See the long list of
health studies and
other reports concerning ozone and greenhouse effects
from chlorodifluoromethane that are available from the
National Technical Information Service (NTIS).
- INITIAL SUBMISSION: EMBRYOTOXIC AND TERATOGENIC STUDIES
IN RATS WITH INHALED CHLORODIFLUOROMETHANE WITH COVER
LETTER DATED 06-15-92 AND ATTACHMENTS
(FC-22) was evaluated for embyotoxicity and teratogenicity
in groups of 40 pregnant Charles River rats exposed
to the test substance by inhalation at concentrations
of 0, 0.05, 0.10, and 2.00% on days 6-15 of gestation.
No clinical signs of toxicity were observed in maternal
animals. The number of implantations, early and late
resorptions, and number of live fetuses per litter were
unaffected. There was a sporadic
appearance of major malformations of the eye in all
test groups. The increased incidence of eye defects
was not statistically significant. Authors believe that
the test substance may have interacted with the genetic
make-up of affected fetuses and caused the increased
expressivity of a mutant gene. The
authors considered the test substance to be a mutagen
under the conditions of this study.
EPA/OTS; Doc #88-920004258
OF ACRTON 22 ON PREGNANT RATS: RELATIONSHIP TO ANOPHTHALMIA
AND MICROPHTHALMIA WITH ATTACHMENTS AND COVER LETTER
was evaluated in 4 groups of 19 pregnant CD female rats
receiving Arcton 22 via inhalation at concentration
levels of 0, 100, 1,000 and 50,000 ppm for 6 hours per
day on gestation days 6 through 15. There were no treatment-related
effects in appearance, behavior, mortality, or pregnancy
rate. At 50,000 ppm maternal weight gain was slightly
lower than the control. There were no effects on body
weight at 100 or 1,000 ppm. In all test groups litter
size, post-implantation loss, litter wight, and mean
fetal weight were similar to the control. At
50,000, there was an increased incidence of anophthalmic•
Absence of an eye(s). It can be a congenital
(born without) or an acquired condition (surgically
EPA/OTS; Doc #87-890000011
Environment ; Volume 31, Issue 6 , March 1997,
Estimated national releases
to the atmosphere of chlorodifluoromethane (HCFC-22)
M. Midgley (a) and Archie McCulloch (b)
Consulting, Ludwig str. 49, Leinfelden Musberg, D-70771,
ICI Chemicals & Polymers Ltd,
Runcorn, WA7 4QF, U.K.
(HCFC-22), the most widely used substitute for chlorofluorocarbons,
is currently emitted into the atmosphere at a global
rate of about 220,000 tyr-1.
In this work, national emissions of HCFC-22 for the
year 1990 are estimated using the calculated emissions
of CFC-12 as a surrogate distribution function. The
releases so calculated match the sp arse published data
in most cases.
Health 2002 Jun;28(3):205-7
of decomposed chlorodifluoromethane (freon-22) and myocardial
Sjogren B, Gunnare S, Sandler H.
Work Environment Toxicology, Institute of Environmental
Medicine, Karolinska Institutet, Stockholm, Sweden. Bengt.Sjogren@niwl.se
After exposure to decomposed chlorodifluoromethane
(freon-22), a 65-year-old man developed respiratory symptoms
such as cough, blood-stained sputum, and increasing dyspnea.
Three weeks later, his family doctor diagnosed infectious bronchitis.
Another week later he died due to myocardial
infarction. The discussion focuses on an inflammatory
process caused by the inhalation of decomposed freon and its
possible association with myocardial infarction.
PMID: 12109561 [PubMed - indexed for MEDLINE]
of dyspnea - shortness
of breath, a subjective difficulty or distress
in breathing, usually associated with disease of the heart or
lungs; occurs normally during intense physical exertion or at
a high altitude.
Ref: Stedman's Concise Medical Distionary for the Health Professions.
Illustrated 4th edition. 2001.]
of phosgene during welding activities
in an atmosphere containing chlorinated hydrocarbons.
Nieuwenhuizen MS, Groeneveld
TNO Prins Maurits Laboratory, Rijswijk, The
The formation of phosgene During welding activities
in an atmosphere containing chlorinated hydrocarbons was investigated.
Four different chlorinated hydrocarbons were studied under laboratory
conditions. Results are presented as time-averaged phosgene
concentration in a total volume of 250 L of air being purged
through a 52-L reaction vessel during 20 min.
It was found that the formation of phosgene was in the order
dichloromethane < Freon-22 < carbon tetrachloride << trichoroethylene.
Local concentrations may be higher depending on dispersion phenomena.
The interpretation in terms of occupational health was
rather difficult because of the interaction with smoke particles
and because of possible nonhomogeneous dispersion of phosgene
around the workers. In the case of dichloromethane and carbon
tetrachloride the short-term maximum allowable concentration
(MAC) of phosgene was not attained at the respective MAC values
of the chlorinated hydrocarbons themselves. In the case of trichloroethylene
and Freon-22, however, the short-term MAC-value of phosgene
was attained even when the concentration was still much below
the respective MAC-values.
PMID: 10976684 [PubMed - indexed for MEDLINE]
Eval Carcinog Risks Hum 1999;71
PMID: 10476408 [PubMed - indexed for MEDLINE]
Eval Carcinog Risk Chem Hum 1986;41:237-52
PMID: 3473028 [PubMed - indexed for MEDLINE]
injury and airway threat from inhalant abuse: a case report.
Kurbat RS, Pollack CV Jr.
Department of Emergency Medicine, Maricopa Medical
Center, Phoenix, Arizona, USA.
Fluorinated hydrocarbons cause toxicity in humans
via their dysrhythmogenic potential and their local physical
effects on the skin and mucous membranes. The former is generally
the more life-threatening toxic consequence. We present a case
of fluorinated hydrocarbon injury resulting from an intentional
inhalation exposure that created facial frostbite, which threatened
the patient's airway. The clinical range and management of these
tissue-toxic effects are reviewed.
PMID: 9543396 [PubMed - indexed for MEDLINE]
Sci Int 1996 Sep 30;82(2):171-5
GC/MS testing for chlorodifluoromethane in two fatal cases.
Kintz P, Baccino E, Tracqui A,
Institut de Medecine, Legale, Strasbourg, France.
Two cases of lethal poisoning due to chlorodifluoromethane
(Freon 22) inhalation are described. The fluorocarbon was determined
in biological tissues by headspace gas chromatography/mass spectrometry.
Ions monitored were m/z 67, 86 and 51, the latter being used
for quantification. Blood concentrations were 26.0 and 37.1
microliters/ml. In both cases, the drug was also identified
in urine, vitreous humor and bile, but in much lower concentrations.
PMID: 8885375 [PubMed
- indexed for MEDLINE]
J 1996 May;89(5):516-8
arterial hypertension linked to
Naval School of Health Sciences Bethesda Detachment,
Fort Sam Houston, Tex., USA.
Freons are generally considered to be minimally
toxic. There are no reports in the literature of Freons causing
secondary arterial hypertension. We report two cases of acute,
massive Freon exposure that preceded secondary arterial hypertension.
We hypothesize that the arterial hypertension was precipitated
by renal proximal tubular damage, although several other mechanisms
PMID: 8638181 [PubMed - indexed for MEDLINE]
Emerg Med 1995 Sep;12(3):212-3
a case report and review.
Wyatt JP, Allister CA.
Department of Accident and Emergency, Royal
Alexandra Hospital, Paisley, Strathclyde, UK.
Phosgene is a highly toxic gas to which some
workers may be occupationally exposed. This case report demonstrates
the possibility of refrigeration workers suffering phosgene
poisoning after heating certain chlorinated fluorocarbons ('freons').
The need to suspect phosgene exposure and observe such patients
is emphasized, especially in view of the delay in clinical deterioration
observed in some patients who subsequently
develop adult respiratory distress syndrome.
[PubMed - indexed for MEDLINE]
Sci 1993 Mar;38(2):477-83
due to recreational use of chlorodifluoromethane
Fitzgerald RL, Fishel CE, Bush
Mass Spectrometry Laboratory, VA Hospital, San
Reports on fatalities of chlorofluorocarbons
usually involve chlorotrifluoroethane, trichlorofluoromethane,
dichlorodifluoromethane or chlorodifluoromethane,
where analysis was done using packed column gas chromatography.
In this case a death was caused by an azeotropic mixture of
chlorodifluoromethane and chloropentafluoroethane, a combination
that has not previously been reported in the forensic literature.
This report details the analysis using mass selective detection
employing capillary gas chromatography columns currently used
in many toxicology laboratories. Postmortem toxicology revealed
blood concentrations of chlorodifluoromethane
and chloropentafluoroethane of 71 mg/L
and 0.30 mg/L, respectively. Brain, liver,
and lung concentrations of chlorodifluoromethane were (mg/kg)
2.8, 4.4, and 1.6, respectively. Brain, liver, and lung
concentrations of chloropentafluoroethane were (mg/kg) 0.80,
0.80, and 0.11, respectively. The victim's blood contained 5.5
mg/L caffeine. Lidocaine, used in resuscitation attempts, was
also present in the victim's blood. No other alkali-extractable
drugs or volatile alcohols were detected in the victim's blood.
The cause of death was acute respiratory arrest due to chlorofluorocarbon
PMID: 8455004 [PubMed - indexed for MEDLINE]
death caused by freon 22?]
[Article in Italian]
Dal Grande M, Zanderigo C, Coato F, Menegolli
S, Cipriani E, Pancheri V, Malesani F, Perbellini L.
ULSS 26 della Regione Veneto, Servizio di Prevenzione
Igiene e Sicurezza negli Ambienti di Lavoro (S.P.I.S.A.L.),
Case report of a plumber's fatal work accident.
Investigations on the causes of death made at post mortem showed
that the worker had absorbed a large quantity
of freon 22 (chlorodifluoromethane) which
is known to be a narcotic agent and capable of inducing cardiac
arrhythmia. It is believed freon inhalation was the cause
of loss of consciousness with consequent death from drowning
in the water issuing from the pipes. It is concluded that preventive
measures need to be reinforced by adequate information to the
workforce on the risks connected to this type of gas.
PMID: 1461194 [PubMed - indexed for MEDLINE]
Occup Environ Health 1992;64(5):383-7
inhalation pharmacokinetics of chlorodifluoromethane
Woollen BH, Marsh JR, Mahler JD, Auton
TR, Makepeace D, Cocker J, Blain PG.
Human Toxicology Team, ICI Central Toxicology
Laboratory, Macclesfield, Cheshire, UK.
Two groups of three male volunteers were exposed
to atmospheric concentrations of either 327 or 1833 mg m-3 chlorodifluoromethane
(HCFC22) for 4 h. Blood, urine and expired air samples were
taken during and after the exposure period and analysed for
HCFC22. Urine samples were also analysed for fluoride ion. During
the exposure period, blood concentrations of HCFC22 approached
a plateau, and the average peak blood concentrations of 0.25
and 1.36 micrograms cm-3 were proportional to dose. HCFC22 concentrations
in expired air were similar to the exposure concentration during
the exposure period. The ratio between venous blood and breath
concentrations of HCFC22 towards the end of the exposure period
was on average 0.77, which is consistent with in vitro estimates
of the partition coefficient. In the post-exposure period, three
phases for the elimination of HCFC22 were identified, with estimated
half-lives of 0.005, 0.2 and 2.6h. HCFC22 was detected in urine
samples taken in the post-exposure period, and the rate of decline
was consistent with the terminal rate of elimination estimated
from blood and breath measurements. On average 2.1% of the inhaled
HCFC22 was recovered in breath within 26 h of exposure. This
is consistent with the low solubility in blood and fat. Minimal
changes in fluoride ion concentrations in urine following exposure
indicate that HCFC22 is unlikely to be metabolised to a significant
extent. Following inhalational exposure HCFC22 is poorly absorbed
and is rapidly eliminated from the body. Possible biological
monitoring strategies could be based on measurements of HCFC22
in urine or breath samples collected after the end of an exposure
PMID: 1487335 [PubMed - indexed for MEDLINE]
Environ Health Perspect 1991
and toxicity of hydrochlorofluorocarbons: current knowledge
and needs for the future.
Department of Pharmacology, University of Rochester,
Hydrochlorofluorocarbons (HCFCs) are being developed
as replacements for chlorofluorocarbons (CFCs) that deplete
stratospheric ozone. The depletion of stratospheric ozone may
increase the intensity of ultraviolet radiation at the earth's
surface, which may be associated with global, adverse human
health effects. The greater tropospheric lability of HCFCs,
which is due to the presence of C-H bonds, reduces HCFC migration
to the stratosphere; HCFCs should, therefore, cause less depletion
of stratospheric ozone than CFCs. HCFCs under development include
HCFC-22 (chlorodifluoromethane), HCFC-123 (2,2-dichloro-1,1,1-trifluoroethane),
HCFC-132b (1,2-dichloro-1,1-difluoroethane), HCFC-134a (1,1,1,2-tetrafluoroethane),
HCFC-141b (1,1-dichloro-1-fluoroethane, and HCFC-142b (1-chloro-1,1-difluoroethane).
With the exception of HCFC-22, which is already in use, the
metabolism and toxicity of HCFCs have not been studied in detail.
By analogy to chlorinated ethanes, predictions can be made about
the possible metabolism of HCFCs, but there are insufficient
data available to predict rates of metabolism.
Although most HCFCs appear to show low acute toxicity, some
HCFCs are mutagenic in the Ames test. Hence, future research
on HCFCs should include studies on the in vivo and in vitro
metabolism of HCFCs as well as on their toxicity in in vivo
and in vitro systems.
[PubMed - indexed for MEDLINE]
Br J Ind
Med 1990 Mar;47(3):207-12
arrhythmia in refrigerator repairmen exposed
Edling C, Ohlson CG, Ljungkvist
G, Oliv A, Soderholm B.
Department of Occupational Medicine, University
Hospital, Uppsala, Sweden.
A field study of 89 refrigerator repairmen was
carried out to ascertain whether occupational exposure to fluorocarbons
induces cardiac arrhythmia. The concentrations of fluorocarbons
in the breathing zones and the heart activity were recorded
simultaneously. Most cooling systems contained FC 12 or FC
22. The highest level recorded in one minute was 14,000
ppm and the highest time weighted level during eight hours was
280 ppm. Two types of arrhythmia were
recorded, ectopic beats and sudden bradycardia. A within
subject comparison design was applied and the main parameter
was the difference in arrhythmia frequencies between exposed
and unexposed periods. No appreciable differences between exposed
and unexposed periods and no consistent dose effect relations
were observed, although subjects in the medium exposure category
showed a difference of borderline significance (Wilcoxon's test:
p = 0.05, one tailed). The frequencies of arrhythmia when unexposed
were somewhat higher than previously reported. Misclassification
of the exposure and the possible confounding effect of physical
workload and psychological strain may have obscured a causal
relation and therefore a minor effect cannot be ruled out. The
results do not support the notion that fluorocarbons induce
cardiac arrhythmia in occupationally exposed refrigerator repairmen.
PMID: 2328227 [PubMed - indexed for MEDLINE]
Br J Ind
Med 1990 Feb;47(2):138-40
arrhythmias during occupational exposure
to fluorinated hydrocarbons.
Antti-Poika M, Heikkila J, Saarinen
Institute of Occupational Health, Helsinki,
The effects of occupational exposure to chlorodifluoromethane
(FC 22) and dichlorodifluoromethane
(FC 12) on cardiac rhythm were examined. The subjects were six
men who repaired refrigerators (age 31-56, mean 46 years) and
a control group of six plumbers (age 29-54, mean 45 years).
Ambulatory electrocardiograms (ECG) were recorded for 24 hours
on the day of exposure and on a control day. The ECG tapes were
automatically analysed with a Reynolds pathfinder 3 apparatus
and all aberrant complexes recorded by the machine were checked.
One person read all the tapes without knowing whether or not
they were recorded during exposure. The number of ventricular
ectopic beats were compared between the day of exposure and
the control day and with the tape of the control. In addition,
the number of ventricular ectopic beats during exposure was
compared with the number occurring during the rest of the day.
The concentrations of fluorocarbons were measured in four instances.
High peak concentrations of fluorocarbons (1300-10,000 cm3/m3)
were measured during refrigerator repair work. No clear connection
between fluorocarbons and cardiac arrhythmia was found, although
one subject had several ventricular ectopic beats which may
have been connected with exposure.
PMID: 2310718 [PubMed - indexed for MEDLINE]
J Appl Physiol
of Freon 22 in human blood and lung tissue.
Varene N, Choukroun ML, Marthan
R, Varene P.
Laboratoire d'Exploration Fonctionnelle Respiratoire
Centre Hospitalier Regional de Bordeaux, Universite de Bordeaux
The solubility of Freon 22 in human blood and
lung tissue was determined using the chromatographic method
of Wagner et al. (J. Appl. Physiol. 36: 600-605, 1974). In normal
human blood, the mean Bunsen coefficient of solubility (alpha
B) was 0.804 cm3 STPD.cm-3.ATA-1 at 37 degrees C. It increased
with hematocrit (Hct) according to the equation alpha B = 0.274
Hct + 0.691. Tissue homogenates were prepared from macroscopically
normal lung pieces obtained at thoracotomy from eight patients
undergoing resection for lung carcinoma. The Bunsen solubility
coefficients were 0.537 +/- 0.068 and 0.635 +/- 0.091 in washed
and unwashed lung, respectively. These values can be used in
the determination of both cardiac output and pulmonary tissue
volume in humans by use of the rebreathing technique.
PMID: 2745307 [PubMed - indexed for MEDLINE]
Br J Anaesth
of freon-22 in blood and lung tissue.
Franks PJ, Hooper RH, Jones PR.
Department of Human Sciences, Loughborough University
Despite the frequent use of freon-22 (e.g. to
measure pulmonary blood flow), there is no agreement on its
solubility in water or body fluids. The values in the literature
vary, often quoted without reference to measurement or identification
as Ostwald or Bunsen coefficients. We used a Scholander apparatus
and determined the Bunsen solubility coefficient (mlgas.(mlfluid.atmosphere)-1)
at 37 degrees C as: 0.476 in water; 0.673 in human whole blood;
0.479 in human plasma; 0.662 in canine whole blood; 0.437 in
canine plasma; and 1.077 in homogenized canine lung tissue.
As pure freon was used, these solubilities may not be applicable
if freon-22 does not obey Henry's law. In man, the Ostwald solubility
coefficient is calculated as 0.76 ml/ml whole blood at BTPS.
These results provide information for further studies involving
freon-22, and clear the confusion which has arisen from poorly
defined solubility coefficients.
PMID: 2706179 [PubMed - indexed for MEDLINE]
Zasshi 1988 Aug;42(4-5):372-80
toxicological study of the effects
of freon 22 inhalation--the behavior
of rats exposed to freon inhalation and an evaluation of freon
concentrations in their tissue]
[Article in Japanese]
Komoriya H, Nakamura I, Ohya I.
PMID: 3204706 [PubMed - indexed for MEDLINE]
Ann N Y
Acad Sci 1988;534:261-82
carcinogenicity bioassays on three chlorofluorocarbons (trichlorofluoromethane,
FC11; dichlorodifluoromethane, FC12; chlorodifluoromethane,
FC22) administered by inhalation to Sprague-Dawley rats and
Maltoni C, Lefemine G, Tovoli
D, Perino G.
Institute of Oncology F. Addarii, Bologna, Italy.
Three propellant chlorofluorocarbons, namely
trichlorofluoromethane (FC11), dichlorodifluoromethane (FC12),
and chlorodifluoromethane (FC22)
were administered by inhalation at a concentration of 5000,
1000 and 0 ppm, 4 hours daily, 5 days weekly, for 104 and 78
weeks, to rats and mice, respectively. The animals were kept
under observation until spontaneous death. Under the experimental
conditions, all three compounds failed to show any carcinogenic
PMID: 3389660 [PubMed - indexed for MEDLINE]
Biol Res 1985;163B:301-5
relevance for man of animal data on reproductive toxicity of
Sullivan FM, Barlow SM.
PMID: 3920665 [PubMed - indexed for MEDLINE]
Ital Biol Sper 1984 Sep 30;60(9):1811-7
of the use of FRIGEN (AG-Ffm-HOECST) on the determination of
blood levels of some proteins (IgA, IgM,
IgG, C3c, C4) in cord blood of healthy newborn infants
at term by laser nephelometry]
[Article in Italian]
Costanzo A, Meninno V, Addeo L, Canzano
G, Lombardi S.
The purpose of this paper is to establishes the FRIGEN effects
on the determination of IgA, IgM, IgG, C3c, C4 cord-blood levels,
by means of laser-nephelometry. The results
show substantial interferences only in the IgA levels,
whereas the other on almost all proteins are not affected, the
found interference can be due to the amount of IgA bound to
B-lipoprotein, that are precipitated by FRIGEN.
PMID: 6525301 [PubMed - indexed for MEDLINE]
Toxicol 1984 Jun;22(6):465-75
toxicological evaluation of chlorofluorocarbon
22 (CFC 22).
Litchfield MH, Longstaff E.
PMID: 6539738 [PubMed - indexed for MEDLINE]
Appl Pharmacol 1981 Jun 15;59(1):64-70
toxicity of fluorocarbon-22:
toxic symptoms, lethal concentration, and its fate in rabbit
Sakata M, Kazama H, Miki A, Yoshida
A, Haga M, Morita M.
PMID: 7256758 [PubMed - indexed for MEDLINE]
Toxicol 1981 May-Jun;1(3):266-70
on the male
reproductive toxicity of Freon 22.
Lee IP, Suzuki K.
Freons have been used extensively as refrigerants
and as propellants in household products, and yet their possible
effects on male reproduction have received little attention.
In the present study, adult male Sprague-Dawley rats (nine weeks
of age) were exposed to 50 000 ppm Freon 22, five hrs per day
for eight weeks. The control group received filtered air at
an identical flow rate. At the end of the eight week exposure
period, body and organ weights, hematology, blood chemistry,
plasma gonadotropins, and fertility parameters
were not significantly different from controls, with the exception
of serum cholesterol levels, which were slightly higher, and
glucose and triglyceride levels which were lower. The weight
of coagulating glands was also lower than those of controls,
but did not interfere with fertility function.
PMID: 6820943 [PubMed - indexed for MEDLINE]
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