneous. O u r

knowledge of economic adjustments to changing

production conditions recognizes that adjustments will be made in the enterprise combinations and in factor combinations for producing a

particular food product. If a significant portion of

the total production is removed from use or a specific location is no longer capable of producing a

safe food product, the ensuing production adjustments will not be limited to factors of production,

but may also include changing the foods produced

or the location of production. The amount consumed of the food for which a new tolerance level

is being established will probably adjust to

changes in the cost of obtaining the food in a safe

form (within tolerance levels). The alternative

cost approach ignores all of this knowledge by assuming that the food in question, using the next

best alternative, will be produced at the same

level as before.

The conceptual error leads to a second error—

the overstatement of the costs associated with the

tolerance level, Because this approach ignores

the adjustments in the amount of a food product

produced, it leads the analyst to a cost figure that

is greater than the one that would actually result.

As production costs increase it is likely that the

quantity produced will decrease. Thus, the alternative cost approach has the analyst multiply a

higher cost per unit by more units than would actually be produced. This leads to an erroneous

calculation of the change in consumer surplus

and to the overstatement of the cost of setting

tolerance at a particular level.
172 ● Environmental Contaminants in Food

The major advantage of the opportunity cost

approach is conceptual: it allows the analyst t o

see the adjustments that the economy is likely to

make in response to changing production costs as

a new tolerance level removes some of the product from the market. Where agricultural products

are involved, the use of an econometric model of

the agricultural sector facilitates the analysis of

changing comparative advantage and the resulting production pattern, This gives a more accurate indication of the ultimate cost of making the

tolerance level decision,

The use of models can also facilitate distributional analysis if those models have spatial (regional) variables introduced into them. Through

the use of regional supply and demand models,

the analyst is able to estimate not only the market

equilibrium supply and demand adjustments, but

also the regional production adjustments in response to the overall market changes. It is thus

possible to note changes in the regional location

of production and to estimate the impact of these

changes on various income and social groups that

are distributed differently in the various regions

of the country. Thus, the models that are used for

the opportunity cost approach can facilitate a

more detailed and sophisticated analysis of the effects of a change in the tolerance level. The reasons for examining distributional effects as well

as a brief description of some ways these may be

done are included in the next section of this

paper.

The major disadvantage of the opportunity cost

approach is that it requires a very large amount

of data. Production costs, outputs, factor requirements, factor prices, and a variety of other bits of

information are required for each alternative

food production activity in each region including

alternative ways of producing the food under consideration. Even if the supply equations and activities are limited to those most likely to enter into

the solution, the requirements are formidable for

most agricultural and fishery commodities. The

demand side also requires regional consideration

with specification of the demand for each of the

commodities included in the supply side of the

model. Careful attention must be given to the inclusion of complements and substitutes so that the

- model will give a reasonable approximation of actual market adjustments.

A second disadvantage of the opportunity cost

approach is that the models developed for analyzing production and market shifts are usually

short-run and static, This means that these

models must be revised periodically in order to include new developments in factor prices, product

prices, and production technology. Thus, the models are expensive to maintain. They are also expensive to create in the first place. Most models

require a great deal of prior research on the technical relationships in production and specification of the factors related to consumption. While

much of this work has been done for agricultural

commodities, it is recognized that the material is

frequently inexact and often the models are out of

date, It would be necessary, therefore, to undertake some rather expensive research in order to

incorporate the opportunity cost approach for a

commodity that did not already have substantial

prior work. This is likely to be the case for seafoods, freshwater fish, and certain agricultural

products produced in a few local areas.

Obviously, the detailed knowledge of production relationships and therefore the expense is reduced if one uses the budgeting method rather

than the modeling method in the opportunity cost

approach, Budgets usually involve a partial analysis of the adjustments and therefore do not require the development of production relationships

for commodities not closely related to the commodity under consideration, Even so, the budgeting approach requires more information than the

alternative cost approach because of the consideration of production changes. It is unlikely that

the budgeting approach can be used for a regionalization analysis that involves more than a very

few regions. Thus, the lesser cost produces less

information.

Since the two approaches, alternative cost and

opportunity cost, differ in the amount of data that

they require and in the cost of acquiring and processing the data, it is necessary for an analyst to

choose between these two methods. Several

points should be considered when making a selection of the most appropriate analytical method.

Demand Elasticity

If the product for which the tolerance level decision is being made has a very inelastic demand, ’

it may be appropriate to use the alternative cost

approach. With a very inelastic demand, it is likely that the assumption of producing the same

quantity regardless of cost is a reasonably close

approximation to reality, Thus, the disadvantages

enumerated above for the alternative cost approach are of less significance for many agricul-
Appendix E—Measuring Benefits and Costs . 173

tural products, such as certain vegetables, sugar,

and cereals for human consumption, as well as

for fish.

Information Availability

Since the opportunity cost approach requires a

great deal of information about production relationships, not only for the commodity under consideration but for alternative commodities, it is

helpful to have these relationships previously developed. Much of this information is so time consuming to develop that it would be virtually impossible to create a research program that could give

results in time to be useful for any action level

decision if a great deal of groundwork had not

been laid prior to that research effort. If no information is available concerning production of

the product in question or the alternative product

that might be produced or consumed, it is likely

that the alternative cost approach would be

adopted. This approach requires less data and

the material that it requires probably can be produced in time to be useful in making a tolerance

level decision.

Complexity of Interrelationships

If a product is produced in many areas with a

large variety of production alternatives, both with

regard to factors of production and to alternative

products, one needs to use an opportunity cost approach. In such a situation the interrelationships

are so complex that it is difficult to judge from

observation of the data the likely combination

that will result from a tolerance level decision.

Under these conditions it is very desirable to use

the opportunity cost approach if at all possible.

Availability y of Mathematical Models

The stage of development of the mathematical

programing models for a particular product or

sector of the economy is an important consideration in choosing a method. If programing models

are fairly well-developed for most of the important alternative commodities as well as the commodity under consideration, it may be possible to

modify the existing work relatively inexpensively

to obtain the information needed for the tolerance

level decision, For example, a great deal of work

has been done with the feed grain-food grain sectors of American agriculture. Less work has been

done on the livestock sectors, although there are

some models that incorporate feed grains and

livestock and some models include the dairy subsector. If the decision to be made involves food or

food grains, serious consideration should be given

to using the opportunity cost approach and some

of the models that have been developed, with

whatever modification seems appropriate. On the

other hand, there has been very little modeling

that includes specialty crops, such as specific

fruits and vegetables, into a general agricultural

model. It would be expensive and of dubious value

to develop a programing model for a tolerance

level decision involving those crops.

. It is readily apparent that the key assumption

of the alternative cost approach—no change in

the quantity of product produced after restricting

the amount of a particular contaminant that may

be present—is not realistic in most cases and can

lead to substantial error in estimating the social

costs of a decision. It is the opinion of the author

that the alternative cost approach is appropriate

only in those cases where an alternative source of

the product is available at virtually the same

effective price or where alternative production

techniques are available at no increase in per

unit cost of production and which would involve

not more than negligible shifts in the location of

production. These are very restrictive conditions.

For most tolerance level decisions involving major

agricultural products these conditions do not hold

and the opportunity cost approach is strongly advised.

DISTRIBUTION EFFECTS

The previous two sections have outlined consid- jor interest here is the analysis of how a decision

erations and methods for determining the benefits impacts on various groups within society. Even

and costs of a change in tolerance level for a par- though a decision may produce an improvement in

ticular contaminant in a specific food product. welfare for the whole of society, there may be

From an economic perspective and a society-as-a- particular groups for which welfare is reduced.

whole viewpoint, these sections cover the econom- Such distribution effects may be due to the beneic analysis of welfare changes. There are, how- fits and costs being shared differently by difever, related areas of concern which may be cru- ferent income groups or by different regions of

cial to the social acceptability of a decision and the country, There may also be concern about

for which economic analysis can be useful. Of ma- how the consequences of the decision affect the
174 ● Environmental Contaminants in Food

environment in various locations or its effect of

esthetic considerations. Each of these points is reviewed briefly in this section.

The analysis of benefits and costs may show

greater addition to benefits from a particular tolerance level change than the addition to costs;

thus, a desirable decision, The consequences of

that decision may not, however, be desirable for

all affected parties, It is, therefore, important in

some cases to examine the distribution of benefits

and costs among social and economic groups.

For example, the decision to set a very restrictive tolerance level on a particular contaminant

in fish may mean that fishing in certain bodies of

water is no longer possible. That may have a very

slight effect on consumers, since they can easily

switch to fish from other areas. The fishermen

who lose their employment may, however, have

much lower incomes than the average consumer

and may have few or no alternative sources of employment. In this case the benefits in health

hazard avoided by a large number of people may

greatly exceed the costs of idled resources in fishing and thus, the decision is appropriate. It is well

for a decisionmaker to realize, however, that the

major portion of the costs will be borne by people

of much below average incomes with few alternatives to mitigate the losses.

Another decision may involve restriction of

contaminant levels in a food eaten primarily by a

specific ethnic or racial minority whose members

have low incomes, The producers of this food may

have several alternative products they can produce and the consumers may also find substitutes

readily available. In this case the costs are slight

and a low-income minority receives substantial

health benefits.

Most of the data needed to describe the distribution of effects among income groups is available from the analysis of benefits and costs. In

some cases it is not clear which income or social

group is affected, but the analyst can usually determine this at the time he collects the data on effects. Thus, it is important that benefit-cost analysts be alert for information about the incidence

of effects as they collect their data. What may be

relatively easy to determine while the original

source is being contacted may be time-consuming

and difficult to find out at a later point in the

analysis. The presentation of distributive impacts

would probably be in narrative form rather than

a quantitative analysis. The important point is to

include this additional information for the decisionmaker so that the fullest possible knowledge

of impacts is available when the decision is made.

The interregional differences in the impact of

benefits and costs may also be of interest to the

decisionmaker. Frequently the alternative source

of product to replace that which is contaminated

above the new tolerance level will be in a different area. Where a particular stream or valley

produces contaminated food, the production may

shift only a few miles to a nearby river or valley.

Then the impact on the economy of a particular

community may be slight. In other cases, a widespread area, such as a large estuary or part of a

State, may be contaminated and production will

shift to a completely different part of the country,

Interregional differences may arise from products which are produced in one area, but consumed in another, For example, most of the winter

head lettuce eaten in the United States is grown in

the Imperial Valley of California, yet only a minuscule portion of the crop is consumed there. If a tolerance level for some contaminant made it impossible to sell Imperial Valley lettuce, almost all of

the cost would be borne by that small part of California while the health hazard reduction would be

shared throughout the rest of the country.

The data for constructing the regional impacts

of a tolerance level decision can be found most

easily in mathematical programing analyses under the opportunity cost approach. Not all programing models have regional specifications, but

most agricultural models do, Careful review of

budgeting results by experts on the production

and marketing of the foods in question can also reveal some of the regional impacts or can call attention to the likely importance of regional differences. Further regional analysis can be performed if desired. The alternative cost approach

does not provide much data on regional impacts.

Here again, however, a careful review of the results by a knowledgeable analyst can suggest the

likelihood of regional shifts that warrant further

analysis with finer detail on regional specification.

The fact that a particular decision will severely

harm a particular region or social group does not

necessarily imply that the decision should be

avoided. If the society-wide analysis of benefits

and costs suggests a net gain from the decision,

there is good reason to go ahead. The analysis of

the distribution of effects may serve to point out

the need for special programs to assist those

harmed adjust to the decision. For example, regional impact analysis may point out the need for

a retraining program for unemployed workers in

a particular region far enough in advance that the
Appendix E—Measuring Benefits and Costs ● 175

program can be ready to go when the tolerance

level decision takes effect.

The analysis of impacts on various regions and

social groups can provide the starting point for

analysis of the sociological and psychological impacts of the tolerance level decision. In some, perhaps many, cases the effect on a particular community or group of people may have serious consequences for social structure, organizational

stability, and even the mental health of the affected people. Such a possibility was pointed out

and briefly discussed by O’Mara and Reynolds

(P P. 61-66) in their analysis of restricting fishing

in the James River of Virginia due to kepone contamination. Since the present report is directed

toward economic analysis, the techniques of sociological analysis will not be discussed here. Some

of the analyses likely to be used are briefly outlined in Epp, et al. (pp. 134-138).

Another area of potential concern is the impact

of a tolerance level decision on the environment

or on the esthetic properties of a region. It is possible that a tolerance level decision may cause

production to shift to an area where environmental damage would increase.

For example, prohibiting the sale of milk from

one area may cause production to concentrate in

another, leading to increased wastes from dairy

farm holding pens and milk-processing plants.

What may have been an acceptable load on the

environment previously may become excessive.

Analysts should be alert to the possible environmental and esthetic impacts of decisions. In some

cases these effects can be measured in monetary

terms and compared with benefits and costs. In

other cases, the effects must remain in biological

terms, but described in such a way as to make

them useful in a tolerance level decision. The use

of environmental food chain models and impact

matrices has been suggested by the author with

respect to pesticide decisions (Epp, et al., chs. 5

and 6) and the interested reader is referred to

that discussion for greater detail, Not all tolerance level decisions will involve a significant environmental effect, but the procedure of analysis

should include a notation to check for such effects

and an analytical protocol for use when needed.

ALTERNATIVE TOLERANCE LEVELS

The sections on benefits, costs, and distribution

effects have described how an analysis might be

conducted of a particular decision to change the

tolerance level from one point to another. For example, one decision might move from no restriction to prohibiting the sale of a particular food

with 5 ppm or more of a specific contaminant. If

benefits exceed costs and distributional as well

as other effects are not overwhelming, then the

move to a 5-ppm tolerance is efficient. That does

not say that 5 ppm is the most efficient tolerance

level. There may be some other level, say 2 ppm,

that would produce even greater net benefits. The

proper use of economic methods requires that

consideration be given to the likely changes in

benefits and costs if the tolerance level were

changed a little either way. If it seems possible

that net benefits would increase significantly by

moving to a different tolerance level, then a detailed analysis as described above should be

made of the change from the originally proposed

tolerance level (5 ppm in the example) to the new

level (2 ppm).
176 ● Environmental Contaminants in Food

LITERATURE CITED IN APPENDIX E

Brookshire, D. S,, B. C. Ives, and W. D, Schulze, 1976,

“The Valuation of Aesthetic Preferences,”’ }ournul

of Environment ta] Economics and A4anagement

3:325-346.

Epp, D. J., et al., 1977, Identification una’ Specification

of Inputs for Benefit-Cost A40deiing of Pesticide Use,

EPA-600/5-77-01 2, U. S. Environmental Protection

Agency. Washington, D,C.

George, P. S., and G. A. King, 1971, “Consumer Demand

for Food Commodities in the United States with Projections for 1980, ” Giannini Foundation Monograph

Number 26, California Agricultural Experiment

Station, Berkeley.

I,eW,is, p F., 1977. “Economic Impact Assessment for

Proposed Reduction of Temporary Tolerances for

Polychlorinated 13iphenyls in F’ood. ”” Unpublished

manuscript, U.S. Food and Drug Administration,

Washington, D.C,

hlann. S. H., et al., 1976 , “The Determination of the

Economic Effects of Pesticide Use on Human Health:

A Gaming Approach to Willingness-to-Pay, ” VVorking Paper Series No. 32. ‘rhe Center for the Study of

Environmental Policy. The Pennsylvania State University, University Park, Pa.

LlcNally, J. M.. 1978a, “Poly(:h(llorirl[~ted” Biphenyls:

Environmental Contamination of k’oad, ” Congression:i 1 Research Service, Washington, D. C., OTA

Wrorking Pi]per.

McNally, J. M., 1978b, “Polybrominated Biphenyls: Environmental Contamina t ion of Food, ” Congressional

Research Service, Washington, D. C., OTA Working

Paper.

0’Mara, G. K,, and R. R. Reynolds, 1976, Evaluation of

Economic and Social Conseffuences of Restricting

Fishing Due to Kepone Pol]ution in the ~arnes River,

Virginiu, U. S. Environmental Protection Agency,

Washington, D,C.

Randall, A. B., et al,, 1974, “Benefits of Abating Aesthetic Environmental Damage from the Four Corners Power Plant. ” New Nlexico State University

Agricultural Experiment Station Bulletin, Las

Cruces, N. Mex.

Randall, A., et al., 1978, “Reclaiming Coal Surface

Mines in Central Appalachia: A Case Study of Benefits and Costs,”’ L(~nd Economics 54:472-489.

Reichelderfer, K. H., et al., 1979, “’Pesticide Policy Evaluation i?lo(iels, ” NRED Working Paper (unnumbered draft), Natural Resource Economics Division,

Economics, Statistics, and Cooperatives Service,

U.S. Department of Agriculture, VVashington, D.C.

Thaler, R.. and S, Rosen, 1973, The V(llue of Saving a

Life: Evidence from the I.(lhor Market. National Burea u of Economic Rcsca rch, Con ference on Income

and Weal t h.

‘1’racer Jitco, Inc., 1978, “Risk Assessment of Polybromina ted 13iphenyls, ‘“ 0’1’A Ll}orking Paper,
Appendix F

Priority Setting of Toxic Substances

for Guiding Monitoring Programs *

by Clement Associates, Inc.

INTRODUCTORY REMARKS ON THE ESTABLISHMENT

OF PRIORITIES

There are many purposes for which the Federal

Government must set priorities among toxic chemicals in the environment. The universe of environmental contaminants is very large, and resources

for research, testing, monitoring, and regulation

are limited. Some statutes explicitly require Government agencies to set priorities for testing or

regulation, and in many other cases agencies may

be called on to explain their decisions to tackle

some problems before others. Accordingly it is

very desirable to develop rational systems for setting priorities.

Establishment of priorities involves preparing a

list of problems, ordered according to their perceived *’importance” or urgency, before attempting to solve them. It is by definition a preliminary

step and should be designed to maximize the efficiency of the problem-solving process, Although it

is desirable to use as much relevant information

as possible in setting priorities, it is also possible

to use too much information. If too much time is

spent in overelaborate priority-setting exercises

the gain in efficiency achieved by tackling the

most urgent problems first is offset by a delay in

taking any action at all. The first task in designing

an efficient priority-setting system is thus to make

a reasonable compromise between the effort expended on this preliminary step and the gain in efficiency achieved by doing it well.

Priority-setting exercises are usually limited

primarily by the unavailability of data. (If extensive data are available, then it is usually obvious

which problems should be tackled first. ) For this

reason there is usually little to be gained by developing elaborate multifactorial schemes to rank

*Excerpt from OTA Working Paper entitled “Priority Setting

of Toxic Substances for Guiding Monitoring Programs. ” A complete copy of the paper can be obtained from the National

“rechnical Information Service. (See app. j.)

problems in numerical order. Good systems for establishing priorities will inevitably involve a substantial element of sound scientific judgment in

weighing and interpreting incomplete and unsystematic data. The second task in designing an efficient priority-setting system is thus to make a reasonable compromise between the use of objective

criteria and scientific judgment.

This report is concerned specifically with the

establishment of priorities for monitoring toxic

chemicals in food. There are two general methods

by which this might be done: 1) directly, by sampling the food supply for chemical contaminants

and ranking them according to potential hazard;

and 2) indirectly, by surveying the universe of industrial chemicals and ranking them according to

their potential for entering the food supply in toxic amounts. The first method has obvious advantages and in fact has been pursued by FDA. The

method is, however, limited by the available analytical methodology: specifically, most of the

chemicals recognized to date as food contaminants are those relatively easily detected by gas

chromatography or atomic absorption spectrometry. The principal question addressed in this

report, therefore, is whether the second method

can complement the first by identifying potentially significant contaminants that have not yet been

detected in foods. Although this report indicates

that it can do so, it should be recognized that the

second method also is limited to some extent by

available analytical methodology. The factors we

can use to identify the potential of a chemical for

entering the food supply are selected on the basis

of a knowledge of the properties and environmental behavior of other chemicals already known to

do so. This in turn is based on our knowledge of

the extent of contamination and hence on our analytical capabilities. Thus, there is an inherent

bias towards identifying as potential food con177
178 ● Environmental Contaminants in Food

taminants those chemicals that are similar to in all systems for setting priorities: chemicals on

chemicals already identified in food. This bias which there is no information at all will automatican only be offset by the use of good scientific cally be given low priority, unless some room is

judgment. This point illustrates a general problem left for largely intuitive judgments,

CRITERIA AND METHODS USED IN PREVIOUS EFFORTS

TO ESTABLISH PRIORITIES AMONG TOXIC CHEMICALS

IN THE ENVIRONMENT

Survey of Toxic Chemical

Priority Lists

Thirty-two priority lists of toxic chemicals compiled during the last 5 years have been identified.

Most of these lists (28 out of 32) were prepared

for the Federal Government. For each list, a description sheet indicating the purpose of the list

and the criteria used in selecting chemicals was

prepared. In addition, the name of the list, the

Federal agency or other institution for which the

list was compiled, the date of completion, the contract or document number, type of substances,

the number of chemical substances, the means by

which the chemical was identified (for example,

CAS number or chemical name), whether the list

is machine readable, and relevant comments

were included.

Methods

Chemical Selection

Compiling a comprehensive list. The first step

in priority-setting efforts is usually compilation of

a comprehensive list defining the universe of

chemicals under consideration. Since chemical

compounds and mixtures are often referred to by

several different names, each chemical compound

on the comprehensive list should be uniquely identified. This can be done by specifying for each

chemical on the list the IUPAC chemical name,

synonyms, molecular structure, and/or the Chemical Abstracts Service (CAS) registry number. The

use of CAS numbers facilitates computerization.

Most often, the source of chemicals for this

comprehensive list is previously existing lists.

Errors of omission are likely with this method. A

chemical not considered previously will not be

considered by someone using existing lists as a

source, The more comprehensive the source lists,

the less likely chemicals are to be omitted from

consideration. An alternative method for selecting chemicals for consideration is reliance on

recommendations of experts. The likelihood of

errors of omission when this method is used will

depend on the extent of knowledge and experience of the experts. These methods can be combined by supplementing source lists with chemicals of concern to experts.

Reducing the size of the comprehensive list. It

is almost always necessary to reduce the size of

the comprehensive list before ranking. Since the

resources needed for compiling and evaluating

the necessary data for setting priorities are usually limited, a “narrowing” or “truncating” step

is performed. Errors are very likely to occur at

this step because, for practical reasons, decisions

at this stage are usually based on incomplete information, In a multistage priority selection

scheme, such as the one by which the TSCA Interagency Testing Committee selected chemicals to

recommend to the EPA Administrator for testing,

additional information is obtained at each stage

of reduction. In that effort, an initial listing of

3,650 substances was reduced to a master file of

1,700 substances, then to a preliminary list of 330

substances from which approximately 100 chemicals were selected for dossier preparation. Twenty-one chemicals or groups of chemicals from that

list have been designated for recommendation by

the committee. In this type of process, the earliest

stages may be the most subjective and the most

likely to result in errors of omission.

Grouping. Individual chemicals are often combined in groups or classes. This is usually done in

an attempt to reduce a list of chemicals to a more

manageable set, There are, however, other reasons for grouping. Some monitoring or analytical

techniques do not distinguish between closely related chemicals. Some classes of chemicals, such

as fluorocarbons, may be considered as a group

for regulatory purposes. Such chemicals as PCBs

are not manufactured or used as individual chemical compounds and are, therefore, nearly always

considered as a group. Groups can be based on

chemical and physical properties, on chemical
Appendix F—Priority Setting of TOXIC Substances for Guiding Monitoring Programs ● 179

structure, on uses (e.g., flame retardants, fluorescent brighteners), or on some combination of

these factors. Sometimes a single compound or

several compounds are selected as representative

of the group.

An advantage of grouping chemicals with similar structure or functional groups is that it sometimes allows chemical, physical, and biological

properties of individual compounds to be predicted. Members of a chemical class may behave

in a qualitatively similar fashion. In addition,

some properties increase or decrease systematically along homologous series. Attempts to derive

structure-activity correlations are much more

likely to be successful for chemical and physical

properties than for biological properties. Because

of some unique properties of biological systems,

such as enzyme specificity, it is possible for closely related chemical compounds, even such stereoisomers as aldrin, dieldrin, and endrin, to have

very different biological properties.

Some weaknesses associated with grouping

are:

●

●

●

Members of the group may vary widely with

respect to the factor being scored, making it

difficult or meaningless to assign a single

score to the group.

No single compound can truly represent an

entire class.

It is often difficult to assign compounds with

several different functional groups to a

single chemical class. This difficulty can

sometimes be overcome by computerized

substructure search systems that allow all

chemical compounds with a specific functional group to be retrieved regardless of the

presence or absence of other functional

groups.

At one stage of the National Science Foundation (NSF) Workshop Panel, multistage effort

grouping was done in an attempt to reduce the list

of chemicals to a more manageable set. Fourteen

chemical classes were defined, and a representative chemical was identified for each. Weaknesses the panel found to be associated with this

procedure included:

● The classes were not completely valid either

chemically or functionally.

● The physical and biological properties of

compounds in a given class varied widely.

● No single compound was truly representative of a class.

The class concept was abandoned in the next

stage of the effort and selected members were

considered as individual chemicals.

Determining Factors To Be

Considered in Setting Priorities

The purpose for which the list is to be used

must be clarified. Once the problem the priority

list is intended to solve is understood, factors relevant to that problem can be determined. Criteria

based on those factors can then be formulated for

assigning chemicals a place on the list. General

criteria must often be defined in terms of specific

parameters for which information is available.

Those parameters for which quantitative data

are readily available are the easiest to use for

scoring and ranking. On the other hand, data are

frequently lacking on the factors of greatest

relevance to the specific problem. In such cases

factors of less relevance may have to be selected.

The choice of factors to be used in setting priorities often involves a compromise between the factors that are most relevant and the factors on

which sufficient information is available.

Assembling Data on Each Chemical

Sound decisions on assignment of priorities

require reliable data on each chemical to be

ranked. The available information may, however,

be massive, contradictory, unverifiable, scanty,

or absent. It is usually difficult or impossible to

obtain existing information that has been classified as proprietary or confidential.

When information is needed on a large number

of chemicals and only a limited amount of time or

money is available for assembling data, secondary sources are usually relied on. Certain types of

information (e. g., annual production volume, LD~l~,

octanol-water partition coefficients) are often

tabulated in secondary sources. Other types of information (e.g., fate and transport in the environment, metabolic pathways) may be obtainable

only from primary reports of research studies.

These individual studies require considerable

time and effort to locate, obtain, and review. In a

multistage screening process, primary sources

may be used only in the last stage, when the number of chemicals has been reduced to a small portion of the comprehensive initial list. In a very limited effort, primary sources may not be used at

all.

Assigning Priorities

Two general methods used for assigning priorities to toxic chemicals are the ranking of individual chemicals [or classes) and the assigning of individual chemicals (or classes) to priority categories. Only 6 of the 32 lists surveyed are actually

ranked. In most of the other lists, chemicals were
180 ● Environmental Contaminants in Food

either assigned to a single “high priority” category or distributed among several priority level

categories.

Some numerical index or score is nearly always

used for ranking and often used for assigning

chemicals to priority level categories. When

chemicals are to be ranked solely by parameters

for which comparable quantitative information is

available (e.g., oral LDfO in the rat or annual production volume) these data can be used directly.

When the criteria for ranking cannot be defined

in terms of parameters for which comparable

quantitative information is available for all chemicals under consideration, chemicals are usually

assigned scores. Scoring is also usually used

when quantitative and nonquantitative factors

are jointly considered for ranking.

The scoring process involves assigning numerical values to one or more parameters to produce

an index or series of indices for each chemical. Indices can then be weighted and combined to produce a single score for each chemical,

Scoring can be totally subjective, totally objective, or somewhere in between, Subjective scoring

involves the use of experts to assign priorities.

The experts may be provided with information on

each chemical or may simply be asked for their

opinion. The credibility of subjective scoring will

depend on the perceived expertness of panel

members. Delphi techniques can be used to improve the validity or rankings, Scoring systems

based on the Delphi method rely on the development of consensus among experts acting independently or as part of a panel. In the NSF Workshop Panel effort to select organic compounds

hazardous to the environment, panel members

identified chemicals of concern on the basis of

their own experience and refined their judgments

by considering available data for production, imports, uses, disposal, and toxicity. Through successive examinations by panel members, individually and together, in progressively greater detail,

a priority list was developed. A weakness of such

subjective scoring methods is their probable lack

of reproducibility, which exists because different

experts would be likely to reach different conclusions, (However, we know of no investigation of

the reproducibility of such results in which different groups of experts were asked to assign scores

to the same chemical s.)

Where scores can be assigned to specific values of parameters for which quantitative information is available, objective scoring may be preferable. Often, however, modifying factors may make

the use of some degree of subjective judgment desirable in the assignment of scores even where

quantitative information is available. For example, the octanol-water partition coefficient can be

used as an index of bioaccumulation, but a more

sophisticated scoring system would consider such

other factors as chemical reactivity, metabolic

fate, and vapor pressure of the compound.

The human health hazard posed by a chemical

substance is a function of exposure to the substance and the inherent toxicity of the substance

itself. Scores for various exposure and toxicity

factors are usually combined for hazard-ranking

purposes, No consensus has yet been developed,

however, as to the optimum algorithm for hazard

ranking in this way.

Linear weighting schemes are efficient and

easy to use, and they have produced reasonable

results. These schemes rely on the assignment of

scores to a number of factors. Weights are assigned to each factor, and the weighted factor

scores are summed to produce an overall score

for the chemical. The choice of weight is usually a

subjective judgment, involving consideration of

both the importance of each factor and the reliability of the information used in assigning the

score.

Multiplication of individual factor scores provides a wider spread of overall scores, Multiplication is frequently used with actual unscored quantitative data. This is especially likely where some

of the data are in the form of fractions. For example, fraction of production lost would be multiplied by total production or fraction of dose absorbed would be multiplied by total administered

dose. Multiplication cannot be used unless some

correction is applied to allow for data gaps. In the

development of one list, an algorithm for toxicity

was applied which compensated for types of toxicities for which data were unavailable. The

scores actually assigned to a chemical for various

categories of toxicity were summed [T(total)]. The

maximum toxicity possible for each of these categories for which data were available were also

summed [T(possible)]. The ratio of these sums

[T(total) ÷ T(possible)] was used as the toxicity

factor in the hazard-ranking algorithm. The hazard-ranking algorithm used for ranking manufactured organic air pollutants was:
Append/x F— Priority Setting of TOXIC Substances for Guiding Monitoring Programs ● 181

In some cases the scores assigned to certain

factors are logarithms of data or are selected subjectively in such a way as to approximate logarithms. In such cases, addition of the scores

achieves the same result as multiplication of the

actual data. Weighting of the factors before addition then corresponds to changing the base of the

logarithm.

Criteria

The two general criteria used for assessments

of health hazard are exposure and toxicity. Previous efforts to set priorities among toxic chemicals

in the environment have been reviewed, and specific criteria used to assess the extent of exposure

to these chemicals or the toxicity of these chemicals have been considered.

Exposure

The three aspects of exposure that are of greatest importance in hazard ranking are the number

of people exposed, the frequency of exposure, and

the quantities of the chemical to which they are

exposed. Where direct information is available on

these exposure factors, e.g., from monitoring of

the ambient environment, of food, or of human tissue, it is obviously desirable to use this information. In most cases, however, we do not have direct information regarding the amount of a chemical to which members of a population are exposed, so that we must rely on indirect information, Several factors have been used, alone or in

combination, as surrogates for direct measures of

exposure.

Production.—The most commonly used index of

exposure is the annual production volume. Since

this information is quantitative, it is easy to use

for scoring or ranking. In most cases, production

volume does provide a rough indication of the

amount of a chemical substance potentially available for release into the environment. However,

the fraction actually released may vary over several orders of magnitude, from less than 0.001 for

well-contained industrial intermediates to 1 for

chemicals which are used dispersively.

For organic compounds produced by three or

more manufacturers and produced in volumes

greater than 5,000 lbs, production information is

compiled in the annual reports of the International Trade Commission and is easily available.

production information can sometimes also b e

found in other literature sources or obtained from

manufacturers or trade associations, but it is not

easy to acquire and will be missing for a large

number of chemicals. Production data for chemicals produced by less than three manufacturers

are considered proprietary. In the near future,

the EPA Toxic Inventory List, being prepared

under section 8 of the Toxic Substance Control

Act, may be a convenient source of production information, but at this time it is not clear how much

of this information will be released to the public.

In addition to annual production volume, data

on production capacity, transport volumes, imports, exports, net sales, or levels of consumption

may sometimes be available. A major problem

with using any of those figures as indices of environmental exposure is that these figures are

based on commercial production and sales. The

amounts of a chemical used as a captive intermediate are not included although such a chemical may be an occupational health hazard or a

neighborhood pollutant in the vicinity of the plant.

Very toxic and highly reactive chemicals are

often manufactured at the same plant in which

they are used. Manufacturing byproducts may

never enter commerce but because they are

waste products they are very likely to be released

to the environment in plant emissions and in effluents. Toxic chemicals formed in the environment (byproducts of microbial degradation or

photochemical reaction) also will not be reflected

in production figures.

For naturally occurring chemical substances,

such as heavy metals, the most relevant parameter is not production, but transfer from one compartment of the environment to another or conversion from one chemical or physical form to

another. Such transfers are measures of the increase in the amount of the substance converted

into a form in which it is potentially available for

human exposure.

Occurrence in the environment. Actual measurements of chemicals occurring in the environment are available for only a small number of substances. Federal agencies tend to monitor on a

regular basis only when required to by law. Air

pollution measurements are available for carbon

monoxide, total hydrocarbons, nitrogen oxides,

sulfur oxides, total suspended particulate, and

photochemical oxidants. Water pollution monitoring data are available primarily for pesticides,

PCBs, and heavy metals. Monitoring information

in Government data banks is often not retrievable

in readily usable form. There may be a timelag of

several years before a Federal agency summarizes, analyzes, and reports monitoring data. For

qualitative or quantitative data on occurrence in

the environment of chemicals not included in
182 ● Environmental Contaminants in Food

monitoring programs, it is necessary to search the

literature for individual studies. Since these

studies will usually report data for a small number of samplings at a limited number of locations

(often one), they are difficult to use as a basis for

the comparisons needed for ranking chemicals.

The number of reported incidents of environmental occurrence will often be a function of interest

in the compound rather than of actual frequency

of occurrence.

An advantage of using this type of information,

when available, is that it provides direct evidence

that the chemical is an environmental contaminant.

Use. Patterns of use can be very useful indicators of potential for human exposure. A greater

exposure risk is usually associated with dispersive uses than contained uses. Contained uses are

those in which the chemical is not systematically

released to the environment as a direct result of

use (e.g., PCBs in transformers). In dispersive

uses, chemicals are released to the environment

as a direct consequence of use (e.g., pesticides,

aerosols, and volatile solvents). The size of the

population at risk is usually greater for consumer

uses than for commercial or industrial uses. The

class of the use (e. g., food additive, pesticide, or

drug) will often determine which Federal agency

has regulatory responsibility for a chemical. The

use pattern will be a major determinant of the

type, frequency, and amount of human contact

with a chemical substance.

Unfortunately, accurate, complete, and up-todate use information is very difficult to acquire.

Many industrial uses are considered “proprietary. ” Uses can change rapidly so that information compiled in secondary sources is frequently

out of date. One problem encountered in using use

information is the difficulty of obtaining quantitative data. Since some uses are much more likely to

lead to human exposure than others, a quantitative breakdown of uses would be particularly valuable. Even when use data are available, it is important to realize that not all human exposure to

chemicals occurs during use. Exposure can also

occur during production, formulation, and disposal or after environmental transformation.

Release. The rate at which a chemical substance is released into the environment can be a

useful parameter in ranking toxic chemicals.

Chemicals that are found in effluents or emissions

are most likely to become environmental pollutants. Information on routes of entry of chemicals

into the environment can in certain cases be

essential to determining population exposure. In

1971 the sole U.S. producer of PCBs voluntarily

restricted sales to those for closed-system applications. They assumed that this would minimize risk to human health and the environment.

They overlooked the fact that most environmental

release of PCBs occurs, not through use, but

rather through disposal.

The quantity of a chemical released into the environment is usually unknown so that scores assigned for this factor must be based on estimates.

The “release rate” is an interesting index recently developed by the NSF Workshop Panel to

Select Organic Compounds Hazardous to the Environment. The release rate (R) was defined as follows:

where P = overall annual U.S. production

I = annual quantity imported

L = fraction of the production lost at plant site during

manufacturing, conversion, and formulation

D = fraction of the material which goes to nonintermediate dispersive uses

Estimates of L and D are usually semisubjective, based on knowledge of the manufacturing

process and on the likely breakdown of uses.

Environmental transport. A universal or widely

dispersed contaminant will usually be given

higher priority than a contaminant found only at

specific locations or a contaminant whose entry

into the environment results from a unique event

or sporadic events.

For a persistent chemical, the distinction between a local, widely dispersed, or universal contaminant may be a function of time. Unexpectedly

wide transport has been observed in recent years

for chemicals such as DDE and PCBs, PBBs entered the environment as a result of a single accidental occurrence and contaminated a small number of Michigan farms. Since these chemicals are

persistent and have entered the soil, water, and

food supply, they will continue to disperse.

Substances that appear to be relatively innocuous or inert at their point of release may be transported to segments of the environment where they

have significant adverse effects. Useful models

for the reliable prediction of the movement of

chemicals in the environment would be extremely

valuable for setting priorities among toxic chemicals for purposes of monitoring, control, or regulation. Such information would also be valuable in

determining which segments of the environment

should be monitored or controlled. Unfortunately,

although models are available for problems such

as plume dispersion for stack emissions, there are

no generally accepted, easy to apply, widely used
Appendix F—Priority Setting of Toxic Substances for Guiding Monitoring Programs ● 183

models for environmental transport. Moreover,

realistic models of environmental transport are

usually extremely complex, and it is impracticable to use them in priority-setting exercises.

Persistence. Chemicals can be transformed and

degraded in the environment through chemical,

photochemical, or microbial processes. The relative importance of these processes will be influenced by the compartment of the environment

with which we are primarily concerned. Reactions leading to simpler compounds which are

part of a series leading ultimately to the free elements or elemental oxides are considered to represent “degradation,” Other reactions lead to

‘‘secondary pollutants.

Persistent chemicals are often given priority

over easily degraded or transformed chemicals in

hazard assessment systems, on the assumption

that persistent chemicals are more likely to

spread through the environment and will continue

to accumulate as long as they are released. When

persistence is used as a criterion for hazard

assessment, it is important to be aware, however,

that there are cases in which degradation products or secondary pollutants are more toxic than

the chemical substances initially released,

Biodegradability. Although all living things can

play a role in transformation of chemicals in the

environment, the lead role is attributed to microorganisms. The role of micro-organisms in transforming chemicals is extremely important in the

lithosphere and also important in the hydrosphere. Micro-organisms are frequently efficient

at metabolizing natural chemicals in their environment. Industrial chemicals are inherently less

likely to be rapidly degraded by micro-organisms.

Parameters often used as indices of biodegradability are the biochemical oxygen demand (BOD)

or chemical oxygen demand (COD), Estimates of

biodegradability can sometimes be based on

chemical structure.

Chemical reactivity. The assessment of the

chemical reactivity of a compound is often based

on known physical and chemical properties such

as:

●

●

●

●

●

●

b

●

physical state,

vapor pressure,

solubilities,

auto-oxidation propensity,

redox potential,

acid-base characteristics,

rate of hydrolysis, and

rate of photochemical degradation.

One parameter which can-be used for persistence in the environment is half-life, the time required for removal of half of the molecules of a

given compound from the environment or from a

specific compartment of the environment. Halflife in the atmosphere, for example, would be a

function of such properties as photoreactivity,

reactivity towards active forms of oxygen, water

volubility, volatility, and adsorption to fine particulate .

Bioaccumulation. Bioaccumulation can be defined as the long-term presence of a xenobiotic

substance in living tissue at concentrations significantly higher than those in the surrounding environment. Chemicals that bioaccumulate are

often given priority over other chemicals in hazard-assessment schemes. Concentrations of chemicals that bioaccumulate are likely to increase

along a food chain, a process referred to as “biomagnification. ” For such chemicals, residue

levels tend to be higher in herbivorous animals

than in plants, higher in carnivorous animals than

in herbivores, and highest in carnivores that eat

other carnivores. Since humans may eat organisms in any of these categories and since chemicals which bioaccumulate will usually be stored

in human tissues, if such chemicals have any toxic

properties they may pose a higher risk to human

health than would be predicted on the basis of environmental concentrations alone.

Since bioaccumulation is often associated with

a high lipid volubility relative to water volubility,

the partition coefficient can be used as an indicator of the tendency to bioaccumulate. The partition coefficient is a measure of the distribution of

a solute between two immiscible liquid phases in

which it is soluble. For a single molecular species,

the partition coefficient is a constant and does not

depend on relative volumes of solutions used. The

most commonly used coefficient indicates relative

volubility in organic and aqueous phases, providing information on the hydrophobic or hydrophilic

nature of the compound.

Although absorption and accumulation of toxic

pollutants are related to their partition coefficients, partition coefficient alone does not determine bioaccumulation. Other characteristics of

the chemical (reactivity, vapor pressure) and of

the organism (metabolic pathways, nutritional

status, fat content of body tissue) will also influence the extent of bioaccumulation. Active accumulation of a substance that resembles another

chemical is frequently predictable from the properties and structures of both,

For inorganic compounds relative volubility is

not the primary factor in determining extent of

storage in body tissues. Passive accumulation

r .- II - “ 1 - 1 ‘,
184 w Environmental Contaminants in Food

through formation of complexes with organic

ligands, especially those containing sulfhydryl

and amine groups, can also occur. The synthetic

compounds most likely to accumulate in this way

are organometallic chemicals. The tendency of a

chemical to accumulate in this way can be predicted from knowledge of the likelihood of the

chemical to form complexes with natural bases.

Population at risk. The size or type of population exposed may be considered as a factor in setting priorities for toxic chemicals. Types of populations at risk could be:

● the general human population,

Q population of a geographical region,

“ population of a specific neighborhood,

● population in the immediate vicinity of an industrial plant,

● people whose diets contain a high amount of

particular foods,

● occupational groups, and

● highly susceptible groups.

Population groups can be further classified according to whether their exposure is voluntary or

involuntary. Priority considerations should be

given to chemicals to which there is extensive involuntary public exposure or to which susceptible

segments of the population are exposed. Some

ranking schemes consider certain segments of the

population more ‘‘valuable’ than others (e.g., the

young more “valuable" than the old). This approach is highly subjective and ethically questionable.

Toxicity

The toxicity of a chemical is the second determinant of hazard. The difficulties encountered in

estimating the biological activity of a chemical

are as severe as those encountered in estimating

exposure. Here we find ourselves at ‘‘the frontiers of scientific knowledge” in attempting to

evaluate the significance of laboratory data for

human experience.

Most priority-setting efforts have scored chemicals on a series of toxic effects, There are, however, some general indices of toxicity, such as the

threshold limit values for atmospheric exposure

in the workplace established by the U.S. Department of Labor and the American Council of Governmental and Industrial Hygienists, tolerance

levels for pesticides in food set by EPA, or “action

levels’” for food contaminants set by FDA. These

indices are based on reviews of a range of toxicity

data and represent attempts to identify threshold

levels for hazard or for lack of assurance of safety. Although the reliability of such indices as

precise measures of degrees of hazard is debatable, where available they are useful in prioritysetting exercises because they represent an attempt to weigh all toxicity data available at the

time when they were established.

Metabolic factors.

1. Uptake and absorption.—Even if the amounts

2.

3.

to which people ‘may be exposed could be

determined, we still would not know the

amount that could be expected to enter the

human body and cause biological damages.

The term “penetrability” is sometimes used

to represent that portion of the chemical to

which the person is exposed that is expected

to be absorbed into the body, This factor includes consideration of both the routes of exposure and the fraction of the chemical absorbed after exposure by each route,

Biotransformation. -The metabolic conversion of a chemical within the human body

should be considered, as far as possible, in

assessing potential health effects. A chemical can be detoxified, activated, or converted

to a compound with different biological properties. The metabolic pathway can be dosedependent.

Elimination. —The turnover rate in th e

human body can be an important factor in

assessing biological effects. If, however, a

chemical has been scored for bioaccumulation as an exposure factor, it may not be necessary for it to be scored for turnover in

humans, as these factors are closely related,

Absorption, bioconversion, and elimination are

complex factors and are difficult to handle for

ranking purposes, Information is not readily

available and is rarely compiled in easy-to-use

secondary sources. For many chemicals, no metabolic information is available. When metabolic

studies are found, they are often reported in

qualitative rather than quantitative form. Relating metabolic information to adverse health effects often requires a high level of expertise in

toxicology. Despite all these problems, a toxicological ranking system which takes into account

these metabolic factors is more sophisticated

than and usually superior to a system which does

not,

Acute toxicity. The biological effect of a chemical depends on the quantity of the chemical with

which the organism must deal, Chemicals having

adverse effects at low dosage would be considered more toxic than chemicals having similar effects only at much higher dose levels. It is difficult

to perform this ranking at low effect levels. The
Append/x F—Priority Setting of TOXIC Substances for Guiding Monitoring Programs ● 185

effects of low dosages are often subtle. Direct experimental estimation of the level affecting 1 percent of the population may require several hundred animals to obtain adequate statistical precision. For these reasons, lethal dosage levels are

usually used in ranking chemicals for acute toxic i t y.

A common parameter of acute toxicity is the

animals would die. To be comparable, results

should be based on animals of the same species,

strain, sex, and age. The same route of administ ration should be used.

Other commonly used parameters of acute toxicity based on lethal doses are:

LC-,(; =

LD, ,, =

LC,,, =

the concentration which is lethal to half

the test population. The duration of exposure should be specified. LC is usually used for concentration in air, but

can also be used for concentration in

the ambient water to which aquatic organisms are exposed

the lowest reported lethal dose

the lowest reported lethal concentration

Available data on these parameters for 16,500

different chemicals are summarized in the Registry of Toxic Effects of Chemical Substances pub -

lished by NIOSH. The major objection to acute

lethality as a basis for ranking environmental

contaminants is that the acute lethal doses are

very much higher than those levels one would expect to find in the environment. Furthermore,

values for acute lethality can vary widely between species. Use of this parameter can be justified, however, on the basis that the LD-),, is at least

a crude index of biological activity. It is reasonable to consider a chemical w i t h a very low LD,(, to

be a relatively toxic chemical. on the other hand,

a chemical with a high LD,,, is not necessarily

safe, since long-term exposure a t low concentrations may have such adverse effects as carcinogenicity or damage to the reproductive system.

Data on acute toxic effects other than lethality

are less frequently compiled, are more difficult to

use for ranking purposes since they arc not usually reported in numerical form, and may not be indicative of effects occurring at the low dosage

levels ordinarily found in the environment. Nevertheless, nonlethal acute effects can provide useful

information about target organs and should be

considered as part of the overall picture when

subjective judgments are made.

Carcinogenicity. In principle, it would be useful

to categorize chemicals as strongly carcinogenic,

moderately carcinogenic, weakly carcinogenic,

co-carcinogenic, or having no neoplastic effects.

There is usually not enough information available, however, to do this. Dose-response curves

are rarely determined for carcinogens. Negative

results in carcinogenicity tests are usually not accepted as proof of noncarcinogenicity. Comparisons between carcinogenic “potency’ of various

chemicals have been made on the basis of percent age of a test population developing malignant

tumors, the number or types of species in which

positive results have been reported, the types of

tumors observed, the lowest dosage causing malignancy, or the lag time between administration

of chemical and observation of tumors.

Chemicals are sometimes classified with respect to the degree of certainty of their carcinogenicity (e. g., known carcinogen or suspected carcinogen). EPA has recently attempted to order the

NIOSH list of suspected carcinogens according to

the relative degree of concern that might be warranted regarding possible human carcinogenic

potential. A four-digit code was used. The first

digit represented the species in which carcinogenic response was reported. The second digit

designated the number of different species for

which a carcinogenic response was reported. The

third digit was assigned on the basis of route of

administration. The last digit was a count of the

number of different species-route combinations.

The most complete source of data and references related to chemical carcinogenesis is the

Public Health Service’s Survey of Compound s

Which Have Been Tested for Carcinogenic Activity. A master index of the series is maintained on

tape at the National Cancer Institute headquarters.

Evaluations of carcinogenic risk are made by

the International Agency for Research on Cancer

under the auspices of the World Health Organization. They do not use a formal ranking system.

Mutagenicity, A mutation is defined as any heritable change in genetic material. The results of

mutations are usually undesirable and may include abortion, congenital anomaly, genetic disease, lowered resistance to disease, decreased

lifespan, infertility, mental retardation, senility,

or cancer.

The reliability and accuracy of the prediction

of mutagenicity in man from the ability of a chemical to produce mutations in experimental tests

systems is controversial. Many types of tests are

currently available for use as indicators of mutagenic potential. Some (e. g., the Ames test, the

dominant lethal test) are actual tests for mutage-
186 ● Environmental Contaminants in Food

nicity. Others test for a variety of events relating

to, or at least correlated with, mutagenesis. Some

such tests are for chromosome aberrations, DNA

damage or repair, increased rate of sister chromatid exchange, or other phenomena considered

to be relevant to mutagenic potential. Because

even those tests that actually demonstrate mutagenicity are highly specific for detecting a single

type of mutation, results of a battery of tests are

desirable for an evaluation of mutagenic potential

of a chemical substance,

Structure-activity relationships have met with

limited success in prediction of mutagenicity.

Many chemical mutagens (but not all) act as electrophiles permitting a prediction of mutagenic potential of compounds that might form a reactive

electrophilic species.

Many difficulties are encountered in extrapolating to man results obtained in microbial, mammalian cell culture, or test animal systems. Potential for mutagenic effects in man should be assessed only after results of testing in various experimental systems are considered in conjunction

with other relevant factors such as chemical

structure, biochemical activity, and metabolism

in man.

Teratogenicity. Certain chemicals, when administered to a pregnant female, can interfere at

a critical stage of embryogenesis or organogenesis and can cause embryonic death or malformation, A chemical with such properties is a teratogen. Testing for teratogenicity should ideally involve administration of the test substance only at

the period critical for organogenesis of the system

sensitive to the teratogen. Sensitive periods of organogenesis are characteristic of particular

chemical teratogens.

At the present time, only tests in pregnant

mammals are generally accepted by scientists

and regulatory agencies as valid tests for teratogenicity, because the maternal-placental embryonic relationship cannot be duplicated in submammalian test systems. Other test systems

sometimes used as indicators of teratogenic potential include bacteria and other unicellular

organisms, somatic cells in culture, tissue culture,

organ culture, intact invertebrate embryos, cultured mammalian embryos, and incubating chick

embryos. Of these systems, chicks and to a lesser

extent fish are the most widely used,

It is difficult to rank chemicals on the basis of

teratogenic potency. The type of dose-response

data needed for quantification of teratogenic risk

is seldom available. Interspecies extrapolation is

poorly understood. There is an enormous range of

variability of teratological end points. Chemical

structure has been found to be of little use in

predicting teratogenicity.

Other toxic effects.

1, Effects observed in humans, —Reports of tox2.

. .

ic effects in humans can be based on epidemiological or clinical observations. There

are severe problems in interpreting this type

of information. Humans are rarely exposed

to only a single chemical substance, It is

usually difficult to find control groups with

zero exposure to an environmental contaminant. Results based on occupational exposure may underestimate risk, because susceptible segments of the population (infants,

children, the aged, the chronically ill) are excluded from the workplace. When workers

become sick they often stop working and are

no longer part of the occupational cohort.

Another problem in interpreting human data

is that the doses are often unknown.

Chronic toxicity, —Biological effects of a

chemical administered in low doses over an

extended period of time may be quite different from acute effects. Chronic exposure

test protocols are more relevant than are

acute protocols to the types of exposure due

to environmental contaminants.

Because of the wide range of end points

observed during chronic exposure tests,

comparisons are difficult to make. Comparing one type of effect with another (for example, comparing impaired fertility with liver

damage) on the basis of severity is highly

subjective. Ranking chemicals on the basis of

chronic toxicity therefore requires a high

level of scientific expertise.
Appendix G

Approaches to Monitoring Organic

Environmental Contaminants in Food*

by John L. Laseter, Ph.D.

INTRODUCTION

Trace quantities of potentially toxic organic

compounds are frequently found in the environment. These compounds sometimes possess properties that may have teratogenic, mutagenic, and

even carcinogenic effects on humans and animals. Some of the compounds, such as pesticides,

have been intentionally released into the environment (1), while others have found their way into

the environment by accident, through carelessness, or as byproducts of industrial processes.

Many of these compounds are subject to breakdown in the environment as a result of both physiochemical and biological processes, such as

chemical weathering, photodecomposition, metabolism, and biodegradation by micro-organisms

(1,2). In many cases, it is not uncommon for the

breakdown products to have greater health effects on humans and animals, than the parent

compounds.

Because of the potentially toxic properties of so

many of these compounds and their breakdown

products, several pieces of Federal legislation

have been enacted in recent years to monitor,

evaluate, and control the amounts of the pollutants in order to protect our health and environment. As a result, monitoring] (screening) programs have been established for many types of organic pollutants in the environment. All of these

programs rely heavily on the ability of analysts to

correctly identify and quantify these compounds

at the parts per million (ppm) and parts per billion

(ppb) levels in a variety of sample matrices (3). In

order to successfully obtain useful information a t

these concentration levels, it is essential tha t

methods which are sensitive and selective be de -

veloped and used. Whatever method is ultimately

* ~~t)r purp{)st’s of this (i[)fwmont. fl)()[l r(?pr(w}nts ,ill st)ll(i,

sf)m IS(JI i(i, ;I n(i IICIII i[i forms of f{)()[i pro(iu{ts. including I)l)t t I[v I

w,1 t [’r, ( t )Ils u m[ x ] I]v m:] n.

“I I1(! t[’rms ‘‘m{ Im t I ) r I n:” :] n(i ‘‘ S( rm’n i n~” ;I rc usmi in t (>r-

( il(i nq(’,~l)ii I n t il is (iIJ{ L]m(’n t.

selected, it is imperative that it provide unequivocal results.

Most methods for monitoring and for the analysis for trace levels of organic pollutants in the environment necessarily consist of several steps <

These include sample collection and storage, sample workup, and component identification and

quantification.

The collection and storage of samples is an important phase of an analytical method if meaningful interpretation of the data obtained is to be

achieved. The sample selected for analysis must

be representative of the whole system being examined, and must be free of contamination due to

improper collection and handling techniques.

Once collected, the samples must be stored under

conditions that will reduce or eliminate changes

in their composition.

Another important phase in an analytical

method is the sample workup. During this stage,

the sample usually undergoes an extraction process whereby the compounds of interest are removed from the sample matrix. Organic solvents,

and in some cases inert gases, are usually employed in the extraction process. Because the extraction process is seldom very selective, many

organic compounds in addition to those of interest

are also extracted. In order to reduce the

amounts of these other compounds that may interfere with the analysis, a sample cleanup procedure usually follows the extraction process.

The last and most difficult phase of an analytical method is the identification and quantification

stage. The identification process is often accomplished by comparison of the physical and chemical properties of the unknown compound against

the same properties of an authentic standard

compound. For complete unknowns, the identification process can be very difficult. The quantification process can only be accomplished after the

unknown compound has been identified and usu187
188 ● Environmental Contaminants in Food

ally involves comparison of the detector response

for the compound of interest against the detector

response for known quantities of an authentic

standard.

In the analysis for trace levels2 of organic compounds in the environment, it is often very difficult to obtain accurate and reliable qualitative as

well as quantitative results. This is evident by the

countless examples in the literature of errors in

both qualitative identifications and quantitative

estimations of trace quantities of many organic

compounds in the environment (5).

Of the many methods currently available for

the qualitative identification and quantification of

organic compounds, few are sensitive and specific enough for meaningful trace analysis. Table

G-1 summarizes the techniques for organic analysis and some of their advantages and disadvantages (4,6).

The most common techniques in use for trace

organic analysis are gas chromatography with

the use of selective detectors (7) such as the electron capture (EC). Hall electrolytic conductivity,

and flame photometric detectors; high performance liquid chromatography (HPLC) (8); and combined gas chromatography-mass spectrometry

(GC-MS). Selective detectors for gas chromatography are necessary because environmental

samples are often very complex and the selectivity of the detectors simplifies the analysis by

allowing only certain compound classes to be detected at any one time. The most powerful of these

techniques is the GC-MS technique (4,6,9-1 1),

since it not only provides qualitative information

of nanogram quantities of single compounds present in the sample, but also provides information

which can be used for quantification of individual

components in the sample.

A more recent technique involves the combination of liquid chromatography and mass spectromE’Or purposes Of this II[)fument, ‘‘~ rare levels” is df?finfxi [ls a

ronccn tr(] t ion helt)w lhf’ IOU p{] rts-pcr-m ill ion level. I)ctf?rtion

at these rf)nrcnt r{) t ions is import;lnt he(tius[! m:inv org:]nirs

arc biologir{i 1 Ii’ ~] (’ t ivc even :] t t hf: pa rts-pf!r-t rl I lion If?vel.

etry (12-14). This technique expands the area of

trace organic analysis to the identification and

quantification of compounds that are not suitable

for analysis by gas chromatographic techniques.

Table G-1 .—Techniques Available for Qualitative

and Quantitative Organic Analysis

detection Specificity or

common uses

Detects most

compounds

Halides, conjugated

carbonyls. nit riles. diand trisulfides

Phosphorus, sulfur

Nitrogen, phosphorus

Compound type

determination

Classical functionality

determination

Sulfur, nitrogen,

halogens

Best for complete

identification,

molecular weight

structure, and

function Confirm any

compound
Append/x G—Approaches to Monitoring Organic Environmental Contaminants in Food ● 189

ANALYSIS FOR EPA PRIORITY POLLUTANTS

IN FOODS AND WATER

The recent EPA/NRDC consent decree estab- food samples. An estimate of the space, manlished an analytical procedure for the analysis of

129 priority pollutants (chemical indicators of organic pollution) in industrial waste water (1 5). Of

these, 15 pollutants are metal, with the remainder

being individual organic compounds and compound classes. The procedure for the analysis of

the organics is strictly a GC-MS computer method

designed to provide qualitative as well as quantitative information about the presence of the

priority pollutants in waste waters.

Basically, the procedure requires that fou r

separate analyses be performed on the sample.

These are an analysis for the more volatile orpower, and cost associated with the analysis of

the present 114 organic EPA priority pollutants in

food and water samples is given in table G-2. It

should be pointed out that considerable research

and development effort must be expended to

adopt the methods proposed to foods in general.

Figure G-1 .—A Simplified Diagram for the

Qualitative and Quantitative Analysis of

the Organic EPA Priority Pollutants

involve liquid-liquid extractions, and subsequent NOTES
190 ● Environmental Contaminants in Food

Table G-2.—Estimated Space, Manpower, and Cost Associated With the Analysis of

Priority Pollutants in Tissue and Water Samples

According to EPA Analytical Protocola

Category Response and/or cost

A. Instrumentation . . . . . . . . . . . GC-MS data system with automated Iiquid injection

device.

-$200,000 each

B. Space. . . . . . . . . . . . . . . . . . . . 1,500 ft2 equipped with typicalb laboratory facilities and

furniture including adequate air-conditioning.

C. Downtime for instrumentation 30% (this figure can vary from 20 to 50% as a function of

staff experience and logistics support).

D. Minimum assignable . . . . . . . Ph. D or equivalent - 1

manpower M.S. or equivalent - 1

B.S. or equivalent - 2

Total 4C

Estimated operational cost per routine sample -$2,000 to $2,500 (Scheme One as illustrated in

figure G-l).

Estimated operational cost per routine sample -$2,500 to $3,000 (Scheme Two as illustrated

in figure G-2, as a function of cleanup difficulty).

a It , ~ a~~umed t-hat the laboratory ha~-~ther ~n~~ing actlvlt Ies and further that samples would be analyzed on Iy once and In

succession The ultimate size and cost of such a monitoring faclllty IS based on processing only a few hundred samples per

year No capital costs are calculated Into the operational cost per sample

bTyplcal laboratory facllltles and furniture Include laboratory benches tables with sinks shelves for rea9ents and equl Pment.

vented hoods, refrigerators, laboratory balances and scales, pH meters, hot plates, laboratory glassware, c hem Ical, etc This

Includes special toxic chemical and carcinogen processing fac I I ltles Laboratory space of the type desc rlbed dbOW cost on

the order of $lOO/ft Z

CManpower requ ,rements are not Included for maintenance and 1091Stlc suPPort

SCREENING FOR UNSPECIFIED POTENTIALLY TOXIC

COMPOUNDS AND CHEMICAL CLASSES IN FOOD AND WATER

There is a possibility that other compounds or

classes of compounds not included in the EPA

priority pollutants list will find their way into the

environment. For this reason, it is essential that

some form of monitoring system be established

that will look for the appearance of particular

compounds or classes of compounds in food and

water over a period of time. A recent National

Research Council report on environmental monitoring (20) recommends the establishment of new

monitoring programs to anticipate pollution problems and to discover environmental pollutants in

their early stages of development so that appropriate corrective measures can be implemented before the problem becomes unmanageable, or worse, irreversible. A typical monitoring

program is the EPA Mussel Watch Program (2 I),

the EPA National Pesticide Monitoring Program,

and the National Pesticide Monitoring Network

for Birds operated by the U.S. Fish and Wildlife

Service.

In establishing a monitoring program, the type

of compounds to be monitored would be selected

as candidate compounds on the basis of their

chemical class, their use, and their suspected toxicity, These candidate compounds might include

steroids, phenols, amines, halogenated organics,

polynuclear aromatic hydrocarbons, and any

newly appearing organic that illustrates a

marked increase in concentration over a period of

time.

The monitoring program design would involve

the establishment of appropriate sampling and

sample-handling guidelines, together with the

modification of currently used analytical procedures to include the new compounds or classes

of compounds. A typical monitoring program

would involve the use of high-resolution gas

chromatographic techniques using the universal

flame ionization detector (FID) capable of detecting traces of known candidate compounds, and

computer techniques that allow for rapid comparisons of samples to establish trends. With the

use of high-resolution gas chromatography (employing glass capillary columns”), one can readily

separate in an environmentally derived sample,
Appendix G—Approaches to Monitoring Organ/c Environmental Contaminants in Food . 191

several hundred organic species, the vast majority of which have not been characterized.

The analytical program would involve a preliminary screening to establish baseline levels of the

candidate compounds in samples of foods and

water, or selected indicator species over a given

period of time, followed by periodic screening of

similar samples to determine changes or trends

with time. If alarming trends are observed, corrective actions and measures can be implemented.

Of the techniques available for analysis, the

methods best suited for the class or classes of

compounds under consideration would be selected for routine monitoring. These would include high-resolution gas chromatography or

high-performance liquid chromatography and

supporting computer methods which would include the use of internal and external standards,

and use of pattern recognition techniques. 5 T h e

monitoring would be set at a concentration level

below the actual legal accepted 1evel (for example, 0.01 ppm or one-tenth of the action level if it is

known),

Should the screening result in an observation of

an increase in levels of either unknown or selected compounds or classes of compounds, suggesting the entry into the food or water of new

materials, additional analytical efforts would be

employed to attempt characterization of the new

compound(s) observed. Preliminary information

would be transmitted to associated toxicologists

for evaluation and comparison with information

available on known toxic compounds.

LABORATORY REQUIREMENTS

Because organic analysis at the submicrogram

(ppm and ppb) levels is a complicated and difficult

process requiring sophisticated instrumentation

and expertise, the laboratory selected to perform

analyses for trace organics in foods and water

must be equipped with state-of-the art technology

and experienced personnel. The best setting for

such a laboratory is in a location where it can

establish ties with the R&D community where experts in a variety of disciplines can be found who

can serve and participate as consultants at various levels. It should be pointed out that analytical

techniques may require modifications to upgrade

the technology and a substantial expenditure of

funds to keep the program operating at maximum

efficiency and information output.

The typical nationwide monitoring program

would have several regional centers, each wellequipped with the appropriate instrumentation

and personnel to perform the analyses and conduct the program. In addition each center would

have a review board composed of senior scientific

personnel in such fields as toxicology, analytical

chemistry, environmental chemistry, etc., to assess and interpret the data developed. To facilitate the handling of all the data acquired, each

center would be equipped with data-archiving facilities for both GC, LC, and GC-MS data and dataprocessing methods that would allow for rapid retrieval, comparison, and evaluation of these data,

Some of these data-handling techniques are now

available and others are under development

(23-26] for such a central data management system (see table G-3). Figure G-3 illustrates a proposed analytical scheme to monitor for the appearance of unknown organics in addition to the

current EPA priority pollutants in food and water

samples.

In support of the nationwide monitoring program would be a quality control laboratory which

would coordinate intercenter calibrations, and

would spot-check and confirm selected data developed by the regional laboratories. Of necessity, the quality control laboratory would be better

equipped than the regional centers, so that it

could resolve the problems and issues that can occur during routine analyses. A minimum of 10 percent of all samples analyzed by the regional centers would be confirmed by the quality control

laboratory, Additionally, a library of samples

used in the actual analytical studies would be

stored for future reference.
192 “ Environmental Contaminants in Food

Table G-3.—Estimated Space, Manpower, and Cost

Associated With the Monitoring of Unknown

Potentially Toxic Compounds in Addition to

the EPA Priority Pollutants

Category

A Instrumentation

B Space

C Downtime for

Instrumentation

D Minimum

assignable

manpower

E Estimated

operational cost

per routine

sampIe

a

b

c

d

(?

Response and/or cost

Small, high throughput

GC-MS data-system with

automated Iiquid injected device

-$50,000.

El/Cl-equipped high-resolution

MS-data system with automated injection device -$200,000 to

$300,000

GC-FID-EC system $15,000 (additional chromatographic systems

may be required).

LC Interfaced into MS system

-$20,000

Central data management system

Figure G-3.—General Analytical Scheme To Detect

and Monitor New Trace Organics and Priority

Pollutants in Food and Water Samples

I

I I

I r,

I

I z i ~ratl ,n

~

NOTES

1 A vdrlel} of f r,+c I Ionat 1011 .in[j I>oldl ion pro( (>(1 (J ret

t ion to I Ia u I(i I I(I u Id ex t rdc t Ion
Appendix G—Approaches to Monitoring Organic Environmental Contaminants in Food ● 193

DEVELOPMENTS THAT WILL IMPACT

LOW CONCENTRATION ORGANIC MONITORING

Of all the developments in technology for chem- (FT-IR) detectors; and 3) developments in comical analysis, those which will have a greater im- puter system software capable of handling maspact on monitoring programs are the following: sive volumes of chromatographic as well as mass

1 ) developments in mass spectrometry instrumen- spectrometric data of the type obtained in a monitation, such as pulsed positive-negative chemical toring program. Developments in other methods

ionization and detection techniques; 2) develop- such as electrochemical techniques and plasma

ments in selective detectors for gas chromatogra- chromatography show some promise for trace orphy and liquid chromatography, such as atomic ganic monitoring, but will only be useful if they

absorption (AA) and atomic fluorescence (AF) can be coupled to GC or LC systems.

spectrometry, and Fourier transform-infrared

ACKNOWLEDGEMENTS

The technical assistance and cooperation of 1. FDA and EPA and Mr. R. Finnigan, of Finnigan

R. DeLeon and the help of D, Trernbley in prepar- Corpora t ion, for their helpful technical discusing this manuscript is gratefully acknowledged. sions.

The author also mishes to thank the personnel of

SELECTED REFERENCES

6.

7.

8.

9.

1 (),

11.

4’2, 3 ( 1978).

15. U.S. Envi ronmen t{]) Pr[)tert i[)n AgencP’, ‘‘Sampling

and A II;] lYIS is Procedu r [?s f( )r S r re[?ni n~ I ndus t r i:] I

Efflut?nts for Prioritl’ Pollutants,”” ( ;in(innnti, ohio”

(Revised, April 1977).

16. 1. R. Poli tzer, S. Gi t hens, B, J, L)(Iw tk, and J. 1,. 1,asetf;r, ]. (l]r~)m(lt[)~r. Sci., 13, 378 ( 1 975).

17. B, J. Dowtpr, 1., E, (;ret;n, :]nd J. L. L{]set[?r, AIIIII

(;hem., 48, 947( 1976].

18. I. R. Poli tzer, B. J. Ilowtl, :ind J. 1,. I,[]s[?t(!r,(linic[rl

(;hf?m., 22, 1775( 1976).

19. I). L\’. Kuehl, An(l). f;hem., 50, 182 ( 1978).

20. “‘Environmental hioni torirl~, ~’(llllm(l IL’, N:) t ion:]l

A(:adem; of Scien(:c?s, [\’[lshing ton. ]]. (;., pp. 6- 8

( 1977).

21. E. I). (j[)ldhf:rg, ~’ ‘l’. 130wen, J. bf’. F’a rrington. (;,

Htlrvey, J. 11. hlartin, p l,. p:] rkcr, ~. P\’. Riset)rough, W“, Robertson, E. S(:hnci(i[?r, an(i E. (;aml)l(~.

Fl]iiron, CI)ns(>rv. 5, 1 ( 1978).

22. ‘1’. L. Iserlhour, H. R. Kow[llski, and P. (;, Jurs, (;li(;

(Jritic(ll }ICJ in An~lJ (jh[~m, (July 1974).

23. E. B. Ov[?rton, (1. F’, Steele, and J. 1,, Las(?ter, ‘ ‘Improved Data Prwx?ssing Software fur (;1:{ss (;iipillar~ Separ~]ti(Jn of (;omplf?x Erliir(]rlnl[?rlt:l! S;lmpies, ” Pittsl)ur~h (h)nf[?r~?nc[? F’t;h. 27-hli~r. :3, 1978,

(;level:~n(i, ohio.” 22,

24. 1. I{. Suffet :ln(i E. R. (jl;]s(?r, /, ( ;h r~)rn~l t{),gr. .${i,, 1 (;,

12 ( 1978),

25.1. t!’. h:]r[~sok.. ln~lut(ri(~l R ‘/1, ,20, 113 (April 1978).

~ [j. J-:. 13. ( )v(lr t on, (;, F. S I (?(?1 [?. i 111( i J. 1,. 1,:] s[; t [: r, J. H i v 1)

H(~t{)l~l [](~n (;lll~)r]lflff)gz{]]~llk (sul)mitt[”(i 1 978].
194 ● Environmental Contaminants in Food

GLOSSARY OF ABBREVIATIONS AND TERMS USED

Abbreviations

AA—atomic absorption

AF—atomic fluorescence

CI—chemical ionization

DS—data system

EC—electron capture

EI—electron impact

FID—flame ionization detector

FT-IR-Fourier transform infrared

GC—gas chromatography

GC-MS--combined gas chromatography-mass

spectrometry

HPLC--high performance liquid chromatography

LC—liquid chromatography

LC-MS--combined liquid chromatography-mass

spectrometry

MS—mass spectrometry

TLC--thin-layer chromatography

UV—ultraviolet

Terms

Atomic Absorption Spectrometry—a form of spectrochemical analysis usually applied to the determination of the elements. The sample is heated to a relatively high temperature to cause dissociation of the

chemical compounds into atoms. A source of radiation characteristic of the element to be determined is

passed through the sample. If the sample contains

the element, absorption of the radiation by the sample atoms occurs and the amount of absorption can

be measured for quantitative determinations.

Atomic Fluorescence Spectrometry—a form of spectrochemical analysis usually applied to many organic

compounds and some inorganic compounds which

emit radiation energy after they have first absorbed

radiant energy of a particular frequency. The simplest form of AF is the fluorescence provided by a

monoatomic vapor, such as sodium.

Chemical Ionization—a method for ionizing samples for

mass spectrometric analysis. The ionization of the

sample results from the reaction between the sample

molecules and low-velocity reagent ions which results in the transfer of a charged species other than

an electron.

Electron Capture Detector—a very sensitive and selective detector for gas chromatography. This detector

responds to the presence of a variety of compounds

containing atoms with an affinity for electrons, such

as the halogens--chlorine, bromine, and fluorine—

and o t her atoms, such as oxygen, and sometimes.

even sulfur.

Electron Impact—a method for ionizing samples for

mass spectrometric analysis. The ionization of the

sample results from the bombardment under high

vacuum of the sample molecules by a beam of electrons, usually at an energy of 70 electron volts (eV).

Flame Ionization Detector—a universal detector fo r

gas chromatography. This detector is fairly sensitive

and very linear, and responds well to most organic

compounds.

Fourier Transform-Infrared Spectrometry—this is the

state-of-the art of infrared spectrometry. This technique employs minicomputers and Fourier transform

methods in the acquisition of infrared spectra. Advantages of this technique include the making of

measurements in a fraction of the time required for

the more conventional methods, and increased sensitivity .

Gas Chromatography —one of the most widely used

analytical techniques for trace organic analysis. The

technique is simple and very rapid to use, is extremely sensitive, allowing the use of minute amounts of

samples, and can be very useful for preliminary

screening of environmental samples.

Gas Chromatography-Mass Spectrometry—a very

powerful analytical technique that combines the

features of gas chromatography and mass spectrometry.

High-Performance Liquid Chromatography—high-resolution, high-speed, and high-sensitivity liquid chromatography.

Liquid Chromatography —a separation technique that

allows the partition of the sample between two

phases, a liquid and a solid, or two liquid phases.

Liquid Chromatography-Mass Spectrometry—a recently developed analytical technique that combines

the features of liquid chromatography and mass

spectrometry.

Mass Spectrometry—a very powerful tool for providing the structural identity of complex organic molecules. Mass spectra furnish information about the

radical ion, which is usually produced by electron

bombardment in the ion source of the mass spectrometry.

Thin-Layer Chromatography—a form of liquid-solid

chromatography conducted on the surface of specially prepared plates. This technique is generally

very quick and simple to use and is effective in performing separations of small amounts of sample.

Ultraviolet Spectrometry—a form of absorption spectrometry generally suited for analysis of compounds

that are capable of absorbing ultraviolet radiation.

These include aromatic compounds, conjugated ketones, and other conjugated compounds, such as

polyolefins.
Appendix H

Analytical Systems for the

Determination of Metals in

Food and Water Supplies

by R. K. Skogerboe, Ph. D.

INTRODUCTION

The analysis of food products or water supplies

for toxic or potentially toxic elements, e.g., heavy

metals, is the central problem addressed in this

report. An evaluation of this problem in terms of

the capabilities and limitations of applicable analytical techniques is the primary thrust of this

report. Thus, recommendations regarding the selection of the best analytical methods and techniques for the determination of toxic elements are

presented below. Before doing so, it is appropriate to delineate the criteria used in the development of the recommendations and to discuss philosophical rationales on which these judgmental

guidelines are based.

The Analytical Process

Any chemical analysis can be divided into three

sequential steps: 1) collection of the sample(s);

2) chemical and/or physical preparation of the

sample(s) for analysis: and 3) measurement of the

concentrations of the target constituents in the

sample(s). Although these steps are interdependent and should not be considered otherwise, the

present discussion will focus on sample preparation and measurement. Sampling should be discussed in the broader context of the overall problem of monitoring. The selection of an appropriate

analytical technique must be based on the type of

information desired and the purposes of collecting that information. In the present context, this

may be delineated in fairly general terms.

The Monitoring Question

With rare exceptions, the central question associated with a monitoring program is:

● Are there one or more chemical entities present in the target material (e.g., food or water)

in sufficient quantities to cause deleterious

effects on the consumer population?

This question may be considered qualitative in

that it actually requires only a yes or no answer.

Given the knowledge that each of the chemicals

being monitored must be present at or above some

threshold’ concentration before they individually

or collectively produce observable effects on the

recipient population, the answer is no if all are

below their respective threshold effect levels and

yes if one or more is above. As a result, it is quite

common to use analysis approaches capable of

determining or detecting the chemicals only at

levels down to, but not below, their respective

threshold levels. Although this practice can often

be justified on an economic basis, it is subject to

challenge for scientific reasons.

The astute recipient of the answer to the central question will immediately raise other questions regardless of whether the answer is positive

or negative. If informed that all constituents of

concern are below their individual or collective

threshold levels, two questions are obvious:

● What degree of confidence can be assigned

to the results?

195
196 c Environmental Contaminants in Food

● Are the concentrations of any chemicals increasing significantly over time for a particular monitor and/or a particular collection

site?

When advised that one or more constituents

are present above threshold levels, these same

two questions are raised and a third becomes pertinent, i.e.,

● What is the cause or source of the observed

contamination?

These questions are clearly quantitative in

nature. Decisions regarding possible impacts on

consumer populations, or the prevention thereof,

should not be based on less than quantitative and

defensible information. Adherence to this philosophy is complicated by the facts that reliable designations of threshold effect levels are often lacking

and that two or more contaminants may act synergistically or antagonistically.

There is one general criterion that may be defined on the basis of the above discussion. All

analyses should rely on analytical methods that

are capable of determining all target contaminants at concentration levels below the threshold

effect levels. While methods capable of making

these measurements at concentrations 100 to

1,000 times below these levels would clearly be

desirable, the use of methods providing measurement capabilities 10 to 100 times below the levels

may prove more practical on an economic basis.

This discussion provides a basis for delineating

a general protocol for the operation of the analytical laboratory responsible for answering the

above questions. A brief discussion of this is presented here to provide a general basis for succeeding topics.

OPERATIONAL PROTOCOL FOR A MONITORING LABORATORY

A general flow diagram of the laboratory operation is presented in figure H-1. The analysis sequence given is depicted in the context of the monitoring questions, the checks required to validate

the results, and the regulatory actions likely to

prevail. Examination of this protocol indicates the

probable need for inclusion of: 1) a quality-assurance program as a means of validating results;

2) complementary analytical methods to ensure

that all required analyses can be completed and

to provide comparative information relevant to

validation of results; and 3) a data storage-retrieval system consistent with the requirements of

the monitoring questions, the quality assurance

program, and regulatory actions. The general utility of this protocol diagram and the actions it portrays will be expanded upon below.

CRITERIA FOR SELECTION OF ANALYSIS METHODS

The selection of an appropriate analysis approach must be based on the information requirements. These may be formulated on the basis of

the answers to two questions:

. What are the chemical entities that must be

determined?

c What are the concentration levels (threshold

levels) of primary concern for these target

entities?

Although answering the first question should

not be particularly difficult in most instances, the

issue for toxic elements has often been obscured

by the use of expedient analysis approaches

which may or may not provide the information required. Historically, most analysis methods used

for the determination of elements simply measure

the total amount of an element present without

differentiating between the various chemical

states of the element that may be present. Such

measurements may, in fact, be relatively nonspecific indicators of potential or actual deleterious

effects on biological systems. In numerous instances, the identification and measurement of

the active or functioning forms of the elements is

actually needed. The following examples testify to

the general importance of this statement.

1.

2.

3.

Although-arsenic is toxic, the plus three oxidation state (As(III)) is clearly more toxic

than the plus five state (As(V)); the compound

arsine (AsH,) is perhaps the most toxic chemical form of arsenic.

Although chromium is classified as a nutritionally essential element, Cr(III) is toxic

while Cr(VI) is relatively innocuous.

A measurement of the level of vitamin Bl~ in

animal tissue is ordinarily more useful than a
Appendix H—Analytical Systems for the Determination of Metals in Food and Water Supplies ● 1 9 7

+7 ’+7

element (in all of its chemical forms) can be rationalized. For example, if the analysis indicates

that the total concentration is below the threshold

effect level for any one or combination of the particular chemical forms for an element, the need

for measurement of the concentrations of the

chemical forms is negated. The total concentration measurement consequently serves as a

screening device indicative of the possible need

for chemical form measurements.

Once the elements and the concentration

ranges of interest for each have been defined, the

criteria which must be invoked in the selection of

ty, selectivity, reliability, scope, sample preparation requirements, and time-cost considerations.

It would be folly to select an approach incapable

of providing measurements a t or below the required concentration (threshold effect) levels.

Thus, selection of a sufficiently sensitive method

is of paramount importance. Although it is common to discuss sensitivity in the context of the

term detection limit, it is also usually impossible

to obtain a sufficiently accurate concentration

measurement when said concentration is barely

detectable. Thus, sensitivity should be considered

in association with the term determination limit,

i.e., the lowest concentration at which a sufficiently reliable concentration measurement can

be carried out.

The scope of an analytical approach is defined

on several bases. The ability to determine reliably

large numbers of individual chemical constituents

each of which may be present in a variety of sample types within a broad concentration range is

the primary connotation, Thus, universal applicability (utility) is an alternate terminology implying

the ideal case. It can also be argued that an analytical method which requires simple sample

preparation operations offers greater scope than

one requiring more complex preparative steps:

the ideal case involves direct analysis of the

samples without prior chemical treatment.

Analytical selectivity is usually interpreted

synonymously with specificity. The analysis approach used must provide an unequivocal means

of identifying each chemical constituent of interest irrespective of the compositional characteristics of the sample material being analyzed. In addition, the measurement of the concentration of

a n y constituent of interest should provide accurate results independent of the variations in the

concentrations of other constituents present in

the sample materials. Analysis methods that do

not satisfy these conditions lack selectivity (or
198 ● Environmental Contaminants in Food

specificity): such methods are subject to what are

often termed interference or matrix effects, In

essence, reliability (accuracy) is the criterion

which defines a sufficiently selective analysis;

confidence in the results and the decision(s) based

on them is explicit.

Minimization of the time-cost commitments

must be an objective considered in the selection of

an analysis approach. It is unfortunate that this

consideration often leads to one of two extreme

stances. Management often opts for the adoption

of analytical technology of limited utility on the

basis of lower initial capital costs and/or the fact

that such technologies frequently can be applied

by analysts with lower levels of expertise. Such

selections are often economic errors when considered on a longer term basis, At the other extreme,

management may invest in expensive facilities

and expertise and then require that they be used

to carry out analyses that can be accomplished

more economically via another approach. This,

too, can prove to be a false economy.

Summary

This background discussion has been presented as a preface to the evaluations presented

below; the intent has been to provide a common

basis for comments, evaluations, and suggestions

which follow.

PREMISES FOR SELECTION OF LABORATORY FACILITIES

In considering the operation of a laboratory

dedicated to monitoring food and water supplies

for toxic elements, several premises may be established. These are essential in defining the necessary facilities and require discussion. The following list is not necessarily all inclusive nor is it

set down in order of importance.

1.

2.

3.

4.

The majority of analysis requests will require the determination of several elements

per sample.

To be most effective, the laboratory must be

able to comply with these requests in a reasonable (short ) time.

The analyses carried out should be accomplished at reasonable costs.

The analytical results must be sufficiently

accurate to avoid challenge of the integrity

of any decisions based on them.

The combination of these premises clearly implies that the ideal laboratory facility would be

one capable of accurately analyzing for all constituents requested at concentration levels down

to and below their respective threshold effect levels in a short period of time. The use of a system

capable of simultaneously measuring all constituents of interest in each sample is definitely implied. The time and cost premises further imply

the desirability of utilizing analysis techniques

which do not require extensive sample preparation operations: the ability to directly analyze

samples in an “as received” form may be considered ideal. Sample preparation operations are

also primary sources of contamination or loss of

the analytical constituents. The direct analysis,

minimal preparations, capability is desirable

from the accuracy standpoint as well. Finally, the

accuracy requirement indicates the need for a

highly specific analysis approach which is not

subject to significant interference problems and

the maintenance of a quality assurance program.

No single analytical technique will necessarily

satisfy all of these requirements for the elements

and/or sample types of interest; a combination of

techniques will be required. Properly selected,

the techniques used may be complementary in

terms of providing the range of elemental analyses required and in terms of providing redundant analyses for some elements. The latter will

be useful for accuracy validation purposes (see

discussion below).

In effect, these premises lead to the defensible

conclusions that: 1) the laboratory facilities

should be primarily comprised of multicomponent

analysis systems; 2) more than one such system

will likely be required: 3) the selection of systems

that will provide some redundant analytical information is desirable; and 4) the inclusion of

secondary analytical systems to be used in supportive capacities may be essential. The following

evaluation is predicated on these bases.
Appendix H—Analytical Systems for the Determination of Metals in Food and Water Supplies ● 199

EVALUATION OF ANALYTICAL TECHNIQUES FOR THE

DETERMINATION OF

The qualitative identification and quantitative

determination of toxic or potentially toxic elements in food products and water can be based on

several different analytical techniques for which

commercially available instrumentation exists.

The primary techniques to be considered include:

1.

2.

3.

4.

5.

6.

7.

neutron activation analysis (NAA);

molecular absorption and fluorescence spectrophotometry:

solids (spark source) mass spectrometry

(SMS);

atomic absorption (AAS) and atomic emission spectrophotometry (AES);

electrochemical techniques

—anodic stripping voltammetry (ASV),

—differential pulse polarography (DPP);

plasma emission spectrometry (PES);

X-ray techniques

—X-ray emission spectrometry (XES),

—proton-induced X-ray emission spectrometry (PIXE).

Each of these are considered below.

Neutron Activation Analysis

This technique is perhaps the most sensitive of

those available when all elements are considered.

Absolute determination limits, expressed as nanograms (1 x 10-(J gm) that must be present in the

sample for quantitative determination, are summarized in table H-1. Such determination limits

should be converted to actual concentrations to

lend them perspective for the present evaluation.

For the analysis of food products or water, a 10-

gm or 10-ml sample generally represents a reasonable upper limit on the sample size that can be

activated for analysis. Thus, taking 0.5 ng as the

determination limit for arsenic as an example

(table H-1) this element can be determined at approximately 0.5 ng/10 gm = 0,05 ng/gm (rig/ml for

water) or 0.05 parts per billion by NAA. Evaluation of the other elements of interest on this proximate basis indicates that most could readily be

determined at required concentration levels via

this technique. While this is an encouraging conclusion, there are other factors which detract

from it.

TOXIC ELEMENTS

Table H-1 .—Determination Limits for Neutron

Activation Analysesa

—

Element

Ag ... . . . .

As . . . . . . . . .

Be . . . . . . . . . . . . .

Bi

Cd : : : : : : : : : : : :

Co . . . . . . . .

Cr. .,

C u

Fe . . . . . .

Hg . .

Mn . . . . . . .

Mo . . . . .

Ni

Pb : : : : : : : : : : : :

Sb . . . . . . . . . .

Se . . . . . . . . . .

Sn ... .

Te. . .

TI ., .

V . . . . . . . . . . .

Zn. . . . . . . . . . . . . .

Concentration

value, ppbc

0.005

0.05

2.5

25

2,5

0.25

50

0.05

2,500

0.5

0.003

5

2.5

500

0.25

250

25

2.5 —

0.05

5

aData taken from R- K Skogerboe and G H Morrison, Trace Analys!s E ssen

tlal Aspects, In Treatise on Analy~lcal Chernls(ry (1 M Kolthoff and P J El

vlng, eds ), New York Wiley and Sons, 1971, pp 5842-5843

bNanograms of element that must be present In sample activated to Permit a

quantitative determlnatlon, detection Ilmlts are approximately a factor of 5

lower Interference free measurement condt!lons are assumed

cAss\, mlng a 10 gm samp Ie IS act Ivated, thus concen trat Ion values = absolute

values – 10 These values should be Increased by a factor of 100 to 1 000 !O

compensate for the 10ss of neutron flux I f a neutron accelerator were used I n

stea[j of a nuclear reactor

To achieve the sensitivity required, the use of a

nuclear reactor providing a high flux of thermal

neutrons is required. The acquisition cost of the

reactor is several million dollars; the operational

costs are also comparatively high. Considerable

reduction of these can be achieved by replacement of the reactor with a neutron accelerator.

The neutron fluxes available with such accelerators are, however, about a factor of 100 to 1,000

less than those typical of a reactor. The analytical

sensitivity available is reduced in proportion [see

footnote to table H-1).

If chemical separations are carried out after

activation of the samples, proponents of NAA

argue that analytical interferences can be virtually eliminated. This argument is often specious

simply because the use of chemical separations is
200 ● Environmental Contaminants in Food

often a primary source of errors. Since such separations, even when free of errors, are time consuming and add to the expense; activation analysts usually prefer what is called the purely instrumental approach.

Two types of interferences are common to this

approach. Direct interferences occur when two

or more sample constituents emit radiation (gamma rays or beta particles) of nearly the same energy. If the emitting species undergo radioactive

decay at significantly different rates, correction

for these interferences can be based on measurement of the radiation at different times. Otherwise, the interfering species must be chemically

separated prior to the measurement step. Indirect

interferences due to contributions to the sample

spectrum from Bremsstrahlung and Compton interactions are also common, Correction for these

must be obtained by subtraction techniques. The

net effect is, however, a reduction in the analytical sensitivity and/or an increase in the uncertainties associated with the measurements, While

these instrumental approaches are widely used in

NAA to avoid the need for chemical separations,

such avoidance still restricts the potential scope

of the analyses. They also tend to lengthen the

time required to obtain analysis results. On these

bases, NAA does not appear to be the best choice

for a laboratory facility: capital costs, operational

costs, and operator training requirements are primary weighting factors influencing this negative

judgment.

Molecular Absorption and

Fluorescence Spectrophotometry

These techniques have been used extensively

for elemental analysis. They generally rely on carrying out a reaction of the element of interest with

a reagent (or series of reagents) to form a product

which has properties required for the absorption

of light. Identification of the element incorporated

into the light-absorbing product is based on the

wavelength of light absorbed while measurement

of the concentration relies on the extent of absorption; hence the term molecular absorption,

Some light-absorbing species regain a more stable

energy configuration by release of the light energy absorbed as light (fluorescence or phosphorescence). Measurement of the wavelength at

which this occurs and the intensity of the light

emitted is used to identify the species responsible

and the amount present,

The use of these techniques requires that specific or semispecific chemical reactions be used

for the formation of the absorptive and/or fluorescent products, While such reactions are generally

available for the elements of interest, the analysis

of any one sample for several constituents would

necessarily have to rely on carrying out several

individual reactions. Even then, there are only

limited instances for which a reaction will occur

for only one constituent (a specific reaction). Most

reactions involving a particular reagent set tend

to occur for each of several elements having similar properties and, as a result, their absorption of

fluorescence spectra tend to be quite similar.

Such spectra are subject to some degree of wavelength coincidence such that spectral interferences are not uncommon; the measurements are

less specific than desirable, While other features

of these techniques could be discussed, their

chemical reaction requirements coupled with the

specificity problem are deleterious from the multicomponent analysis standpoint. The techniques

should not be classified as essential for the present elemental analysis purposes.

Solids Mass Spectrometry

This analytical technique offers sensitivity

competitive with that characteristic of NAA (see

table H-1) for a wide range of elements. To utilize

it, nonconducting samples must be rendered electrically conducting. The constituents of an aqueous sample would ordinarily be analyzed after the

water was evaporated away; the residue would

be mixed with a conductor for analysis. Solid

materials such as foods are also typically nonconductive; by mixing them with a conductor such

as graphite or silver powder they become conductive. Food products must also be oxidized (by wet

or dry oxidation techniques) to destroy the organic constituents which cause serious spectral interferences in the analysis step. 2 These sample

preparation steps are quite extensive and can obviously be the sources of serious errors unless

carried out with caution.

In practice, the analyses must be based on two

sample mixtures to obtain a complete analysis

subject to less interference problems. Elemental

subset A may be determined based, for example,

on mixing the sample residue or ash with highpurity graphite. However, the carbon polymers of

which graphite is composed are observed in the

mass spectrum and preclude the possibility of

analyzing for those elements that would normally

See the following” reference for [i more complete discussion

of the prohlems tind r;]p{~bilities: C. A. Evans and G. H. Morrison, Anal. (;hem., W, 869 ( 1969).
Append/x H—Analytical Systems for the Determination of Metals in Food and Water Supplies ● 201

be measured at these mass positions. The analysis

for elemental subset B would subsequently be

based on the use of high-purity silver, gold, copper, or aluminum powder as the conducting matrix. Again, the use of any of these choices to

achieve sample conductivity results in spectral interferences which necessitate analyses based on

two or more subsets of elements. The conductive

materials used must be high purity, i.e., 6-9s or

99.9999-percent pure. This requirement limits the

possibilities and affects their costs, Finally, it

should be noted that solid mass spectrometric

analyses require unusually long times even

though it is possible to obtain analyses for -40 to

60 elements on each sample. Although the sample

preparations required are time consuming, the

analysis itself is also rather slow. Given samples

ready for analysis, a well-organized SMS laboratory would be hard-pressed to analyze more than

5 to 10 samples per man-day. These factors, coupled with high acquisition costs (~$250,000) and

high operational and instrument maintenance

costs, place solids mass spectrometry in a negative posit ion relative to other possibilities,

Atomic Absorption and

Emission Spectrophotometry

Recent instrument sales figures indicate that

only gas chromatography is more widely used

than atomic absorption spectrophotometry. When

a flame is used as the energy source required to

produce the gaseous atomic populations from the

sample dissolved in aqueous solution, atomic absorption offers favorable analysis capabilities for

a reasonably impressive array of elements (see

table H-2]. Atomic emission from the same atom

populations in the flame is totally complementary

and supplementary to atomic absorption. Factors

which affect absorption also tend to affect emission; the ultimate sensitivity achieved with either

measurement approach is limited by the ability to

produce the atomic populations. As a result, it

can be shown that atomic absorption is generally

most favorable (on the basis of sensitivity) for the

determination of those elements requiring more

energy to produce atomic emission, i.e., an excitation potential above approximately 4.5 electron

volts (eV). Elements with lower excitation potentable H-2.—Determination Limits for Flame Atomic Absorption and Emission and Furnace Atomic Absorption’

Elements

Ag

A s

B e

B i

C d

c o

C r

Cu

Fe

Hg

Mn

Mo

N i

P b

Sb

Se.

S n

T e

T I

V .

Z n

Flame methods b

Atomic Atomic

absorption emission

002

05

001

02

0005

003

002

001

0.02

1 0

001

02

002

0.05

05

05

01

0 5

01

01

001

0.04

5

0.5

2

2

0.1

002

005

0.1

2.0

0.02

05

0.1

05

2

10

2

200

0.1

0.05

0.2

Flame AA

analysis of

tissue digestsc

0.2

5

0.1

2

0.05

0.3

0.2

0.1

0.2

10

0.1

2

0.2

0.5

5

5

1

5

1

1

01

Furnace

atomic

absorption

000004

0.02

00002

0.001

0.00002

0.001

0.001

0.001

0.0006

0.02

0.0001

0,008

0.002

0.001

0.006

0.02

0.01

005

0.0006

002

0.00002

Furnace AA

analysis of

tissue digestsc

0.0004

0 2

000 2

0.01

0.0002

0.01

0.01

0.01

0.006

0.2

0.001

0.08

0.02

0.01

0.06

0 2

0.01

0 5

0.06

0 2

0.0002

‘Data I rom J D VJI n~ fordner el al APPI SPec trosc Rev/e ws 712J 147 (1973) A II va I ~jes g lven In P 9 m I for aqueo~ls sol ~~ tlons

tlDeflne{j for ~)e~t flafllf> con(jltlons for each element values In l,q ml ~ppm~

r Based on [1 I SSOIVI n q 10 q m o f h(r]locjlcal I I s$ue I wet welg ht I per 100 m I of dc Id va Iues I n Ig g m (ppm) wet wmg h I

d~ef, nP(f for ~lDt, n),)” f”, “ac e ~ ~ncj, 1,Ons , n ea~ h case and “se of a 25,, I sample lnjec I Ion values In ,,g m I (ppm)
202 “ Environmental Contaminants in Food

tials are best determined by atomic emission

when flames are the energy media. These generalizations require the use of an instrument that is

well-designed for both absorption and emission

measurements (two of the three major U.S. atomic

absorption manufacturers supply such instruments).

In spite of the combined capabilities offered by

flame emission and absorption, they are frequently inadequate for the types of analyses in question

unless preconcentration and/or separation procedures (e.g., solvent extraction) are used. These inadequacies may be due to a lack of sufficient sensitivity and/or to the occurrence of interference

effects. These, coupled with the difficulties attendant to separation/preconcentration procedures, have led to the development of what is

often called nonflame atomic absorption. The first

significant development in this area involved the

reduction of mercury ion in aqueous solution to

atomic mercury (Hg) such that it could be carried

directly to the gas phase into the optical path of

an AA instrument for measurement. The measurement actually involves separation of the Hg

from the sample under conditions less subject to

interferences. If carried out under appropriate

conditions so that the Hg arrives at the measurement cell rapidly, an effective preconcentration is

also realized. In effect, the measurement sensitivity is determined by the concentration of atoms

delivered to the measurement cell per unit time.

The nonflame methods are all designed to take advantage of this thereby enhancing the ability to

analyze at lower concentrations; methodological

developments for this purpose have taken two

general tacts, i.e., chemical generation and furnace vaporization.

Beyond the Hg method described above, the

hydride generation method for the determination

of arsenic, selenium, germanium, lead, tellurium,

tin, antimony, and bismuth has received wide attention. The hydrides of these elements are rapidly formed by reaction in acid media with sodium

borohydride. The metal hydrides, being gases at

ambient temperatures, are readily transported

via carrier gas to a flame or a heated ( - 800° C)

quartz cell for atomization and measurement. The

success of this general approach has led to the

commercial availability of hydride generator accessories for atomic absorption. It has also been

adopted in commercial autoanalyzer systems. Detection limits of less than 1 ng metal/ml (1 ppb)

solution are readily obtained.

Furnaces, fabricated from graphite or tungsten, that can be temperature ramped by resistance heating have been developed to high levels

of refinement. Liquid samples are delivered to a

furnace, which is resident in the optical path of

an AA unit, and a programed heating cycle is initiated, In this cycle, the liquid is first evaporated

a t ~120° C; the salt residue remaining is “ashed”

to convert it to a “common” chemical form at

-3000 to 50 0

0 C; and the ash is rapidly vaporized

and atomized at -2,0000 C for the absorption

measurement. The use of such systems provides

improvements in the analytical sensitivity for

most elements (see table H-2). The extent of improvement is limited by the amount of sample that

can be placed in the furnace ( ~25 to 50 μ1) but

generally amounts to a factor of 10 to 100 when

compared with flame AA capabilities.

These capabilities combined with the general

simplicity of operation and lower instrument costs

have been largely responsible for the widespread

acceptance of atomic absorption. During the principal time of AA development, the primary competing techniques were flame, arc, and sparkemission spectrometry. The last two were rather

quickly abandoned by the analytical spectrometry

community because they were “notably subject to

interference problems associated with the vaporization-atomization system. It is rather ironic that

the same community, in less than 10 years, reverted to the use of furnace AAS systems which

are subject to the same interference problems for

the same reasons. It is also ironic that an extensive fraction of the furnace AA research reported

in the past 5 to 10 years has dealt with the study

of interference effects and means for their elimination. A large percentage of these studies are

reaching the same conclusions and developing the

same compensatory methods that resulted from

arc and spark spectrometry interference effect

studies before the advent of atomic absorption.

Nevertheless, atomic absorption analysis is wellestablished and here to stay. The furnace methods, in particular, clearly offer the required sensitivities for a wide range of analysis problems.

A primary historic limitation has been that

atomic absorption has been basically a single element analysis technique; analyses for several elements in a sample are carried out sequentially in

time. The emergence of plasma emission spectrometric systems which allow the simultaneous

analysis of several elements (to be discussed

below) has forced the atomic absorption community to the development of multicomponent analysis systems. Only one commercial instrument offering this capability for more than two elements

is available at this date, This unit is, in fact, a se-
Appendix H—Analytical Systems for the Determination of Metals in Food and Water Supplies ● 203

quential analysis system since the elements of interest are not measured simultaneously. Its use

saves analysis time but not as much as it would in

the simultaneous mode. At least one other manufacturer will introduce a truly simultaneous multielement AA analysis system in the next 1 to 2

years. Prototypes of such a unit have been developed and tested at Colorado State University.3 The

tests have shown that sets of 5 to 10 elements can

be determined simultaneously without sacrifice of

analytical sensitivity. The availability of such instrumentation will advance the state of the art for

atomic absorption.

The inclusion of atomic absorption in an elemental analysis laboratory may be considered

worthwhile as a secondary facility at least. If said

instrument offers the simultaneous measurement

capability, the inclusion may be justified on a better economic basis.

Electrochemical Techniques

These techniques are perhaps the most classical of those considered herein, And yet, electrochemistry has been reborn in the past two decades largely through the development of what

may be classified as pulse or differential techniques. The electrochemical techniques of primary interest in the present context rely on the

measurement of the Faradaic current (FC) produced or used during oxidation or reduction reactions involving the element to be determined; the

potentials at which FC changes occur depend on

the elements (ions) involved in the reactions. Such

reactions are almost universally accompanied by

non-Faradaic processes involving other sample

constituents which also result in the production

or utilization of current. In classical direct current polarography or voltammetry, the ability to

measure a low Faradaic current (low analyte concentration) is limited by the magnitude of the nonFaradaic current changes occurring simultaneously. The revitalization of electrochemistry has

been largely based on the fact that when the potential required to induce a redox reaction is removed, the non-Faradaic current decays more

rapidly than the Faradaic current. Thus, by

“pulsing” the potential up to the reaction level required, shifting it back to below the reaction level,

and waiting an appropriate time period for the

non-Faradaic current to decay; the Faradaic to

non-Faradaic current ratio can be significantly

‘See for example: F, S. Chuang, D. F. S. Natusch, and K. R.

0’Keefe, Anal, Chem. 50, 525 [1978).

improved. A variety of these differential pulse approaches have been developed to achieve analytical measurements at concentrations 10 to 1,000

times lower than previously possible. The techniques which appear to offer the most significant

capabilities are differential pulse polarography

(DPP) and differential pulse anodic stripping voltammetry (DPASV). At least one commercial instrument offering both of these measurement capabilities is available.

The electrochemical literature indicates that

-16 to 20 elements can be determined by DPP,

DPASV, or cathodic stripping voltammetry (CSV).

This is true, but all such elements cannot be determined under a single set of experimental conditions. Some must be determined using a gold

working electrode (for example) while others require the use of a mercury electrode. Some determinations require the use of a specific supporting

electrolyte solution while others do not. Finally,

the redox potentials of some entities are sufficiently similar that they cannot be determined in

the presence of each other without the use of correction techniques. In some cases, prior separations are required.

The electrochemical analysis literature indicates that Cd, Cu, Pb, Zn, Tl, and Fe can usually

be determined simultaneously in a single supporting electrolyte solution using mercury as the

working electrode material, These elements can

be determined at levels of 1 ng/ml or less in the

electrolyte solution by DPP or DPASV. As a result,

these techniques are quite widely used for the

analysis of the above elements. Although Cu and

Zn interfere with each other via formation of the

Cu:Zn intermetallic in the mercury electrode and

the reduction of Fe(III) to Fe(II) interferes with the

Cu determination, these can be corrected via use

of expedient instrumental procedures. Other elements frequently determined are As(III) by

DPASV or DPP and Se(H) by CSV. Again, analyses

at or below the part per billion concentration

level are common.

The electrochemical methods detect only the

electroactive species, e.g., the ions, This statement must be qualified in terms of the time-scale

of the measurement step. To illustrate, consider

an electroactive metal ion (M+ 11) which may be

present in the sample solution primarily as a complexed or molecular species designated, for example, by MXn

. To measure the total M+ n plus MXn

concentration, the following reaction must occur

either prior to or during the measurement period:

MXn

-, M + n + nX -

If the duration of the measurement is short, the

above reaction must go to a reproducible state of
204 ● Environmental Contaminants in Food

completion within that time period; in such cases

the complexed/molecular entity may be classed as

labile. Thus, there is a growing investigative effort in the electrochemical community involving

the use of this conceptual approach as a means

for the identification of the chemical forms of

metals in natural systems. The general thrust of

these efforts involves either the use of chemical or

electrochemical means for systematically shifting

the above type of reactions toward the formation

of an electroactive species for identification purposes. A typical electrochemically induced shift

experiment, for example, might involve ASV. By

electrodepositing from the sample solution for

successively longer periods and measuring the

amount of M + I’ reduced during each period, the

time required to drive the above type of reaction

to completion might be deduced. This may be indicative of the “lability” of the complexed/molecular form, i.e., its thermodynamic or kinetic stability, Extensive research must be completed to establish the potential utility of such approaches.

However, these possibilities combined with the

high sensitivities that can be achieved with modern electrochemical techniques suggest that such

facilities should prove to be valuable laboratory

facilities. (See further discussion below.)

Plasma Emission Spectrometry

It has been suggested that atomic emission

spectrometry offers what may approximate the

ideal approach to multielement analyses. Indeed,

the use of the radio frequency inductively coupled

plasma (ICP) as the atomic excitation source in

combination with a direct-reading emission spectrometer permits the simultaneous determination

of numerous elements at low concentration levels. 4 Similarly, the use of a direct current plasma

(DCP) excitation source for direct-reading emission spectrometry shows comparable promise.

The evolution of such systems over the past decade has brought emission spectrometric analysis

back to the forefront of analytical capabilities.

Such plasmas are principally used to excite analytical constituents delivered to them via solution

nebulization (aerosol production) systems. The

conversion of solid samples to aqueous solutions

for analysis (e.g., by wet oxidation) results in

elimination of many of the major compositional

differences between samples such that interfer4 A good introductory review has been presented by V. A.

Fassel and R. N. Kniseley, Anal. Chem, 46, 11 10A (1974). See

also, %ience, 202, 183( 1978).

ence effects due to matrix differences may be

eliminated or reduced. As a result, a single set of

operational conditions may be used for the simultaneous determination of 20 to 60 elements,

Quantitative determination limits for the ICPand DCP-Multielement Atomic Emission Analysis

Systems (MAES) are listed in table H-3. Examination of these data indicates that these systems are

adequate for the simultaneous determination of a

major fraction of the elements of interest at levels

commensurate with the anticipated threshold effect concentrations. This is one reason why the

ICP-MAES and DCP-MAES manufacturers have

enjoyed significant annual sales improvements

over the past 5 years.

Some elements of high concern, because of

their toxicities or propensities for bioaccumulation, cannot be determined at low enough concentrations by direct solution analysis, e.g., Hg, As,

and Se. However, the hydride generation approaches used to solve this problem when AAS is

the analysis method, are equally applicable to

MAES. In fact, all hydride-forming elements can

Table H-3.—Multielement Atomic Emission

Determination Limits for Two Common

Plasma Excitation Systemsa

ICP-MAES DCP-MAES

For tissue Tissue

In solution, digest in solution, digest

~lglml ~lg/gm (ppm)b ~~g/ml g/gin (ppm)b

0.01 0.1 — —

0.3 3 0.2 2

0.02 0.2 0.02 0.2

0.002 0.02 0.05 0.5

0.2 2 — —

0.01 0.1 0.05 0.5

0.01 0.1 0.08 0.8

0.02 0.2 0.02 0.2

0.005 0.05 0.01 0.1

0,01 01 0.01 0.1

0.1 1 0.01 0.1

001 01 0.05 0.5

0.03 0.3 0.05 0.5

0.05 0.5 0.05 0.5

0.1 1 0.05 0.5

1 10 — —

0.2 2 0.2 2.0

1 10 1 10

0.4 4 — —

1 10 — —

0,2 2 0.5 5

0,02 0.2 0.02 0.2

0.01 0.1 0.02 0,2

aData for the Icp trom R K Wlncje et al S~ectrochlm Acta, 326 327 ( 1977)

Data for the DCP from R K Skog;rboe H E Taylor and G W Johnson, Spectrochlm Acta, In press

bFor 10 ~m O( biological Ilssue (wet wt ) dissolved In too ml of Solutlon
Appendix H—Analytical Systems for the Determination of Metals in Food and Water Supplies ● 205

be determined at required concentrations on a simultaneous basis. (Tissue detection limits of 0.01

μg/gm (ppm wet weight) can be achieved. )

Although the measurement of atomic emission

offers a high degree of qualitative specificity,

there are two common types of interferences

which affect the quantitative specificities of such

systems. Both plasma types are highly efficient

excitation media. As a result, extremely intense

radiation from common elements such as Ca and

Mg is delivered to the spectrometer-measurement

system, The result is the observation of stray light

interference effects for some other elements. The

magnitudes of these effects depend on: the design

characteristics of the spectrometer used, the concentrations of the elements from which the stray

light originates, the concentrations of the elements subject to the interferences, and the types

of approaches used to alleviate the effects. An expedient means of correcting for these effects may

be based on determination of the concentrations

of the causative elements. To illustrate, let C m

represent the measured concentration of a particular element (analyte) subject to interference due

to a concomitant constituent present at concentration C(. The true (corrected) concentration (C1)

of the analyte may be determined from:

where a is a correction coefficient determined by

simple experimental procedures.

The other type of interference effect involves

interelemental processes in which the presence of

one constituent changes the extent of excitation

of another in the plasma, While such interelement

effects are less common, the above correction

procedure can also be used for compensation.

Commercial ICP- and DCP-MAES systems are routinely equipped with minicomputer or microprocessor systems for control, data acquisition, and

data correction purposes. The use of the types of

corrective procedures described above is, thus,

easily automated.

In effect, the general capabilities of plasmaMAES are such that it should be considered a primary facility.

X-Ray Emission Techniques

The bombardment of samples with X-rays to

produce X-ray fluorescence (XRF) has remained

in wide usage. In fact, the development of the lithium drifted germanium, Ge(Li), or silicon, Si(Li), detectors has advanced the status of this approach

by the reduction of spectral interference problems and a general increase in the sensitivity

available. Such energy-dispersive detection systems have rather rapidly replaced the conventional wavelength-dispersion units. The production of

X-ray fluorescence (emission) by X-ray bombardment and measurement with an energy dispersive

detector offers reasonable analysis capabilities

for several elements of interest (see table H-4).

In 1970, the potential of heavy, charged particles for X-ray excitation was recognized, and improved capabilities have been demonstrated. The

capability improvements of accelerator (particle)

beams are due to: 1) the high particle fluxes available, Z) the relatively low background radiation

associated with the excitation process: 3) the fact

that the excitation cross-sections of many elements for particles are higher than for photons or

electrons, and 4) a single charged particle can induce emission of several X-ray photons as it pene-
206 ● Environmental Contaminants in Food

trates the sample. As a result, proton induced Xray emission analysis (PIXE) has rapidly emerged

as a sensitive analysis approach which may be

subject to fewer interference problems than Xray induced emission. Thus, the X-ray source is

replaced by a van de Graaff accelerator to produce proton beams in the 2.5 to 3.0 Mev energy

range.

A potentially significant capability associated

with PIXE analysis is that of direct analysis of biological tissue sections or blood. Recent publications 5 6 have shown that Cl, K, Fe, Cu, Zn, Pb, Se,

Br, Sr, and S could be directly measured in a 30

μm thick section of human kidney; that the same

elements plus Mn, Ni, Hg, Rb, and Zr could be determined in a thick section of carp muscle; and

that several elements can be directly measured in

tissue sections of liver, kidney, lung, and bone.

The analysis of liquid- or wet-digested materials

may be based on evaporation of the liquid phase

to leave a residue deposit on an appropriate ana-

‘lJ. L. Campbell et al. “Acivances in X-ray Analysis, ” vol. 17

(C. L. Grant et al,, eris.), Plenum Press, New York, 1974, pp.

457-466.

‘P. S. ong et al., [bid., vol. 16 (L. S. Birks et al., ecis. ), 1973,

pp. 124-133.

PREPARATION OF

lytical substrate, Ions in solution may also be preconcentrated for analysis using filters impregnated with ion exchange resins. ’ Determination

capabilities for XRF and PIXE are listed in table

H-4,

The general capabilities of these techniques

are such that they can be used in a laboratory of

the type considered. It should be emphasized,

however, that quantitation of the measurements

is subject to difficulties particularly for direct

measurements. Proponents of the techniques

argue that these problems can be readily overcome; others (cynics??) argue that this will require extensive development efforts. The truth

appears to be intermediate between these extremes. The ultimate decision to include the X-ray

capabilities in the laboratory facility should probably be based on the essentiality (desirability) of

being able to analyze solid samples (e.g., tissue

thin sections) directly for several elements of potential interest. This capability may be considered by some to be advantageous simply from the

semiquantitative screening standpoint.

S. L. Law and W. J, Campbell, “Advances in X-ray Analysis, ” vol. 17, Plenum Press, New York, 1974, pp. 457-466.

(BIOLOGICAL TISSUE) FOR ANALYSIS

Many techniques require that solid samples be

converted to solution form for analysis. The literature on methodology for sample decomposition is

immense, The procedures cited find both wet-

(acid digestion) and dry-(ashing) oxidation methods extensively used. Dry-ashing methods are usually implicated when problems with recovery or

losses of analytical constituents are reported. In

comparing wet- and dry-ashing methods, the paucity of data specific to real-life samples makes it

inappropriate to state categorically that one

method is superior to another. Some generalizations can, however, be made on the basis of procedural differences. Wet oxidation has the advantage of requiring a minimum of apparatus and is

less prone to volatilization and retention losses

than dry-ashing. Wet-ashing may suffer in that

relatively large amounts of reagents having significant levels of contamination may be required and

contact with glassware may account for a higher

risk of contamination than dry-ashing. Dry-ashing

requires few, if any, reagents and handling of

larger samples presents less problems. The risk of

volatilization, convection, and retention losses is

higher, however, unless ashing conditions are

carefully controlled, These risks have led to the

fairly widespread adoption of low temperature

ashing (LTA) based on reaction of the sample of

the oxygen free radical generated via a radio frequency field. While it is true that materials can be

converted to oxides under these conditions, it is

also apparent that several elements may still be

lost by volatilization at typical operational temperatures of 100° to 150° C. These are largely elements with a tendency to form volatile chlorides,

oxychlorides, or hydrides, Thus, the extent of

their loss may be particularly influenced by the

halogen (chloride) content of each sample, The

use of programed-temperature ashing furnaces

has been shown to be effective in preventing or

reducing volatilization losses. Raising the temperature at a rate permitting slow charring and oxidation of the sample is to be highly recommended.

Nitric acid is a universally used wet-oxidant,

The azeotrope boils at 120° C, a factor which assists in its removal after oxidation but also limits
Appendix H—Analytical Systems for the Determination of Metals in Food and Water Supplies ● 207

its effectiveness in completing the oxidation process. The most effective medium for wet oxidation

is a mixture of nitric and perchloric acid; the azeotrope boils at 180° C to force oxidation. Extraordinary care to avoid explosions and fume hoods

is required. The precaution of keeping sufficient

nitric acid present until all easily oxidized material is gone (cessation of brown fumes) is particularly important in wet digestion of tissues having

lipid (fat) contents. Because the acids used are

never absolutely free of metal contamination, the

objective of wet oxidation should always be to

complete the oxidation with the smallest possible

amount of acid. This minimizes the blank problem.

The use of reflux digestion apparatus equipped

with condensers is focused on this objective as

well as that of minimizing losses. Recent systems

which rely on microwave ovens for heating the

acid-sample mixture also show considerable

promise. 8 9 The microwave system heats the solu-

“A. Abu-Samr~, ]. S. Alorris, ~n[j S. R. Koirtyohann, Anal.

Chem., 47, 1475 (1975].

‘IU. S. Patent No. 4,080.168 (Mar. 21, 1978).

tion rapidly and prevents bumping and frothing.

Recovery studies run on a range of elements suggest that loss problems are minimal. Bovine liver

is notorious for being difficult to wet digest. The

report

10 that 2 gm (wet weight) or 1 gm (dry

weight) of beef liver can be digested in 10 ml of nitric/perchloric acid in 2 to 3 minutes indicates an

attractive capability that will surely guarantee

extensive use of the microwave system.

For any of the analysis techniques which require sample dissolution, the approximate upper

limit of “dissolved salts” that can be tolerated is 2

percent (wt/vol). Thus, for a wet biological tissue

which yields 10 percent ash, this upper limit

would be equivalent to dissolving 20 gm of the

tissue (wet wt) per 100 ml of analytical solution.

Working with half that weight per 100 ml would

have practical advantages.

“’Report to the U.S. FDA (Contract No. 223-75-2268] Der. 2,

1976.

ASSURANCE OF ANALYTICAL ACCURACY

Quality assurance in an analysis laboratory refers specifically to the question: Are the analytical results valid (accurate or reliable]? Obtaining

the answer is complicated by the fact that all

analyses are subject to random (indeterminate)

errors and may also be subject to systematic (determinate) errors. Errors are cumulative; those

which characterize the accuracy of any analysis

result may include the composite contributions of

the random and systematic errors inherent in the

analysis method(s) used and those characteristic

of each analyst, Laboratory, or set of equipment

involved in the analysis. To maintain quality assurance, an operating laboratory must base its

program on some combination of the possible strategic approaches. These include:

1. Recycling of submitted samples to obtain

cross check analyses,

2. Recycling of certified or secondary standard

reference materials to estimate analytical

accuracy,

3. Spike-recovery studies to estimate accuracy,

4. Participation in collaborative test programs,

and

5. Comparison of results obtained by independent analysis methods.

Each of these provides specific types of relevant

information but all should be included in the program. Moreover, any of the above tests should be

carried out incognito. Otherwise, the analysts

may be tempted to devote inordinate attention to

the check analyses.

All of these methods add to the expense of lab

operation. It is necessary, however, for the lab

personnel to be acutely aware of the ways in

which they or their analytical methods can fail

and (ideally) know when they have failed. Otherwise, their products—the analysis results—will

be subject to challenge. Experience with the legal

process suggests that the agreement between results obtained by two or more independent analytical methods is a primary indicator of success (accurate analyses). Thus, the planned inclusion of

analysis redundancy (5 above in particular) in the

laboratory operation is to be recommended; a typical quality assurance program would involve

check analyses amounting to 5 to 10 percent of

the total load.

‘ I An expanded discussion of quality assurance programs and

the necessity thereof is given in the paper by R, K. Skogerboe

and S. R. Koirtyohann, 4’Accuracy Assurance in the Analysis of

Environmental Samples.’” NBS Special Bulletin 422 ( 1976).
208 ● Environmental Contaminants in Food

LABORATORY INSTRUMENTATION AND

FACILITIES REQUIREMENTS

Consideration of the above discussion indicates

that the majority of the analytical requirements

can be satisfied by plasma emission spectrometry

or by atomic absorption spectrometry with heavy

reliance on furnace atomization systems. The inclusion of more than one measurement technique

in the laboratory can also be justified on various

bases. The advantages, limitations, and tradeoffs

involved will be considered below. Regardless of

which instrumentation facilities are chosen as

primary; the space requirements, ancillary facilities requirements, and personnel requirements

are comparable. Thus, discussion of these prior to

consideration of the analytical instrumentation

facilities is appropriate,

Personnel, Space, and Ancillary

Facility Requirements

The general design of the laboratory should include four physically separated types of space:

1) office space for personnel, 2) a sample receiving and storage room, 3) a sample preparation

laboratory, and 4) the analysis laboratory. Working desk space should be included in the last three

types of space in addition to the facilities discussed below. All lab facilities will require temperature control to plus or minus 5° F and humidity control (less than 50 percent).

It is recommended that computer capabilities

should be a primary ancillary facility included in

the laboratory operation. This is based on several

rationales including:

1.

2.

3.

several types of instrumentation likely to be

present are most effectively used under a

computer control-data acquisition mode of

operation:

personnel requirements, time commitments,

and human errors can be reduced in a computer-oriented operation; and

a computer system may be essential as a

data management, quality assurance evaluation, warning assessment, and report preparation tool in a laboratory operation of the

size likely for the present program.

Although the computer configuration selected will

be dependent on the laboratory purpose(s), the

analytical facilities installed, the size of the operation, and other subsidiary factors, it is likely a

computer acquired with one of the instruments

described below could be adapted for use in an intralaboratory, interactive (time-shared) mode and

tied to a larger computer system (external to the

laboratory) which would perform those data management functions that need not be carried out on

a real-time (fast response) basis. Systems which

use internal, instrumentation-coupled, computers

for control and data acquisition purposes and

transmit the data to central management computers are presently in operation at the USGS Water

Resources Laboratory in Denver and the EPA Laboratories in Cincinnati. Although these operations

may not be the best model examples, the conceptual approach which they embody is recommended for the present operation. Further comments relating to this are inserted in appropriate

sections which follow.

Sample Receiving and Storage Room—The receiving operation will necessarily include facilities for logging in samples and the associated analytical work requests. A computer terminal

should provide the most effective capability. The

storage facilities should include: shelving or cabinets for those samples that can be stored under

ambient conditions, a cold room (4°C) for storage

of water samples, and a freezer for storage of certain biological samples. The size of the room and

storage facilities required will depend on the anticipated sample load and variations in the sample submission rate. Since such data have not

been supplied, size estimates and costs are not included in this report,

Sample Preparation Laboratory—The design of

this laboratory will be sample type and sample

load dependent. If the sample types to be analyzed include those which must be ground in the

dry form such that atmospheric contamination

can occur, the grinding facilities should be physically isolated from the other sample preparation

operations, In addition, the sample preparation

lab should basically be a clean room12 operation

or it should be equipped with laminar flow, filter

hoods in which certain sample preparation operations can be carried out. Both wet- and dry-oxida-

(;lean room or clean hood environments are classified on

the b[]sis of (x)ntroliing the concentrations of particles (dust) in

air which rnn cont:lminate the samples by f;~llout. A class-100

(’le;~n room, for t:xtlmple, must ht]ve no more than 100 particles

in the 0.5- to 5- micrometer diameter size range per cubic foot

of air. A cI:lss- 1,000 room permits 1,000 pa rticu]a tes per cubic

foot in the ahove r:tn,gc. ‘1’o meet these specifications, air filtration is re(~uire(i. S(;e th[! 1963 Fe(teral Stand[~rd No. 209:1,
Appendix H—Analytical Systems for the Determination of Metals in Food and Water Supplies ● 209

tion facilities should be included in the laboratory

plan to permit handling of various sample types in

the most expeditious manner. A list of sample

preparation facilities likely to be required is given

with their approximate costs in table H-5. Access

to a computer terminal to permit convenient entry

of sample preparation data is also recommended.

Analysis Laboratory —The instruments selected will influence the facilities and size requirements of this laboratory. It is assumed that

the prepared samples will be delivered to this lab

in closed containers and will be handled in ways

that will minimize the probability of contamination via atmospheric contact or fallout. Thus, although rigorous clean room operation has not

been recommended for this lab, it will be necessary that all analytical operations which can result in simple vaporization be carried out under

ventilation conditions where the discharge is external to the lab.

Personnel Requirements and Performance—

Stipulation of exact personnel requirements will

again be dependent on the sample load and the

types of samples received. The sample logging

operation can be handled by an individual with no

chemical training but with secretarial or keypunch skills: this individual might also perform

some of the simpler sample preparation operations, e.g., weighing and grinding. The preparation laboratory should be staffed by individuals

with B.S. degree training in chemistry with 1 to 3

years of wet chemical experience.13 One such individual can typically prepare 15 to 30 biological

tissue samples per day by wet- or dry-oxidation

techniques depending on the complexity of the

preparativ e steps involved. The analysis la b

should also be staffed by chemists with at least

B.S. degree training plus 2 to 4 years of experience.

14 The experience should preferably be in the

general area of instrumental trace analysis dealing particularly with the types of instrumentation

to be used. A working familiarity with basic electronics and minicomputers would be desirable.

The availability of major repair capabilities

through instrument maintenance contracts

should be insured.

For the lab personnel, it may be assumed that

the average analysis production hours per manday will range between 5 and 6. The remaining

time will be utilized for preventive maintenance

of equipment, recordkeeping, cleanup, etc. Although there are nominally 260 working days per

annum, this reduces to about 200 days when vacations, holidays, sick leave, and refresher training

time are taken into account. The number of personnel required and the sample throughput capabilities of the lab must be defined on this basis.

Table H-5.— List of Sample Preparation

Facilities Required

Preparation facility Approximate cost, $a

$2.500

8.000 automatic

3,000 manual

4.000

4.000

8.000

6,000

8,000

4,500

2,000

$5,000-10,000

ANALYTICAL INSTRUMENTATION

The previous discussion has presented the gen- H-6. Although the data presented in that summary

eral analytical features, capabilities, and limita- have been based on personal experience and distions of the various analytical techniques consid- cussions with other practicing analysts, they must

ered applicable to the present problem. A summa- be considered as estimates only. This applies in

ry of the cost, space, and throughput features of particular to the cost per analysis because it will

these types of instrumentation is given in table be strongly influenced by the applicable salary
210 ● Environmental Contaminants in Food

Table H-6.—Summary of Cost-Productivity Estimates for Various Analytical Techniques

Approximate- Space - ————— Estimated Approximate Data Estimated

acquisition requirements no. analyses cost per system down

Instrument facility cost, $a

sq. ft.b

per man-dayc analysis, $d requirement e time, % f

ICP-MAES. ,-:- . . . . . . . . . . . . . . ; .-:

——————

100,000 200-400 1,500-2,000 0.1-0.3 Yes” 3-5%

DCP-MAES . . . . . . . . . 60,000 200-400 1,200-1,500 0.1-0.3 Yes* 3-5%

Flame & furnace AAS

Single element mode

g

. . 25,000 200-400 100-200 (flame) 0.7- 1.0 Desirable 3-5%

50-100 furnace 1.0- 1.5 Desirable 3-5%

Multielement modeh 

. . . . . . . 40,000 200-400 400-800 (flame) 0.3-0.5 Yes’ 3-5%

200-400 (furnace) 0.5-0.8

Electrochemical i . ... . . 25,000 200-400 50-100 1.0- 1.5 Yes* 3-50/0

N. A.A.J. ... . 40-50,000k

200-400 200-700 ? Yes* ?

X-ray fluorescence . . . 60-100,000 200-400 200-700 7 Yes* 3-50/0

PIXEJ . . . . . . . . . . . . . . ., 300,0001 300-500 400-800 7 Yes* ?

— aFOr ~o.~~e-ment ~“~1~ SIs Capab;l llles lncludl~g ;strument mstallatlon

bin addltlon 10 sample preparation and office space but allowlng for adjacent working sPace.

Csamples Previously prepared for analysls, data management system available, 5 hours on the Instrument per 8.hour day, one anal Ysls defined as determination of one

element per sample, approximately 10 percent of total analytical load I nvolvlng quail ty assurance assumed, all analyses to Involve simultaneous multlcomponent

determinations of 10 to 15 elements on each sample

dcost per elementper Sample, :jamples Previously prepared for analysis, approx 5-year instrument depredation assumed, see footnote C above

el nstrument control, data acquls.ltlon and data management system considered essential for all facllltles, . Ind!cates Incluslon of a minicomputer or microprocessor of

at least 8K memory In acquwtlon costs

fAn Upper Ilmlt estimate Intenderj to Include preventive mmlenance

9AnalYSeS based on rjeternllnatlon of one element at a time Cost estimate Includes hollow cathode lamps for 30 elements and for autOmatlC sample lnjeCtlOn but nOt

for a computerlmlcroprocessor system

hAnalySes based on determination of 5 t. 7 elements at a tfme cost estimate Includes hollow cathode lamps for 30 elements, an auton’ratlc samplelnJE!CtOr, and a data

acquislt!on and control system

‘Llmlted principally to analyses for As, Cd Cu, Fe, Pb, Se, Tl, and Zn, other metal analyses possible but not widely practiced

Isame type of readout facllltlescould be used for botf’r tecflnlques Radlatlon protection required particularly for NAA and PIXE systems

‘Does not Include reactor costs

IReduce by -2513000 If surplus van de Graaff accelerator IS available

structure, to actual types and numbers of analyses to be performed, the efficiencies of the employees involved, and the final laboratory design

configuration, The instrument acquisition estimates include initial installation and assume that

the experience of the operating analyst will minimize startup time requirements. The estimated

number of analyses per 8-hour day assume samples have been previously prepared for the analysis; that the instrument operation will rely on

computer-controlled data acquisition and management; that the salary of the operation would

approximate $20,000 to $24,000 per annum; and

that the instrument would depreciate completely

over a 5-year period. These estimates do not allow

for laboratory refitting or remodeling costs or for

overhead costs above the direct instrument operational costs. Such factors have been excluded

because the costs involved are highly contingent

on the extent of lab refitting required, the location

of the lab, and the wide variations in overhead

charges. It should also be noted that the overhead

costs will be essentially the same regardless of

the lab instrumentation facilities selected. The

footnotes to table H-6 provide further qualifying

information.

The decision to exclude estimates of the costs

of preparing the samples for the analyses has

been based on several factors including: 1) lack of

information regarding sample types and numbers,

2) the influences of the preparation procedures

actually selected on costs, and 3) the fact that the

sample prep costs will be essentially the same for

each of the analytical techniques considered.

Comparisons of the estimates presented indicate that the plasma emission techniques offer

superior economic advantages which are complementary to the sensitivity advantages previously

discussed. Although more analyses per day can

be carried out with the plasma techniques, the

present estimates have been based on the expectation that it will be necessary to analyze each

sample via two different sample introduction

methods to achieve the required sensitivity. Thus,

several elements may be determined by direct

nebulization of the aqueous sample solutions. A

second set of elements, e.g., As, Bi, Hg, Sb, Se, and

Sn, may have to be determined using the hydride

generation method to achieve the required sensitivity (low-threshold effect levels). A similar situation is anticipated for atomic absorption spectrophotometry; direct flame measurements will be

adequate for some elements while furnace measurements will be required for others. Analysis in

the single-element mode for AAS is clearly more

costly. The inclusion of the simultaneous multiele-
Appendix H—Analytical Systems for the Determination of Metals in Food and Water Supplies ● 211

ment AAS estimates is based on present experience at Colorado State University. Conversion of

single-element AAS units to the multielement capability can be anticipated in the near future. The

long-term cost advantages are obvious.

The restricted capabilities of the electrochemical system tend to remove it from competition except as a supplementary or specialized capability.

Primary arguments for the use of NAA or the Xray techniques are based on the ability to directly

analyze tissue (solid) samples without dissolution.

Unless this capability is important, the cost differentials evident in table H-6 argue against their

use.

In view of these data, the use of the ICP-MAES

system as the primary instrument appears quite

rational, The inclusion of an AAS system and an

electrochemical (EC) system as support (e.g.,

cross-check) techniques should be recommended.

The cost estimates given for the AAS and EU units

in table H-6 were based on the expectation that

each might be the primary lab facility. When their

roles are reduced to a secondary (support) level,

less sophisticated (high versatility and production) units may be acceptable. The cost of an adequate AAS facility could thus be reduced by

-$8,000 to $10,000 and that for the electrochemical unit by -$5,000 to $10,000. It should also be

noted that these lower cost units could be interfaced to the ICP-MAES computer system preferably using inexpensive ($300 to $500) microprocessors as buffers.

ESTIMATED ANNUAL SAMPLE

The above estimates of sample throughput capabilities may be used to approximate annual analytical productivities. These are based on a total

of 260 working days per annum minus 60 days for

vacations, holidays, downtime, quality assurance

time, etc., leaving 200 effective 8-hour days. The

projection below is based on the assumption that

the primary load will involve the analysis of biological (organic) tissues; such analyses probably

represent the most rigorous time/cost requirements,

Using the estimate of 15 to 30 samples per day

as the load that can be handled by a sample preparation technician, the annual preparative capability ranges from 3,000 to 6,000 samples. Analysis of these samples for 30 elements (as an upper

limit example) using the plasma emission capability involves performing 90,000 to 180,000 analyses. Applying the lowest analytical throughput

(1,500 analyses/day; table H-6) suggests that 60 to

120 days would be required for these analyses

once the samples were prepared. In essence. this

emphasizes a fairly universal observation, i.e.,

preparation of samples for analysis is often the

factor which limits laboratory productivity. Several inferences may be drawn from the above

sample preparation and analysis estimates:

1. The analytical capability proposed is suffi2

cient to keep 2 to 4 sample preparation personnel busy if biological tissues comprise the

principal workload of the lab.

The sample preparation methods used need

to be upgraded in terms of throughput per

unit time.

3.

THROUGHPUT LOAD

The analytical facility could be used for additional types of analyses which do not require

sophisticated (time consuming) sample preparation operations, e.g., water samples.

Comments on the last two possibilities are appropriate.

Primary factors which affect the sample preparation time/cost requirements include: the elements to be determined and the types of samples.

The determination of toxic elements in natural

and effluent waters is perhaps the simplest case.

The water samples must be filtered and appropriate preservatives added; these operations must

be carried out as soon after sample collection as

possible and preferably in the field so essentially

no lab prep operations are required, Such analyses could occupy the additional time available on

the instrumentation. The preparation of animal

tissues (particularly liver) is at the other extreme.

These contain varying amounts of fatty materials

(lipids) which are difficult to decompose by wet

oxidation techniques thereby requiring that rigorous conditions be used. Although dry oxidation essentially circumvents this problem, the fact that

several elements may be lost by volatilization

forces the use of slower oxidative methods, e.g.,

temperature-programed furnaces, low-temperature ashing units, or sealed [high-pressure) bomb

systems. The estimates given above have been

predicated on the use of wet oxidation (reflux)

techniques in common use; these appear to be less

susceptible to problems than the dry techniques.

It has also been assumed that complete destruc-
212 ● Environmental Contaminants in Food

tion of lipids present is required. An examination

of the literature, however, has not produced convincing evidence that this is essential. The point

raised is simply: Can the most significant fraction

(e.g., >90 percent) of the elements of interest be

“extracted” from the tissue matrices via wet digestion without complete destruction of the fat,

lipids, or cellulose present? If so, the sample preparation times can be prominently reduced. Finally, it should be noted that the wet ashing of biological materials in microwave ovens shows promise in alleviating the digestion time problem. 15 

Spike-recovery studies carried out when food

products were digested via this method are very

encouraging. The ability to reduce sample digestion times by a factor of two or more appears to be

a reasonable estimate. Factors of this nature

must be considered in the final planning stage for

the present program.

Ad[;] At)u-%mra, J. S. hlorris, and S. R. Koirtyohann, An:il.

Chem., 47. 1475 ( 1975). Set! a]so reports on L?SPH contrnct No.

223-75-2268 and U.S. P{~tent 4,080,1 t38.

ANALYTICAL ACCURACY COMPARISONS

As emphasized above, the validity (accuracy) of

the measurements strongly influences the integrity of any decision based on the results, Any measurement is subject to errors which may be influenced by several factors including the measurement methods used and the analyst responsible.

This is the primary reason for stressing the importance of a quality assurance program. The general degree of accuracy that can be achieved with

analytical techniques discussed above can be anticipated to be essentially the same for all techniques. This first approximation expectation is

based on the following. First, each of the techniques discussed essentially requires the same

sample preparation procedures. Since these are

likely to prove to be significant (primary?) sources

of analytical errors, the errors which may accrue

during the preparative steps will be essentially

the same for all techniques. Second, the analysts

involved can be responsible for the cause or prevention of errors depending on the expertise and

caution they exercise. The analyst that tends to

use poor technique or judgment when applying

analysis method A will, in all probability, do the

same for method B; the errors for which he is responsible will be comparable in both cases. Finally, the measurement accuracies of each technique

discussed above are generally similar. As a result, there are no clear-cut, easily defensible reasons for suggesting preference for one approach

over another on the basis of improved accuracy.

RESEARCH NEEDS ASSOCIATED WITH THE PRESENT PROGRAM

In the section discussing the criteria involved in

the selection of an analytical method, the general

importance of being able to identify and measure

the chemical forms or oxidation states of several

elements was emphasized. This emphasis was

based on the fact that all segments of the ecological system are affected to varying extents by the

elements (e.g., metals) present. Indeed, the statement that “the life processes of every living cell

are conditioned by the types and amounts of metals present” would be accepted by a majority of

scientists. Some metals are essential to the health

of living systems and, yet, they may also be insidious pollutants because of their generally nonbiodegradable nature. Only a few metals are completely nontoxic at any concentration level; most

cause deleterious effects at some exposure level.

The ultimate definition of: 1) what constitutes a

deleterious effect?; 2) what actually causes it?;

and 3) what are the operative threshold-effect

concentration levels? cannot be considered trivial

problems. It is unfortunate that simply measuring

the total amount of a particular element present

in an ecological system may, in fact, be only a

gross indicator of potential or actual deleterious

effects, What is often needed is the identification

of the active or functioning forms of the elements

in question. Although numerous examples which

support this statement can be cited, the fact remains that chemical form is often extremely important.

For this reason, the development and refinement of analytical methods and techniques for the

identification of chemical form (chemical speciation), at the trace to ultratrace concentration

levels so often of interest, has received considerable attention in the past decade, Although this is
Appendix H—Analytical Systems for the Determination of Metals in Food and Water Supplies ● 213

clearly an important area of research, progress

has been slow for several reasons. These include:

1.

2.

3.

4.

5.

The analytical techniques most suitable for

the determination of chemical form are also

generally those which lack sufficient sensitivity for use at the low concentrations characteristic of many elements in biological systems.

Biological systems are inherently very complex mixtures of a wide variety of chemical

constituents. It is a truism that the complexity of the identification problem is dramatically enhanced by the compositional complexity of the target system.

While it can be argued that chemical identification techniques are necessary for the

delineation of what chemical forms are biologically or toxicologically important, it appears equally valid to argue that such knowledge on an a priori basis is highly beneficial

as a n aid i n focusing the development t work.

The analytical chemical community is often

only partially aware of what types of chemical speciation measurements are considered

most important by the medical, toxicology,

and ecology communities. Similarly, the latter are often only peripherally aware of the

most promising emergent analytical technology.

The scientific communities involved in this

chemical speciation question have often

been forced by the pressing circumstances

so frequently associated with deleterious effects to expend their efforts on the use of less

than satisfactory approaches leaving less

time for the required types of development.

Although other contributing factors could be

cited, the case in point is simply that the chemical

speciation capabilities so badly needed are available in only limited instances. The development of

adequate speciation technology should be a central thrust of research efforts involving collaborative efforts between the toxicology, biological effects, and analytical chemical communities. Governmental and private funding agencies should

strongly encourage these efforts, Because propogation of chemical speciation developments will

ultimately be essential to the success of the overall monitoring program, the laboratory facilities

available at the outset should take advantage of

present capabilities. Moreover, the prime stance

of the program should be that of providing feedback to the relevant scientific communities as one

means of focusing speciation research efforts on

/

those elements which may appear to be more important from the effects standpoint.

Technology presently exists for the differentiation between the organic (alkylated) and inorganic forms of the toxic elements: arsenic, lead, mercury, and selenium. These rely on the fact that the

inorganic forms can be easily converted to gaseous forms (mercury vapor and the hydrides) by

reaction with borohydride while the organic

forms must first be photodecomposed by exposure

to ultraviolet (UV) radiation, Thus, analysis of the

gaseous reaction products before and after UV

irradiation provides measurements of the relevant organic and inorganic concentrations. This

chemical differentiation approach has been interfaced with atomic absorption and emission spectrometry as the measurement tools; inclusion of

this capability in the laboratory is recommended.

Similarly, the ability to differentiate between

the possible oxidation states for some metals is

important, e.g., As(III) versus AS(V) or Cr(III) versus Cr(VI), Such differentiation for As, Cr, and

some other metals can be accomplished by use of

selective oxidation-reduction (redox) reactions.

The redox reactions may be controlled by proper

selection of chemical reagents or by judicious use

of electrochemical (polarographic or voltammetric) principles. Electrochemical measurements

can also be used to differentiate between electroactive and nonelectroactive (chemically bound)

forms of some elements and between “labile” and

‘‘nonlabile”’ bound forms of some elements. In this

context, labile and nonlabile refer to the thermodynamic and/or kinetic stabilities of the metalligand systems in question. Although this type of

differentiation may be only semiquantitative or

semiempirical in nature, such measurements

have been shown in some instances to be pertinent in experimentally defining bioavailability,

transfer mechanisms, transfer rates. etc. It is certain that research must still be done to further delineate the diagnostic potentials of such types of

differential measurements, Present knowledge

seems sufficient, however, to support the inclusion of polarographic and voltammetric instrumentation in the laboratory facilities for “lability’” and/or oxidation state measurements.

A limited number of other possibilities exist for

chemical speciation measurements. These are

largely very specialized in terms of applicability

to certain types of samples and will not be discussed herein. It is certain that the need for chemical speciation exists and that its importance will

become even more apparent as more definitive
214 “ Environmental Contaminants in Food

monitoring programs evolve. It is also certain that tion problems will involve the application of some

no single analytical technique for speciation or combination of chemical and physical principles,

any other purpose will be a universal panacea. The research programs most cognizant of this are

The ultimate solutions to the majority of specia- most likely to be successful.

GLOSSARY OF ABBREVIATIONS

AAS—atomic absorption spectrophotometry

AES—atomic emission spectrometry

ASV—anodic stripping voltammetry

cc—cubic centimeters

cm--square centimeters

DCP—direct current plasma

DPP—differential pulse polarography

FC—Faradaic or analytical current

Ge(Li)—designates a germanium crystal which has

lithium drifted into it to give it uniquely defined

properties

gin-gram

ICP—inductively coupled (radiofrequency) plasma

MAES—multielement atomic emission spectrometry

Mev--million electron volts

ml—milliliter

NAA—neutron activation analysis

Ng—nanograms—one billionth of a gram

PES—plasma emission spectrometry

PIXE—proton induced X-ray emission (spectrometry)

ppb—parts per billion ( 1 x 10-’) gms/gm on a weight

basis or 1 x 10-j μg/ml on a weight per unit volume

basis)

ppm—parts per million ( 1 x 10-6; gm/gm or 1 μg/ml as for

ppb)

Si(Li)--a silicon crystal which has lithium drifted into it

to provide unique physical properties

SMS—solids mass spectrometry

μg—one millionth of a gram

μl—one millionth of a liter

μm—one millionth of a meter

XES—X-ray emission spectrometry

XRF—X-ray fluorescence (emission spectrometry)
Appendix I

Analysis of Foods for Radioactivity*

by Naomi H. Harley

The analysis of foods for radioactivity should

not be considered as a primary defense against

human intake. The first indication should always

come from information on releases or from measurements of radioactivity in the airborne or waterborne releases. Once the existence of contamination has been established then the foods can be

analyzed to evaluate potential hazard to man.

In contrast to most other pollutants the effects

of radiation are considered to have a linear response regardless of the level, thus, there is no

threshold and no absolutely safe limit. Instead it

is necessary to set some lower level below which

the radioactivity in foods is no longer of interest

as compared with other sources of radiation or

other hazards of life. The analytical significance

of this is that the lower limits of detection for radioactive substances have been brought down to

very low levels and the simple yes or no testing for

acceptability that satisfies regulations for many

other pollutants in foods cannot be used.

The radionuclides of interest in the case of contaminating events are almost all present now in

foods in measurable quantities. Short-lived nuclides are the exception and the transuranic elements are only present at levels that require conThe most useful classifications of a radionuclide are those based on the characteristics of the

radiation emitted and by the identity of the chemical element. The former is both a guide to the nature of the hazard involved and to the measurement required. The chemical species (e.g., element, oxidation state) regulates the metabolic

pathways in the biosphere as well as the nature of

any chemical separations required in the measurement procedure.

* f{k( [:rpi from [III () I A 11 ~~rhllw I)(lp[’r l:rl II tlfxj “‘Arl;ili \is [II

1 II{)(Is for R:i[iro;i(ll\it} .’” A (l)mpl{’tc rIIpV of the p(iper (:ln 1)()

{ )t) t ii I rl~x 1 [rt )m t ht; Nii t I I JIII i 1 1 I;( h rl] ~ i~ I I n [( )rm; i t I( )rl S(I rv I( t’. ( SC(?

i i[)~). J . )

siderable effort in analysis. Since most of the radionuclides are already present, measurements

made for background information should produce

a numerical answer, not merely an indication that

the amount is less than some pre-set value. The

accumulation of background data provides a valuable baseline for evaluating excursions following

a contamination event, The natural activity data

are equally valuable since the amount of information on food concentrations is presently insufficient for valid comparisons with manmade radioactivity.

This report will describe the requirements and

considerations for establishing a system to produce acceptably accurate measurements of radionuclides in foodstuffs. The basic concepts will be

described, but to maintain the necessary brevity,

the detailed procedures that might be used will be

given only by reference.

During the preparation of this report, FDA has

proposed certain recommendations for State and

local agencies on Accidental Radioactive Contamination of Human Food and Animal Feeds. This

material appeared in the Federal Register for December 15, 1978, page 58790, and is interesting

background material for this topic.

RADIONUCLIDES

The emitted radiations are generally grouped

as alpha (cY), beta (ß), and gamma (~). Alpha radiation is characteristic of the natural and artificial

radionuclides of high atomic weight and consists

of energetic particles with very low penetrating

power. Its hazard is significant only within the

body, where alpha-emitting nuclides can irradiate

specific sensitive tissues. Beta radiation appears

in both heavy and light natural and manmade radionuclides, and consists of electrons possessing

kinetic energy and having modest penetrating

power. Gamma radiation is pure electromagnetic

radiation and is extremely penetrating. Thus, it

can be a hazard externally as well as when it is

215
216 ● Environmental Contaminants in Food

present in the body. For the present purpose, we

are only concerned that the penetrating nature of

gamma radiation allows its direct measurement

in foodstuffs, while alpha and beta emitters generally must be separated from the bulk constituents of the sample before measurement is possible.

There are other processes in radioactive disintegration that produce emissions. Alpha emission

is usually accompanied by low-energy gamma

rays that may be used for measurement. X-rays

can be produced by electron capture and some

gamma emitters decay by internal conversion, a

process where a fraction of the gamma rays are

converted to monoenergetic electrons. These

processes do not really modify our measurement

concepts but the decay modes of the significant

radionuclides must be known for their accurate

measurement.

The physical half-life of the radionuclide tends

to control its persistence in the environment. For

example iodine-l 31, with a half-life of about 8

days, is important for only a few weeks, while

cesium-137, with a half-life of about 30 years, may

be a problem for centuries.

A third classification that has some value is the

source that produced the radionuclides. Knowledge of the source of radioactive contamination

gives a good indication of the nuclides that are to

be expected in the sample. This is of considerable

assistance in planning the analysis since requesting a complete analysis for all radionuclides or

even for all types of radioactivity in a single sample would lead to a lengthy and expensive operation. Many radionuclides are not potent health

hazards, particularly those that are not metabolized by the body. The general groups of nuclides

to be expected include the natural activities, specifically radioactive potassium and members of

the uranium and thorium series, and the artificial

fission products, transuranic elements, and other

activation products that result from nuclear

weapon explosions and nuclear reactor operations.

Fission products are a very complex mixture at

the time of formation but the short-lived radionuclides die out rapidly and the mixture becomes

simpler within a few days, The transuranics (plutonium, americium, etc., formed by activation of

the basic fissionable material) are of some interest because of their high toxicity when incorporated into the body but present evidence indicates

that their uptake through the gut is relatively

small and that dietary intake is not a significant

problem. This should be true particularly if the

relative hazard of other radioactive contaminants

probably present in the same sample is taken into

account, The other activation products are frequently elements that make up steel or other

metal containers or structural elements. Radioactive manganese, chromium, cobalt, zinc, and iron

are particularly common and result from interactions of the materials with neutrons released in

the nuclear reaction. It is worth pointing out that

contamination of foodstuffs with single nuclides is

extremely unlikely, and that more than one member of any group will probably be present in any

sample.

DISTRIBUTION OF RADIONUCLIDES

The source of the radionuclides involved will

generally control their distribution in the environment and their consequent transfer to the food

chain. The sources considered here will include

natural radioactivity, releases from operation of

nuclear reactors and processing plants, and fallout from nuclear weapons tests.

Natural activity may be of concern when it is

enhanced by man’s intervention, say by mining to

bring material to the surface and processing the

ore to yield either products or wastes that may

concentrate the radionuclides. Good examples

are radium in uranium tailings, in phosphate rock

waste, or in slags from phosphorus production,

Radium may enter the food chain by dissolving in

ground water and transferring through plant

roots.

Nuclear reactors in normal operation release

chiefly the radioactive noble gases that are not of

interest in considering foods. Reactors do contain

large inventories of fission products, transuranics, and other activation products, however, and

accidental releases can contaminate vegetation

by deposition or through the water pathway. Gaseous releases would most likely involve the volatile elements such as iodine and tritium or those

with volatile precursors, such as strontium-90

and cesium-137, Aqueous releases would follow

failure of the onsite ion exchange cleanup system

and any water-soluble elements could be involved.

Processing plants could also have either gaseous or aqueous releases, but only fuel reprocessing is likely to be a significant contributor. In
Appendix I— Analysis of Foods for Radioactivity ● 2 1 7

this case, the fission products are aged before

processing and iodine and the gaseous precursor

radionuclides are not released. Tritium and carbon-14 are the major airborne products, while the

waterborne radionuclides are the same as for

reactors.

Atmospheric nuclear weapons tests distribute

their fission products, transuranics, and other activation products globally, with local deposition

being more or less, depending on the size of the

weapon and the conditions of firing (high altitude,

surface, underground).

In summary, the deposition of airborne material on vegetation or on soil is the route by which

foodstuffs become contaminated and the subsequent behavior of the radionuclide is controlled

by its chemical nature, including solubility and

plant or animal metabolism.

CONTAMINATION OF FOODSTUFFS

Contamination of foods can occur either

through atmospheric deposition or by transfer

with water. In the first case it is possible for the

radioactive material to be in the form of insoluble

particulates rather than in a more available form

where it will follow the chemistry of the elements

involved. A knowledge of the pathway is not absolutely necessary but it does assist in deciding on

the proper preliminary treatment of the sample of

evaluating exposure. For example, surface contamination may have a different significance than

the same material present in a plant through root

uptake.

Since pathway information is not always available i t is generally considered proper to measure

radioactivity in samples that have been prepared

as if for eating, so as to approximate the true expected intake. This will usually result in stripping

off or washing off of a considerable fraction of

surface contamination. Cooking is generally not

part of the preparation, as the mode of cooking

and the use o f j u ices, cooking water, and the like

cannot be predicted,

Milk is often recommended as an indicator food

for studying radioactive contamination. It has

many advantages:

1. It is available locally at most desired sampling locations.

2. It is marketed rapidly, so that short-lived radionuclides. such as iodine-l31, can be evaluated.

3. It is a major diet component in the United

States, both directly and as an ingredient of

prepared foods.

4. There is a lot of background information

available on previous contaminating events.

It is worth noting that some of these “advantages’ are the factors that contribute t o the role

of milk as a source of human exposure.

Milk is a poor indicator of many contaminants.

The natural activities, the transuranics. and the

activation products have relatively low concentrations in milk. The first two are low because of

poor biological transfer and the last because their

pathways are almost entirely through the aquatic

or marine food chain. Thus, the best approach is

to know what is in the environment through other

monitoring systems, and to design the food analysis program to fit the circumstances.

Other monitoring data are also necessary in

fixing the geographical extent of a contaminating

event. As a general rule, nuclear tests are global

in radionuclide distribution, with enhanced levels

near the test site. Releases from other nuclear operations tend to be more local in their effects and

the food-monitoring plan can be modified to suit.

SAMPLING

The mechanics of obtaining representative food

samples will not be considered here since the procedures are common to all types of food analysis.

There are certain points that must be considered

however. The first is whether the measurements

are being made to determine human intake or the

source of the contamination. In the latter case the

early approach used by FDA(1) for radioactivity is

approp r i a t e. There, each sample was identified

as to its place of origin. For evaluating intake i t is

possible to collect total diet samples for a particular population group and to measure the radioactivity in this composite diet. This approach has

been described by FDA(2) and by EPA(3) and is

normally applied in institutions where mass feeding is carried out. A more elaborate procedure is

to simulate a total diet by measuring a number of

component food classes selected on the basis of
218 ● Environmental Contaminants in Food

statistical information regarding consumption.

This approach was originally used by the Atomic

Energy Commission(4) and was applied originally

to three major cities. This approach does allow

identification of specific food types that are contaminated but requires much greater effort and

cost in analysis.

The use of indicator foods as an intermediate

type of monitoring is widespread. As mentioned

previously, most of the systems depend on the

sampling of milk which is available in most parts

of the country either with specific information as

to place of origin or the general area of the milkshed. Part of the reason for using milk is the ease

in sampling but it also has significance as a primary food for the youngest and most susceptible

population group and it also does tend to pick up

several of the fission product nuclides of dietary

significance such as radiostrontium, radiocesium,

and radioiodine. Most other foods give limited

geographical or seasonal coverage and are less

satisfactory.

The preservation of samples in the field during

transport and in the laboratory awaiting analysis

is only an esthetic matter in the case of radionuelides. Decomposition processes do not change

the radioactivity, and sample contamination by

radioactivity is unlikely. Thus, freezing, formaldehyde addition, or any other method that will maintain the sample is adequate. Any additive should

be checked to assure it does not contain significant amounts of the radionuclide sought.

For the purpose of this report we will assume

that an adequate quantity of a representative

sample is available for analysis and that another

portion is available for storage, either permanently or until the analytical results are accepted as

satisfactory.

SAMPLE PREPARATION

The measurement of radioactivity is a physical

process and it is most efficient when the radioactivity from a relatively large sample can be placed

close to the detector. This means that direct measurements of bulk samples are only useful at relatively high levels of contamination and that most

measurements are preceded by preparation and

possibly chemical separation to reduce the bulk of

the material and to improve the efficiency of the

measurement.

As mentioned previously, sample preparation

may include removal of inedible portions of the

foods or those portions not generally eaten. For

example, citrus rinds, apple cores, outer leaves of

leafy vegetables, and aboveground portions of

root vegetables would normally be discarded. The

general goal is to prepare the foods as if for cooking or consumption.

Foods generally have a high water content and

a primary method of bulk reduction is drying at

room temperature, at elevated temperatures, or

freeze drying, Most of the radionuclides of interest are not volatile under these conditions and

losses must be considered only for elements such

as tritium and iodine. The dried material can be

reduced further by ashing at elevated temperatures, by cold ashing with activated oxygen, or by

wet ashing with oxidizing acids. The sample dryashing process is most likely to lead to loss of

volatile elements but with care even cesium, polonium, and lead can be retained, The other processes should not lead to losses of elements of interest with the exception of iodine and tritium,

mentioned above, and of carbon.

Another approach that is essentially one of reducing bulk is to extract either the original sample or the dried or ashed material with acids or

other solvents and thus remove the desired elements from the bulk of the sample. This requires

considerable testing beforehand to be certain

that the process operates in the desired manner.

All of these procedures reduce the bulk of the

sample and in the case of extraction may also

separate the desired constituents from some of

the remaining inert material. They do not, however, separate the radionuclides of interest completely from the other radionuclides present in

the sample. Such separations will be covered in

the next section, but they may not be necessary if

the measurement technique can provide both

qualitative and quantitative information. In most

cases this limits the possibilities to gamma spectrometry on the prepared sample.

If the samples are going to be subjected to

chemical analysis, the sample preparation must

include the dissolution of the dried or ashed material. This has already been done, of course, in

preparing the wet ashed or extracted solutions.

The radionuclides of interest in ashed foods

should be soluble in strong acids if ashing temperatures have not been excessive, and this treatment is usually accepted. If there is concern that
Appendix l—Analysis of Foods for Radioactivity “ 219

insoluble particulate may be present, it is necessary to use more drastic methods such as fusion to

bring the sample into solution. This should not be

necessary, however, if human hazard is the problem under consideration.

At the time of preparation, if not before, the

basis of measurement must be established. Depending on the use of the data, wet weight, dry

weight, ash weight, volume, or even numerical

count (e. g., eggs) has to be determined. Frequently, this may have to be done in the field, but fortunately, relatively crude measures are adequate,

Since unforeseen questions often arise, it is recommended that as many of these quantities be

measured as is possible.

The requirements for measurement of radionuclides in foods are such that sample preparation

is best handled by the group responsible for the

rest of the analysis. The chief difference from

other types of analytical work is the initial sample. The usual range is from 1 to 20 kg, and the

reduction of this amount of material is a specialized problem.

RADIOCHEMICAL SEPARATIONS

Radiochemical

late the desired

separations are required to isoradionuclide both from the remaining bulk constituents and from other radionuclides which would interfere in the measurement.

In addition, it is necessary to convert the final

product to a form suitable for presentation to the

counter. This may involve elect redeposition, precipitation, or other processes. There are a number of manuals giving the details of specific radiochemical procedures and these details will not be

repeated here. There are a few generalities however that may be of interest.

The actual mass of radionuclide that is measured is almost always vanishingly small. This

means that many of the normal chemical reactions used in analytical chemistry will not take

place; for instance precipitates will not form. For

this reason it is common to add a few milligrams

of carrier material which is preferably the inert

form of the same element. Where this does not exist it is frequently possible to use similar elements

as carrier, such as the substitution of barium for

radium. The inert form then follows normal chemistry, carrying the radionuclide with it. It is also

worth noting that even when the separation technique does not depend on the mass of element

present, a carrier may still be useful in preventing unwanted coprecipitation or absorption on

glassware.

Because of the high degree of purification required in radiochemistry, it has been customary

to make a number of repeated separations either

identical or different to insure purity. To carry

these out in a reasonable time it is better to lose a

small amount of the nuclide sought while removing a large fraction of the undesired material

rather than retaining all of the nuclide and much

of the undesired material. Fortunately, it is possible to measure these losses in analysis and to

make a correction at the end. One approach is to

measure the carrier at the end of the analysis

either by gravimetric or instrumental analysis. If

there was none of the carrier substance present

in the initial sample, the fraction recovered will

be equal to the fraction of desired radionuclide

recovered. Where carriers are not available or

where they are present in variable amounts in the

original sample it is frequently possible to use

radioactive tracers, that is radioactive isotopes of

the same element or a similar element. The fraction of the amount added that is left at the end of

the analysis can be used to determine the recovery of the radionuclide sought.

In the chemical separations there is considerable use of classical analytical chemistry based

on precipitation and in most cases it will at least

appear as a final collection step to put the desired

radionuclide in a condition suitable for counting.

In addition the general techniques of ion exchange, liquid extraction, distillation, and electrolysis are used.

Since many of the separations in radiochemical

analysis are carried out in small volumes the centrifuge is widely applied, It has become common

practice to redissolve and reprecipitate rather

than to wash precipitates carefully. This may be

repeated several times very rapidly and will generally give good decontamination (separation

from other radionuclides). As noted above, where

the element sought and the contaminant have

similar properties it is preferable to use two different precipitations, a precipitation followed by

an extraction, or any two widely different steps to

achieve good decontamination.

One process that is frequently of value is called

scavenging. This term is usually applied to a pre-
220 ● Environmental Contaminants in Food

cipitation carried out to remove contaminating radionuclides after the bulk matrix of the sample

has been removed. The process involves the addition of a group carrier, precipitation, and discarding of the precipitate. A typical example would be

an addition of iron carrier followed by hydroxide

precipitation to remove rare earths and other

heavy metals in a determination of an alkali or

alkaline earth. Frequently the scavenging procedure is repeated to improve decontamination, but

it is only rarely that the scavenge precipitate is

redissolved and reprecipitated to recover any of

the desired constituent that may have been absorbed.

After suitable radiochemical separations have

been made, it is necessary to collect and mount

the sample for counting. This is most often done

by precipitation or by elect redeposition. In the

section on measurement, the requirements for

sample preparation are discussed: for example,

the sample area and mass should be reproducible

and the sample should be mounted on a sample

holder identical with that used for the counter

standard. Since it is frequently necessary to determine the weight of precipitate for recovery determination, this factor must also be considered.

The selection of a mounting technique is usually a compromise between convenience and the

counting requirements. Besides consideration of

the type and energy of emission, practical matters

such as the counter size and sample mounts available must be weighed,

In certain cases, the total amount of sample

available may be limited and analysis for several

radionuclides may be required. Procedures

should be on hand for the sequential analysis of

single samples, even though separate samples are

used for routine work.

MEASUREMENT

The method of measurement to be selected depends on the type of radiation, the form of the

sample, and to some extent on the amount of radioactivity. It is necessary that the complete analytical procedure be designed so that the sample

is brought to a suitable form for the equipment

and conditions that exist.

It is possible to measure the total gamma, total

beta, or even the total alpha activity on a sample

of food, Unfortunately, such data are valueless in

estimating human exposure. The accuracy of the

determination is very poor, natural potassium

usually interferes, and the chemical and radiation characteristics needed to evaluate possible

hazard are not known. It is possible, however, to

set a particular total activity level as a screening

level for a specific food. If the measured value is

below the screening level, no analyses for individual radionuclides are performed. In such a case,

the measurements should be considered as internal data only and the numerical results should not

be published. Any report should merely list the

samples as having activities below the stated

screening level.

Qualitative identification of radionuclides on

original samples of foods is limited to gamma emitters at relatively high levels. The sensitivity can

be increased if some bulk reduction, as described

under “Sample Preparation, ” is carried out. The

identification of alpha and beta emitters depends

on radiochemical separation for element identification and the measurement of energy or half-life

on the separated material for radionuclide identification. The latter step may be omitted if other

considerations limit the possibility to a single radionuclide.

The equipment available for quantitative measurement of radioactivity is sufficiently sensitive

for all foreseeable cases. Instruments for detection of the three major emissions are described

here, and their applications are shown in table 20

(chapter VIII) in terms of the detection limits for

various radionuclides.

It is worth pointing out that a number of the instruments described are not commercially available. They have been in the past, but the low demand has removed them from the market, The

necessary electronic components are available

but the mechanical assemblies for the detectors

are not, and the larger laboratories tend to build

their own systems.

Alpha Emitters. The measurement of alpha activity is best carried out on a very thin sample to

avoid self-absorption of the alpha particles. This

is even more true for spectrometry since degradation of the original alpha energy will give a spectrum with poor resolution. The measurement of

the total alpha activity can be carried out either

in thin-window counters or by scintillation counting with zinc sulfide phosphor. Both techniques

have high efficiency but the scintillation method

can give a considerably lower background with a

consequently lower limit of detection. Unfortunately, neither system is readily available as a
Appendix I— Analysis of Foods for Radioactivity . 22 1
222 “ Environmental Contaminants in Food

Figure I-1 .—Comparison of Gamma Spectra Taken With a Sodium Iodide Detector (Upper Curve) and

a Germanium Diode Detector (Lower Curve). Note that the main single peak in the sodium iodide spectrum is

resolved into 9 peaks for 6 radionuclides with the germanium diode spectrum “

o

purities are greatly reduced compared to spectra

from sodium iodide detectors. The efficiency of

the diode is low and, for many analyses, a spectrometer can only be used for one measurement a

day. Another disadvantage is that the detector

must be kept at liquid nitrogen temperature to

maintain its detection capability. Newer diodes

have been developed that do not require storage

at liquid nitrogen temperatures; however, they

must be cooled during measurement. Since the

system is in use most of the time, this may not be a

significant advantage.

Diode spectrometers may also be used to measure the low-energy gamma-rays that accompany

alpha emission. This allows direct measurement

in some environmental samples, but the levels in

foods have not been high enough for this technique.

General Requirements. The choice of a counting procedure depends on the precision required.

In turn, the relative precision of a quantitative

counting measurement is inversely proportional

to the square root of the number of counts obtained. Thus, any improvement in precision must

be obtained by increasing the number of counts.

This can be done by using larger samples, by

counting for longer times, or by using counters

with higher efficiency. A secondary improvement

is possible for low-activity samples by decreasing

the background. Each of these improvements has

some drawback, and selection of the optimum balance requires a degree of experience to weigh
Appendix l—Analysis of Foods for Radioactivity “ 223

cost, manpower, and quality. For example, handling larger samples increases the effort in sample preparation and radiochemistry while longer

counting times require more counters, and increased counter efficiency or lower background

is expensive.

Counting-room operation requires the maintenance of detailed records on standardization,

background, and sample measurement. This information can frequently allow the recovery of

bad data or the correction of calculational errors.

In addition, maintenance of control charts(5) will

signal when instrument problems arise.

Experience with modern nuclear instrumentation has been good, and downtime of the order of 5

percent is common. This requires that service be

available immediately or the next day following a

breakdown. The increasing complexity of measuring systems tends to preclude in-house servicing

in most cases, but some diagnostic capability and

competence in minor repairs is very valuable.

CONTROLS

An analytical laboratory carrying out measurements of radioactivity in foodstuffs will require a

program to document the validity of the measurements, This is necessary in legal cases and is also

highly desirable when data are being presented

for use in decisionmaking. A suitable program of

quality control should be carried on in addition to

the necessary calibrations and standardizations.

Calibration is the determination of the relationship between a desired quantity and the response

of a particular instrument. In the case of radioactive materials this may mean that the instrument

must be calibrated with each radionuclide to be

measured unless there is evidence that the instrument response is independent of the energy or

other characteristics of the radiation. Alternatively a complete response v. energy calibration

may be substituted. These calibrations, to have a

legal standing, should probably be traceable to

the U.S. National Bureau of Standards or comparable authority. This turns out to be a requirement

that is far from trivial in the effort required.

Fortunately, a complete calibration is not required at frequent intervals and, depending on

experience, may not be needed oftener than every

few months. In the meantime of course it is necessary to have assurance of the proper operation of

measuring equipment but this can be done with

simple standards or even with samples that are

reproducible over a period of time. For example, a

simple counter standard may be run every morning before starting operations just to be sure that

the counter is working properly. Similar standards should also be available for checking spectrometer energy response.

An ideal quality control program should include the checking of the complete procedure

from sample preparation through measurement.

This requires that standard samples be available

for testing the full procedure. Additional controls

would include running of blind duplicate samples

to test reproducibility of analyses, and blank

samples to check on the possibility of laboratory

or reagent contamination. These three types of

samples should make up at least 10 percent of the

laboratory output if the quality of measurement is

to be followed closely. It is also necessary that the

data be published with the ordinary laboratory

results and that any deviations from the expected

results should be used to make suitable corrections in laboratory operations.

There is always some danger that a laboratory

may drift out of control in spite of an adequate internal quality control program, This is possible

since an internal program may emphasize consistency while the absolute values drift. Therefore,

some part of the quality control effort must be

devoted to intercomparisons with established

groups, such as IAEA or EPA. This should be done

on an annual basis, at least.

It must be noted that standard samples are frequently not available, and recourse must be had

to “spiking,” which is the addition of a known

amount of a radionuclide to a sample that is relatively free of that nuclide. Recovery of the spike is

not necessarily a good test of a chemical procedure, since a natural sample may be more difficult to analyze.

A final component of a good quality control system is a careful, responsible review of all the data

produced. This means checking the arithmetic,

knowing the characteristics of the equipment and,

hopefully, having a sixth sense that recognizes

that certain results do not look right. This is

especially true when relying on automatic counters or on computer processing of the data.
224 . Environmental Contaminants in Food

STAFF AND FACILITIES

A minimum facility could be designed around a

staff of six, including a B.S. or M.S. senior chemist

with experience, a B.S. junior chemist and three

technicians for chemistry, sample preparation,

and counting-maintenance, A- secretary-administrative assistant could handle reports, local purchasing, and similar duties. With this small staff,

considerable versatility and flexibility would be

required.

The measurement of radioactivity in foods requires fairly extensive facilities to handle the

varied analyses that might be called for, In addition to a modest office space, separate rooms

would be necessary for sample preparation, wet

chemistry, measuring equipment, and for maintenance support and storage. The first two laboratory rooms would require hoods, chemical

benches, and laboratory safety devices such as

showers and eye fountains. Since the samples to

be measured are normal foods there are no special requirements for radiation safety, If the samples were radioactive enough to be a personnel

hazard in the laboratory they certainly would not

require this type of precise measurement.

If the laboratory is to be in continuous operation it is most likely that the principal chemical

and measurement systems will have to be available at least in duplicate. This and similar considerations lead to the conclusion that a certain

minimum size and sample throughput are not necessary if the radioactivity laboratory is part of a

larger operation which can furnish support. One

continuing problem is the need for electronic

maintenance of radiation measuring equipment.

This is rather specialized and must be considered

either when staffing the laboratory or in locating

it where such services are readily available.

It is not always possible to purchase the ideal

counting equipment for a particular purpose. The

total demand for many systems is small and commercial instrument makers are not interested.

Large laboratories can make some of their own

equipment but this is not possible for the group

described here. The construction of alpha and

beta radiation detectors requires services of a

first-class machinist plus sufficient electronic

know-how to transfer the detector signal to the

available commercial equipment. Where such capability already exists in the overall organization,

it may be fruitful to copy advanced noncommercial instruments, but staffing specifically for this

function is probably not economical. Thus, most

small laboratories must operate with the lessthan-optimum commercial equipment,

If significant uses are to be made of gamma

spectrometry there will be a need for at least

modest computing facilities. These can be part of

the purchased spectrometer system but this is an

expensive method if suitable computer time is

available otherwise. The former approach is used

here, and it might be noted that the spectrometer

computer has capacity for other work.

Additional space is required not only for stocking necessary reagents and materials but also for

storage of incoming samples and for storage of

residual material from samples that have been

run. As a general rule it is desirable to take a

larger sample than would be required and to set

aside a portion of this for possible contingencies

or if the data are later brought into question.

The output of a group this size should run between 1,000 and 4,000 samples] a year, depending

on the difficulty and the activity level, One limiting factor is that, at background levels, each

counter can only turn out one or two samples per

day. Following a contaminating event, it should be

possible to process smaller samples and to count

for shorter times, both of which would allow higher output. It might be possible to add 3 more laboratory staff plus 50 percent more space and

equipment dollars and essentially double the output. Further increases would probabl y run into

other bottlenecks due to the need for added support.

Table I-1 details the costs for space modification and furnishings ($140,000), for equipment

($200,000), and for supplies ($20,000). These costs

are based on a building in place, lights and partitions in place, and utility stubs in each room, It is

also assumed that building services are provided.

IA sample is defined as a ~x]mp]ete gamm{i spectral an[]lysis

or a single raciionuclicie an[]lysis that requires preparation plus

r:idi(x:hemist rv.
Appendix I— Analysis of Foods for Radioactivity ● 225

Table I-1. —Costs for Space, Furnishings, Equipment, and Supplies

Cost cost

Space modification and furnishings

Chemical laboratory—20 x 30 ft.

Base cabinets $ 8,500

Wall cabinets

Storage cabinets

Sinks (2 )

Hoods (3)

Services and Installation .

Preparation area— 10x 30 ft.

Base Cabinets

Wall cabinets

Storage cabinets

Sink

Hood

Benches

Services and Installation

Counting area— 10x 20 ft. (air-conditioned)

Benches

Rack

Base cabinets

Wall cabinets

Desk, etc.

Services and installation

Storage area— 10x 20 ft.

Acid storage

Solvent storage ,.

Cabinets

Services and Installation

Office area —library 10x 20 ft.

Desks, etc (4)

Cabinets, bookcase s

Services and Installation

Equipment

Chemistry area

Hot plates (2)

Stirring plates (6)

pH meter

Demineralizer

Centrifuges (3)

Platinum ware(12 items)

2,500

1,800

1,200

7,000

40,000

3.800

1,800

1.500

600

2,500

600

25,000

1,200

1,000

1,700

600

500

12,000

800

600

3,000

1,500

2,000

3,000

1,000

600

900

350

500

1,800

12,000

APPENDIX I REFERENCES

1.

2.

3.

E. P. I.aug, et al. ‘radioactivity in F’oods, ”’ journal

A(~A(; 44, 52.3-30 ( 1961), :+Iso 4’Strontium-90 An~~lyses of I [uman an(i Animal Foods, H(l(liologic(]] 4.

HefJ](h fljt{] 1, 36-40 (hfay 1960).

‘1’een-Ager Diet Survey, Food and Drug Administration, ll{~(lif)]f)gicfl) Fff?fI)th ll{!(fl 4, 18-22 ( 1963)

R. E. Simpson, E. J. Barat ta, and (;. h’. Jelinek, “Radio- 5.

nucli[ies in F’(Nxis: Nloni (orin~ Program. ” Rcl(fio (i{)n

Data un(~ Heports 15, 647-56 ( 1974). (rI’his is a later

report thti t summa rizes much of the EPA program. )

J. H. Harley and Joseph Rivera, Summ[lr} of Av(lilable h] ta on the Stron fium-{~[~ Con tent of F(mds (]n(l

Total Diets in the United St{ltcs, LJ, S. AEC Report

HASL-90 (August 1960).

J. 11. Ilarley IEciitor). EML Procmiures M(lnu(ll, U.S .

I)OE Report F{ ASL-300 ( 1972, revised annually).
226 ● Environmental Contaminants in Food

GENERAL REFERENCES

Radiochemical Methods

National Academy of Sciences, Nuclear Science Series

(NAS-NS 3001 ff), Office of ‘1’echnical Services,

Washington (1960 and later), A Series of Monographs on Individual Elements and Techniques.

WHO-FAO-IAEA, Methods of Radiochemical Analysis,

World Health Organization, Geneva ( 1966).

Johns (Editor), National Environmental Research Center, Las Vegas, Handbook of Radiochemical Analytical Methods, EPA-680/4-75-001, February 1975.

Harley (Editor), Environmental Measurements Laboratory, DOE, EML Procedures Manual, HASL-300,

1972 (Updated Annually).

International Atomic Energy Agency, Reference Methods for Marine Radioactivity Studies (Sr, Cs, Ce, Co,

Zn), Technical Reports Series No. 118 (1970).

Ibid. (Transuranics, Ru, Zr, Ag, I)

Technical Reports Series No. 169 (1975)

Measurement of Radioactivity

National Council on Radiation Protection and Measurements, A Manual of Radioactivity Measurements Procedures, Report 58 ( 1977).

National Council on Radiation Protection and Measurements, Environmental Radiation Measurements,

Report 50 (1976).

International Commission on Radiation Units and Measurements, Measurement of Low-Level Radioactivity, Report 22 ( 1972).

International Atomic Energy Agency, Measurement of

Short-Range Radiations, Technical Reports Series

No. 150 ( 1973).

International Atomic Energy Agency, Metrology and

Radionuclides (Symposium), IAEA, Vienna ( 1960).

Crouthamel (Editor), Revised by Adams and Dams, Applied Gamma-Ray Spectrometry, Pergamon, New

York (1970).

Data Compilations

Lederer and Shirley, Table of Isotopes—7th Edition,

John Wiley, New York (1978).

Health, Scintillation Spectrometry, Gamma-Ray Spectrum Catolog (3rd Edition), USAEC Repor t

ANCR-lOOO ( 1974).

Chanda and Deal, Catolog of Semiconductor Alpha-Particle Spectra, USAEC Report IN-1261, March 1970,

Niday and Gunnink, Computerized Quantitative Analysis of Gamma-Ray Spectrometry, USAEC Report

UCRL-51061, 4 Volumes (Includes Decay Scheme

Data Library).

Quality Assurance

Kanipe, Handbook for Analytical Quality Control in Radioanalytical Laboratories, EPA Report 600/7 -

77-088 (April 1977),

Ziegler and Hunt, Quality Control for Environmental

Measurements using Gamma-Ray Spectrometry,

EPA Report 600/7-77-144 (I)ecember 1977).

See also:

Metrology Needs in the Measurement of Environmental

Radioactivity Environment International 1, 7 ff

(1978),

GLOSSARY

Activation Products—The radionuclides formed in

either fissionable material or in surrounding material during a nuclear reaction, usually by capture of

neutrons,

Carrier—A stable element added in radiochemical

analysis to provide sufficient mass that a radionuclide can follow various separation steps.

Detector—Any device that transforms the radiation

emitted by a radionuclide into a signal that can be

handled electronically. The most usual signal is an

electrical pulse which can be recorded.

Disintegration-The spontaneous process by which a

radionuclide gives off energy in the form of nuclear

radiation.

Fissionable Material—Any of the heavy radionuclides

which can undergo fission, or splitting into two or

more lighter atoms. The fission process is accompanied by a large release of energy.

Fission Products—The radionuclides formed when fissionable material splits into two or more atoms.

Geiger Counter— A detector based on gas ionization

which converts any ionization within the detector

into a large electrical pulse.

Germanium Diode Detector—A gamma-ray detector

composed of very pure germanium, usually activated with lithium.

Indicator Food—A food that is measured to give an

estimate of the total dietary intake of man.

Ionization Chamber—A radiation detector based on

gas ionization which converts any ionization within

the chamber into an equivalent electrical pulse.

Pathway—The route by which a radionuclide is transferred from the source through the environment to

man.

Picocurie—See units of radioactivity. Equal to 2.2 disintegrations per minute.
Proportional Counter—A detector based on gas ionization which converts any ionization within the detector into an amplified electrical pulse proportional to

the amount of ionization.

Radionuclide—Any atomic species which is unstable

and gives off nuclear radiation to attain stability.

Scintillation Detector—A detector which converts nuclear radiation to a pulse of light. This, in turn, can

be converted to an electrical pulse with a phototube.

Sodium Iodide Detector—A scintillation gamma-ray detector made up of a single crystal of sodium iodide

activated with silver.

Spectrometry—The measurement of the energy of radiation emitted during decay of a radionuclide or mixture of radionuclides. Quantitative as well as qualitative information may usually be derived.

Appendix I—Analysis of Foods for Radioactivity . 22 7

Tracer—A radionuclide added in radiochemical analysis to follow the distribution of the desired constituent in various separation steps.

Transuranic Element—An artificial element having a

higher atomic number than uranium, formed by activation, usually with neutrons.

Units of Radioactivity—There are various ways of expressing the disintegration rate of a radionuclide.

In this report the disintegrations per minute (dpm)

unit is used. In other reports, the curie and its submultiple (millicurie, microcurie, picocurie) are

used and the new International Standard nomenclature is the bequerel, equal to one disintegration

per second.
Commissioned

Appendix

Papers

1, Clement Associates, Inc., Washington, D. C.,

“Priority Setting of Toxic Substances for

Guiding Monitoring Programs. ”

2. Congressional Research Service, Science Policv Research Division,

●

●

●

Christopher H. Dodge, “Contamination of

Food by Radioactive Nuclides. ’

Sarah L. Hartman, “Nitrate Food Contamination: A Case Study. ”

Jo-Ann M. McNally, “Mercury: Environmental Contamination of Food, ” “Polybrominated Biphenyls: Environmental Contamination of Food, ‘“Polychlorinated Biphenyls:

Environmental Contamination of Food. ”

3. Dr. William E. Cooper and R. V, Farace, Department of Zoology, Michigan State University, “Toxic Substances in Food Information

System: Design and Management.”’

4. Dr. Kenny S. Crump and Marjory D. Masterman, Science Research Systems. Ruston, La.,

5

6.

7.

8,

90

“Assessment of Carcinogenic Risks From

PCBS in Food. ”

Dr. Donald Epp, Department of Agricultural

Economics and Rural Sociology, Pennsylvania

State University, “Determining the Economic

Impact of Alternative Action Levels. ”

Dr. Naomi H, Harlev, Institute of Environmental Sciences, New “York University Medical

Center, “Analysis of Foods for Radioactivity. ”

Dr. John L. Laseter, Environmental Affairs,

Inc., New Orleans, La. “Approaches to Monitoring Organic Environmental Contaminants

in Food’ (appendix G).

Dr. Frank Lu, School of Medicine, University

of Miami, “Environmental Contaminants in

Food: International Activities. ”

Dr. Rodney K. Skogerboe, Department of

Chemistry, Colorado State University, “Analytical Systems for the Determination of Metals in Food and Water Supplies” (appendix H),

10. SRI International, Menlo Park, Calif., “Assessment of Methods for Regulating ‘Unavoidable’

Contaminants in the Food Supply.”’

11, Tracer Jitco, Inc., Rockville, Md., “Cas e

Studies on Consumer Risk from Environmental

Contaminants in Food. ”

,

228
Appendix K

Executive Agency Observers at

Advisory Panel Meetings

U.S. Environmental Protection Agency

Fred Arnold* Marty Halper*

Rufus Morrison Janice Ryan

U.S. Department of Health, Education, and Welfare

Food and Drug Administration

John Wessel* Charles Jelinek Pasquale Lombardo

Bart Puma Sidney Williams

U.S. Department of Agriculture

Food Safety and Quality Service

Grace Clark* Richard Ellis

William Leese John Spaulding

*Official agency liaison to the assessment,

229