INV-462 -HQ
JUNE 30, 1977
ry-	1
Submitted, by: Arnold J'j Schneider
Kenneth J. WiLk
Approved by; Francis B. Dukes
Inspection Branch

P i ctp
Exhibits	ii
Predication	1
Summary*	1
Details	2
James Michael Conlon	2
Fitzhugh Green	2
Lamar B. Dale, Jr.	3
Jean Pulliam	4
Mrs. Leonard Axelrod	4
Kenneth O. Olsen	5
Edwin L. Johnson	5
Irwin Baumel	6
Robin Zener	6
Jefiery Howard	5
Lee Schroer	7
Pair. SyriOnds	3
Jane Stieoer	3
Mary Rusnak	3
William Vernon Hartwell	3
W a y 1 a nd H a ye s	9
Eli Swisher	10
Compilation of EPA Agency Policy and DHETv"
Regulations involving testing on Human Subjects	10

A.	Copies of Newspaper Articles from the Washington Post of
May 11, 1977 and the New York Times of May 12, 19 77
B.	Congressional Inquiry from Senators Warren Magnuson and
Adlai Stevenson dated May 11, 1977
C.	Proposal for a sole source contract to test thyroid effects, of
selected EBDC fungicides and their Metabolites in Humans
D.	EPA Order 4540.1, Clearance of Foreign Grant and Contract
E.	Memorandum dated March 5, 1973 from Dr. H. Fairchila,
Special Pesticide Review Group to Dr. H. Korp, Deputy
Assistant Administrator, Office cf Pesticide Programs
F.	Memorandum dated March 12, 1974 from Dr. W. Roessler
Deputy Director of Criteria and Evaluation Division to DAA
for Pesticide Programs
G.	The Vanderbilt University proposal submitted by Dr. W. Hayes
on September 20, 191
H.	Memorandum dated C ctober 2, 1974, from Dr. L. Dale to
Director, Criteria ard Evaluation Division
I.	Memorandum dated v ;tcber 9, 1974, from Dr. Axelrod to
the DAA for Pesticide Programs
J. Memorandum dated November 7, 1974, from Dr. Axelrod to
the DAA for Pesticide Programs
K. Handwritten note dated December 13, 1974, from Edwin L.
Johnson to Dr. Axelrod
L. Internal review dated February 1975 of Ethylene Biscithio-
carbamate Fungicide'" and their Residues dated February 1975
M. 1975 FOI Request from the Environmental Defense Fund;
Health Research Group; a citizen; and the answers
N. Disapproval of the proposal for the sole source contract to
test thyroid effects of selected EBDC fungicides and their
metabolites in Man
O. Memorandum dated April 29, 1975 from Lee Schroer, Attorney
to Jeffery H. Howard, Associate General Counsel.

P. C&P Telephone printout of Long Distance Telephone Service
Q. Compilation of EPA Agency policy and DHEW Regulations
involving testing on Human Subjects

This investigation is predicated upon an oral request from
James M. Conlon, Associate Deputy Assistant Administrator for
Pesticide Programs to investigate the facts surrounding the
proposal to test the fungicide, EBDC, and its metabolite, ETU,
on human subjects in Mexico in order to be familiar with and
responsive to the report on this proposal that appeared in the
Washington Post on May 11, 1977 (Exhibit A).
Subsequently, a request for an investigation into this matter was
received from Senators Warren Magnuson and Adlai Stevenson
(Exhibit B).
Ethylene bisdithiocarbamate (EBDC) is a widely used fungicide
which degrades into ethylene thiourea (ETU) and appears as a
residue in food and feed crops. High levels of ETU in diets of
experimental animals result in hyperplasia and adenocarcinoma
of the thyroid gland. While tolerance levels exist for the EBDC
fungicide, no tolerance levels have been established for ETU.
With this problem and the fact that EBDC is on the list of fungi-
cides to be re-registered under the Pesticide Act, the Criteria
and Evaluation Division attempted to find a way to set the toler-
ance levels. From 1974 to April 1975 memoranda, reports, and
proposals were made concerning the testing for tolerance levels
of EBDC and ETU, including testing in humans.
In April 1975, a proposal was prepared by Dr. Axelrod, Director
of the Criteria and Evaluation Division, requesting a contract be
awarded to a researcher in a Mexico City hospital to conduct human
testing involving EBDC and ETU in Mexico City.
Since 1972, EPA has incorporated Department of Health, Educa-
tion and Welfare (DHEW) regulations concerning any testing
involving human subjects. EPA also has a procedure which must
be followed in all foreign contracts and grants. As the proposal
in question involved both of these elements, it would have been
subjected to these provisions. Modifications would, necessarily,
have to have been made and various approval outside of the Office
of Pesticides were needed, including that of the Department of
There is no evidence that the proposal was written by anyone
other than Dr. Axelrod; and approvals appearing on the proposal
were routine approvals within Pesticide Programs. The proposal
was disapproved by the Deputy/ Assistant Administrator for Pesti-
cide Programs and never reached the formal contract stage where
outside approvals would have been needed.

Interview of James Michael Conion
Mr. Cordon, Associate Deputy Assistant Administrator for Pesti-
cide Programs was interviewed on May 14, 1977. According to
Conlon, a contract proposal was written by the Criteria and
Evaluation Division (Exhibit C). It proposed that a sole-source
contract be entered into with a hospital in Mexico City for the
purpose of studying the effects of selected EBDC fungicides on
humans. The proposal was disapproved by Dr. Edwin L. Johnson,
Deputy Assistant Administrator (DAA) for Pesticide Programs.
Interview of Fitzhugh Green
Mr. Green, who in 1975 was the Director of the Office of Inter-
national Activities for EPA, was interviewed on May 23, 1977.
He said that he received a telephone call from someone in
Dr. Axelrod's office who made an inquiry about giving a contract
to a researcher in Mexico. Green described this inquiry as a
trial balloon. He was not sure of the identity of the caller but
did remember that the proposal was explained and that the reason
given for going to Mexico was to avoid the DHEW "prohibition"
on testing humans. Green said he responded to the caller that
this was a "bum idea." The caller said, "How could you make
up your mind without seeing the proposal?" Green said he told
the person to bring the proposal to his office. He added that was
the last he heard of it.
He said the next time he saw Johnson, Green asked about the
proposal. Johnson said that he "canned it," Green said that any
indication that he approved the proposal, as reported in the
newspaper, is a "total lie."
NOTE: EPA Order 4540.1, dated December 2 9, 1972, requires
the formal and signed approval of the Office of International
Activities and the concurrence of the Department of State on ail
proposals for awarding foreign grants and contracts (Exhibit D1*.
This proposal had not reached the stage where this procedure
would have taken place. Consequently, formal, signed approval
of the Office of International Activities or concurrence of the
Department of State was never obtained. The procedure based on
this order is for the program to request clearance of foreign
research award from International Activities. International
Activities sends the scope of work on the proposal with a request
to the Department of State for its concurrence. The Department
of State notifies the U. S. Embassy in the country where the con-
tractor or researcher is located. The U. S. Embassy then verifies
the reputation of the researcher and the affiliated comoany or

universitv. After the concurrence and the award of the contract,
EPA advises the State Department and the U. S. Embassy of
the status of the project.
Interview of Dr. Lamar B. Dale, Jr.
Dr. Dale was interviewed on May 25, 1977. He stated that he told
the newspaper reporter that the proposal was Dr. Axelrod1 s idea.
The concept of testing on humans to determine tolerances for EBDC
and ETU began with a memorandum (Exhibit E) dated March 5,
1973, from Mr. Homer Fairchild, Acting Coordinator, Special
Pesticide Review Group, to Dr. Henry J. Korp, Deputy Assistant
Administrator, Office of Pesticide Programs (OPP).
Dr. Dale said any contract for human testing would have to be
given to a qualified clinician who would have to go before a DHEW
panel for permission to do the study. After permission is given,
the contract study could begin.
Dr. Dale stated that the idea of human testing continued to be
entertained, and the need for a contract was discussed in a memo-
randum from William Roessler, Deputy Director, Criteria and
Evaluation Division, to the DAA of Pesticide Programs (Exhibit F).
In September 1974, according to Dr. Dale, an unsolicited proposal,
was received from Dr. Wayland J. Hayes, Jr. of Vanderbilt
University to test dithiocarbamate fungicides (EBDC) on humans
(Exhibit G).
Dr. Dale said Dr. Axelrod did not think the proposal was accept-
able because it did not include a stud3/- of ETU. Dr. Dale also
expressed the opinion that he thought even Dr. Hayes wasn't con-
fident that the proposal would be approved.
Dr. Dale wrote Dr. Axelrod on October 2, 1974, he considered
the Vanderbilt proposal to be excellent, and with minor alterations,
would provide the data needed for a decision on EBDC (Exhibit H).
Dr. Axelrod then wrote the DAA for Pesticide Programs support-
ing the proposal stating, . .As 3/ou know, the previous studies
and analyses of animal experimentation have yielded equivocal data,
and we would have the privilege of an ethical and acceptable human
experimentation..." (Exhibit I).
Dr. Dale drafted a memorandum on November 7, 1974, for
Dr. Axelrod's signature to the DAA for Pesticide Programs
criticizing the Vanderbilt proposal and suggesting the addition
of "short term studies in humans with ETU to establish a level
which has no adverse effect on thyroid function" (Exhibit J).

Dr. Johnson, DAA for Pesticide Programs, replied on December 13,
1974, to Dr. Axelrod's memorandum of November 7, 1974 with a
handwritten note expressing doubt for the need of the Vanderbilt
study, but leaving it up to Dr. Axelrod to decide whether to proceed
with the study (Exhibit K).
Dr. Dale said he felt any human study should be done by industry,
but Dr. Axelrod felt EPA should do it as the public would not
trust the results from industry.
Nothing came of the Vanderbilt study. In February 1975, an internal
review was completed on EBDC, which, among other issues identified
the need to study EBDC and ETU in humans (Exhibit L title page
and pertinent pages only).
Dr. Dale said that he was told by Dr. Axelrod that he (Dr. A.xelrod)
was "going to Mexico" on a proposal for EBDC. Dr. Axelrod also
told Dr. Dale, that he (Dr. Axelrod) had talked with Fitzhugh
Green of International Activities concerning a contract in Mexico.
Dr. Dale said the next thing he knew was that the contract proposal
was on Johnson's desk and a Freedom of Information (FOI) request
had been received from the Environmental Defense Fund (EDF) re-
garding the proposal. Dr. Dale added that Dr. Irwin Baumel, a
toxicologist who formerly worked for him, may have worked on
the contract proposal since Baumel was the Branch's "EBDC man."
Interview of Jean Pulliam
Jean Pulliam, Research Progress Coordinator, OPP, was inter-
viewed on May 26, 1977. She worked for Dr. Axelrod as a branch
chief during the period in question, and she was an associate of his
when both were employed by Southwest Research Institute in San
Antonio, Texas. She denied any involvement in the planning of the
"Mexican proposal" and did not know who else ma;/ have been in-
volved besides Dr. A.xelrod. Pulliam considered herself to be a
close personal friend of Dr. Axelrod and because of their friendship,
she took responsibility for removing Dr. Axelrod's personal effects
from his office after his death in August 1975 and giving them to
Mrs. Axelrod.
Interview of Mrs. Leonard Axelrod
On June 3, 1977, Mrs. A.xelrod was contacted telephonically to
arrange for an interview. Mrs. Axelrod advised she had no informa-
tion to offer regarding this investigation. She also stated that the
boxes of her husband's personal effects, which had been returned
to her by Jean Pulliam, did not contain any office files. Since the
boxes only contained personal effects, Mrs. Axelrod said she would
object to EPA investigators looking through them.

Interview of Kenneth 0. Olsen
Kenneth O. Olsen, Supervisor of Information and Management Group,
Office of Toxic Substances, was interviewed on May 2 7 and May 31,
1977. During the period in question he was a program manager for
Dr. Axelrod. Olsen maintained that he had an administrative function
within the group and had no action involving the proposal other than
seeing that funds were available. Olsen said that one of his duties
was to write status reports of projects and that is why his name
appears on office memoranda. He denied any involvement in the
proposal or any knowledge of how it was prepared.
Interview of Edwin L. Johnson
Edwin L. Johnson, Deputy Assistant Administrator for Pesticide
Programs, was interviewed on June 1, 1977. Johnson said he was
Acting DAA during 1972 and most of 1973, and occupied a staff
position in the DAA's immediate office during the latter part of
1973 and most of 1974. In November 1974, he became Acting DAA;
and in April 1975, he was appointed DAA.
He stated he hadn't seen the proposal until it arrived on his desk,
as he was responsible for signing sole-source justifications. After
his approval, the proposal would have gone to contracts. He said
he didn't like the Vanderbilt proposal and the suggestions of human
testing in several prior documents. Johnson said he didn't know if
the proposal was legal or what regulations were governing human
testing so he sent it to Robert Zener, EPA's General Counsel.
Zener telephoned Johnson to say the proposal was given to Jeffery
Howard, an attorney on the staff.
Johnson further stated that Howard telephoned him to say the
proposal was "atrocious" and told Johnson to expect a telephone
call from Ms. Hinkle of EDF. Howard told Johnson that EDF would
file an FOI request for the proposal. Johnson asked whether EDF
should get a copy of the proposal, and Howard said to give it to
them because they already had a copy. From this conversation,
Johnson inferred that Howard had notified EDF of the proposal
and gave them a copy.
NOTE: On April 29, 1975, EDF representative Maureen Hinkle
requested the proposal under the Freedom, of Information Act
(Exhibit M). Besides the EDF request this exhibit includes: EDF's
reaction dated May 5, 1975, written by William Butler, Washington,
counsel for EDF; Dr. Talley's answer to the Butler letter; a copy
of the FOI request from the Health Research Group dated June 3,
1975; and copies of two other private FOI requests.
Mr. Johnson said that he told Dr. Axelrod that he planned to dis-
approve the proposal unless Dr. Axelrod could give a better reason

for testing on human subjects and particularly why it should be
conducted in Mexico. Then, on May 1, 1975, Johnson notified
Dr. Axelrod of the disapproval (Exhibit N).
Interview of Irwin Saumel
Dr. Baumel was interviewed on June 7, 1977. He was with EPA
from January 1975 to August 1975 and during that time, he worked
for Dr. Axelrod. According to Dr. Baumel, Dr. Axelrod pushed
for human experimentation, not Dr. Dale. Dr. Baumel stated
that Dr. Axelrod worked very closely with Kenneth Olsen and when
Dr. Axelrod was not in the division it was Olsen who ran the
division. Though Dr. Baumel was the person usually in charge
of the EBDC projects, Dr. Axelrod informed Dr. Baumel that
he, Dr. Axelrod, would be the project officer on the proposal.
Dr. Axelrod went on to say the proposal he had in mind was
going to be conducted in Mexico. Later Dr. Baumel overheard
Dr. Axelrod tell Olsen "We got the Mexican deal" and Dr. Axelrod
seemed very happy. In Dr. Baumel's opinion, Dr. Axelrod thought
this "study was really needed."
Interview of Robert Zener
Mr. Zener was the General Counsel for the Agency during the
time of the proposal. When interviewed on June 7, 1977, he said
he vaguely remembers the circumstances but does recall he was
"appalled" and there was "general shock or outrage" concerning
the human testing features of the proposal. He said he gave the
proposal to Jeffery Howard to handle and he felt it was obvious
the proposal would be disapproved. Zener said he wasn't surprised
the proposal was "leaked" to the EDF, but denied he did it and
had no idea whether Howard did it.
Zener said he did not research the matter ana was not familiar
with regulations governing human testing.
Interview of Jefferv Howard
Mr. Howard had been a member of the staff of the General Counsel
during the period in question and was interviewed on June 9, 1977.
He said he first became aware of the proposal when he received it
from Johnson as a package (originals and copies) with a routing slip
from Johnson asking, "is this legal?" Howard said his first reaction
was that he was "flabbergasted" at the idea of human testing. Howard
gave some background concerning the relationship between Pesticide
Programs ana Office of General Counsel; a oart of this relationshio
was an understanding whereby contracts involving pesticides would
be reviewed by Office of General Counsel,

Howard said he had a telephone call from Dr. Axelrod concerning
the proposal. Howard questioned the term "knowing consent" in
the contract and he told Dr. Axelrod that DHEW had a moratorium,
on human testing until its regulation could be written. According to
Howard, this information about the moratorium came from a
memorandum prepared by Lee Schroer of the staff of OC-C.
Howard quoted Dr. Axelrod as saying that the researcher men-
tioned in the proposal was an old friend and that Dr. Axelrod was
concerned that there was no standard for ETU. Dr. Axelrod,
according to Howard, felt animal studies could not provide a
standard and human studies were needed.
Howard said he became concerned that nothing would be done to
stop the proposal from becoming a contract. He said he wrote
a memorandum to Mr. Train, who was then Administrator of EPA,
telling him about the proposal and citing reasons for stopping it.
Howard said he talked with Mr. Butler of EDF about the proposal
and told him what to put in the FOI reauest ana then Howard tele-
phoned Johnson. Howard said he was ""horrified" that the FOI was
sent to Dr. Talley to answer instead of CGC where Howard would
have had a chance to reply to the request.
Howard denied he was responsible for the 1977 newspaper article.
He said that when he left EPA, he took his own files and records
which included the original proposal in question and several copies.
All of these records were stored in his garage until six months
ago when he threw them out. Howard did say that when he left the
agency he gave copies of the proposal to Congressional investigators
and in. particular members of the Kennedy committee.
NOTE: A search of the files of CGC was made to find a cony of the
memoranda referred to by Howard. Of particular interest was
the memorandum written by Lee Schroer (Exhibit C) and the
memorandum written to Mr. Train. The Train memorandum was
never found.
Interview of Lee Schroer
Mr. Schroer, Attorney Office of General Counsel, was interviewed
on June 14, 1977. He said he vaguely remembers a contract which
concerned testing of skin tissue on aborted fetuses. Based on
a request from Howard, Schroer wrote a memorandum (Exhibit O)
dated April 2 9, 19 75 discussing the fetus contract and the DHZVv
prohibition on fetus study (this memorandum does not address
itself to the "Mexican proposal"), Schroer doesn't remember
seeing the "Mexican proposal" and doubts that he wrote a memo-
randum concerning it. He expressed the ooinion that Howard may
have confused the aborted fetus contract with the "Mexican tsrocosal."

Interview of Pam Symonds
Ms. Symonds was Dr. Axelrod's secretary and she has since left
EPA. Several telephone interviews were conducted. Symonds does
not remember typing the proposal. She read the recent newspaper
articles (Exhibit A) and said she thought it concerned the aborted
fetus contract and not the EBDC proposal. She said the person
who could answer most of the questions about the EBDC proposal
would be Kenneth Olsen as he was the person closest to Dr. Axelrod.
Symonds does remember placing a long distance telephone call to
Mexico City for Dr. Axelrod (Exhibit P). She said the phone number
would be in the telephone directory she kept in the office.
NOTE: The following name, phone number, and address were
found in that directory:
Dr. Emanuel Macheo
(905) 536-7500 (Area code 905 is Mexico Cit3/)
Head Pathology,
Hospital of Gynecology and Obstetrics,
Gabriel Marcera #222, Mexico City.
Interview of Jane Stieber
Ms. Stieber, an Environmental Protection Specialist, wasOlsen's
secretary--. She said she talked with Ms. Symonds about the news-
paper articles. Ms. Stieber does not remember typing the proposal;
however, she said that Olsen would be able to answer any questions
on the proposal.
Interview of Mary Rusnak
Ms. Rusnak, a secretary in Technical Transfer, was the secre-
tary to Dr. Dale. She also said she didn't remember the proposal
but also said that Mr. Olsen had all the needed information.
Interview of William Vernon Hartwell
Mr. Hartwell was interviewed on June 2 3, 1977, via telephone
(377-2338). He is presently employed by the U. S. Department of
Interior and in 1974 was employed by EPA. His branch chief was
Dr. Axelrod. One of Mr. Hartwell1 s functions at EPA was to head
a review team concerning an examination of the literature and the
needs concerning testing of EBDC fungicides. Hartwell said he left
EPA in July 1974 to join Interior and during the interim he took a
vacation. Dr. Axelrod requested Hartwell to deliver a package to
Dr. Hayes at Vanderbil: University during this vacation period.
Hart-well said he wasn't sure what was in the package, but he sus-
pects it was the background literature he had prepared for Axelrod

on EBDC. Hartwell thought Axelrod was giving the package to
Haves because he was an expert in this field and anv testing would
be cleared through the University Clinical Review Board. Hartwell
said he had worked for Dr. Hayes when they were both with the
Public Health Service. Dr. Hayes was in charge of the Toxicology
Section of the Technology Branch in Atlanta, Georgia and Hartwell
was a member of the group stationed in Phoenix, Arizona.
Interview of Wayland Hayes
Two telephonic interviews were conducted with Wayland Hayes
(Area Code 615-322-2262) on June 23 and 24, 1977. According to
Dr. Hayes, Mr. Hartwell came with a "great pile of paper" which
was information on EBDC. Hayes made a proposal to study the
drug disulfivam on alcoholics at a V.A. hospital and the EBDC
fungicide, maneb on prisoners at a State prison. Dr. Meal was
going to assist in the study and do his study on animals. One of the
problems involved in the study was how to get sensitive measure-
ments of the drug's (disulfivam) effect in the body. Disulfivam
is chemically similar to EBDC.
Dr. Hayes said the study would have to be approved by the University?-
Clinical Review Board and he saw no problem as this drug was
already being given to humans.
Dr. Hayes came to EPA and met with Dr. Axelrod concerning the
proposal. Axelrod told Hayes the study should include ETU.
Hayes said no and "the chances of an ETU study being approved by
the board were exactly zero." Dr. Hayes said he came to discuss
maneb part of the proposal and Axelrod wanted to substitute ETU
and the meeting ended without an agreement. Hayes said he wasn't
interested in testing ETU's.
As far as Hayes is concerned, nothing happened with the proposal
and the proposal was never presented to the Review Board. In
response to the question concerning Dr. Meal's statement in the
newspaper stating that the Board disapproved the study, Hayes
said Meal is mistaken, the proposal never went to the Board.
Dr. Hayes was questioned whether he had any connection with Rohm
and Hass, a chemical firm concerning this proposal. He said there
was no relationship between him and the company.
Dr. Hayes explained the procedures on how the Review Board
functions. He said when the committees were first organized,
they were "very constructive" but have become "very conservative."
A proposal involving human testing is given to the Board for review
and it may suggest or recommend procedure changes. If approval
is granted, the committee monitors the study. At the end of the
study when the report is written, a statement is usually included
concerning subjects' rights and the procedures used.

Interview of Eli Swisher
Dr. Eli Swisher is the manager of agricultural chemical standards
for Rohm and Haas Company, Philadelphia, Pennsylvania, and was
interviewed on June 2 9, 1977. He stated except as noted below
his company has no contracts or proposals with EPA.
In 1973, Rohm and Haas (R&H) was asked for suggestions for testing
EBDC. This request was made by Dr. Axelrod. EPA had told
R&H that tests were needed but the agency would contract for the
study and it would not be conducted by R&H or the chemical industry.
According to Dr. Swisher, nothing developed which involved R&H
in 1974; however, he learned that there had been a problem between
an agency sponsored study and a university. After this happened,
Dr. Axelrod had asked for a proposal from R&H.
In February 1975, R&H submitted what Dr. Swisher refers to as
a protocol to test EBDC. Included in this protocol was what
Dr. Swisher characterized as a toxicologist's view of now such
a study could be made. There was the suggestion that medical
students be used as subjects because they would better understand
the purpose of the study, be able to articulate any side effects,
and there would be no question as to knowing consent.
Dr. Swisher was asked about the confidential memorandum referred
to in a newspaper article. He said the memorandum was markec
"Company Confidential" because it came from R&H research divi-
sion and was attached to the front of the orotocol which was sent
Compilation of EPA Agency Policy and DHEW Regulations involving
testing on Human Subjects (Exhibit Q)
1.	A memorandum from Contracts Management dated March 7,
1972, to all Directors of Contracts notifying them of the DHEW
publication (NEH) 72-102 dated December 1, 1971, regarding policy
on Protection of Human Subjects and a December 20, 1971 memo-
randum entitled "Human Experimentation Under EPA- Contracts."
2.	A copy of the May 15, 1973, Federal Register, Volume 33,
Number 93, page 12734-12 737: Publicizes the EPA regulations on
Human Testing financed by Research and Demonstration Grants.
3.	A copy of page 30962 from the Federal Register, Volume 39,
Number 167, dated August 27, 1974, declaring a moratorium on
fetus research.

4.	A copy of the Federal Register, Volume 40, Number 50,
dated March 13, 19 75, pages 11854 to 1185 8, concerning Protection
of Human Subjects.
5.	A copy of 40 CFR, Part 40 codifying the new regulations for
Research and Demonstration Grants involving human subjects in
40. 135-2 as amended in May 8, 1975.
6.	A copy of a memorandum dated May 22, 1975 from Mr. Train
to each of his Assistant Administrators that all human testing must
observe the DHEW regulations and the Office of Research and
Development is responsible for human testing information and
7.	A copy of 45 CFR, Part 46 codifying the DHEW regulations on
fetus research in 46.2 01 dated August 8, 1975.
8.	A copy of the standard phrase added to all contracts involving
human testing dated November 21, 1975.


JUL 1 1977
Property of
US En'.'ironmpr.is! Prelection Agency
L:;.;:ry Rsffon X
U"j J:;uh Avenue
Sc^'s, M 3101
OCT 2 ( }'$}}
Honorable Warren G. Magnuson
Chairman, Conmittae on Commerce, Science
- and Transportation
United States Senate
Washington, D.C. 20510
Dear Mr. Chairman:
As Mr. Costle promised in his letter of May 18, 1977, I am enclosing
a full report of our inquiry into the proposed, but disapproved, study
on feeding the fungicide, ethylene bisdithiocarbamate, (EBDC) to human
subjects in Mexico (hereinafter called the Mexico proposal). This report
provides a factual chronology, as best we can determine, of the events
surrounding the proposal and includes all of the documents that we have
been able to locate pertaining to this matter. This report also- covers
a proposed, but never funded, study submitted by researchers at Vanderbilt
University (hereinafter called the Vanderbilt proposal) to test one of the
EBDC pesticides on volunteer inmates from the Tennessee State prison as
well as test a chemically-related drug on patients from a Veterans Admini-
stration hospital. This proposal was part of the chronology leading tc
the proposal to conduct tests in Mexico City.
This inquiry involved the full-time efforts of two professional
investigators for three full weeks and considerable additional time by
Mr. Dietrich, Director, Program and Management Operations for the Office
of Water and Hazardous Materials. These people were not affiliated with
the Office of Pesticide Programs and were not aware of this matter before
it was reported in the Washington Post on May 11, 1977. I am confident
of the completeness "and integrity of this inquiry.
While zhe enclosed report provides the full details of our findings,
I would like to summarize and comment on what, in my judgment, are the
principal findings:
1. Over a two-year period, prior to the Mexican proposal, tjiere
was considerable professional scientific debate within EPA cn
the adequacy of the data available to elucidate the health effects
of the EBDC and ethylene thiourea (ETU). Animals tested with ETU,

- 2 -
an impurity in manufactured E5DC products as well as a decomposi-
tion and metabolic product of E3DC, showed adverse effects on the
thyroid, including cancer or cancer-like effects. Some scientists,
including Dr. Axelrod and Dr. Dale, felt that there were"undeter-
mined threshold levels for EBDC and ETU which, if exceeded, would
cause, in man, the adverse effects observed in animals. They
believed that the only way to determine those threshold levels
for man was to test both EBDC and ETU in the human system. They
did not believe that such threshold levels could be extrapolated
from animal studies or that such extrapolated results from ani-
mal studies could be used to make defensible regulatory decisions
on EBDC or ETU. They firmly believed that human studies were
necessary to establish safe tolerance levels for residues of
EBDC and ETU on food products to sufficiently protect all human
2.	In September 1974, Dr. Hayes of Vanderbilt University submitted
to ERA a proposal (1) to first test disulfuram (a drug which
is chemically similar to EBDC) on patients at a nearby Veterans
Administration hospital who were already receiving this drug for
the treatment of alcoholism, and (2) to then test one of the six
manufactured E3DC fungicides on inmates at the Tennessee State
Prison. Our evidence indicates that Dr. Axelrod had informally
discussed the EBDC problem with Dr. Hayes and invited him to sub-
mit a proposal. Our evidence does not indicate that Dr. Axelrod
had worked in cooperation with a major manufacturer of E3DC in
developing the Vanderbilt proposal as alleged in an article in
the Washington Post on June 23, 1977. However, Dr. Axelrod,
apparently", had informally and professionally discussed the
testing of EBDC with Dr. Swisher of the Rohm and Haas Company,
one of the manufacturers of EBDC. Such professional discussions
with representatives of registrants is not unusual and, in fact,
is a necessary aspect of EPA's pesticide regulatory activities.
The Vanderbilt proposal clearly indicated that the details of
the human testing were quite tentative and had to be further
worked out. More importantly, the proposal clearly delineatec
that testing would be conducted under the "full and continuing
consent and in conformity with...procedures established by the
Vanderbilt University Clinical Investigation Committee." This
meant that the testing would have been carried out .in a fully
ethical manner, with legally effective consent on the part of
the participants being tested and in full conformity with pre-
vailing HEW guidelines on human testing.
3.	After reviewing the proposal, Dr. Axelrod recommended that it
be modified to also include the human testing of ETU. Apparently,
Dr. Axelrod suggested this modification to Dr. Hayes who rejected
the modification because it would have involved the testing of
a suspected carcinogen or humans and therefore would not have

been approved by the University's Clinical Investigation Committee.
In addition, Mr. Johnson, Deputy Assistant Administrator, expressed
severe reservations about the proposal because, in his opinion, he
did not feel that EPA needed to supplement existing animal, studies
data on E3DC and ETU with human data to make a regulatory decision.
(Mr. Johnson did authorize Dr. Axel rod to proceed with the
proposal if he felt he must, but this tentative approval was
based on the submitted proposal that excluded the testing of ETU.)
As a result of both events, the Vanderbilt proposal was not further
considered. Thus it did not proceed into formal processing within
EPA, which would have required Mr. Johnson's formal approval by
signature on a special form, nor did it proceed further at Vander-
bilt University where it would have had to be approved by
the Vanderbilt University Clinical Investigation Committee.
In February 1975, Dr. Swisher of the Rohm and Haas Company
apparently submitted to Dr. Axel rod a suggested protocol for
testing E3DC in which he suggested conducting the tests on
medical students. We are still trying to locate this sub-
mission in our files. Our current evidence indicates, however,
that this proposal was never seriously considered; certainly,
it was not entered into any formal processing which would be
necessary to carry it to a point of funding.
In April 1975, a proposal was developed for a sole source
contract to be awarded to the Hospital de Gineco-Obstretricia
in Mexico City. Our evidence strongly suggests that this
proposal was conceptualized, articulated and written solely
by Dr. Leonard R. Axel rod, former Director of the Criteria
and Evaluation Division of the Office of Pesticide Programs.
Our evidence also indicates, circumstantially, that Dr. Axel rod
discussed this proposal with someone at the Mexico City hospital.
We cannot, of course, verify these inferences because Dr. Axel rod
died shortly after the proposal was written. However, we have not
been able to find any evidence, circumstantial or otherwise,
of co-authors, cooperators or participants in the development: of
the Mexican proposal.
Pursuant to routine Agency procedures, the Mexican proposal
would have had to go through several reviews before the Contract
Management Division of EPA could have negotiated and awarded a
contract to the Hospital de Gir.eco-Cbstretricia. The first
required review was that of the Deputy Assistant Administrator
for Pesticide Programs. That review was accomplished and resulted
in a disapproval of the proposal by Mr. Edwin L. Johnson, the
Deputy Assistant Administrator. This disapproval was based on
Mr. Johnson's own dislike for human testing and on the advice of
Mr. Jeffery H. Howard, Associate General Counsel. The proposal
did not proceed into subsequent steps of routine processing after
this disapproval and was not again repropcsed or reconsidered. I
should point out, at this point, that the Washington Post article

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was incorrect in implying that the proposal was fashioned in a way
to avo-id the routine review by the Deputy Assistant Administrator
and other offices and was in error in stating that the rejection
of the proposal was the result of an "administrative fluke."
7.	If the Mexican proposal had proceeded into subsequent steps, it
would have had to pass two critical reviews which I believe would
have resulted in its rejection or its modification to provide
for ethical human testing adhering to, or equivalent to, the
HEW regulation on Protection of Human Subjects. The first review
would have been that of the Contracts Management Division which,
among other things, would have reviewed the proposal for consistency
with HEW policy on human testing. The second review would have
been that of EPA1s Office of International Activities and the
Department of State which I believe would have resulted in a
review by the United States Embassy in Mexico. Although our
evidence reveals that Dr. Axel rod discussed this proposal with
Mr. Fitzhugn Green, Director of the Office of International
Activities, those discussions were informal and preliminary and
did not result in Mr. Green's approval.
8.	At the time that both the Vanderbilt and Mexican proposals
were developed, parts of EPA had, or were developing, policy
and procedures governing human testing. Hcv/ever, during that
period the Office of Pesticide Programs had no policy or
procedures on human testing. In this context, although I
can fault Dr. Axel rod for his lack of good judgment in
developing'a proposal that failed to explicitly require
ethical human testing, I cannot conclude that he, or any other
persons, who might have been aware of the Mexican proposal,
violated EPA regulations or any Federal statue.
I believe the above summary and comments respond to your first question.
In overall comment, I would conclude that there was a sincere and
strongly held scientific belief, cn the part of Dr. Axelrcd, that human
testing was essential to make a difficult regulatory decision on toler-.r~es
for EBDC and ETU residues on food crops. I cannot, however, conclude, in
his absence, that there was deliberate attempt on his part to sponsor un-
ethical human testing. I suspect that he gave little attention to the
ethical protocols that would have to be followed in human testing, and
preferred to leave those aspects to the institution performing the tests.
I do not agree with this passive approach. I believe we have an obligation
to positively assure ethical testing or, and in seme cases, reject nurnan

- 5 -
Relative to your second question, there is no evidence that officials
within the Department of Health, Education and Welfare or other agencies,
such as the Department of State, were consulted in the development of
the proposal. This, in part, was because the Mexican proposal (also the
Vanderbilt proposal) did not get beyond its early stage of development
and into formal processing. In remaining part, it was because there was
no legal requirement and little or no programmatic need to consult with
the Department of Health, Education and Welfare.
In response to your third question, let me first make the following
1.	On May 15, 1973, EPA promulgated regulations governing EPA-
funded research and demonstration grants. These regulations
specifically required compliance with HEW guidelines on human
2.	We have procedures within our Contracts Management Division
which require review of proposals involving human testing.
3.	On May 22, 1975, shortly after the disapproval of the proposal,
Mr. Russel E. Train, former Administrator of EPA, reinforced
Agency policy on human testing by issuing a directive to all
offices of the Agency requiring compliance with the HEW regula-
tion on Protection of Human Subjects. That directive is included
in the enclosures of the enclosed report and is still in effect.
4.	We conduct and sponsor (through grants and contracts) and
have conducted and sponsored since the establishment of EPA,
the clinical testing of air pollutants on human subjects at,
or through, our Health Effects Research Laboratory at Research
Triangle Park, North Carolina. This testing is strictly con-
trolled and managed, and strictly adheres to all current Federal
statutes, regulations and guidelines on human testing. In the
nearly seven years of testing under EPA, and in prior years
of testing under the National Air Pollution Control Administration,
we have never experienced any abnormal or adverse incidents. I
am not including any details on this program because I understand
that your current interest is restricted to the proposals discussed
above, but I will be most happy to provide you with,any informa-
tion on this program that you may desire.
5.	Human testing is not banned by any Federal statute or any HEi-J
regulation but is strictly limited to ethical testing by Federal
statutes and regulations. The HEW regulation on Protection of
Human Subjects, to which I have referred at several points in
this response, allows human testing but only under several strict
conditions. The two principal conditions are (a) that "legally
effective informed consent" is obtained from the human subjects

- 6 -
on which testing is performed and (b) that an "Institutional
Board'1 composed of qualified, mature and experienced experts
must be established to review and approve proposal's for, and
continuously monitor, the conduct of human testing programs to
assure "safeguarding of the rights and welfare of human subjects."
As indicated above, EPA's current policy requires compliance with
the HEW regulation on Protection of Human Subjects. I have directed that
this policy be reviewed and strengthened, and implemented through the estab-
lishment of very strict procedures issued through an EPA Order to make certain
that all EPA tasting meets the most rigid legal and ethical standards. I
expect to issue such an Order within three weeks.
Relative to your last question, and in addition to issuing an EPA
Order, I have called for a full accounting of all human tasting, past and
current, within EPA and intend to carefully evaluate the findings.
I hope that I have been fully responsive to your questions and
your concerns on this matter. I regret the occurrence of this incident,
but am gratified that EPA management had the good judgment to reject
the Mexican proposal. If I can provide you with any additional infor-
mation, I shall be happy to do so.
Sinc&yely yours
Barbara Blum
Deputy Administrator