Chlorofluorocarbons, fully halogenated (EHC 113, 1990)

INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

ENVIRONMENTAL HEALTH CRITERIA 113

FULLY HALOGENATED CHLOROFLUOROCARBONS

This report contains the collective views of an international group of
experts and does not necessarily represent the decisions or the stated
policy of the United Nations Environment Programme, the International
Labour Organisation, or the World Health Organization.

Published under the joint sponsorship of
the United Nations Environment Programme,
the International Labour Organisation,
and the World Health Organization

World Health Orgnization
Geneva, 1990

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WHO Library Cataloguing in Publication Data

Fully halogenated chlorofluorocarbons.

(Environmental health criteria ; 113)

1.Freons - adverse effects 2.Freons - toxicity
I.Series

ISBN 92 4 157113 6 0 (NLM Classification: QV 633)
ISSN 0250-863X

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CONTENTS

ENVIRONMENTAL HEALTH CRITERIA FOR FULLY HALOGENATED CHLOROFLUOROCARBONS

1. SUMMARY

1.1. Identity, physical and chemical properties, analytical methods
1.2. Sources of human and environmental exposure
1.3. Environmental transport, distribution, and transformation
1.4. Environmental levels and human exposure
1.5. Kinetics and metabolism
1.6. Effects on the environment
1.7. Effects on experimental animals and in vitro systems
1.8. Effects on humans
1.9. Evaluation of human health risks

2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

2.1. Identity
2.1.1. Technical product
2.2. Physical and chemical properties
2.3. Conversion factors
2.4. Analytical methods

3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

3.1. Natural occurrence
3.2. Man-made sources
3.2.1. Production levels
3.2.2. Manufacturing processes
3.2.3. Loss during disposal of wastes
3.2.4. Release from transport, storage, and accidents
3.2.4.1 Transport and storage
3.2.4.2 Accidents
3.3. Use patterns
3.3.1. Major uses
3.3.2. Release from use: controlled or uncontrolled

4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

4.1. Transport between media
4.2. Environmental transformation and degradation processes
4.2.1. Oxidation
4.2.2. Hydrolysis
4.2.3. Photolysis
4.2.3.1 Photochemistry
4.2.3.2 Environmental transformation
4.2.4. Biodegradation
4.3. Interaction with other physical, chemical, or biological factors
4.4. Bioconcentration and bioaccumulation

5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

5.1. Environmental levels
5.1.1. Air

5.1.2. Water
5.1.3. Food and other edible products
5.2. Occupational exposure

6. ECOLOGICAL EFFECTS OF STRATOSPHERIC OZONE DEPLETION

6.1. Introduction
6.2. Terrestrial plants
6.3. Aquatic organisms
6.4. Research needs

7. KINETICS AND METABOLISM

7.1. Absorption
7.2. Distribution
7.3. Metabolic transformation
7.4. Elimination and excretion in expired air, faeces, and urine
7.5. Retention and turnover
7.6. Reaction with body components

8. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS

8.1. Single exposures
8.1.1. Acute inhalation toxicity
8.1.2. Acute oral toxicity
8.2. Short-term exposures
8.2.1. Inhalation exposure
8.2.2. Oral toxicity
8.2.3. Dermal toxicity
8.3. Skin and eye irritation; sensitization
8.4. Long-term exposures
8.4.1. Inhalation toxicity
8.4.2. Oral toxicity
8.5. Reproduction and developmental toxicity
8.5.1. Reproduction
8.5.2. Developmental toxicity
8.6. Mutagenicity and related end-points
8.7. Carcinogenicity
8.8. Special studies - cardiopulmonary effects
8.8.1. Cardiac sensitization in response to exogenous
adrenaline-induced arrhythmia
8.8.2. Cardiac sensitization and asphyxia-induced arrhythmia
8.8.3. Arrhythmia not associated with asphyxia or adrenaline
8.9. Mechanisms of toxicity - mode of action

9. EFFECTS ON HUMANS

9.1. Controlled studies with volunteers
9.2. Occupational exposure
9.3. Non-occupational exposures
9.4. Health effects associated with stratospheric ozone depletion
9.4.1. Skin cancer effects
9.4.2. Immunotoxic effects
9.4.3. Ocular effects

9.4.4. Effects on vitamin D synthesis
9.4.5. Exacerbation of photochemical smog formation and
effects

10. EVALUATION OF HUMAN HEALTH RISKS AND EFFECTS ON THE ENVIRONMENT

10.1. Evaluation of human health risks
10.1.1. Direct health effects resulting from exposure to fully
halogenated chlorofluorocarbons
10.1.2. Health effects expected from reduction of stratospheric
ozone by chlorofluorocarbons
10.2. Effects on the environment
10.3. Conclusions

11. RECOMMENDATIONS

REFERENCES

RESUME

EVALUATION DES RISQUES POUR LA SANTE HUMAINE ET EFFETS SUR L'ENVIRONNEMENT

RECOMMANDATIONS

RESUMEN

EVALUACION DE LOS RIESGOS PARA LA SALUD HUMANA Y DE LOS EFFECTOS EN EL
MEDIO AMBIENTE

RECOMENDACIONES

WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR FULLY HALOGENATED
CHLOROFLUOROCARBONS

Members

Dr B. Gilbert, Company for the Development of Technology
Transfer, Cidade Universitaria, Campinas, Brazil
(Rapporteur)

Professor H.A. Greim, Institute of Toxicology and Biochem-
istry, Association for Radiation and Environmental
Research, Neuherberg, Federal Republic of Germany
(Chairman)

Dr L. Hinkova, Toxicologist, Institute of Hygiene and
Occupational Health, Sofia, Bulgaria

Dr Y. Lessard, Laboratory of Medical Physiology, Faculty
of Medicine, University of Rennes, France

Dr M. Morita, Department of Legal Medicine, Sapporo Medi-
cal College, Sapporo, Japan

Dr G. Neumeier, Federal Office for the Environment,
Berlin, Federal Republic of Germany

Professor M. Noweir, Occupational Health Research Centre,
Higher Institute of Public Health, University of
Alexandria, Alexandria, Egypt

Dr J. Sokal, Department of Toxicity Evaluation, Institute
of Occupational Medicine, Lodz, Poland

Professor J.C. Van der Leun, Institute of Dermatology,
State University Hospital of Utrecht, Utrecht,
Netherlands

Dr K. Victorin, National Institute of Environmental Medi-
cine, Department of Environmental Hygiene, Stockholm,
Sweden

Dr W.D. Wagner, National Institute of Occupational Safety
and Health, Cincinnati, Ohio, USA

Dr R.C. Worrest, Stratospheric Ozone Research Program,
Office of Environmental Processes and Effects Research,
US Environmental Protection Agency, Washington, D.C.,
USA

Observers

Dr D. Mayer, Toxicology Department, Hoechst AG, Frankfurt
am Main, Federal Republic of Germany

Dr H. Trochimowicz, E.I. Du Pont de Nemours, Haskell Lab-
oratory for Toxicology and Industrial Medicine, Newark,
Delaware, USA

Representatives of Host Country

Dr U. Schlottmann, Federal Ministry for the Environment,
Nature Conservation and Nuclear Safety, Bonn, Federal
Republic of Germany^b

Dr V. Quarg, Federal Ministry for the Environment, Nature
Conservation and Nuclear Safety, Bonn, Federal Republic
of Germany^b

Secretariat

Professor F. Valic, IPCS Consultant, World Health Organiz-
ation, Geneva, Switzerland (Responsible Officer and
Secretary)^a

Dr S. Lutkenhoff, Office of Health and Environmental
Assessment, US Environmental Protection Agency,
Cincinnati, Ohio, USA

Dr G. Quélennec, Division of Vector Biology and Control,
World Health Organization, Geneva, Switzerland

-------------------------------------------------------
^a Vice-rector, University of Zagreb, Zagreb, Yugoslavia.
^b Present for part of the meeting only.

NOTE TO READERS OF THE CRITERIA MONOGRAPHS

Every effort has been made to present information in
the criteria monographs as accurately as possible without
unduly delaying their publication. In the interest of all
users of the environmental health criteria monographs,
readers are kindly requested to communicate any errors
that may have occurred to the Manager of the International
Programme on Chemical Safety, World Health Organization,
Geneva, Switzerland, in order that they may be included in
corrigenda, which will appear in subsequent volumes.

* * *

A detailed data profile and a legal file can be
obtained from the International Register of Potentially
Toxic Chemicals, Palais des Nations, 1211 Geneva 10,
Switzerland (Telephone No. 7988400 or 7985850).

ENVIRONMENTAL HEALTH CRITERIA FOR FULLY HALOGENATED
CHLOROFLUOROCARBONS

A WHO Task Group on Environmental Health Criteria for
Fully Halogenated Chlorofluorocarbons met at the Institute
of Toxicology and Biochemistry, Neuherberg, Federal Repub-
lic of Germany, from 21 to 25 November 1988. Professor
H.A. Greim opened the meeting on behalf of the host insti-
tute. Dr U. Schlottmann spoke on behalf of the Federal
Government, which sponsored the meeting. Professor
F. Valic welcomed the members on behalf of the three
cooperating organizations of the IPCS (UNEP/ILO/WHO). The
Task Group reviewed and revised the draft criteria mono-
graph and made an evaluation of the risks for human health
and the environment from exposure to fully halogenated
chlorofluorocarbons.

The drafts of this monograph were prepared by the
Office of Health and Environmental Assessment, US Environ-
mental Protection Agency, under the direction of Dr J.
STARA and Dr S. LUTKENHOFF. The chapter on the ecological
effects of stratospheric ozone depletion was prepared by
Dr R.C. WORREST and the section on the health effects
associated with stratospheric ozone depletion by Dr L.
GRANT, both of the US Environmental Protection Agency.
Professor F. Valic and Dr P.G. Jenkins (IPCS) were respon-
sible for the overall scientific content and editing,
respectively.

ABBREVIATIONS

ADI Acceptable daily intake

ADP Adenosine diphosphate

bw Body weight

CFC Chlorofluorocarbon

EC Electron capture

ECG Electrocardiogram

EEG Electroencephalogram

FEV Forced expiratory volume

FI Flame ionization

GC Gas chromatography

HCFH-22 Chlorodifluoromethane (CHClF₂)

LDH Lactate dehydrogenase

LOEL Lowest-observed-effect level

MS Mass spectrometry

NMR Nuclear magnetic resonance

NOEL No-observed-effect level

ppb Parts per billion

ppm Parts per million

ppt Parts per trillion

SGOT Serum glutamic oxaloacetic transaminase

SGPT Serum glutamic pyruvic transaminase

TWA Time-weighted average

UV Ultraviolet

v/v Volume per volume

w/v Weight per volume

1. SUMMARY

1.1. Identity, physical and chemical properties, analytical methods

This monograph concerns only those chlorofluorocarbons
(CFCs) that are derived from the complete substitution of
the hydrogen atoms in methane and ethane with both fluor-
ine and chlorine atoms. Many of these compounds are of
commercial significance and some of them are known to con-
tribute to ozone depletion. Compounds considered in this
report include: trichlorofluoromethane (CFC-11), dichloro-
difluoromethane (CFC-12), chlorotrifluoromethane (CFC-13),
1,2-difluoro-1,1,2,2-tetrachloroethane (CFC-112), 1,1-difluoro-
1,2,2,2-tetrachloroethane (CFC-112a), 1,1,2-trichloro-1,2,2-
trifluoroethane (CFC-113), 1,1,1-trichloro-2,2,2-trifluoroeth-
ane (CFC-113a), 1,2-dichloro-1,1,2,2-tetrafluoroethane (CFC-
114), 1,1-dichloro-1,2,2,2-tetrafluoroethane (CFC-114a), and
1-chloro-1,1,2,2,2-pentafluoroethane (CFC-115). Compounds
not containing chlorine have not been considered. Those
compounds containing hydrogen will be reviewed in a sub-
sequent report.

Commercial chlorofluorocarbons rank among the highest
purity organic chemicals available. They are usually
characterized by high vapour pressure and density and low
viscosity, surface tension, refractive index, and solu-
bility in water. The degree of fluorine substitution
greatly affects the physical properties and, in general,
as fluorine substitution increases, the vapour pressure
increases, and the boiling point, density, and solubility
in water decrease.

The chlorofluorocarbons reviewed in this monograph are
reasonably stable chemically and, in the absence of metal
catalysts, exhibit low rates of hydrolysis. They are
highly resistant to attack by conventional oxidizing
agents at temperatures below 200 °C. In general, chloro-
fluorocarbons show a high degree of thermal stability and
are extremely resistant to almost all chemical reagents.
However, they will interact violently with chemically
reactive metals.

Several analytical methods are available for the de-
termination of chlorofluorocarbons in various media. These
include spectrophotometry, gas chromatography with several
quantification methods, and mass spectrometry. The
majority of methods utilize gas chromatography with
various detection techniques, and detection limits are
often of the order of 1 part per trillion (ppt). Methods
for sample collection have been modified to achieve
greater selectivity and sensitivity.

1.2. Sources of human and environmental exposure

The chlorofluorocarbons discussed in this monograph
are not known to occur naturally in the environment, but
practically all chlorofluorocarbons, except those used as
chemical intermediates, are released into the environment.
The estimated world production of the important poten-
tially ozone-depleting chlorofluorocarbons (CFC-11, CFC-
12, CFC-113) in 1985 was at least a million tonnes. Manu-
facture is not limited to major industrial nations; it
occurs in at least 16 countries. With the implementation
of the Montreal Protocol, the present growth trend in the
production of these chlorofluorocarbons will probably be
reversed.

The most important method for manufacturing the major
chlorofluorocarbons is the catalytic displacement of
chlorine from chlorocarbons with fluorine by reaction with
anhydrous hydrogen fluoride. Most release to the environ-
ment occurs during the disposal of waste refrigerant-
containing equipment, and not during manufacture, storage,
or handling. The release of propellant chlorofluorocarbons
has decreased as a result of legislative restrictions on
their use in many countries, and the release of blowing
agents is small. Because of the high vapour pressure of
these compounds at ambient temperatures, almost all of the
amount released into the environment eventually accumu-
lates in the atmosphere. The estimated total annual
release of about one million tonnes consisted in 1985
largely of CFC-11 and CFC-12, and the cumulative release
of these chlorofluorocarbons from 1931 to 1985 was about
13.5 million tonnes.

The approximate world use pattern of chlorofluorocar-
bons in 1985 was as follows: refrigerants, 15%; foam-
blowing agents, 35%; aerosol propellants, 31%; miscel-
laneous, 7%, and unallocated, 12%. In the USA, the aerosol
propellant use was much lower because of restrictions.

1.3. Environmental transport, distribution, and transformation

The commercial chlorofluorocarbons are persistent in
the environment because of their chemical stability. The
average residence times in the atmosphere are estimated to
be 65, 110, 400, 90, 180, and 380 years for CFC-11, CFC-
12, CFC-13, CFC-113, CFC-114, and CFC-115, respectively.
These long residence times will ensure diffusion into the
stratosphere where, via photochemically-produced chlorine
atoms, the chlorofluorocarbons will react with the ozone
layer. Additionally, these compounds will contribute to
the greenhouse effect.

1.4. Environmental levels and human exposure

The global distribution of chlorofluorocarbons has
been reported by several investigators. Recent measure-
ments of latitudinal variations of chlorofluorocarbon con-
centrations indicate little difference in CFC-11 and CFC-
12 concentrations between the northern and southern hemi-
spheres. Also there is no significant variation with alti-
tude up to 6 km above the Earth's surface. The measured
concentrations of chlorofluorocarbons in urban/suburban
air are higher than those in rural/remote areas because of
contributions from local sources of emission.

Atmospheric levels of CFC-11 and CFC-12 increased
steadily up to 1985, when combined levels for these two
compounds in the USA were 9120 ng/m³ in urban/suburban
areas and 2720 ng/m³ in rural/remote areas for both com-
pounds. From these data, human inhalation intake has been
estimated at 182 and 54 mg/day in these two types of
areas.

The mean surface ocean concentrations of CFC-11 and
CFC-12, reported from three mutually distant locations,
were of the order of 0.2 ng/litre. However, 0.62 ng CFC-11
per litre was measured in the Greenland Sea in 1982 and
values of up to 0.54 ng/litre have been measured in
Japanese coastal waters. The highest value for CFC-12
reported was 0.33 ng/litre in these same coastal waters.
Much higher levels have been measured in fresh water in
Lake Ontario where 249 mg CFC-11 per litre and 572 ng CFC-
12 per litre have been recorded. Chlorofluorocarbons have
not been detected in drinking-water, but have been found
in snow and rain water in Alaska, in Lake Ontario, and in
the Niagara river. CFC-11 has been detected at levels of
0.1-5 µg/kg (ppb) (dry weight basis) in various organs of
fish and molluscs. However, the presence of chlorofluoro-
carbons in processed food has not been documented.

1.5. Kinetics and metabolism

Chlorofluorocarbons may enter the human organism by
inhalation, ingestion, or dermal contact. Inhalation is
the most common and important route of entry, and exha-
lation is the most significant route of elimination from
the body. Controlled studies with volunteer subjects and
experimental animals have provided substantial data from
exposures to a number of the chlorofluorocarbons. These
data indicate that chlorofluorocarbons:

* can be absorbed across the alveolar membrane, gastro-
intestinal tract, or the skin;
* are absorbed rapidly into the blood, following inha-
lation;
* are absorbed into the blood at a decreasing rate as
blood concentration increases;

* once in the blood, are absorbed by various tissues;
* will reach a stable blood level if exposure is suf-
ficiently long, indicating an equilibrium between the
air containing the chlorofluorocarbons and the
blood;
* are still absorbed by body tissue, after the initial
blood level stabilization, and continue to enter the
body.

Studies with animals indicate that chlorofluorocarbons
are rapidly absorbed after inhalation and are distributed
by blood into practically all tissues of the body. The
highest concentrations are usually found in fatty or
lipid-containing tissues. However, chlorofluorocarbons are
also found in organs with a good blood supply, e.g.,
heart, lung, kidney, muscle.

Results from animal and human metabolic studies have
demonstrated the resistance of chlorofluorocarbons to
breakdown or metabolic transformation in biological sys-
tems. These results suggest that chlorofluorocarbons, in
general, are metabolized to a very small degree, if at
all, following exposure.

Regardless of the route of entry, chlorofluorocarbons
are eliminated almost exclusively through the respiratory
tract via exhaled air. No significant recovery of chloro-
fluorocarbons or their metabolites has been reported in
studies attempting to identify metabolic transformation
products via elimination in urine or faeces.

1.6. Effects on the environment

Certain chlorofluorocarbons, including CFC-11, 12,
113, 114, and 115, are extremely stable under conditions
found in the lower atmosphere. It is not until these
gases migrate into the high-energy radiation environment
of the upper stratosphere that photolytic processes split
the chlorine off from the chlorofluorocarbons. These
chlorine radicals catalytically destroy ozone. Strato-
spheric ozone absorbs solar ultra-violet radiation (UV-B:
280-320 nm wavelength) allowing only reduced UV-B radi-
ation to penetrate to the surface of the earth.

Experimental evidence suggests that increased UV-B
irradiation at the Earth's surface, resulting from ozone
depletion, would have deleterious effects on both terres-
trial and aquatic biota. Despite uncertainties resulting
from the complexities of field experiments, the data cur-
rently available suggest that crop yields and forest pro-
ductivity are vulnerable to increased levels of solar UV-B
radiation. Existing data also suggest that increased UV-B
radiation will modify the distribution and abundance of
plants, and change ecosystem structure.

Various studies of marine ecosystems have demonstrated
that UV-B radiation causes damage to fish larvae and juv-
eniles, shrimp larvae, crab larvae, copepods, and plants
essential to the marine food web. These damaging effects
include decreased fecundity, growth, and survival. Exper-
imental evidence suggests that even small increases in
ambient UV-B exposure could result in significant ecosys-
tem changes.

1.7. Effects on experimental animals and in vitro systems

The acute inhalation toxicity of chlorofluorocarbons
has been extensively studied. The chlorofluorocarbons con-
sidered in this monograph show low acute inhalation tox-
icity. The symptomatology of acute intoxication involves
CNS effects, secondary effects on the cardiovascular sys-
tem, and irritation of the respiratory tract. The limited
information available on the acute oral toxicity of
chlorofluorocarbons indicates low toxicity. When applied
dermally in high doses, CFC-112, CFC-112a, and CFC-113
cause various degrees of irritation but no other signifi-
cant effects.

Short-term inhalation studies have been reported for
CFC-11, CFC-12, CFC-112, CFC-113, CFC-114, and CFC-115.
The results showed low toxicity, and the effects observed
were related mainly to the CNS, respiratory tract, and the
liver. Oral toxicity studies have confirmed the low tox-
icity.

In a long-term inhalation study, rats were exposed to
CFC-113 at 0.2, 1, or 2% (15.3, 76.6, or 183 g/m³) 6 h
per day, 5 days/week for up to 2 years. No histopathologi-
cal effects or changes in clinical laboratory values were
observed. The only finding considered by the authors to
be treatment-related was a reduction in body weight gain
in the groups exposed to the two highest doses.

The available information indicates that the fully
halogenated chlorofluorocarbons evaluated in this mono-
graph have little or no mutagenic or carcinogenic poten-
tial. Negative results have been obtained in vitro using
bacteria and mammalian cells with or without metabolic
activation and in the dominant lethal test.

Long-term carcinogenicity studies (by oral and inha-
lation routes) with CFC-11 and CFC-12 in rats and mice
showed negative results. Although a tumorogenic response
in the nasal cavity was observed in rats upon inhalation
of CFC-113, this response was considered equivocal. The
tumours were of various morphologies and the incidences
were not dose-related.

Of the eight chlorofluorocarbons reviewed in this
document, developmental toxicity studies have been
reported in the available scientific literature for CFC-
11, CFC-12, and CFC-113. No evidence of embryotoxicity,
fetotoxicity, or teratogenicity has been documented for
any of these three chlorofluorocarbons.

1.8. Effects on humans

Controlled studies of volunteers using CFC-11 and
CFC-12 revealed no observable effects on clinical haema-
tology and chemistry, EEG, or neurological parameters.

At high concentrations, subjects experienced a
tingling sensation, humming in the ears, and apprehension.
EEG changes were noted as well as slurred speech and de-
creased performance in psychological tests. An exposure to
an 11%^a (545 g/m³) concentration of CFC-12 for 11 min
caused a significant degree of cardiac arrythmia, followed
by a decrease in consciousness with amnesia after 10 min.
Following exposure to CFC-12 at a concentration of 1%
(50 g/m³) for 150 min, a 7% decrease in psychomotor test
scores was noted, but no effects were observed at 0.1%
(5 g/m³).

In a study in which 10 subjects were exposed to CFC-
11, CFC-12, CFC-114, two mixtures of CFC-11 and CFC-12,
and a mixture of CFC-12 and CFC-114 (breathing concen-
trations between 16 and 150 g/m³) for 15, 45, or 60 sec-
onds, significant acute reduction of ventilatory lung
capacity (FEF50, FEF25) was reported in each case, as well
as bradycardia and increased variability in heart rate and
atrioventricular block.

Psychomotor performance was evaluated using CFC-113 at
concentrations of 0.15% (12 g/m³), 0.25% (19 g/m³),
0.35% (27 g/m³), or 0.45% (35 g/m³) for 165 min. There
was no effect at the lowest concentration, but there was
difficulty in mental concentration and some decrease in
test scores beginning at 0.35% (27 g/m³).

----------------------------------------------------------------------------
^a Throughout this monograph, percentages of chlorofluorocarbons
in air are expressed as the volume of chlorofluorocarbon divided
by the volume of air.

Limited studies indicate that individuals with a prior
history of skin reaction to deodorant sprays containing
CFC-11 or CFC-12 may become sensitized to dermal appli-
cations of certain chlorofluorocarbons. The tracheal
mucociliary function in five non-smokers was not impaired
by exposure to CFC-11.

Two studies suggest that normal occupational exposure
to CFC-113 does not pose a serious health hazard. No
adverse effects occurred at occupational levels as high as
0.47% (36.7 g/m³), with an average level of 0.07%
(5.4 g/m³).

Although chlorofluorocarbons have been used for over
50 years, only one cohort study (539 exposed workers) is
available. No increase in total deaths or tumour deaths
was observed.

Significant acute reduction in the ventilatory lung
capacity of hairdressers using chlorofluorocarbon-contain-
ing hairsprays was observed in several studies. Cases of
neurological effects attributed to occupational exposure
to chlorofluorocarbons have been reported. One case of
neuropathy in a laundry worker, exposed to tetrachloro-
ethene and to undetermined levels of CFC-113 for 6 years,
has been described.

Non-occupational exposure and accidental or abusive
inhalation of aerosols have also been documented, the main
symptoms being CNS depression and cardiovascular reac-
tions. Cardiac arrythmia, possibly aggravated by elevated
levels of catecholamines due to stress or by moderate
hypercapnia, is suggested as the cause of these adverse
responses, which may lead to death.

Increased UV-B radiation is expected to lead to pre-
dominantly adverse effects on human health, but the state
of knowledge varies greatly from one effect to another.
It is virtually undisputed that the incidence of non-
melanoma skin cancers will increase. Projections based on
recent data indicate that the incidence of non-melanoma
skin cancers will increase by 3% for every 1% depletion of
ozone. On this basis, an ozone depletion by 5% would lead,
after several decades, to about 240 000 additional new
cases of non-melanoma skin cancer per year, worldwide.

UV-B radiation appears also to play a role in the for-
mation of the more dangerous cutaneous melanomas. However,
there is insufficient knowledge to determine accurate
dose-response relationships.

The immune system is influenced by UV-B radiation in
various ways. Although the knowledge available is insuf-
ficient to predict the consequences of ozone depletion for

human health, increased incidence of some infectious dis-
eases might be one of the consequences.

The most important effect for the human eye would be
an increase in the incidence of cataracts, a permanent
clouding of the eye lens which leads, even at current
levels of UV-B radiation, to impaired vision and blindness
in many people.

Increased UV-B radiation would be expected to increase
photochemical smog, and this would aggravate the related
health problems in urban and industrialized areas.

1.9. Evaluation of human health risks

The most important direct effects on humans from ex-
posure to chlorofluorocarbons are caused by the excessive
concentrations resulting from industrial accidents or poor
occupational practices and from misuse or abuse of the
chemicals when used as solvents or as propellant gases.
Release of chlorofluorocarbons into the global environment
during use, disposal of wastes, transport, and storage are
an increasing concern because of the potential impact such
uncontrolled releases may have on the future health of
mankind, mainly through the depletion of stratospheric
ozone.

2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

2.1. Identity

The chlorofluorocarbons (CFCs) considered in this
monograph are compounds derived by the complete substi-
tution of the hydrogen atoms in methane and ethane with
both fluorine and chlorine atoms. Chlorofluorocarbons con-
taining hydrogen (designated HCFC) will be reviewed in a
subsequent report. The chemical formulae, relative molecu-
lar masses, common names, common synonyms, and CAS Regis-
try numbers of some of the chlorofluorocarbons reviewed
(CFCs 11, 12, 13, 112, 112a, 113, 113a, 114, 114a, 115)
are given in Table 1.

Chlorofluorocarbons are marketed under many different
trade names, e.g., Algcon, Algofrene, Arcton, Eskimon,
Flugene, Forane, Freon, Frigen, Genetron, Isceon, Osotron,
Khladon. The individual chemical substances are character-
ized by code numbers, as defined in DIN 89 62, which are
very widely adopted and uniformly used.

2.1.1. Technical product

Commercial chlorofluorocarbons rank among the highest
purity organic chemicals sold in the USA (Bower, 1973),
the purity of commercial CFC-11 and CFC-12 commonly ex-
ceeding 99.9% (Hamilton, 1962). The predominant isomers of
the ethane series (CFC-113, CFC-114) are the more symmetri-
cal ones (CCl₂F.CClF₂ and CClF₂.CC1F₂). CFC-113 usually
contains no more than a few tenths of 1% of CFC-113a
(CCl₃.CF₃), while CFC-114 usually contains no more
than 7-10% CCl₂F.CF₃. Levels of other impurities in the
four major CFCs (CFC-11, CFC-12, CFC-113, CFC-114) are:
moisture, 10 ppm; residue, a few ppm; acids, much less
than 1 ppm; and non-condensibles (i.e., air components)
100-200 ppm in the liquid phase or 0.5-1.0% in the gas
phase (Hamilton, 1962).

The commercial chlorofluorocarbons may also be formu-
lated with chemicals other than CFCs, such as actone,
ethanol, isopropanol, and methylene chloride. In addition,
nitromethane or other stabilizers are sometimes added to
alcohol-based aerosols (0.3% by weight) (Du Pont, 1980a).

Table 1. Identity and physical and chemical properties of commercially
significant fully halogenated chlorofluorocarbons^a
---------------------------------------------------------------------------------------------------
Chemical formula CCl₃F CCl₂F₂ CClF₃ CC1₂F.CCl₂F CCl₃.CClF₂

Relative molecular 137.37 120.92 104.46 203.82 203.82
mass

Common name trichloro- dichlorodio- chlorotri- 1,2-difluoro- 1,1-difluoro-
fluoro- fluormethane fluoromethane 1,1,2,2-tetra- 1,2,2,2-
methane chloroethane tetrachloro-
ethane

CAS registry number 75-69-4 75-71-8 75-72-9 76-12-0 76-11-9

Common synonyms CFC-11, F-11, CFC-12, F-12, CFC-13, F-13 CFC-112, F-112 CFC-112a,
and trade names Freon 11, Freon 12, F-112a
Frigen 11, Arcton, Frigen 12,
Arcton 9 Genetron 12,
Halon, Osotron 2

Physical state liquid at gas gas solid solid
temperatures
< 23.7 °C

Colour colourless colourless colourless white

Odour faint ethereal nearly ethereal slightly
odourless camphor-like
Melting point (°C) -111 -158 -181 26 40.6

Boiling point (°C) 23.82 -29.79 -81.4 92.8 91.5

Flashpoint^b NF NF NF NF NF

Density of saturated 5.86 6.33 7.01 7.02
vapour at boiling
point (g/litre)

Solubility in water 0.11 0.028 0.009 0.012
(25 °C) (wt %) (saturation pressure)

Conversion factor 5.71 5.03 4.34 8.47 8.47
(ppm(v/v)-> mg/m³)
(20 °C)
---------------------------------------------------------------------------------------------------

Table 1 (contd.)
---------------------------------------------------------------------------------------------------

Chemical formula CCl₂F.CClF₂ CCl₃.CF₃ CClF₂.CClF₂ CCl₂F.CF₃ CClF₂.CF₃

Relative molecular 187.38 187.38 170.92 170.92 154.47
mass

Common name 1,1,2-tri- 1,1,1-tri- 1,2-dichloro- 1,1-dichloro- 1-chloro-1,1,
chloro-1,2,2- chloro-2,2,2- 1,1,2,2-tetra- 1,2,2,2-tetra- 2,2,2-penta-
trifluoro- trifluoro- fluoroethane fluoroethane fluoroethane
ethane ethane

CAS registry number 76-13-1 354-58-5 76-14-2 374-07-2 76-15-3

Common synonyms CFC-113, F-113 CFC-113a CFC-114, CFC-114a, CFC-115, F-115
and trade names Freon 113 F-114 F-114a Freon 115

Physical state liquid liquid gas gas gas

Colour colourless colourless colourless

Odour nearly nearly
odourless odourless

Melting point (°C) -35 14.2 -94 -94 -106

Boiling point (°C) 47.57 45.8 3.77 3.6 -39.1

Flashpoint^b NF NF NF NF NF

Density of saturated 7.38 7.83 8.37
vapour at boiling
point (g/litre)

Solubility in water 0.011 0.009 0.006
(25 °C) (wt %)

Conversion factor 7.79 7.79 7.11 7.11 6.42
(ppm(v/v) -> mg/m³)
(20 °C)
---------------------------------------------------------------------------------------------------
^a From: Du Pont (1980b); Smart (1980); Hawley (1981); and Windholz (1983).
^b NF: non-flammable.
2.2. Physical and chemical properties

Chlorofluorocarbons are usually characterized by high
vapour pressure (low boiling point) and density and low
viscosity, surface tension, refractive index, and solu-
bility in water. The common physical and chemical proper-
ties of the commercially significant chlorofluorocarbons
are given in Table 1.

The degree of fluorine substitution greatly affects
the physical properties of chlorofluorocarbons. In gen-
eral, as the number of fluorine atoms replacing chlorine
increases, the vapour pressure also increases, but the
boiling point, density, and solubility in water decrease.
For example, in the chlorofluoroethane series, vapour
pressure increases with fluorination in the sequence:

CFC-112 < CFC-113 < CFC-114 < CFC-115 < CFC-116

The solvent power of the chlorofluorocarbons ranges
from poor for the highly fluorinated compounds to fairly
good for the less fluorinated compounds (Du Pont, 1980b).
Being typical non-polar liquids, they exhibit low water
solubility.

Apart from their use as chemical intermediates, the
chlorofluorocarbons reviewed find applications that
reflect their chemical stability rather than chemical
reactivity. This chemical stability is a result of the
strength of the C-F bond (Bower, 1973).

Although quite inert, chlorofluorocarbons do exhibit
some chemical reactivity in some applications. For
example, although they exhibit a low rate of hydrolysis
compared with other halogenated compounds, the rate of
hydrolysis is greatly affected by temperature, pressure,
the presence of metals, and the pH of the solution (Du
Pont, 1980a,b). Thus CFC-11 is considered unsuitable for
water-based products packaged in metal containers since
some metals may catalyse the hydrolysis of CFC-11 with
liberation of acid. Sanders (1960) has demonstrated a
free-radical reaction between CFC-11 and alcohols
resulting in dichloromonofluoromethane and small amounts
of tetrachlorodifluoroethane. The reaction is inhibited
by high concentrations of oxygen and, therefore, it is
unlikely that it will occur in nature. In some cases
dechlorination by zinc (also by magnesium and aluminium)
can occur in the presence of polar solvents:

Zn
FCl²C-CClF² -> FClC=CF² + ZnCl²
Alcohol

Chlorofluorocarbons are highly resistant to attack by
conventional oxidizing agents at temperatures <200 °C
(Downing, 1966; Bower, 1973). In general, they exhibit a

high degree of thermal stability, but when pyrolysis
occurs in the presence of humidity the products usually
include hydrofluoric and hydrochloric acid and, in the
presence of either water or oxygen, phosgene.

The photolysis of chlorofluorocarbons is discussed in
section 4.2.3.

The carbon-fluorine bonds in chlorofluorocarbon com-
pounds are extremely resistant to almost all chemical
reagents. Reduction with hydrogen does not occur until
temperatures are >830 °C, and often the C-C bond is also
cleaved. Strong reducing agents such as lithium aluminium
hydride will not reduce the C-F bond. However, chloroflu-
orocarbons react violently with alkali and alkaline earth
metals, such as sodium, potassium, and barium (Bower,
1973).

2.3. Conversion factors

Conversion factors for the chlorofluorocarbons re-
viewed in this monograph are given in Table 1.

2.4. Analytical methods

Several analytical procedures used for the determi-
nation of chlorofluorocarbons are summarized in Table 2.
Methods used include spectrophotometry, gas chromatography
with several quantification procedures, and mass spec-
trometry. However, the majority of methods use gas
chromatography with various detection techniques. Methods
for sample collection have been developed to achieve
greater selectivity and sensitivity.

Table 2. Analytical methods for the determination of chlorofluorocarbons
---------------------------------------------------------------------------------------------------------
Sample Samping method/clean-up Analytical method Detection Reference
type limit
v/v
---------------------------------------------------------------------------------------------------------
Air modified inlet with silicon 100 ppb Collins &
rubber membrane; Utley (1972)
mass spectrometry

Air gas chromatography - electron 50-100 ppb Collins et
capture detection al. (1965)

Air gas chromatography - electron 5-10 ppt Lovelock et
capture detection al. (1973);
Su & Goldberg
(1973); Hester
et al. (1974)

Air sorption on cold (< -50 °C) gas chromatography - electron 1 ppt Paryjczak et
activated carbon capture detection al. (1985)

Air sorption on cold (< -50 °C) gas chromatography - electron 1 ppt Reineke &
Tenax-TA+ activated carbon capture detection Baechmann (1985)

Air cryogenic trapping in porous gas chromatography - electron 1 ppt Rudolph & Jebsen
glass beads capture detection (1983)

Air sorption on cold (liquid gas chromatography - electron 1 ppt Singh et al.
N2) SE-30/glass wool capture detection (1983)

Air sorption on cold (-40 °C) gas chromatography - electron 1 ppt Makide et al.
OV-101 capture detection (1980)

Air sorption on cold (< -50 °C) gas chromatography - 2.6 ppt Crescentini
activated carbon high-resolution et al. (1983)
mass spectrometry

Table 2. (contd.)
---------------------------------------------------------------------------------------------------------
Sample Samping method/clean-up Analytical method Detection Reference
type limit
v/v
---------------------------------------------------------------------------------------------------------

Air absorption spectrometry using Zasavitskii
diode laser et al. (1984)

Air sorption on Tenax GC/ capillary column gas Hanai et al.
activated carbon chromatography - electron (1984)
capture detection

Air spectrophotometry of pyridine 7 ppm Tyras (1981)
(occupational) complex

Sea water dynamic purge and trap gas chromatography - electron 0.003 ng/ Bullister &
capture detection litre Weiss (1983)

Blood head space gas chromatography - electron 0.01-0.01 Ramsey &
capture detection ng/litre Flanagan
(1982)
--------------------------------------------------------------------------------------------------------------------------------------------
3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

3.1. Natural occurrence

The chlorofluorocarbons discussed in this monograph
are not known to occur in nature.

3.2. Man-made sources

Almost all chlorofluorocarbons produced, except for
those used as chemical intermediates, are eventually
released into the environment, whether during manufacture,
handling, use, or disposal. The significance of the
release mechanisms discussed below should be evaluated
with this in mind.

3.2.1. Production levels

The estimated world production of the three important
potentially ozone-depleting chlorofluorocarbons (CFC-11,
CFC-12, and CFC-113) in 1985 was approximately one million
tonnes, about 30% being in the USA (SRI, 1986). Table 3
indicates some of the major world producers in 1985 (CMA,
1986; CMR, 1986; Rand, 1986; SRI, 1986).

The reported total demand for all chlorofluorocarbons
in the USA in 1985 was 458 000 tonnes (CMR, 1986), a 26%
increase from the demand figure in 1980 (CMR, 1981). Pro-
duction figures for CFC-11, CFC-12, and CFC-113 in the USA
for 1974-1985 are given in Table 4. In 1984, these three
CFCs accounted for 83% of the total chlorofluorocarbons
produced in the USA (US ITC, 1985). Based on the 1980
demand and the strong market position in several appli-
cations, CMR (1986) projected that the demand for chloro-
fluorocarbons in the USA would grow to 458 000 tonnes in
1985 and reach 590 000 tonnes by 1990, a positive growth
in this 5-year period of 5% per year. However, this was
before the Montreal Protocol was signed in September
1987.^a The demand for CFC-11, which is used mainly for

------------------------------------------------------------
^a The Montreal Protocol on Substances that Deplete the
Ozone Layer, signed by 24 countries in September 1987,
requires a 20% reduction in use and production of the
chlorofluorocarbons 11, 12, 113, 114, and 115 from 1
July 1993 and a further 30% reduction from 1 July 1998.
It stipulates a number of stepwise importation bans
binding on signatories in order to achieve these
reductions (United Nations Environment Programme.
Montreal Protocol on Substances that Deplete the Ozone
Layer, Final Act, Montreal, 1987).

foam blowing, was largely anticipated to follow the expan-
sion pattern of the construction industry. Demand for flu-
oropolymers made from CFC-113 (as well as from HCFCs 22
and 142b) is expected to grow at a rate of 10% or more
because of electrical and electronic applications. The
demand for CFC-113 is also expected to grow because of its
use as a solvent in the semi-conductor industry and as a
replacement for chlorinated solvents under regulatory
pressure (CMR, 1986). Between 1964 and 1974, the pro-
duction of CFC-11 and CFC-12 increased at 8 and 9% per
year respectively. At that time, the hypothesis that
certain chlorofluorocarbons that accumulate in the upper
atmosphere could deplete the earth's ozone layer had a
major impact on the fluorochemical industry (Smart, 1980).

The US EPA (1978) ruled that most aerosol products con-
taining CFC-11 and CFC-12 propellants could not be manu-
factured in the USA after 15 December, 1978. As a result,
the production of CFC-11 and CFC-12 fell sharply, stabil-
izing in 1980. However, with the entry into force of the
Montreal Protocol, which progressively limited the pro-
duction of CFCs-11, 12, 113, 114, and 115, the release of
all of these chlorofluorocarbons should decline.

Table 3. Some of the major world producers of chlorofluorocarbons
in 1985^a,b
----------------------------------------------------------------------
Country Company name
----------------------------------------------------------------------
Argentina Ducilo S.A. (subsidiary of Du Pont de Nemours and Co.)

Australia Pacific Chemical Industries Pty. Ltd. (subsidiary of
Atochem S.A.); Australian Fluorine Chemical Pty. Ltd.

Brazil Du Pont do Brasil S.A. (subsidiary of Du Pont de Nemours
and Co.); Hoechst do Brasil Quimica e Farmacêutica S.A.
(subsidiary of Hoechst A.G.)

Canada Allied Canada, Inc. (subsidiary of Allied Corp.); Du Pont
Canada Inc.

France Atochem S.A.

Germany, Hoechst AG (Frigen); Kali-Chemie AG (Kaltron)
Federal
Republic of

Greece Société des Industries Chimiques du Nord de la Grèce, S.A.

India Navin Fluorine Industries

Italy Montefluos S.p.A. (Algofren)

Japan Asahi Glass Co., Ltd. (Asahiflon); Daikin Kogyo Co., Ltd.
(Daiflon); Du Pont Mitsui Fluorochemical Co., Ltd. (Flon)
Showa Denko, K.K.

Mexico Quimoleasicos, S.A. (subsidiary of Allied Corp.);
Halocarburos S.A. (subsidiary of E.I. Du Pont de Nemours
and Co., Inc.)

Netherlands Akzochemic B.V.; Du Pont de Nemours (Nederland) B.V.
(subsidiary of E.I. Du Pont de Nemours and Co., Inc)

Spain Ugimica S.A. (subsidiary of Atochem, S.A.); Hoechst
Iberica (subsidiary of Hoechst AG); Kali-Chemie S.A.
(subsidiary to Kali-Chemie AG)

United Imperial Chemical Industries PLC (Arcton); I.S.C.
Kingdom Chemicals Ltd. (Isecon)

USA Allied Corp.; E.I. Du Pont de Nemours and Co. Inc.; Essex
Chemical Corp.; Kaiser Aluminum and Chemical Corp.;
Pennwalt Corp.

Venezuela Produren (subsidiary to Atochem, S.A.)
----------------------------------------------------------------------
^a From: CMA (1986); CMR (1986); and SRI (1986).
^b Trade names are given in parentheses, where available.
From: Noble (1972) and Smart (1980).

Table 4. Production of the major chlorofluorocarbons
in the USA in thousands of tonnes^a
----------------------------------------
Year CFC-11 CFC-12 CFC-113^b
----------------------------------------
1985 73.9^b,c 127.9^b,c 73.2^c
1984 83.9 152.7 65.9^d
1982 63.6 117.0 NA
1980 71.7 133.8 NA
1979 75.8 133.3 NA
1978 87.9 148.4 NA
1977 96.4 162.5 >23.1
1976 116.2 178.3 NA
1975 122.3 178.3 NA
1974 154.6 221.1 29.0
----------------------------------------
^a From: US ITC (1975-85), unless otherwise specified.
^b From: Smart (1980), US EPA (1980), and Rand (1986).
^c It is assumed that consumption was the same as
production volume.
^d Estimated value from the 1985 production data and
the assumption that the 1984 production volume was
10% lower (CMR, 1986).
NA = Not available.

3.2.2. Manufacturing processes

The traditional method for manufacturing the fully
halogenated chlorofluorocarbons is the catalytic displace-
ment of chlorine from chlorocarbons with fluorine by reac-
tion with anhydrous hydrogen fluoride (Hamilton, 1962;
Smart, 1980). Carbon tetrachloride, and hexachloroethane
(or tetrachloroethylene plus chlorine) are commonly used
starting materials for 1- and 2-carbon chlorofluorocar-
bons. Carbon tetrachloride is normally used for producing
CFC-11, CFC-12, and CFC-113. The reaction can occur in
either liquid or vapour phases. The processes use antimony
pentafluoride or an equivalent catalyst, in contact with
which the chlorocarbon and hydrogen fluoride react. Excess
hydrogen fluoride may then be recovered and the chloroflu-
orocarbon stream is neutralised to remove traces of acid
and dried. The chlorofluorocarbons are then separated in
a fractionating column and sent to storage. An alternative
process for the production of the methane-based chloroflu-
orocarbons uses the direct reaction of methane with a
mixture of chlorine and hydrogen fluoride (Noble, 1972).
Other commercially important chlorine-fluorine-substituted
hydrocarbons are manufactured by similar processes
(Lowenheim & Moran, 1975).

The production processes described above give very
high yields. Losses of chlorofluorocarbons are limited to
small mechanical leakage, small amounts leaving with the
by-product hydrogen chloride, and miscellaneous venting.
The total material loss is estimated to be 1% at most

(McCarthy, 1973) for the production operations excluding
transport and storage. Fuller et al. (1976) assumed a
total production loss of 1.5% for the commercially pro-
duced chlorofluorocarbons.

3.2.3. Loss during disposal of wastes

The release of chlorofluorocarbons into the environ-
ment during their disposal arises mainly from pre-fabri-
cated refrigeration and air-conditioning equipment.
Environmental contamination due to chlorofluorocarbon
disposal results principally from the following:

* Unreclaimed refrigerants in the cooling systems of
scrapped pre-fabricated-type refrigeration and air-
conditioning units. Disposal of these old appliances
is usually to scrap yards or waste dumps. Efforts are
made in some countries to remove chlorofluorocarbon
refrigerants before discarding equipment.

* Discarding of vessels containing unused chlorofluoro-
carbons.

* Time-release of trapped blowing agents in rigid
urethane products. This is a minor source of environ-
mental contamination compared with that of scrapped
refrigerants.

Waste disposal streams resulting from manufacturing
operations are very minor contamination sources compared
with scrapped refrigerants.

Because of the high vapour pressure of chlorofluoro-
carbons at ambient temperature, all releases pass eventu-
ally into the atmosphere except in cases where the com-
pounds have been chemically altered.

3.2.4. Release from transport, storage, and accidents

3.2.4.1 Transport and storage

The principal factor required for the transport and
storage of the major chlorofluorocarbons is adequate
design to meet the elevated pressures. The products are
shipped in a wide variety of pressure containers ranging
from 23-litre drums to 91-m³ tank cars.

The containers are fitted with safety valves, rupture
discs, and fusible plugs according to US Interstate
Commerce Commission (ICC) specifications; also included
are requirements for labelling and leak pressure testing.

Loss of product during transport and storage is rela-
tively minor because of the completely closed system used.
Losses are further controlled by monitoring discrepancies,

if any, between product billings and receipts. In
addition, the high cost of the products provides an incen-
tive to control losses. The total industry-wide loss in
transport and storage is <1% of the total quantity pro-
duced.

3.2.4.2 Accidents

Data concerning accidental release are not readily
available. However, it is probable that quantities re-
leased by accident are negligible compared with quantities
released by use and disposal.

3.3. Use patterns

3.3.1. Major uses

Chlorofluorocarbons are commercially important because
of their unique physical and chemical properties and rela-
tively low physiological activity. They are mainly used
as refrigerants, solvents, blowing agents, sterilants,
aerosol propellants, and as intermediates for plastics.
Table 5 lists the estimated use patterns of chlorofluoro-
carbons in the USA for the years 1975, 1978, 1981, and
1985. The aerosol propellant market, which consumed half
of the total chlorofluorocarbon production in 1975, is
currently a minor application because of governmental
restrictions.

Estimated use patterns of CFC-11 and CFC-12 in the USA
and worldwide (excluding eastern European countries) are
given in Tables 6 and 7, respectively (Rand, 1986). The
"unallocated" amounts represent the difference between
the amount of estimated use and the total production data.
According to Rand (1986), part of the unallocated use con-
sists of unreported food refrigeration use and losses
during storage, packaging, and transport.

In countries that signed the Montreal Protocol, the
use of these chlorofluorocarbons will decline.

3.3.2. Release from use: controlled or uncontrolled

The release of CFC-11 and CFC-12 during use has caused the greatest
concern environmentally because of their impact on ozone-depletion.
During the mid-1970s, when aerosol propellant use was the major
chlorofluorocarbon application, aerosols accounted for 75% of the
immediate release of CFC-11 and CFC-12, while refrigerants and
blowing agents accounted for 14% and 12%, respectively (Smart,
1980). Table 8 shows the estimated release of these two
chlorofluorocarbons in 1965, 1970, 1975, 1980, and 1985. CMA (1986)
estimated that the total cumulative worldwide (with the exception
of eastern European countries) release of CFC-11 and CFC-12 as a
result of their use since 1931 amounted to 13.6 million tonnes in
1985.

Table 5. Estimated use patterns of chlorofluorocarbons
in the USA^a (% total production)
-----------------------------------------------------
Application 1975 1978 1981 1985
-----------------------------------------------------
Aerosol propellants 50 24 <1 2
Refrigerants 28 39 46 39
Foam blowing agents b 12 20 17
Solvents 5 11 16 14
Plastics and resins 10 b 7 14
Sterilant gas b b 2 2
Food freezant b b 1 1
Miscellaneous and export 7 14 7 11
-----------------------------------------------------
^a From: CMR (1975, 1978, 1981, 1986).
b Included in miscellaneous category.

Table 6. Estimated use patterns of CFC-11 in the USA and worldwide^a
(excluding eastern European countries)
-------------------------------------------------------
Use USA World
-------------------------------------------------------
Blowing agent 71% 58%
Refrigeration 6% 3%
Aerosol 5% 31%
Miscellaneous 18% 8%
-------------------------------------------------------
^a From: Rand (1986).

Table 7. Estimated use patterns of CFC-12 in the USA
and worldwide^a (excluding eastern European countries)
---------------------------------------------
Use USA World
---------------------------------------------
Blowing agent 11% 12%
Mobile air-conditioning 37% 20%
Retail food refrigeration 4% 3%
Chillers 1% 1%
Home refrigerators 2% 3%
Aerosol 4% 32%
Miscellaneous 10% 7%
Unallocated 31% 22%
---------------------------------------------
^a From: Rand (1986).

Table 8. Worldwide production and release of CFC-11 and CFC-12 during use
(thousands of tonnes)^a
---------------------------------------------------------------------------------------
Release from:
-------------------------------------------------------
Year Production Refrigeration Refrigeration Blowing agent Other Total
(hermetically- (non-hermetic) (closed-cell sources release
sealed) foam only)
---------------------------------------------------------------------------------------
1965 312.9 0.8 44.9 5.7 232.1 283.5

1970 559.2 1.2 68.5 16.3 420.7 506.7

1975 695.1 1.8 103.8 35.4 574.0 715.0

1980 639.8 2.6 156.1 65.0 359.7 583.4

1985 703.1 3.9 188.2 99.4 357.8 649.3
---------------------------------------------------------------------------------------
^a From: CMA (1986).
4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

4.1. Transport between media

Because of the high vapour pressure of chlorofluoro-
carbons, the major transport medium is the atmosphere. For
example, Lovelock (1972) found that CFC-11 concentrations
in rural southern England and Ireland could be partly
attributed to sources on the continent of Europe.

CFC-11 and CFC-12 introduced into aquatic systems will
most likely volatilize to the atmosphere. Once in the
troposphere, they will eventually diffuse into the strato-
sphere or be carried back to the earth through precipi-
tation (Callahan et al., 1979).

Data pertaining to the adsorption of CFC-11 and CFC-12
onto soils and sediments are inconclusive (Callahan et
al., 1979). However, the octanol/water partition coef-
ficients of CFC-11 (log P = 2.53) and CFC-12 (log P =
2.16) (Hansch et al., 1975) indicate that adsorption onto
organic particulates may be possible. In cases of signifi-
cant sorption to soils, the volatilization of these com-
pounds will be slower than in aquatic systems, though vol-
atilization may still be the major transport process from
soils.

4.2. Environmental transformation and degradation processes

4.2.1. Oxidation

No information is available concerning the oxidation
of CFC-11 or CFC-12 in the aquatic environment under ambi-
ent conditions. These two chlorofluorocarbons are known to
be relatively stable with respect to attack by hydroxyl
radicals present in the troposphere (Lillian et al., 1975;
US EPA, 1975; Cox et al., 1976; Hanst, 1978).

4.2.2. Hydrolysis

As a group, chlorofluorocarbons exhibit a low rate of
hydrolysis compared with other halogenated compounds, and
the rates of hydrolysis are greatly affected by tempera-
ture, pressure, and the presence of catalytic materials
such as metals. Should hydrolysis of CFC-12 and possibly
other chlorofluorocarbons occur, it would proceed at a
negligible rate compared with the rate of volatilization
and subsequent photodissociation.

4.2.3. Photolysis

4.2.3.1 Photochemistry

Atmospheric ozone prevents virtually all sunlight of
wavelengths less than 290 nm from reaching the earth's

surface. Since the wavelength of sunlight at altitudes
below 50 km is greater than 280 nm, which is above the
wavelength absorbed by chlorofluorocarbons (Doucet et al.,
1973, 1974), there is no mechanism for direct photoalter-
ation of these chemicals in the lower atmosphere.

4.2.3.2 Environmental transformation

CFC-11 and CFC-12 do not photodissociate in the tropo-
sphere, since they do not absorb radiation at wavelengths
greater than 200 nm (Hanst, 1978). They eventually diffuse
into the stratosphere (NRC, 1976; Hanst, 1978) where they
are broken down by higher energy, shorter wavelength
ultraviolet radiation (Jayanty et al., 1975; Rebbert &
Ausloos, 1975; US EPA, 1975; Hanst, 1978; Isaksen &
Stordal, 1981).

The photodissociation of CFC-11 and CFC-12 each result
in the release of two chlorine atoms, since less energy is
required to cleave the C-Cl bond than the C-F bond
(Rebbert & Ausloos, 1975). According to Jayanty et al.
(1975), the photolysis of CFC-11 in the presence of O₂ at
213.9 nm and 25 °C leads to the production of CFClO and,
potentially, chlorine molecules (Cl₂), while the pho-
tolysis of CFC-12 under the same conditions leads to the
production of CF₂O and Cl₂. Chlorine atoms, released
by reactions such as these, are catalysts in the destruc-
tion of the stratospheric ozone layer (US EPA, 1975;
Hanst, 1978; Ember, 1986; Zurer, 1988).

Isaksen & Stordal (1981) rationalized the ozone
depletion by way of a cycle involving the intermediate
formation of chlorine oxide (ClO). The net reaction for
each turn of the cycle is as follows:

Cl + O₃ -> ClO + O₂
ClO + O -> Cl + O₂
---------------------------------
Net O + O₃ -> 2O₂

Other sequences involving ultraviolet radiation and rad-
ical species have also been proposed (Ember, 1986).

4.2.4. Biodegradation

No information on the biodegradability of the commer-
cial chlorofluorocarbons is available (Su & Goldberg,
1976; Callahan et al., 1979).

4.3. Interaction with other physical, chemical, or biological factors

As indicated above, the commercial chlorofluorocarbons
are relatively persistent in the environment because of
their chemical stability, although their degree of per-
sistence has not been determined with accuracy. The

current best estimates for the average residence times in
the atmosphere are 65, 110, 400, 90, 180, and 380 years
for CFC-11, CFC-12, CFC-13, CFC-113, CFC-114, and CFC-
115, respectively (NASA, 1986).

Assuming a troposphere-to-stratosphere turnover time
(the time taken for 63% of troposphere air to diffuse into
the stratosphere) of 30 years, tropospheric life-times of
65 and 110 years, respectively, would result in about 86%
of tropospheric CFC-11 and CFC-12 eventually reaching the
stratosphere. The effect of the transport of CFC-11 and
CFC-12 from troposphere to stratosphere has been reviewed
by NASA (1986). The addition of CFC-11 and CFC-12 to the
atmosphere affects the climate in two ways. Firstly, these
compounds have strong absorption bands in the atmospheric
"window" region, that is from 7-13 µm. Therefore, both
CFC-11 and CFC-12 will induce a "greenhouse" warming
effect by direct absorption of terrestrial radiation. The
second effect is due to the depletion of the stratospheric
ozone layer. Mathematical modelling has shown that chloro-
fluorocarbons will reduce the ozone column. For instance,
it has been calculated that a chlorofluorocarbon growth
rate of 3% per year would lead to a 10% ozone depletion
within 70 years (NASA, 1986). Changes of that magnitude,
or even smaller ones, could have important biological
consequences (sections 6 and 9.4). Additions of chloroflu-
orocarbons to the atmosphere are also predicted to modify
the vertical distribution within the ozone column. As a
result of the unique regional meteorology and the presence
of chlorine radicals in the Antarctic stratosphere,
stratospheric ozone reductions of 30-50% have been
recently observed there during the austral spring.

The reduction of stratospheric ozone affects the sur-
face in two ways:

* directly by increasing the penetration of ultraviolet
B radiation (290-320 nm);

* indirectly by enhancing the global warming effects and
altering climatic conditions.

4.4. Bioconcentration and bioaccumulation

Dickson & Riley (1976) have found CFC-11 at levels of
0.6-28 µg/kg (dry weight basis) in various organs of fish
and molluscs. These levels, however, do not necessarily
indicate a potential for bioaccumulation.

Neely et al. (1974) suggested that bioaccumulation is
directly related to the octanol/water partition coef-
ficient (P) of the compound. The experimentally determined
log octanol/water partition coefficients (log P) of CFC-11
and CFC-12 (see section 4.1.1) indicate that the bioac-
cumulation potential in organisms is low.

5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

5.1. Environmental levels

5.1.1. Air

Singh et al. (1979) collected in situ air samples
aboard a US Coast Guard vessel that sailed the Pacific
Ocean from Oakland, California, USA (37 °N) to Wellington,
New Zealand (42 °S). Tyson et al. (1978) made measurements
at latitudes from 74 °N to 62 °S as part of a 1976 NASA
Latitude Survey Mission between Alaska, USA, and New
Zealand. The results of their monitoring are summarized
in Table 9.
Table 9. Global distribution of chlorofluorocarbons in the troposphere (ng/m³)^a
-------------------------------------------------------------------------------------------
Northern hemisphere Southern hemisphere

Chloro- Mean Standard Mean Standard Reference
fluorocarbon deviation deviation
-------------------------------------------------------------------------------------------
CFC-11 747.5 (113) 75.3 (13.4) 668.8 (119) 65.8 (11.7) Singh et al. (1979)
741.8 (132) 50.6 (9) 696.9 (124) 33.7 (6) Tyson et al. (1978)

CFC-12 1138.5 (230) 126.2 (25.5) 1039.5 (210) 124.2 (25.1) Singh et al. (1979)
1079.1 (218) 54.4 (11) 821.7 (166) 39.6 (8) Tyson et al. (1978)

CFC-113 145.9 (19) 26.8 (3.5) 138.1 (18) 23.8 (3.1) Singh et al. (1979)

CFC-114 83.9 (12) 13.3 (1.9) 69.9 (10) 9.1 (1.3) Singh et al. (1979)
-------------------------------------------------------------------------------------------
^a Figures in brackets are in parts per trillion (by volume).

The increased use of chlorofluorocarbons on a world-
wide basis has resulted in an increase in the global
levels of these compounds. The two most abundant chloro-
fluorocarbons in the atmosphere are CFC-11 and CFC-12
(Guicherit & Schulting, 1985). The annual growth rates in
the 1980s appear to be slower than the growth rates in the
1970s (Rasmussen et al., 1981). The annual rate of in-
crease in CFC-11 global levels during the period 1975-1980
was 8-12% (Rasmussen et al., 1981; Fraser et al., 1983;
Singh et al., 1983), whereas it was 6-7% during 1980-1981
(Brice et al., 1982; Cunnold et al., 1983b; Prinn et al.,
1983; Rasmussen & Khalil, 1986). Similarly, although the
average annual growth rate for global levels of CFC-12
during 1975-1980 was 8-9% (Rasmussen et al., 1981; Singh
et al., 1983), it was only 6% in 1980 (Cunnold et al.,
1983b; Prinn et al., 1983; Rasmussen & Khalil, 1986). Both
CFC-11 and CFC-12 showed an accumulative increase of about
60% during the decade 1975-1985 (Rasmussen & Khalil,
1986).

Data on the atmospheric concentrations of chlorofluo-
rocarbons are shown in Table 10. Measurements of atmos-
pheric chlorofluorocarbon concentrations up to an altitude
of 6 km did not reveal any significant concentration
changes with increasing altitude (Rasmussen & Khalil,
1982, 1983, 1986; Robinson et al., 1983). Hunter-Smith et
al. (1983), Rasmussen & Khalil (1983), and Singh et al.
(1983) studied the latitudinal variation in chlorofluoro-
carbon concentrations between the northern and southern
hemisphere and reported inter-hemispheric contrasts (ratio
of concentration between northern and southern hemi-
spheres) of 1.08 for CFC-11, 1.07-1.08 for CFC-12,
1.10-1.25 for CFC-113, and 1.08 for CFC-114. Table 10
reveals that the concentrations of chlorofluorocarbons are
higher in urban areas than in remote areas, this being the
result of local emission sources. The urban concentrations
of chlorofluorocarbons (CFC-11 and CFC-12) in the People's
Republic of China, with the exception of Beijing, are the
same as background levels in the USA. This is probably due
to the less extensive use of these compounds in urban
areas in China (Rasmussen et al., 1982).

Median concentrations of the most abundant compounds,
CFC-11 and CFC-12, in several urban/suburban areas and
rural/remote areas in the USA are reported in Table 10
(Brodzinsky & Singh, 1982). These measurements were made
from 1972 to 1980, the median year being 1975. Median con-
centration values of 1090 and 3420 ng/m³ for CFC-11, and
1630 and 5700 ng/m³ for CFC-12, in rural/remote and
urban/suburban areas, respectively, were projected for
1985, assuming that the average annual growth rate for
both compounds would be 5% (NASA, 1986). Assuming that an
individual inhales 20 m³ air/day, the total inhalation
exposure (CFC-11 plus CFC-12) in 1985 would be 54 or
182 µg/day in rural/remote or urban/suburban areas of the
USA, respectively. Using the 1985 data from Ragged Point,
Barbados, as a basis, the inhalation for combined CFC-11
and CFC-12 in rural/remote areas in late 1985 would have
been 66 µg/day.
Table 10. Some worldwide measurements of the atmospheric
concentrations of chlorofluorocarbons
---------------------------------------------------------------------------------------------
Concentration of
Location Year chlorofluorocarbons (ng/m³) Reference
CFC-11 CFC-12 CFC-113 CFC-114
---------------------------------------------------------------------------------------------
Barbados

Ragged Point 1980 NR 1499 NR NR Cunnold et al. (1983b)

1985 1313 2012 NR NR NASA (1986)

Samoa (American)

Point Matatula 1980 NR 1433 NR NR Cunnold et al. (1983b)

Table 10. (contd.)
---------------------------------------------------------------------------------------------
Concentration of
Location Year chlorofluorocarbons (ng/m³) Reference
CFC-11 CFC-12 CFC-113 CFC-114
---------------------------------------------------------------------------------------------
United Kingdom

Harwell 1980 1342 NR NR NR Brice et al. (1982)

Adrigole, Ireland 1980 NR 1564 NR NR Cunnold et al. (1983b)

USA

Phoenix, Arizona 1979 1423 NR 1192 NR Singh et al. (1981)

Los Angeles, 1979 2700 NR 2376 NR Singh et al. (1981)
California

Oakland, California 1979 1365 NR 381 NR Singh et al. (1981)

USA rural/remote 1973- 685 1911 241 64 Brodzinsky & Singh (1982)
(median concentration) 1980

USA urban/suburban 1972- 1199 3521 1324 199 Brodzinsky & Singh (1982)
(median concentration) 1980

Pacific Northwest 1980 1073 1620 132 NR Rasmussen et al. (1981)

Northern hemisphere 1978 919 1378 101 NR Rasmussen & Khalil (1982)

Northern hemisphere 1978 1062 1534 179 100 Singh et al. (1983)

Southern hemisphere 1978 845 1283 93 NR Rasmussen & Khalil (1982)

Southern hemisphere 1978 982 1418 164 92 Singh et al. (1983)

Arctic 1982 1174 1780 175 NR Rasmussen & Khalil (1983)

Arctic haze 1979 1097 1633 NR NR Khalil & Rasmussen (1983)

South Pole 1980 948 1428 86 NR Rasmussen et al. (1981)

Over Atlantic Ocean 1981 1056 NR NR NR Brice et al. (1982)

Global average 1980 959 NR NR NR Fraser et al. (1983)
---------------------------------------------------------------------------------------------
NR = not reported.
5.1.2. Water

Singh et al. (1979) measured CFC-11 and CFC-12 concen-
trations in 1977 at various locations in the Pacific
Ocean. The average surface concentration of CFC-11 was
0.13 (± 0.006) ng/litre, while the CFC-12 concentration

was 0.28 (± 0.15) ng/litre. The average concentrations at
a depth of 300 m were 0.06 and 0.21 ng/litre for CFC-11
and CFC-12, respectively. The concentrations of CFC-11 and
CFC-12 at various locations in the eastern Pacific Ocean
(surface waters) during 1979-1981 were 0.22 and 0.25
ng/litre (Singh et al., 1983), in Greenland Sea surface
water in 1982 were 0.61 and 0.21 ng/litre (Bullister &
Weiss, 1983), and in Japanese coastal waters were
0.20-0.54 and 0.19-0.33 ng/litre, respectively (Tomita et
al., 1983).

Samples of water from Lake Ontario analysed for vol-
atile halocarbon contaminants contained mean concen-
trations for CFC-11 and CFC-12 of 249 and 572 ng/litre,
respectively (Kaiser et al., 1983). An alluvial aquifer
in Southington, Connecticut, USA, adjacent to a solvent-
recovery operation was analysed in 1980 for volatile
organic compounds, but CFC-12 was not detected (detection
limit not specified) in water obtained from various depths
(Hall, 1984). CFC-11 and CFC-12 have been detected in sur-
face snow and rainwater in Alaska (Su & Goldberg, 1976).
The detection of chlorofluorocarbons in drinking-water has
not been reported.

5.1.3. Food and other edible products

With the exception of a few scattered reports (section
4.4), chlorofluorocarbons have not been measured in food.

5.2. Occupational exposure

Information on occupational exposure is summarized in
section 9.2.

6. ECOLOGICAL EFFECTS OF STRATOSPHERIC OZONE DEPLETION

6.1. Introduction

Speculation on the possibility of stratospheric ozone
reduction first appeared in the early 1970's and focused
on the consequences of large quantities of nitrogen oxides
being injected into the upper atmosphere by supersonic
aircraft flying at high altitudes. Other sources of nitro-
gen oxides originating from the earth's surface were also
considered. These concerns gradually diminished, because
the quantities of nitrogen oxides likely to be involved
were insufficient to cause a serious threat to the ozone
layer. However, concern over halogen pollution of the
upper atmosphere arose during the mid-1970s (section
4.2.3). The halogens of immediate concern were chlorine
and bromine. The main source for chlorine is chlorofluoro-
carbons, which are released worldwide from such sources as
aerosol spray cans, certain plastic foams, refrigerators,
and refrigerative air conditioners.

Many gases emitted as a result of industrial and agri-
cultural activities can accumulate in the Earth's atmos-
phere and ultimately contribute to alterations in the ver-
tical distribution and concentrations of stratospheric
ozone. Among the most important are those trace gases that
have long residence times in the atmosphere. This allows
accumulation in the troposphere and a gradual upward
migration of the gases into the stratosphere where they
contribute to depletion of stratospheric ozone. The atmos-
pheric and chemical processes involved are extremely
complex (US EPA, 1987a). Trace gases of particular concern
include certain long-lived chlorofluorocarbons, such as
CFC-11, CFC-12, and CFC-113 (for atmospheric residence
times see section 4.3). Since the transport of these gases
to the stratosphere is slow, their residence times there
are long, and the removal processes are slow, any effect
on stratospheric ozone already seen is probably the result
of anthropogenic emissions of these gases several decades
ago. Those gases already in the atmosphere will continue
to exert stratospheric ozone depletion effects well into
the next century.

The atmospheric models that predict future ozone
depletion are in a continual process of refinement. Over
the years, predicted decreases in stratospheric ozone have
ranged from 4 to 18%, based on the stratospheric concen-
trations of chlorine expected from the 1974 levels of CFC-
11 and CFC-12 emissions. However, it has gradually been
realized that other gases will influence column ozone and
that the size and direction of the predicted change in
total ozone during the next century depend critically on
the assumption of the multiple trace-gas scenarios. Many
of the modelling scenarios tended to assume relatively
uniform rates of ozone layer reduction widely distributed

above all regions of the Earth. However, areas of dis-
tinctly greater depletion (ranging from 15 to 40% in
recent years) have been identified over the South Polar
region during September to November of each year. The
evidence suggests a likely gradual expansion of this
"Antarctic Ozone Hole" ultimately to extend beyond the
South Polar region, possibly coming to reach over more
heavily populated areas of the Southern Hemisphere. Simi-
larly, it is considered likely that an analogous, though
less intense, zone of upper level ozone reduction will
occur over the North Polar region and expand over popu-
lated areas of the Northern Hemisphere.

Although ozone constitutes a very small proportion of
the stratosphere, it plays a major role in protecting life
on this planet. The result of changes in the density of
the total ozone column could, therefore, be far-reaching.
The natural distribution of ozone in the Earth's atmos-
phere, concentrated most heavily in a diffuse layer in the
stratosphere, is crucial in helping to protect human
beings, other biological systems, and man-made materials
from the harmful effects of certain wavelengths of sun-
light. Stratospheric ozone exerts its beneficial effects
by absorbing ultraviolet radiation in the 200- to 320-nm
range, allowing only reduced amounts of UV-B radiation
(280- to 320-nm waveband) to penetrate to the Earth's
surface. In addition, the vertical distribution of strato-
spheric ozone and relative dryness of the air in the
stratosphere help to maintain the radiative balance of the
Earth. Depletion of the stratospheric ozone layer can,
therefore, be expected to lead to damaging effects on
human health and the environment (i) directly by increased
penetration of UV-B radiation to the Earth's surface and
(ii) indirectly through the influence of changes in the
vertical distribution of stratospheric ozone and water
vapour that contribute to global warming effects and
altered climatic conditions. The possibility of increased
exposure to solar UV-B radiation is a particular cause for
concern because of its effect on humans, other animals,
plants, certain manufactured materials, and photochemical
smog production. Most of the known biological effects of
UV-B radiation are damaging. Detailed discussions of
evolving concern about stratospheric ozone depletion and
assessment of the scientific base underlying such concern
can be found in several recent national and international
expert work group reports or symposia (e.g., US EPA,
1987a; Schneider et al., 1989; WMO/Canada DOE, 1989). The
following sections summarize key points from such sources
and discuss their implications for the development of
effective international efforts to cope with ozone layer
depletion.

6.2. Terrestrial plants

Increased UV-B irradiation of the Earth's surface due
to ozone layer depletion can be expected to have a nega-
tive impact on both terrestrial and aquatic biota. In as-
sessing the impact of increased exposure to UV-B radiation
for crops and terrestrial ecosystems, it must be recog-
nized that existing knowledge is in many ways deficient.
The effects of enhanced levels of UV-B radiation have been
studied in only a few representative species from some of
the major terrestrial ecosystems. Most knowledge has been
derived from studies that focused upon agricultural crops
and were conducted at mid-latitudes. Despite uncertainties
resulting from the complexities of field experiments, the
available data suggest that crop yields are vulnerable to
increased levels of solar UV-B radiation. Unlike drought
or other geographically isolated stresses, stratospheric
ozone depletion would affect all areas of the world,
including ecosystems whose UV-B sensitivity has not been
investigated.

Out of more than 200 species and cultivars screened
for UV tolerance, about two-thirds have been found to be
sensitive. Most tests were done in controlled environments
with UV radiation from artificial sources. The UV sensi-
tivity was usually exaggerated when compared to results
obtained by exposure to solar radiation in the field. The
most sensitive plant groups include crops related to peas
and beans, melons, mustard, and cabbage, but there are
large differences in sensitivity between the various crops
studied in the field (US EPA, 1987b). In general, UV radi-
ation causes reduced leaf and stem growth, lower total dry
weight, and lower photosynthetic activity in sensitive
cultivars (Tevini & Iwanzik, 1986). These results were
corroborated in an experiment simulating a 25% enhancement
of solar UV-B radiation (equivalent to 12% ozone
reduction), where UV-B exposure was controlled by an arti-
ficial ozone filter at a high altitude and at a southern
latitude (Tevini et al., 1986). Members of the grass
family were generally less sensitive (with some notable
exceptions), possibly due to protective abilities such as
photorepair or production of screening pigments (Beggs et
al., 1986).

The large variation in sensitivity that exists among
cultivars within each crop species suggests that some
degree of UV tolerance must be present in the existing
gene pool. The genetic basis for differences in UV-B sen-
sitivity is not fully understood. However, it is possible
that selective crop breeding might help mitigate some of
the potentially deleterious effects (Teramura, 1983).

In addition to other factors, the quality of crop
yield may be reduced by increased levels of UV-B radi-
ation. Changes in crop quality have not been specifically

examined in many studies, but reduced quality has been
noted in certain cultivars of tomato, potato, sugar beet,
and soybean. The protein and oil content of specific
cultivars of soybean seeds were reduced by up to 10% when
plants were exposed to UV levels equivalent to a 25% ozone
depletion (US EPA, 1987b).

Increased levels of UV-B radiation may also affect
forest productivity. Only limited data are available on
coniferous species, but in studies by Sullivan & Teramura
(1988) about one-half of the species of seedlings were
adversely affected by UV-B radiation. In loblolly pine
seedlings, growth and photosynthesis were reduced in field
studies simulating a 40% ozone reduction (Teramura &
Sullivan, 1988). However, extrapolation from the results
of seedling studies to forested ecosystems is not poss-
ible, nor is interpolation of predicted results at ex-
posure levels simulating a lower level of ozone reduction.

The existing data also suggest that increased UV-B
radiation will modify the distribution and abundance of
plants, and potentially change ecosystem structure as a
result of an alteration of the competitive balance between
different species. Even small changes in competitive bal-
ance over a period of time can result in large changes in
community structure and composition (Gold & Caldwell,
1983). The shift in competitive balance may occur in
response to subtle changes in plant growth, without large
changes in fundamental physiological processes such as
photosynthesis (Beyschlag et al., 1988). The alteration
of the competitive balance of species is a dynamic process
affected by the competing species and their immediate
environment. Unfortunately, neither a quantitative nor a
qualitative prediction of how these ecosystems might be
altered can be determined from the current knowledge
base.

6.3. Aquatic organisms

Various experiments have demonstrated that UV-B radi-
ation causes damage to fish larvae and juveniles, shrimp
larvae, crab larvae, copepods, and plants essential to the
marine food web. These damaging effects include decreased
fecundity, growth, survival, and other reduced functions
in these organisms (Worrest, 1982; US EPA, 1987c). Evi-
dence indicates that ambient solar UV-B radiation,
although not nearly as important as light, temperature, or
nutrient levels, is currently an important limiting eco-
logical factor, and that even small increases in UV-B
exposure could result in significant ecosystem changes
(Damkaer, 1982).

Effects induced by solar UV-B radiation have been
measured to a depth of more than 20 metres in clear waters
and more than five metres in less clear water. The

euphotic zone (i.e. water depth with levels of light suf-
ficient for positive net photosynthesis) is frequently
taken as the water column that reaches down to the depth
at which photosynthetically active radiation is reduced by
99%. In marine ecosystems, UV-B radiation penetrates
approximately the upper 10% of the marine euphotic zone
before it is reduced by 99% of its surface irradiance.
Penetration of UV-B radiation into natural waters is a key
variable in assessing the potential impact of this radi-
ation on any aquatic ecosystem (US EPA, 1987c).

In marine plant communities a change in species compo-
sition rather than a decrease in net production would be
the probable result of increased UV-B exposure (Worrest,
1983). A change in community composition at the base of
food webs may produce instabilities within ecosystems that
could affect higher trophic levels (Kelly, 1986). The
generation time of marine phytoplankton is in the range of
hours to days, whereas the potential increase in ambient
levels of solar UV-B irradiance will occur over decades.
The question remains as to whether the gene pool within
species is capable of adapting during this relatively
gradual (relative to the generation time of the target
organisms) change in exposure to UV-B radiation. There is
evidence that a decrease in column ozone abundance could
diminish the near-surface season of invertebrate zooplank-
ton populations. For some zooplankton, the time spent at
or near the surface is critical for food gathering and
breeding. Whether these populations could endure a sig-
nificant shortening of the surface season is unknown
(Damkaer et al., 1980).

The direct effect of UV-B radiation on edible fish
larvae closely parallels the effect on invertebrate
zooplankton. More information is required on seasonal
abundances and vertical distributions of fish larvae, ver-
tical mixing, and penetration of UV-B radiation into
appropriate water columns before effects of exposure to
solar UV-B radiation can be predicted. However, in one
study involving anchovy larvae, it was calculated that a
20% increase in UV-B radiation (which would accompany a 9%
depletion of total column ozone) would result in the death
of about 8% of the annual larval population (Hunter et
al., 1982). This one study was performed in the labora-
tory, and even the control animals had significant mor-
tality at the end of the normal larval period. This high-
lights the need for caution when trying to extrapolate
conclusions to natural conditions when those conclusions
are based on results from laboratory studies.

In many countries marine species supply more than 50%
of the dietary protein, and in developing countries this
percentage is often higher. Research is needed to improve
our understanding of how stratospheric ozone depletion

could influence the world food supply. However, effective
steps to minimize stratospheric zone depletion cannot
await the outcome of such research.

6.4. Research needs

Future work concerning UV-B effects on terrestrial
ecosystems must proceed on a broad front. Sensitivity
screenings and dose-response studies must expand to
include representative species from a wider range of eco-
system types and a wider range of plant types within eco-
systems of particular interest. Knowledge of species sen-
sitivities and their geographic ranges can then be com-
bined with information on current and projected levels of
UV-B in order to identify areas of greatest concern. An
understanding of how sensitivity to UV-B is affected by
other environmental factors will aid in this process.
Additional work at the biochemical level is needed to
clarify interactions of UV-B radiation and plant metab-
olism as well as the nature of effects of UV-B radiation
on pests and pathogens.

Ultimately, the information gathered in field and lab-
oratory studies must be put into the context of ecosystem
properties, including primary productivity, nutrient
cycling, resistance to disturbance, and the capacity to
recover from disturbance. Efforts are clearly needed to
integrate what is known about the influences of elevated
UV-B irradiance on plants with what is known about plant
stress associated with other human-induced changes in the
environment.

In order to quantify the effects on marine systems of
UV-B radiation on an ocean-wide basis, there is a need for
additional data on the penetration of UV-B radiation as a
function of water mass, concentration of particulates, and
presence of plankton. These data must be combined with
accurate measurements of total incident radiation, as a
function of angle of incidence and time, to arrive at
reliable estimates of both total UV-B radiation dose and
dose rate.

There is a clear need to measure fish-larval sensi-
tivity to UV-B radiation for many resource species, refine
the links between exposure of primary producers to UV-B
radiation and effects on fish, assess the impact of food-
web changes on fish yield, and delineate the mitigating
mechanisms available to the organism.

Studies on changes in population size and diversity as
a result of stress would provide insights for predictions
of the effects of UV-B increases in a given ecological
niche (Worrest et al., 1978, 1981a,b; Worrest, 1983). Data
describing changes resulting from environmental stress,
such as contamination from toxic substances or temperature

change, could be combined with data on the efficiency of
energy conversion between trophic levels, upon which a re-
source species relies, to estimate the potential reduction
in fish catch. To narrow the reliability limits of such
predictions, field investigations into the resiliency of
affected populations are required.

There is a paucity of information on the impact of
UV-B radiation on marine resource species. The fact that
dose-response sensitivity data exist for only a few
species greatly impedes our ability to extrapolate to an
overall assessment of the risk to marine fisheries. It is
important to be able to translate known intracellular
cause-and-effect relationships of UV damage to effects on
simple or single-celled organisms and to population
effects.

Knowledge of adaptive or protective mechanisms by
which marine organisms minimize the effects of increased
UV-B radiation in the ocean's surface layers is lacking.
No avoidance mechanisms specific to UV-B radiation have
been described for marine organisms, although avoidance
mechanisms to visible light may lessen the impact of the
concurrent UV radiation. While pigmentation occurs exten-
sively in marine organisms, the degree to which it con-
tributes to UV-B protection is unknown.

The time scale of adaptation or repair, compared to
the time scale of increased UV-B radiation, is an import-
ant factor. Are genetic mechanisms sufficient to obviate
the negative impacts? Do they affect competitor species
over similar time scales? What organisms are pre-disposed
to environmental (i.e. non-genetic) protective behaviour?
These questions must be addressed as part of the framework
of risk assessment.

7. KINETICS AND METABOLISM

7.1. Absorption

Chlorofluorocarbon propellants and solvents may pre-
sent a hazard for human beings by inhalation, ingestion,
and dermal absorption. However, because of the physical
properties and uses of these compounds, inhalation is the
most common route of entry, and exhalation is the most
significant route of elimination.

Information concerning chlorofluorocarbon absorption
has been obtained in two types of studies:

* chlorofluorocarbon retention in the lungs;
* chlorofluorocarbon blood levels after inhalation.

The relative amounts of CFC-11, CFC-12, CFC-113, and
CFC-114 absorbed by human beings have been measured in
breath-holding studies (Paulet & Chevrier, 1969; Morgan
et al., 1972). Retention was measured using radioiso-
topically marked chlorofluorocarbons by subtracting the
radioactivity exhaled 30 min after inhalation from the
amount of radioactivity inhaled with a single breath. In
terms of absorption the following order was obtained:
CFC-11 ~ CFC-113 > CFC-114 ~ CFC-12, with retentions
of 23%, 19.8%, 12.2%, and 10.3%, respectively. Shargel &
Koss (1972) exposed dogs to an equal weight mixture of
CFC-11, CFC-12, CFC-113, and CFC-114, and obtained similar
results.

In other studies, human volunteers (Aviado & Micozzi,
1981) and dogs (Azar et al., 1973) were exposed to CFC-11
at a concentration of 5710 mg/m³ (1000 ppm) and for a
period of 8 h or 10 min, respectively. The blood levels in
the human volunteers were 4.69 µg/ml and in the dogs
6.5-10 µg/ml. According to a mathematical model developed
for the description of the pharmacokinetics, 77% of the
dose applied was absorbed.

Azar et al. (1973) determined the corresponding data
for CFC-12 in beagle dogs. After an exposure to 5030
mg/m³ (1000 ppm) for a period of 10 min, 1.1 µg/ml was
found in the arterial blood and 0.4 µg/ml in the venous
system. At higher concentrations, the arterial and venous
concentrations were similar. Trochimowicz et al. (1974)
found, under similar conditions (1000 ppm, 1 min inha-
lation period), that the blood level in dogs for CFC-113
was 2.7 µg/ml (arterial) and 1.9 µg/ml (venous), and for
CFC-114 0.4 µg/ml and 0.2 µg/ml, respectively.

In a study by Angerer et al. (1985), three volunteers
were exposed to a CFC-11 concentration of 3750 mg/m³ (657
ppm). The average value of pulmonary retention was 18.9%.
CFC-11 levels in alveolar air and blood were 3066 mg/m³
(537 ppm) and 2.8 µg/ml, respectively.

Further absorption and elimination data from CFC-11
and CFC-12 atomizer administrations indicated that, while
CFC-11 is more readily absorbed by mammals (including
humans) than CFC-12, the degree of preferential absorption
may vary among individuals (Dollery et al., 1970; Allen &
Hanburys Ltd, 1971; Paterson et al., 1971; Shargel & Koss,
1972). Similar information on the different absorption
rates has been obtained from other studies. Chlorofluoro-
carbons were administered to dogs for 5 min at fixed con-
centrations between 0.3 and 10 vol % in the inspired air.
The blood concentrations determined up to 60 min after
exposure indicated that CFC-11 is more readily absorbed
than CFC-12 or CFC-114 (Clark & Tinston, 1972a).

The results of Adir et al. (1975) and Brugnone et al.
(1984) provide additional evidence that CFC-11 is absorbed
to a greater extent than CFC-12 in dogs and rabbits. The
absorption data correlate well with the liquid/gas par-
tition coefficients for these compounds in whole blood,
serum, and olive oil shown in Table 11.

CFC-12 was absorbed 4 times more readily than CFC-114
in a study by Rauws et al. (1973) in which rats were ex-
posed to a mixture of CFC-11, CFC-12, and CFC-114 (weight
ratio of 1:2:1). A similar pattern was also seen in
monkeys by Taylor et al. (1971). In each instance, the
ratio of CFC-12 to CFC-114 in arterial blood was higher
than the ratio of exposure concentrations, indicating that
CFC-12 was slightly more readily absorbed than CFC-114.

The available data on chlorofluorocarbon uptake indi-
cate that chlorofluorocarbons can be absorbed across the
alveolar membrane, gastro-intestinal tract, the skin, and
internal organs. Following inhalation, they are absorbed
rapidly by the blood. Blood-tissue absorption is probably
the rate-limiting step. After an initial, rapid blood
level stabilization, chlorofluorocarbons are still ab-
sorbed by body tissues and continue to enter the body.

Table 11. Partition coefficients of various chlorofluorocarbons
---------------------------------------------------------
Compound Whole blood^a Whole blood^b Serum^c Olive
(rat) (human) (human) oil^c
---------------------------------------------------------
CFC-11 1.4 0.87 0.9 27
CFC-12 0.2 0.15 0.2 3
CFC-113 0.8 32
CFC-114 0.15 0.2 5
---------------------------------------------------------
^a From: Allen & Hanburys, Ltd (1971).
^b From: Chiou & Niazi (1973).
^c From: Morgan et al. (1972).

7.2. Distribution

Allen & Hanburys, Ltd. (1971) found in mice that both
CFC-11 and CFC-12 are taken up by heart, fat, and adrenal
tissue after 5-min inhalation exposures. CFC-11 is concen-
trated from the blood to the greatest extent in the
adrenals followed by the fat, then the heart. A similar,
though less pronounced, pattern is evident for CFC-12 but
CFC-11 is absorbed and concentrated in all of these tis-
sues to a much greater extent than CFC-12. Paulet et al.
(1975) noted that both CFC-11 and CFC-12 are distributed
to the cerebrospinal fluid of dogs after inhalation
exposure.

Following inhalation exposures lasting 7-14 days,
Carter (1970) noted distribution patterns for CFC-113 in
rats that were qualitatively similar to those noted for
CFC-11 and CFC-12 by Allen & Hanburys, Ltd. (1971). The
major difference from the CFC-11 and CFC-12 results was
that almost all of the CFC-113 concentration occurred in
the fat, while adrenal levels were relatively low and even
decreased as exposure continued (it should be emphasized
that the exposures to CFC-11 and CFC-12 were for only
5 min). The other organ levels did not change signifi-
cantly from a 7-day to a 14-day exposure, which is con-
sistent with the idea that such concentrations will
stabilize as equilibria between ambient air concentration,
blood level, and tissue levels are reached. In rats and
guinea-pigs, shortly after exposure to CFC-113, Furuya
(1979) noted the following tissue distribution in
decreasing order: fat, brain, liver, kidney, heart, lung,
muscle, and blood.

In summary, chlorofluorocarbons are rapidly absorbed
after inhalation and are distributed by blood into practi-
cally all tissues. Relatively high concentrations are
found in fat, but also in organs with good blood supply.

7.3. Metabolic transformation

Of the nine chlorofluorocarbons reviewed in this docu-
ment, some data regarding metabolism exists only for CFC-
11, CFC-12, CFC-112a, and CFC-113a.

Cox et al. (1972a) found no evidence of reductive
dehalogenation of CFC-11 in microsomal preparations from
rats, chickens, or other species. However, the reductive
dechlorination in vitro of CFC-11 to HCFC-21 by rat liver
microsomes was reported by Wolf et al. (1978). In vitro
metabolism studies suggested that CFC-112a and CFC-113a
can be metabolized by reductive dechlorination and that
the reaction is catalyzed by cytochrome P-450 from rat
liver microsomes. However, no metabolites of either
compound were identified (Salmon et al., 1981, 1985;
Nastainczyk et al., 1982a,b).

Published studies on in vivo metabolism exist only for
CFC-11 and CFC-12. Eddy & Griffith (1971) administered
14C-labelled CFC-12 to rats by the oral route and
reported a small amount of metabolism. About 2% of the
total dose was exhaled as ¹⁴CO₂ and 0.5% was excreted in
urine. CFC-12 and/or its metabolites were no longer
detectable in the body 30 h after administration.

Blake & Mergner (1974) exposed beagle dogs for 6-20
min to CFC-11 (5710 to 28 550 mg/m³; 1000 to 5000 ppm,
v/v) or CFC-12 (40 240 to 60 380 mg/m³; 8000 to 12 000
ppm, v/v) containing up to 180 µCi of ¹⁴C-chlorofluoro-
carbon. Virtually all the administered chlorofluorocarbon
was recovered in exhaled air within one hour with either
material. Only traces of radioactivity were found in urine
or exhaled CO₂ and may have represented unavoidable
radiolabelled impurities rather than metabolites. The
authors concluded that less than 1% of either CFC-11 or
CFC-12 is metabolized after inhalation. The preceding
results were essentially confirmed in human volunteers by
the same authors (Mergner et al., 1975). Radiolabelled
CFC-11 (571 mg/m³; 100 ppm) and CFC-12 (503 mg/m³; 100
ppm) were given by inhalation to one male and one female
volunteer for 7-17 min. As was the case in dogs, little
or no biotransformation of either chlorofluorocarbon was
observed. Total metabolites were equal to, or less than,
0.2% of the administered dose.

The results of the preceding studies suggest that CFC-
11 and CFC-12 are metabolized to a very small extent, if
at all, in mammals following brief inhalation exposures.

7.4. Elimination and excretion in expired air, faeces, and urine

Regardless of the route of entry, chlorofluorocarbons
appear to be eliminated almost exclusively through the
repiratory tract. Little, if any, chlorofluorocarbon or
metabolite has ever been reported in urine or faeces
(Matsumoto et al., 1963; Blake & Mergner, 1974; Mergner et
al., 1975).

7.5. Retention and turnover

When exposure is terminated, the more readily absorbed
compounds are retained longer. The retention of chloroflu-
orocarbons after inhalation follows the same order as the
amount absorbed during exposure:

CFC-11 ~ CFC-113 > CFC-114 ~ CFC-12

In human studies designed to mimic exposures to
chlorofluorocarbons from atomizers, the initial blood
half-lives for CFC-11 were in the range of 6 seconds to
1 min (Paterson et al., 1971).

In one study, volunteers exposed to CFC-11 at 3751
mg/m³ (657 ppm) for 150-210 min showed half-lives for the
initial and second phases of elimination from venous blood
of 11 min and 1 h, respectively (Angerer et al., 1985).
Half-lives for the initial and second phases of CFC-11
elimination in alveolar air were 7 min and 1.8 h, respect-
ively (Angerer et al., 1985). Average pulmonary retention
at an apparent steady state after 1 h of exposure was
18.2%. Similarly, the data of Brugnone et al. (1984)
indicate a pulmonary retention of 19% for CFC-11 and 18%
for CFC-12 in workers during occupational exposure.

Studies in which dogs were administered CFC-11 or CFC-
12 by intravenous infusion indicated that the elimination
of CFC-11 and CFC-12 from venous blood was triphasic
(Niazi & Chiou, 1975, 1977). A 3-compartment model was
proposed with initial, intermediate, and terminal half-
lives of 3.2, 16, and 93 min for CFC-11 and 1.47, 7.95,
and 58.50 min for CFC-12. Adir et al. (1975) also fitted
their venous blood elimination data to a 3-compartment
model. Estimates of half-lives for the terminal phases of
CFC-11 elimination were 6.30 and 24.75 min for two human
volunteers and 13.86-21 min (mean, 18.34) for four dogs.
For the terminal phases of CFC-12 elimination, the half-
lives were 9.63 min for one human volunteer and 8.45-11.35
min (mean, 9.90) for three dogs.

In dogs exposed to CFC-11 by atomizers, the initial
and terminal half-lives in venous blood were at 0.6 and
4.03 min, respectively (McClure, 1972). The terminal half-
life of 80 min in dogs after exposures to ambient CFC-11
concentrations of 2, 5, and 7.5% (Amin et al., 1979) is
close to the terminal half-lives reported by Niazi & Chiou
(1975).

Reinhardt et al. (1971a) conducted retention studies
on CFC-113 in human volunteers over occupationally rel-
evant periods. They measured the chlorofluorocarbon con-
centration in the expired air of volunteers exposed to
3835 mg/m³ (0.05%) or 7670 mg/m³ (0.1%) for 3 h in the
morning and 3 h in the afternoon. Although there was no
indication of chlorofluorocarbon accumulation, detectable
levels were retained overnight in four cases at 3835
mg/m³ and in 14 cases at 7670 mg/m³. In one instance,
there was a detectable level on a Monday morning following
a final exposure to 7670 mg/m³ (0.1%) on the previous
Friday.

7.6. Reaction with body components

Lessard & Paulet (1985) concluded that simple dissol-
ution of CFC-12 in the lipid layer of biological membranes
with ensuing alteration of membrane configuration may
account for its anaesthetic effect and some of its cardiac

effects. Young & Parker (1972), however, suggested that
CFC-12 is bound to the hydrophilic areas of various phos-
pholipids and that potassium chloride may stop adrenaline-
induced arrhythmia in hearts sensitized by CFC-12 by dis-
placing the CFC-12 molecule held by the phospholipid.

CFC-11 has been shown to bind in vitro to liver micro-
somal protein and lipid (Uehleke et al., 1977; Cox et al.,
1972a,b) and to cytochrome P-450 (Cox et al., 1972a,b;
Wolf et al., 1977, 1978). Vainio et al., (1980) also dem-
onstrated binding of CFC-113 to cytochrome P-450. In view
of the very low liver toxicity potential of CFC-11 and
CFC-113, the toxicological significance of the P-450
binding is unknown.

8. EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS

8.1. Single exposures

8.1.1. Acute inhalation toxicity

A number of chlorofluoromethanes and chlorofluoroeth-
anes have been tested for acute inhalation toxicity in
laboratory animals. Because most of the information is of
limited importance for a quantitative risk assessment, it
will not be discussed in detail. The data are presented
in Table 12.

Of the fully halogenated chlorofluoromethanes, CFC-12
and CFC-13 show extremely low acute inhalation toxicity.
CFC-11 also has low acute inhalation toxicity, lethal
concentrations being in the range of 571-1427 g/m³
(100 000-250 000 ppm).

Within the chlorofluoroethanes, CFC-114 and 115 seem
to be of an extremely low acute toxicity, followed by CFC-
113 and CFC-112.

The symptomatology of acute intoxication is character-
ized by central nervous system effects and secondary
effects on the cardiovascular and respiratory systems.

8.1.2. Acute oral toxicity

Very little information is available on the acute oral
toxicity of chlorofluorocarbons. The lethality data for
some chlorofluorocarbons are summarized in Table 13. With
the exception of a slight increase in liver weight follow-
ing exposure to CFC-112 and CFC-112a at 25 000 mg/kg, no
gross or histological abnormalities were noted by Clayton
(1966).

8.2. Short-term exposures

In this monograph, short-term exposures are defined as
those involving repeated daily exposure up to 90 days and
long-term studies as those longer than 90 days (see 8.4).

Table 12. Acute inhalation toxicity of fully halogenated chlorofluorocarbons
----------------------------------------------------------------------------------------
Compound Conc.^a Conc.^b Exposure Effects observed Reference
and period
species (min)
----------------------------------------------------------------------------------------
CFC-11

Guinea-pig 22-25 125-143 120 tremor, dyspnoea Nuckolls (1933)
45-51 257-291 120 tremor, incipient
narcosis
100 571 50 deep narcosis Scholz (1961)
250 1427 30 death (LC₅₀) Caujolle (1964)
Paulet (1969)

Mouse 10 57 1440 no clinical signs Quevauviller et al. (1963)
100 571 30 de