Interoffice Correspondence

MEETING MINUTES MEETING WITH H.C. HODGE

JUNE 7, 1979

THOSE PRESENT:
M.T.
F.D.
H.C.
L.C.
J.D.
R.E.
J.A.
R.A.
F.A.
R.A.

CASE - 218-2
GRIFFITH - 220-2E
HODGE - U. OF CALIFORNIA
KROGH - 223-6SE
LAZERTE - 236-1
OBER - 218-2
PENDERGRASS - 220-2E
PROKOP - 236-2B
UBEL - 220-2E
Nelson - 218-3

Those present met on April 12, 1979 at the Hilton Hotel in
San Francisco California to review recent results which are
relevant to the Fluorochemioals in Blood Program and to
discuss future plans.
R.A. Prokop began the meeting by giving background on FC-807.
FC-807 is used in combination with a hydrocarbon sizing agentto give oil and water repellency to paper and paperboard. One
of its principle uses is as an indirect food additive, and a
petition was granted in the late 1960’s for its use as such.
It is manufactured by reacting perfluorooctanesulfonyl fluoride
with ethyl amine. Subsequent reaction of the sulfonamide with
ethylene carbonate followed by sequential reaction with POCl3/H20
and ammonia give FC-807.
(See attached f!owsheets) It is sold
as a 35-40% solution in isopropyl alcohol.
F.A. Obel reviewed recent developments in the areas of serum
organic fluorine levels, human health and epidemiology as they
relate to the fluorochemicals in blood program.
The serum organic fluorine level of t~e individual who was
previously removed from fluorochemical exposure when his serum
organic fluorine level rose to 70 ppm has recently been
measured. The level was found to be 45 + 5 ppm. The amount

of FC-143 in his urine was found to be 2~0 ug for a 24 hour
period.

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3MA00592803

 ~erum oruanic ~luorine levels have recently been measured on
selected employees at Cordova, Decatur and Chemolite. In
comparison with levels measured in 1976 and 1977, there has
been little change.
The serum organic fluorine levels of 15 Chemolite employees
were measured in 1978 prior to their being involved in the
packaging of FC-143. Repeat measurements ~f their serum
organic fluorine taken recently showed some unexpected
elevations in levels. Inorganic levels were also higher than
expected. Contamination with inorganic fluoride is suspected
to be the cause of the high inorganic levels in serum, but the
entire set of results will be reviewed to see if any errors
were made to relate exposure to serum organic fluorine levels.
Eight serum samples from rural China were analyzed for organic
and inorganic fluorine levels. Organic fluorine levels ranged
from 0.004 ppm to 0.017 ppm and inorganic fluoride levels from
0.044 to 0.076 ppm. In the U.S. serum organic fluorine levels
range from 0.002 to 0.13 ppm and inorganic levels from 0.003 to
0.17 ppm.
The epidemiology study is still in progress. The study involves
tracing about 3500 people and involves about 100 deaths. So far
the~e does not appear to be what might be considered as "unusual
causes of death".
H.C. Hedge commented that data from this epidemology study is
very important and that the study should be carried out carefully. Criteria set forth by the N.C.I. should be followed.
Dr. Hedge further stated that he would rather accept data from
this type of study for identifying human health effects than
data from animal studies, but that the National Cancer Institute
would not agree.
F.A. Ubel summarized a conversation with two Mayo Clinic
physicians regarding the significance of slightly elevated liver
enzyme levels in some of the Chemolite employees. No definite
conclusions were reached, except that the values were very slightly
elevated and in some instances were felt to be compatible with
their history of alcohol ingestion. They could not make any
statement unless they had a chance to examine the employees
personally.
Dr. Hedge was shown a summary of the abnormal findings in those
3M employees who had known fluorochemical blood levels. He was
given a copy.
The results of the physical examinations done on Decatur and
Cordova employees look very good. There does not appear to be
evidence of a work related problem. The Chemolite employees

showed more abnormalities, but the majority of these appeared to
be related to a known medical problem or medication.

It was the

conclusion of the physicians who supervised the examinations that
there did not appear to be a problem which could be identified as
work related. Additional analysis of the data will be done.

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 J.A. l’cndcrgrass i:eviewed data on workplace concentrations of
various fluorochemicals in Alabama and Minnesoha plants. In
most cases the workplace concentrations of fluorochemicals
are low-lower than some time weight averages recommended for
known or suspected carcinogens. Fluorochemical salts are
exceptions. Due to their dusty nature workplace concentra~
tions are higher. Levels of one of these materials, FC-143,
have been reduced to an acceptable value. Work is underway
to reduce exposure to other fluorochemical salts.
R.A. Nelson reviewed results of 90 day subacute toxicity
studies using FC-95, FC-143 and FM-3422.~ (Slides attached)
Of these compounds FC-95 was the most toxic. It produced
deaths in the monkey at 4.5 mg/Kg and in the rat at %10 mg/
Kg. Target organs in the rat were liver hematopoietic tissue,
stomach and small intestine. In monkeys, the apparent target
organ was the upper G.I. tract.
The liver and possibly the kidney and G.I. tract were target
organs in the rats fed FM-3422. In the case of monkeys there
was clinical evidence of G.I. toxicity.
FC-143 produced liver changes in rats at the highest dose. In
monkeys hema~opoietic tissue was affected at lethal doses and
there was evidence of gastrointestinal toxicity. H.C. Hedge
also presented his summary of results of the 90 day studies on
FC-143, FM-3422 and FC-95 (attached). His projected no-effect
levels were 1.5 mg/Kg for FC-143 and FM-3422 in the rat, and
3 mg/Kg in the monkey. For FC-95 there was no no-effect level
in the rat and no data for estimating a no-effect level in the
monkey. There appears to be an indication of liver effects
from FC-95, FM-3422 and FC-143 at all dose levels in the rat
studies.
H.C. Hedge questioned whether some of the toxic effects observed
in the animal studies might be due to low surface tension.
Surface active agents are known to be capable of causing a
problem in the gut. It was pointed out that some fluorochemicals
are the most potent surfactants known.
F.A. Griffith pointed out that toxic effect such as those observed
with FC-95, FM-3422 and FC-143 are common with surfactants.
R.A. Nelson pointed out that the liver effects are probably
reversible, but this would require further study to prove.
H.C. Hedge pointed out that a buildup of
detected most rapidly in the bon~. Thus
fluorochemicals to fluoride ion could be
Bone should be collected at the end of a
analyzed for fluoride.

fluoride ion can be
evidence of breakdown of
detected in the bone.
chronic study and

H.C. Hedge was then asked for his recommendations on future work.
After a brief review of customer exposure to 3M fluorochemieals
Dr. Hedge recomended the following:

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 It dOeS not appear that there is a toxicity problem outside
3M. However we do not know if there are toxicity problems
due to employee exposure. Reduction in exposure should
have top priority.
Metabolic instead of Chronic studies should be done next.
Sequestering kinetics and metabolites should be looked at.
3.

Reproduction studies, including teratology, should be given
high priority. Two generations should be used. Such studies
should take less than one year.
Carcinogenicity of fluorochemicals should be looked at.
Start with Ames testing and continue to more sophisticated
mutagenicity tests. If any of these turn out positive it
will be necessary to go on to a chronic study.

R.A. Nelson questioned the reliability of tests other than the Ames.
The transformation test may be on the way out. Different regulatory
agencies are not getting results which agree.
M.T. Case outlined proposed studies on FC-807-and studies being
considered for FC-95 and FC-143.
(Slides attached) A question
was raised on the FC-807 study as to whether the F.D.A. should be
aksed about the protocol. It was suggested that we should proceed
without consulting the FoD.A. since the study is scientifically
valid.
R.E. Ober outlined planned work in the metabolic area.
(Slides
attached) This proposed work involved metabolism of FC-807,
persistence of FC-95 and FC-143, and ~kin absorption studies.
It was suggested that H.C. Hodge be given more time to consider
the proposed slides on FC-807, FC-95, FC-143 and the metabolism
work before being asked for an opinion.

ADDENDUM
i called Dr. Hodge on April 20, 1979 to give him the acute oral
toxicity data on FC-95, FC-143 and FM-3422 which was generated at
IRDC prior to ~he 90 day studies. He asked that the following
be added to the meeting minutes=
The study of levels of FC-807 or its metabolites is of utmost
importance in determining possible future problems. It should
be determined if FC-807 or its metabolites are present in man,
what level they are present, and the degree of p~rs~stence (halflife) of these materials.

RAP/ko
At tachmen ts

Made Available by 3M for Inspection and Copying as Confidential Information:
Subject to Protective Order In Palmer v. 3M, No. C2-04-6309

1210.0004

3MA00592806