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FORMALDEHYDE
CASRN: 50-00-0 For other data, click on the Table of Contents
Human Health Effects:
Evidence for Carcinogenicity:
CLASSIFICATION: B1; probable human carcinogen. BASIS FOR CLASSIFICATION:
Based on limited evidence in humans, and sufficient evidence in animals. Human
data include nine studies that show statistically significant associations
between site-specific respiratory neoplasms and exposure to formaldehyde
or formaldehyde-containing products. An increased incidence of
nasal squamous cell carcinomas was observed in long-term inhalation studies in
rats and in mice. The classification is supported by in vitro genotoxicity data
and formaldehyde's structural relationships to other
carcinogenic aldehydes such as acetaldehyde. HUMAN CARCINOGENICITY DATA:
Limited. ANIMAL CARCINOGENICITY DATA: Sufficient.
A2. A2= Suspected human carcinogen.
Evaluation: There is limited evidence in humans for the carcinogenicity of formaldehyde.
There is sufficient evidence in experimental animals for the carcinogenicity of formaldehyde.
Overall evaluation: Formaldehyde is probably carcinogenic to
humans (Group 2A).
Human Toxicity Excerpts:
IF SOLN IS INGESTED, MUCOUS MEMBRANES OF MOUTH, THROAT, & INTESTINAL
TRACT ARE IRRITATED, & SEVERE PAIN, VOMITING, & DIARRHEA RESULT. AFTER
ABSORPTION, FORMALDEHYDE DEPRESSES CNS & SYMPTOMS NOT
UNLIKE THOSE OF ALC INTOXICATION ARE NOTED. THEY CONSIST OF VERTIGO, DEPRESSION,
& COMA. RARELY CONVULSIONS ARE OBSERVED.
ALTERATION OF TISSUE PROTEINS BY FORMALDEHYDE CAUSES LOCAL
TOXICITY & PROMOTES ALLERGIC REACTIONS. REPEATED CONTACT WITH SOLN ... MAY
CAUSE ECZEMATOID DERMATITIS. DERMATITIS FROM CLOTHING TREATED WITH FORMALDEHYDE
... HAS OCCURRED.
AQ SOLN ... SPLASHED OR DROPPED ON HUMAN EYES HAVE CAUSED INJURIES RANGING
FROM SEVERE PERMANENT CORNEAL OPACIFICATION & LOSS OF VISION TO MINOR
TRANSIENT INJURY OR DISCOMFORT, DEPENDING UPON WHETHER SOLN WERE OF HIGH OR LOW
CONCN.
INHALATION OF HIGH CONCN ... CAUSED SEVERE IRRITATION OF RESP TRACT, LEADING
IN 2 INSTANCES TO DEATH. ... PULMONARY EDEMA, WITH RESIDUAL CARDIAC IMPAIRMENT
IN 1 CASE, WAS REPORTEDLY CAUSED BY SINGLE ACUTE INHALATIONS ... .
IN SENSITIZED SUBJECTS SPECIFIC LATE ASTHMATIC REACTIONS MAY BE PROVOKED BY
BRIEF EXPOSURES AT APPROX 3 PPM.
Ingestion of formaldehyde can cause a reduction in body
temperature.
Symptoms related to ingestion of formaldehyde include:
jaundice, acidosis, & hematuria. Symptoms related to inhalation include:
rhinitis, anosmia, laryngospasm, tracheitis, & gastroenteritis.
In a survey of 57 embalmers who were exposed to atmospheric concn below 2 ppm,
there was a high incidence of symptoms of irritant effects on the eyes (81%)
nose & throat (75%). Other respiratory effects included cough (33%), chest
tightness (23%), wheezing (12%), & shortness of breath (11%). On the basis
of the results, 10% were acute bronchitics, & 30% were chronic bronchitics.
No control group was used & cigarette smoking was not taken into account.
Eyes: concn 1-10 ppm may produce appreciable eye irritation on initial
exposure; lacrimation occurs at about 4 ppm.
CULTURED BRONCHIAL & FIBROBLASTIC CELLS FROM HUMANS WERE USED TO STUDY
DNA DAMAGE & TOXICITY. FORMATION OF CROSSLINKS BETWEEN DNA & PROTEINS,
CAUSED SINGLE-STRAND BREAKS IN DNA, & INHIBITED RESEALING OF SINGLE-STRAND
BREAKS PRODUCED BY IONIZING RADIATION.
Formaldehyde induced a 1.5-3 fold increase in sister
chromatid exchanges in ... human lymphocytes in culture.
Formaldehyde was mutagenic for diploid human lymphoblasts in
culture ... /inducing an incr number of mutations at/ 130 uM or 4 ppm by weight.
OUTBREAK OF HEMOLYTIC ANEMIA, ATTRIBUTED TO ACCIDENTAL EXPOSURE ... OCCURRED
AMONG PATIENTS ON HEMODIALYSIS. 41 YR OLD WOMAN DIED 28 HR AFTER INGESTING 120
ML OF ... SOLN (37% WT/VOL FORMALDEHYDE, 12.5% VOL/VOL
METHANOL, CONTAINING NO FORMIC ACID).
EFFECTS IN WOMEN ATTRIBUTED TO EXPOSURE ... INCL MENSTRUAL DISORDERS &
SECONDARY STERILITY.
SYMPTOMATOLOGY: A. Inhalation: 1. Irritation of mucous membranes, especially
of eyes, nose & upper respiratory tract. 2. With higher concn, cough,
dysphagia, bronchitis, pneumonia, edema or spasm of the larynx. Pulmonary edema
is uncommon. B. Ingestion. 1. Immediate intense pain in mouth, pharynx &
stomach. 2. Nausea, vomiting, hematemesis, abdominal pain & occasionally
diarrhea (which may be bloody). 3. Pale, clammy skin & other signs of shock.
4. Difficult micturition, hematuria, anuria. 5. Vertigo, convulsions, stupor,
& coma. 6. Death due to respiratory failure. C. Skin contact: 1. Irritation
& hardening of skin. Strong solutions produce coagulation necrosis. 2.
Dermatitis & hypersensitivity from prolonged or repeated exposure.
INVESTIGATIONS OF CILIOSTATIC EFFECT OF ALDEHYDES ARE OF SPECIAL INTEREST
SINCE MANY HAVE IRRITATING EFFECT ON TRACHEAL MUCOSA. COMPARISON OF CILIOSTATIC
EFFECT SHOWED FORMALDEHYDE TO BE MOST TOXIC FOLLOWED BY
ACETALDEHYDE & ACROLEIN. CROTONALDEHYDE & METHACROLEIN SHOWED WEAKEST
EFFECT. TECHNIQUE USED FOR OBSERVING TRACHEAL CILIARY ACTIVITY WAS THE IN VITRO
TECHNIQUE.
One hundred nine workers & 254 control subjects were studied to evaluate
the effects of formaldehyde on the mucous membranes &
lungs. A modified, respiratory symptom questionnaire & spirometry were admin
to all study participants before & after their work shift, & formaldehyde
levels were determined for each test subject. Over the course of the monitored
work shift, test subjects demonstrated a dose-dependent excess of irritant
symptoms & a statistically significant decline in certain lung function
parameters. Baseline spirometry values were not significantly different between
test & control groups, & formaldehyde-exposed workers
did not report an excess of respiratory symptoms. Formaldehyde
is a dose-dependent irritant of the eyes & mucous membranes at low-level
exposures. It can exert a small, across-shift effect on airways but after a mean
exposure of 10 yr does not appear to cause permanent respiratory impairment.
The effect of formaldehyde exposure on medical students
conducting dissections in the gross anatomy laboratory course /was evaluated
using/ self-administered questionnaires designed to assess the frequency of
occurrence of various symptoms indicating the acute effects of formaldehyde
exposure. The questionnaires were given to a cohort of 1st-yr medical students
on completion of the gross anatomy lab course. Air sampling of formaldehyde
levels in the anatomy labs was carried out on one day during the time in which
these students were conducting dissections. ... Although the results of the air
sampling showed formaldehyde levels to be well below current
occupational standards, significant numbers of students reported experiencing
symptoms associated with formaldehyde exposure. Estimates of
the relative risk of experiencing formaldehyde-related symptoms
in the anatomy laboratories compared to the control laboratories ranged from
2.0-19.0, depending on the particular symptom. In addn, it was found that female
students were 3 times more likely to report formaldehyde-related
symptoms than male students.
A population based case control study was undertaken in 13 counties of
western Washington to determine if occupational formaldehyde
exposure was related to cancer of the oropharynx & hypopharynx (OHPC,
N=205), nasopharynx (NPC, N=27) or sinus & nasal cavity (SNC, N=53).
Controls were selected by random digit dialing (N= 552). A telephone interview
inquired about lifetime occupational history as well as a number of potential
confounding factors, including smoking & drinking. Approximately half
(N=143) of the case interviews were with next of kin. ... Logistic regression
was used to estimate exposure odds ratios STET while taking into account
multiple risk factors for each site. No significant associations were found
between occupational formaldehyde exposure & any of the
cancer sites under study. However, relative risk estimates associated with the
highest exposure score categories were evaluated for oropharynx &
hypopharynx (OR=1.3, 95% Confidence Interval= 0.6-3.1) & nasopharynx
(OR=2.1, 95% Cl=0.4-10.0). When an induction period was accounted for only
oropharynx & hypopharynx & nasopharynx increased to 1.7 & 3.1,
respectively. Several limitations in the study tend to conservatively bias the
results. ...
Because of the paucity of scientific data concerning the inhalation toxicity
of formaldehyde in humans, determinations of the symptoms &
alterations in pulmonary function resulting from inhalation for 1 hr of 3 ppm formaldehyde
were studied. The protocol consisted of randomized exposure of each subject to
clean air or 3.0 ppm formaldehyde on 2 separate days.
Twenty-two healthy normal subjects engaged in intermittent heavy exercise (VE=
65/min) & 16 asthmatic subjects performed intermittent moderate exercise (VE=
37/min). Symptoms & pulmonary functions were assessed during the time course
of exposure; nonspecific airway reactivity was assessed after exposure. Both
groups exhibited similar, significant (p<0.01) increases in perceived odor,
nose/throat irritation, & eye irritation throughout the exposure. The
non-asthmatic group had the following slight but statistically significant
(p<0.02) lower pulmonary functions after 55 min of exposure to formaldehyde
as compared to clean air: 3.8% in FEV1, 2.6% in FVC, & 2.8% in FEV3. The
asthmatic group showed no statistically significant decrements in pulmonary
function.
A retrospective mortality analysis was conducted in a cohort of 9,365
individuals employed as of 1940 in two chrome leather tanneries in the United
States and followed to the end of 1982. Vital status as of the closing date was
determined for over 95% of the cohort. Potential hazardous workplace exposures
varied with department and included ... formaldehyde. ...
Mortality from all causes combined was lower than expected for each tannery. ...
Deaths from cancer of each site, including the lung, were also lower than
expected compared to those of either the population of the United States or of
local state rates. A significant excess of deaths was observed, however, due to
accidental causes in one tannery and cirrhosis of the liver, suicide, and
alcoholism in the other. These excesses did not appear to be casually associated
with occupational exposures.
Infectivity of human T-cell lymphotropic virus, Type III (HTLV-III) was ...
efficiently inactivated by formalin ... .
Eight symptomatic individuals chronically exposed to indoor formaldehyde
at low concentrations (0.07-0.55 ppm) were compared to 8 nonexposed subjects
with respect to: (1) presence of IgG and IgE antibodies to formaldehyde
conjugated to human serum albumin (F-HSA); (2) the percentage of venous blood T-
and B-cells by E- and EAC-rosetting; and (3) the ability of T- and B-cells to
undergo mitogen (phytohemagglutin and pokeweed) stimulated blastogenesis as
measured by the incorporation of tritiated thymidine. Anti-F-HSA IgG, but not
IgE, antibodies were detected in the sera of the 8 exposed subjects; none were
found in 7 of the controls. T-lymphocytes were decreased in the exposed (48%)
compared to the control (65.9%) subjects (p< 0.01). B-cells were 12.6%
(exposed group) and 14.75% (controls) (p< 0.05). The incorporation of labeled
thymidine by T-cells (phytohemagglutin) was decreased: 17,882 cpm (exposed
group) and 28,576 cpm (p< 0.01). T- and B-cell blastogenesis (pokeweed) was
9,698 cpm (exposed group) and 11,279 (controls) (p< 0.1).
Both death and survival from 4-oz formalin ingestions have
been reported in adults. The probable mean lethal adult dose is 1 to 2 oz. Death
may occur within 3 hours; survival past 48 hours usually means recovery.
An environmental survey of 2 wood products (plywood, particle-board)
companies revealed mean concns in the plywood forming areas of 0.8 ppm &, in
2 particle-board forming areas, of 1.1 to 1.4 ppm /formaldehyde/.
Ophthalmologic evaluations were conducted & eye irritation self-reports were
collected from 84 subject workers, including unexposed controls, from various
areas in the plants. Results from both were unremarkable, as were tests mapping
their visual fields. However, there were subjective reports of at least
occasional eye irritation in 67% of the exposed subjects, with more such reports
coming from workers in areas of the plant with the higher concns. An explosion
at the factory closed a major product line & resulted in laying off many of
the volunteer subjects prior to performance testing; the remaining 49 workers
were tested before & after their workshift (& 13 of them were tested on
2 days) in order to assess acute effects of formaldehyde on
visual acuity, depth perception, peripheral vision, accommodation, eye movement
& fixation, divided attention, & color vision. Subjective reports of eye
irritation on the day of testing did not correlate, or correlated negatively,
with formaldehyde concns on the test day, which averaged 0.4
ppm. Average visual test scores were better at the end of the day than at the
beginning, & there was a trend for those with higher formaldehyde
levels to demonstrate greater improvement. Some of the changes reached
traditional levels of statistical significance. The results from this
investigation, while relevant to the neurotoxicity of formaldehyde,
suffer from the small sample size & the possibility that the comparison
subjects had also experienced formaldehyde exposure. With these
caveats, this study suggests that mean formaldehyde exposures
at 0.4 ppm produce no deleterious acute effects on visual performance, but
chronic exposures between 0.8 & 1.4 ppm may produce an increased incidence
of self reported symptoms of eye irritation in persons who do not have clinical
ophthalmologic defects.
Symptoms: Local: Conjunctivitis, corneal burns; brownish discoloration of
skin; dermatitis, urticaria (hives), pustulovesicular eruption. Inhalation:
rhinitis & anosmia (loss of sense of smell); pharyngitis, laryngospasm;
tracheitis & bronchitis; pulmonary edema, cough, constriction in chest;
dypsnea (difficult breathing), headache, weakness, palpitation (rapid heart
beat), gastro enteritis (inflammation of the stomach & intestines).
Ingestion: Burning in mouth & esophagus; nausea & vomiting; abdominal
pain, diarrhea, vertigo (dizziness), unconsciousness, jaundice, albuminuria,
hematuria, anuria, acidosis, convulsions.
Aldehydes increase airflow at concentrations below those that decrease
respiratory frequency. /Aldehydes/
Data on concentration of formaldehyde and 15 organic
solvents in Finnish furniture factories from 1975 to 1984 were presented.
Workers often complained of severe eye, nose, and upper respiratory tract
irritation. Formaldehyde was collected in a 1% sodium bisulfite
solution and analyzed by the chromatropic method. The solvents were adsorbed in
a charcoal tube, desorbed with carbon-disulfide or dimethylformamide, and
analyzed by gas chromatography. All highly exposed workers were monitored. The
widest range of formaldehyde concentration was recorded in the
operation of the curtain painting furniture receiving operation, which was
between 0.2 and 5.4 ppm. The mean concentrations of most organic solvents
studied ranged from 4 to 66 ppm. Formaldehyde levels were high
and the 1 ppm exposure limit, defined as the 15 minute time weighted average by
the Finnish Board of Labor Protection, was exceeded about 40% of the time.
A study of 759 histologically verified cancers of the nasal cavity (287
cases), paranasal sinuses (179 cases), and nasopharynx (293 cases) and 2465
cancer controls diagnosed in Denmark between 1970 and 1982 was conducted to
investigate the importance of occupational exposure to formaldehyde.
Information on job history for cases and controls was derived from a national
data linkage system and exposure to formaldehyde and wood dust
was assessed by industrial hygienists unaware of the case control status of the
patients. The exposure rates for formaldehyde among male and
female controls were 4.2% and 0.1% respectively. After proper adjustment for
contemporary wood dust exposure, relative risk of 2.3 (95% CI= 0.9-5.8) for
squamous cell carcinoma and 2.2 (95% CI= 7-7.2) for adenocarcinoma of the nasal
cavity and paranasal sinuses were detected among men who have been exposed to formaldehyde
in their job compared with those never exposed.
The National Cancer Institute study on the relationship between exposure to formaldehyde
& mortality from nasophryngeal cancer was evaluated. The study had indicated
little evidence of a link between formaldehyde at concns
normally encountered in the workplace & risk of nasopharyngeal cancer.
Although the overall standardized mortality ration was significantly elevated in
subjects exposed to formaldehyde, the overall risk did not incr
with increasing intensity of exposure. A reanalysis, however, suggested that
simultaneous exposure to particulates & formaldehyde could
be a risk factor. A further review of the National Cancer Institute findings
showed that the significant excess mortality was based on deaths occurring in a
single factory (factory-A) & occurred primarily in short term employees.
When the data were analyzed in terms of cumulative exposures that were known to
include both formaldehyde & particulates, only the highest
exposure group had a significantly increased excess nasopharyngeal cancer
mortality. This excess was clearly located in factory-A. A follow-up study of
factory-A that added 5 more years of follow-up was initiated. It showed no
additional deaths from nasopharyngeal cancer even among workers with the highest
formaldehyde & particulate exposures. The four deaths from
nasopharyngeal cancer in this factory occurred in workers employed in the same
department & hired between 1949 & 1955. Although these workers were
exposed to formaldehyde & particulates, they were not among
the most highly exposed.
This study evaluates the histological changes, especially the presence of
possible precancerous lesions, in the nasal mucosa of workers exposed to formaldehyde.
Nasal biopsies of 37 workers occupationally exposed to formaldehyde
for more than five years and 37 age matched referents showed a higher degree of
metaplastic alterations in the former group. In addition, three cases of
epithelial dysplasia were observed among the exposed. These results indicate
that formaldehyde may be potentially carcinogenic in man.
Combination of this finding with the inconclusive epidemiological studies
suggests that formaldehyde is a weak carcinogen and that
occupational exposure to formaldehyde alone is insufficient to
induce nasal cancer.
Clinical & animal studies suggest that formaldehyde
adsorbed on respirable particles may elicit a greater pulmonary physiologic
& inflammatory effect than gaseous formaldehyde alone. This
study was to determine if respirable carbon particles have a synergistic effect
on the acute symptomatic & pulmonary physiologic response to formaldehyde
inhalation. Normal, nonsmoking, methacholine-nonreactive subjects were exposed
to 2 hr each of clean air, 3 ppm formaldehyde, 0.5 mg/cu m
respirable activated carbon aerosol, & the combination of 3 ppm formaldehyde
plus activated carbon aerosol. The subjects engaged in intermittent heavy
exercise (VE= 57 1/min) for 15 min each half hour. Formaldehyde
exposure was associated with significant increases in reported eye irritation,
nasal irritation, throat irritation, headache, chest discomfort, & odor.
Synergistic increases in cough, but not in other irritant respiratory tract
symptoms, were observed with inhalation of formaldehyde &
carbon. Small (<5%) synergistic decreases in FVC & FEV3 were also seen.
No formaldehyde effect was observed on FEV1; however, we did
observe small (<10%) significant decreases in FEF25-75%, which may be
indicative of increased airway tone. Overall, results demonstrated synergism,
but the effect is small & its clinical significance is uncertain.
To study the cytotoxic effect of formaldehyde on the human
nasal mucosa 75 men with occupational exposure to formaldehyde
or to formaldehyde & wood dust, were examined, looking
particularly at early signs of irritative effects & histopathological
changes in the nasal mucosa. A nasal biopsy specimen was graded from 0-8
according to the morphological changes. A high frequency of nasal symptoms,
mostly a running nose & crusting, was related to exposure to formaldehyde.
Only three men had a normal mucosa; the remainder has loss of cilia & goblet
cell hyperplasia (11%) & squamous metapolasia (78%); in 6 cases (8%) there
was a mild dysplasia. The histological grading showed a significantly higher
score when compared with unexposed controls (2.9 v 1.8). There was no dose
response relation, no malignancies, & no difference in the histological
score between those exposed to formaldehyde or to formaldehyde
& wood dust.
A study of respiratory symptoms and pathophysiological effects associated
with occupational exposure to formaldehyde and wood dust was
conducted. The cohort consisted of 70 Swedish workers exposed to formaldehyde
during the production of formaldehyde and formaldehyde
based products (formaldehyde group) and 100 furniture workers
exposed to formaldehyde and wood dust (formaldehyde/wood
dust group). The comparisons consisted of 36 local government clerks. The formaldehyde
group was exposed to 0.05 to 0.5 mg/cu m formaldehyde and the
furniture workers to 0.2 to 0.3 mg/cu m formaldehyde and 1 to 2
mg/cu m wood dust. Annual formaldehyde exposures of the
comparisons averaged 0.09 mg/cu m. Sixty four percent of the formaldehyde
group, 53% of the formaldehyde/wood dust group, and 25% of the
comparisons reported nasal discomfort. Symptoms from the lower airways were
reported by 44% of the formaldehyde group, 39% of the formaldehyde/wood
dust group, and 14 % of the comparisons. Symptoms of nasal obstruction and
watery discharges were more frequent in the exposed subjects than in the
comparisons. More pronounced nasal swelling was found in the cohort than in the
comparisons. 20% of the formaldehyde and 15% of the formaldehyde/wood
dust group had impaired mucociliary clearance versus only 3% of the comparisons.
Both exposed groups had a reduced sense of smell. Forced vital capacity was
significantly decreased in the exposed groups.
A study was conducted to determine if pathologists with exposure to formaldehyde
demonstrate an excess risk of cancer, particularly cancers of the nasopharyngeal
and pharyngeal areas. A population of 6411 physicians with occupational formaldehyde
exposure participated in the study. The occurrence of these types of cancers was
4.7 times higher in these persons than in a comparable sized group of
psychiatrists, but even so it is difficult to determine the importance of this
increased risk as being directly tied to formaldehyde exposure.
Pathologists and other members of the study group were exposed to other
chemicals and infectious agents as well as formaldehyde. There
was an apparent excess of mortality from pancreatic cancer and brain cancers as
well as leukemia.
The relation of chronic respiratory symptoms & pulmonary function to formaldehyde
in homes was studied in a sample of 298 children (6-15 yr of age) & 613
adults. Formaldehyde measurements were made with passive
samplers during two 1 wk periods. Significantly greater prevalence rates of
asthma & chronic bronchitis were found in children from houses with formaldehyde
levels 60-120 ppb than in those less exposed, especially in children also
exposed to environmental tobacco smoke. In children, levels of peak expiratory
flow rates decreased linearly with formaldehyde exposure, with
the estimated decr due to 60 ppb of formaldehyde equivalent to
22% of peak expiratory flow rates level in nonexposed children. The effects in
asthmatic children exposed to formaldehyde below 50 ppb were
greater than in healthy ones. The effects in adults were less evident:
decrements in peak expiratory flow rates due to formaldehyde
over 40 ppb were seen only in the morning, & mainly in smokers.
The long term effects of formaldehyde on the respiratory
tract have been investigated in a group of 164 workers exposed daily to the
chemical during the production of urea formaldehyde resin,
together with 129 workers not exposed to free formaldehyde.
Exposure was classified as high (corresponding to an 8 hr time weighted exposure
of >2.0 ppm), medium (0.6-2.0 ppm), or low (0.1-0.5 ppm). 25% of workers had
high exposure at some time & 17% moderate exposure. Both exposed &
unexposed groups had an annual assessment that included lung function. The
proportion with self reported respiratory symptoms was similar in the two
groups, 12% & 16% reporting breathlessness on hurrying & 26% & 20%
wheezing. The initial forced expiratory volume in 1 sec was within 0.5 l (approx
on standard deviation) of the predicted value (by age & height) in 65% of
the exposed & 59% of unexposed workers & >0.5 l below the predicted
value in 9% of exposed & 11% unexposed workers. The mean decline in forced
expiratory volume in 1 sec was 42 ml/yr (standard deviation 45) in the exposed
& 41 ml/yr in the unexposed group (standard deviation 40 ml/yr). The rate of
decline showed the expected association with smoking in the unexposed group, but
in the exposed group the mean rate of decline in the never smokers was similar
to that in current smokers. There were, however, relatively few never smokers
& considerable variation in the rates of decline. In the exposed group no
association was found between the rate of decline & indices of exposure to formaldehyde.
Thus there is no evidence from this study of an excess of respiratory symptoms
or decline in lung function in the workers exposed to formaldehyde.
The similar rate of decline of forced expiratory volume in 1 sec however in
never smokers & smokers of the exposed group is consistent with finding of
other studies for workers exposed to formaldehyde.
A prospective evaluation of pulmonary function & respiratory symptoms was
conducted among 103 medical students exposed to formaldehyde
over a 7 month period to determine the incidence of bronchoconstriction &
respiratory symptoms in response to exposure. Time-weighted average formaldehyde
exposures were generally <1 ppm & peak exposures were <5 ppm. Acute
symptoms of eye & upper respiratory irritation were significantly associated
with exposure. There was no pattern of bronchoconstriction in response to
exposure after either 2 wks or 7 months. Twelve subjects had a history of
asthma; they were likely to have symptoms of respiratory irritation or changes
in pulmonary function than those without such a history. These findings are
consistent with previous case reports that indicate exposure to formaldehyde
vapor at levels that are commonly encountered in occupational & residential
seetings do not commonly cause significant bronchonconstriction, even among
subjects with preexisting asthma.
A case of anaphylactoid reaction to a patch test with formaldehyde
was described. The 40 year old woman developed bronchospasm and laryngospasm
following the inhalation of formaldehyde vapor. A year later
she accidentally entered a hospital room relatively soon after it had been
disinfected, and was hospitalized with dyspnea, cyanosis, bronchospasm, and
laryngospasm. Days later she did react to a patch test with a 1% solution of formaldehyde
in water. Pulmonary function tests 20 min after the patch test revealed a 50%
reduction in FEV1 and a 63% reduction in MEF 25.
Four groups of patients with long-term inhalation exposure to formaldehyde
were compared with controls who had short-term periodic exposure to formaldehyde.
The following were determined for all groups: total white cell, lymphocyte, and
T cell counts; T helper/suppressor ratios; total Ta1+, IL2+, and B cell counts;
antibodies to formaldehyde-human serum albumin conjugate and
autoantibodies. When compared with the controls, the patients had significantly
higer antibody titers to formaldehyde-human serum albumin. In
addition, significant increases in Ta1+, IL2+, and B cells and autoantibodies
were observed. Immune activation, autoantibodies, and anti formaldehyde-human
serum albumin antibodies are associated with long-term formaldehyde
inhalation.
The incidence of spontaneous abortions among hospital staff who used ethylene
oxide, glutaral (glutaraldehyde) & formaldehyde for the
chemical sterilization of instruments was studied using data from a
questionnaire & a hospital discharge register. ... When the staff were
concerned in sterilizing during their pregnancy the frequency was 16.7% compared
with 5.6% for the nonexposed pregnancies. The incr frequency ... correlated with
exposure to ethylene oxide but not with exposure to glutaral or formaldehyde.
Employees exposed to formaldehyde in the woodworking
industry and nonexposed control subjects were examined by spirometry and the
nitrogen washout technique. A dose-response relationship was found between
exposure to formaldehyde and decrease in lung function.
Industrial exposure to formaldehyde causes transient lung
function impairment over a work shift, with a cumulative effect over the years.
The impairment, however, can be reversed with 4 wk of no exposure.
The mortality of 1,332 male workers employed at least 30 days in 1959-1980 in
a resins-manufacturing plant was examined. Ambient measurements taken in the
plant between 1974 and 1979 documented a potential for exposure to levels of formaldehyde
as high or greater than 3.0 mg/cu m. Vital status was ascertained for 98.6% of
the cohort members, and their mortality was compared with expected deaths drawn
from the national and local population rates. A statistically significant
increase in lung cancer was observed, based on 18 deaths, which was not fully
accounted for by possible confounding factors linked to personal habits or
sociocultural characteristics. This elevated risk, however, could not be
attributed specifically to exposure to formaldehyde. Mortality
from digestive cancer (14 deaths observed) and hematologic neoplasms (5 deaths
observed) was not substantially higher than expected.
Formaldehyde has been found to cause bronchial asthma-like
symptoms in humans. A young male neurology resident who spent 2 hr in autopsy of
formaldehyde-preserved human brains experienced both
conjunctival & nasal irritation while working; however, over the next 15 hr
after cessation of exposure, he developed progressive dyspnea & tightness in
the chest. Early edema indicative of pneumonitis was visible on Xray, &
after treatment with aminophyline, hydrocortisone, & oxygen (nasal prong at
4 l/min), he gradually improved over the following 2 days. He continued to need
prednisone (20 mg every other day for 2 wk), & he had fully recovered 5 wk
after the onset of his hypersensitivity reaction to inhaled formaldehyde.
In cultured human bronchial fibroblasts exposed to the carcinogen N-methyl-N-nitrosourea
(NMU) in combination with formaldehyde, formaldehyde
was observed to inhibit repair of alkylation of DNA at the O6 guanine position
induced by NMU. Whether formaldehyde enhances the effects of
other DNA-damaging agents has not yet been evaluated.
Hemodialysis patients are exposed chronically to trace levels of formaldehyde
(by formalin sterilization of their dialyzers to permit reuse).
Erythrocytes can be characterized in terms of MN phenotypes, analogous to the
AB-O system. The normal distribution of MM, NN, an MN phenotypes is about 25,
25, and 50%, respectively. Only 25% of the population would be expected to have
anti-N antibodies. Formaldehyde exposure may be followed by the
development of anti-N-like antibodies probably as a result of reaction with the
dissolved form of formaldehyde, methylene glycol. The
anti-N-like antibodies are also found following exposure to sodium hypochlorite.
The use of formaldehyde as a nail hardener, on the other
hand, is accompanied by a significant number of serious injuries to sensitive
nail and adnexal tissues. This type of exposure may contribute substantially to
that portion of the 4% sensitization index seen in clinical patients which is
cosmetic-related.
In a study ..., a group of 33 observers judged the perceived irritation &
odor of formaldehyde during 29-min chamber esposures to concns
ranging from 0.3-2.4 mg/cu m. The sensory irritation increased with time for the
lower concns & decreased with time for the highest. This effect was true for
irritation of eyes, nose, & throat & the sensitivity proved to be
roughly equal for all three sites. The sensory irritant effect of formaldehyde
at 1.2 mg/cu m was shown to decr when the chemical pyridine was injected into
the chanber; such sensory interactions occur in environmentally realistic
situations.
... Healthy volunteers (24 men, 9 women) /were exposed/ to formaldehyde
concns ranging between 0.036 & 4.8 mg/cu m air (33 volunteers for 35 min, 48
volunteers for 1.5 min. Eye blinking rates as well as subjective irritation
effects were determined. The irritation threshold was found to range between 1.2
& 2.4 mg formaldehyde/cu m. A similar threshold (1 mg/cu m)
was found in other studies. ... /It was/ noted that 9 out of 53 medical student
volunteers exposed to formaldehyde concns of between 0.39 &
0.60 mg/cu m for 8 hr/wk, complained of headaches, a burning sensation in the
eyes, sore throat, & annoyance because of the smell.
A 60-yr old man swallowed 60-90 mg of a 40% formaldehyde
soln. Thirty hr after death, the mucosa of the lowere part of the esophagus,
stomach, & first portion of duodenum were dark chocolate brown in color
& of the consistency of leather. All organs & tissues in contact with
the stomach were "hardened" to a depth of about 8 mm.
Workers exposed to 0.35-1.0 ppm (0.43-1.2 mg/cu m) for 6 minutes had a
significant irritation response at 1.0 ppm; nonsignificant responses were
reported at 0.7 and 0.9 ppm(0.9 and 1.1 mg/cu m).
Formaldehyde vapor is very irritating to the mucous
membranes and toxic to animals, including man.
... examined smears of nasal respiratory mucosa cells sampled from the inner
turbinate of 15 nonsmokers who were exposed to formaldehyde
released from a urea-formaldehyde glue used in a plywood
factory and 15 age- and sex-matched nonexposed clerks from outside of the
factory. Estimates of formaldehyde air conc ranged from : 0.21
to 0.60 (mean 0.39 + or - 0.20 ppm) in the warehouse where seven subject worked,
0.08 to 0.14 ppm (mean 0.1 + or - 0.02 ppm) in the shearing press where six
subjects worked, and 0.09 ppm (only one sample taken) in the sawmill area where
two subjects worked. Mean wood dust concn for the three areas were 0.23 + or -
0.1 mg/m3, 0.41 + or - 0.21 mg/m3, and 0.73 mg/m3, respectively. Exposed
subjects worked at the factory for 2-19 yr (mean 6.8 + or - 5.0 yr). Nasal
mucosal slides were scored as follows: normal cellularity, 1; number of
mucus-secreting cells greater than ciliated cells, 1.5; hyperplasia, 2; squamous
metaplasia, 2.5; mild dysplasia, 3; moderate dysplasia, 4; severe dysplasia, 5;
and malignant cells, 6. In the exposed group, all subjects had a greater number
of nonciliated than ciliated cells, 40% had hyperplasia, 67% had squamous
metaplasia, and 6% slight dysplasia. In controls, 26% had normal cytology, 67%
had more ciliated than nonciliated cells, 33% had hyperplasia, and 6% had
squamous metaplasia. The mean cytology score for the exposed group (2.3 + or -
0.5) was reported to be statistically significantly greater than the control
score (1.6 + or - 0.5). Also found in this study was a statistically
significantly higher percentage of micronucleated mucosal cells in the exposed
group compared with the control group (0.91% + or - 0.47 versus 0.25% + or -
0.22).
Mean baseline PEFR /(peak expiratory flow rate)/ declined by about 2% over a
10-wk period in a group of 24 physical therapy students who dissected cadavers
for 3-hr periods/wk ... . Estimates of breathing zone formaldehyde
concn ranged from 0.49-0.93 ppm (geometric mean 0.72 + or - 1.22 ppm). PEFR, the
only pulmonary function variable measured in this study, was measured before
& after each exposure period. Postexposure PEFR means were 1-3% lower than
preexposure PEFR means during the first 4 wk, but this difference was not
apparent during the last 6 wk. Fourteen wk after the end of the 10-wk period,
the mean PEFR for the group returned to the preexposure baseline value.
... evaluated the immunologic response of asthmatic subjects exposed to urea-formaldehyde
foam insulation (UFFI) off-gas products. Subjects consisted of 23 individuals
with a history of asthmatic symptoms attributed to UFFI & 4 individuals
(controls) with asthma unrelated to UFFI by-products. Subjects were exposed to
one of the following: room air (placebo) for 30 min; 1 ppm formaldehyde
gas for 3 hr; UFFI particles (4 um, 0.5 particles/ml) for 3 hr, commencing 48 hr
after formaldehyde gas exposure; & UFFI off-gas products
for 3 hr, commencing 48 hr after UFFI particle exposure. There were no
significant alterations in any of the white blood cell populations ... .
However, there was a significant incr in the % & absolute number of
eosinophils & basophils in the subject (who also lived in UFFI-homes) after
exposure to UFFI in the exposure chamber when compared to the white blood cell
values obtained before chamber exposure to UFFI.
Occupational exposures to formaldehyde have been assoc with
dermal irritation and the diagnosis of allergic contact dermatitis by patch
testing. Reported historical percentages of subjects with skin problems showing
positive responses to formaldehyde in patch tests performed by
dermatologists using aqueous soln with 1 or 2% formaldehyde
incl 7.8% in North America between 1992 and 1994 ... 1.6% in a 1983-1984 Swedish
study ... 2.6% in a 1988-1989 European study ... and 3.7% in a 1990-1994 Polish
study ... . Lack of case-specific exposure info for these patients precludes the
determination of the degree to which sensitization may have been caused by
direct dermal contact to formaldehyde in liquids or by contact
with formaldehyde gas in air, but the widespread use of formaldehyde
or formaldehyde-releasing chemicals in cosmetics and cleaning
agents ... suggest that the dermal route of exposure may be the more important
sensitizing route.
... measured elevated levels of formaldehyde-specific IgE in
24/62 8-yr old children who were students in three particle board-paneled
classrooms with est formaldehyde air concn of 0.075, 0.069, and
0.043 ppm. In a health survey, the children reported headaches (29/62), fatigue
(21/62), dry nasal mucosa (9/62), rhinitis (23/62) cough (15/62), and nosebleeds
(14/62). Sums of numbers of children with each of nine symptoms for each
classroom decr with decr formaldehyde conc (49, 47, and 24,
respectively for the 0.075-, 0.069-, and 0.043-ppm classrooms), but the
investigators reported that elevated levels of specific IgE did not correlate
with the number and severity of symptoms. The children were moved to a new
school without particle board paneling and were evaluated again, 3 mo after
moving. Est formaldehyde concn in the new classrooms were
0.029, 0.023, and 0.026 ppm. The numbers of children reporting symptoms decr
significantly compared with premoving reporting figures, and mean serum levels
of formaldehyde-specific IgE, measured in 20 of the children,
declined significantly compared with premoving mean levels.
... investigated the correlation between formaldehyde-induced
contact dermatitis and granulocyte chemiluminescence resulting from free-radical
release in healthy and formaldehyde-sensitive patients.
Thirteen patients with contact dermatitis who were occupationally exposed to formaldehyde
and five healthy volunteers participated in the study. All subjects underwent
skin-prick tests for common allergens as well as a histamine inhalation
provocation test. Subjects were exposed to 0.5 mg/m3 (0.41 ppm) formaldehyde
for 2 hr, and peak expiratory flow was measured immediately before exposure, at
60 and 120 min of exposure, and at 6 and 21 hr after completion of exposure. In formaldehyde-sensitive
patients, skin-prick tests and total serum IgE were normal; no antiformaldehyde
IgE was detected. In formaldehyde-sensitive patients,
peripheral blood granulocyte chemiluminescence significantly incr within 30 min
of exposure commencement, and remained elevated 24 hr later, compared to initial
values. Granulocyte chemiluminescence did not incr in healthy patients.
... measured the formation of DNA-protein cross links in peripheral white
blood cells of occupationally exposed workers (n=12) & unexposed controls
(n=8). The avg length of ... exposure was 13 yr. ... Venous blood samples were
collected ... . Personal & room concn of formaldehyde were
collected at various periods during the working day among the exposed subjects,
with formaldehyde room concn ranging from 1.38-1.6 ppm.
Personal monitoring devices indicated formaldehyde concn of
2.8-3.1 ppm during peak work & an avg concn of 1.46 ppm at times when work
was usually completed. Exposure to formaldehyde resulted in a
significant incr in the incidence of DNA-protein cross links. Mean ...
incidences in exposed & nonexposed workers were 28 + or - 6 & 22 + or -
6%, respectively. Within the exposed workers group, technicians had
significantly greater levels of DNA-protein cross links than physicians (32.3 +
or - 4.3 & 26.3 + or - 4.4%, respectively). A linear relationship between yr
of exposure & DNA-protein cross links formation was also detected. When the
data were analyzed considering worker smoking habits, DNA-protein cross links
was consistently elevated among formaldehyde-exposed versus
corresponding controls (p=0.03).
The finding of nasal tumors in rodents exposed to high levels of airborne formaldehyde
in the early 1980s ... led to a concern for cancer effect in occupationally
exposed workers. There are now more than 40 epidemiology studies examining the
potential for occupational formaldehyde exposure to cause
cancer in humans. The studies include cohort mortality studies of formaldehyde-exposed
industrial workers, cohort mortality studies of formaldehyde-exposed
professionals or medical specialists, & case-control studies that looked for
assoc between occupational exposure to formaldehyde &
cancers of the nose, pharynx, or lung. ... Although some of the epidemiological
studies have found some scattered evidence for extra-respiratory site cancers in
groups of formaldehyde-exposed workers, the data are not
consistent across studies & adjustment for potential confounding cancer risk
factors has not often been possible. Most, if not all reviewers, have agreed
that cancer of the respiratory tract, particularly the upper respiratory tract,
is more biologically plausible than formaldehyde-induced cancer
at distant sites given the reactivity of formaldehyde, the
capacity of tissues to metabolize formaldehyde, & the
results from chronic rodent inhalation studies showing that formaldehyde-induced
nonneoplastic & neoplastic effects are restricted to the upper respiratory
tract with exposures to concn below 5-10 ppm. Accordingly, the meta-analyses of
the human data have focused on the findings for respiratory cancer deaths in
occupationally exposed humans.
... describe the case of a 58-yr old man who swallowed 4 ounces of formalin
(517 mg formaldehyde/kg) in a suicide attempt. The man was
found unconscious by a co-worker about 1 hr after his shift began. In the
emergency room, the subject regained consciousness but was lethargic. Lab
results indicated significant acidosis. Approx 3 hr after ingesting the formalin,
the patient complained of abdominal pain & began retching without emesis; he
was admitted for observation & treated with ethanol. The patient's abdominal
pains became more severe & he had difficulty breathing. At 5.5 hr after
ingestion, the patient became obtund, & both his respiratory rate &
blood pressure fell significantly; he was intubated & placed on 100% oxygen.
Shortly thereafter, the patient began to experience seizures; treatment with
diazepam & phenytoin was unproductive, but pancuronium was effective in
treating the seizures. IV bicarbonate & ethanol therapies were begun after
the seizures started. The patient was transported for dialysis, but on arrival,
had clinical signs of intravascular coagulopathy. He subsequently sustained a
cardiac arrest from which he could not be revived. At autopsy, the patient's
stomach was hard, white, & leathery; the esophagus & intestines appeared
to be normal.
A 55-yr old woman and a 34-yr old man ingested, with suicidal intent, an
unknown amt of what was reported to have been formalin ... .
The female patient was found in a coma and admitted to the hospital with shock
(systolic blood pressure 50 mm Hg), respiratory insufficiency, and metabolic
acidosis. The male patient, who had a history of alcohol abuse, was also
hospitalized with shock (systolic blood pressure 60 mm Hg), respiratory
insufficiency, and metabolic acidosis. Both patients underwent hemodialysis and
hemofiltration treatment. Analysis of the formaldehyde samples
ingested by both patients showed no evidence that these products contained
methanol, although it was expected to have been detected. A
chemical-toxicological screening /of blood samples/ indicated that no drugs
other than formaldehyde had been ingested ... . Three wk after
ingestion of formaldehyde, the female patient died of cardiac
failure refractory to catecholamine therapy. The male patient developed adult
respiratory distress syndrome and died 8 wk after formaldehyde
ingestion with signs of cardiac failure.
Human lymphoblast mutants at the X-linked hprt locus have been examined by
Southern blot, Northern blot & DNA sequence analysis. A previous study had
shown that approx a third of the spontaneously arising mutants & half those
induced by formaldehyde showed no alteration in restriction
fragment pattern & thus were classified as point mutation. In this report,
these point mutants fall into 4 catagories: normal size & amount of RNA,
normal size but reduced amounts, reduced size RNA or no RNA. Sequence analyses
of cDNAs prepared from hprt mRNAs were performed on 1 spontaneous & 7 formaldehyde
induced mutants were base substitutions, all of which occurred at AT base-pairs.
There was an apparent hot spot, in that 4/6 independent mutants were AT----CG
transversions at one specific site. The remaining mutant had lost exon 8.
Human Toxicity Values:
The probable mean lethal adult dose is 1-2 oz.
Skin, Eye and Respiratory Irritations:
Contact with the skin causes irritation, tanning effect, and allergic
sensitization. Contact with eyes causes irritation, itching, & lacrimation.
...
Formaldehyde vapor is very irritating to the mucous
membranes and toxic to animals, including man.
Medical Surveillance:
Consider the skin, eyes, & resp tract in any placement or periodic
examination, esp if the patient has a history of allergies.
PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is
indicated, in particular when exposure to a carcinogen has occurred, ad hoc
decisions should be taken concerning ... /cytogenetic and/or other/ tests that
might become useful or mandatory. /Chemical Carcinogens/
... No biologic monitoring techniques exist at present, either for the
reliable determineation of formaldehyde levels in tissue or for
the determination of formaldehyde adducts formed with
macromolecules. Techniques are under development for nonspecific monitoring of
exposure through periodic assessment of chromosome damage (micronucleus
formation or sister chromatid exchange frequency) in workers exposed to formaldehyde.
Preemployment baseline data should be recorded for the respiratory tract,
liver, and skin condition of any worker who will be exposed to formaldehyde.
Thereafter, periodic monitoring should be conducted to detect symptoms of
pulmonary or skin sensitization or effects on the liver.
The assessment of formaldehyde exposure can be accomplished
through measurement of the metabolite formic acid. Formic acid is also an
endogenously produced substance formed by the degradation of glycine. There was
no information in the literature that showed a correlation between urinary
formic acid levels & formaldehyde exposure levels. This
measurement is also a poor indicator of the extent of formaldehyde
absorption, due to the high endogenous levels of formic acid. Urine Reference
Ranges: Normal- normal population level: 21 mg/l (endogenously produced formic
acid); Exposed- not established; Toxic- not established.
Respiratory Symptom Questionnaires: Questionnaires published by the American
Thoracic Society (ATS) & the British Medical Research Council have proven
useful for identifying people with chronic bronchitis. Certain pulmonary
function tests such as the FEV1 have been found to be better predictors of
chronic airflow obstruction.
Chest Radiography: Chest radiographs are widely used to assess pulmonary
disease. They are useful for detecting early lung cancer in asymptomatic people,
& especially for detecting peripheral tumors such as adenocarcinomas.
However, even though OSHA mandates this test for exposure to some toxicants such
asbestos, experts' views on the risk-to-benefit ratio in detection of pulmonary
disease conflict, so routine annual chest x-rays are not recommended for all
people.
Pulmonary Function Tests: The tests that have been found to be practical for
population monitoring include: Spirometry & expiratory flow-volume curves;
Determination of lung volumes; Diffusing capacity for carbon monoxide;
Single-breath nitrogen washout; Inhalation challenge tests; Serial measurements
of peak expiratory flow; Exercise testing.
Urine Albumin: Albuminuria has been shown to be a specific marker of
glomerular dysfunction. Tubular damage, however, can also result in increased
levels of albumin in the urine.
Urinary Beta-2-Microglobulin &/or Retinal Binding Protein: Measurements
for the presence of either of these low molecular weight proteins are useful in
detection of early impairment of proximal tubular function. However,
beta-2-microglobulin is unstable at urinary pH <6, & may degrade in the
bladder prior to collection & subsequent neutralization of the urine sample.
Measurement of retinal binding protein appears to be a better marker for early
tubular dysfunction due to its stability in the urine subsequent to collection
& analysis. However, retinal binding protein is produced in the liver &
not a constitutive protein of the kidney, so that its presence in the kidney
provides only indirect evidence of tubular damage.
Urinary Enzyme N-Acetylglucosaminidase: This lysosomal enzyme has shown
promise in assessment of subclinical nephrotoxic injury. This enzyme is not
normally filtered at the glomerulus due to its high molecular weight. In the
absence of glomerular injury, this enzyme will be detected in the urine as a
result of leakage or exocytosis from damaged, stimulated, or exfoliated renal
cells. The sensitivity of measurement for this enzyme has not been thoroughly
studied, but it's usefulness has shown some promise. However, this enzyme is
unstable at urinary pH >8, which could diminish the sensitivity of the
measurement due to enzyme degradation.
DNA-Protein Crosslinks: Measurement of DNA-protein crosslinks in white blood
cells may be a useful test for assessing formaldehyde exposure.
In addition, measurement of these crosslinks in other formaldehyde
sensitive tissues, such as the upper respiratory tract, may be a useful
indicator of formaldehyde exposure. However, other toxicants
may cause similar crosslinks, so that the specificity of this test for assessing
only formaldehyde exposure is questionable.
Routine Urinalysis: Performing a routine urinalysis including parameters such
as specific gravity, glucose, & microscopic exam may be useful for assessing
renal toxicity.
Urinary Alpha & Pi Isoenzymes of Glutathione S-Transferase:
Radio-immunological & Elisa techniques have been developed for quantitation
of /alpha/ & /pi/ isoenzymes of glutathione S-transferase, which are
constitutive proteins in the kidney. The /alpha/ isoenzyme is located only in
the proximal tubule, while the /pi/ isoenzyme is located in the distal
convoluted tubule, the loop of Henle, & the collecting ducts of the kidney.
Damage to epithelial cell membranes can result in the increased excretion of
these isoenzymes in the urine. This test for assessing renal tubular damage
appears to have many advantages over other available tests, such as: (1) the
/alpha/ & /pi/ isoenzymes are constitutive proteins in the kidney; (2) these
isoenzymes are stable in the urine; (3) the test is simple & reproducible;
& (4) due to selective localization of the isoenzymes, differential
diagnosis of specific tubular damage is possible. In addition, increased levels
of these isoenzymes were seen in patients previously exposed to nephrotoxicants
where conventional tests for kidney function were normal, indicating a high
degree of sensitivity.
Populations at Special Risk:
Mean formaldehyde levels are highest in hospital autopsy
rooms compared with other commercial settings. /Hospital autopsy workers are
possibly exposed/.
Release of /formaldehyde/ vapors in mobile homes has been
associated with headache & pulmonary & dermal irritation. /Occupants of
mobile homes are possibly exposed/.
Two populations of humans have received considerable attention in the
literature as being particularly sensitive to formaldehyde
exposure following inhalation and/or dermal routes. The first population is
asthmatics, and concern focuses on the changes in lung function parameters that formaldehyde
may produce ... . Most of these studies concluded that there is no evidence of
incr airway reactivity as a result of formaldehyde exposure in
either normal or asthmatic individuals. ... The second population of potential
concern is people with dermal sensitization ... Formaldehyde
liquid, but neither the gaseous phase nor formalin, is
considered to be a dermal sensitizer ... . Anaphylactic reactions have been
reported ... . Dermal allergic reactions have also been reported in doctors and
nurses exposed to formaldehyde ... as well as in fiberglass
workers ... .
Workers in industries where formaldehyde is used or released
may receive potentially high exposures. Members of the general population who
live in newly constructed homes or homes where pressed wood products have
recently been installed may be exposed to high levels of formaldehyde
by inhalation for short periods of time until the latent formaldehyde
has been released. Exposure in mobile homes are expected to be higher than
conventional homes due to their lower rate of air exchange ... . Members of the
general population that handle large amt of permanent press fabrics treated with
formaldehyde-releasing resins may also receive potentially high
exposures. The use of some cosmetics, such as nail hardeners, may result in high
short-term exposure.
Smokers and persons who live in a home with a cigarette smoker also may be
exposed to higher levels of formaldehyde. Environmental tobacco
smoke, which is a combination of diluted sidestream smoke released form a
cigarette's burning end and mainstream smoke exhaled by an active smoker, can
contribute 10-25% (0.1-1 mg/day) of the total average indoor exposure to
formadehyde ... .
Probable Routes of Human Exposure:
... /VAPORS/ GIVEN OFF DURING HOT MOLDING OF SYNTH RESINS (/IS A/ COMMON
SOURCE OF EXPOSURE) ... A SURVEY OF 6 FUNERAL HOMES ... REVEALED MEAN CONCN, IN
DIFFERENT ESTABLISHMENTS, BETWEEN 0.25 & 1.39 PPM. ... /EXPOSURES ARE
ENCOUNTERED/ IN PHENOL-FORMALDEHYDE RESIN MOULDING PLANT ...
/FROM WHICH/ CHRONIC AIRWAY OBSTRUCTION LOWERED FORCED EXPIRATORY VOL/FORCED VOL
CAPACITY RATIO & EYE, NOSE & THROAT IRRITATION & LOWER RESP TRACT
SYMPTOMS /HAVE BEEN OBSERVED/.
... /EXPOSURES TO/ FORMALDEHYDE VAPOR EMISSIONS IN
PERMANENT-PRESS FABRICS INDUSTRY (8 PLANTS) /HAVE BEEN REPORTED IN WHICH/ CONCN
RANGING ... FROM 0.3 TO 2.7 PPM (IN SEWING AREA) WITH AVG OF 0.68 PPM /WERE
DETECTED/. COMPLAINTS CONSISTED OF ANNOYING ODOR (ODOR THRESHOLD, BELOW 1.0
PPM), CONSTANT PRICKLING IRRITATION OF MUCOUS MEMBRANES & DISTURBED SLEEP.
NIOSH (NOES Survey 1981-1983) has statistically estimated that 1,329,322
workers (441,902 of these are female) are potentially exposed to formaldehyde
in the US(1). The NOES Survey does not include farm workers(SRC). Occupational
exposure to formaldehyde may occur through inhalation and
dermal contact with this compound at workplaces where formaldehyde
is produced or used(2). Monitoring data indicate that the general population may
be exposed to formaldehyde via inhalation of ambient air,
ingestion of food, and dermal contact with cosmetic and aerosol products
containing formaldehyde(2).
Humans are exposed to formaldehyde from a variety of
sources. The major source of atmospheric discharge is from combustion processes
specifically from auto emissions and also from the photooxidation of
hydrocarbons in auto emissions(1,2). Additional exposure to formaldehyde
emissions comes from its use as an embalming fluid in anatomy labs, morgues, etc
and its use as a fumigant and sterilant(1). Resin treated fabric, rugs, paper,
etc and materials such as particle board and plywood which use resin adhesives
and foam insulation release formaldehyde which may build up in
homes and occupational atmospheres(1,2). Contact with industrial waste water,
especially from lumber related operations where formaldehyde is
used in adhesives, has resulted in the Pacific Northwest, Northeast, parts of
Texas, and lumber areas of the south(1)(SRC). The estimated daily intake of formaldehyde
among exposed Finnish workers is 3000 ug, whereas heavily exposed workers
(particle-board and glue production, foundry work) is 10,000 ug(3).
In a 12-week study of exposure in a gross anatomy lab of a medical school,
44% of breathing room samples and 11% of ambient air samples were >1.0 ppm
the ceiling recommended by ACGIH; Half the breathing zone samples were between
0.6-1.0 ppm and the range was 0.3-2.63 ppm(1). A 1976 report estimates that 8000
US workers were potentially exposed to formaldehyde during its
production(3). A more recent estimate of the number of exposed workers in
industries producing and using formaldehyde and its derivatives
range from 1.4-1.75 million(2). Concentrations of formaldehyde
in occupational areas dating from the 1960's and early 1970's are: textile plant
0-2.7 ppm, 0.68 ppm avg; garment factory 0.9-2.7 ppm; clothing store 0.9-3.3
ppm; laminating plant 0.04-10 ppm; funeral homes 0.09-5.26 ppm, 0.25-1.39 ppm
avg; resin manufacture and paper production 16-30 ppm; paper conditioning
0.9-1.6 ppm; wood processing 31.2 ppm max(2). Concns in occupational settings
dating from the late 70's are: textile plants 0.1-0.5 ppm, 0.2 ppm avg; shoe
factory 0.9-2.7 ppm, 1.9 ppm avg; particle board plant 0.1-4.9 ppm, 1.15 ppm
avg; plywood plant 0.1-1.2 ppm, 0.35 ppm avg; wooden furniture manufacturing
plant 0.1-5.4 ppm, 1.35 ppm avg; adhesive plants 0.8-3.5 ppm, 1.75 ppm avg;
foundries 0.05-2.0 ppm, 0.6 ppm avg; construction sites 0.5-7.0 ppm, 2.8 ppm
avg; hospitals and clinics 0.05-3.5 ppm, 0.7 ppm avg(2). More recent survey
results for occupational environments include: fertilizer production 0.2-1.9
ppm; dyestuffs <0.1-5.8 ppm; textile manufacture <0.1-1.4 ppm; resins
(foundry) <0.1-5.5 ppm; bronze foundry 0.12-0.8 ppm; iron foundry
<0.02-18.3 ppm; treated paper 0.14-0.99 ppm; hospital autopsy room 2.2-7.9
ppm; plywood industry 1.0-2.5 ppm; urea-formaldehyde foam
applicators <0.08-2.4 ppm(4).
Potential occupational exposure to formaldehyde are as
follows: agricultural workers, anatomists, beauticians, biologists, bookbinders,
botanists, chemical production workers, cosmetic formulators, crease-resistant
textile finishers, disinfectant makers, disinfectors, dress-goods shop
personnel, electrical insulation makers, embalmers, embalming fluid makers,
fireproofers, formaldehyde production workers, formaldehyde
resin makers, foundry employees, fumigators, fur processors, furniture makers,
glue and adhesive makers, hide preservers, histology technicians (including
necropsy and autopsy technicians), ink makers, lacquerers and lacquer makers,
medical personnel (including pathologists), mirror manufacturers, paper makers,
particle-board makers, photographic film makers, plastic workers, plywood
makers, rubber makers, taxidermists, textiles mordanters and printers, textiles
waterproofers, varnish workers, wood preservers(1).
The avg concn of formaldehyde in workroom air in formaldehyde
and resin manufacturing plants ranged from 0.1-14.2 mg/cu m(1). The avg concn of
formaldehyde in workroom air of plywood mills, particle-board
mills, furniture factories, other wood product and paper mills ranged from
0.08-7.4 mg/cu m(1). The avg concn of formaldehyde in workroom
air in textile mills and garment factories ranged from 0.1 to 1.9 mg/cu m(1).
The avg concn of formaldehyde in workroom air in foundries and
other industrial facilities ranged from 0.04 to 38.2 mg/cu m(1). The avg concn
of formaldehyde in workroom air in mortuaries, hospitals, and
laboratories ranged from 0.05 to 4.2 mg/cu m(1). The avg concn of formaldehyde
in workroom air in building sites, agriculture, forestry, and misc other
activities ranged from <0.1 to 4.3 mg/cu m(1).
Cigarette smoke and products of combustion contain formaldehyde(1).
Cigarette smoke contains 15 to 20 mg formaldehyde per
cigarette(1). Avg formaldehyde exposure from passive smoking is
between 0.23 to 0.27 ppm(1). A 'pack-a-day' smoker may inhale as much as 0.4-2.0
mg formaldehyde(1).
Several studies have been conducted to determine exposure of students in
laboratories(1). The concn of formaldehyde in the breathing
zone at dissecting tables and in the ambient air in a medical school in the
United States was found to be >1.2 mg/cu m in 44% of the breathing zone
samples and 11 ambient air samples; 50% of the breathing zone samples contained
0.7-1.2 mg/cu m, with a range of 0.4-3.2 mg/cu m(1). During the 1982-82 academic
year, the airborne concn of formaldehyde at a university in the
US was 7-16.5 ppm in the laboratory, 1.97-2.62 ppm in the stockroom, and <1
ppm in the public hallway(1). In another study, of 253 samples of air taken
during laboratory dissection classes at a university in the US, 97 contained
concns above the detection limit of 0.01 mg/cu m; all but four samples had
levels <1.2 mg/cu m(1). The avg concn detected was 0.5 mg/cu m(1).
Average Daily Intake:
AIR INTAKE: Assume 1 to 100 ug/cu m(1), 20 ug to 2,000 ug formaldehyde(SRC).
In Sweden between Dec 1986 to Aug 1987, the mean yearly exposure to formaldehyde
from air pollution was 1.2 ug/cu m(1). The estimated daily exposure of the
Finnish population to formaldehyde from community air is 100 ug
and from the home environment, 1,000 ug(2).
Minimum Fatal Dose Level:
Approximate Minimum Lethal Dose (MLD) (150-lb man): 30 ml
Male single oral ingestion 517 mg/kg
Emergency Medical Treatment:
Emergency Medical Treatment:
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MICROMEDEX, SHOULD BE CONSULTED FOR ASSISTANCE IN THE DIAGNOSIS OR TREATMENT OF
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strictly prohibited.
The following Overview, *** FORMALDEHYDE ***, is relevant
for this HSDB record chemical.
Life Support:
o This overview assumes that basic life support measures
have been instituted.
Clinical Effects:
SUMMARY OF EXPOSURE
0.2.1.1 ACUTE EXPOSURE
o Formadehyde may be irritating to the eyes, skin, and
mucous membranes. Ingestion may cause corrosive injury
to the gastrointestinal mucosa, with nausea, vomiting,
pain, hematemesis, and perforation. Systemic effects
include CNS depression, seizures, coma, jaundice,
albuminuria, hematuria, anuria, and metabolic acidosis.
o Inhalation can cause respiratory tract irritation,
rhinitis, anosmia, cough, dyspnea, wheezing,
tracheitis, bronchitis, laryngospasm, pulmonary edema,
headache, weakness, dizziness, and palpitations.
o Dermatitis, brownish discoloration of the skin,
urticaria, and pustulovesicular eruptions, may develop
from dermal exposure. Concentrated solutions can
cause coagulation necrosis.
o Irritation, lacrimation, and conjunctivitis may develop
with exposure to vapors. Eye exposure to solutions
with high formaldehyde concentrations may produce
severe corneal opacification and loss of vision.
Solutions containing low formaldehyde concentrations
may produce transient discomfort and irritation.
VITAL SIGNS
0.2.3.1 ACUTE EXPOSURE
o Shock may develop with severe exposures. Tachypnea may
develop in patients with metabolic acidosis. Reduction
in body temperature may be seen.
HEENT
0.2.4.1 ACUTE EXPOSURE
o IRRITATION of the eyes, nose, and throat may occur
following exposure to formaldehyde OR fumes from
urea-formaldehyde foam and adhesive resins.
o Corneal opacification and loss of vision may occur
following direct eye splash exposure to solutions
containing high concentrations of formaldehyde.
Transient discomfort and irritation may result from eye
exposure to solutions containing low concentrations of
formaldehyde.
CARDIOVASCULAR
0.2.5.1 ACUTE EXPOSURE
o Hypotension and cardiovascular collapse may occur with
severe ingestion.
RESPIRATORY
0.2.6.1 ACUTE EXPOSURE
o Inhalation of formaldehyde vapors at elevated
concentrations may result in upper respiratory tract
irritation and coughing. Severe exposure may result in
serious lower respiratory effects, such as bronchitis,
pulmonary edema, or pneumonia. Reactive airways may
develop in susceptible individuals.
o Respiratory distress and ARDS has been reported
following ingestion or transdermal absorption of
formaldehyde-containing compounds.
NEUROLOGIC
0.2.7.1 ACUTE EXPOSURE
o Lethargy and coma may occur following large ingestions
or marked inhalation exposure.
0.2.7.2 CHRONIC EXPOSURE
o Chronic exposure may result in malaise, headache,
sleeping disturbances and irritability.
GASTROINTESTINAL
0.2.8.1 ACUTE EXPOSURE
o Nausea, vomiting, and severe abdominal pain may occur
following ingestion. Corrosive gastritis, hematemesis,
and edema and ulceration of the esophagus may occur.
Strictures and perforation are possible delayed
complications.
HEPATIC
0.2.9.1 ACUTE EXPOSURE
o Hepatotoxicity has been associated with inhalation
exposure in animals and suggested in humans.
o Hyperbilirubinemia has been reported following
ingestion.
o Biliary sclerosis occurred following formalin
instillation into hydatid cyst.
GENITOURINARY
0.2.10.1 ACUTE EXPOSURE
o Nephritis and acute renal failure may occur.
Membranous nephropathy has been associated with
formaldehyde exposure.
ACID-BASE
0.2.11.1 ACUTE EXPOSURE
o Metabolic acidosis and hyperlactacidemia may occur.
HEMATOLOGIC
0.2.13.1 ACUTE EXPOSURE
o Intravascular hemolysis has been reported in dialysis
patients receiving doses of formaldehyde during
treatment.
DERMATOLOGIC
0.2.14.1 ACUTE EXPOSURE
o Allergic dermatitis and rash may occur.
IMMUNOLOGIC
0.2.19.1 ACUTE EXPOSURE
o Antibodies to formaldehyde (Types I and II reactions)
have been measured in exposed persons with clinical
effects ranging from irritation to severe
hypersensitivity reactions. Type IV reactions may
result in allergic contact dermatitis. Immunologic
reactions may be delayed by hours to months.
o Asthma-like signs and symptoms have been reported.
Evidence of formaldehyde sensitization or allergy
causing true asthma is inconclusive. Respiratory
effects do not consistently correlate with the
development of formaldehyde-specific immunoglobulins.
o Membranous nephropathy has been associated with
immunologic reaction to suspected formaldehyde
exposure.
0.2.19.2 CHRONIC EXPOSURE
o Allergic contact dermatitis, eczema and other signs
have been attributed to formaldehyde sensitivity.
REPRODUCTIVE HAZARDS
o Formaldehyde has not been shown definitely to be
teratogenic in animals. Formaldehyde probably presents
little or no risk as a potential human teratogen.
o Menstrual disorders have been reported in women
occupationally exposed to formaldehyde, but these
results are controversial. In experimental animal
studies, some effects on spermatogenesis have been
reported.
o Occupational exposure at recommended limits is not
thought to present a reproductive risk. Formaldehyde
exposure among female hospital workers did not correlate
with an increase in spontaneous abortion in one study,
but did correlate in another.
1. Low-birthweight children have been reported in female
workers exposed to urea-formaldehyde resin, but studies
are inconclusive. Formaldehyde appears to cross the
placental barrier in mice.
CARCINOGENICITY
0.2.21.2 HUMAN OVERVIEW
o Formaldehyde is a probable human nasopharyngeal
carcinogen (IARC 2A Limited evidence in humans and
sufficient evidence in animals).
1. Occupational exposure to formaldehyde has been linked
to the development of buccal and nasopharyngeal
metaplasia/neoplasia, and to a lesser extent cancers
of the nasal cavities.
2. Formaldehyde's role in lower respiratory tract cancer
etiology has not been substantiated. Consensus on
data collection and analysis methods will be necessary
to evaluate the link between formaldehyde and lung
cancer.
3. Formaldehyde reacts with HYDROGEN CHLORIDE to form
BIS-CHLOROMETHYL ETHER, a known human carcinogen.
GENOTOXICITY
o Formaldehyde appears to be mutagenic. The basis for its
genetic activity is its ability to form cross-links in
DNA and proteins.
Laboratory:
o FORMALDEHYDE PLASMA LEVELS are not widely available, but
may help in dialysis monitoring.
o Monitor acid base status in symptomatic patients. Monitor
liver function tests. Monitor hematocrit and hemoglobin
concentration in dialysis patients repeatedly exposed
parenterally to formaldehyde. Monitor blood METHANOL
levels after significant formalin ingestion.
o Pulmonary function testing and nasal and bronchial
provocation tests may be recommended in patients with
signs and symptoms of reactive airways dysfunction
following inhalation of formaldehyde.
Treatment Overview:
ORAL EXPOSURE
o EMESIS: Ipecac-induced emesis is not recommended
because of the potential for cardiovascular instability.
o DILUTION: Following ingestion and/or prior to gastric
evacuation, immediately dilute with 4 to 8 ounces (120
to 240 mL) of milk or water (not to exceed 15 mL/kg in a
child).
o After ingestion of concentrated formaldehyde, gastric
lavage with a soft small-bore NG tube may facilitate
removal. Risk of further mucosal injury should be
weighed against potential benefit. Although no data on
adsorption to activated charcoal could be found, it
should be considered following lavage, although it may
obscure endoscopy findings.
o ACTIVATED CHARCOAL: Administer charcoal as a slurry
(240 mL water/30 g charcoal). Usual dose: 25 to 100 g
in adults/adolescents, 25 to 50 g in children (1 to 12
years), and 1 g/kg in infants less than 1 year old.
o MONITOR ECG AND VITAL SIGNS and acid base status.
Monitor methanol levels.
o ENDOSCOPY: Because acid ingestion may cause severe
gastric burns with relatively few initial signs and
symptoms, endoscopic evaluation is recommended within 24
hours in any patient with a definite history of
ingesting a strong acid, even if asymptomatic. If burns
are found, follow 10 to 20 days later with a barium
swallow.
o PHARMACOLOGIC TREATMENT: Corticosteroids are
controversial. Consider use in second degree burns
within 48 hours of ingestion in patients without
gastrointestinal bleeding or evidence of perforation.
Antibiotics are indicated for suspected perforation or
infection and in patients receiving corticosteroids.
o SURGICAL OPTIONS: Initially, if severe esophageal burns
are found a string may be placed in the stomach to
facilitate later dilation. Insertion of a specialized
nasogastric tube after confirmation of a circumferential
burn may prevent strictures. Dilation is indicated
after 2 to 4 weeks if strictures are confirmed; if
unsuccessful, either colonic intraposition or gastric
tube placement may be performed. Consider early
laparotomy in patients with severe esophageal and/or
gastric burns.
o Administer ethanol or fomepizole in patients with
significant methanol levels. HEMODIALYSIS should be
considered in those patients with severe acid-base
disturbances refractory to conventional therapy, or in
cases with significant methanol levels.
o HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid,
place in Trendelenburg position. If hypotension
persists, administer dopamine (5 to 20 mcg/kg/min) or
norepinephrine (0.1 to 0.2 mcg/kg/min), titrate to
desired response.
INHALATION EXPOSURE
o INHALATION: Move patient to fresh air. Monitor for
respiratory distress. If cough or difficulty breathing
develops, evaluate for respiratory tract irritation,
bronchitis, or pneumonitis. Administer oxygen and
assist ventilation as required. Treat bronchospasm with
beta2 agonist and corticosteroid aerosols.
EYE EXPOSURE
o MEDICAL FACILITY: Irrigate with sterile 0.9% saline for
at least an hour or until the cul-de-sacs are free of
particulate matter and returned to neutrality (confirm
with pH paper).
DERMAL EXPOSURE
o DECONTAMINATION: Remove contaminated clothing and wash
exposed area thoroughly with soap and water. A
physician may need to examine the area if irritation or
pain persists.
Range of Toxicity:
o INGESTION of as little as 30 mL of a 37% solution of
formaldehyde has resulted in death in an adult.
Antidote and Emergency Treatment:
Decontamination: Dilute with milk or water in alert patients as a first aid
measure may reduce corrosive effects at the scene. If ingestion has occurred
within 1 hr before presentation, gentle gastric aspiration with a soft
nasogastric tube may limit systemic absorption. There is little evidence to
support the use of activated charcoal to absorb formate or formaldehyde.
... Elimination enhancement: Severe acidosis & deteriorating vital signs are
indications for considering dialysis, but the literature does not contain
adequate case studies to guide treatment. Aggressive sodium bicarbonate therapy
& frequent monitoring of arterial blood gases may be useful. There are no
antidotes. Supportive care: 1. Monitor electrolytes, fluids, acid-base, &
kidney function closely. 2. Watch for signs of GI hemorrhage & perforation
with serial vital signs, abdominal exams, & complete blood counts. 3. Check
blood methanol levels & treat accordingly in formalin
ingestions. 4. Fibrosis of stomach has required partial gastrectomy in the past.
Irrigate eyes with water. Wash contaminated areas of body with soap and
water. Gastric lavage (stomach wash), if swallowed, using 1% ammonium carbonate
and followed by saline catharsis. Oxygen, if indicated.
Basic Treatment: Skin- Treated as any burn to prevent allergic contact
dermatitis, exposure to formaldehyde or formaldehyde-containing
products should be minimized. Inhalation- Patients should be removed from
exposure. If symptoms persist, hospitalization may be required. Very high levels
(100 ppm) may be lethal. Pulmonary damage may occur. Oral- high concn of formaldehyde
may be irritating to the GI tract. Ingestion can result in metabolic responses
similar to methanol poisoning. Hemodialysis is efficacious just as in methanol
poisoning & should be considered if metabolic acidosis occurs.
Basic treatment: Establish a patent airway. Suction if necessary. Watch for
signs of respiratory insufficiency and assist ventilations if necessary.
Aggressive airway management may be necessary. Administer oxygen by
nonrebreather mask at 10 to 15 L/min. Anticipate seizures and treat if necessary
... . Monitor for shock and treat if necessary ... . Monitor for pulmonary edema
and treat if necessary ... . For eye contamination, flush eyes immediately with
water. Irrigate each eye continuously with normal saline during transport ... .
Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200
ml of water for dilution if the patient can swallow, has a strong gag reflex,
and does not drool. Administer activated charcoal ... . /Aldehydes and related
compounds/
Advanced treatment: Consider orotracheal or nasotracheal intubation for
airway control in the patient who is unconscious or in respiratory arrest.
Intubation should be considered at the first sign of upper airway obstruction
caused by edema. Positive pressure ventilation techniques with a bag-valve-mask
device may be beneficial. Start an IV with D5W /SRP: "To keep open",
minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present.
Watch for signs of fluid overload. Treat seizures with diazepam ... . For
hypotension with signs of hypovolemia, administer fluid cautiously. Consider
vasopressors if patient is hypotensive with a normal fluid volume. Watch for
signs of fluid overload ... . Consider drug therapy for pulmonary edema ... .
Use proparacaine hydrochloride to assist eye irrigation ... . /Aldehydes and
related compounds/
Animal Toxicity Studies:
Evidence for Carcinogenicity:
CLASSIFICATION: B1; probable human carcinogen. BASIS FOR CLASSIFICATION:
Based on limited evidence in humans, and sufficient evidence in animals. Human
data include nine studies that show statistically significant associations
between site-specific respiratory neoplasms and exposure to formaldehyde
or formaldehyde-containing products. An increased incidence of
nasal squamous cell carcinomas was observed in long-term inhalation studies in
rats and in mice. The classification is supported by in vitro genotoxicity data
and formaldehyde's structural relationships to other
carcinogenic aldehydes such as acetaldehyde. HUMAN CARCINOGENICITY DATA:
Limited. ANIMAL CARCINOGENICITY DATA: Sufficient.
A2. A2= Suspected human carcinogen.
Evaluation: There is limited evidence in humans for the carcinogenicity of formaldehyde.
There is sufficient evidence in experimental animals for the carcinogenicity of formaldehyde.
Overall evaluation: Formaldehyde is probably carcinogenic to
humans (Group 2A).
Non-Human Toxicity Excerpts:
INHALATION ... BY ANIMALS CAUSES PROMPT & SEVERE IRRITATION OF EYES &
RESP TRACT. ... EDEMA & HEMORRHAGES OF ... LUNG, & SIGNS OF HYPEREMIA
& PERIVASCULAR EDEMA IN THE LIVER AND KIDNEYS.
PROLONGED EXPOSURE OF RABBITS TO FORMALDEHYDE CAUSED ACID
PHOSPHATASE, TWEEN-60-ESTERASE, NAPHTHOL-AS-D-ACETATE-ESTERASE, PROLINE-OXIDASE
& HYDROXYPROLINE-2-EPIMERASE ACTIVITIES TO INCREASE &
LEUCYL-AMINOPEPTIDASE & BETA-GLUCURONIDASE TO DECREASE. IT INDUCED BRONCHIAL
CELL HYPERPLASIA WITH HYPERMUCIGENESIS, EXTRUSION OF BRONCHIAL CELLS,
BRONCHIOLAR HYPERMUCIGENESIS, PARCELLARY SQUAMOUS METAPLASIA OR NECROBIOSIS OF
EPITHELIA.
CD-1 MICE WERE GIVEN UP TO 185 MG/KG BODY WT FORMALDEHYDE BY
GAVAGE ON DAYS 6-15 OF GESTATION. HIGHEST DOSE WAS ... TOXIC TO DAMS, BUT NO
EMBRYOTOXICITY OR TERATOGENICITY WAS SEEN WITH ANY DOSE.
ACUTE ... EFFECTS ... IN RATS ... /& OTHER EXPTL ANIMALS/ TO LOW (LESS
THAN 1 PPM) OR MODERATE (10-50 PPM) ... /OF/ VAPOR RESULTED IN INCREASED AIRWAY
RESISTANCE, DECR SENSITIVITY OF NASOPALATINE NERVE, IRRITATION OF EYES & OF
RESP SYSTEM, & CHANGES IN HYPOTHALAMUS. EXPOSURE TO HIGH DOSES (ABOVE 100
PPM) ... CAUSED SALIVATION, ACUTE DYSPNEA, VOMITING, CRAMPS & DEATH ... .
EXPOSURE BY INHALATION FOR UP TO 90 DAYS PRODUCED INTERSTITIAL INFLAMMATION
IN LUNGS OF DOGS, RATS, MONKEYS, RABBITS & GUINEA-PIGS. ... HAIR
DEPIGMENTATION WAS OBSERVED IN BLACK MICE AT SITE OF SC INJECTION OF 100 UG FORMALDEHYDE.
... MICE TREATED WITH FORMALDEHYDE ON SKIN DEVELOPED SEVERE
LIVER DAMAGE.
GROUPS OF 119-120 MALE & 120 FEMALE FISCHER 344 RATS, 7 WK OF AGE WERE
EXPOSED TO 0, 2, 5.6 OR 14.3 PPM (0, 2.5, 6.9, 17.6 MG/CU M) ... GREATER THAN
97.5% PURE VAPOR BY WHOLE-BODY EXPOSURE FOR 6 HR/DAY ON 5 DAYS/WK FOR UP TO 24
MO, FOLLOWED BY 6 MO OBSERVATION PERIOD. ... LIFE-TABLE ANALYSIS OF ... DATA
REVEALED SIGNIFICANT INCR (P< 0.0167) IN INCIDENCES OF SQUAMOUS-CELL
CARCINOMAS IN /NASAL CAVITY OF RATS/ EXPOSED TO 14.3 PPM FORMALDEHYDE
VAPOR; NO OTHER NEOPLASM WAS INCREASED SIGNIFICANTLY. THE INCIDENCE OF A VARIETY
OF NON-NEOPLASTIC LESIONS WERE SIGNIFICANTLY INCREASED IN RATS EXPOSED TO FORMALDEHYDE.
GROUPS OF 6 MALE CYNOMOLGUS MONKEYS ... & 10 MALE & 10 FEMALE SYRIAN
GOLDEN HAMSTERS WERE EXPOSED TO 0, 0.2, 1.0 OR 3 PPM (0, 0.24, 1.2 OR 3.7 MG/CU
M) FORMALDEHYDE VAPOR (98.8% PURE) FOR 22 HR/DAY ON 7 DAYS/WK
FOR 26 WK. SQUAMOUS METAPLASIA OF NASAL TURBINATES WERE EVIDENT IN 6/6 MONKEYS
EXPOSED TO 3 PPM & IN 1/6 EXPOSED TO 1 PPM. ... NO EXPOSURE-RELATED EFFECTS
WERE DEMONSTRATED IN HAMSTERS.
REPEATED INHALATION EXPOSURE TO VAPORS AT 15 PPM IN MALE CHARLES RIVER CD
RATS & MALE C57BL6/F1 MICE WAS STUDIED. RATS WERE RELATIVELY INSENSITIVE TO
IRRITANT ACTION WHILE MICE WERE MORE SENSITIVE, SHOWING COMPARABLE REDUCTION IN
TIDAL VOL, BUT GREATER DECR IN RESPIRATORY RATE & MINUTE VOL. CARBON DIOXIDE
PRODUCTION AS WELL AS BODY TEMP WERE DECR TO GREATER EXTENT IN MICE THAN IN
RATS.
With Salmonella typhimurium, the minimum concn required to induce
8-azaguanine resistance was 170 uM.
15 ppm formaldehyde caused an initial wave of cell
replication in the nasal cavity of mice and rats 18 hr after a 6 hr exposure.
The /percentage/ of replicating cells remained ... elevated for 3-5 days and
then began to decrease. Similar elevations occurred following 3 daily exposures
to 6 ppm formaldehyde in rats, but not mice. ...
... Threshold concn of sensitization effect of /formaldehyde/
in guinea pigs was 0.5 mg/cu m. ... Quantitative changes were seen only in
B-lymphocytes, whereas T-lymphocytes were essentially unchanged. At 3 mg/cu m
the sensitization effect was seen in all the animals. The T-lymphocytes
decreased substantially but B-lymphocytes increased. ...
... Primary hamster embryo cells were treated by exposure to gaseous formaldehyde
or by incorporation into the medium, a dose-related incr in the frequency of SA7
virus transformation was produced. ... Length of chemical treatment and the time
interval before subsequent addition of transforming virus was critical, with 2
hr treatment times being most efficient. ... 2.2 ug/ml produced significantly
enhanced viral transformation. ...
... RATS /EXPOSED/ CONTINUOUSLY DURING PREGNANCY TO ... VAPORS (1 MG/CU M)
... /SHOWED/ NO VISIBLE FETAL MALFORMATIONS. ASCORBIC ACID CONTENT OF TREATED
FETUSES WAS LOWER THAN CONTROLS BUT BODY WT WAS INCR. FETAL DNA CONTENT WAS DECR
& RNA CONTENT WAS INCR.
GROUPS OF 100 MALE SPRAGUE-DAWLEY RATS WERE EXPOSED FROM 9 WK OF AGE TO (A)
14.3 PPM (17.44 MG/CU M) FORMALDEHYDE (PURITY UNSPECIFIED)
& 10 PPM (16.2 MG/CU M) HYDROGEN CHLORIDE GAS BEFORE DILN IN EXPOSURE
CHAMBER TO MAXIMIZE FORMATION OF BIS(CHLOROMETHYL)ETHER; (B) 14.1 PPM (17.2
MG/CU M) FORMALDEHYDE & 9.5 PPM 115.48 MG/CU M) HYDROGEN
CHLORIDE NOT MIXED BEFORE INTRODUCTION INTO ... CHAMBER; (C)14.2 PPM (17.32
MG/CU M) FORMALDEHYDE VAPOR ALONE; (D) HYDROGEN CHLORIDE GAS
ALONE (10.2 PPM); OR (E) AIR (SHAM-EXPOSED CONTROLS). AFTER ... 382 EXPOSURES
OVER ... 588 DAYS (19.4 MO), 10 HISTOLOGICALLY CONFIRMED, GROSSLY VISIBLE NASAL
SQUAMOUS-CELL CARCINOMAS WERE OBSERVED IN RATS EXPOSED TO FORMALDEHYDE
ALONE; NONE WERE SEEN IN CONTROLS OR IN RATS EXPOSED TO HYDROGEN CHLORIDE ALONE
... COMBINED EXPOSURE TO FORMALDEHYDE & HYDROGEN CHLORIDE
DID NOT PRODUCE STATISTICALLY SIGNIFICANT INCR IN INCIDENCE OF NASAL
SQUAMOUS-CELL CARCINOMAS OVER THAT OBTAINED WITH FORMALDEHYDE
ALONE. ...
EXPOSURE OF CULTURED MONKEY KIDNEY CELLS TO 1-16 MMOL ... FOR 15 MIN