DR. S.R. EVELYN
SRE/PSB/46D-10 L&M GR&DC 15th March, 1984
R E 3 T R I C T E D
REVIEW OF FREON 11 IN TOBACCO PROCESSING
This review updates one undertaken in February 1983 and
incorporates:
1. Legislation: In relation to depletion of ozone in the
C* upper atmosphere.
2. A view of possible Public Affairs aspects.
3. The use of G13 treated tobacco in cigarettes:
(a) toxicology and (b) residue levels achieved in
practice.
Attached is a copy of a memorandum by Dr. D.G. Felton
incorporating the AGP Minute of 1973.
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LEGISLATION
SEC Council decision (26th March, 1980) stipulated
that M production capacity of CFCs 11 and 12 should
not be increased in any Member State and that by 31st
December. 1901, there should be a reduction of at least
30% of the use of CFCs in aerosols. (This reduction has
been achieved).
The Danish National board of Environment Protection
has propo-ne-a-ItNe prohibition at fully halogenated CFCs in
propellants In aerosols: Greece and Switzerland hLV0
similar plans.
Other European Countries
Sweden banned the manufacture and use of CFCs an
aeroacT -propellants after June 1079 and a similar ban
case into force in Norway an lat July, 1981. (Some
medical products may be exempted).
USA Non-essential propellant uses of CFCs banned
in 29737
Canada CFCs classified as substances Posing a
signiTro-&-if danger to the environment or health In 1979.
Their use in hair sprays, deodorants and antiperspirants
was banned in 1980. Freon 11 and 12 may not be used for
foods.
Recent Developments
In 1982 the German Government was seeking further
reductions in the use of CFCs in aerosols: the proposal
was to reduce usage to 50% of the 1076 level (rather than
30%).
Nor* recently the "Nordic Proposal". (made by Sweden,
Norway and Finland) Called for a world-wide ban on Inon-
essential' aerosol uses of CFCs. This proposal, put to
the United Nations Environmental Programme's Working Group
In Geneva, was supported by the US State Department
delegation. The proposal was to:
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(1) Take all appropriate measures to and the use of
CFC-11 and -12 in aerosols, except for essential
uses.
(2)- Agree and implement measures to control, limit and
reduce emissions of fully halogenated CFCs used in
plastic foams, refrigeration, solvents, etc.
(3) Provide the UN with data on production, capacity,
use In aerosols. and other relevant data.
The US delegation did not support item (2).
Unofficially it is understood that:
(a) there was no-concensus on the proposal,
(b) there in division between the EPA and
State Department,
(a) the proposal was supported by
Switzerland and The Netherlands,
while UK. France, Italy, Japan and the
Eastern block remained negIILtiVe/ueutrLl,
2. A vrzw op PUBLIC AFFAIRS ASPECTS
Even it there are no current pressures or regulations
in particular countries, it would be relatively easy for
0- our critics to attack the use of Freon in the 3rd World
and BAT in particular.
Such attacks could be made on two obyious fronts, to
follows:
(A) On a national basis relating to the use of Freon when
it in clear that a 'softer' alternative in being
introduced and used in Europe and North American.
This would be difficult to defend since It could be
claimed that the Company in 'switching' to less safe
processes in the 3rd World.
The recent attack which forced 13AT to stop using
specific pesticides In Kenya Indicates that the
environmentLli4t* and anti-tobacco lobby in becoming
much more sophisticated.
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(B) It also has to be recognised that the effect of CFCs
on the ozone layer is an international and not solely
national problem. Thus even If there is not a strong
environmental lobby in a particular country, environ-
mentalists in other countries will be able to identify
and attack major users of CFCs. Perhaps, as a current
example, it is only necessary to cite the UK "liability"
for acid rain in Scandinavia.
3. (A) TOXICOLOGY IN RELATION TO PROCESS RESIDUES
IN CIGARETTES tFreon 11)
Two. prime sources have been used in thin
review, which has been restricted primarily to
human data and to specific relevant aspects of the
animal data. These are (a) Confidential report by
Alan Rodgman of R.J. Reynolds and (b) a review
from BIBRA. (Received February 1983).
The report and the review indicate, with a
reasonable degree of confidence, that there is no
definitive evidence which would suggest that Freon
11 in carcinogenic, via the oral or inhalation
routes of administration.
The Muftggnie studiAG are LIGO negative or
equivocal and a single reproduction study Indicated
that there were no significant effects.
The position Is rather different, however, in
relation to effects on the respiratory system and
heart.
01- In the animal studies, for example, exposure
by the oral and inhalation routes appears to present
no particular problems until (page 6) equivocal
results are noted in relation to neuronal oedema,
emphysema and lung o*dwm. Pulmonary irritation,
congestion Lad 122,411morrhage have also boom reported
following short (2-24 hour) exposures to high levels
of Freon 11. It is also noted that those effects
vary widely between species. Similarly, species
dependent, effects on heart rate, hypotonsion and
cardiac arrhythmis, have been reported in relation
to the Cardiovascular system.
Although theme aspects are reviewed in some
detail by Rodgmen, they are eventually dismissed in
relation to the levels of exposure from cigarettes
containing 013 expanded tobacco.
It ix-notable that Rodgman drawn attention to
an excellent review by Charlenworth (1). Nevertheless.
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be fails to point out, as Cbarleawortb does, that
the authors "consider the use of Freon Fll and P21
an aerosol prooollants inadmissible ... because
they are more potent than other fluorocarbons in
inducing cardiac arrbythmia in the mouse". Similarly,
Charlesworth comments that "Fll increased pulmonary
resistance and decreased pulmonary compliance and
tidal volume in the rat". Both these effects were
found at significantly lower concentrations.
Bodgman also referx directly to a paper by BelaJ
ot al. (2) stating that the threshold tar arrbytbmia
Tn--Me monkey was 5% Freon 11. Although this state-
ment in correct, no mention in made that there was
a does-reLLted fall in blood pressure and depressed
miocardial contractability at 0.5%, while heart
rate acceleration was also demonstrRted but was not
done-roluted.
Aviado and Belaj (3) draw the conclusion that
"the continued use of class 1 propellants (inclu-
ding Fll) in aerosols should be seriously questioned".
Human Studies
In addition to these offsets noted In the animal
studies, it in considered that the respiratory and
cardiovascular-evidence from hwwno gives rise for
considerable concern, although this in not reflected
strongly LA the BIBRA review.
For example, on page 9, the reviewer states that
no serious effects wore seen on the EEG of 10 subjects
exposed to TCFM for 15 or 43 seconds. Nevertheless,
the reviewer notes (page 9) "most of the subjects
developed respiratory sinus arrhythmia and bradycardia
and each exhibited a byphssic reduction in maximum
C10- expiratory flow rate (MBF). Following a 60 second
ezposuro there van a transitory tachyeardia with
negative T waves in 2 of the subjects".
In the following paragraph the reviewer con-
siders two other studies. These lead essentially to
the conclusion that, &part from a slight decline In
cognative function, there are no untoward effects an
the heart, lung or nervous system.
As theme two references are critical to the
assessment of the human data, the original papers
were examined in detail.
Tho.papor by R.D. Otowart ot al. (4). which
concluded that "none, of the subl-ecto showed any
decrement In pulmonary function or alteration in
cardiac rhythm", was based on excellent methodology
and both short- Lad long-term exposure (8 hours) of
43 male and 32 female subjects. In practice the M)
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studies specific to Freon 11 (as distinct from those
on certain solvents) were for periods of 1, 2 or 8
bourn at nominal levels of 250. 500 or 1,000 ppm.
In contrast, the work of F. Valic et &1. (5)
examined the effects of short-term expoiu'res (15, 45
and 60 seconds) in 10 subjects. Detailed examination
of lung function, i.e. mazimum expiratory flow at
25% and 50% of vital capacity, showed that there wax
a reduction of between 6% to 10% in ventilatory
capacity. Theme reductions were biphasic, occurring
after a few minutes and subsequently after 13 to 30
minutes. Freon 11 bad the greatest effect of the
materials studied.
Although Valic reported that there was no serious
cardiac effect, most subjects developed respiratory
sinus Lrrhythmia. Bradycardia. and increased variability
of heart rate occurred In the majority of the other
7 subjects. VLlIZ concluded that "our studies show
that both respiratory and cardiac effects may.follow
inhalation of Freons. it may well be that these
effects are more serious in those who already have
respiratory or cardiac disease".
Additional independent comments on these papers
have been obtained and can be al-rised to follows:
(a) The measurement of respiratory function employed
in both studies in comparable but somewhat
dated and in insensitive by current standards.
(b) The test used by Valic in applied after a short-
term exposure (15-45 seconds). with observations
being uLde after one minute but extending to
one hour following exposure. In contrast. the
long-term exposure of several hours used by
Stewart et &I., while appropriate to industrial
exposure, 010iffl subjects to accommodate to the
effects.
(c) The work of Valle also demonstrates that the
effects of Freonn; can be sinotistic (FIL and
F12). On this basis the Possibility of syner-
gistic effects between F11 and tobacco moke
Cannot be overlooked.
Conclusions
Whilet there are no-grounds for refuting the
review and appraisal made by BIBRA, it In apparent
that it was prepared as a balanced appraisal in
relation to the Industrial use of Freon, particularly
at levels up to %be threshold limit Value.
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In contrast SAT in concerned with the use of Freon
in a tobacco expansion process and the subsequent use of
the processed tobacco in cigarettes.
It is submitted that our prime need Is to consider
the possible effects in circumstances where:
(a) Large numbers of subjects are exposed.
(b) The exposure in to low residual levels but
in frequently repeated.
(c) Those exposed are people of all ages (10
upwards), in all states of health, which will
certainly include those with pro-existing
pulmonary and heart disease of any etiology.
(d) The exposure to Freon in coupled with
,simultaneous exposure to a very wide tango
of other chemicals which exist, mostly at
very or extremely low levels, in cigarette
smoke.
With this background, the continuous exposure of
healthy subjects to relatively high levels of Freon
11 Is lose appropriate than short-term exposure. On
this basis alone the work of Valle ot &I. In more
relevant than that of atowart ot &I.
It should be noted further that the conclusions
of Valle are effectively reinforced by the observa-
tions in animals. An noted above, the BIBRA appraisal
(page 6) comments on a variety of bronchopulmonary
effects in relation to Freon 11 in different species:
those effects include respiratory function, pulmonary
ciroulatiog, bronchoconstrictiou and dilation.
Biallarly, In relation to the cardiovascular
system the animal studi*e show that brt4yeardift and
taebyeardia, occur In various species whilst there
are numerous observations of Inhaled Freon 11 causing
hypoteasion and cardiac arrhythalas. rt is also
noted that dogs and monkeys are particularly sensitive
and susceptible to secondary offsets such as coronary
ischasmis and cardiac necrosis.
In summary therefore, It in contended that prime
consideration must be given to:
(1) the particular circumstances of the cigar-
ette industry and the attacks which are
mads, against It,
(2) the human data reported by Valle on healthy
subject* which In supported and amplified
by the animal data.
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Conversely, the data related to industrial
exposure of identified, relatively small numbers
of "healthy" subjects is regarded as less relevant.
On the basis of the evidence, it in recommended
that the use of Freon 11 In tobacco products should
be phased out as quickly as practicable. Given a
satisfactory alternative, I would recommend that
Freon 11 should not be regarded as an acceptable
process residue.
3. (B) RESIDUE LEVELS ACHIEVED IN PRACTICE
The AGP Minute (1073-14) advises that residue
levels should "remain consistently lower than a
maximilm level of 50 ppm" (see memorandum from
Dr. D.G. Felton dated 3rd September, 1980: copy
attached).
It must be omphasised that this level relates
to processed tobacco and not the final Cigarettes.
Throughout the Reynolds' reports it in assumed
that the residual level of marketed cigarettes in
5 ppm.
Various analyses undertaken In GR&DC (March
1082 and January 1983) on cigarettes manufactured
from various types of tobacco have indicated that
substantially higher values may be found in
practice. In one instance, the mean values for
different grades were 140, 100 and 230 ppm even
after Ignoring high "outlies". In another examina-
01- tion the range of mean value varied from 41 to 131
(average 82).
. Although Information on the residue levels have
not boon given In relation to tobaccos processed in
Australia, it in clear from a number of progress
reports that the dissipation of fluorocarbons from
expanded tobaccos is a continuing topic of investiga-
tion.
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S.R. EVELYN
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References
(1) F.A. Charlesworth, Food Ik cosmetics Toxicology 1975, 13,
393-396.
(2) M.A. Belaj. D.G. Smith and D.M. Aviado, Toxicology 1974,
2. 381-395.
(3) D.M. Aviado and M.A. Delaj, Toxicology 1974, 2, 31-42.
(4) R.D. Stewart, P.R. Newton, S.D. Baretta, A.A. Herrman,
N.V. Forster and R.J. Soto. Physiological Response to
Aerosol Propellants, Envir. Hltb Perspect. 1978, 26,
275-285.
(5) F. Valic, Z. Skuric, Z. Bantic, M. Rudar and H. Recej.
Effects of Fluorocarbon Propellants on Respiratory Flow
and RCG, Dr. j. ind. Ned. 1977, 34, 130-i3a.
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