P382-162397
Formaldehyde Health Effects
Midwest Research Inst.
Kansas City, MO
Prepared for
Environmental Protection Agency
Ann Arbor, MI
21 December 1981
U.S. DEPARTMENT OF COMMERCE
National Technical Information Service
NTIS
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United States
Environmental Protection
Agency
Office of Mobile Source Air Pollution Control
Emission Control Technology Division
2565 Plymouth Road
Ann Arbor. Ml 48105 ^ _ „
P382-16233
EPA-460 3-31 -033
c/EFA
Formaldehyde Health Effects
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TECHNICAL REPORT DATA
:P!ease reed Instructions on the reverse before completing!
REPCR
EPA 460/3-81-033
I
13. RECIPIENT'S ACCSSSIOIVNO.
PB32 162397.
•i. TITLE AND SUBTITLE
5. REPORT DATE
September 1981
Formaldehyde Health Effects
6. PERFORMING ORGANIZATION CODE
7. AUTHORS)
Bonnie L. Carson, Cecily M. Beall, Harry V. Ellis III,
Joy L. MeCaim, Larry Baker, Betty L. Herndon, Eileen It.
8. PERFORMING ORGANIZATION REPORT NO,
Horn
. PERFORMING ORGANIZATION NAV.E AND ADDRESS
Midwest Research Institute
425 Volker Boulevard
Kansas City, Missouri 64110
10. PROGRAM ELEMENT NO.
11. CONTRACT/GRANT NO.
68-03-2928
12. SPONSORING AGENCY NAME AND ADDRESS
Environmental Protection Agency
Office of Mobile Source Air Pollution Control
Emission Control Technology Division
2565 Plymouth Road, Ann Arbor, Michigan 48102
13. TYPE OF REPORT AND PERIOD COVEREO
Final Report
14. SPONSORING AGENCY CODE
15. SUPPLEMENTARY NOTES
16. ABSTRACT ~~~
Health effects literature primarily related to inhalation exposure to formaldehyde
was collected, evaluated, tabulated, and summarized. Approximately 425 documents were
collected from computerized and manual literature searches covering the period 1905-
1981. Pharmacologists and an M.D. epidemiologist rated the documents according to
their applicability to the study and their methodology. The approximately 110 docu-
ments considered useful for deriving a range of concern for human exposure to
formaldehyde from automotive emissions were tabulated. The 145 pages of tables
detail the results of acute, repeated dose, and chronic testing of mice, hamsters,
rats, guinea pigs, rabbits, cats, pigs, dogs, monkeys, and humans as well as human
occupational and epidemiological studies. Most of the documents evaluated are de-
scribed in an annotated bibliography.
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.IDENTIFIERS/OPEN ENDED TERMS
c. COSATI Field/Grouo
Toxicity
Formaldehyde
Aldehydes
Mammals
Bibliographies
Toxic Tolerances
Occupational Diseases
Epidemiology
Respiratory System
Inhalation Health Effect
06T
3. 2I3TRI3UTICN STATEMENT
Release Unlimited
i 19. SECURITY CLASS iTna Report)
Unclassified
21. NO. OF PAG-S
|20. SECURITY CLASS /This page/
1 Unclassified
22. PRICE
£?A Form 2220-1 (9-73)
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NOTICE
THIS DOCUMENT HAS BEEN REPRODUCED
FROM THE BEST COPY FURNISHED US BY
THE SPONSORING AGENCY. ALTHOUGH IT
IS RECOGNIZED THAT CERTAIN PORTIONS
ARE ILLEGIBLE, IT IS BEING RELEASED
IN THE INTEREST OF MAKING AVAILABLE
AS MUCH INFORMATION AS POSSIBLE.
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FORMALDEHYDE HEALTH EFFECTS
with Contributions by
Bonnie L. Carson Joy L. McCann
Cecily M. Beall Larry H. Baker
Harry V. Ellis III Eileen M. Horn
Bettv L. Herndon
FINAL TASK 5 REPORT
December 21, 1981
Contract No. 68-03-2928
Task Specification No. 5
"Health Effects Support for the Emission Control
Technology Division"
For
Emission Control Technology Division
Office of Mobile Source Air Pollution Control
U.S. Environmental Protection Agency
2565 Plymouth Road
Ann Arbor, Michigan 48105
Attn: Robert J. Garbe
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PREFACE
This report on health effects of formaldehyde was prepared by Mid-
west Research Institute (MRI) as Task No. 5 under Contract No. 68-03-2928,
"Health Effects Support for the Emission Control Technology Division," U.S.
Environmental Protection Agency.
Health effects literature primarily related to inhalation expos-
ures to formaldehyde has been collected, evaluated, tabulated, and summar-
ized so that this report can be used to derive a range of concern for human
exposure to formaldehyde from vehicular emissions to the air.
Task activities were coordinated by the project leader, Mrs. Bonnie L.
Carson, Senior Chemist, and the co-task leader, Ms. Cecily M. Beall, Assistant
Scientist. Documents were rated and summarized by senior pharmacologists
Drs. Harry V. Ellis III and Betty L. Herndon, of MRI, and consultant epidemi-
ologist Larry H. Baker, M.D., MRI consultant, who is an Associate Professor
of Community Health at the University of Kansas Medical Center. Contribu-
tors to the tables and annotated bibliography included the above as well as
Ms. Joy L. McCann, Assistant Scientist, and Ms. Eileen M. Horn, Junior Chemist.
Ms. Carol Foret served as a literature aide. This study was performed under
the general supervision of Dr. Edward W. Lawless, Head, Chemical Impact As-
sessment Section.
Mr. Robert J. Garbe was the project officer for the Emission Con-
trol Technology Division, U.S. Environmental Protection Agency, and Ms. Colleen
DeMeyer served as Branch Technical Representative.
Approved for:
MIDWEST RESEARCH INSTITUTE
' J \
Bruce W. Macy, Director
Center for Technoeconomic
Analysis
111
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TABLE OF CONTENTS
Preface
Figures vi
Tables vii
Summary 1
Goals and Methods 1
Bioassay Tests 2
Animal Exposure Studies 2
Human Exposure Studies 2
Recommended Range of Concern 9
I. Introduction 13
II. Bioassay Tests 17
III. Experimental Animal Inhalation Exposures 21
IV. Experimental Human Inhalation Exposures 95
V. Epidemiology and Related Human Exposures Ill
Occupational Exposures Ill
Exposures of the General Public Ill
VI. Summary of Health Effects Information 169
Background 169
Bioassay Tests 1/1
Animal Exposure Studies 173
Human Exposure Studies 176
VII. Human Exposures to Formaldehyde and Recommendations
for a Range of Concern 179
Human Exposures 179
International Standards and Recommendations 183
Recommended Range of Concern 183
Annotated Bibliography 189
Appendix A - Human Studies in Progress A-l
v
Preceding page blank
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FIGURES
Number
1-1 Form for Report Rating
VI-1 Formaldehyde Metabolism by the Tetrahydrofolic
Acid-Depeadent Pathway
VI
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TABLES
Number Page
S-l Summary of Studies of Animal Exposures to
Formaldehyde (ECHO) Up to 6 mg/m3 3
S-2 Summary of Acute Human Experimental Exposure
to Formaldehyde 7
S-3 Summary of Occupational and Epidemiological
Studies of Exposures to Formaldehyde 10
II-l Respiratory Tract Bioassays 18
III-l Mice—Acute Experimental Exposure to Formaldehyde
(HCHO) 22
III-2 Mice—Repeated Dose Experimental Exposure to
Formaldehyde (HCHO) 26
III-3 Mice—Chronic Experimental Exposure to Formaldehyde
(HCHO) 29
III-4 Hamsters—Acute Experimental Exposure to Formaldehyde
(HCHO) 31
III-5 Hamsters—Repeated Dose and Chronic Experimental
Exposure to Formaldehyde (HCHO) 35
III-6 Rats—Acute Experimental Exposure to Formaldehyde
(HCHO) 37
III-7 Rats—Repeated Dose Experimental Exposure to
Formaldehyde (HCHO) 40
III-8 Rats—Chronic Experimental Exposure to Formaldehyde
(HCHO) 55
III-9 Guinea Pigs—Acute Experimental Exposure to
Formaldehyde (HCHO) 65
111-10 Guinea Pigs—Repeated Dose Experimental Exposure to
Formaldehyde (HCHO) 71
III-11 Rabbits—Acute Experimental Exposure to Formaldehyde
(HCHO) 77
111-12 Rabbits—Repeated Dose Experimental Exposure to
Formaldehyde (HCHO) 81
111-13 Cats—Acute Experimental Exposure to Formaldehyde
(HCHO) 83
III-14 Pigs—Acute Experimental Exposure to Formaldehyde
(HCHO) 85
111-15 Dogs—Repeated Dose Experimental Exposure to
Formaldehyde (HCHO) 86
III-16 Monkeys—Repeated Dose and Chronic Experimental
Exposure to Formaldehyde (HCHO) 87
III-17 Summary of Animal Exposures to Formaldehyde (HCHO) .... 88
vii
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TABLES (concluded)
Number
IV-1 Humans—Acute Experimental Inhalation Exposure to
Formaldehyde (HCHO) 96
V-l Studies of Occupational Exposure to Formaldehyde (HCHO). . 113
V-2 Epidemiological and Other Studies Relevant to
Formaldehyde Inhalation Exposure of the General Public . 154
VII-1 Representative Indoor and Outdoor Atmospheric Levels
of Formaldehyde 180
VII-2 Summary of Regulations and Recommendations for Human
Formaldehyde Exposures 184
Vlll
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SUMMARY
This summary is organized into the following sections: Goals and Methods,
Bioassay Tests, Animal Exposure Studies, Human Exposure Studies, and Recommended
Range of Concern.
GOALS AND METHODS
The purpose of this compilation of data on the health effects of inhala-
tion exposures to formaldehyde (HCHO) is to assist the Emission Control Tech-
nology Division (ECTD) of the U.S. Environmental Protection Agency (EPA) to
establish the ranges of exposure conditions that are of concern for HCHO in
exhausts from vehicles equipped with catalytic converters, and to be able
to advise automobile manufacturers thereof. The situations of particular
concern are during malfunctions and during exposures in traffic jams, parking
and home garages, and other situations where little dilution of the exhaust
is expected before inhalation. Most of the report is, as directed by ECTD,
in the form of tables based on the literature reviewed. Data from exposures
at levels higher than those of primary concern are included because strictly
relevant information was scarce and these related data might prove helpful
in assessing health effects at lower levels. This report focuses on the
noncarcinogenic effects of formaldehyde rather than on its carcinogenicity
to humans. The latter is an unresolved question of much importance, but
regardless of whether it is a carcinogen, gaseous formaldehyde is strongly
irritating to the human eye, nose, and throat and capable of causing allergic
sensitization at the levels of concern identified herein.
Documents on inhalation effects of HCHO identified from manual and com-
puterized literature searches were rated in a two-step process by the project
pharmacologist and epidemiologist. First, the document received an A, B,
C, or D rating according to its applicability for deriving a range of concern
for HCHO in automobile emissions. Second, if the paper was not a low-rated,
foreign language document,"" a theoretical paper, a review, or a nontoxicol-
ogy experimental paper, it received a numerical score based on itemized fea-
tures that should be present in an ideal report. For the most part, only
A- and B-rated documents were tabulated; but when any C- or D-rated studies
involved low-level HCHO exposures, these were also tabulated. Blanks in
the tables should be construed as denoting missing information in the docu-
ments .
v Most foreign language articles rated C and D were usually not translated.
Each foreign language document tentatively rated A or B from an English
language abstract or brief examination of the paper was translated in
sufficient degree to judge the experimental design and details. These
papers were numerically scored from the translation.
1
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BIOASSAY TESTS
Rabbit and rat trachea! tissue exposed very briefly to 0.6-125 mg HCHO/m3
showed cessation of ciliary movement, with decreasing concentrations showing
increasing time to ciliostasis. Exposure to 0.6 mg HCHO/m3 caused ciliostasis
within 2.5 min followed by recovery within 10-30 s after exposure stopped.
All the other concentrations studied were above 3 mg HCHO/m3, the threshold
limit value.
ANIiMAL EXPOSURE STUDIES
Animal exposure studies show that the animal organism can recover from
moderately irritating doses of inhaled HCHO. However, there is a limit to
this recovery, as shown by the progressively increasing time to recovery
and the nasal cancers observed in rats and mice after long-term exposures
to 7 and/or 17-19 mg HCHO/m3, although not all studies increased tumor inci-
dence in animals exposed to these levels.
Table S-l summarizes studies of animal exposures to HCHO at concentra-
tions up to 6 mg/m3 (twice the threshold limit value).
There is no evidence of major differences in response to inhaled HCHO
among the species tested. Moderate amounts of evidence show simple additiv-
ity with other irritants and with other air pollutants having different
effects. The minimal adverse effects seem to be local irritation and subse-
quent tissue reactions, especially in the pulmonary system. Such adverse
effects appear at levels at or above 1 mg/m3, whether the animals were
acutely or chronically exposed. In chronic studies, biochemical and inflam-
matory changes were reported at concentrations >^ 0.035 mg/m3. Rats exposed
for only 8-12 wk to 0.012 mg/m3 have also shown such changes.
HUMAN EXPOSURE STUDIES
Experimental Studies
Results of studies of acute human experimental exposure to HCHO are
summarized in Table S-2. Moderate to severe irritation of the eye, nose,
and throat was observed at concentrations of 1.25-17.3 mg/m3. At ~ 1 rag
HCHO/m3, eye irritation is slight, but distortions occur in breathing and
a-rhythms. The threshold for eye irritation is 0.2-0.25 mg/m3. The re-
ported odor thresholds range from 0.4 to ~ 0.1 mg/m3.
Several studies found minimal effects at ~ 0.05-0.08 mg/m3 (such as
the electroencephalographic response to light). Exposures to 0.0024 to
0.029 mg/m3 were said to cause effects ranging from mood changes to nervous
system irritation (0.016 mg/m3), thresholds of respiratory irritation
(0.075 mg/m3), and salivary action.
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TABLE S-l. SUMMARY OF STUDIES OF ANIMAL EXPOSURES TO
FORMALDEHYDE (ECHO) UP TO 6 mg/m3*
Level
(mg/m3) Time
3.5-6 10 s
5 4 h
Species
RBT
RAT
Effects
Threshold of olfactory sensitivity.
Decreased blood pressure; neutro-
5-6
4.6
4.6
4.6
2-4.6
90 d
90 d
90 d
53-90 d
RBT
DOG
MKY
GPG
0.7-4.5
1.6-3.8
philia; eosinophilia; minor irri-
tation to lungs, spleen, and
marrow.
4 h/d, 20 d RAT Slight effect on neuromuscular
system, slightly higher pre-
implantation mortality of em-
bryos, development of offspring
normal except for decreased spon-
taneous mobility.
Blood normal, inflammation in lungs.
Blood normal, inflammation in lungs.
Blood normal, inflammation in lungs.
No deaths; slight cholinesterase
and leukocyte effects; inflamma-
tion in lung, heart, and kidneys.
Allergic effects appeared at 14 d.
RAT Lower body weight; slight inflamma-
tion of lungs, heart, and kidneys;
and decreased DNA-ase activity
of liver. Change in chronaxy
ratio of antagonistic muscles;
mild biochemical changes in brain,
liver, kidneys, and blood. In
lungs, hyperemia, desquamation
and proliferation of lymphohisti-
ocytic elements.
MUS Respiration rate decreased 26 to
53%, with or without prior ex-
posure to HCHO.
45-90 d
10 min
* This level, which is twice the threshold limit value (TLV), was arbitrarily
chosen.
(continued)
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TABLE S-l (continued)
Level
(mg/ra3)
Time Species
Effects
1-4 3 h/d, 4 d MUS Initial respiration rate decrease
of 18 to 72% at beginning of each
exposure. Some recovery during
exposure, less each day.
3.75 22 h/d RAT Nasal discharge in MKY; decreased
7 d/wk HAM weight gain in RAT
6 mo MKY
2-3.5 10 s - 10 min RBT Disturbance in nervous system
responses.
2.5 6 h PIG No change in lung function, but
moderate morphologic changes,
more so in dorsal than ventral
section. Changes included
desquamation, interstitial edema,
emphysema, and atelectasis.
1-2 4 h RAT No effect.
1.25 22 h/d RAT Nasal discharge in MKY; no other
7 d/wk HAM effects.
6 mo MKY
1.0 8 wk RAT Significant changes in ascorbic
acid, nucleic acids, DNA levels
in females and fetuses. Length
of pregnancy increased, number
of fetuses decreased, no defor-
mities. Histochemical changes
in heart, liver, and kidneys of
fetuses.
1.0 8 mo RAT No effect on body weight or blood
chemistry for either first gen-
eration or exposed offspring.
Offspring had some morphological
changes in lungs after 8-mo ex-
posure.
(continued)
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TABLE S-l (continued)
Level
(mg/m3)
0-.69
Time
10 min
Species Effects
MUS Respiration rate decreased 14 to
16% with or without prior expo-
sure to HCHO.
0.6-2.5
0.4-0.5
0.5
0.038-0.5
0.06-0.39
0.1
1-4 h RAT
4 h/d, 19-20 d RAT
4-5 h/d, 4-6 mo RAT
5-8 h/d, 21-28 d GPG
0.035
1 h
69-90 d
0.031-0.035 90-98 d
3-8 h/d, 6 mo
GPG
0.03-0.25
0.25
6 h
J. h/d
7 d/wk
6 mo
PIG
RAT
HAM
MKY
RAT
RAT
RAT
Depression of nasal sensory re-
sponse, partial recovery within
1 h.
No overall toxic effects, fetuses
normal.
No effects on general health, minor
changes in blood and urine param-
eters.
No effect on general health, minor
changes in blood and urine param-
eters, formation of antibodies.
Significant change in lung func-
tion, some recovery within 1 h
post-exposure.
Change in lung function and slight
lung inflammation.
No effect.
Signs of beginning damage to nasal
mucosa. DNA-ase activity of liver
increased; of spleen, decreased.
No effect on overall health, nervous
system response slowed slightly,
slight inflammation areas in
lungs and liver.
No effect on general condition,
changes in metabolic processes
of liver, blood changes, and
testicular biochemical changes.
Decreased sperm mobility.
(continued)
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TABLE S-l (concluded)
Level
(mg/m3) Time Species Effects
0.012 8-12 wk RAT No effect on overall health, ner-
vous system slowed slightly,
slight inflammation in areas of
lungs. Biochemical changes in
livers of females and fetuses, in-
creased length of pregnancy, de-
creased number of fetuses, no
deformities. Histochemical changes
in heart and kidneys of fetuses.
0.011 7-8 h/d, 21-30 d GPG Blood unaffected, phagocytic activ-
ity increased, formation of anti-
bodies. When stressed 2 mo later
by hypoxia, immune response and
phagocytic activity adversely
affected.
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TABLE S-2. SUMMARY OF ACUTE HUMAN EXPERIMENTAL EXPOSURE
TO FORMALDEHYDE.
Level (mg/m3) Effects
9.6 - 17.3 Irritation of the mucous membranes of the eyes,
nose, and upper respiratory tract.
5.0 - 6.25 Moderate to severe eye irritation in most
subjects, some nasal and throat irritation.
3.75-4.0 Moderate to severe eye irritation and throat
irritation initially. Some adaptation by
30 min.
2.5 Moderate to severe eye irritation in some
subjects; some nose and throat irritation.
2.0 Slight, insignificant changes in airway re-
sistance; decreased nasal mucus flow rate;
slight discomfort, with some acclimatization;
no change in performance tests.
1.71 Decreased sensitivity to light in all subjects.
1.25 A few subjects experienced moderate to severe
eye irritation; generally zero to moderate
eye, nose, and throat irritation; lowest con-
centration at which the odor was recognized.
1.0 Slight, insignificant changes in airway re-
sistance; slight discomfort in all subjects;
no change in performance tests.
0.95 - 1.0 Slight irritation of the eyes and upper respi-
tory tract; odor perceived; some changes in
breathing rhythm and a-rhythms.
0.53 Threshold value for effect on electrical
activity of the human brain.
0.5 Slight, insignificant changes in airway re-
sistance; decreased nasal mucus flow rate;
very slight discomfort in all subjects;
no change in perf oraan.ce tests.
0.3 - 0.4 Odor perceived; change in bioelectric skin
potential; delay in adaptation to darkness.
(continued)
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TABLE S-2 (concluded)
Level (mg/m3) Effects
0.3 Slight, insignificant changes in airway re-
sistance; decreased nasal mucus flow rate;
slight subjective discomfort in 3/15 sub-
jects; no change in performance tests.
0.2 - 0.25 Threshold for eye irritation; increased
sensitivity to light.
0.08 - 0.098 Minimum detectable odor level for some;
threshold for eliciting reflex activity
on optical chronaxy and dark adaptation.
0.07 - 0.077 Odor threshold for ~ 50% of the subjects;
subthreshold level for effect on optical
chronaxy and rheobase.
0.062 - 0.065 Odor threshold for 4/18, subthreshold for
others.
0.05 - 0.054 Subthreshold value for odor detection;
threshold value for EEC changes following
flashing light.
0.04 - 0.046 Changes in the electrocortical conditioned
reflex study; subthreshold value for EEC
changes following flashing light.
0.035 Subthreshold value for the electrocortical
conditioned reflex study.
0.029 Threshold of salivary action.
0.016 Threshold of irritation of the nervous
system.
0.0024 Threshold of effect on the mood of human
subjects.
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Environmental Exposures
The occupational and epidemiological studies of HCHO exposures are sum-
marized in Table S-3. Occupational studies were generally of a rather low
quality, being confounded by exposure to other agents with similar irritat-
ing effects and having poor or no controls. Mucous membrane irritation was
observed in occupational exposures to concentrations as low as 0.035-0.48 mg
HCHO/m3. Occupational studies are in progress, as described in Appendix A,
with mortuary workers and histotechnologists who can have cutaneous as well
as inhalation exposure. Definitive results are not yet available.
Most of the epidemiological studies and other reports of HCHO exposures
of the general public are defective due to poor or no controls, selection
bias, or lack of measurements of HCHO concentrations. Eye and upper respira-
tory tract irritation were reported at levels as low as 0.211 mg HCHO/m3.
RECOMMENDED RANGE OF CONCERN
Human studies indicate that the range of concern in long-term or acute
exposures to HCHO should be 0.06 (the lowest reported odor threshold) or
0.2 (the threshold for eye irritation) to ~ 1 mg/m3 (where slight eye irrita-
tion and other minor disturbances occur). If animal studies could be directly
extrapolated to humans, the lower limit of the range of concern might be
extended to values as low as 0.01-0.04 mg HCHO/m3.
The value of 0.2 mg/m3 may be the most defensible choice since both
nonsmoking and smoking humans sometimes contain HCHO in the breath at levels
as high as ~ 0.1 mg/m3, HCHO being a normal metabolite and a metabolite of
exogenous substances. This value is frequently the maximum value reported
for urban polluted air. However, authorities in the USSR have promulgated
a standard of 0.01 mg/m3 for HCHO in outdoor air, which is an order of magni-
tude lower than these values.
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TABLE S-3. SUMMARY OF OCCUPATIONAL AND EPIDEMIOLOGICAL STUDIES
OF EXPOSURES TO FORMALDEHYDE
Level
(rag/m3)
Exposure
Time Table
Effects
0.06-12.5
0.11-6.53
£6.25
1.5-4.5
0.38-3.88
0.04-1.76
and
wood dust
0.25-1.25
V-2
8 mo
V-l
V-2
64% worked
5 10 y
V-l
6 mo
avg.
5.9 y
V-2
V-l
V-2
Residents of homes with urea-HCHO (UF)
foam insulation: eye irritation and
conjunctivitis, nose and throat ir-
ritation, respiratory symptoms,
dizziness, nausea, drowsiness,
memory lapse, headache, coughing,
sneezing, fatigue, aches, rash,
and skin growths.
Embalmers: eye and nose burns, sneez-
ing, coughing, headaches, sinus, asth-
ma, dermatitis.
Children in a school where HCHO was
present complained of burning eyes,
abdominal pain, eye pain, nausea,
vomiting, thirst, and apathy.
Textile workers: increases in various
menstrual disorders, inflammatory gen-
ital disease, primary and secondary
sterility, maternal problems during
pregnancy and delivery, and decreased
neonatal weight.
Employees and customers in a shopping
center: eye (occasional lacrimation),
nose, and throat irritation.
Employees in wood processing plant.
Those exposed to higher levels per-
formed visual tests less quickly and
efficiently both before and after work
than the lower-exposure group. Head-
ache, eye irritation, fatigue; com-
plaints less frequent in the highest
exposure group.
Residents of homes with HCHO present:
eye, nose, and throat irritation most
frequent in adults. Coughing, wheez-
ing, and skin rash most frequent in
< 13-y-olds.
(continued)
10
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TABLE S-3 (concluded)
Level
(mg/m3)
Exposure
Time Table
Effects
0.1-1.21
V-2
0-0.98
0.17-0.85
0.25-0.75
0.05-0.7
0.035-0.48
0.211
0.08-0.13
1-40 mo
V-2
< 10-
> 20 y
V-l
56% worked
^ 10 y
£ 1 y ?
V-2
V-l
V-l
V-2
V-2
Teachers and students in school with
HCHO present: headache, lack of con-
centration, dizziness, nausea, and
respiratory tract irritation.
Residents of homes with UF insulation:
burning or tearing of eyes, runny nose,
wheezing or breathing difficulty, head-
ache, sleeping problems, and skin rash.
Sales persons in fabric shops. Mucus
discharge, sleep disturbance, pains in
the heart, angina, and nausea. Head
pain, dizziness, irritation, stomach
pains, and skin rash most common in
the group with shorter employment.
Cough, tickling in the nasopharynx,
catarrh, poor appetite, and pains in
the joints and small of the back more
common in the group with longer em-
ployment.
Residents of apartment building where
HCHO was present: burning eyes,
lacrimation, and coughing.
Inspectors in textile warehouses:
various menstrual disorders; increased
inflammatory genital disease, primary
sterility, and problems during birth;
decreased neonatal weights.
Garment factory workers: cutaneous
and mucous membrane irritation.
Eye and upper respiratory tract ir-
ritation was reported by some of the
residents living near a formalin-
producing plant.
No complaints by residents of an apart-
ment building. No complaints or in-
creased absenteeism in children in a
school where HCHO was present.
11
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SECTION I
INTRODUCTION
This report was compiled as the fifth of several tasks under Contract
No. 68-03-2928, "Health Effects Support for the Emission Control Technology
Division (U.S. Environmental Protection Agency, Ann Arbor, Michigan)." The
goal of the project is to evaluate health effects literature on specific
compounds emitted from automobiles equipped with emission-control devices
(specifically catalytic converters), not for the purpose of creating a cri-
teria document but to identify a range of concern or a no-observable-effect
level for each compound to serve as guidance to automobile manufacturers in
their development of future emission-control devices.
The present report was meant to be largely a series of charts or tables
of pertinent data with the tests logically ordered according to exposure
levels. The narrative summary was not meant to describe each paper in de-
tail. There are admittedly some disadvantages in not doing so; e.g., some
of the gradations in effect that the authors of a particular paper observed
may be diluted or lost when the details are spread throughout an exceptionally
large table, or between several tables. Papers described in a largely narra-
tive fashion, however, often are difficult to compare. Results that appear
within their source paper to be quite definitive may appear less so or even
anomalous when juxtaposed in tabular format with other results from similar
studies. Hence, the present format was designed to facilitate comparisons.
Literature related to health effects of inhaled formaldehyde (HCHO)
was collected mainly by computer searches of TOXLINE and TOXBACK and manual
searches through several major review documents. Approximately 425 papers
and other documents were evaluated, of which approximately 110 contained
original data suitable for tabulation.
Experimental animal and human exposure studies and bioassay studies
were evaluated and summarized by senior Ph.D. pharmacologists. Occupational
and general public exposures were rated by an epidemiologist with an M.D.
degree. Figure 1-1 is the form used for rating documents by the project
pharmacologist and epidemiologist. Each document was rated in a two-step
procedure according to the applicability of its subject matter and to the
quality of the experimental methodology. The letter assigned in rating the
document A, B, C, or D was derived from the corresponding lower case letters
under item 7 in Figure 1-1. Thus, a study was rated A if it directly applies
to or assists in establishing a range of concern for exposure to HCHO. The
second part of the rating is the methodology score. The document reviewer
checked off which score should be given for each of the first six items in
Figure 1-1, and the total was written at the top of the page along with the
-------
Article No. 4997-5-
CHECK WHERE APPROPRIATE:
PAPER
DEFECTIVE
PAPER IS! STANDARD
SUB- i QUALITY
STANDARD i
1 ! 2
SUPERIOR
PAPER
1. Do they state/limit the problem?
;2. Adequacy of sample
13. Replicability
4. Controls/control procedures
5. Completeness and comprehensibility
of results
6. Validity of conclusions, inter-
pretation of data
7. Applicability to health effects of HCHO as guidance for establishing a range
of concern for HCHO in automobile exhaust.
a. Clearly, directly applies/assists in establishing a range of concern.
b. Research requires major inferences; potentially applicable.
c. Useful hints or suggestions; tentatively applicable.
d. Not directly applicable (peripheral useful information).
Figure 1-1 - Form for Report Rating
-------
letter that rated the paper's applicability. In some'cases, such as reviews,
theoretical papers, and low-rated foreign language documents, a paper may
have received an applicability rating (generally C or D) but none on methodol-
ogy-
Data, including the MRI-assigned rating, from the A-, B-, and some C-
and D-rated papers were tabulated by senior and mid-level scientists. Infor-
mation for each topic heading was carefully sought; so if blanks appear in
the table, the reader can generally assume the data were not given. Informa-
tion which was unclear in the original document but needed for tabulation
is preceded in the tables by a qualifying word such as "apparently." Some-
times a group published several papers that described the same tests. To
avoid redundancy, all pertinent papers were cited and the test was described
as well as possible from all the papers' descriptions.
The final written summary of the tabulated data was also performed by
a senior pharmacologist. This summary attempts to reflect objectively the
scientific community's thought as a whole and does not reflect the tabular
material by weight. The tables reflect the amount of data generated, and
the summary puts the evaluated data in perspective with the overall scien-
tific community's opinions.
The references are cited in an annotated bibliography that includes
not only each document's rating but also a brief comment on its pertinence
(or lack of same) to the study. English titles are given for foreign lan-
guage documents and an abbreviation of the language is given in parentheses
at the end of the citation.
The report is organized into the following chapters: II. Bioassay
Tests, III. Experimental Animal Inhalation Exposures, IV. Experimental Human
Inhalation Exposures, V. Epidemiology and Related Human Exposures, VI. Sum-
mary of Health Effects Information, and VII. Human Exposures to Formaldehyde
and Recommendations for a Range of Concern. The Summary precedes the report,
and the Annotated Bibliography follows it. Appendix A describes human studies
in progress.
15
-------
SECTION II
BIOASSAY TESTS
The area of concern for this task report is the effects of HCHO inhala-
tion. For that reason, only bioassays dealing with gaseous HCHO and respira-
tory tissues are tabulated in this chapter. However, Chapter VI contains a
discussion not only of these results but also of mutagenicity tests.
17
Preceding page blank
-------
Compound anil
Concent rat ion
TAIII.K 11-1. HKSI'IHATORY THACT IIIOASSAYS
lie I alive Humidity/
Temperature
Preparal ion
Exposed
Description of Tests
anil Duration
Results
Referent e
anil
Rat ing
IICIIO 1.6-163 tig/ml.
(unclear if tliis
was the level iii
air or solution)
IICIIO 22.5-125
(18-100)
37°C
30-31"C
IICIIO It.6-61.7
IICIIO 27.5
(22)
IICIIO
(10)
12.5
34°C,
90-95%
34°C,
90-95%
Cell cultures of alveolar
inacrophagcs obtained by
lavage of the lungs of
lightly anesthetized
ratihils.
Fresh (< 2.5 h) excised
rabbit tradical tissue.
Rabbit trachea)
sections.
Ral trachcas, apparently
opened arid exposed in sitn.
Rat tracheas, apparently
opened and exposed in
situ.
Cell cultures in Rait solu-
tions were incubated with bac-
teria (Slaphylpcoccns a Urns)
and HCflO. iiactciial counts
were made by standard agar pour-
plate procedures at 0, 1.5,
and 3 li. Decreased counts indi-
cate phagocytic ability.
Section was placed in a
tissue chamber and IICIIO
gas added for 5-10 mill at
a flow rate similar to that
in the trachea of a living
rabbit. Ciliary activity
was observed microscopically
during and after exposure.
IICIIO from an air nebulizer was
added to a moist, temperate
chamber at the rale of 54 I./h,
for a maximum ol 60 mill.
Ciliary beating was monitored
(method not given) during expo-
sure, but no recovery period wus
included.
Ciliary activity was continuously
observed microscopically for < 10
mill, willi coiil iniious gas flow over
the tracheas.
Ciliary activity was continuously
observed microscopically for < 10
mill, with continuous n;lb flow over
the tracheas.
No effect on alveolar macrophage
act ivity.
Green and
Carol in
Five-minute exposure to 38 mjj/in1
or 10-min exposure to 22.5 mg/m3
caused cessation of ciliary
activity without recovery in air.
Five-minute exposure to 75-125
mg/iii1 caused cessation of ciliary
activity without recovery in
Ringer's solution.
Ciliary activity stopped immedi-
ately after exposure to 61.7 mg/m1.
Decreasing concent rations caused
increasing time to ciliostasis
(48 mil) for 11.6 mg/m1).
Ciliary movement ceased in 10 s.
Ciliary movement ceased in 30 s.
D-
Cral ley
(1942)
C-IO
I),i Hi,nun and
Koseugreu
(1971)
0-5
D.illicimu
(I9r>6)
0-6
Dal damn
(1956)
C-6
(continued)
-------
TABLE 11-1 (concluded)
COIII|>OIIIK| and
Concent rat ion
ing/in3 (ppm)
Relative Humidity/
Temperature
Prrpai.il ton
Exposed
Description of Tests
and Duration
Results
Reference
.mil
U.i I i ng
IICIIO 5
37°C
Excised rabbit trachcas
opened longitiKliii.il ly.
IICIIO 3.75
O)
IICIIO 0.6
(0.5)
34 °C,
90-95%
90-95%
Rat tracheas, apparently
opened and exposed
in situ.
Rat tracheas, apparently
opened and exposed in
situ.
>£>
Tissue was exposed to 6 tig IICIIO/
12-s puffs (40 ml.), ~ I rain
apart, for 8 puffs. The time for
the ciliary transport of tracer
particles (soot and lycopodium
particles) a distance of 5 nun
was measured.
Ciliary activity was continuously
observed microscopically for < 10
min, with continuous gas flow over
the tracheas.
Ciliary activity was continuously
observed microscopically for < 10
min, with continuous gas flow over
the tracheas, then for a short
recovery period.
The dose required per puff to
produce a 50% inhibition of
ciliary transport rate after
8 puffs was 6 |Jg/puff (150 mg/m1).
This contrasts with the 2 |ig/
puff given as the IICIIO level
in cigarette smoke.
Ciliary movement ceased in 50 s.
Ciliary movement ceased in 2.5 min.
Heating began again 10-30 s after
exposure stopped.
Kensler
and Hal list,i
(1963)
11-11
Da 1 tiamn
(1956)
C-6
Da Ihamii
(I95C.)
C-6
-------
SECTION III
EXPERIMENTAL ANIMAL INHALATION EXPOSURES
The essential parameters of numerous animal inhalation exposure experi-
ments are tabulated in this section. The primary organization of data is
by species, in order of increasing weight (mice to monkeys in this case).
Within a species, studies are divided by dosing duration: acute exposure
(H 24 h), repeated exposure, and chronic exposure (> 90 d) . A summary of
the data for all species ordered by decreasing HCHO concentration is in
Table 111-17.
The tables have been grouped by species and arranged by decreasing HCHO
concentration for the following reasons: (a) there were about 170 separate
tests tabulated; (b) there are distinct differences in lung anatomy among
the laboratory species used, and the differences seen in their relative re-
sponses may have been largely due to these anatomical differences; and (c)
by putting the highest concentrations and worst effects first, one can more
readily understand the significance of minor or less-severe changes occur-
ring at lower levels.
The general rating system described in Figure 1-1 was modified for
assigning applicability ratings to the animal exposure documents. Those
studies with data on chronic exposure or acute exposure with minimal effects
were rated B. Studies with acute exposures and severe effects or any study
with unusual endpoints not obvir isly important to respiratory exposure were
rated C. Exposures which were Confounded by the presence of other compounds,
or were measured by very unusual endpoints of doubtful significance were
rated D. The C- and D-rated studies were tabulated if the confounding com-
pounds are also found in automotive exhaust, if HCHO was the primary toxi-
cant, or if the HCHO level was low. No animal studies were rated A because
of the controversy surrounding extrapolation of effects observed in animals
to humans.
In the animal exposure tables in this section, the column headed "Total
Length of Experiment" includes not only the total length of exposure to HCHO,
but also any recovery time observed in the study. This recovery time was
included to note the endurance or reversibility of the toxic effects.
Chapter VI contains a discussion of the animal exposure data.
Preceding page blank
-------
TABLE 111-1. MICE—ACUTK EXPERIMENTAL EXPOSURE TO FOKMAI.IiEIIYOK (IICIIO)
K>
Coinpoimd(s) and
Concent r.it ion(t>) ,
miS/m1 (p|im)
IICIIO 900
IICIIO -16.8
(13. A)
IICIIO -12.6
(10. 1)
„
IICIIO ~ 12.16
(9.73)
Acrolein
~ 20.61
(8.97)
IICIIO ~ 9.88
(7.90)
IICIIO -8.96
(7.17)
Acrolein
~ 1.68
(0.73)
Humidity/ Mode of
Temperature Exposure
Inhala-
tion
chamber,
623-L
Head
only,
2.1-L
inhala-
tion
chamber
Head
only,
2.1-L
inhala-
tion
chamber
Inlia la-
lion
chamber
Head
only,
2.1-L
inhala-
tion
chamber
Inhala-
tion
chamber
S|ie< ies/Slrain/ No. of No. ot
Age/Weight Test Animnls Controls
Mice, Not given Not
C3H strain given
Mice, A M Served
Swiss-Webster, as own
Specific control
Pathogen Free,
20-30 g
Mice, AM Served
Swiss-Webster, as own
Specific control
Pathogen Free,
20-30 g
Mice, A H
Swiss-Webster,
Specific
Pathogen Free,
20-30 g
Mice, AM Served
Swiss-Webster, as own
Specific control
Pathogen Free,
20-30 g
Mice, A M
Swiss-Webster,
Specific
Pathogen Free,
20-30 g
Dnr.it ion and Total
Frequency of Length of
Exposure Experiment Effects
2 h, 2 h Death of animals from massive
once pulmonary hemorrhage and
edem.'i .
10 min, 10 min Respiration rate decreased
once 77.5%.
10 min 10 min Respiration rate decreased
once 73.7%.
10 min, 10 min, Maximum decrease in respira-
once lory rate was 7A.A%.
10 min, 10 min Respiration rate decreased
once 65.6%.
10 min, 10 min Maximum decrease in respira-
oiice lory rate was 69.6%.
Refeience
iind Hating
Morion et
(1961)
H-IO
Kane and
(1977)
nt ')
~ I I
Kane am)
(1977)
ni i
~ i i
Kane and
(1978)
II- 10
Kane and
(1977)
U-I2
Kane and
(1978)
n- 10
al.
Alarie
Alarie
Alarie
Alarie
Alarie
(continued)
-------
TABLE lll-l ( con I i lined)
Coni|iomxl(s) ami
Concent ralion(s), llumidi ly/
mg/in1 (ppm) Teinperalnre
IICIIO - 5.61
(4.49)
Aero lei ii
- 18.31
(7.96)
IICIIO - 4.30
(3.44)
Ac ro 1 e i n
" 4.00
(1.74)
IICIIO ~ 3.8 ± 0.35
(3.010.28)
IICIIO - 3.8
(.1)
IICIIO ~ 3.50
(2.80)
IICIIO ~ 3. 13
(2.50)
Acrolein ~ 4. 72
(2.05)
Mode of
Exposure
Inhala-
tion
chamber
Inhala-
tion
chamber
Head
only,
2.1-F.
inhal-
alion
chamber
Inhala-
tion
chamber
Trachea 1
cannula
inserted
under
anes-
thesia
Head
only,
2.1-1.
inhala-
tion
chamber
Inhala-
tion
chamber
Duration and Total
Species/Strain/ No. of No. of Frequency of l.englh of
Age/Wefghl Test Animals Controls Exposure Experiment Kffecls
Mice, 4 H 10 min, 10 min Maximum decrease in respira-
Swiss -Webster, once lory rale was 71.3%.
Specific-
Pathogen Free,
20-30 g
Mice, 4 M 10 min 10 min Maximum decrease in respira-
Swiss-Websler, once lory rale was 62.0%.
Specific
Pathogen Free,
20-30 g
Mice, 20 M Served 10 min, 10 min Decrease in respiralory rate
Swiss-Webster, (5 groups as own once of 54%.
Specific of 4 control
Pathogen Free, animals)
20-30 g
Mice, ? M 1 H 10 rain, 10 min Kespiration rate decreased 54%
Swiss -Webster, Controls once vs. 4.2% for controls.
Specific had been
Pathogen Free, aneslhe-
20-30 g tized
only
Mice, 4 H Served 10 min, 10 min Kespi ration rait decreased
Swiss-Webster, as own once 51.5%.
Specific control
Pathogen Free,
20-30 g
Mice, 4 M 10 mill, 10 min Maximum decrease in respi la-
Swiss-Webster , once lory rate was 61.8%.
Specific
Pathogen Free,
20-30 g
Itelen'nce
and Ital injj
Kane and Alarie
(1978)
B-IO
Kane anil Alarie
(1978)
n-io
Kane anil Alarie
(1977)
D-12
Kane anil Alarie
(1977)
U-12
Kane anil Alarie
(1977)
U-12
Kane anil Alarie
(1978)
It- 10
(cont i lined)
-------
TAIII.E 111-1 (continued)
Conipimnd(s) und
CoiuiMit nil ion(s) ,
mg/m1 (ppm)
IICIIO ~ 3.13
(2.50)
Ac ro 1 <• i H
- 1.56
(0.68)
IICIIO -1.89
(1.51)
IICIIO ~ 1.78
(1.42)
At: role in
- 4.30
(1.87)
IICIIO
- 1.54 ± 0.24
(1.23 t 0.19)
IICIIO - 1.63
(1.30)
IICIIO - 1.08
(0.86)
Ac role in
-1.29
(0.56)
Humidity/ Mode of
Temperature Exposure
Inhala-
tion
chamber
Mead
only,
2.1-1.
inhala-
tion
chamber
Inhala-
tion
chamber
Head
only,
2.1-L
inhala-
tion
chamber
Head
only,
2.1-f,
inhala-
t ion
chamber
Inhala-
tion
chamber
Duration and Total
Species/Strain/ No. of No. of Frequency of Length of
Age/Weight Test Animals Controls Exposure Experiment
Mice, 4 M 10 min, 10 min
Swiss-Webster, once
Specific
Pathogen Free,
20-30 g
Mice, 4 M Served 10 min, 10 min
Swiss-Webster, as own once
Specific control
Pathogen Free,
20-30 g
Nice, 4 M 10 nin, 10 min
Swiss-Webster, once
Specific
Pathogen Free,
20-30 g
Mice, 36 M Served 10 min, 10 min
Swiss-Webster, (9 groups as own once
Specific of 4 ani- control
Pathogen Free, mats)
20-30 g
Mice, 4 M Served 10 min, 10 min
Swiss-Webster, as own once
Specific control
Pathogen Free,
20-30 g
Mice, 4 H 10 min, 10 min
Swiss-Webster, once
Speci fie
Pathogen Free,
20-30 g
Ma>
toi
Ret
41,
Na>
lui
l)e<
of
Ret
27
Mai
toi
Effects
Maximum decrease in respira-
tory rale was 52.8%.
Respiration rate decreased
Maximum decrease in respira-
tory was 60.7%.
Decrease in respiratory rate
Respiration rate decreased
Maximum decrease in respira-
tory rate was 41.4%.
Reference
nnd Rating
Kane and Al.n ic
(1978)
H-10
Kane and Al.irie
(1977)
B-12
Kane and Marie
(1978)
11-10
Kane and Alarie
(1977)
n-12
Kane and Alaric
(1977)
fi-12
Kane and Alaiic
(1978)
11-10
(continued)
-------
TABI.K III-l (concluded)
Compound (s) and
Conceit I rat ion(b) ,
mg/iii1 (|)|)m)
IICIIO ~ 0.9
-------
Compound(s) and
Concent ralioii(u),
ing/in3 (|i|)n)
TAW.K UI-2. rllCK--RKI'KATKI) WISE KXI'KKIHKNTAI. KXIUSIiKK I'd K)RNAI,I>KIIYI)K (IICIIO)
Humidity/
Temperature
Mode of
Exposure
Species/Strain/
Age/Weight
No. of
Test Animals
Duration and Total
No. of Frequency of Length of
Controls Exposure Experiment
Effects
Reference
and Haling
IICIIO 200
t-o
IICIIO. 140
IICIIO ~ 16.
(13.4)
IICIIO -12.6
(10.1)
Inliala- Mice,
lion C31I strain
chamber,
623-1,
.r>«J
3 d/wk
~ 2*1 d, Exposures woic slopped alter llorton el al.
II expo- II Ix-cansc of high number of (I'J6I)
sines dealhs--l!> animals died. II- 10
Tracheohronchial i-pi I he I inm
of tlu; lungs of 5 mice that
died had atypical metaplasia
and 7 had sqiiainous-cell meta-
plasia. Of 35 lungs examined,
2 had no changes; 4, basal-eel I
hyperplasia; 8, stratification;
16, sr|iiainous-cell metaplasia;
5, atypical metaplasia, and
0, tumors. Majority of con-
trol animals showed no sig-
nificant changes of lungs.
Inhala-
tion
chamber,
623-1.
Head
only,
2.1-L
inhala-
tion
chamber
Head
only,
2.1-L
inhala-
tion
chamber
Mice,
C3II strain
Nice,
Swiss-Webster,
Specific
Pathogen Free,
20-30 g
Mice,
Swiss-Webster,
Specific
Pathogen Free,
20-30 g
Not given
8 H
Exposed to
0.31 ppm
IICIIO 3 h/d
for 3 d
prior to
this expo-
sure.
8 M
Exposed to
0.31 ppm
IICIIO 3 h/d
for 3 d
prior to
this expo-
sure.
Not 2 h/d
given
Served 10 win,
as own once
control
Served 10 min,
as own once
control
4 d No signs of substantial dis-
tress or (oss of weight.
Morton
(1963)
11-10
et al.
10 min Respiration rale decreased Kane and Alarie
77.8% with no evidence of (l'J77)
prior exposure having caused D-12
sensitizalion when results
from this test and similar
one with no pie-exposure
are compared.
10 min Respiration rale decreased Kane and Alarie
68.4% with no evidence of (1977)
prior exposure having caused B-12
sensiti/ation when results
from this test and similar
one with no pre-exposure
are compared.
(continued)
-------
TAfil.E 111-2 (1:011 tinned)
Compourid(s) arid
Conrriilralion(s) ,
nig/m3 (ppm)
IICIIO ~ 9.88
(7.90)
IICIIO -3.9
(3.1)
IICIIO ~ 3.50
(2.80)
IICIIO -1.89
(1.51)
Hum id i ty/ Mode of
Temperature KxpoBiire
Head
only,
2.1-1.
inhala-
tion
chamber
Mead
only,
2.1-L
inhala-
t i on
chamber
Head
only,
2.1-1
inhala-
tion
chamber
Head
only,
2.1-1.
inhala-
tion
chamber
Species/Si rain/
Age/Weight
Mice,
Swiss-Webster,
Specific
Pathogen Free,
20-30 g
Mice,
Swiss-Webster,
Specific
Pathogen Free,
20-30 g
Mice,
Swiss-Webster,
Specific
Pathogen Free,
20-30 g
Mice,
Swiss-Webster,
Specific
Pathogen Free,
20-30 g
No. of
Test Animals
8 M
Exposed to
0.31 ppm
IICIIO 3 h/d
for 3 d
prior to
this expo-
sure.
4 M
8 M
Exposed to
0.31 ppm
IICIIO 3 h/d
for 3 d
prior to
this expo-
sure.
8 M
Exposed to
0.31 ppm
IICIIO 3 h/d
for 3 d
prior to
III is expo-
sure.
No. of
Conl rols
Served
as own
control
Served
as own
coiilrol
Served
as own
control
Served
as own
control
Duration and Total
Frequency of Length of
Exposure Experiment Effects
10 min, 10 min Inspiration rate decreased
once 66.5% with no evidence of
prior exposure having caused
sensil ization when results
from this test and similar
one with no pre-exposure
arc compared.
3 h/d 4 d The respiration rate de-
creased during the first 10
min from 46% on d 1 to 72%
on d It. Rale i net eased
somewhat over remainder of
exposure period, but recov-
ery was slower each d. On
d 4 respiration rate at end
of 3 h was still 50% less
than control rate.
10 inin, 10 min Kespi ration rale decreased
once 49.4% with no evidence of
prior exposure having caused
sensilization when results
from this test and similar
one with no pre-exposure
are compared.
10 min, 10 min Respiration rale decreased
once 36.8% with no evidence of
prior exposure having caused
sens! tizalion when results
from this lest and similar
one with no pre-exposuie
are compared.
and Rot ing
Kane ami Alarie
(1977)
11-12
Kane and Alarie
(1977)
fl-12
Kane and Alarie
(1977)
11-12
Kane arid Alarie
(1977)
11-12
(continued)
-------
TABLE 111-2 (concluded)
Compound!B) and
Com I'M 1 rat ion(s),
mg/m1 (ppm)
IICIIO ~ 1.6.J
(1.30)
IICIIO -1.3
(1.0)
IICIIO -0.69
(0.55)
Humidity/ Mode of
Temperature Exposure
Head
only,
2.1-t
inhala-
tion
chamber
Head
only,
2.1-L
inha la-
lion
chamber
Head
only,
2.1-L
inhala-
tion
chamber
Species/Strain/
Ago/Weight
Mice,
Swiss-Webster,
Specific
Pathogen Free,
20-30 g
Mice,
Swiss-Wehster,
Specific
Pathogen Free,
20-30 g
Hice,
Swiss-Webster,
Specific
Pathogen Free,
20-30 g
No. of
Test Animals
B H
Exposed to
0.31 ppm
IICIIO 3 h/d
for 3 d
prior to
this expo-
sure.
4 H
8 M
Exposed to
0.31 ppm
IICIIO 3 li/
-------
TABI.K HI-'J. HICF.--CHKONIC KXI'KIWIKNI'AI. I'iXI'O.SIIKK TO KOKHAUJMIIYDK (IICIIO)
Compound(s) and
Concentration(s),
mg/iii3
Iliiniiility/
Temperature
Node of
Kxposure
Species/Strain/
Age/Weight
Duration anil Total
No. of No. of Frequency of Length of
Test Animals Controls Kxpo.sure Kxperimenl
Effects
Reference
and Hating
IICIIO 100
Inhal-
ation
chamber,
623-L
Mice,
C3II strain
60
IICIIO 50, then
raised to 150
Inhal-
ation
chamber,
623-L
Mice,
C3II strain
60
36 (sec-
ond phase)
59 I h/il, .15 wk Animals tolerated exposure Morton el al.
3 d/wk with avg. vl. rising nor- (1963)
in.illy. The Iracheohronchial 11-10
epithclia of 35 lung were
examined and 4 had no changes;
10, hasal-cel) hypcrplasia;
l/i, slrutification; 6,
sqnantoiiK-cell metaplasia; and
0, atypical metaplasia or tu-
mors. Kxtens ion of epithelial
changeii into major hronchi wns
inlrei|uent and none in the
smaller hronchi. Majority of
control animals showed no sig-
nificant changes of lungs.
59 1 h/d, 35 wk at Animals tolerated exposure Morton ct al.
3 d/wk lower wilh avg. wt. rising nor- (1963)
level, mally. Some basal-cell hy- 11-10
33 wk at perplasia in 6 and stratifi-
higher cation in 9 tradieoliroiulii.il
level. cpillielia of 23 lungs exam-
ined after first 35 wk of
exposure. During second ex-
posure period, 15 animals
died, lint none had squamous-
cell tumors in lungs. The
changes in epithelium began
extending into the major
bronchi during the second
phase. Majority of control
animals showed no significant
changes of lungs.
(continued)
-------
TABLE 111-3 (ronelulled)
CO
O
Compound ( » ) and
Concent rat ion(s),
ing/in1 (ppm)
IICIIO ~ 19
(15)*
IICIIO -7.5
(6)
IICIIO 2.5
(2)
Duration and Total
Humidity/ Mode of Species/Strain/ No. of No. of Frequency of Length of
Temperature Exposure Age/Weight Test Animals Controls Exposure Experiment ' Effects
45 i 5X Ilinners- Nice, 120 H 120 H 6 h/d 24 mo No tumors at 18 mo but two of
20-22°C type in- B6C3FI 120 F 120 F 5 d/wk 85 had developed sqiiamous
inhal- 7 7 cell carcinomas of the nasal
tiori turbtnates after 24 mo. Only
chamber spontaneous levels of cancer
12 air were found in other organs
chauges/h and tissues.
45 t 5% Ilinners- Nice, 120 H 120 M 6 h/d 24 no No tumors.
20-22°C type U6C3FI 120 F 120 F 5 d/wk
inhal- 7 ?
tion
chamber
12 air
changes/h
45 i 5X Ilinners- Mice, 120 M 120 M 6 h/d 24 mo No tumors.
20-22°C type B6C3F1 120 F 120 F 5 d/wk
inhal- 7 7
lion
chamber
12 air
changes/h
Reference
and Kali UK
NIOSII/OSIIA
(1980)
C--
Swenlwrg i.'l al .
(I960)
B-15
Set ikolf and
Hammond
(1981)
C--
Anonyinons (1981)
NIOSII/OSIIA
(1980)
C--
Swenherg el al .
(1980)
li-15
Sel ikotf and
Hammond
(I'JIil)
C--
NIOSII/OSIIA
(1980)
C--
Swenl«:rg <•! al .
(1980)
B-15
Sclikolf and
Hammond
(1981)
Al the CUT Conference on November 20-21, 1980, Dr. Craig Barrow and Dr. James Swenlicrg of CUT indicated that "because of a difference in
behavioral pattern, the effective exposure in the mice was about bait that for rats. Thus, the cancer incidence in mice at 15 ppm ran
be considered comparable to that of rats at 6 ppm." (CI'SC, 1981).
-------
Compound(s) ami
Concent rut ion(s),
mg/mj (ppm)
TAIIl.t: II1-4. HAMSTERS—ACUTE F.XI'KKINKNTAI. KXI'OSIMK TO FOKHAI.DIillYDK (IICIIO)
Duration and Total
Frequency of Length of
Exposure Experiment
Humidity/
Temperature
Mode of
Exposure
Species/Strain/
Ago/Weight
No. of
Test Animals
No. of
Controls
Effects
Referente
.mil li.il ing
IICIIO -712
(570)
Inhata- Hamsters,
lion Syrian golden,
chamber, avg. 100 g
~ 1 ft3
8 « & F
None
IICIIO ~ 525
(420)
Carhon 21
Inhala-
tion
chamber,
~ 1 ft3
Hamsters,
Syrian golden,
avg. 100 g
8 H & F
12 H & F
Exposed
to 1,032
nig C/m3
alone.
Animals
sacri-
f iced
and ex-
amined
6, 12,
24, and
48 h
after
begin-
ning
expo-
sure.
4 li,
once
4 h,
once
6, 12,
24, 48,
and 96 li
jifter be-
ginning,
2 animals
were sac-
ri fired.
48 lij,
6, 12,
24, and
48 h
after be-
ginning,
2 animals
were sac-
rificed.
No recruitment of polyiuorpho- Kilhtirn ;iml
nuclear leukocytes to airway McKenzie
cells. Cytotoxic effects on (1978)
airway cells; 34-100% of tra- 11-11
chea cells and 5% of bronchial
cells were exfoliated.
Recruitment of polymorpho- Killmrn and
nuclear leukocytes to airway McKeii/.ie
cells; no recruitment in con- (1978)
trols. Limited cyloloxic el- B-11
feet on trachea cells; 7%
were exfoliated.
(continued)
-------
TAIII.E II1-4 (continued)
Coiii|>oui>il(ti) ami
Com I'MlniLloiifu),
ing/m3 (ppm)
IIC1IO ~ 250-113
(200-250)
Carbon 700
(Carhou coaled
with IICIIO.)
IICIIO ~ 258
(206)
Carbon 567
(Carbon coated
will) IICIIO.)
Humidity/ Mode of Species/Strain/ No. of No. of
Temperature Exposure Age/Weight Tent Animals Controls
Inhala- Hamsters, 6 H 6 F 12 H & F
tion Syrian golden,
chamber, avg. 100 g Exposed
~ 1 ft1 to 1,032
mg C/m1
alone.
An 1 ma 1 s
sacri-
riflccd
and ex-
amined
6, 12,
24, and
48 h
alter
begin-
ning
expo-
sure.
Inhala- Hamsters, 7 M & F 12 M & f
lion Syrian golden,
chamber, avg. 100 g Exposed
~ 1 ft' to 1,032
nig C/m1
a 1 one .
Animals
sacri-
ficed
and ex-
amined
6, 12,
24, and
48 h
after
begin-
ning
expo-
sure.
Dnr.it ion and Total
Frequency of Length of
Exposure Experiment
4 h, 24 h;
once
6, 12.
24, and
48 h
after he-
ginning,
2 animals
were sac-
rificed.
4 h, 48 h;
once
6, 12,
24, and
48 h
after be-
ginning,
1-2 ani-
mals were
sacri 1 iced.
Effects
Recruitment of polymorplio-
nuclear leukocytes to airway
cells, no recruitment In con-
trols. Cytotoxic effect to
airway cells, especially ex-
foliation of traclical and
bronchial cells.
llecrui Intent of polymorpho-
nuclear leukocytes to airway
cells; no recruitment in con-
trols. Cytotoxic effects to
airway cells; 75-100% of
tracheal cells and £ 25% of
bronchial cells were exfoli-
ated.
Reference
Ki I burn •ind
NcKrnzie
(I'J7H)
I)-11
Ki I limn and
McKrnzi c
(1978)
I)-11
(continued)
-------
TABLE II1-4 (continued)
Compound (s) and
Coiicenlral fon(s), Humidity/ Mode of Species/Strain/ No. of No. of
mg/m} (p|>m) Temperature Exposure Age/Weight Test Animals Con I ro Is
11CIIO 12.5 Inhala- Syrian golden ? H ? M
(10) alien hamsters
chamber
IICIKI ~ 8 Inhala- Hamsters, 12 M & V None
(6) tion Syrian golden,
chamber, avg. 100 g
~ 1 ft1
to
OJ
HCIIO ~ 8 Inhala- Hamsters, 12 M & F 12 M & F
(6) tion Syrian golden,
Car lion 805 chamber, avg. 100 g Exposed
(Carbon coated ~ 1 ft1 to 1,032
with HCIIO.) rag C/m3
alone.
Animals
sacri-
ficed
and ex-
amined
6, 12,
24, and
48 b
after
begin-
ning
expo-
sure.
Duration and Total
Frequency of Length of
Exposure F.xper intent
5 h 4 d
4 h, 96 h;
once
6, 12,
24, 48
and 96
h after
beg i n-
'"g, 2
animals
were
sacri-
ficed.
4 h, 62 d.
once
1, 2, 4,
8, 16.
32, and
64 d af-
ter begin-
ning, 1-
2 animals
were sac-
rificed.
Reference
Effects and KaliiiK
No increase in 311-thymidine Dal boy (1981)
incorporation (measuring cell 1)12
proliferation) in nasal
turbinates or tracheal
epithelium, indicating little
cell damage and subsequent
repa ir.
No recruitment of polymorpho- Kilburn and
nuclear leukocytes to airway McKcnzic
cells. Cytotoxic effects on (1978)
airway cells; ~ 20% of tra- fl- 1 1
cheat and bronchial cells were
exfoliated.
Recruitment of polymorpho- Kilburn and
nuclear leukocytes to airway He Kenz it-
cells, no recruitment in con- (1978)
trols. Cytotoxic effect to B- 1 1
airway cells.; 18-36% of tra-
cheal cells but only 2% of
bronchial cells were exfoliated.
(continued)
-------
TAI1I.E 111-4 (concluded)
CoflipouiidCs) anil
Concent rat ion (s) , Humidity/ Mode of Species/Strain/
rag/in1 (ppm) Tempera 1 u re Exposure Ago/We iglil
HCIIQ ~ 4 Inliala- Hamsters,
(3) lion Syrian golden,
Car hon 131 chamber, avg. 100 g
~ 1 ft1
No. of No. of
Tesl Animals Controls
6 M & F 12 H & F
Exposed
to 1,0)2
mg C/m1
alone.
Ani mills
sacri-
ficed
and ex-
amined
6, 12,
24, and
48 li
after
begin-
ning
expo-
sine.
Duration and Total
Frequency of Length of
Exposure Experiment
4 h, 48 h;
once
6, 12,
24, and
48 h af-
ter begin-
ning, 1-
2 animals
were sac-
rificed.
Reference
Effects .mil K.it in);
Kecruilment of polymorpho- Kilbnin an
-------
TABLE II1-5. IIAMSTF.RS--REI'F.ATEI> DOSE AND CHRONIC EXPERIMENTAL EXPOSURE TO FORMALDEHYDE (IIC1IO)
Coinpound(s) and
Concent ratinn(s) ,
mg/m1 (ppm)
HCIIO ~ 312.5
(250)
IICHO 62.5
(50)
IICHO 31.2
(25)
IICHO 12.5
(10)
IICHO 3.75
(3)
IICHO - 3
(2)
Humidity/ Mode of
Temperature Exposure
Inhala-
tion
chamber
Inhala-
tion
chamber
Cages in
a 1.5 m3
inhala-
tion
chamber
Inhala-
tion
lion
chaniber,
~ 1 ft5
Species/Strain/ No. of
Age/Weight Test Animals
Hamsters, 34
Syrian golden,
3 mo
Syrian golden ? M
hamsters
Syrian golden 7 M
hamsters
Syrian golden 88 H
hamsters
Hamsters 10
Syrian golden, given
avg. 100 g
Duration and
No. of Frequency of
Controls Exposure
5 1 li/d
1-15 expo-
sures
132 H once/week
17 wk
? H 5 h, on
days I
and 7
132 N 5 d/wk,
"lifetime"
(10-26 mo)
10 22/h/d
7 d/wk
6 mo
given every 3rd
d for 6-
10 expos-
Total
Length of
Experiment
5 animals
killed 2
d after
1, 2, 5,
and !5lh
exposure ,
3 animals
killed
1st, 2nd,
and 6th
wk after
last ex-
posure .
17 wk
11 d
"Lifetime"
(10-26
mo)
6 mo
Effects
Ilistologic and cytologic
changes in tracheobronchial
epithelium such as the
appearance of very pleomor-
phic, large, poorly differ-
entiated squamous cells with
abnormal poly lobulated nuclei.
All changes were reversible as
no abnormalities were observed
in animals killed 2 or 6 wk
after exposure (Milled.
No toxicity to nasal
epithelium.
Increased 311-thymidine in-
corporation (measuring cell
proliferation) for several
days, indicating cell damage
and repair; greater in nasal
tiirbinutcs than trachea. Less
incorporation after second ex-
posure, indicating possible
adaptat ion.
Decreased survival time. No
resfkiratory tract tumors.
Little evidence of toxicity
in nasal epithelium.
No adverse effects noted during
exposure .
Iracjieal cells and changes
in epithelium but no increase
in |>olyuiorphonuclear leuko-
cytes in airway cells over
conl rols .
Reference
and Rating
Schreiber
et al.
(1979)
C-8
Dalbey (1981)
B-12
Ualbey (1981)
B-12
Dalbey (1981)
B-12
Clary (1980)
B--
HiKenzie
(1978)
B-ll
(conlinued)
-------
TAItl.E 111-5 (concluded)
u>
ON
Compound(s) and Uiirution and Total
Concent nil iou(a), Humidity/ Mode of Species/Strain/ No. of No. of Frequency of Length of
mg/iii1 (|)|>m) Temperature Exposure Age/Weight Test Animals Controls Exposure Experiment
Effects
Reference
,-ind K.I I iiifi
IICIIO 1.25
(I)
IICIIO 0.25
(0.2)
inhala- Hamsters
lion
Inhala- llanisters
tion
10
10
10
10
22 h/d
7 d/wk
22 h/d
7 d/wk
6 mo No adverse effects noted during Clary (l"80)
exposure or on pathological B--
cvaluation.
6 no No adverse eflefts noted while Clary (1
-------
TABLE 111-6. KATS--ACUTE EXPERIMENTAL EXI'OSUKK TO FOKNAI.DEIIYDK (IICIIO)
Coui|>oiiii
-------
TAIII.K I 11-6 (continued)
C(ini|ii>nn(l(s) anil
Concent rution(s),
rog/m1 (ppm)
IICIIO 18
IICIIO -12.5
(ID)
Humidity/
Temperature
Node of
Kxposurc
Inhala-
tion
chamber
Inhala-
tion
chamber
Species/Strain/ No. of
Age/Weight Test Animals
Albino 10-12 N
rats,
180-240 g
Rats, 10 M
Spragiie-Uawley,
I2-I? wk
Dm at ion and
No. of Frequency of
Controls Kxposure
10-12 M Not given
'1 ft 24 h,
once
Total
Length of
Kxperiment
Not given
24 h
intact
exposure;
Klfects
The acceptable limit as to
general toxic effect as mea-
sured by reduction of Oj up-
take.
I'll 1 iinmary alveolar macropliage
cells were collected from rats
and cultured, then challenged
Reference
and Rat tu
Nagornyi i
( WJ)
11-9
Kalz anil i
(1977)
C-7
I.as kin
cells--
7 d in
culture
OJ
00
IICIIO 5
Inhal-
ation
chamber
Rats
20 ?
20 7 i, h 1
with polystyrene latex spheres.
Cells from exposed rats ini-
tially had increased phagocytic
activity but were similar to
controls in total sphere uptake.
Cells exhibited significantly
increased adhesion to culture
surface compared to controls.
Decreased blood pressure, iieu-
trophilia (with toxic gran-
ulations id the neutroplii Is),
shift to the left of the dif-
ferential white blood cell
counts, and eosinophiIia (ex-
pressed most on the following
days with the appearance of
juvenile forms and hi nucleated
lymphocytes) were observed im-
mediately after exposure. Signs
of minor irritation of the limgs,
spleen, and marrow.
Zaeva et
(1968)
H-5
al.
(continued)
-------
TAIIIi; ill-6 (concluded)
Compound (s) and
Cnncentration(s) , Humidity/
mg/m3 (ppm) Temperature
IICIIO ~ 0.6-3.2
(0.5-2.5)
IICIIO ~ 0.6-2.5
(0.5-2.0)
IICIIO I -2
Mode of Species/Strain/
Exposure Age/Weight
Nose Rats,
mask, Sprague-Dawley,
breath- 250-400 g
ing
through
cannula
in tra-
chea,
second
cannula
allowed
IICIIO to
be circu-
lated
through
nasal
cavity.
Nose Rats,--
mask, Sprague-Dawley,
breath- 250-400 g
i»g
through
cannula
in tra-
chea ,
second
cannula
allowed
IICIIO to
be circu-
lated
through
nasal
cavity.
Julia 1- Rats
ation
Duration and Total
No. of No. of Frequency of Length of
Test Animals Controls Exposure Experiment
3 H Served 2 min/ S 2.3 h
as own exposure,
control 4-7 uiin
between
exposures,
~ 16 expo-
sures for
3 animals.
10 M Served 1 h/expo- 2 4 h *
as own sure, test 1 h in
control between air
exposures
with amyl
alcohol
to test
nerve re-
sponse .
Up to 4
1-h expo-
sures with
some of the
test animals.
4 It
Reference
Effects and Rating
Decrease in nasal sensory re- Kulle and Copper
spouse with increased concen- (19/5)
tration. C-ll
Exposure to IICIIO consistently Kulle and Copper
produced significant depres- (1975)
siori of amyl alcohol response C-ll
of nasal nerves. Depression
of nasal sensory response pro-
gressed with increased IICIIO ex-
posure. Partial recovery of
sensory response upon exposure
to air only for 1 h .
No functional or organic Zaeva et a).
changes detected. (1968)
11-5
-------
TABLE III-/. RATS—RKI'KATEH IK)HK KXI'KKIHKNTAL F.'XI'OSIIKK TO MKHAI.IIKMVWK (IIOIIO)
('ompouml(K) dud
Com cut rat ion(s),
iiiK/iii1 (ppm)
Humidity/
Temperature
Mode of
Exposure
Species/Strain/
Age/Weight
No. of
Test AuimaIn
Dur.it ion anil total
No. of Frequency of Length of
Controls Exposure Experiment
Effects
I in)!
IICIIO 50-100
IICIIO 20
Not given
Inhal-
ation
Inliala- Albino rats,
lion 130-140 g
chamber
20 M
20 M
0 «l; un-
clear if
exposure
was ron-
tiniions or
intermittent
3 h/%
(control level was I mg%).
8 wk Group I showed aggressiveness,
weighed 80% less than Group
2, and showed a significant
increase in the duration of
alcohol and hexobarbital
narcosis. The protective
effect of lipoamide appeared
to be due to its activation
of liver microsomal enzymes
participating in the oxidative
deslriict ion of these narcotics.
Group I also had a 6 t 0.8%
lower total serum protein con-
tent, lower albumin, higher
gnnni.i-globiil ins , and lower
Kcrum Sll groups. Group I rats
showed dystrophic and necrotic
changes in the liver cells
that were not apparent in the
rats protected by Iipoamide.
Lower levels of general and
reduced ascorbic acid and higher
levels of its oxidized form were
observed in the livers of the
unprotected rats.
The 1979 abstract may indicate
a different study: rats protec-
ted by !)2% protein in the diet
compared to those receiving 18%
protein showed normal protein
me. t a bo I i.SHI. This abstract also
does not give the frequency of
exposures.
(1968)
11-5
(ioloshchapov
and Agninovski i
(1976)
(Ml
Golosbfhapov
(1979)
C-5
-------
TABLE [11-7 (cont iiincd)
Compound(s) am)
Concent ralion(s),
mg/iii3
Iliiuhdi Ly/
Tcni|ie ratnre
Mode of
Exposure
Species/Strain/
Age/Weight
Duration and Tola)
No. of No. of Frequency of l.i'nglli of
Test Animals Controls Exposure Experiment
Ef fee-Is
Reference
and li.'iling
IICIIO 15
IICIIO 10.1 ± 2
(8.07 ± 1.62)
60%
2J°C
Inhala-
tion
IICIIO 7
IICIIO
6.0 ±
0.3
Albino rats,
no specific
strain
Kats,
Specific
Pathogenic
Free,
32-40 d
M; No.
not given
25 H
M; No. Continuous
not given
50 I)
25 H
Continuous
2 mo
Albino rats,
no specific
strain
Inhala- Albino
lion rats,
chamber 200-230 g
(non-pregnant)
M; No.
not given
8-32 F
M; No. Continuous
not given
8-32 F 4 h/d
> 168 h
(7 d)
20 d
The time until the increase in Oslapovich
leukocyte no. was 129% that of (1975)
controls was 15 h. Time until C-6
decrease in cholinesterase act-
ivity was 72% that of con-
trols was 50 h.
Sneezing and nasal discharge Duhicuil et
from 1st day of exposure, yel- (1976)
low coloration of fur, anil 2 It-10
had serous discharge in eyes.
Significantly lower body weight
and relative liver weight than
controls. Increased pulmonary
niacrophages, lymphocytes, mid
polynnclear cells. Reduced
phagocytic activity, which sug-
gested increase in number of
small-sized inacrophages.
The lime until the increase in Ustapovich
leukocyte no. was 132% that of (1975)
controls was 60 h. Time until C-6
decrease in choliuesterase activ-
ity was 70% that of controls
was 168 h.
Changes reported in kidney
functions--decrease in daily
diuresis and concentration
of chlorides in urine and in-
crease in concentration of
albumin in urine. Change in
liver function indicated by
decrease in excretion of
hippnric acid in urine after
a sodium benzoale load. No
effects on weight, nervous
system function, or respir-
at ion.
Sanolski i
(1976)
11-8
el al.
(continued)
-------
TAIll.lv 111-7 (lonlinue.l)
Compound(s) and
(loin cnl rat iun(u) ,
rag/in' (ppro)
IICIIO
6.0 1 0.3
IICIIO ~ 5.7 ± 0.7
(4.55 1 0.53)
IICIIO
5 t 0.2
Humid ity/ Mode of
Temperature Exposure
Inlia la-
lion
chamber
601 Inhala-
23°C lion
chamber
Inhala-
tion
chamber
Species/Strain/ No. of No. of
Age/Weight Teat Animals Controls
Albino 8-32 ¥ 8-32 ¥
rats,
200-230 g
(pregnant)
Rats, 25 M 25 H
Specific
Pathogen
Free,
32-10 d
Rats -19 F -19 F
(pregnant)
Durat ion .mil Total
Frequency of Length at
Exposure Experiment
4 l./d 20 (1
Continuous 1.5 mo
4 li/d 19 d
for 19 il for 15
rats;
others
through
Ue livery
and growth
of off-
' spring
Effects
Decrease in the concent rat ion
of hemoglobin in blood was 1 ho
only reported effect. No el-
fccls on kidney function,
weight, or respiration.
Body weight slightly lower
than controls, also yellow
coloration of fur beginning
from d 20.
Overall toxic effects observed
were a lowering of the thresh-
old of neuromuscular excitabil-
ity, of recta) temperature, of
hemoglobin in blood and a
change in spontaneous mobility
of post-experimental animals.
Examination of females and fet-
uses at 20lli d of pregnancy
showed no deformities, but
slightly higher preimplantalion
mortality of embryos. Develop-
ment of offspring was normal ex-
Reference
and Kilting
Sanolskii el a
(1976)
B-8
Ihihreuil i'l al
(1976)
B-IO
Sheveleva
(1971)
D-ll
cepl for a decrease in spontaneous
moliility at one mo of age, which
was also observed in female off-
spring at two mo. Some changes
in peripheral blood compos it ion
were reported at 2 mo.*
The Formaldehyde Panel (Griesemcr ct al., 1980) felt the no. of animal per dose level and no. of dose levels were inadequate and skeletal and soft
tissue analyses were missing. Still, the Panel felt there were indications IICIIO affected reproductive potential.
(continued)
-------
TABLE 111-7 (continued)
Compound(s) arid
Concentration(s),
nig/ui1 (ppm)
Humidity/
Temperature
Mode of
Exposure
Species/Strain/
Age/Weight
Duration anil Tola!
No. of Ho. of Frequency of Length of
Test Animals Controls Exposure Experiment
Effects
Reference
and Rating
IICIIO
4.6 ± 0.4
IICIIO 3.9
50% Inhala- Rats, 15 M&F Not Continuous
77 ± 2°F tion Long Evans given for 90 d
chamber and Spragne- (< 2.2%
(modi- Dawley down time)
fled
Rochester-
type)
Special Albino 50 M 50 M Continuous
I m3 rats
chambers 130-
240 g
90 d One death; others showed no Coon et al.
signs of illness or toxicity. (1970)
llematologic values were normal, B-12
hearts and kidneys showed fo-
cal chronic inflammatory changes
and lungs showed varying degrees
of interstitial inflamination.
60 d The trend toward increasing Tiunov and
6-10 rats DNA-ase activity of Ihe liver Ivanova
sacrificed seen at 0.1 and 0.7 ing HCIIO/ni1 (1976)
every continued, but the decrease B-8)
30 d. in spleen DNA-ase seen al these
levels became a sharp increase
at 3.9 ing/ui3. An increase in
tissue DNA-ase agrees with re-
ports of a decrease in tissue
DNA seen in IICIIO poisoning of
rats.
(cont ilined)
-------
iAItl.K III-? (continued)
Coiupound(s) and
Coiiccnlration(s) ,
rag/m J (ppm)
IICIIO 3
Humidity/ Mode of
Temperature Exposure
100-L
chambers;
30 L air
+ IICIIO
per min
Species/Strain/ No. of No. of
Age/Weight Tent Animals Controls
Albino 15 M 15 H
rats
Duration and
Frequency of
Exposure
Continuous
(?) for 3 mo
Tula)
Length of
Experiment
3 mo
Effects
Definite structural ami cy to-
chemical shifts compared to
the amygdaloid complexes of
control rats are described.
The effects on the olfactory
Reference
and Rating
Bonashcvskaya
(1973)
ll-fi
IICIIO
3.0 t 0.064
Inhala-
tion
chamber;
100-L
with air
flow of
30 L/min
Albino
rats
25
analyzer are ascribed to tlie
action of absorbed IICIIO raUier
than to toxic irritation of
the receptor regions.
The relation of the clironaxy
of the muscles-antagonists had
become distorted by the end of
the 2nd wk of poisoning. The
distinct shortening of the
chrouaxy of the extensors was
preserved until the end of
poisoning.
Significant lowering of choli-
neslerase activity occurred.
25 M Continuous 3 «o * No effect on behavior or weight
15-d changes of animals. From end
recovery of 2nd wk chronaxial ratio of
period antagonistic muscles was in-
verted. Significant change
in cliol inesterase activity.
In the lungs, a proliferation
of lymphohisliocytic elements
in the interalveolar walls and
in the pcribronchial and peri-
vascular spaces, against a back-
ground of moderate hyperemin.
Alveophages occurred in the1 al-
veolar lumiiii. l)esi]iianiation of
the bronchial epithelium. Mild
cytological and cytochemical al-
terations in the liver, kidneys,
anil brain. Adaptive responses
from thyroid and adrenals.
Fel '(linon and
liunaslii'vsk.iy.i
(1971)
B-10
(continued)
-------
TAUI.E 111-7 (continued)
Compound(s) and
Concent rat iori(s),
.nig /in3 (pun)
IICIIO ~2±0.4
(1.60 ± 0.3)
IICIIO
2
IICIIO 1.7 ± 0.3
(1.36 ± 0.20)
Acrolciu - 1. 1 t 0
(0.48 ± 0.12)
Total aldehydes
calcd. as IICIIO
~ 22. 1 ± 0.8
(17.7 ± 0.6)
CO (< 20)
Part iculates
8.0 i 0.6
IICIIO ~ 1.7 t 0.3
(1.36 ± 0.20)
Acrolein ~ 1 . 1 ± 0.
(0.48 ± 0.12)
Total aldehyde
calcd. as IICIIO
-22.1 i 0.8
(17.7 ± 0.6)
CO (S 20)
('articulates 8.0 ±
Humidity/ Mode of
Temperature Exposure
60% Iiiliala-
23°C tion
chamber
Inhala-
tion
.3 chamber
Inhala-
tion
. 3 chamber
0.6
Duration and
Species/Strain/ No. of No. of Frequency of
Age/Weight Test Animals Controls Exposure
Rats, 25 H 25 M Continuous
Specific
Pathogen
Free,
32-40 d
Albino rats, M M Continuous
no specific No. No.
strain not not
given given
Rats, 20 M 20 M 6 d,
Wistar, 5 d/wfc
240 ± 22 g
Rats, 20 M 20 M 6 li,
Wistar, 5 d/wk
240 ± 22 g
Total
Length of
Experiment Effects
3 mo No effect other than progres-
sive yellowing of fur.
i 1,758 h The time until the increase in
(73.25 d) leukocyte number was 133% that
of controls was 456 h. Time un-
til decrease in choliuesterase
activity was 72% that of con-
trols was 1,758 h.
5 wk Animals were inactive during
exposure period, preening in-
creased, and fur became dis-
colored. After exposures,
animals were killed and brains
analyzed. RNA and microsomal
superoxide dismutase were sig-
nificantly increased. Gluta-
thione and lysosomal acid pro-
teinase activity and glycosyla-
tion of protein in vitro were
unchanged. NADPII-diaphorase
activity was decreased signi-
ficantly.
3 wk Same effects as after 5 wk
except RNA and microsomal
superoxide dismutase activ-
ity were unchanged.
Reference
and Rating
Dutiroiii 1 el al
(1976)
11-10
Oslapovi cli
(1975)
C-6
Zitting and
.S.ivcil.j iru-n
( 1979)
C-10
7.i U ing and
Savola inen
(1979)
C-IO
(continued)
-------
TABLE 111-7 (continued)
<:c>1ll|HPCIIul(s) itlld
Concent nition(s) , Humidity/
nig/in3 (|>|>iii) Temperature
IICIIO ~ 1.7 t 0.3
(1.36 i 0.20)
Acroleln ~ I.I ±0.1
(0.48 i 0. 12)
To I ill a I iteliy ite
caitd. as IICIIO
~ 22.1 t 0.8
(17.7 1 0.6)
CO (S 20)
Participates 8.0 i 0.6
IICIIO 1
IICIIO
1.0 i 0.03
Mode of Species/Strain/
Exposure Age/Wei glil
Inliala- Kals,
tion Wistar,
chamber 240 i 22 g
100*1. Albino rats
Chambers ;
30 !. air
+ IICIIO
per mill
1 filial a- Albino
tion rats
chamber.
100 I
with
air flow
of 30 !./
mill
Duration and Total
No. of No. of Frequency of Length of
Test Animals Controls Exposure Kxper intent
20 H 20 H 6 h, 2 wk
5 d/wk
15 M IS H Continuous 3 no
(?) for 3 mo Not
stated
how long
after
end of
poison ing
the rats
were
killed
by decapi-
tation
25 M 25 H Continuous 3 mo
+ 15-d
recovery
period
Reference
Effects and Hal ing
Same effects as after 5 wk Zilting ami
except microsoinal superoxide Savolaincn
disinntase Activity unchanged. (1979)
C-10
A disturbance in the normal re- Ronashcvsk.iya
lation of the chronaxy of tin- (1973)
muscles-antagonists was noted li-8
at the end of 2 mo.
This parameter of poisoning
did not attain the original
level even after cessation
of poisoning. No statistical
change in chol inesterase
activity.
No effect on behavior or weight Kc 1 ' ilui.in and
changes of animals. £nd of Hun.islicvsk.iyM
2nd mo, chronaxial ratio of (1971)
antagonistic muscles became It- 10
altered, recovery by ISth d.
In the lungs, a prolifer-
ation of lyniplioliistiocylic
elements in the intcr.il veolar
walls and in the pcritironchtal
and pcrivascutar spaces, against
a background of moderate hyper-
emia. Alveopliages occurred in
the alveolar liunini. Desquain-
alion of the bronchial epithel-
ium. Mild cytological anil cy-
to( Item icjil alterations in the
liver, kidneys and braid.
Adaptive responses from thyroid
and adrenals.
(i out iiincil)
-------
Compound(s) and
Coiicenlraljon(s),
ing/in1 (|>pm)
Humidity/
TemperaIure
Mode of
Exposure
Species/Strain/
Age/Weiglil
TABLE II1-7 (continue.!)
Duration and Total
No. of No. of Kre<|iiency of Length of
Test Animals Controls Exposure Experiment
Effects
Kef creni <•
and Hal ing
IICIIO 1.0
Inhala-
tion
chamber
AI hi no
rats
10-12 V 10-12 F Continuous ~ 8 wk Significant decrease in ascor- I'ushki 11,1 and
20 d; pre- liic acid in whole fetus, in fe- Gofmeklcr
mating mule's liver, slight decrease (I'ldHj
III rough in placenta. Significant in- l)-6
pregnancy crea.se in nucleic acids in hold Golmekler et .1
female's and fetus' liver. (1%K)
Significant decrease in UNA in 0-6
female's and fetus' liver. (iufmekler
Mean duration of pregnancy (1%8)
(irolonged 14.5%. Avg. no. of l)-5
fetuses B.6 compared to 11.3 Cofmekler and
in controls. Significant de- lionashevskaya
crease in fetal lung and liver (196'J)
wl. ; significant increase in l)-5
thymus, adrenals, and kidney
wt. No external deformities,
no inhibition of development
of hody systems, no macro-
scopic structural alterations
in fetuses. Ilistocheinical
changes in fetuses included re-
duced glycogen content in the
myocardium, acciumilal ion of
matter with a positive reaction
to Schiff's reagent in the kid-
neys, and the presence of iron
in Kupffer's cells. Some fetuses
exhibited involution of lymplioid
tissue indicating enhanced produc-
tion ol corlicosteroid hormones in
stress reactions, mild liypert rophy
of Kupffer's cells, and numerous
extramedullary myclopoiclic centers
in I he liver."
The Formaldehyde Panel (Griesemer et a!., I960) did not support the conclusions ol Uofmekler el al. (1968) (hat IICIIO significantly inhihiled I he uyntheuiu
of nucleic acid; they also point out the data do not support reported avg. no. of fetuses/I itter; different articles give different nos. of lemales
and fetuses.
(cont i lined)
-------
TAIU.E 111-7 (continued)
Compound ( s ) and
Concentral lon(s) , Humidity/
mg/ra1 (ppm) Temperature
IICIIO 0.7
IICIIO S 0.635
CO 5 5
C02 S 0.005 vol. X
Benzene £ 20 for
group 1 but 0.06-0.8
by day 10; 1.2-5 for
Group 2. Concentra-
tions were unchanged
when fresh daily poly-
mer was used but de-
creased when the same
portion of polymer
wan used throughout
the test
Hode of Species/Strain/
Exposure Age/Weight
Special Albino
1 Hi1 rats,
chambers 130-240 g
Gases Albino rats,
were 160-270 g
evolved
from the
heating
of poly
(me thy 1-
phenyl-
siloxane)
at 90°C
in a 100- 1.
chambe r
using either
fresh daily
100 ml. por-
tions or the
same 100 nl.
portion of
the po 1 ymo r .
Air stream
at It L/min
No. of No. of
Test Animals Controls
50 M 50 H
10 f each 10 F
Group 1
(same portion
of polymer)
Group 2
(fresh daily
polymer)
Duration and Total
Frequency of Length of
Exposure Experiment
Continuous 60 d
(6-10
rats
sacri-
ficed
every
30 d)
4 h/d, i 2 mo
5 dM,
2 mo
Effects
UNA-ase activity of the liver
increased and of the spleen
decreased. The effects were
greater than those seen at
0.1 nig HCIIU/m1.
No significant differences in
general condition, summation
threshold, 02 consumption,
morphological condition of the
blood, and growth dynamics be-
tween the test animals and the
controls.
Reference
and Raling
Tiiinov and Ivnnova
(1976)
11-8
DatuI in c( .il .
(1972)
0-9
(cunt limed)
-------
Coinponnd(s) and
Concentration(s),
mg/iii1 (ppm)
TABLE 111-7 (conlilined)
Ilinniilily/
Temperature
Mode of
Exposure
Species/Strain/
Age/Wei glit
Duration anil Tol.il
No. of No. of l"re(|iieiicy of Length of
Test Animals Controls Kx|>o*sure Experiment
Kfl'et-ls
lielei em i'
.'Hid It.11 ing
IICIIO
0.5 ±
0.02
IICIIO
0.4 1
0.02
IICIIO
0.4 ± 0.02
IICIIO 0.2
+
Plieuol 0.5
+
oilier resin
dccomposition
products
Inhala-
tion
chamber
Rats
(pregnant)
~ 19 r'
~ 19 r' 4 h/d,
for 19
-------
TAIII.I. Ill-/ (mill imi.M
Componnd(s) UIK)
Concentration^),
rnn/iii1 (ppm)
Humjdily/
Tempe ra t ii re
Mole of
Exposure
Species/Strain/
Age/Weight
No. of
Test Anima IB
Duration and Tola!
No. ol I re(|iirmy nl Length ol
Controls Kxposure Experiment
Effects
Reference
,niil Kal i»
IICIIO 0.12
t
0.005 ing IICIIO/1.
orally
IICIIO 0.12
Dynamic
inhala-
tion
chambers
llermet-
ically
sealed
chambers
Rats
Random-
bred rats
S 3 H
Not given
H;
No.
not given
Not Daily for
given 3 mo
Progeny
studied
up to 1
mo alter
birth
1 mo
Ul
o
IICIIO 0.1
Special Albino rats,
1 «3 130-240 g
chambers
50 M
SO H
90 d,
continuous;
6-10 rats
s.irr i 1 ictul
every JO d
90 d
The exposed males showed n nor- (iusevn
mat capacity to iiii|ir<'gnalr le- (\')J2)
males with normal numbers of H-0
(irum.il ollsjuing.
Small regions of proliferation
in Die nasal nm
-------
TAIll.K 111-7 (cunt i lined)
Coiuponnd(s) iind
Concentration(s),
nig/m1 (ppm)
Humidily/
Temperalure
Mode of
Exposure
Species/Strain/
Age/Wei glil
No. of
TORI Animals
Duration anil Tola I
No. of Frequency of Length of
Controls Kxposiire Kxperimcnl
Kffects
Uefereme
and Hal ing
IICIIO 0.035
IICIIO
0.035 i 0.004
100-I, Albino rats 1% H
chambers;
30 I, air
i IICIIO
per mill
Inliala- Albino 25 H
lion rats
chamber,
100-L wild
air flow
of 30 I./
min
15 h
Continuous
for 3 mo
25 H
Continuous
3 mo
i 15-d
recovery
period
Tlio slruclure of Die amygdaloid Ilonashcvskaya
complex was not diffcrenl cytol- (197!))
ogically or neurological ly from II- K
tbal of llie coiilrols.
No change of clironaxy of Die
muscles-antagonists .
No .statistical cbange in
cho) iiiestcrase activity.
Ho effect on behavior or weight Tel'diuan and
changes of animals. No effect Donashrvskaya
on clironaxy of antagonistic (I'J7I)
muscles. No change in l)N/t or 11-10
combined nucleic acids in
cerebral hemispheres.
(cont inned)
-------
1AIII.K III-/ (continued)
(.'oni|iuiind(s) and
('on
cent rat ion(s) ,
uig/ro3 (ppm)
Humid lly/
Tcmperaluie
Mode of
Exposure
Species/Strain/
Age/Weight
No
Test
. of
Animals
No. of
Conl ro
Is
Diir.il ion and
Frequency of
Kxposure
Total
Length of
Experiment
Effects
Deference
and Rat ing
IICIIO
0.011 1 0.002
100-L Rats; avg.
chambers; wt. of lest
IICIIO •» rat a, 179.0 ±
air in- 7.I g; avg.
treduced w(. of ton-
al 30 I./ Irols, 162.0 i
mln 4.4 g
15-17 M
15-I/ M
Conl inuous
for 98 d
except for
days off
and iso-
lated
working
days
98 d + a No diflercuce in behavior he-
recovery twei'ii test and control rats.
period Significant intreuse in weight
whose gain compared lo controls;
length 331.0 1 12.5 g compared li>
was not 301.0 t 6.0 g for the controls.
slated However, the initial weight of
the lest group was also higher:
179.0 Jt 7.1 vs. 162.0 t it.lt g.
From 2 2 mo, the change in the
summation of threshold indexes
was significant (determined by
electrical stimulation of a hind
paw). With anodization of the
brain as a functional stress,
more distinct changes of the Mini-
mal ion of threshold indexes oc-
curred. Choi ineslcrase activ-
ity tended to decrease compared
to that of the controls. No
statistically significant ef-
fect on oxidasc activity, SOOT,
or erythrocyte and hemoglobin
content of blood. The rhythm
frequency of the heart action
tended to increase and the
electrical activity tended to
decrease. There was also a
decrease in the [heart) con-
tent of lipids and cholines-
lerase. The lungs showed
weakly expressed fine foci ol
catarrh and foci of interstitial
pneumonia; the liver, weakly
expressed "hyperfitnct ional"
regions of hepatocyles; lira in
cells, depletion of Nissl .sub-
stance of the nerve cells hav-
ing a disperse cliaraclet in the
cortex and especially in the
I'm kin je cells. These changes
were preserved throughout the
recovery period.
Dulirovskaya el a I .
(I976a)
11-8
-------
TAIII.K 111-7 (continued)
Compound(s) and
Concenlrat ion(s),
mg/m3 (|i|>ra)
1ICIIO
0.012 i 0.0015
IICIIO 0.012
IICIIO 0.012
IICIIO
0.012 1 0.002
Humidity/ Mode of Species/Strain/ No. of
Temper a I u re Exposure Age/We iglil Test Animals
100-1. Rats 15-17 ft
chambers;
IICIIO +
air in-
troduced
at 30 L/
min
llermet- Random- Not
ically bred given
sealed rats
chambers
100-1. Albino 15 M
chambers; rats
30 L air
+ IICIIO
per min
Inliala- Albino 25 M
lion rats
chamber;
100 L
with air
(low of
30 1,/min
Duration and Total
No. of Frequency of Length of
Controls Exposure RxperimiMil
15-17 M Continuous 98 it t
for 98 d an uu-
oxcepl for specified
days off recovery
and iso- period
la ted
working
days
Not Daily for 3 mo
given 3 mo
15 H Continuous 3 mo
for 3 mo
25 M Continuous 3 mo
+ 15-d
recovery
per ioil
(continued)
i: fleets
No difference in behavior be-
tween test and control rats.
Significant difference in the
summation of threshold indexes
at the end of the poisoning
period (determined by electri-
cal stimulation of a hind paw).
Clio 1 i nes t erase activity tended
to decrease compared to that of
the controls. As at 0.031 mg
HCIIO/ui3, there were changes in
heart action—the rhythm fre-
quency increased and the electri
cal activity decreased. No ex-
pressed pathological changes in
the lungs, brain, and other or-
gans except foci of catarrhal
pneumonia and a focal (chiefly
prol iferative) process in the
i nLfi alveolar septa, which de-
creased. Nerve cells recovered
ill the recovery period |one rat1
brain cortex cells showed a lowe
ing of Nissl substance].
Nasal imicusa was no different
from that of the controls.
The structure of the amygdaloid
complex was not different cy-
tologically or neurological ly
from that of the controls.
No change in the chronaxy of
the muscles-antagonists. No
statistical change in chol-
inesterase activity.
No effect on behavior or weight
changes of animals. No ef-
fect on (liion.ixy of antago-
nistic muscles.
Iteleieni e
and Kaling
Oubrovskny.i rt ;il
( 1976a )
11-8
-
s
r-
Itonashevskaya
(1975)
C-6
llouaslicv.sk, iy.1
(19/3)
B-8
Fel 'dm. in and
llouashevskaya
(1971)
It- 10
-------
TAIII.K 111-7 (concluded)
CoinuoiiiuKs) an-5
liver weight and significant
increase in weight of adrenals.
No external deformities, no
inhibitions of development of
body systems, no macroscopic
structural alterations in
fetuses. Ilistocheniical changes
in fetuses included reduced gly-
cogen content in the myocardium,
accumulation of matter with a
positive reaction to Schiff's
reagent in the kidneys, and the
presence of iron in Kupffer's
cells.-
••'• The Formaldehyde Panel (Orieseroer et al., 1980) did not support the conclusions of Gofmekler. el at. (1968) that IICIIO significantly inhibited the
synthesis of nucleic acid; they also point out the data do not support reported avg. no. of fetuses/litter; different articles give different
HOB. of females and fetuses.
-------
TAIII.K 111-8. RATS--CHRONIC KXI'KIWIENTAI. EXI'OSUKE TO HWMAI.UKIiyDH (IICIIO)
Comppund(s) and
Concent ni Iion(s),
nig/in3 (ppm)
Iliiuiidily/
Temperature
Duration and Total
Mode of Species/Strain/ No. of No. of Frequency of Length of
Exposure Age/Weight Test Animals Controls Exposure Experiment
Effects
Reference
and Hating
IICIIO ~ 18.3 (14.6)
IICI (10.6)
Bis(clilorometliyl)
etlier (0.001
estimated)
Hals, Spragiie- 100 M Presum- 6 li/d, 814 d
Dawley al)ly none .5 d/wk,
for 544 d
Ui
Si)iiaiuous cell carcinomas of I lie
nasal cavity developed in 25
rats; 2 developed benign papil-
lomas of the nasal cavity.
First deaths from cancer
occurred at .105 d. Deaths
occurred at 305-705 d from 1st
exposure.
Nelson (1979)
B-7
Selikoff and
and Hammond
(1981)
C--
Griest'iiK'i el a I .
(1980)
A--
Tlie most common type of nasal
cancer caused by I>is(cliloroinethy])
etlier (BCHE), the reaction product
of IICIIO t IICI, is eslliesioneuro-
epiIhe 1ioma (tumor of the nerve
tissue) and very seldom squamous
cell carcinoma. This latter type
of cancer had never been observed
to occur spontaneously over many
years of research with > 2,000 con-
trol animals, but it is the same
type of tumor produced by approxi-
mately the same concentration of
IICIIO in the CUT study with rats
(Swcnberg et al., 1980). In
addition, no rat in this study
developed lung cancer, but they
dill in 11CNIC inhalation studies.
(continued)
-------
TABLE III-R (continued)
Compound(s) arid
Conccntrat fon(s),
mg/m1 (ppm)
IICIIO -17.6
Duration and Tula!
Humidity/ Mode of Species/Strain/ No. of No. of Frequency of Length of
Temperature Exposure Age/Weight Test Animals Controls Exposure Experiment
45 + 5%
20-2"2°C
Iliimcrs- Hats, 120 N
type in- Fislier 344, 120 f
halation 7 wk
chamber;
12 air
clianges/h
120 H 6 h/d, 18 mo
120 F 5 d/wk (of 24-»o
study)
Dose
weigl
of h
of wl
1, e|
squai
Kffects
Reference
anil Ruling
Dose-related decrease in hody Swenherg cl al.
weight and yellow discoloration (l')KO)
of haircoat. Forty-four deaths B-15
of which I had osleomalacia;
, epithelial dysplasia; :)H,
squamous metaplasia; II, squamous
or epithelial hypcrplasia; 6,
squainons papillary hyperplasia;
3, squamoiis metaplasia with cel-
lular alypia; 4, squamous papil-
loma; 28, squamous cell curcinoma;
and 1, spindle cell sarcoma.
Forty animals were sacrificed and
nasal turbinates examined; 2 had
focal turbinate atrophy; 13,
epithelial dysplasia; 19, sqii.iinous
metaplasia; 15, squamous or epithelial
hyperplasia; 4, squamous papillary
hyperplasia; 7, squamous metaplasia
with cellular alypia; 1, adenoma tons
polyp; and 8, scpiamous cell carcinoma.
Host of the animals examined had
rhinitis, acute siippurative or
seropiirulcnt. Most of the lesions
were dose-related with respect liolh
to severity and extent of involve-
ment. Sharp increase in deaths
after 12 mu. No abnormalities in
other tissues or control animals.
Initiating and/or promoting activi-
ties of sialodacryoadenitis virus
cannot be ruled out. Mice exposed
to this concentration did not
develop nasal cavity tumors.
Selikoff and Iliimmond (1'JSl) con-
cluded after they had examined
the 2A-mo results (a total of
95 nasal cavity carcinomas had
developed) that the "IICIIO ex-
posure and not the viral infec-
uppeaiu to lie I he crucial fac-
tor in development ol naual
in tlu':: sfndy.
(.cunt i
-------
TAW.E 111-8 (continue.))
Compound ( s ) and
Coucefil rat ion(s),
mg/m1 (ppm)
IICIIO ~ 7.0 (S.6)
lluniility/ Mode of Spec its/Strain/ No. of
Temperature Exposure Age/Weight Test Animals
45 1 51 Dinners- Rats, 120 M
20-22°C type in- Fischer 344, 120F
halation 7 wk
chamber;
12 air
changes/li
Duration and Total
No. of Frequency of Length of
Controls Exposure Experiment Effects
120 H 6 h/d, 18 no Dose-related decrease in body
120F 5 d/wk (of 24-wn weight and yellow discoloration
study) of haircoat. Eight deaths, of
which all had epithelial
dysplasla and 6 sqnamous
metaplasia of the nasal
lurblnales. Forty animals were
sacrificed and nasal titrbinates
examined; 37 had epithelial
dyuplasia, 35 had stjuamoiis
Reference
and Rating
Swcnberg el al
(19(10)
B-15
NIOSII/OSHA
(1980)
C--
metaplasia, arid 1 had adenomatoiis
IICIIO 3.75
(3)
IICIIO ~ 2.6 (2.1)
IICIIO 1.25
(1)
Inhala- Rats 20 H
tion 20 f
45 1 5% Dinners- Rats, 120 N
20-22°C type In- Fischer 344, 120 F
halation 7 wk
chamber;
12 air
changes/h
Inhala- Kats 20 N
lion 20 F
polyp. Seven of the 40 had
rhinitis, acute suupuralive or
seropurulent . No abnormalities
in other tissues or in controls.
By 16 ino, one rat developed a
uijnamoiis cell carcinoma of the
facial skin that did not extend
into the turblnatc. At 24 mo,
2 rats had developed squamous
cell carcinomas of the nasal
lurbinares .
20 M 22 h/d 6 mo Decreased rate of body weight
20 F 7 d/wk gain.
6 mo
120 H 6 h/d, IB mo Dose-related decrease in body
120 F 5 d/wk (of 24-rao weight and yellow discoloration
study) of haircoal. Two deaths, of
whl ill one had epithelial
dysplatiia of ttie nasal tlirbi-
nates. Forty animals .were
sacrificed and nasal turbinates
examined; 35 had epithelial
dysfilasia and 24 had scjuamous
metaplasia. Two of the 40 had
rhinitis, acute Hti|ipuralive or
seropuriilenl . No abnormalities
in oilier tissues or in controls.
20 H 22 h/d 6 mo No adverse effects noted while
20 F 7 d/wk exposed or on pathological
6 mo eva luat ion.
(Continued)
Clary (1980)
B--
Swenberg et al
(1980)
B-15
Clary (1 ')«())
B--
-------
TAUI.E 11 [-8 (continued)
Compound(s) and
Concent rat ion(s), Humidity/
uig/m1 (ppm) Temperature
IICIIO 1.0
IICIIO 1.0
,
Node of
Exposure
150-1.
inhala-
tion
chamber
witli air
flow of
30 L/min
150-L
inhala-
tion
chamber
with
air
flow of
30 L/
mil.
Species/Strain/
Age/Weight
Albino rats,
Wistar,
130-150 g
Pregnant
during 8th
mo.
Rats,
offspring of
mothers ex-
posed to
1 rag IICHO/m1
for 8 mo
including
duration
of preg-
nancy
Duration and Total
No. of No. of Frequency of Length of
Test Animals Controls Exposure Experiment
8 F 8 F Continuous, 8 mo
8 mo
Nos. not Nos. not Continuous, 8 no
given given, 8 mo
Group 1
offspring
of ex-
posed
mothers ,
Group 1 1 ,
offspring
of unexposed
mothers
Effects
IICIIO 0.5-0.6
MoOII 5.0-6.0
lit) lowing intra-
tracheal Intro-
duct ion of res iii-
trealed or un-
treated COill
(lllKl
Rats
Not given No. not 6 mo, con-
given, tiniious 'I
Rats dosed
with un-
treated
cual dual
and not ex-
posed to
IICIIO and
McOII
6 mo
Reference
and Kuting
Misiakicwicz el a
(l'J77)
C-7
Body wt. increased during ex-
posure, no significant differ-
ereuce in blood cliol inesterase
activity, erythrocyte count,
and hemoglobin level or in
the activity of asparagine
aminotransferase in the blood
plasma.
Exposed rats had a 10% smaller Misiakicwicz el al
increase in body wt.; controls (1977)
in Group I had a 7.5% smaller C-7
Increase than controls in
Group 11. Between the 3 groups,
no significant differences in
bloorl cliol ineslerase activity,
erythrocyte count, and hemo-
globin level or in the activity
of asparagine aminolians-
ferase" in the blood plasma. No
significant differences in wt.
coefficients of kidneys, spleen,
or liver of 3 groups except for a
significant decrease in wt. co-
efficient of liver of exposed rats
compared to control Group II.
Morphological changes In upper
respiratory tract in control Group
I. Same changes but more numerous
in exposed rats compared to com-
pletely unexposed control Group II.
The collagen content per Gadzhicv i't al .
identical lung weight was (1977)
significantly higher in the 0-4
exposed group that had been
dosed with untreated coal
dust .
More severe disturbances in
lung structure both in the
bronchial tree and the respi-
ratory branch occurred in ex-
posed rats pre-dosed with
t MM ted diihl The changcf in
I lit' bronchi were also more
-------
Compound(s) and
Concent ralion(ti),
nig/in1 (ppm)
Iliimiili ty/
Temperature
Hode of
Exposure
Species/Sirain/
Age/Weight
TABLE 111-8 (cont iniied)
Ouralion and Total
No. of No. of FrcMpiem y of Length of
Test Animals Controls Exposure Experiment
Effects
Keferencr
nnil Killing
IICIIO 0.5
f 0. I IICIIO/1.
oral ly
Inhala-
tion
chambers
Kala
20 H
20 M
4 li/d,
5X/wk for
7 mo (oral
doses intro-
ijiiccd through
a probe in the
same period)
(conl ilined)
7 mo 2 nio--l)isturbance in condi- C-nseva
tioned reflex shown by lowering C-8
of latent period toward light.
Tendency to increased alanine
aminotransferase and cholin-
eslerase activities and the
amount of protein in the blood
serum.
3 mo--(,'liai)ge in biochemical in-
dexes of the blood. Increases
in content of hislamine and Sll
groups, decrease in the activity
of alanine aminotransferase, and
a tendency toward lowering oxidase
activity.
6-6 nio--Normal izat ion of all
earlier appearing shifts
5 nio--Tests using hexobarbi tal,
alcohol, or brain anodizalion
as stresses showed inhibition
of conditioned reflex activity
and the brain cortex.
7 mo--Increase of hislamine in
blood. Huiiimi f ication of cell-
ular elements in the epithelium
of the respiratory tract and
upper portions of the alimentary
tract.
Activities of chol ineiilerase and
alanine aminotransferase in the
liver increased but cholines-
terase decreased in brain tis-
sue. The increase in Vitamin C
in the adrenals indicated dis-
turbance of compensating mechan-
isms. Degenerative changes
were found in the olfactory,
optic, and auditory analyzers.
-------
TABU: in-s (continued)
Compound(s) and
Conceiilration(s),
mg/ro1 (ppm)
Diiraljou anil Total
Humidity/ Mode of Species/Strain/ No. of No. of frequency of Length of
Temperature Exposure Age/Weight Test Animals Controls Exposure Experiment
Effects
Reference
and K.it ing
IICIIO 0.5
+ O.I rag IICIIO/f.
orally
Dynamic Rats
inhala-
tion
chambers
> 3 H
M;
No. not
given
<• h,
SX/wk
for 6
mo
(Oral
doses
given at
EH me time)
6 mo I
progeny
studied
up to 1 mo
after
birth
The alii lily of the exposed
males to impregnate untreated
females (2 per test male) was
not affected. The number and
weight of the fetuses and new-
horn rats fathered by the
treated males did not differ
significantly from those of
the control group. Defects
and anomalies were not found
in the offspring nor did any
significant differences de-
velop in the offspring in
their first month after birth.
Pituitary preparation from
the exposed rats did not
cause any differences in
gonadotropic reaction when
injected into immature fe-
males.
A significant decrease was
observed in the amount of
nucleic acids in the males'
testicles, which watt attributed
to gonadotropic poisoning by
IICIIO.
Guseva
(1972)
n-6
(conl iniicil)
-------
TAHLIi III-B (mill inucil)
Componnd(s) ami
Concentration(s),
ing/m3 (ppm)
Humidity/
Temperature
Mode of
Exposure
Duration and Total
Species/Strain/ No. of No. of Frequency of Length of
Age/Weight Test Animals Controls Exposure Experiment
Effects
Reference
and Rating
IICIIO 0.5
Inhala- Albino
lion rats,
chamber 180-240 g
60 H
IICIIO 0.5
200-1.
inhala-
tion
chambers
Rats
25 F
60 H 5h/d, 6 mo > General health good, behavior Nagorciyi el at.
6 d/wk 1-mo normal, and body weight in- (197'')
recovery creased steadily. No sub- II-')
stiintial change in the struc-
ture of the upper respiratory
tract, lungs, or other internal
organs. Minor changes in blood
anil urine parameters reported.
During the 2nd mo, the
eosinophil count increased sig-
nificantly as did the daily
phenol red excretion in the
urine. Urinary liippuric acid
secretion dropped signifi-
cantly. At end of study, the
weight coefficient of the
testicles had decreased sig-
nificantly. At 1 mo post-
exposure, only the phenol red
excretion in the urine was
still significantly higher; all
other factors had returned to
normal (weight coefficients not
determined).
25 F It h/d A mo Within 2-3.A mo, exposure to I'od''yacheva
for 4 mo IICIIO (and in a separate cxperi- (1977)
nient to the same level of C-9
phenol) increased the activities
of cholineslerase, oxidase, and
glitta
-------
TAIII.K 111-8 (continued)
Coinponnd(s) and
Concentralion(K) ,
niR/m3 (ppm)
IICIIO 0.25 +
0.01 mg
IICIIO/ 1,
orally
ll.imi.lity/ Nude of Species/Strain/ No. of
Temperature Exposure Age /Weight Test Animals
Inhala- Hals 20 M
lion
chambers
Duration anil Total
No. of Frequency of Length of
Control a Exposure Exper intent
20 M 4 h/il 7 wo
5X/wk for
7 mo
(Oral
doses
through
a probe in
the same
period. )
Reference
Effects ami Rating
No reliable difference in the Gusevi
indexes of the conditioned C-B
reflex 1 rom those of the con-
trol group during the whole
study.
< 3 mo- -Change of biochemical
indexes of blood characterized
chiefly by a tendency to an in-
crease in cholincslerase activity,
histamine content, and number of
SII groups .
i (197-1)
N)
IICIIO
IICIIO
Phenol
0.25 +
0.01 mg
IICIIO/1,
orally
0.25
0.25
Dynamic Rats
inhala-
tion
chambers
200-L
inhala-
tion
chambers
Rats
> 3 M;
No. not
given
25 F
No. not
given
25 F
4 h
5X/wk for
6 mo (oral
doses given
at same lime)
It h/d
for 4 mo
(continued)
4-6 HIO--A11 indexes studied within
physiological norms.
5 mo--Tests using hexotiarbital,
alcohol, brain anodization as
stresses showed inhibition of
conditioned reflex activity and
the brain cortex.
7 mo—Slight increase in histamine
content and amount of protein in
blood scrum.
6 mo A significant decrease was Cnseva (1972)
observed in the amount of 11-6
nucleic acids in the males'
testicles, which was attributed
to gonadolrupic poisoning by
IICIIO.
4 »o The effects at 0.5 mg IICIIO l>od"yacheva
or phenol per cubic meter (1977)
air were duplicated when the C-9
two were combined at 0.25 mg/m3
each. However, the changes
occurred sooner--at 0.5-1 mo
compared to 2-3.4 mo.
-------
TAIII.K I I 1-8 (continued)
Compound (s) and
Concent ratiou(s) ,
nig/in3 (ppm)
1ICIIO 0.25
(0.2)
Humidity/
Temperature
Mode of
Exposure
Inhala-
tion
Species/Strain/
Age/Weight
Rats
IICIIO
0.12 +
0.005 mg
MCllO/1.
orally
Inhala-
tion
chambers
Rats
No. of
Test Animals
20 M
20 F
20 M
No. of
Controls
20 M
20 F
Duration ami
Frequency of
Exposure
22 h/d
7 d/wk
6 mo
Total
Length of
Experiment
6 mo
No adverse
exposed or
evaluation.
Effects
effects noted while
on pathological
.Reference
anil Kating
Clary (1980)
B-~
20 M 4 h/d 7 mo No significant differences in
5X/wk for the conditioned reflex action
7 1110 (oral or of the liiocheniical indexes
doscu given of the blood during the whole
in same experiment. No significant
period) differences in cholinesterase
activity, alanine and asparagine
aminotransferase activities, and
hi si amine content in the liver;
cholinesterase in the brain; or
vitamin C in the adrenals.
No abnormalities found in
pathomurphologlcal and
neurohistological studies.
Little or no change in CNS
activity from that of con-
trols upon stressing with
alcohol or brain anodiza-
tion in the 5th mo.
Guscva (197:))
C-8
(Continued)
-------
TABLE II1-8 (concluded)
s) and
Concentration^),
mg/m1 (ppm)
Humidity/
Temperature
Node of
Exposure
Species/Strain/
Age/Weight
Duration and Tola I
No. of No. of Frequency of Length of
Test Animals Controls Exposure Experiment
Effects
Deference
and Hal ing
IICIID 0.03!>
100-1. Rats,
inliala- Wislar,
lion 180 1 10 g
clumber
30 M
IICIIO 0.035
Albino
rats,
Wistar,
180 ± 10 g
20 M
30 H 3 h/d, 6 no No observed changes in be- l)asmad/.liieva el
60 nio havior, general condition, and (1974)
wt. of rats. Significant de- B-9
crease of 20-30% or more in
the lifaenergetic metabolism
processes in the mitochondria 1
fraction of liver. Processes
with such decreases were:
activity of cytoclirome oxidase,
and surcinic ileliydrogenase; res-
piration; 02 consumption; C02
elimination; esterlficall on of
Inorganic phosphorus; and rate
of oxidative pliosphorylation.
Slight Increase in lactic acid
content of blood. Significant
increase of pyruvic acid in
blood and hemoglobin content
in serum. All the above
changes were noted in mo 1
and continued through mo 6.
20 M 8 h/d, 6 no No observed changes in be- Davidkova and
6 mo havior and general condition Basmadzhlcva
of animals. After 2 and 6 mo, (197
-------
TABI.K 111-9. GUINEA l'ICS--ACUTK EXI'KRIHKNTAI. EXPOStMK TO FUKHAI.OKIIYIIK (IICIIO)
Com)mmid(s) and
Concent r»t ion(s) ,
mg/m3 (ppm)
IICIIO ~ 63 (50)
IICIIO ~ 63 ± 10
(5018)
IICIIO ~ 62.5
(50)
IICIIO -62.5
(50)
IICIIO -61 ± 11
Ci9 1 9)
Humidity/ Mode of
Tempera 1 11 re Exposure
Dynamic
inliala-
l ion
chamber
Dynamic
inhala-
tion
cliatnber
Inhala-
t i on
chamber,
exposed
head only
Inhala-
tion
chamber,
exposed
head only
Dynamic
inhala-
tion
chamber
Species/Strain/ No. of
Age/Weight Test Animals
Gn i noa Pigs 3
Guinea Pigs 6
breathing
through can-
nu la in
trachea
Guinea Pigs Not given
Guinea Pigs Not given
breathing
through
t racheotomy
Guinea Pigs 11
No. ol
Controls
Served
as own
Control
Served
as own
control
Not
given
Not
given
Served
as own
control
Duration and Total
Frequency of Length of
Kxposure Experiment
tt h, 6.5 h
once
1 h, 2.5 h
once
1 h, 1 h
once
1 h, 1 h
once
1 li, 2.5 h
once
Effects
Lung resistance more than tri-
pled in lirsl h to its highest
level during the exposure but
had not returned to normal 2 h
post-exposure .
Significant increase in lung
resistance and in work required
to breathe and significant de-
crease in lung compliance,
breathing frequency, anil minute
volume. At 1 h post-exposure,
lung resistance was still sig-
nificantly higher than pre-
exposuic.
Significant increase in resis-
tance and tidal volume and sig-
nificant decrease in respir-
atory rate and minute volume
of lungs. No change in lung
compl iance.
No change in lung compliance,
resistance, tidal volume,
minute volume, or respiratory
rale.
Highly significant increase in
lung resistance and decrease
in lung compliance and breath-
ing fre«|uency. Significant
Reference
and Hal ing
Aiiuliir
(1960)
11-13
Amdur
(I960)
11-11
Da v i s e t a 1
(1965)
C-5
Davis ct .1 1
(1967)
l)-6
'Javis el al
(1965) C-5
Davis e t a 1
(1967)
I)- 6
Amdur
(I960)
11-13
increase in work required to
breathe and in lung tidal
volume, slightly significant
decrease in lung minute volume.
Al 1 h post-exposure, lung
resistance was still .signifi-
cantly higher than (ire-exposure.
(continued)
-------
TAHI.K in-1) (continued)
Com|iomi(l(s) and
Concent ration(s),
mg/m1 (ppra)
IICIIO ~ 59 ± 16
(47 i 13)
NaCI 10.0 t 1.9
IICIIO ~ 34 ± 8
(27 ± 6)
NaCI 12.1 i 2.1
IICIIO ~ 25 i 4.8
(20 t 3.8)
IICIIO ~ 15.6
(12.5)
Humidity/ Hc.de of Species/Strain/ No. of
Temperature Exposure Age/Wo iglit Test Animals
Dynamic Guinea Pigs 8
inhala-
tion
chamber
Dynamic Guinea Pigs 12
inhala-
tion
chamber
Dynamic Guinea Pigs 10
inhala-
tion
chamber.
Breathing
through
cannula
in trachea
Hose Guinea Pigs 9
mask
No. of
Controls
Served
as own
control
Served
as own
control
Served
as own
control
Served
as own
control
DM rail on and Total
frequency of Length of
Exposure Experiment Effects
1 h, 2.5 h Highly significant increase in
once lung resistance. Significant
decrease in compliance, breath-
ing frequency, and minute
volume and increase in tidal
volume and work required to
breathe. At 1 h post-exposure,
lung resistance was still sig-
nificantly increased over pre-
exposure.
1 h, 2.5 h Highly significant increase in
once lung resistance. Significant
decrease in compliance and
breathing frequency and in-
crease in tidal volume and
work required to breathe. At
1 h post-exposure, lung resis-
tance was still significantly
increased over pie-exposure.
1 h, 2.5 h Highly significant increase in
once lung resistance and decrease
of compliance. Significant
decrease in breathing frequen-
cy and lung minute volume.
Insignificant increase in work
required to breathe. At 1 h
post-exposure, lung resistance
was still slightly but insig-
nificantly increased over pre-
exposure.
1.5 h, 1.5 h, Significant increase in respir-
once atory rate, flow resistance,
and tidal volume compared to
Reference
.UK! K.I 1 1 UK
Amdu r
(I960)
u-n
Auidur
(I960)
n-n
Amdu r
(I960)
B-13
Murphy am
(1964)
U-5
pre-exposure values.
(cont inucd)
-------
Compound(s) and
Concent rat iofi(s),
nig/in1 (ppm)
TABLE 111-9 (coiil Inui-.l)
Duration anil Total
Humidity/ Modi; of Species/Strain/ No. of No. of Frequency of Length of
Temperature Exposure Age/Weight Test Animals Controls Exposure Kxperiiurnl
Kffecfs
Reference
.mil Killing
IICIIO ~ n.8 1
(11.0 12.9)
3.6
IICIIO ~ 13.5 ± 0.6
(10.8 1 0.5)
NaCI 10.7 t 1.7
IICIIO ~ 6.5 ± 0.08
(5.2 i 0.07)
IICIIO -4.9
(3.9)
Dynamic
inhala-
t ion
clianibe r
Guinea Pigs
10
Dynamic
i nhaI a -
lion
chamber
Guinea Pigs
Dynamic Guinea Pigs
inhala-
tion
chamber.
Breathing
through
cannula
in trachea
Nose
mask
Guinea Pigs
10
Served I h,
as own once
control
Served 1 h,
as own once
control
Served 1 h,
as own once
control
Served
as own
control
1.5 h
once
2.5 h Significant increase in lung Aimlui
resistance, highly significant (I960)
(((•crease in lung compliance. 11-1.3
Slight hut insignificant in-
crease in work required to
breathe. Significant decrease
in breathing frequency and
minute volume of lungs. At
I h post-exposure, lung resis-
tance still slightly but insig-
nificantly increased over pre-
exposure.
2.5 h Highly siguifjcant increase in Auidur
lung resistance and decrease in (1960)
lung minute volume. Signifi- 11-13
cant decrease in compliance
and slightly significant in-
crease in work required to
breathe. At 1 h post-exposure,
lung resistance was still sig-
nificantly increased over pre-
exposure.
2.5 h Significant increase in lung Amdiir
resistance; significant de- (I960)
crease in compliance, breath- 11-13
ing frequency, and lung minute
volume. Slight insignificant
increase in work required to
breathe and in lung resistance
I h post-exposure compared to
pre-exposiire.
1.5 h Significant increase in respir- Murphy and Illricb
iilory rate, flow resistance, (1964)
and tidal volume compared to 11-5
pie-exposure values.
(continued)
-------
TAIII.K III-1) (continued)
Co
Compound ( 8 ) and
Concent rat ionfs), Humid lly/
nig/m' (ppm) Temperature
IICIIO ~ 4.5 i 0.6
(3.6 i 0.5)
NaCI 10
IICIIO ~ A. 5 t 0.4
(3.6 i 0.3)
IICIIO ~ 3.3 ± 0.4
(2.6 ± 0.3)
NaCI 8.7 t 0.9
IICIIO ~ 1.52 ± 0.29
(1.22 t 0.23)
Mode of Species/Strain/
Exposure Age/Weight
Dynamic Guinea Pigs
inhala-
tion
chamber.
Breathing
through
raniuila
in trachea
Dynamic Guinea Pigs
inhala-
tion
chamber
Dynamic Guinea Pigs
inhala-
tion
chamber
Dynamic Guinea Pigs
inhala-
tion
chamber
Duration and Total
No. of No. of Frequency of Length of
Test Animals Controls Exposure Experiment
6 Served 1 h, 2.5 h
as own once
control
10 Served 1 h, 2.5 h
as own once
control
B Served 1 h, 2.5 h
as own once
control
4 Served 1 h, 2.5 h
as own once
control
Effects
Significant increase in lung
resistance and decrease in
compliance, breathing fre-
quency, and minute volume.
Slight but insignificant in-
crease in work required to
breathe. At 1 h post-exposure,
lung resistance was still sig-
nificantly higher than pre-
cxposurc.
Highly significant increase in
lung resistance, significant
increase in work required to
breathe. Slightly significant
decrease in lung compliance.
At J h post-exposure, lung re-
sistance still slightly but
insignificantly increased over
pie-exposure.
Highly significant increase in
lung resistance. Significant
decrease In compliance and in-
crease in work required to
breathe. At 1 h post-exposure,
lung resistance was still sig-
nificantly increased over pre-
exposure.
Significant increase in lung
resistance and in work re-
quired to breathe. Slight
decrease in lung compliance
and breathing frequency. At
1 h post-exposure, lung resis-
tance still slightly but in-
significantly increased over
pre-exposure.
Kclereiice
.nut Hating
Anuliir
(I960)
fl-11
Amdur
(I960)
U-13
Amdur
(I960)
B-13
A rod ur
(1960)
11-13
(continued)
-------
TABLE 111-9 (continued)
Compound ( s ) and
Concent rnlion(s), Humidity/
mg/m1 (|i[im) Temperature
IICIIO ~ 1.43 1 O.I
NaCI 10
IICIIO ~ 1.13 ± O.I
(0.90 1 O.OS)
IICJIO ~ 0.96 i 0.34
(0.76 t 0.27)
NaCI 12.8 1 2.0
IICIIO ~ 0.73 ± 0.1
(0.58 1 0.08)
IICIIO - 0.4 t 0.03
(0.32 1 0.02)
NaCI 11.3 t 1.6
Haiif of Species/Strain/ No. of
Exposure Age/Weight Test Animals
Dynamic Guinea 1'lgs 8
Inhala-
tion
chamber .
Breathing
Lhrougli
cannula
in trachea
Dynamic Guinea Pigs 7
inhala-
tion
chamber.
Breathing
through
cannula
In tracttea
Dynamic Guinea Pigs 8
inhala-
tion
chamber
Dynamic Guinea Pigs 2.3
Inhala-
tion
chambe r
Dynamic Guinea Pigs 8
inhala-
tion
chamber
No. of
Controls
Served
as own
control
Served
as own
control
Served
as own
cont rol
Served
as own
control
Served
as own
control
Duration and Total
Frequency of Length of
Exposure Experiment Effects
1 h, 2.5 h fifgnlf icant increase in lung
on it resistance and in work required
to breathe. Significant de-
crease in lung compliance. At
1 h post-expoiurc, lung resis-
tance was still significantly
higher than fire-exposure.
I b, 2.S h Highly significant increase in
once lung resistance and decrease
in compliance and insignificant
increase in work required to
breathe. At 1 h post-exposure,
lung resistance was still
slightly but insignificantly
increased over pre-cxposurc.
1 h, 2.5 h Highly significant increase in
once lung resistance and signifi-
cant decrease in compliance.
Slightly significant increase
in work required to breathe.
At t h post-exposure, lung re-
sistance was still significantly
increased over nre-exnosure.
1 h, 2.5 h Highly significant increase in
once lung resistance and decrease
in conqil lance. Insignificant
increase in work required to
breathe. At 1 h post-exposure,
lung resistance still slightly
but Insignificantly increased
over pre-exnosure.
1 li, 2.5 h Significant increase in lung
once resistance arid decrease in
compliance. Slightly signi-
Reference
and Rating
Airulnr
(l%0)
B-U
Amdur
(I960)
II- 1.3
Amdur
(I960)
D-13
Amdur
(I960)
B-13
Amdur
(I960)
11-13
(cont inueil)
quired to breathe. At 1 li
pust-exposure, Inug res 1st ante
was still significantly In-
i rciisetl over |> re - expo tt tire.
-------
TAItl.K III-') (concluded)
Compound(B) and
Concentration^),
rog/ni1 (ppm)
llumidily/
Temperature
Mode, of
Exposure
Spec ies/Sl rain/
Age/Weight
Duration autl Total
No. ol No. of Froi|imncy of Length of
Test Animals Controls Exposure Experiment
IICIIO ~ 0.39 i O.I
(O.:il 1 0.08)
IICIIO ~ 0.09 ± 0.01
NaCl 7.5 ± 0.7
IICIIO ~ 0.06 ± 0.03
(0.05 ± 0.02)
Dynami c
inhala-
tion
chamber
Dynamic
inhala-
tion
chamber
Dynamic
inhala-
tion
chamber
Guinea Pigs
13
Guinea Pigs
Served I h,
as own once
control
Served 1 h,
as own once
control
Guinea Pigs
IB
Served 1 h,
us own once
control
2.5 h
2.5 h
2.5 h
Reference
Effects and Hating
Significant increase in lung Amdur
resistance and decrease in (l'J60)
lung compliance. Insigni- H-13
fic.-ml increase in work re-
quired to hreal he. At 1 h
post-exposure, lung resistance
near normal.
Significant increase in lung Amdur
resistance. Insignificant dc- (I960)
crease- in compliance and in- II-Ki
crease in work required to
breathe. At I h post-exposure,
lung resistance was still
slightly but insignificantly
increased over pre-expomire.
Slight but insignificant in- Amdur
crease in lung resistance and (I960)
work required to breathe, 11-13
slight decrease in lung com-
pliance. At 1 h post-exposure,
lung resistance still slightly
but insignificantly increased
over pre-exposiire.
-------
TABLE 111-10. GIIINKA I'lfiS--l(KI'KATF.I) DOSE KXI'KKIMKNTAI. KXI'OSUKG TO KIKMAI.DKIIYDK (IICIIO)
Componnd(s) anil
Conccnlration(s),
iiiK/m1 (ppm)
Hum i ilily/
Temperature
Mode of
Exposure
Species/Strain/
Age/Weighl
No. of
Test Animals
No. of
Cent rols
Dura I ion and
Kre<|iiency of
Kxposure
Tola!
Length of
Kxporimcnl
liffecls
Reference
.mil U.iI ing
IICIIO 15
IICIIO -12.5
00)
IICIIO 7
Guinea Pigs, H M Continuous 39 It Time until cliol ineslerase act- Oslapovich
liglit colored No. not No. not + 1 mo ivity was lowered by 25-30% (1975)
given given compared to Hut of the cuii- (.'-6
trols--39 h. Time until leu-
kocyte number was increased
by 25-30% compared to that of
controls--39 h. Allergic ef-
fects were not observed.
Not Guinea Pigs Not given Not 6 b/d, 13 wk Lung glutalliione significantly Heeler
given given 5 d/wk * 3 d higher compared to controls. (19/8)
Liver and kidney glutat.hionc l)-4
levels were lower but not sig-
nificantly different. Uluta-
thione reduclase activities of
lung, liver, and kidney were
lower; liver and kidney de-
creases were significant.
Guinea Pigs, H Continuous 168 h Time until tlioline.ster.-i.se act- Ostapovich
light colored (7 d) ivity was lowered by 25-30% (1975)
1 1 mo compared to that of the con- C-6
trols--12() h. Time until leu-
kocyte number was increased
by 25-30% compared to that of
the controls--144 h. Time
until allergic effecls--l68 h.
Thus, toxic effects appeared
somewhat sooner than allergic
effects.
(continued)
-------
TABLE 11 (-10 ( con I i mictt)
Cuni|>()iin
-------
TABLE 111-10 (continued)
Ci>inpoui>d(s) ami
Concent rat i on (s), Iliimidily/ Mode of
nig/in1 (ppm) Temperature Exposure
IICIIO 2
I1CIIO O.T> Inlia la-
Li on
chamber
Species/Strain/
Age/Weight
Guinea Pigs,
light colored
Guinea I'igs
No. of
Test Animals
H
No.
not
given
15
No. of
Controls
M
No.
not
given
15
Dnrat ion ami
Frequency ol
Exposure
Conl iniious
5 b/il,
6 d/wk
Total
Length Of
Experiment
1,272 h
(53 d)
» 1 mo
1 mo
Effects
Tiiiu1 until chol inesterase act-
ivity was 25-30% leas than
that of the controls--! ,272 h.
Time until leukocyte nuiuher
was 25-30% higher than that
of I lie coiilrols--936 h. Time
until allergic effecls--336 h.
Thus, allergic effects appeared
much sooner than toxic effects.
General health good and body
weight increased steadily.
No Riilititanl ial change in the
He f erenre
• and Hat ing
Oslapovi t h
(1975)
C-6
Nagornyi et al .
(1979)
11-9
IICIIO 0.38
(Level chosen
because it is
similar to a
typical main
highway concen-
tration)
structure of the upper respir-
atory tract, lungs, or other
internal organs. Minor changes
in blood and urine parameters
reported.
Not Guinea Pigs H & F M & F 8 h/d 5 wk Injury of the neutrophiIs.
given No. not No. not for 21 d Degranulation of hasophilic
given given cells after the 2|-d period
of sens itization and 2 wk
after was less than that seen
when the guinea pigs were ex-
posed to 0.038 and 0.011 mg
llCIIO/m1. Others have also noted
that chemical allergens give the
most expressed sensitizing ef-
fect at the lowest concentrations.
FormaI ion of antibodies occurred.
Vinogradnv et a I.
(I9M)
11-7
(ton! imied)
-------
TABLE 111-10 (lontiwicd)
Cum|)cmntl((i) and
Coin fill r»t ion(a),
Humidity/
Temperature
Mode of
ExpoKure
Species/Strain/
Age/Weight
Doration and Total
No. of No. of Frequency of Length or
Test Animalw Controls Exposure Experiment
Effects
IICIIO 0.038
Not
given
Guinea Pigs
H & F
No. not
given
M & f
No. not
given
B li/d 5 wk Injury of the netitrophi Is not
for 21 d so extensive as at 0.38 and
0.011 mg llCIIO/m3. Uegranula-
tion of basophiIs less than
at 0.011 ing/ro.1 and more than
at 0.38 mg/m1 after the 21
d scnsitization period hut was
highest 2 wk later. A higher
liter of antibodies in hound
complement was found at both
times than when the guinea pigs
had been exposed to 0.011 or
0.38 mg IICIIO/ra3.
Reference
anil KilUii
Vinogradov cl .11 .
I)-7
(< out imicil)
-------
TABLE III-IO (i oriLimu-.l)
Coiii|Kiiiii(l(.s) arid
Concent r»linn(s),
Illg/lll1 (|l|Hll)
lliuuiiliLy/
Temperature
Mode of
Exposure
Spec i es/St ra i n/
Age/Weight
Duration anil To I a I
No. of No. of Frequency of Length of
Tesl Animals Controls Exposure Experiment
Effects
Hi1 f«' relief
anil Killing
IICIIO 0.01 I
Special Guinea figs,
inliala- avg. wt.
lion 200-250 g
chambers
~ 16
~ 16
7 h/d
for 30
(COIII illlied)
> 3 mo Four weeks of poisoning l>y HOMO Vinograduv
causeil an active pliagocylic re- anil [(inlncv
action related mostly to I lie (1976)
digestive function of the cells. 11-7
The pliagocylic alii lily of the
neulrophits was greatest It wk
after tlie end of poisoning.
Within 2 uio after poisoning,
all the increased indexes of
absorptive and digestive
functions seen at It wk alter
were normal. An especially
high liter of serum complement
was noted within 2 wk after the
end of poisoning. The basic in-
dexes of the white blood were
little changed and were within
I lie norms during or after poison-
ing-
After 2 mo of observation alter
the poisoning, the animals were
subjected to stress in the form
of bypoxia. The test animals
showed a lowering of the content
of most of the cellular elements
after hypoxia while the controls
generally showed increases. The
immune response of previously
poisoned animals was sign)Iiranlly
depressed compared to controls
after hypoxia. In the controls,
hypoxia caused a decrease in
phagocytic number and index but
did not change the digestion pro-
cess appreciably. In the lest
animals, hypoxia depressed the
indexes of phagocytosis, espe-
cially the digestive capacity of
the neutrophils. Hypoxia led lo
an insignificant lowering of the
liter of serum complement in the
controls, whereas Ihe lest an-
imals showed a significant lower-
ing of complement activity.
-------
TAIH.E MI-10 (romliidml)
Compound (s) and
Concent rat ion(s),
nig/in' (ppm)
IICIIO 0.011
Humidity/
Temperature
Node of
Exposure
Not
given
Species/Strain/
Age/Weight
Guinea Pigs
No. of
Test Animals
M & F
No. not
given
No. of
Controls
M & F
No. not
given
Dm at ion and
Frequency of
Exposure
8 h/d
for 21 d
Total
Length of
Experiment
5 wk
Effects
Injury of the neiitrophi Is.
Degrnnulalion of uasophils
was highest at this level
Helen-lire
and Kal ing
Vinogradov cl
(1974)
II- 7
al
after 21 d
Others have also noled that
chemical allergens give the
most expressed sensitizing
effect at the lowest concen-
trations. Formation of anti-
bodies occurred.
-------
TAHI.K III-ll. KAHHITS--ACIITI'. KXI'KIU MI.NTAI. KXI'OSUUK TO KUIUIAI.DKIIYDK
Coni|)ouii(l(s) and
Conceutration(s) , Humid i I y/
nig/m1 (|>|>ni) Temperature
IICIIO 3.5-6.5
IICIIO ~ 6
(5)
Mode of
Exposure
Head
only,
with ex-
S|iecics/Strain/ Mo. of
Age/ Wei ght Test Animals
Kal>bils S 47
Rabbit 2-5 M
2.8-3.4 kg
No. of
Controls
Not
given
Duration anil
Frequency of
Exposure
10 s
once
3-4 win
Total
1.6'llglll of
Exper imeiil
15-20 s
Effects
Threshold of individual sensi-
tivity for an adaptive olfactory
reaction. Fast recovery to
original stale.
Decrease in blood pressure,
marked decrease in heart rate
.iml respiratory movement.
Jfeferenre
•ind Rating
llokinn anil Kksler
(1973)
B-7
Iked,) el al .
(1980)
C-7
posure
mask,
air flow
4 I./min
IICIIO 2-3.5
Rabbits
47
Not
given
10 min
Dislurbance in Hie long-term
(3-5 min) synchronized rliyllim
and breathing disorganization.
Changes in the functional con-
dition of the rabbits were
characterized by prolonged
periods of Iheta-rhythm in the
electrical activity of the
brain. The reaction was early,
generalized, and more distinct
with IICIIO than with 03. The
effect of IICIIO may be its effect
on the trigeminal nerve and the
connection of this nerve with
the reticular formation, uhicli
in ils turn diffusely activates
the whole brain.
Uokina and Eksler
(1973)
B-7
(continued)
-------
TABLE 111-II (continued)
Compound (s) and
Com ent rut ion(s) ,
nig/in1 (ppra)
Humidity/
Temperature
Mode of
Exposure
Species/Strain/
Age/Weight
No. of
Tent Animals
No. of
Controls
Duration and
Frequency of
ExpoHiire
To t.il
Length of
Kxpcr incut
Elf cuts
Reformer
and Kal ing
IICIIO 2-3.5
Kabbils
47
Not
given
10 s
once
00
15-20 s Threshold of individual sensi-
tivity for the orienlalion-
ex|tloratory reaction, i.e.,
the Pavlovian reflex that en-
sures a response from the CNS
lo constantly changing condi-
tions. Fast recovery to orig-
inal state. The nonspecific
reaction of orientation and
exploration is characterized
by the appearance in the neo-
cortex of individual flashes of
activity and by quickened res-
piration. Olfactory analyzer
structures show no change In EEG
activity. The form of the EEC
response to concentrations of
chemical substances eliciting
the orienting-exploratory re-
action coincides with that lo
light and sound. Thus, the CNS
evaluates these sensory stimuli
as undifferentialed (l)okina et al.,
1976).
Itokina ami Kkslcr
(197:))
B-7
(continued)
-------
TAI1I.K I 11-11 (roiitiiiueil)
Compound (s) and
Concent rati on (s), Iliimiili ty/
nig/in1 (ppm) Temperature
IIC1IO 0.65
I bjnonilar 1 ighl
stimulation: A
series of 1 iglil
flashes comprising
10 impulses with
frequencies of 4
and 7 llz, both of
which were tested
5 times in a given
segment of the test
with 15-20 s between
the separate series.
--1
~o
Duration and Total
Mode of Species/Strain/ No. of No. of Frequency of Length of
Exposure Age/Weight Test Animals Controls Exposure Experiment
Constant Kabbits 5 M 5 H 20 min 30 uiin
stream 2.5 kg
of IICIIO-
air mix-
ture
(pure air
for the
controls)
supplied
at a rale
of 8 L/inin,
which pro-
duced an
insignif i-
canl tac-
tile action.
Light source
was a gas-
discharge
lamp at 20
cm from the
head of con-
st raicred rabbit.
The series of
flashes of
both frequen-
cies were im-
posed 4 times:
in the back-
ground period,
at the 10th
and 20 Ih min
of exposure,
and within
10 min after
exposure
ended .
Reference
Effects and Kating
Reactions of rearrangement Kol '
-------
TABLE (11-11 (conrliiileil)
CompoimiKs) mid
Concent rat ion (s),
HiR/m1 (ppm)
IICIIO 0.035
1 binocular light
si i mu I ill ion:
Humidity/
Temperature
Mode of
Exposure
See pre-
vious
entry
Species/Strain/ No. of
Age/Weight Test Animals
Kabbits 5 H
2.5 kg
No. of
Controls
S M
Duration and
Frequency of
Kxposnre
20 win
Total
Length of
Experiment
30 nin
meets
A series of light
flashes comprising
10 impulses with
frequencies of 4
and 7 llz, both of
which were tested
5 limes in a given
segment of the test
with 15-20 s be-
tween Hie separate
series.
No effect on the* reaction of
the rearrangement of rhythm
or on the overall electrical
activity of the brain.
Ke I cn-iirc
and Knt ing
Fel 'ilman anil Kk.slci
(IU75)
11-7
lloItiua and Kkstei
(1973)
B-7
-------
TAHI.K 111-12. HAIiniTH--l(EI'KATKI) DOSK K.XI'KKIMKNTAI, KXI'OSIMK TO KOKhAI.DKIIYnK (IICIIU)
C<>III|UIIIII(|(H) and
Concent ralion(ti),
mg/ni1 (ppm)
IIC 110 3.7-6.5
t Noise
IICIIO It. 6 ± 0.4
Humidity/ Mode of Species/Strain/ No. of No. of
Temperature Kxposore Age/Weight Test Animals Controls
Rabbits S 47 NoL
given
50% Inhala- Rabbits, 3 H No.
77 1 2°F lion New Zealand not
chamber albino given
(mod i -
tied
Rochester-
type)
Airflow
1.2 in3/
mill.
Diii.il ion anil Total
t're(|ii(Micy of l.rnglli ot
Kxposure Kxppriment Klfeils
Not "Short ll.ilii tuat ion to the irritant
given term" occurred. IICIIO changed the
total functional condition
of the brain (activation).
The high sensory input into
llu: olfactory structures, the
authors proposed, leads to
development of paroxysmal act-
ivity in the olfactory analy-
zer structures.
Continuous 90 d No deaths, llematologic values
for 90 d were normal. I.ungs showed
varying degrees of intersti-
tial inflammation.
Keference
anil Kal ing
' link ina and Kkslrr
(1973)
11-7
Coon ct al .
(1970)
B.-I2
IICIIO 2-:). 7
IICIIO 0.6'S
I stress by
rhythmic
light
Rabbits
Rabbits
S 47
Not
given
2-'. wk
Intermittent
exposure;
lime not
spec! fied
Slight drowsiness as evidenced
by KKti.
Provocation in the olfactory
bulb and corlicoinedial amyg-
dala of latent hidden foci of
paroxysmal activity. Thus,
the specific structures of
the olfactory analyzer are
Die initial respomlers to the
pathological actions of odor-
ous substances.
Bokinu and Kksler
(1973)
II-/
bokin,i and Kksler
(1973)
11-7
(continued)
-------
TAIU.E III-12 (concluded)
00
t-0
Compound(s) and
Coiirentration(s),
Humidity/
Temperature
Hode of
Exposure
IICIIO O.I
* functional
stress by
pecitylcnetelra-
zole
Species/Strain/
Age/Weight
Rabbits
No. of
Test Animals
No. of
Controls
Not
given
Hit rat ion and Total
Frequency of Length of
Exposure Experiment
I.S no
Kffe
-------
TAULE 111-13. CATS--ACUTE EXPERIMENTAL EXIKiSURE TO FORMALDEHYDE (IICIIO)
Compound(s) .mil
Coiictiiit ration(s),
ing/in3 (ppm)
Hum i (lily/
Temperature
Mode of
Exposure
Species/Si rain/
Agc/WeigliL
Duration and Total
No. of No. of Frequency of Length of
Test Animals Controls Exposure Experiment
Effects
Reference
and Rating
IICIIO 9,630
Inlia la-
lion
chamber
Cat,
3.2 kg
None
3.3 h
oo
LO
IICIIO 6,330
Inhala- Cat,
tion 2 kg
chamber
None
3 h,
once
3.3 h Immediate sneezing, tearing, • Iwanolf
saliva secretion, mouth (1911)
breathing, and dyspnea. C-8
Vomiting movements later; at
1.5 h, cat lying down; after
2 h, unable to stand up.
Respiration continued very
irregularly along with body
spasms until death at 200
min. Autopsy found blood
in nose, larynx damaged, tra-
chea! mucosa loosened, heart
damaged, eyes bloody.
3.3 h Immediate restlessness, saliva Iwanoff
secretion, eyes closed, respir- (1911)
ation 28. Later respiration C-8
decreased, dyspnea. After
2 h, vomiting of white foamy
liquid. Death 20 min after
exposure ends. Autopsy finds
normal eyes, mouth, nose, heart,
and kidneys. Slight hyperemia
of brain, coagulated fibrinous
liquid in trachea, and 1/3 of
lung functioning hindered by
hyperemia, edema, and bleeding.
(continued)
-------
TAIII.K 111-I I (.omlud.-d)
C(impound(s) anil
Comcnl ral lon(s),
rag/ro1 (ppm)
Humidity/
Temperature
Node of
Exposure
Species/Strain/
Age/Weight
Duration and Total
No. of No. of Frequency of Length of
Test Animals Controls Kxposurr Kxpcriwnl
Kfleits
Rot i-rent •<:
and Kill ing
IICIIO 2,010
Inhala-
tion
chamber
Cat,
2.0 kg
None 4.6 h, 4 d Immediate and ilistincl ct-
once fects: tearing, sneezing,
coughing, irregular lireath-
ing. Later, dyspnea and
wo(itli breathing, vomiting of
white foamy liquid. At end
of exposure', severe dyspnea
unil death on 4th d.
Iwrinof f
(1911)
C-8
IICIIO 825
oo
IICIIO 820
IICIIO 820
IICIIO 260
Inhala- Cat,
tion 2.6 kg
chamber
Inhala- Cat,
tion 2.7 kg
chamber
Inhala- Cat,
tion 1.8 kg
chamber
Inhala- Cat,
tion 3 kg
chamber
None
None
None
None
8 h,
once
8.6 h,
once
4 d
6 d
4 h,
once
3.5 h,
once
Observed
for sev-
eral days
after
exposure
Observed
for sev-
eral days
after ex-
posure
Irregular respiration, dyspnea, Iwanoff
coughing, body trembling, vom- (1911)
it ing movement a. At end of C-A
exposure, cat breathing with
difficulty, condition worsened,
death on 4th d.
Respiration increased, fiieez- Iwanoff
ing, coughing, difficulty in (1911)
breathing, increased saliva C-8
secretion. No recovery after
exposure; cat died on 6th d.
Coughing, respiration 16, in- Iwauoff
creased saliva secretion, con- (1911)
ditiou worsened during expos- C-8
tire. Cat recovered after sev-
eral days.
Respiration stowed, sneezing, Iwanoff
coughing, increased saliva (1911)
and tear secretion, eyes kept C-8
closed after 2 h, slight dys-
pnea. Cat recovered after
exposure.
-------
IAH/.K nr-i«. i'itis--AcuTK KXI'KIWIKNTAI. KXIUSIIXK TO KOHMAI.DKIIVDK (nciio)
CO
U!
Compound (s) and
Concent ration(s),
niK/m1 (ppm)
IICIIO -2.5
(2.0)
IICIIO ~ 0.25
(0.2)
IICIIO -0.03
(0.02)
Humidity/ Mode of
Temperature Exposure
Anesthe-
lixetl,
with
arti-
ficial
venti-
lation
Anesthe-
tized,
with
artifi-
cial
venti-
lation
Anellie-
tized,
with
arti-
ficial
venti-
lation
Duration and Total
Species/Strain/ No. of No. of i"rei|uency of Length of
Age/Weight Test Animals Controls Exposure Experiment
Pigs, 8 None 6 It, 6 h
21.7 i 1.4 kg, once
6-6 wk
Pigs, 7 None 6 h, 6 h
21.7 ± 1.4 kg, once
6-8 wk
I'igs, B None. 6 h, 6 h
21.7 t 1.4 kg, Actually once
6-8 wk this was
meant to
be the
control
group
for the
teals at
2.S and
0.25 mg/m3
levels
Keferen
Effects and li.it
No significant change in lung ' Frey el
compliance values or blood gas (1979)
values. Moderate morphologic H-12
changes in lungs, det>
-------
TABLE 111-15. DOOS—KEI'KATBI) U08K EXPERIMENTAL EXPOSURE TO FORMALDEHYDE (IICIIO)
Compound (8) anil
Concent ration(s),
nig/in1 (|>|>m)
Humidity/
Tempera I u re
IICIIO
4.6 t
0.4
50%
77 ± 2°K
Mode of
Exposure
Species/Strain/
Age/Weight
No. of
Test Animals
No. of
Controls
Duration and Total
Frequency of Length of
Exposure Experiment
Effects
Re f fruiter
ami Kaling
Inhala- Dogs,
tion purebred
chamber beagle
(modi-
fied
Rochester-
type)
Air flow
1.2 i
2 M
Not
given
Continuous
for 90
-------
TAIII.K 111-16. MONKEYS--REPEATED DOSE AND C1IKONIC EXPERIMENTAL EXPOSURE TO FORMAI.DKIIYUE (IICIIO)
Compoiind(s) and
Coiicentr.it ion(.s),
nig/ni1 (ppm)
IICIIO
4.6 t 0.4
IICIIO 3.75
Ci)
IICIIO 1.25
(1)
IICIIO 0.25
(0.2)
Humidity/ Mode of
Temperature Exposure
50% Inhala-
77 t 2°K lion
chamber
(modi-
fied
Rochester-
type)
Air flow
1.2 iiiVmin
Inhala-
tion
Inhala-
tion
Inhala-
tion
Species/Si rain/ No. of No. of
Age/Weight Test. Animals Controls
Squirrel 3 H Not
monkey given
I
Monkeys 6 M 6 M
Monkeys 6 M 6 M
Monkeys 6 M 6 M
Duration and Total
Krctjuency of Length ol
Exposure Experiment
Continuous 90 d
for 90 d
22 h/d 6 mo
7 d/wk
6 mo
22 h/d 6 mo
7 d/wk
6 mo
22 h/d 6 mo
7 d/wk
6 mo
Effects
No deaths, llemalologic values
were normal. Lungs showed
varying degrees of interstitial
inflammation.
Nasal discharge
Nasal discharge. No adverse
effects noted on pathological
eval nation.
No adverse effects noted
while exposed or on
pathological evaluation.
Reference
and Rat ing
Coon et a 1 .
(1970)
11-12
Clary (1980)
11- -
Clary (1980)
B--
Cliiry (1980)
11- -
-------
TABLE III-17. SUMMARY OF ANIMAL EXPOSURES TO FORMALDEHYDE (HCHO)
Level
(mg/m3)
6,330-9,630
820-2,010
600-1,700
900
712
312
260
200
140
50-150
Time
~ 3.5 h
4.6-8.6 h
30 min
2 h
4 h
1 h/d, 1-15 d
3.5 h
1 h/d, 3 d/wk,
4 wk
2 h/d, 4 d
1 h/d, 3 d/wk,
Species
CAT
CAT
RAT
MUS
HAM
HAM
CAT
MUS
MUS
MUS
Effects
Innnediate physical discomfort,
death near end of exposure.
Immediate discomfort, respiratory
difficulties, dyspnea, death in
4 to 6 d.
LD50: 1,000 mg/m3.
Death from massive pulmonary hemor-
rhage and edema.
Exfoliation of 34 to 100% of
trachea cells.
Histologic and cytologic changes in
tracheobronchial cells, recovery
2 to 6 wk.
Discomfort, respiratory difficul-
ties.
Death of 30%, metaplasia and hyper-
plasia of tracheobronchial epi-
thelium.
No significant effect. .
Weight gain normal, some basal-cell
35 wk hyperplasia and squamous-cell
metaplasia of tracheobronchial
epithelium.
10-100 40-60 d RAT HCHO level in blood increased 5X.
Eye and nose discomfort, lower body
weight and relative liver weight.
increased lung defense cells.
13-63 1 h GPG Significant changes in lung func-
tions; limited or no recovery
at 1 h post-exposure.
(Continued)
88
-------
TABLE 111-17. (continued)
Level
(mg/m3)
12.5-63
Time
4-24 h
Species
RAT
62.5
31.2
- 25
17-19
10-16
15
12.5
~ 12.5
12.5
3-8
once/wk
17 wk
5 h, twice
24 h
6 h/d, 24 mo
10 min
39 h
5 d/wk
"lifetime"
4 h/d, 5 d/wk,
13 wk
5 h
4 h, 1-10X
HAM
HAM
RAT
RAT
MUS
MUS
GPG
HAM
GPG
HAM
HAM
Effects
Range of concentrations causing
beginning toxic effects, sig-
nificantly increased alkaline
phosphatase activity of liver,
both increased and decreased
phagocytic activity of lung
macrophage cells, and slight
blood changes.
No effect.
Cell damage and repair, primarily
in turbinates; some adaptation to
irritant effects.
Decreased phagocytic activity of
lung macrophage cells.
Weight loss, deaths, squamous or
epithelial metaplasia, hyper-
plasia, and carcinomas in nasal
cavity.
Respiration rate decreased 66 to
77%.
Effect on blood cholinesterase and
leukocytes.
Decreased survival time; no effect
on nasal epithelium.
Significant changes of biochemical
indexes in lung, liver, and
kidneys.
Little cell damage and repair in
nasal turbinates and trachea.
Damage to airway cells, exfolia-
tion of tracheal and bronchial cells.
(Continued)
89
-------
TABLE III-17. (continued)
Level
(mg/m3) Time Species Effects
2 -6-7 6 h/d, 5 d/wk, RAT Decreased weight, ~ 5% deaths, dys-
24 mo plasia, metaplasia, and carcinoma
of nasal turbinates .
7 7 d RAT Decreased blood cholinesterase and
increased leukocytes .
7 7 d - 29 d GPG Decreased blood cholinesterase and
increased leukocytes ; greater
effects from continuous 7-d ex-
posure than longer intermittent
exposure.
0.7-6.5 1-1.5 h GPG Significant detrimental changes in
lung functions.
6 3-4 min RBT Decreased blood pressure, heart
rate, and respiratory rate.
3-5-6 10 s RBT Threshold of olfactory sensitivity.
5 ^ h RAT Decreased blood pressure; neutro-
philia; eosinophilia; minor irri-
tation to lungs, spleen, and
marrow.
5'6 4 h/d, 20 d RAT Slight effect on neuromuscular
system, slightly higher pre-
implantation mortality of em-
bryos, development of offspring
normal except for decreased spon-
taneous mobility.
4-6 90 d RBT Blood normal, inflammation in lungs
4-6 90 d DOG Blood normal, inflammation in
lungs.
4-6 90 d MKY Blood normal, inflammation in
lungs.
(Continued)
90
-------
TABLE 111-17. (continued)
Level
(mg/m3)
2-4.6
0.7-4.5
1.6-3.8
1-4
3.75
2-3.5
2.5
0.6-2.5
45-90 d
10 rain
3 h/d, 4 d
22 h/d
7 d/wk
6 mo
10 s - 10 min
6 h
Species Effects
GPG No deaths; slight cholinesterase
and leukocyte effects; inflamma-
tion in lung, heart, and kidneys.
Allergic effects appeared at
14 d.
RAT Lower body weight, slight inflamma-
tion of lungs, heart, and kidneys;
and decreased DNA-ase activity
of liver. Change in chronaxy
ratio of antagonistic muscles,
mild biochemical changes in brain,
liver, kidneys, and blood. In
lungs, hyperemia, desquamation
and proliferation, of lymphohisti-
ocytic elements.'
MUS Respiration rate decreased 26 to
53%, with or without prior ex-
posure to HCHO.
MUS Initial respiration rate decrease
of 18 to 72% at beginning of each
exposure. Some recovery during
exposure, less each day.
RAT
HAM
MKY
RBT
PIG
1-4 h
Nasal discharge in MKY; decreased
weight gain in RAT.
Disturbance in nervous system
responses.
No change in lung function, but
moderate morphologic changes,
more so in dorsal than ventral
section. Changes included
desquamation, interstitial edema,
emphysema, and atelectasis.
RAT Depression of nasal sensory re-
sponse, partial recovery within
1 h.
(Continued)
91
-------
TABLE 111-17. (continued)
Level
(mg/m3)
1-2
1.25
1.0
1.0
0.69
0.4-0.5
0.5
0.038-0.5
0.06-0.39
0.03-0.25
Time
4 h
Species
RAT
22 h/d
7 d/wk
6 mo
8 wk
8 mo
10 rain
4 h/d, 19-20 d
4-5 h/d, 4-6 mo
5-8 h/d, 21-28 d GPG
1 h
6 h
Effects
No effect.
RAT Nasal discharge in MKY; no other
HAM effects.
MKY
RAT Significant changes in ascorbic
acid, nucleic acids, DNA levels
in females and fetuses. Length
of pregnancy increased, number
of fetuses decreased, no defor-
mities. Histochemical changes
in heart, liver, and kidneys of
fetuses.
RAT No effect on body weight or blood
chemistry for either first gen-
eration or exposed offspring.
Offspring had some morphological
changes in lungs after 8-mo ex-
posure.
MUS Respiration rate decreased 14 to
16% with or without prior expo-
sure to HCHO.
RAT No overall toxic effects, fetuses
normal.
RAT No effects on general health, minor
changes in blood and urine param-
eters .
No effect on general health, minor
changes in blood and urine param-
eters, formation of antibodies.
GPG Significant change in lung func-
tion, some recovery within 1 h
post-exposure.
PIG Change in lung function and slight
lung inflammation.
(Continued)
92
-------
TABLE 111-17. (concluded)
Level
(mg/m3)
0.25
Time
22 h/d
7 d/wk
6 mo
Species
RAT No effect.
HAM
MKY
Effects
0.1
69-90 d
0.031-0.035 90-98 d
RAT
RAT
0.035
3-8 h/d, 6 mo
RAT
0.012
8-12 wk
RAT
0.011
7-8 h/d, 21-30 d GPG
Signs of beginning damage to nasal
mucosa; DNA-ase activity of liver
increased, spleen decreased.
No effect on overall health, nervous
system response slowed s-lightly,
slight inflammation areas in
lungs and liver.
No effect in general condition,
changes in metabolic processes
of liver, blood changes, and
testicular biochemical changes.
Decreased sperm mobility.
No effect on overall health, ner-
vous system slowed slightly,
slight inflammation in areas of
lungs. Biochemical changes in
liver of female and fetuses, in-
creased length of pregnancy, de-
creased number of fetuses, no
deformities. Histochemical
changes in heart and kidneys of
fetuses.
Blood unaffected, phagocytic activ-
ity increased, formation of anti-
bodies; when stressed 2 mo later
by hypoxia, immune response and
phagocytic activity adversely af-
fected.
93
-------
SECTION IV
EXPERIMENTAL HUMAN INHALATION EXPOSURES
Table IV-1 describes acute laboratory human exposures to formaldehyde.
In the Summary, Table S-2 condenses all the information regarding experi-
mental human exposure, from about 17 mg/m3 to 0.0024 mg/m3. The American
Conference of Governmental Industrial Hygienists gives 3.0 mg/m3 as the
time-weighted-average threshold limit value (ACGIH, 1980).
95
-------
TABLE IV-I. IIIIMANS--ACIITK EXPERIMENTAL INHALATION EXPOSURE TO FORMALDEHYDE (IICIIO)
Compoimd(s) and
Concenlralion(s)
in ing/m' (ppm)
IICIIO 17.3
(13.8)
IICIIO 1-9.6
IICIIO 6.25
(5)
Mode of
Exposure
Inhala-
tion
chamber
Eye
goggles,
static
flow
condi-
tions
No. of
Test Subjects
12 M,
18-45 y;
all exposed
simultane-
ously
13-20, for
a total of
27 exposures
No. of
Controls
Controls
used; no
number
given
Served
as own
controls
Duration and Total
Frequency of Length of
Exposure Experiment
30 min Not given
5 min Not given
(up to 3
exposures)
Effects
Nasal and eye irritation when
first entering chamber, con-
tinued mild lacrimalion. Eye
irritation wore off after 10
min in chamber.
Irritation (if the mucous mem-
branes of the eyes and upper
respiratory tract.
18 positive responses (of 27)
indicating moderate or severe
irritation to the eyes.
Reference
and Rating
Sim and fall le
(1957)
B-9
Lazarcv
(1965);
cited in
Zaeva ct al .
(1968)
B-5
Stephens et al
(1961)
A-9
IICIIO 5.0
(4)
IICIIO 5.0
Climatic 35 M
chamber, 13 F,
30 in3 "healthy
students"
Served
as own
controls
Eye
goggles,
dynamic
flow
condi-
tions
A total of
7 exposures
Served
as own
controls
7.5 min;
5 x 1.5-min
exposures
at 8-min
intervals
5 min
39.5 min
10 min
(a 5-miii
pre-
exposure
control
period)
Irritant indexes* high for each Weber-
exposure, and above the values Tschopp
for lower exposure levels, both et al.
intermittent and continuous. (1977)
Irritation of nose and throat A-IS
more marked than in continuous
exposure. No effects felt
after 4-5 min of recovery.
7 of 7 positive responses indi- Stephens
eating moderate to severe eye et al.
irritation. (1961)
A-9
*Irritant indexes included eye irritation, frequency of blinking, nasal irritation, irritation of the throat, and
distress (e.g., "desire to leave the room").
(continued)
-------
TABLE IV-1 (continued)
Coni|>ound(s) ami
Comciilrat ion(s)
In ing/oi1 (ppm)
IICIIO 5
(4)
Mode of No. of
Exposure Tcsl Subjects
Eye Not given
irrita-
tion
booth
connected
to a
chamber
No. of
Cont rols
Not
given
Duration and
Frequency of
Exposure
5 min
Total
Length of
Experiment Effects
5 mill Caused medium to severe eye
irritation.
Reference
mid Kali UK
Schuck and
Renzett i
(1960)
C-8
Scliuck and
Doyle
(1959)
C-8
IICIIO 2.5-5.0
(2-4)
IICIIO 4.0
(3.2)
Exposure con-
centration in-
creased steadily
to this level
Kye
goggles,
static
flow
condi-
tions
13-20, for a
total of 47
exposures
Served
as own
controls
5 min
(up to 4
different
exposures)
Not
given
Climatic 24 H Served
chamber, 9 f, as own
30 m1 "healthy controls
students"
37 mill
37 min
16 positive responses (of 47) Stephens
Indicating moderate or severe et al.
eye irritation. (1961)
A-9
Adaptation to irritant occurred Weber-
to some extent during first few Tschopp
minutes of exposure. Irritant et al.
indexes4 rose with increasing (1977)
concentration in all cases ex- A-15
cept for throat irritation.
Irritation to the eyes more
marked and nose and throat ir-
ritation less marked than In
intermittent exposures to the
same levels.
IICIIO 3.75 Climatic 35 N Served 7.5 min; 39.5 min Irritant indexes* ranged from Weber-
O) chamber, 13 F, as own 5 x 1.5-min slight lo strong; values above Tschopp
30m1 "healthy controls exposures those for inlermittent expos- et al.
students" at 8-min lire (o lower levels and con- (1977)
intervals tinuoiis exposure to all levels A-15
(S 4.0 mg/ui1). Irritation of nose
and throat more marked and eye
irritation less marked than in
exposure to a similar level
during continuously rising
exposure.
* irritant indexes included eye irritation, frequency of blinking, nasal irritation, irritation of the throat, and
(e.g., "desire to leave the room").
(emit iniied)
-------
Compound(&) anil
Com cut i at ion(s)
In mg/iii3 (|)|)ra)
Mode of
Exposure
TABLE IV-1 (toiiliimed)
No. of
Test Subjects
Nu. of
ConIroIs
Dnrntion ami
Frequency of
Kxposure
Total
Length of
Experiment
Effects
Reference
and Haling
IICIIO 1.75
O)
IICIIO 3
Eye
ports in
a chamber,
or face
masks at-
tached
to the
chamber
Not given
Not given 5 mill
When exposure was through the
hooils, noderato to severe eye
irritation occurred. When
exposure was through the ports,
even more severe irritation
occurred, with lacrlmation in
> 50% of the subjects.
Threshold of irritation.
Rf'iizrll i
Schuck
(1961)
C-8
Isachcnko
(1940);
cited in
Melekhina
(1960)
A-9
and
CO
IICIIO 2.S
(2)
IICIIO 2.5
(2)
Eye
goggles,
dynamic
flow
condi-
tions
Climatic
chamber,
30 m1
13-20, for a
total of 37
exposures
35 M
13 F,
"healthy
students"
Served
as own
controls
Served
as own
controls
12 min
(up to 4
exposures)
7.5 min;
5 x 1 .5 -min
exposures
at 8 -in in
intervals
Not given 9 positive responses (of 37) Stephens et al.
indicating moderate to severe (1961)
eye irritation. A-9
39.5 min Irritant indexes* ranged from Weber-
almust none to strong; values Tscliopp
above those for intermittent et al.
exposures to lower levels and (1977)
continuous exposure to all A-15
levels (5 4.0 nig/in1). Irritation
of nose and throat more marked
and eye irritation less marked
than in exposure to a similar
level during continuously rising
exposure.
Irritant indexes included eye irritation, frequency of blinking, nasal irritation, irritation of the throat, and
distress (e.g., "desire to leave the room").
(continued)
-------
TABLE IV-I (continued)
Compound(B) and
Concenlratioii(s)
In wg/m1 (ppa)
IICIIO 2.5
IICIIO 2.0
Node of
Exposure
Not
given
Inhala-
tion
chamber
No. of No. of
Test Subjects Controls
1 Not
given
16 Served
as own
controls
Duration and
Frequency of
Exposure
Not
given
5 h
Total
Length of
Experiment
Not
given
7-8 h;
2-h pre-
exposure
period
Effects
No changes were noted in the
frequency and rhythm of respir-
ation at IICIIO levels helow this.
Slight, statistically in-
significant changes in air-
way resistance parameters:
FEV., FEF,5_m, VC, and nasal
Reference
and Hating
fie It kill fia
(1964)
A-9
Helekhina
(I960)
A-9
Andersen
(1979)
A- 14
odor threshold for ethyl-
valeriate after 2 and 4 h
of exposure. Nasal mucus
flow rate was decreased in
the first third of the none,
•ore so after 4 than after 2 h
of exposure. Slight subjective
disconforl (1-18 on a scale
of 100), increasing to IB by 2-3 h,
then decreasing to 11 by 3-5 h of
exposure. This decrease indi-
cates that acclimatization occurred.
IS/15 complained of conjunctivaI
irritation and dryness in the
nose and throat. No symptoms the
following morning. No change in
various performance tests (arithme-
tic and card punching).
IICIIO 1.71
Nut
given
Served
as own
controls
4.5
15 Hill
Caused a sharp decrease ill
sensitivity to light in all
subject a.
Helekhina
(1964)
A-9
Melekhina
(I960)
A-9
(continued)
-------
TAMI.E IV-I (continued)
o
o
Compound (B) and
Concent rat ion(s)
in mg/m1 (ppm)
IICIIO 1.25
(1)
IICIIO 1.25
O)
Node o f
Kxposure
Eye
goggles,
static
flow
coiul i -
lions
Climatic
chamber,
30 m1
No. of No. of
Tesl Subjects Controls
13-20, for a Served
total of 75 as own
exposures controls
35 M Served
13 F, as own
"healthy controls
students"
Duration and Total
Frequency of Length of
Exposure Kxperinicnl
5 min Not
(up lo 8 given
dii re rent
exposures)
7.5 rain; 39.5 min
5 x 1.5-min
exposures
at 8-min
intervals
Kf fuels
6 positive responses (of 75)
i ndical ing moderate lo severe
eye irritation.
Irritant indexes* ranged from
almosl none lo moderate; values
below all Ihose for intermit-
tent exposure lo higher levels
(2.5-5.0 mg/m3) and above some
of Ihose for continuous exposures
(< A mg/m1). Nasal irritalion *tt
general distress were grealer,
throat irritation equal to,
and eye irritation less than
thai for exposure lo a similar
level during a continuously
rising exposure.
Reference
and Ral ing
Stephens et al
(1961)
A-9
Weber-
Tschopp
el al .
(1977)
A-15
d
IICIIO 1.2S
(1.0)
Odor 4 Irained Served
lesl odor analysis as own
room controls
Lowest concentration at which Leonardos
all the subjects positively el al.
recognized the odor. (1969)
A-ll
Irritant indexes included eye irritalion, frequency of blinking, nasal irritation, irrilation of the throal, and
distress (e.g., "desire to leave Ihe room").
(continued)
-------
TAIH.E IV-1 (contiimcil)
Coiu|>oiiiMl(a) and
Content ra I ion (a)
III Kg/Ill1 (|>|HO)
1ICIIO 1.0
Nude or No. of
Exposure Tea I Subjects
Ii.hala- 16
lion
chamber
No. of
Controls
Served
as own
controls
Duration and
Frequency of
Exposure
5 h
Total
Length of
Experiment
7-8 h;
2-h pre-
exposure
period
effects
Slight, statistically in-
significant changes in air-
way resistance parameters:
rev., FEF,, .... VC, and
Reference
and Killing
Andersen
(1979)
A-14
IICKO 1.0
Exposure
chamber
with
respir-
ator
helmet
10 «ln
Not given
IICIIO 0.95-1.0
nasal preBSnrE'Mrop. No
change in the odor threshold
for ethylvalerlate, or nasal
mums flow rate. Slight sub-
jective discomfort (1-10 on a
scale of 100), generally in-
creasing for 3 h then remain-
ing steady. Below the discom-
fort reported for 2.0 mg/ra', and
above that for 0.3 and 0.5 rng/m1.
15/15 complained of conjunctival
irritation and dryness of the nose
throat. No complaints the follow-
ing morning. No change in various
performance tests (arithmetic and
curd punching).
Odor perception in all individ-
uals. Two experienced upper
respiratory tract Irritation.
Majority experienced distor-
tions of the breathing rhythm,
skin-galvanic reaction, heart
action, and KEG changes in
a-rhythms indicating possible
development of a cortical in-
hibition process. There was
also some involuntary muscle
and eye movement. Author rec-
ommended a max Imum permissible
concentration of 1 mg/in3.
Slight irritating effect to
I In' mucous nifiiihrune of the
eye and to the niiicoKa of tilt*
upper respiratory tract.
Sgibnev
(1968)
A-7
Shi 1 ilia M;
cited in
Mclekhiiiii
(I960)
A-9
ilined)
-------
TABLE 1V-I (t-oiitinucil)
Compound (s) arid
Concent ration(s)
in mg/m3 (ppm)
IICIIO 0.53
IICIIO 0.5
Duration and
Mode of No. of No. of Frequency of
Exposure Test Subjects Controls Exposure
5 M,
10-32 y;
persons most
sensitive to
odor of the
IICIIO from
previous
testing wilh
larger group
Inliala- 16 Served 5 h
lion as own
chamber controls
Total
Length of
Experiment
7-fl h;
2-h pre-
cxposure
Effects
Caused a statistically signifi-
cant lowering of the amplitude
of the total EEC and the Iheta
rhythm in mosl of the subjects.
Considered the threshold value
for effect on electrical activ-
ity of the human brain.
Slight, statistically insig-
nificant changes in airway
resistance parameters:
deference
and Rating
Fel MIJI.III
(1972)
B-7
Andersen
(1979)
A-14
t-1
O
f-J
IICIIO 0.3-0.4
Exposure
chamber
wilh
respir-
ator
helmet
10 mill
period FKV VC, Ffcf'oij.is'y > an
-------
TABLE IV-t (continued)
Compound(s) and
Concentratioufs)
In rag/m* (pp«)
Node of
Exposure
No. of
Test Subjects
No. of
Controls
Duration anil
Frequency of
Exposure
Total
Length of
Experiment
Effects
Reference
and K.il ing
IICIIO 0.3
Inhala-
tion
chamber
16
Served
as own
controls
5 li
7-8 h;
2-h |>re-
exposurc
period
o
UJ
IICIIO 0.3
Not
given
Served
as own
controls
4.5 nin
15 min
Slight, statistically insig-
nificant changes in airway
parameters: FEV., VC,
FEF,, ,»*. and nasal pres-
sure drop. No change in
the odor threshold for
elhylvaleriale. Nasal mucus
flow rate was decreased in
the* first third of the nose,
more so after 4 than after 2 h
of exposure. Only slight sub-
jective discomfort was reported
(1-9 on a scale of 100), gen-
erally increasing with time.
Above that reported for ex-
posure to 0.5 mg/m1, and he-
low that for 1 or 2 rag/m1.
3/15 complained of conjunrtival
irritation and dryness in the
nose and throat. No complaints
the following morning. No
change in various performance
tests (arithmetic and card
punching).
Caused a delay in adaptation
to darkness in 2/3.
Andersen
(1979)
A-14
Nelekhina
A-9
Helekhina
(1960)
A-9
IICIIO 0.25
(0.2)
Eye ex-
posure,
hag with
controlled
flow rate
10-22,
19-32-y-old
Not
g i vcn
.100 s,
onre
Not given Threshold for eye irritation.
Okawada el al.
(1979)
A-ll
(continued)
-------
TABLE IV-I (continued)
Comp»nnd(s) and
Concent rat ion(s)
in mg/m1 (ppro)
HCliO 0.2
IICIIO 0.098
IICIIO 0.090
IICIIO 0.084
IICIIO 0.080
IICIIO 0.077
IICIIO
0.068-0.075
Mode of No. of No. of
Exposure Test Subjects Controls
Not 3 Served
given as own
controls
3 Served
as own
controls
Not IS, Served
given 17-44 y as own
controls
3 Served
as own
controls
Not 15, Served
given 17-44 y as own
controls
Not 28, Not
given 20-30 y, given
"practically
healthy11
Not 3 Served
given as own
controls
Duration and Total
Frequency of Length of
Exposure Experiment Effects
4.5 min 15 min Increased sensitivity to light
in 3/3.
4.5 roin 15 rain Threshold of formaldehyde vapor
reflex effect on the functional
state of the cerebral cortex,
as determined by dark adapta-
tion (no effect on 3/3).
Not given Not given Minimum detectable odor con-
centration for 4/15.
15 min Not given Threshold for eliciting reflex
activity in optical chronaxy.*
Not given Not given Only 11/15 could smell this
level, and it was the minimum
detectable concentration for
4 of them.
Not Not Odor threshold for persons
given given who are most sensitive to
IICIIO.
15 min Not Snbthreshold concentration for
given effect on optical chronaxy* or
on the rheobase.**
Uelerem e
and Katinf>
Melekliina
(1964)
A-9
Helekhina
(1960)
A-9
Melekhina
(1964)
A-9
Melekhina
(I960)
A-9
Fel 'dmaii and
Honashevskaya
(1971)
A- 10
Helekhina
(1964)
A-9
Helekhina
(1960)
A-9
Pel "din. in and
Donashevskaya
(1971)
A-10
Makeicheva
(1978)
11-9
Melekhina
(1964)
A-9
Helekhina
(1960)
A-9
The chronaxy is the time required for the excitation of a nervous clement by a stimulus; minimum lime at which a
stimulus just double the rhcobase** will excite contraction of a muscle.
** The rheobase is the minimum potential of electric current necessary to produce si him I all on of a nerve.
(conli lined)
-------
TAIII.K IV-1 (cunt inuc
-------
TABLE IV* I (continued)
Compound (s) anil
Concent rut iuri(s) Mode of
in ing/Hi1 (|i]>m) Exposure
IICIIO 0.054 Not
given
IICIIO 0.054 Not
jj i von
IICIIO 0.053 Not
given
IICIIO 0.05 Inhala-
tion
IICIIO 0.05 Inlia la-
lion
IICIIO 0.046
Durat ii
Nil. of No. of Krei|iiei
Test Subjects Controls Expo:
28, Not Nut
"clinically given given
healthy,"
17-48 y
15, Served Not
17-44 y as own given
controls
5 Served 20 min
(of most as own
sensitive controls
from ol-
factory
tests)
12, Not
19-64 y given
64.
17-63-
y-old
5 , Not Not
with dis- given given
linct o-
rliythm
To1.11
Length of
Experiment
Not
given
Not
given
Kffecls
Maximum iindelectablc odor con-
cent rat ion for the subjects
most sens it ive to IICIIO.
None could detect IICIIO at this
level. 7/15 subjects found
this level to he the maximum
undetectahle odor concen-
tration.
35 min;
5 min
before and
10 inin
after ex-
posure for
comparison;
repeated 3-4
t imes at un-
known intervals
Threshold concentration for
EEC changes after stimulation
by flashing light.
Not given;
was re-
peated on
3 succes-
sive days
Suhthreshold concentration for
olfactory recognition even in
the subjects most sensitive to
IICIIO (7/12).
Odor threshold.
Not
given
Elicited significant desynchro-
nization of the o-rhythm of
all subjects in the electro-
cortical conditioned reflex
study.
Kel erciicr
ami Kill hi);
tel'dinan
(1974)
A-9
Kel 'dinarI mid
Donaslievskaya
(1971)
A-10
Pel'dman
(1974)
A-9
Fel '
-------
TAHI.K IV-1 (fuiilimicil)
Compound(a) and
Coficeutrition(s)
in mg/mj (ppn)
IICIIU 0.01,
O
IICIIO 0.035
IICIIO 0.029
IICIIO 0.023
N02 0.08
flexune 40.0
IICIIO 0.016
Mode of No. of
Exposure Teat Subjects
Not 5 H,
given 18-32 y
(uost sen-
sitive from
olfactory
tests)
Duration and Total
No. of Frequency of Length of
Controls Exposure Experiment
Served 20 min 35 win;
as awn 5 min
controls before and
10 nin af-
ter expos-
ure for
comparison;
repeated 3-4
times at un-
Effect*
Subthreshold concentration for
KKG changes after stimulation
by flashing light.
known intervals
5,
with dis-
tinct o-
rhythm
Not 23,
given 14-48 y
Not Not Not
given given given
Not Perhaps Not
given 7 s given
Apparently inactive in the
elect rocortical conditioned
reflex study. Proposed one-
tiae MAC in atmospheric air
should be at inactive level.
Threshold of salivary action.
17/23 detected an odor. A sub-
threshold mixture for the re-
maining 6.
Threshold of Irritation of
the nervous system.
Reference
and Kating
Fel ' ilma n
(1974)
A-9
Kel 'dman and
Ronatihcviikayii
(1971)
A-10
Fcl 'dmari
(1972)
B-7
Nakcicbeva
(1978)
U-9
Van Ven' -yon'
(1956);
cited in
Zaeva et al.
(1968)
B-5
Fel'diiuin
(1974)
A-9
Van Veil1 -yan'
(1956);
cited in
Zaeva et al .
(1968)
11-5
(conl inuiMl)
-------
TAIII.K IV-I (continued)
O
CO
Compound (s) and
Coiicenlral ion(s)
i g/m1 (ppm)
IICIIO 0.016
N02 0.05
llexane 29.0
IICIIO 0.014
CO 1.4
NOZ 0.046
llexnne 23.0
IICIIO 0.01
CO 1.1
N02 0.029
Ilex, -me 18.3
Mode of No. of
Exposure Test Subjects
Not 23,
given 14-48 y
Not 5 (most
given sensitive
from ol-
factory
tests)
Not 5 (most
given sensitive
from ol -
factory
tests)
Duration and Total
No. ol Frequency of Length ol
Controls Exposure Experiment
Not Perhaps Not
given 7 s given
Served 20 min 3S in in;
as own S min he-
controls (ore and
10 min
after ex-
posure for
comparison;
repeated
3-4 times
at unknown
intervals
Served 20 min 15 win;
as own 5 min
controls before
and 10 niin
after ex-
posure for
comparison;
repeated
3-4 times at
unknown in-
tervals.
Effects
No oddr was delected by any of
the subjects.
Significant changes in EEC fol-
lowing stimulation by flashing
light were observed in 4/5 sub-
jects. Exact nature of the
changes varied between indi-
viduals. The effect of Ibis
mixture appears to be simply
additive.
No effect on EEC following
stimulation by flashing light
was noted in any subject.
Reference
and Rating
Eel 'dinaii
(1974)
A-9
Fel 'dman
(1974)
A-9
Fel'dman
(1974)
A-9
(continued)
-------
Comj)oitml(s) and
Concent rat ion(s)
in mg/rn1 (ppm)
TABLE IV-1 (continued)
Mode of
Exposure
No. of
Test Subjects
No. of
Controls
Duration and
Frequency of
Exposure
Total
l.cnglli of
Experiment
meets
Reference
ami K.il Ing
O
vo
IICIIO 0.01
Acetic acid 0.006
Acetic anhydride
0.052
Acetone 0.22
Phenol 0.004
IIC1 0.07
Inhala-
tion
18 M,
17-35 y
IICIIO 0.0085
Acetone 0.075
Phenol 0.0027
Acetic acid 0.046
Acetic anhydride
0.031
1IC1 0.072
IICIIO 0.0075
3 H
IICIIO 0.0075
Phenol 0.0025
Acetic acid 0.038
Acetic anhydride
0.025
IICI 0.055
Ace tune: 0.063
3 M
Odor of mixture imperceptible.
The index of total concentra-
lions (the sum of the fraction
of each compound present rela-
tive to its isolated threshold
value) was < 0.90. Mix-
tures of these substances were
iiaperceptible by odor when the
index of total concentration
was ci|ual or near to 0.97-1. OB,
which attests to the simple
summation effect, where the
simultaneous presence of dif-
ferent atmospheric contaminants
is caused by their nonspecific
action at low concentrations.
The index of total concentra-
tion was 1.04. Caused a sta-
tistically significant change
in the desyiichronization of
the u-rhythms of the drain cor-
tex in all subjects.
Threshold of respiratory
irritation.
The index of total concentra-
tion was 0.86. Had no effect
on the electrical activity of
the brain cottex (electrocor-
tual condit i uned reflex study)
Tiikhirnv
(1974)
11-8
Takhlrov
(1974)
B-8
Van Ven'-yan1
(1956);
cited In
Zaeva et
(1968)
B-5
Takhlrov
(1974)
11-8
al
(rout limed)
-------
1—'
O
TABLE IV-I (run. hided)
Coiii|)<)iiii
-------
SECTION V
EPIDEMIOLOGY AND RELATED HUMAN EXPOSURES
Chapter VI contains a discussion of the epidemiclogical studies. The
Summary contains a table, S-3, condensing the better data. A discussion
of on-going epidemiological studies is given in Appendix A. Studies tabu-
lated herein are classified according to whether the exposures were occupa-
tional or of the general public.
OCCUPATIONAL EXPOSURES
Data for the occupational exposures to HCHO are given in Table V-l.
The information is ordered by decreasing HCHO concentration. Maximum values
determine the place in the table where ranges are given. Studies with no
HCHO concentrations reported were generally placed at the end of the table.
However, as with the mortician studies, when a similar study was tabulated
that did report HCHO levels, the no-concentration entry immediately followed
it.
The usefulness of the studies is limited by the frequent presence of
confounding factors (especially dusts and phenol), the one-time measurement
of HCHO levels during chronic exposure, the probable variations in HCHO level
with time, and the usual lack of an adequate control or comparison group.
The general system for assigning applicability ratings to the documents
as described in Figure 1-1 was modified to accommodate the kinds of occupa-
tional exposures described. Studies describing long-term, nonconfounded
exposure, with symptoms correlated to HCHO concentration, were rated A.
Similar long-term studies, but with slightly confounded exposure or non-
respiratory endpoints and symptoms measured, received B ratings. Short-
term exposure studies, those with more serious confounding, those which
lacked correlation with HCHO level, or those which provided no concentra-
tions were rated C. D-ratings were given to studies which had multiple
problems, or were badly confounded.
EXPOSURES OF THE GENERAL PUBLIC
Data from epidemiological studies of exposure of the general public
are given in Table V-2, listed in order of decreasing HCHO concentration.
The maximum concentration was used to decide placement in the table when
ranges were given. Again, the studies were of limited usefulness due to
111
-------
lack of proper control groups, no reasonable estimates of HCHO exposure,
and severe selection bias. No study received an A-rating, because they
lacked chronic (in terms of the human lifespan) exposure and had only one-
time HCHO measurements during an exposure in which the HCHO levels probably
continuously decreased with time. Thus, dose-response relationships could
not be determined. Lack of concentration information resulted in a C-rating,
and combined with a lack of formal study design resulted in a D-rating.
112
-------
TAHI.E V-l. STUD IKS OK OCCUPATIONAL KXl'OSIIRK TO KOHNAMtKIIYUK (IICIIO)
Conipound(s) anil
Conccntratinii(s)
in mg/m3 dipin)
_ _________
Description
___ ___
Exposed ConliroTs
K fleets
Rematks
Reference
ami
Ral iiiK
IICIIO
5-78
He Ilia no 1
2.1-7.5
Elhanol
47.5-110
Workers in I lie for-
malin depl. of •
sheepskin dyeing
factory
99 f; 84 F Complaints of persistent head-
25-40- in other ache, vcrligo, irritability,
y-old; shops, and tendency to weep. Skin
worked free of temperature was measured on
for 5- IICIIO the forehead, chest, and fote-
20 y vapors arm, and Hie variations be-
tween the left and right sides
of the body reported. The in-
cidence of physiological ther-
mal asymmetry (a difference of
0.1-0.5 °C) before work was
43.3% in the exposed group and
27.2% in the controls. The
incidence of pathological ther-
mal asymmetry (0.6-2.2 °C) be-
fore work was 48.4% in the test
group and 3.0% in the controls.
Alter work, the physiological
asymmetry was about equal in
both groups (33% vs. 34.5% in
the controls), and the path-
ological asymmetry increased
to 60% in the lest group, com-
pared to 8.6% in the control
group. The authors consider
this evidence of adverse ef-
fects on Hie CNS, including
the thermnregulatory center.
Essentially a prospective do- K.imi liat nov
sign. The exposure was con- and Guyazova
founded by the presence of (19/1)
ellianol and meth.inol vapors, C-8
and monochloroacetic acid.
Comparability of the controls
is not discussed.
(continued)
-------
TAIII.K V-l (continued)
Compound(H) anil
Concealrat ion(u) ''"Llu'aL!oJ!L?lro/lI) _
in mg/m3 (ppm) Description Exposed
Controls
filfeels
Remarks
!<<•!eieui e
ami
Hat ing
Working chamber:
IICIIO, uvg. 0.56;
12-35 °C; rela-
tive humidity,
20-92%.
Antechamber
ot lite dis-
inice I ion
chamber: IICIIO,
0.33-42.0.
Mean concen-
tration at 4
sites: 2.25-
12.4
Workers servicing
formal in vapor dis-
inlecliun chamliei s.
Various construction
delects and incorrectly
followed procedures
allowed contamination
of the air with IICIIO.
Most IICIIO evolved while
pouring the formalin.
Higher IICIIO concentra-
tions were found at
the ceiling than at
the breathing zone
and the floor.
Hospital examina-
tions were performed
in 1967 and 1969.
93 Not Diseases of the autoiioiuic nei-
(1967) given vous system were observed in
24 persons; pneumosclerosis,
emphysema ot the lungs, and
chronic bronchitis in 17;
chronic sub- and alrophic
pharyngilin in 13; hyper-
thyroidism in 5; bronchial
asthma in 3; dyskinesia of
the bile ducts in 5; and
thrombocylopenia in 41.
223 Not Diseases of the heart and ves-
(from given sels were observed in 41; auto-
total of nomic dystonia and aulonomic
285 neuroses in 29; diseases of I lie
workers liver and bile ducts, in 14;
in same subatrophic rhinotraclieolaryn-
depart- gitis, in 20; cerebrosclerosis,
meut) in IS; pneiiniosclerosis, empliy-
(1969) sema of the lungs, chronic bron-
chitis, and bronchial astluna, in
5; hyperthy to id ism in 2; chronic
tonsillitis, in 9; chronic con-
junctivitis, in 2; neuritis of
the auditory nerve in 2; chronic
eczema, in 2; and facial dermati-
tis in 1. The percent of acelyl-
choline decomposition was lowered
to 27-35% in 23 persons and was
found at the low-normal limit
(36-37%) in yet another 20. In
1969, the choliiieslerase activity
appeared inhibited in 30.4% of
the subjects with another 29.6%
on the lower-norniii 1 boundary.
Descriptive, unconIroI led
study of IICIIO exposure. A
wicle range of exposure con-
centrations are reported, but
symptoms are not correlated
to exposure levels.
I' rave el
(1972)
C-7
a I
(continued)
-------
TAHI.K V-l (continued)
t' 5 y:
38.6 t
3.0 y old.
8 former
production-
line work-
ers and
supervisors
38.0 i 4.3
y old.
Present-line work-
ers had smoked
much less than the
never-on-line
group; but all were
similar in propor-
tions of cigarette
smokers, ex-smokers
and non-smokers at
the time ot this
survey.
All present-lint! groups showed
an excess of chronic cough or
cough and phlegm. All groups
(even controls, though some-
what lower %) complained of
irritation of the eyes, nose,
throat, lower respiratory
tract, and skin. No signifi-
cant differences in FVC (forced
vital capacity) or FEVi (one-
second forced expiratory vol-
ume) among any of the groups
though the S 1 y groups tended
to have higher FVC values.
After adjustment for smoking
habits, the group on the pre-
sent line > 5 y liad signifi-
cantly lower lung function
values, the 1-5 y group
had somewhat lower values,
and the < 1 y group was very
similar to the controls.
Above values were for Hon.
a.m. By Kri., only decreased
FKVj occurred in the exposed
groups.
Remarks
Helerencc
ami
Kali UK
The
Cross-sectional study.
deficiencies include:
(a) small numbers of exposed
and control subjects.
(b) exposure measurements not
made during study.
(r) control subjects were ex-
poued to resin fumes which
would tend to diminish dif-
ferences.
Advantages of the study are the
evaluation of pulinon.iry function
by objective measures (KKV, etc.)
and adjustment for smoking history.
According to the authors, the sim-
ilarity between controls uud pre-
vious-on-line workers suggests
that the chronic effects are re-
versible. The controls were oc-
casionally exposed, explaining
the high prevalence of acute mucous
membrane irritation in that group
(47-80X).
Schoeuherg
and Mitchell
(1975)
C-9
* None of the measurements was made during this survey. They were made (in the same mouth) by un insurance company industrial hygieuisl.
(continued)
-------
TAUI.F. V-l (continued)
Compound(s) and
Com enlral ion(s)
in mg/m3 (ppm)
l'o|)iilat ion Croup
Description Exposed
Control a
IU l
IICIIO $37.5
(S 30)
mostly < 12.5
(mostly < 10)
Workers employed £ 5
y in a factory en-
gaged mainly in mak-
ing urea-HCIIO resin
and molding powders
and some phenol -IICIIO
resin. Some of the
men had spent some
years of service away
from IICIIO exposure.
25 H, None
ages
24-61 y,
5.5-18 y
employ-
ment
Four had shown a mild dermati-
tis that cleared aftet a few
days' treatment. Six showed
blood counts with a temporary
reversal of the polymorphonu-
clear- lymphocyte ratio. In 5
cases t the ratio returned to
normal a few weeks later. Four
men experienced dyspnea on ex-
ertion; one had hypertension,
cardiac enlargement, * and al-
buminnria; the other, bronchial
asthma'""' for several years.
IICIIO
25 (20)
Workers using a gas
chamber to check the
efficiency of a IICIIO
sampler (impinger-
type)
Not
given
None
Immediate irritation of the
eyes and upper respiratory
tract: lacrimatiun within
15-30 B, nose and throat
irritation within 20-30 s,
sneezing within 1-2 min.
Exposure could continue "for
some length of time" but was
distinctly uncomfortable.
Remarks
A descriptive summary of case
reports:
(a) no controls or comparison
group
(b) dermatological problems
improved when the workers
were removed from that
.setting, strongly impli-
cating IICIIO exposure.
Anecdotal account.
Reference
and
Rating
liari i s
(1953.)
C-?
Da rues and
Speicher
(1942)
C-3
/ Only 12 of the mens1 blood counts are listed as "normal." Abnormalities in white cell count were most frequent: counts of 10,000-14,900
in 10 workers and 4,500 and 4,100 in 2 others.
* In the tabulated results, it can be seen that 3 of the 25 men showed cardiac enlargement, but the one who suffered from dyspnea is not
ident i fied.
*'* This worker is not identified from the tabulated results either. Two workers had emphysema.
(cont inued)
-------
TAIILK V-l (continued)
Compound(s) anil
Content ration(s)
in ing/a1 (|>|>in)
___
Description
IICIIO
1.25-13.75
(1-11)
IICIIO
2.5-12.5
(2-10)
Measurements
loader an un-
spetiTied
length of time
after I IIP in-
cident
CarmenI industry
workers using ny-
lon treated with
formaIdehyde-con-
tainiitg flame re-
tardants
Employees of an In-
dustrial garment
company
. _ _
Exposed Controls
Not
given
None
10 F
(6 em-
ployed
in areas
giving
repeated
values
of 10-11
nig IICHO/ra1)
None
Kffeels
Eye, nose, and throat irrita-
tion.
Hrmarks
Historical review of an
industry-side problem asso-
ciatcd witli the manufacture
of flumeproof fabrics. Not
a formal study.
Loss of consciousness shortly
after starting work, 4/10 hav-
ing jerking 1imh movements.
They were Immediately hospi-
talized. After regaining
consciousness, complained of
headache, nausea, dizziness,
ami vomiting. 1/10 continued
to have tremors of the feet
and legs. One required con-
tinued hospitalizalIon. Engi-
neer measuring the IICIIO levels
fell burning sensations of the
eyes and nose along with a
feeling of suffocation. Work-
ers in the room at that time
didn't demonstrate any
detectable dislike or discomfort
indicating possible decreased
susceptibility following re-
peated exposures.
KclcrciM
and
Kill ing
Kttinger ;md
.Je rein ias
Rescript ion of apparent acute
exposure to formaldehyde fumes
(1 locations gave 10-11 mg/rn1).
Physiologic measurements (blood
or urine IICIIO or formate) were
not performed. The uniformity
of complaints and short lime
period suggest a common exposure
Interesting that no one com-
plained of eye irritation or
nasal stuffiness except the en-
vironmental engineer taking
the measurements. The evidence
is highly suggestive tor IICIIO,
but not causal. CO was ruled
out.
C-4
Ahmad and
Whitson
(1973)
C-4
(continued)
-------
TAni.K V-l (conl inued)
Componud(s) nntl
Concent rat ioti(s)
in mg/ni1 (ppm)
Population Group
Description Kxposed
Cunt rols
Workers in a phenol-
IICIIO plastics fac-
tory.
!6-89 Formal Ml depot (re-
quired gas masks)
Total :
~ 34% M
~ 66% F
> 55%
20-39 y
Nine
workers
and met-
allurg-
ical
workers
Loss o
averagi
the si
tal wo
was evi
1962, ,
Phenol (C6ll&OII)
12-43;
avR. 28.3
IICIIO uvg. 5.3
Phenol
0.9-6.0;
avg. 2.8
IICIIO
0.9-11.5
avg. 3.9
30-35°C
Phenol
avg. 1.7
IICIIO
uvg. 6.7
Phenol
avg. 1.3
IICIIO
avg. 2.4
Max. concentration to
which melters of phenol
were exposed 2-5 times
per shift for 4-6 min
each time.
Same general area.
IICIIO escaped from
formalin metering
tank.
Worker beside the
autoclave during load-
ing of the hardened
articles.
Area where articles
were removed from the
molds.
Washing department.
Klfe< Is
Loss of work capacity on the
average significantly exceeded
the sick rates of mine and nie-
s. The sick rate
was even more elevated in 1961,
1962, and 1969--years of grippe
epidemics. Avg. length of ill-
ness in these years was 6.5-
10.3 d.
Sickness rate per 100 workers
per year:
Respiratory organ illness:
77 cases (93% due to grippe)
386 d lost (84% due to
grippe).
(Nos. of cases and days lost
due to grippe were 1.7-1.9
and 1.8-2.2 times higher,
respectively, than in met-
lallurgical workers.)
Illness of alimentary
organs (gastritis,
stomach or duodenal
ulcers, hepatitis,
cholecystitis):
18 cases
149 d lost
Diseases of blood-forming organs:
15 cases
283 d lost
Skin diseases:
10 cases
61 d lost
Remarks
Ul' («' I CIK'
and
llal IIIR
The authors concluded that the Nagornyi
complex of volatile products (1977)
found in the air of workplaces C-5
using phenol-MCIIO resins was
significantly more toxic than
the separate actions ol phenol
and IICIIO. Note that the sick
rates were not related to the
specific exposure levels, or
to duration of exposure.
A descriptive study, with the
exposure confounded by the pre-
sence of phenol, lead, and res in
dust. No controls, only a broad
comparison to mine and metallur-
gical workers. Comparability for
social factors that influence work
absence is not entablished. No
baseline measurements that would
allow workers pre-employinent to
serve controls. The main advan-
tage of the study is the use of
objective outcome measures, i.e.,
days absent, etc. Also fairly
detailed description of symptoms
and iI(ness.
(conI i until)
-------
Compound (B) anil
Content rut ion(a)
In nig/ill3 (ppm)
TABLE V-l (cont inucd)
,. !*?E!ii? i iSD 5 SSSJ?
Description ~ Exposed
Controls
Mfects
Kcniarks
Krf f rencc-
and
Killing
I'henol
avg. 1.8
HOIK)
avg. 2.5
Phenol
avg. 1.5
IICIIO
avg. 1.3
Aerosols of lead
and resin dusts
also contaminated
the workplace air,
I'b 0.006-0.06
Kesin 2.1-9.0;
MAC = 6
Study conducted
for 12 y (1958-
1969)
Curing department
foreman.
Pouring of resin into
tank.
Casting lead molds.
Turning articles on
latlies
In addition, women showed com-
plications nl pregnancy, lahor,
and tho postnatal period.
Various illnesses were diagnosed
In 43% of the workers:
Astlientc syndrome, neurosis,
or neurasthenia 9.5X
Autonomic polyiieuralgia 5.AX
Kadiculltis AX
llepatocholecyslitis
and cholecystitis 5.AX
Chronic gastritis AX
Occupntional dcrroalosis 2.7X
Changes in blood pressure and
pulse rate were observed prin-
cipally in workers with diff-
erent illnesses. Changes in
erythrocyte sedimentation rate
and in the no. of leukocytes
were nearly identical in prac-
tically healthy and sick work-
ers. Practically healthy woik-
crs complained most often of
headaches (9.5X), pains in the
heart region (AX), and pains
in the right subcostal region.
They showed dullness of the
lie-art tones ( 16X), animation,
lowering or inequality of
(he reflexes (1SX), aniso-
chorea, and tremor of the eye-
lidtf and fingers of the ex~
tended hands (2 /X)
(conIInned)
-------
TAIII.K V-l (ioiitiimc.1)
(.'»ni|>(>iniil(s) anil
Concentration(s)
n ing/in* (ppni) Description
Workers involved in
finishing textiles,
in storing then In
warehouses, and in
selling then in
shops.
Exposed
BO in
skin con-
tamina-
tion
study;
100 (77 F,
23 M) in
blood study
20-49 y:
Controls
IB who
didn't
contact
IICIIO in
their
work
Ef foclB
Finger blood samples were
taken at the end of the work
day (S 15-20 min after leaving
workplace) and, for 51 workers,
before the start of work. The
skin was carefully washed be-
fore the blood was drawn. The
IICIIO concentration in the
blood of the controls was not
detectable in 15 and 0.06-0.09
m8% in 3.
IICIIO:
5.1-8.8;
avg. 6.86
ho
O
4-6
4-5
3.17-4.6;
avg. 3.76
Breathing zone of 17
preparers of chem- 1
ical reaclants while 5
dissolving urea-IICIIO 5
resin. Workers had 5
£ 150 mg IICIIO on skin 1
of hands.
Working zone of ten-
ter (drying-stretch-
ing machine). Workers
had S 75 mg IICIIO on
hands.
Warehouses
Specific jobs not 23
identified. 3
9
5
4
2
IICIIO concentrations in workers'
blood in mg%:
< 0.06
0.06-0.10
0.11-0.20
0.21-0.40
0.41-0.70
< 0.06
0.06-0.10
0.11-0.20
0.21-0.40
0.41-0.70
Remarks
Ke/ei <'n
and
Kilting
Uescriptive study. The ron- Volkov.i anil
central ions of IICIIO in the Sidorova
blood are positively corre la- (1971)
ted with inhalation and skin C-9
exposure. No health elicits
of exposed persons were recor-
ded. Only limited controls
were ulili/.ed and insufficient
information is available on the
duration of exposure and specific
Job descriptions. Skin and in-
halation exposures are confounded.
(continued)
-------
TABI.K V-l (mnllniifd)
Com(ionn(l(H) anil
Com rut rat ion(s)
in mg/m1 (|i|im)
(Conl'd)
3-4
1.B3-2.99;
avg. 2.622
1-3
0.55-1.3;
avg. 1.065
0.31-0.42;
avg. 0.384
Po|)ulat ion GIOIII>
Description Exposed Controls
Finisher's working
zone
Specific jobs not 32
identified. 4
9
11
5
3
Zone of service of
the thermal ager
and the calendar.
Specific jobs not 10
identified 5
4
1
Commercial shops 18
5
7
6
Workers be-fore daily 51
exposure. Four of the 45
6 workers with IICIIO 1
in the blood worked at 1
the tenter Machine. 1
Perhaps they carried 1
urea -IICIIO resin home 2
on their clothes.
— .---^ • :-. -;=^- ^=:~. . .; ^- ; .- X- -.- --.-.-- -.-.- .--.--.^- .•;--' .' -~ -:• -~- •'• ~ ~.--:-- -'^ —- - -:- •-
f.Uefla Komarks
< 0.06
0.06-0. 10
0.11-0.20
0.21-0.40
0.41-0.70
0.06-0.10
0.11-0.20
0.21-0.40
< 0.06
0.06-0.10
0.11-0.20
Kange 0.05-0.44
Not detected.
< 0.06
0.06-0.10
0. 11-0.20
0.21-0.40
0.41-0.70
lie I <• ir in «'
and
Killing
Volkova anil
Siiliirova
(lonlM)
Tin- correlations between IICIIO
in the blond and in the air
were signi I irunl. lluwcvi-r,
Hie woikrrx rx|)o»cil to the
higlictil air i oncciil rat ions
of IICIIO veto iiioul iniitjui-
iiniLc-(l on the tikin with IICIIO.
Within IH li iilli-r fxpoNiirc1,
11(110 was usu.illy nut pii-:>iiil
ill the blood.
(com iiiu..ii)
-------
TAHI.K V-l (continue.))
Compound(s) and
Concenli at iun(H)
in ing/in' (l>pra)
IICIIO
2.6-5.3
(Kazan factory
iu> . 1 )
5. 4-7.5
(Kazan factory
no. 2)
2.0-3.5
(Ilelka factory)
Fu rtn i c
acid, MeOII,
and F.tOlf (all
at values < MAC)
Dual particles
Pojuilalion
Description
"Smoothers" in I lie
formalin shops uf 3
USSR fur production
plants who treated
the hair coat of the
hides on roller ma-
chines, regulated
the healing temper-
ature of tlie smooth-
ing roller, and ob-
served the quality.
The work was monoto-
nous , of average
stienuoiisness, and
was performed in a
standing position.
Oroun
Exposed
41 F;
19- to
49-y-
old
3-18 y
of
service
Controls
14 f
not having
contact
with IICIIO
Klli-rts
Iti-m.ii ks
301/cm1; 87%
6 |un in diameter
and 3,420/cm1
< 0.25 M">; 53%
charged (31.4%
positive and 21.6%
negative)
Temperature 16.3-
21.6"C in the cold
and transitional
(weather) periods.
Relative humidity
47-50%
Decreased Ot saturation ol I lie Confounded exposure.
l> I nod occurred in 64-66% of
the cases, which indicated
distinct insuffirienry of
ti&snc respiration. The de-
creases from the control
values increased with in-
creasing IICIIO concentration
in the workplace: 6% al the
Ilelka factory, 17% al factory
no. 1, and 23% al faclory
no. 2. The 02 saturation deficit
was nol recovered hy Ihe loljow-
ing work day.
Workers also showed a decrease in
Ihe pulse rale by 4-10 bcals/min,
and lowering of Ihe coefficienls
of efficiency of the hlood supply
in 25-48% of the cases and also
of Ihe syslolic and diastolic
blood pressure.
Complaints of vertigo, siimulalion
and noise in Ihe ears became
especially pronounced at the end
of I lie shift.
Chronoreflexomelry revealed an in-
crease in the time of reflex action
In 58-66% of the cases.
Al tlie end of Ihe shift, 66-80%
of the smoothers showed a lower-
ing of endurance by 18.4-38.6%
llial altesled Lo their fatigue.
He 11'rence
and
K.I I IIIK
Sarni tova el al.
(1973)
C-K)
(cont i lined)
-------
TAIII.K V-l (
Body temperature was normal, hut
I lie skin became drier during the
work ilay ami ils temperature (on
the face, chest, and back) was
lowered !>y the end of the day.
In 59.3% o( the smoothers vs.
27.2% of tlie controls, the te«|i-
eralure was higher on the right
Bide of the body.
110 F; 124 F The smoothers showed a deviation
20- to not having from normal menstrual function in
40-y- contact 63.08 ± 'ft of the caaeti; 3S.4 i 9.6%
old} with IICIIO of the controls showed similar
2 3 y changed. The incidences of a I go-
of hyiioncnorrhea, hyperpolymenorrhca,
service al godysmenorrlica , and acrylic
blood flow were 5.0 i 4.A, 21.0 t 8,
34.0 t 9.6, and 2.7 t 1% compared to
0.8 t 0, 16.1 * 7.2, 16.1 t 7.2, and
24.0 ±0t, respectively, in the
cont rols.
During pregnancy, early and late
toxicoses were More freijuent in
the smoothers. Pregnancies were
Interrupted in 37.43 t 6.1% of the
smoother* and 22 i 101 ol the 1011-
Irols.
Ham it (i v.i
ft al.
(1973)
(coiitM)
(cont timed)
-------
TAUI.E V-l (rontiniiiMl)
Couipoiiud(s) anil lli'lnt-nr
Concent rat ion( a) Ponijlat ion Group and
in mg/ni' (|i|)n>) Description Exposed Controls Klfeels Hcm.iiks Hating
(Coul'd) Gynecological morbidity compris- Scimitovu
ing prolapse, folding and ilcvi- el al .
ation of the uterus, and benign (197.!))
tumors of the sex organs (no sig- (conl'd)
nifleant difference for the lat-
ter) occurred in 64.8 ± 9.6J of
I he smoothers and 26.6 i 8.7% of
the controls. Prolapse o( the
uterus and appendages occurred
with similar frequency in
smoothers and controls with
length of service < 5 y (~ 3%),
but the frequency was 12.0 t 7%
for the smoothers and 2.32 i 0%
for the controls with > 15 y
i^ of service. Prolapse of the
1 •> internal sex organs orcurrcil
with ~ 9-10% lrf(|iifiicy in
smoothers and controls with
< 5 y of service, but
smoothers showed an incidence
of 48.0 ± 1.2% compared to 6.97 t
3.7% for the controls when
both groups had > IS y ser-
vice.
Varicose dilations of the
leg veins were observed in
32.0 i 1.7% of the smoothers
having > 15 y of service
and 2.32% of the controls
with service > 15 y.
(continued)
-------
TADI.E V-l (coiilliiii(Ml)
to
Coin|>ound(s) and
Conc*nlratiou(a)
in mg/m»
Description
Population Croup
f.x potted Control*
IICIK)
riiuge in the
6 homes:
0.11-6.58
(0.09-5.26);
range of the
avg. COIICIIB.
of each of the
home*:
0.31-J.7A
(0.25-1.39)
Emhalmers in 6
Detroit-area
funeral homes.
77 H
Hone
Effect*
Eye and nose burns, sneezing,
coughing, and headaches.
Tho*e who spent more time em-
balming experienced mare ir-
ritation. 3/7 had sinus or
asthma problem!. 2/7 suf-
fered fro* dermatitis.
Kcnarks
The enviroiuaental Measures of
IICIK) vapors at 6 funeral homou
were compared. 187 samples
ranged from 0,09 to 5.26 ppm
arid were higher where there
was no ventilation (mean 1.34)
than in weil-venti lalcd area*
(•can 0.74). Seven (?) morti-
cians were given a questionnaire
on "known toxic effects of IICIIO."
More attention is given to the
environmental measures than the
recording and analyzing of health
effects. There are no controls,
insufficient numbers for meaning-
ful analysis, no correlation of
symptoms to varying IICIIO concen-
trations, and a strong likelihood
of interview bias (i.e., using a
questionnaire listing the Major
known side-effects of IICIIO).
Symptoms recorded, however, are
consistent with known acute ef-
fects of IICIIO exposure.
Kali lift
Kcrloot anil
Nooney
(1975)
U-4
(continued)
-------
TABLE V-l (continued)
Compound(a) and
Com entraC ion(s)
in mg/m1 (ppm)
_ Population Group
Description Exposed Controls
EfferlH
Remarks
Iteferenrr
iiiul
Rating
IICIIO Not given
Deceased emhaluers
licensed to practice
embalming in New York
Stale between 1902
and 1979, and for
whom death certifi-
cates have been
found.
KJ
ON
67 non- Cause- 50% died before the age of 65.
white H specific Deaths in white males showed:
and 1,010 propor- insignificant increases due
white H; tionale to all malignant neoplasms and
exact mortality cirrhosis of the liver, signi-
Icngth for the ficant increase due to arterio-
of em- U.S. gen- sclerotic heart disease, and
ploy- eral pop- significant deficits due to
menI or ulation pneumonia and accidents. Sim-
liccn- by age, ilar results were found for
sure sex, race, non-whites. Distribution of
unknown and caleii- malignant neoplasms in while
dar year males showed: significant
excess skin cancer, insignifi-
cant excess of colon, kidney,
brain, CNS, and lung cancer
and leukemia, slight deficits
of rectal and prostate cancer,
anil expected level of deaths
due to neoplasms of the bticcal
cavity and pharynx. Those
licensed < 35 y (time from
1st licensure to death) showed
excess kidney cancer mortality.
Those licensed 2 35 y showed
excess skin cancer. Those
licensed only as embaliners
had significantly higher kid-
ney and brain cancer deaths.
Those also licensed as fun-
eral directors (presumably
less IICIIO exposure) had no
unusual mortality.
Proportionate mortality rate Walrath ami
(CNR) analysis of morticians Frauiueni
designed as a preliminary in- (iinjmM .)
vestigation of the chronic C-9
effects of the exposure to
IICIIO. The main deficiency
is inherent to the use of
the I'MK method which ignores
the population at risk. Ex-
cess proportion of deaths
(i.e., from skin cancer) may
only reflect a deficit in pro-
portion of deaths from other
causes. In addition, length
of employment information was
not available to measure or
estimate exposure (length of
exposure is estimated only on
the basis of the 1st year li-
censed). No environmental mea-
sures of lirilO could be made,
and embalming fluids contain a
mixture of oilier chemicals (anti-
septic solutions, dyes, deodor-
izers, etc.) that would further
confound this study. It is in-
teresting that skin cancer is
found in embalmers only (vs. em-
baliners and funeral directors)
and in those with > 35 y from 1st
licensure to death. No stratifi-
cation by birth cohort or by year
of licensure was carried out to
judge if significant changes had
occurred over time (since study
spans 1902-1979).
(continued)
-------
TAHI.E V-l (continued)
CoM|iound(t) and
Concentration(i)
in «g/«» (ppm)
Description
Population Croup
Kxpoied Control*
KCIIO
A nail survey of em-
balmers in 20 full-
er* I homes in Us
Angeles.
Effects
Remarks
Rclcrcni <•
Hllll
Rating
57 H;
•vg. age
of dif-
ferent
groups
was 35-
40 y;
avg. length
of work
for dif-
ferent
groups
was
11-18 y.
None
Reported symptoms: eye, skin,
noae, and throat irritation,
chest tightness, shortness of
bresth, cough, and wheezing.
From respiratory question-
naires, 31/5? were in th« diag-
nostic category of asymptoma-
tic, 9/57 had acute bronchitis,
and 17/57 had chronic bronchi-
tis. The asymptomatic group
reported a longer work history.
Deficiencies include:
(I) 71X response rate (57/80).
(2) No control group.
(3) Opportunity for recall and
questionnaire bias.
(4) No exposure estimates or
Measurements.
(5) Diagnosis of bronchitis
was smile by symptoms on
the questionnaire.
HunkeU nii'1
Haibe 1 a
(1977)
C-4
N)
(tout iimc'il)
-------
TABLE V-l (coiiUmio.l)
Compound(s) and
Concentratioti(ti)
in mg/m1 (ppra)
Popu1ation Croup
Description Exposed
Controls
Effects
Remarks
Reference
and
Hating
IICIIO
1.5-4.5
Triii shop finishers
in 2 textile com-
panies. Work was
light and done
while standing,
with very little
movement.
130 F; 200 F
64% (indus-
worked trial
2 10 y goods
sales
persons);
54.5%
worked
2 10 y.
Of all of the sub-
jects in Shunilina
(1975) study, 70%
were < 40-y old.
00
Dysmenorrhea was greater in
the exposed group (24.3%)
than in the controls (9.2%),
and most frequent in the 31 to
40-y-old women (20.7% vs. 6.7%
in the controls). llypomen-
striial syndrome predominated
and increased as occupational
experience increased, Jlyper-
polymenorrhea and monophasic
menstrual cycles occurred
more often in the exposed
group. Inflammatory genital
disease (36.2% vs. 25.1% for
lighter exposed group), pri-
mary sterility, and secondary
sterility (15.3% vs. 6.5% for
controls) were liigluT in the
exposed group. No differences
in term births or artificial
abortions were reported. Dur-
ing pregnancy, increases in
anemia, late toxicosis, hypo-
tension, and symptoms of im-
pending abortion (31.1% vs.
17.5 % for controls) were re-
ported. There were increased
problems during delivery and
weight of neonates was lower
in the exposed group. Com-
pare with the results for ex-
posure to 0.05-0.7 mg ItCHO/in3
(Shiunilina, 1975).
Comparison bias is likely, KliiimHina
i.e., study is confounded by (1975)
lack of information on com- R-8
parability ot cases and con-
trols (socioeconoinic status,
age, race, smoking history,
etc.):
(a) Differences in socioeconomic
status would be expected in
saleswomen vs. trim shop
workers
(b) hack of information on work
environment of cases vs. con-
trols, and exposure (i.e.,
duration of employment vs.
symptoms).
(c) The gynecological disorders
referred to are much more com-
mon in women of lower socio-
economic status (i.e., pelvic
inflammatory disease).
(d) Many of the disorders are as-
sociated with personal habits
(smoking, alcohol use, etc.) and
nutritional status.
Although the wide spectrum of gyne-
cological disorders and complaints
suggest a major comparison differ-
erence between cases and controls
(i.e., socioeconomic status, etc.),
further studies would be indicated
to be certain of the role of IICIIO.
(continued)
-------
TAIII.F, V-l (continued)
VO
CoMpoundd) anil
Concentration(s)
in
HCIIO S 5.25
(S 4.2)
concentrations
Independent
of temperature
(59-68°F) ami
relative tumid-
ity (36-70%).
Sample! collected
over "a number of
days."
HCIIO
1.1-4.1
(0.9-3.3)
PopulatIon Croup_
Description ~ Exposed
Worker* in the glue,
laminating business'
using phenol-reaor-
ciiiol-IICHO adhesive*.
Not
(iven
Control*
None
KtllTlS
Employee* of •tores
in Pasadena, Calif.
where texiles and
synthetic fiber*
were sold.
Not
given
None
Worker* in the lay-up area felt
that the increased incidence
of accident* involving *mastio
-------
Compound(s) and
Concent rat ion(s)
in mg/mj (ppm)
TAIII.K V-l (continued)
Population Croup
Description Exposed
Controls
El I eels
Remarks
Kcferonci*
anil
KaliMR
IICIIO
1.1-3.4
(0.9-2.7)
Samples taken
from several
locations
where the odor
was most in-
tense
IICIIO
0-3.4 (0-2.7)
avg. < 1.25
(avg. < I)
Employees of o com-
pany manufacturing
permanently pressed
panta, using a cloth
pretreateij with urea,
IICIIO, and glyoxal.
The process had been
in use — 18 wo.
350
(~ 75% F)
Workers in 8 cutting Not
and finishing plants given;
handling permanent ~ 90% F
press fabrics treated
with IICIIO resins.
None The greatest irritation of the
nose and throat and tearing of
the eyes was felt in the areas
with the largest quantities ol
partially completed garments.
The symptoms were strongest at
the beginning of the work day
and after the lunch period.
The effects, in their intense
phase, lasted 15-20 min, then
the Irritation became toler-
able. No conjunctivitis was
found. Older workers fell
"light-headed" and had a
"heavy feeling" in their
chest by the end of the day,
lasting 1-2 h after work.
Greatest discomfort during fog-
gy, humid, or cold weather.
Employees in other areas (e.g.,
warehouse) were unaffected.
These levels were judged not to
be a systemic health hazard,
but changes were made to lower
the levels to avoid irritation
and nuisance.
None Heavy tearing, wheezing, exces-
sive thirst, arid poor sleep.
The incidence of respiratory
illness was ~ 10% higher than
prior to the initiation of the
permanent press process. Min-
imal dcrmalologic effects. On
entering the plant, odor was im-
mediately perceived, decreasing
in intensity during the day,
but just as strong at the be-
ginning of the next day.
Environmental survey of IICIIO Itlejer and
concrntrations accompanied by Miller
an "informal medical inter- (1966)
view." C-3
(a) The number actually inter-
viewed is not given ("at
leant one worker in each
operation was interviewed,"
not all 350 employees).
(h) No i)uantification of symptoms
is given (no. of persons/dm -
at ion of symptoms is not re-
corded) .
(c) Each person interviewed was ».
examined for the presence of
conjunctivitis, but not exam-
ined at the beginning of the
workday. None was found.
(d) Concentrations of IICIIO are not
correlated to symptoms (dif-
ferent areas' of the plant had
different levels).
(e) No control or comparison group
is present.
Heavily biased study. No
measurement or even good
description of health effects.
Simply a survey of complaints
and intermittent air measure-
ments.
Shipkovitz
(1968)
C-5
(continued)
-------
TABLK V-l (conllimi.-il)
Coapound(s) and
Concentration^)
in mg/m1 (ppm)
______ Popu t a 1 1 on C r pup
Descrfption Exposed
__
Con t roll
Effect*
Remarks
KHrriiitco
and:
Hal tun
IICHO:
start of
shift, 0.6;
end of
•hi a, 3.1
I'henol:
start of
shift around
the presses,
i 2; end of
shift, 15.6
Resin dual:
concentration
not |iven;
however, dusti-
neaa also in-
creased as the
day wore on.
Workers engaged in 50:
the production of 30 press*
articles frosi phenol- men
IICHO resins, either 20 pol-
from Molding powders ishers
or from plastics
filled with wood char-
coal and cotton combings.
2-5 y employment except
for 1 who had worked
> 10 y. Young persons
predominated.
Hot Disturbances were seen aw re
given often in the pressmen than in
the polishers, who were ex-
posed to a lower reain dual
concentration.
J?£S!!!!
Five pressmen (moliters) with
service S 2 y showed distur-
bance of the upper respiratory
tract — chronic rhinopharyngitis.
V,P. Malinina-Putsenko (1962) was
cited as reporting lung pathology
in fuch exposures, but these au-
thors did not observe it, perhaps
because the worker* studied had
not had service time enough to
develop it.
Skin
Seventeen persons complained of
skin changes; 7 of the* had skin
irritation in the forms of tler-
sutitis and eczcaui.
Heart
Complaints of stabbtng-conatrict-
ing pain in the heart region were
frequent (13). There was muffling
of the heart tones at the tip (in
17). Half of the subjects showed
a tendency toward hypolonia. Sig-
nificant shifts in the EKC were
not observed. Changes appeared
to be connected with dysfunction
of the aiitotiomic nervous sywlc*,
and as a cons«i|iicnce of this,
with a disturbance oi the bio-
chemistry ol the heart muscle,
which is clinically most often
manifested by mill fling of tones.
IICIK) exposure is confounded Sliafoix.u-v ami
by the presence of phenol and Shipovskikh
resin dust.' The importance (1972)
of this confounding is noted C-6
as disturbances seen more fre-
quently in pressmen exposed to
higher resin dust concent rations.
(i out iiiui'il)
-------
TABLE V-l (continued)
Compound(s) and
Concentration(s) Population Croup __ and
in mg/m1 (ppni) Description Exposed Controls Effects Remarks Rating
(Cunt'd)
Castrointestinal tract ' Shafaiziev and
Anacidic gastritis was observed ShipovsKikh
in 11 subjects; chronic colitis, (1972)
in 4; atrophic and hypertrophic (cont'd)
gastritis, in 3; spastic colitis,
in 5; disturbances in the protein-
forning and antioxidant functions
of the liver, in 8 (the liver pig-
ment formation function was dis-
turbed in only 1).
Nervous system
Disturbances were seen in 24 of
the 30 pressmen in the forms of
i^j as then it and neurotic syndromes
N> and antonomic dystonia.
(cont limed)
-------
TADI.K V-l (continued)
CoMpound(s) anil
Concentrat ion(a)
In mg/w1 (|i|im)
IICIIO ~ 1.5-2.5
Wood dust > MAC
by 1.5-2 tinea
3-y study
(1972, 1974,
1975)
£°j>ul_atioii_Urou]>
Description ~~ "Exposed"" Controls
Effects
KcmarkN
and
Rating
CO
Co
Practically healthy Not given
workers in • plywood- ("13,000
furniture plant up to cases of
SO y old Kith t 5 y Iocs of
of service. Sorters work ca-
worked in 3 shifts; pacity")
2 shifts glued ply-
wood. Heavy lifting
and hauling for sort-
ers, more Mechaniza-
tion for gluers.
None Results of physiological stud-
ies (functional condition of
nolor analyzer, cardiovascu-
lar system, hand resistance,
and pulse frequency) agreed
with the indexes of the sub-
ject ive condition of the
working women in the 1st and
2nd shifts. At the end of
work, complaints increased
about fatigue in the muscles
of the hands and feel, general
weakness, headache, and eye
fatigue.
The highest morbidity was due
to colds and flu (43.4% stated
in text, 46.6% In a figure).
The other illnesses were of
nerves and peripheral ganglia
(15.2%), cardiovascular (7.31)
and skeictomnscular systems
(6.5%), female reproductive
system (2.3%), and miscella-
neous (22.1%).
In plywood production, the
women showed a two-fold higher
frequency than the SMMI in loss
of work capacity per 100 work-
ers (B.1-17.9/100 vs. 3.9-7.6/100).
The incidence of cardiovascular
illnesses was 8.6/100 for the
women and 6.1/100 for the men.
Descriptive, uncontrolled
study of morbidity and loss
of work. Exposure not cor-
related to actual work loss.
Exposure was confounded by
wood dust. Physiologic studies
reflect the nature of the work
more than exposure to IICIIO.
AvdecV'i el a I.
(I960)
D-4
(continued)
-------
TABLE V-l (continued)
Compound(s) and
Concentration(s)
In mg/m1 (|>|>IH)
_ _ Population Group
Description Exposed Controls
Effects
Remarks
Reference
uiul
Rating
-
IICIIO 2.0
(4 x MAC)
Dust 10 x MAC
I'iienol , alde-
hydes,
ClljOII, cyanides,
CO, etc. @ < MAC
Workers in a foundry
plant that had begun
3 y before producing
molding cores from
cold-hardening mixtures
based on a urea-IICIIO
resin and H3P04
Workers were engaged in
core rod forming, mold-
ing, pouring, knocking
out, or trimming.
-
Coremaking depl.:
IICIIO 0.2-1.2
ClljOII 7.6-25.3
Casting dept.:
IICIIO 0.1-0.4
Dust 5.6-18.5
Bciizopyrene
2.4-9.9 x 10"B**
Knocking-oul dept.:
IICIIO trace to 0.2
Dust 7.6-64.3
llenzopyrene 2.4-3.8
543 Not men- The lung-function results were
H and F tioned, examined according to job, age
but a group, Icnglh-of-service group,
range of and sex.
values is normal
referred Coreiiiakers:
to for The inspiration volume was
certain somewhat lowered with age.
lung fuuc- The expiration volume was
tion in- constant except for the 40-
dexes. to 44-y-old group.
The respiratory frequency in-
creased during lowering of the
respiratory volume with in-
creasing age and length of ser-
vice.
The vital capacity was 45% lower
than normal in the 45- to 49-y-
old group and was •» 30% lower
in groups with length of ser-
vice 1, 6-10, 11-15, or 16-20 y.
The minute volume was 26-69%
higher than the upper limits of
the age norm and 23-85% higher
in practically all length-of-
service groups.
The maximum ventilation of the
lungs was 34-46% lower than the
lower limit of the age norm in
all age groups. The minimal
divergence from the proper value
was 25% in the lenglh-of-service
group 6-10 y and the maximum was
64% in the 5-y service group.
Descriptive, essentially un-
controlled study. Ou t come
measures (respiration func-
tions and pathology) were
completely determined, but
exposure is confounded.
Teplyakov ct al. (1980)
concluded that the ex-
posure to the harmful
gases from the use of the
cold-hardening mixture
for 3-4 y prior to the
clinical examination in
1976 had not caused ex-
pressed pathological
changes. Time of lost
work capacity and
morbidity were not ex-
ceptional for any one
di-par linen I.
Chernoaioreki i
et al.
(1978)
D-9
Teplyakov et a I.
(I960)
D-9
* Use of 4-5% free urea before resin hardening by 1I3P04 since the start of 1978 reduced the evolution of IICIIO.
** MAC = 15 x I0"s mg/m3.
(continued)
-------
TABLE V-l (cunliniicd)
Compound(s) and
Concentration(s)
in mg/m* (ppm)
Population Croup
Description Exposed
Controls
Effects
llcnnrka
RofcrtMiri1
ami
Kilting
(Cont'd)
to
01
The coremakers were judged to have
stage 1 respiratory insuf flciency
characterized by changes of vent-
ilation without disturbance of the
arterial composition of the lilood.
Lung pathology was observed In
90.5% of the men and 87.0% of the
women. Hen (23.B t 9.3%) «nd women
(8.5 t 3.3%) of the coremakers and
knocking out workers showed hyper-
trophy of the siurous membrane of
the rear wall of the throat and
hypercmia of the suicous membra ne
of the vocal cords. Lacrlmation
and sharp pain in eyes were com-
plaints of 5.6 t 2.7% of the core -
makers.
CliBrnornorsfci i
et at .
(1978)
(conl'd)
_ _
Respiratory insufficiency was
more expressed in these workers,
who directly contact the cold-
hardening mixture and its de-
gradation products.
Lung pathology was observed on
X-ray examination (see casting
workers) in 85.7% and 91.7% of
the men, respectively. Among
those engaged in knocking out,
11.1 ± 5.2% complained of lacri-
malion and sharp pain in eyes.
Hoarseness, dry cough, and dry-
ness in the nasopharynx were
complaints of
-------
TAIIl.F. V-l (continued)
Compound(s) and
Concentration(s)
in mg/m3 (|>|>ra)
_
Description
Exposed Controls
Effects
Kcronrks
Uofcrrm <•
anil
Raling
(Cont'd)
wojrke rs:
X-ray examination showed deforma-
tion of the lungs, thickening and
dilation of the radix pulmonis, and
the presence of coarse strands to
the diaphragm and periphery, etc.,
in 86.6% of the women and 85.3%
of the men.
Trimmers:
fling pathology was noted in 89.5%
of the women.
Overal1:
l.iing pathology was observed in 95%
of the cases in all production
sections even in those aged 30-40
y and with 1-5 y of service.
The following ailments were recor-
ded during clinical evaluations:
neuroses (17.8 ± 1.6%); diseases of
the nerves and peripheral ganglia
(9.1 t 1.2%); hyperlonic diseases
(7.0 t 1.1%); gastritis and duoden-
itis (7.1 ± 1.1%); and bronchitis,
emphysema, and bronchial asthma
(6.1 ± 1.0%).
Rank of the ailments according
to time of loss of work capa-
city: acute respiratory di-
seases (21.8 t 1.6%), diseases of
the nerves and peripheral ganglia
(5.2 1 0.9%), hypertonic disease
(It.2 ± 0.8%), and chronic respir-
atory diseases (2.5 t 0.7%).
Chernomorski i
et a\.
(1978)
(contM)
(continued)
-------
TAIII.K V-l (roiitinui-d)
CoM|>otmd(s) and
Concentration(s)
in wg/m1 (p|im)
IICIIO 1.1-2.0
(0.9-1.6)
Ammonia, "a
trace"
CO
Description
Two worker* outside
of • booth where •
wood pulp paper for
map-making, which
had been pre-treated
with urea-IICIIO or
Melamine-HCIIO resin,
was treated for
shrinkage control.
Contaminated air
leaked from the
booth into the
workers' breathing
zone. Early I9S9;
the U.S. Army Hap
Service, Far East,
In Tokyo, Japan.
. ________
Exposed Controls
effects
Remarks
None
Workers complained of itching
eyes, dry and sore throats,
disturbed sleep, and unusual
thirst upon awakening in the
morning shortly after the
process was placed in oper-
ation.
Case report of acute exposure.
A question of confounded ex-
posure (ammonia), probably not
sign!fleant.
Krfrremc
ami
K.-it ing
Mor.il I
(1961)
C-4
(con11 lined)
-------
TAUI.K V-l (continued)
Compound(s) and
Concentralion(s)
In rog/m1 (j>|>in)
_ Population Croup
Description Exposed Controls
Effects
Remarks
Reference
iiml
Hating
00
Wood dust, etc.
IICIIO 0.04-1.76;
avg. 0.5
(0.03-1.41;
avg.
Weyerhauscr Company
manufacturing com-
plex in Springfield,
Oregon. A total of
~ 175 workers were
exposed to IICIIO.
Avg. exposures
before curtail-
ment of operations
of particleboard
plant due to an
explosion on October
6 (entire study
period was fall
1974-spring 1975)
were:
I'arl icleboard
plant, (0.66)
Personnel exposure
evaluations:
50 None.
(13 High ex-
twice) posure
compared
to low-
exposure
groups.
Visual function
tests:**
50 Included
those
workers
exposed to
S 0.44 mg
HCIIO/mJ
20-25 workers over
all shifts (mainly
two); avg. length of
service on job, 5.9 y.
Subjects exposed to higher
IICIIO concentrations did not
perform visual tasks signifi-
cantly differently from sub-
jects exposed to lower concen-
trations. The change in per-
formance between pre-work and
post-work tests did not signi-
ficant ly differ according to
IICIIO exposure. Post-work per-
formance was more accurate
than prc-work performance
for all tests and most sub-
jects, but the difference
was significant at the 5X
level for only the depth
perception test.
The high-exposure group, how-
ever, performed less accurately
and less quickly in the visual
tests botli before and after work
than did the low-exposure group.
The post-work improvement in per-
formance was greater for the
high-exposure group. Pro-work
responses were faster than post-
work responses in only the eye
movement and fixation test.
Concentrations of other sub- Wayne.el
stances (particulales, wood (1976)
dust, resin, etc.) to which 11-9
llu> workers were exposed were
not measured.
Comparability of the workers in
various sections of the plant is
not described. Low exposures to
IICIIO may be slight compared to
other substances in the air.
Tlie performance tests may not
have been sensitive enough to
discern difference in IICIIO
exposure level.
*
*-.v
Average before October 6 (0.57); after October 6 (0.19). These are results of personal samplers.
Visual function tests were on central visual acuity, visual acuity under glare, dynamic visual activity, depth perception,
peripheral vision, accommodation, eye movement and fixation, divided attention, and color vision.
(continued)
-------
TABUS V-l (tonlinm-d)
Compound(a) and
Concent ration(•)
in mg/ii1 (ppm)
_____
Description
_Crou|t
Exposed"
Controls
Effects
Remarks
Refcrenrr
find
Haling
(ContM)
UJ
Joint fin Jailing
•rea (0.59)
Plywood Plant
(0.50)
Green end* (IICIIO
not specifically
used here),
(0.19)
Avg. exposure
after October 6
(S 0.04)
~ SO workers in each
shift; avg. length of
service on job,
4.6 y.
Other SO workera were
employed in finishing
or aa Maintenance
•en, fork-lift oper-
ators, laborers,
etc.
Synchronized behav-
ioral and environ-
mental study:
17 part- 21 green
icle- end work-
board era
workers;
30 joint
finishing
dept. work-
ers; and
16 ttom
plywood
plant
The 21- to 64-y-old
workers included 4
K. Length of ser-
vice on current
jobs S mo-18 y;
avg. 3.4 y.
Area where logs anil mulcted veneer arc manipulated.
The general trend toward improved
visual performance after work was
significant at the 1% level.
The subgroup of subjects who ex-
perienced eye irritation or eye
discomfort during work did not
perform significantly differently
from the regaining subjects.
On their uedtrsl histories, ttte
particleboard workers reported
a significantly higher previous
incidence than the other sub-
jects of the following eye
symptoms: "burning or itching,"
"gritty or sandy sensation," and
"pain or discomfort."
Of the workers in the green end
of the plywood plant, a signifi-
cantly smaller fraction reported
eye Symplon* that they fell were
work related.
The frequency of eye symploms on
the days of the visual function
tests was no greater among the
store exposed than in the less
exposed workers.
The lowest frequency of positive
responders to complaints of bod-
ily fatigue, headache, eye dis-
comfort, air unsatisfactory, eye
fatigue, and odor were the 2')X of
the workers wlio h<»l tin- highest
IICIIO cxposiii (•;;.
(ronlimieil)
Wayne
el al.
(1976)
(conl'd)
-------
TAIII.E V-l (continued)
Compound ( s ) and
Concent rat ion(s )
in mg/m1 (ppm)
Copulation Croup
Description Exposed
Controls
Kfferls
Remarks
and
Killing
Shops:
HOMO
0.17-0.85;
avg. S O.S
Warehouses:
IICIIO
avg. 1.69
Chiefly, salespersons
in fabric shops; ~ 5%
of the air sampling
was in warehouses.
Highest IICIIO levels
were by the fabric
cutter^ the sales
counter, and the
stand with the
fabric samples.
Warehouse workers
were not exposed
cont iniiously.
1,000 Persons All but 373 salespersons iom-
(30 in working plained in a questionnaire of
ware- with worsening of their feelings
houses) linen- of well being. A total of
fabrics, 6,181 complaints showed that
which 3,237 (52.4%) were from the
are not group employed $ 10 y; 2,190
finished (35.4%), 11-20 y; and 754
by cliem- (12.2%), > 20 y. For example.
ical com- the no. of complaints on the
pounds. skin-irritating action of the
HCJIO-res in-finished fabrics
was 1.8 x lower in those em-
ployed 11-20 y and almost 6 x
lower in those employed > 20 y
than in those salespersons em-
ployed < 10 y.
With increased length of ser-
vice, the complaints also
changed character. Persons
working in the shops longer
complained less of head pain,
dizziness, irritation, nose
bleeds, and stomach pains but
were more often troubled by
cough, tickling in the naso-
pharynx, catarrh, poor appe-
tite, pains in the joints and
the small of the back, and de-
crease or increase in arterial
pressure.
Complaints independent of length
of service were pains in the
heart, mucus discharge, sleep
disturbance, dyspnea, angina,
and nausea.
The authors recognize that the Narkova and
aging factor with increasing Satitin
length of service of the sales- (1975)
persons may have influenced A-7
the results. It would have
been useful to show the changes
in romp)aims with increasing
length of service in the con-
trol group.
(I) Proportionate ratios (not
rales) arc used to compare
complaints by duration of
employment. Kates are
necessary to make the above
inferences (i.e., no. of com-
plaints/no, of persons < 10 y;
not no. of complaints among
those working < 10 y/total
complaints). Fewer complaints
may be present among those em-
ployed > 20 y because there
are fewer persons in this cate-
gory.
(2) Poorly controlled. No compar-
ability of comparison group
working with other fabrics is
given (i.e., age, race, years
of employment, etc.).
(3) Environmental measures are not
correlated with symptomology
of employees, although indirect
association is present. Other
irritants were not examined.
(4) Standard epidemiologic mea-
sures are not used.
(5) Mainly acule symptoms are
examined. Duration of
symptoms is not stated.
This is especially iropor-
(conlinued)
-------
TABLE V-I (continued)
Compound(<) ami
Concentration(•)
in mg/m1 (ppm)
_____
Description
_ _____
Ttaposed Control*
Kffeels
Remarks
and
Kitting
(ConL'd)
IICIIO avg. 1.28;
range 1.12-1.43
Employees in •
chip board plant
IICIIO avg. 0.78; Medical
range 0.37-1.31 atudents
aod a
laboratory
aasiatant
5,
46 to
50-y-old
None
13 None
(12 medical
student*,
21-25 y;
1 laboratory
preparation
assistant,
50 y)
From 5,105 complaints of sales-
persons contacting different
kinds of fabrics, only 141
(2.8X) were from those sales-
persons in contact with linen.
A very significant increase
was noted in complaints of skin
irritation from staple and vis-
cose fabrics (33.2X and 21.9X
vs. 1.9X for linen fabrics).
Levels in the urine after expo-
sure were:
IICIIO 0.16-0.35 mg X
IICOOII 0.68-21.83 mg X
Levels in the urine after a
144-h elimination period were:
IICIIO 0.15-0.43 mg X
IICOOII 1.02-3.62 mg X
(authors state that this
is a "normal" level)
Compare with the results for
exposure to 0.78 mg/m3
(Einlirodt ct al., 1976).
After a 3-b exposure, avg.
levels were:
blood IICIIO 0.85 mg X
blood IICOOII 9.4 mg X
urine IICIIO 0.10 mg X
urine IICOOII 3.5 mg X
After a 21-h elimination period,
the avg. levels were:
blood IICIIO 0.73 mg X
blood IICOOII 7.0 mg X
urine IICIIO 0.25 mg X
urine IICOOII 5.2 mg X
Compare these values with those
for expoHiire lo 1.28 mg/m3
(Einlirodt el al., 1976).
Iaiil when examining the
length of employment.
Einbrodt
et al.
(1976)
C-6
Authors state that the
results support the theory
that detoxification occurs
immediately after the blood
absorbs the IICIIO, by oxida-
tion to IICOOII.
Ei nl> rod I
et al.
(1976)
C-16
(continued)
-------
C(>I*|>OIIII(|(H) and
Concentralion(s)
in mg/m3 (ppm)
TAIII.K V-l (cool i lined)
__
Description
___ _
Exposed Controls
Ki feels
Hi-narks
lie termer
and
K.I I ing
IICIIO
0.05-0.7
Warehouse inspectors
in a textile company.
Work was light and
done while standing,
with very little
movement.
316 F; 200 K
56.2% (indus-
worked trial
for goods
4 10 y sales
persons);
54.5%
worked
for
* 10 y
70% of all the sub-
jects in Shiimilina
(1975) study were
< 40-y-old.
Various menstrual disorders
were higher in the exposed
group: dysmenorrhca (20.2%
vs. 9.2% for controls), hy-
perpolyinenorrliea, and mono-
phasic menstrual cycles.
Increased incidence of in-
flammatory genital disease
and primary sterility was
reported. No differences
in the number of term births
and artificial abortions. Dur-
ing pregnancy, increases in
anemia, late toxicosis, and
hypotension were noted. No
correlation between work ex-
perience and pregnancy dis-
order incidence was found.
There were increased problems
during birth and lower neonatal
weights in the exposed group.
Compare with the results for
exposure to 1.5-4.5 ng HCIIO/ra1
(Shumilina, 1975).
See the 1.5-4.5 nig/m* entry
(Shumilina, 1975).
.Slinm i I i nn
(I97
11-8
(continued)
-------
TAULE V-l (continued)
Conipound(s) •ml
Concent ration(s)
; in Hg/rn1 (pi*)
IICIIO
0.16-0. 56
(0.13-0. 45)
During injec-
tion, at
pump:
IICIIO 0.4-0.5
(MAO0.5)
HcOII 2.6-10.3
(MAC=5.0)
During clean-up
work:
IICIIO 0.2-0.13
MeOII 0.14-0.8
PopuUlion Groii£
Detcrlption
Controls
Effects
Customers and em-
ployee* of dress
• tores which con-
lain fabrics treated
with IICHO-containing
compounds for flame
retardancy and
wrinkle-proofing.
Worker* in coal mines
wboae air content of
dust and Methane was
controlled by inject-
ing a urea-IICHO resin
into the coal-bearing
strata.
Donets Coal Basin.
1973-1975
(The major effect of
the treatment was the
lowering of the (lusti-
ness by 32%, but the
particles 2.5-5 (MS in
size si ill coaiprised
70-75% of the total
dust particles.)
Not None If the curing is not complete
given during the treatment process,
uncomliined IICIIO can be left
in the cloth, and later given
off by the finished garment.
Symptoms reported were: burn-
ing and stinging eyes, head-
aches, an intolerable, suffo-
cating odor, and irritation
of the nose and throat. Ir-
ritant effects sometimes repor-
ted to be stronger in the spring
perhaps due to the increased
shipment of treated clothing
(cotton and rayon) for the
summer.
Not Workers in Workers examined in the course
given untreated of 1-3 mo after the treatment
mines and 4 mo later did not show
any differences from the norms
or from the control group in
the following indexes: arterial
pressure, pulse rate, C02 content
in air exhaled at rest, vital
capacity of the lungs, muscular
work capacity, rate of processing
information, and blood analysis
values.
Remarks
Anecdotal account of customer
and employee complaints.
Loosely associated with air
samples and samples of wearing
apparel containing measurable
levels of IICIIO. No quantifi-
cation of complaints or no. of
persons with symptoms. No con-
trols or comparison group. Not
s formal study.
Reference
and
Rating
Bourne and
Sefeiian
(1950)
C-3
The exposure is confounded.
The number of persons and
symptoms are not quantified
Gadzhiev el al.
(1977)
0-4
(continued)
-------
TABLE V-l (roil tinned)
Compound(8) and
Com fill ration(s)
in wg/m1 (|>pm)
Population Grouj>_
Description Exposed Controls
Effects
Remarks
Ki'Orcm r
ami
Killing
IICIIO
< 0.5 (the
MAC) except
where the
resin is pro-
duced
I'henol usually
> 5 (the MAC)
Cresol > MAC
only in 1 case
i 70-85%
relative
humidity
Workers in a USSR
phenol-IICIIO resin
plant: male and
female apparatus
workers, male re-
pairmen, female lab.
workers, and female
preparers of the raw
materials. Most of
the women were
molders.
Lost work capacity
studied for the
period 1973-1975.
662,
59.1% f;
since
the
women
were
older
than the
men , a
standard-
ization
was done
to elim-
inate the
effect of
the age
di fference
on the
morbidity
indexes.
257 M
in the
instru-
ment
plant
and 216 F
in plant
manage-
ment
Exposed women generally showed
significantly more morbidity
than (lid the exposed men or
the controls, especially in
respiratory disease, rausculo-
skeletal afflictions (attribu-
ted to the common cold and
physical exertion), and diseas-
es of the nrogenital tract.
In the exposed women, the
frequency of illnesses and
also the percent of Multiple
illnesses was higher (2.3 x
higher than the controls and
1.5 x higher than the exposed
men). The no. of cases (140.6)
and days of lost work capacity
(1,013.A) among the exposed
women exceeded those of the
controls by 1.5-1.6 x. The
exposed men did not show sig-
nificant differences from the
controls.
According to the authors, the
questionnaires showed that
the domestic situations of
the women in both the exposed
and control groups were similar.
However, the possibility of com-
parison bias (especially socio-
economic status and nutrition)
between those who work in the
plant and those in management
would seem likely. The wide
spectrum of problems in the ex-
posed group suggests major dif-
ference in life-style and socio-
economic status between cases
and controls, (iriescmer el al.
(1980) made the observations
that no description of the
methods uiied to determine mor-
bidity was given and that con-
trolled social factors may play
a role, so that increases in
lost workdays and evidence of
respiratory and nrogenital
diseases do not provide defin-
itive evidence concerning the
role of IICIIO, although it is
suggest ive.
Ischenko and
I'lishkinu
(I'J78)
C-8
(continued)
-------
TABLE V-l (continued)
ConMHiund(s) anil
Coiiceittratiou(s)
In tug/in1 (p|>m)
fopuiatton Croup
Description Exposed
Controls
Ambient IICIIO
0.035-0.48.
Highest level
reported at
name IIwe an
peak symptom
period. Free
IICIIO in fabric
ranged from
~ 1.4-2.8
(I.100-1.977).
Vapor discharge
from fabrics
reached max. of
~ 2.9 (2.345).
Garment factory
workers studied
during Feb. I to
Sept. 30, 1977.
3,034
No actual
control
group. Corn-
par I sons
made to
workers
in same
factory
during
sane
time
period
of 1976
when
differ-
erent
lot of
fabric
was being
used.
Effects
Remarks
RefertMirr
and
Hating
Cutaneous and MUCOUS membrane
irritations in 1,044 (30.31) of
the workers. Irritations were:
erythema of the exposed parts
of the body, 291; hyperemia
of the conjunctiva, 25%;
pharyngcal hyperemia and
dysphonia, 20%; conjunctiva)
hyperemia and erythema of
the exposed parts of the
body, 14%; pruritus with
undefined cause, 12%. Ap-
prox. 25% of workers re-
porting irritations had mor-
bid associations that were
presumed to have triggered the
occurrence of the above symp-
toms. These were: prior con-
tact sensibilization, 15%;
neuroses and hyperthyroidism,
12X; pliaryngeal tonsillitis and
chronic laryngitis, 5%; gastro-
hepatitis and metabolic disor-
ders, 4%; chronic conjuctivitis
or refractive defects, 4%; mycosis
and psoriasis, 1%. During study
period 7% of workers were diag-
nosed with illnesses unrelated to
IICIIO exposure. Compared to the year
before, there was ~ 8-fold increase
in incidence, frequency, anil ser-
iousness of incidences of irrita-
tion during the first 2 mo the
new fabrics were used; incidences
decreased but remained consis-
tently higher through the rent
of the study period compared to
the previous year. A remission of
symptoms occurred wlicn the lot
of rubric used during the study
WHS replaced liy other fabric.
Descriptive 2-time-period study Granat! et al.
of symptoms in workers exposed (1978)
to IICIIO. No exposure measure- B-9
mcnts had been made during the
"control" period. Also a
question of bias in the ascer-
tainment of symptoms and signs
of irritation during the exposure
period.
(font limed)
-------
Compoiind(s) anil
Coiiccntratioii(s)
in mg/m1 (|>|>m)
Population Croup
Description Exposed
TABLE V-l (comilined)
Controls
Effects
Remarks
Reference
anil
Rating
IICIIO
0.116 t 0.007 to
0.324 ± 0.02 in
workplaces;
0.00? t 0.001 to
0.046 i 0.002 in
the living
cjuarters
Furniture store work-
ers and i>ersons liv-
ing in apartments
above then.
IICIIO 0.2
(S 0.16)
S02
(<, 0.4)
Employees exposed to
gases in the kiln
room of a company
making ceramic cookie
s I amps. Eiup 1 oy ee s
did not "usually work
in the kiln room on a
regular basis during
the firing of the kilns."
Not given Not given During the sampling, most of
(6 apart- (2 apart- the workers complained upon
mauls ments interrogation of constant
were were headaches and irritation of
above not above the mucous membranes of the
film- furniture eyes. There were statistically
iture stores.) significant changes in some
stores.) indexes of the morphological
composition of the blood. In
3 stores, the specific action
of agglomeration of the leu-
kocytes was 822, 50%, and 61%
compared to 12% for the con-
trol group.
Upon interrogation, the in-
habitants of the living
quarters noted a sharp
strange odor. Both adults
and children noted dif-
ficulty of breathing and
irritation of the mucous
membranes of the eyes with
the most expression in the
night time and early morning
hours (when the store ventila-
tion was off).
Not None Nose and throat irritation.
given The investigator who entered
the room during firing to
check the sampling equipment
"felt an immediate irritation
of the nose and throat; but
it went away upon leaving the
room."
Descriptive study of furniture
store workers and 6 apartments
above the store. Suspect a
relatively small sample size
since only 8 apartments in-
volved. Health survey appears
biased (i.e., both inter-
viewer and interviewee bias).
No measurements of health ef-
fects given. Percentages
are of very small numbers.
Possible confounding with
phenol.
Trubitskaya
(1978)
C-5
(cout iiiiieil)
Although the author did not
consider the exposures detri-
mental, he recommended a
local exhaust ventilation
system. After its installa-
tion, the owner reported a
"t remendous improvement."
Note:
(a) exposure was confounded by
the presence of S02 and
phenols
(I)) documentation of persons
exposed is not given
(c) no controls or comparison
group, except that people
improved alter increased
vent ilatiou.
Apol
(1976)
I)--
-------
TABLE V-l (continued)
Cam|>ound(s) anil
Con<:cn t ra t i on ( •)
in »g/s>J
Poj>ulation Group
Description ~'
ConLrolH
I1CIIO
0.019-0.09
(< 0.014- < 0.04)
Acrolein
< 0.033- <0.09
(< 0.014- < 0.04)
CO
(< 1-15)
NO
(0*03-0.26)
80Z
(< 0.01)
Total partic-
ulates
0.09-0.26
Workers in the Run
and Service Building
of the Union Pacific
Railroad in Pocatello,
Idaho. Air Measure-
ments done on April
9-10, 1972. Medical
evaluation done on
April 19-20, 1972.
KifcclH
90 H
in this
building;
27 M
in other
srcas
(ex- •
posure
levels
of these
•en not
given)
Results of
a study of
10,000 In-
dustrial
workers
used for
compar-
ison to
the
ipi ro-
ne try
test
Remarks
Reference
iiml
Rut hiK
Worker! and sowe of the «M*II
taking air samples coaiplained
of burning eye*. 31/114 were
classified as having sy»ptoais
of bronchitis, as deter*died
by questionnaire. 12/114 ab-
normal splrograiiB (compared
to expected 7.2), not sta-
tistically significant. No
pnniBoconlutic lesions were
identified on chest x-ray.
The conclusion was that ex-
cessive chronic respiratory
disease probably docs not exist.
Prioarily a study of the occur- Apol (1973)
rencc of the gases, not a I1--
health effects survey. For
the purposes of this study,
the effect of IICI10 is con-
founded by the presence of
several other gases.
(continued)
-------
TABLE V-l (roittiniKul)
Compoiind(s) and
Oo
Concentrat ion(s)
in mg/m3 (ppm)
IICIIO, Ee 0.061
En 0.025
Ca 0.046
Totnl mean 0.047
Nil), Ee 0.038
En 0.089
Ca 0.057
Total mean 0.052
Resorcinol ,
Ee 0. 153
En 0.215
Ca 0.295
Total mean 0.213
Respirable par-
ticulatcs, < 0.5
Ho statistically
significant dif-
ferences between
exposure groups
for any of these
pollutants.
Population Group
Description Exposed
Workers in a tire 52
manufacturing plant Group Ee:
using a resin system 19 given
(HR) of hexamethylene- breath-
tetramine (a cyclic ing
condensation product tests
of IICIIO and Nil,) and before
resorcinol. and af-
ter 6 h
of work
with UK
stock.
Group
En: 16
given
these
tests
before
and af-
ter the
shift
on days
they
did not
work
with HR
stock
but at
jobs
similar
to their
normal
jobs.
Controls
50
Group C:
matched
with all
workers in
Group E for
race, shift,
sex, age,
and job.
Given same
question-
naire arid
breathing
tests as
Group E.
Group Ca
comprised
the 19 who
were given
lung func-
tion tests
before and
after work.
55
Group 0:
same age,
sex, and
race dis-
tribution
as Group
E. Se-
lected at
random
from total
plant pop-
ulation
and tested
the same as
Groups E
and C.
Effects
No statistically significant
difference in chronic respir-
atory and cardiovascular symp-
toms among the groups.
Self-reported symptoms were
greater in Group E: itch,
rash, cough, dyspnea at work,
chest tightness, burning eyes,
running nose, burning sensa-
tion in heart region, persis-
tent cough and phlegm. The
excess of symptoms persisted
after accounting for the ef-
fects of smoking and drinking.
Baseline lung function tests
in Groups E, C, anil 0 showed
no differences.
Group Ee showed significant
decrements in lung function
tests measuring "small air-
ways" effects. These are the
first effects to be observed
in a "hostile" atmosphere and
are reversible.
No lung function decrement
occurred in Group En on "non-
exposure" days.
and
Remarks Kill ing
Exposure is confounded by Nil), Gamble cl
resorcinol , IICN, and partic- (1976)
ulates. Furthermore, duration C-9
of employment may not be com-
parable in these groups. Mean
exposure concentrations of
IICIIO between KR-cxposcd, unex-
posed, and control groups were
similar and it is not surprising
that no differences In objective
measures were noted.
The authors point out the lack
of difference in the baseline
function tests may he due to
too short an exposure time for
the appearance of chronic ef-
fects, the HR system produces
no chronic effect, or suscept-
ible workers choose not to work
in the UK exposed jobs.
.ll
(continued)
-------
TABUi V-l (continued)
Co«|>ound(s) and
Concenlration(a)
in wg/B1 (|>IMB)
Population Croup
Description Exposed Control*
Effect*
Kematka
ami
Haling
(Conl'd)
Higher
percent-
age of
light
frequent
ami lower
coniump-
tton
ethyl
alcohol
drinker*
than in
the con-
trol*.
Kcspirable partlculale was re-
lated to functional losacs in
the UK-exposed worker*.
Functional losae* occurring over
a shift were greater in the older
IIR-exposed workers. These workers
were also classified as f moke IB and/
or drinkers; they had acute aympioma
of cough, running nose, and hoarseness.
ftaiiililt i! I
(1976)
(K.nlM)
(cont IIHUM!)
-------
TABLE V-l (ronliimc.l)
CoRipound(s) and
Concent ration(s)
in fflg/m3 (ppin)
Populallon Group
Description Exposed
Controls
Effects
Keinarks
Kef orrllre
ailll
Oi
O
IICIIO
0.025-0.036
(better vent-
ilation; but
0.22 in March
when ventilation
was not used).
0.012-0.04
(Dust 3)
0.11 (poor
ventilation;
dust 1.6 |28
in March))
0.09 (dust con-
tent 28 in
March)
21-26°C in
summer
R.ll. 36-56%
Workers in a plastics
factory producing
plienol-HCHO resin
comprised:
Holders
Not
given
Preparing plant workers
Preforming plant workers
Mechanical treatment
plant workers
Workers were 21 to
45 y old, half with
4-5 y of service and
half > 5 y.
Direct contact with phenol-IICIIO
powders and IICIIO vapors led to
simultaneous action via I lie
respiratory tract, gastroin-
testinal tract, and skin.
In 8% of the workers, clin-
ical changes of the skin were
characterized by lichenifica-
tions, erythema, cracking, and
pueling.
Skin tests with standard al-
lergens and 0.25% aqueous
solution of IICIIO showed that
22% were sensitized to IICIIO.
Application of graduated doses
to the skin gave not only local
but in some cases within 2-3 d
a general reaction in the form
of headache, general weakness,
poor health, and exacerbation
of clinical signs of allergosis.
Signs of a general reaction were
observed twice as often as local
changes. It appeared in persons
with 5 y of service.
In 40% of the subjects, there were
noted in the blood seniia some in-
dexes characterizing the patho-
cheinical stage of the allergic
process.
Apparent descriptive study of KIIZ'nicnko rl
the sensitizing character IK- (1975)
tics of IICIIO. Lack of controls C-4
greatly reduces the usefulness
of these data. Exposure levels
arc not well correlated to out-
come, although duration of ex-
posure of > 5 y correlates with
the frequency of "general reac-
tions" to IICIIO. Standard epidem-
iologic measures (i.e., rates
among exposed and uncxposcd) are
missing. There is a question of
possible confounding with phenol.
(continued)
-------
1'ADI.K V-l (continued)
Compound(s) and
Caucentrstioii(s)
in *g/M
Population Croup
Description Exposed'
Controls
Effects
Rrf rn-ni
ami
Hating
IICIIO,
generally
< the MAC
(0.5 «g/mj
according to
flrieaemer,
et •!., 1980;
5.U Mg/V ac-
cording to
Zaeva el al.,
1968).
Worker* Iron 2 wood- 276: 200 age-
processing concern* 102 H Matched,
using urca-HCHO 176 f; not hav-
re«ins; 71.2% had 74% ing IICIIO
worked S 5 y; 26.6%, < 40-y- exposure
6-10 y; and 2.2%, old
> 10 y
The prevalence of diseases of
the upper respiratory tract
was 28.2-58.3% in the workers
compared to 13.0% in the con-
trol group. This pathology
was BOSl prevslent In workers
of the hot pressing plant
where the IICIIO concentration
was 2.5 x that in the cold
pressing plant (although still
less than the HAC).
Host workers complained
of lowering of the
sense of smell and dry-
ness of the nose and
throat.
Subatrophic changes of the nasal
MUCOUS MCMbrane predominated in
the preparation plant (55.7%)
and in the hot pressing plant
(A 1.9% of the workers).
Hypertrophic changes ot the
nasal SHICOUS membrane occurred
in the cold pressing plant
(74.8%) and in the plant pro-
cessing wood-chip slabs (91.5%).
The prevalence of upper respir-
atory tract pathology was greater
in workers with shorter lengths
of service; e.g. , the morbidity
of chronic rhinitis was 15.7/100
for workers with S 5 y of
experience compared to 2.6-5.2/100
for workers with £ 6-10 y of exper-
ience. Presumably, the workers
with longer service had adapted
to the hazard.
Kficmov concluded that the
occupational exposure to IICIIO
played an important role in
causing functional dis-
turbances of the nasal mucous
membrane and the Marked
catarrha] condition of the
upper respiratory tract.
fiirrniov
(1970)
A-10
The Formaldehyde Panel (Cries-
erne r et al., 1980) concluded
"this report supports the
hypothesis that exposure to
formaldehyde May leud to
chronic respiratory diseases"
if it is assumed that "the age-
matched controls represent an
appropriate comparison group
(uo mention was made of match-
ing on sex and snoking history).
(continued)
-------
TAIII.K V-l (continual)
Coni|>ouii(l(s) and
Concentrulinn(s)
in i»g/ii»s (|i|iM)
Population Group
Description Exposed
Controls
Kllecls
Remarks
Rofrrencr
and
KalinK
COIll'll
The highest level of prevalence
of chronic rhinitis was noted
in persons aged 30-59 y
and more (TJ. 3-48.0/100) . Sim-
ilarly, for chronic pharyngitis,
the prevalence was 33.3/100 for
persons £ 50 y.
50 20 per- The adsorbing function of the
BODS nasal mucous inemlirane was
without judged according to the lime of
respir- appearance of mydriasis (pupil -
alory lary reaction) after a plug wet
tract with a homoIropine solution was
pathology inserted in the nasal cavity.
In the control group this tine
was 41.0 i 4.1 inin. This time
was shorter, indicating accel-
erated absorptive capacity, in
all the workers whether or not
they evinced any nasal pathology.
In the group of workers with
chronic rhinitis, it was 28.4
mill (p < 0.001). In the healthy
workers, the time was 33.3 ± 6.6
mill (p < 0.001 compared to the
control group). The acceleration
was especially intensive in the
30- to 39-y-old persons, the
workers with the highest level
of chronic rhinitis. In persons
with 3-5 y of service, the time
to the pupillary reaction was
30.0 ± 4.0 min.
Klrcmov
(1970)
(conl'd)
(continued)
-------
TABUS V-l (concluded)
Cotipoufid(s) and
Concent rat Ion(s)
in *g/»J (PPM)
Population Croup
Description ~ Exposed ' nlrols
Effects
Remarks
KoOri'iue
mid
Raling
cont'd
100
20
278
20
Ul
OJ
The molive function of the natal
mucous suistbranes of exposed work-
ers, even in those with no ap-
parent pathology, was significantly
retarded tonpared to that of the
persons of the control group. The
retardation was noted siost in
workers with greater length of
service.
In the workers, the odor thresh-
olds for rosemary, tbysral, caaphor,
and tar were 2.3 x higher than those
of the control group. Anosaia was
observed in 19 workers. There was
sn increase in odor thresholds in
172 of the workers, whereas path-
ological changes appeared in the
nasal mucous aeabrane of only Ik.
Kfriwov
(1970)
(conl'd)
-------
TABU V-2. El'IOF.MIOUmiCAI. AND OTHER STUDIES REI.KVANT TO KOHHAI.DKIIVDK INHALATION KXI'OKIIKK OK TDK C.KNKK.M. I'lllll.lC
Compound {ft) and
Concentralion(s)
in mg/m'
Population Group
Description Exposed
Controls
IICIIO nvg. 2.0;
range < 0.8-12.5
(avg. 1.6;
range < 0.5-10)
0.5 ppm was the
lower limit of
detectahility
for the method
used
Connecticut residents 8'i7
of houses, mobile
liowes, and small bus-
iness and public
buildings with urea-
formaldehyde foam in-
sulation installed 3
wk - 4 y (avg. 11.7
mo) earlier. Only
persons making com-
plaints to the Dept.
of Health were
questioned.
None »t
this time,
but may be
done in
the future
IICIIO avg. 2.0;
range 0.8-12.5
(avg. 1.6;
range 0.5-10)
These were the
levels measured
~ 2 y earlier,
when the avg.
foam age was
11.7 mo.
Follow-up survey in- 135/173
volving 173 com- house-
plaints received holds
> 2 y previously, responded
and investigated to the new
then for health survey
effects due to IICIIO
exposure from urea-
formaldehyde foam
insulation (Oiulielti,
1980).
None
Effects
Odor was always detected ut
£ 1.0 ppm. Odor could fre-
quently be ilc tec: ted a I < 0.5
ppm. 70% of the cases involv-
ing health effects claimed to
have delected the odor. Only
one case was found in which
detectable levels of IICIIO
(0.7-1 ppm) caused no reported
symptoms. 524/847 had symp-
toms: eye irritation and con-
junctivitis, nose and throat
irritation, respiratory symp-
toms, nausea, stomach problems,
dizziness, rash, skin growths,
fatigue, aches, and swollen
glands. 52-66% of the symptoms
were found in those exposed to
£ 0.5 ppm, and 34-48% were
found in persons exposed to
< 0.5 ppm.
Of the 138 households which
were symptomatic in the orig-
inal study, 110 responded to
the new survey, and 72 (65%)
of those still complained of
irritation of the nose, head,
lungs, eyes, throat, skin,
and gastrointestinal tract.
They felt that the symptoms
hnd remained the same or
worsened in the ~ 2 y. The
avg. length tit time that the
foam had been in place in
these hoiiKes was 2.3 1 0.8 y.
38/110 (35%) were no longer
symptomatic, for a variety of
reasons including moving and
removal of insulation.
llemarkK
A descriptive, unconlrolled
study of persons complaining
to tlie .Stale llcallh Dept.
The sample was biased
(sell-selection bias).
The described symptoms are
crudely correlated to IICIIO
levels measured. More
symptomatic persons at
nondetectable levels than
at levels between 0.5-10 ppm.
Since the study was only con-
ducted among those who com-
plained, the prevalence of
symptoms cannot be estab-
lished. There was no real
attempt to correlate dose
with symptoms. It is con-
sistent with other studies
suggesting irritation of the
eyes, nose, anil throat at
> 0.1 ppm. For further
comments, see Appendix A.
A lollow-up of Giulietti's
I960 study ill Connecticut.
Survey by self-administered
questionnaire. No new IICIIO
measurements were made. The
study suggests that the orig-
inal symptoms persist in the
highly biased population. No
controls, but the study does
suggest the need for longer-
term evaluation.
Kcfnri'iiri!
•mil
lliil ing
0 i u I i e 11 i
(1980)
fl-f>
Host et
(1981)
IJ-5
nl ,
(continued)
-------
TABI.K V-2 (continued)
CoM(ioiiud(s) 'and
Concentration(•)
In »g/m3
______
Description
Crou£_
Exposed"
__
Control*
Effects
Remarks
iinil
IICIIO 8.7i
(7.0)
IICIIO
6.25
(4 5)
A one-time
measurement,
after tlie
school had
been closed
for holiday*.
Building was
~ 8 mo old.
Ui
v/i
IICIIO 0-6.25
(0-5)
IICIIO 5.0
(4.0)
Residents of homes
with urea-fonsslde-
liyde foasi insulation,
First through third
grade students, in
* prefabricated
school, for the 8
mo after construc-
tion.
«,
adults
and
children
Not
given
None
None
Residents of a home
with urea- f orsulde-
hyde foa* insulation
Residents of * hotse
with urea- formalde-
hyde foa* insulation.
Not
given
None
None
Upper respiratory tract irrita- See entry for 1.13-1.9 mg/m3
tlon. Odor was detected, par- (CPSC, 1978), in this table.
ticularly in humid weather.
A "large ausdier" of the child-
ren complained of different
degrees of burning eyes, head-
sclies, pain in the eyes, ab-
dowinal pains, nausea, vomit-
ing, increased thirst, and
apathy, and were unusually
pale. Odor and symptoms were
particularly strong after
weekends and holidays whnn
there was no ventilation,
and when the heat was on..
There was a degree of habit-
uation (tolerance) after retrain-
ing in the building for noon-
time. Children moved to
another building had no more
symptoms.
Eye and upper respiratory
tract irritation.
Residents complained of odor
and suffered from eye and
respiratory tract irritation.
CI'SC
(1978)
n-2
A descriptive, cross-sectional llulwig
study of suspected exposure to (19/7)
HCI10. No controls and limited R-4
exposure measurements (one-time
levels when the school was
closed). Detailed quantitative
measuremciiln of Hyuptous were
not taken. There appears to be less
biss in this study since the
children were having symptoms
prior to the discovery and
measuresient of IICIIO. Symptoms
resolved when they moved to
another school, but careful,
controlled documentation is
not given.
See entry for 1.13-1.19
•g/ma (CPSC, 1978).
See entry for 1.13-1. 19
mg/m3 (CPSC, 1978).
CPSC
(1978)
B-2
CPSC
(1978)
B-2
(until iniied)
-------
Conipoiind(s) and
Concent rat ion(s)
in rog/m' (ppm)
Population Croup
Description Exposed
TABLE V-2 (coiiliniiiMl)
Controls
Effects
Hcinarks
ami
K.I I ing
IICIIO 0.06-4.25 Survey of 39 con veil- 14 adult
(0.05-3.40); tional homes which H, 18
80% of the had urea-fornalde- adult F,
samples were liyde foam installed, 12
< 0.63 nig/ni3 with residents con- children
plaining of adverse
health effects.
None Irritation ul the eyes, nose,
and respiratory tract were the
moat frequent complaints.
Drowsiness, memory lapse,
chronic headache, nausea,
cold, cough, and sneezing
were also reported. Speci-
fic exposure levels and symp-
toms are given in Breysiie
(1978).
A series of case reports of
persons complaining of IICIIO
exposure. Exposures were
Measured on an individual
basis. Symptoms are quite
consistent, hut there is no
control group and only acute
effects arc reported. Sum-
maries of these data do not
permit an estimate or mea-
surement of the association
between IICIIO exposure and
specific disease or symptom
syndromes.
(1978)
11-6
Breysse
(I979a)
11-6
01
(continued)
-------
TABLE V-2 (continued)
ui
Compound(a) and
Concent ratioit(s)
in mg/w1 (ppm)
IICIIO
< O.I4-> 3.75
(< 0.1103)
Twenty-iix
percent of the
"case-study"
homes exceeded
0.8 ppn; only
2% of the "ran-
dom" homes ex-
ceeded 0.8 ppM.
Population Croup
Description Exposed
Residents of 105 mo- 191
1)1 le hones in
Wisconsin which used
particle board in the
construction. Forty
were randomly se-
lected by the authors
and 65 were taken fro*
complaints received by
the health department.
Controls
None
Effects
Kraarkn
and
Rating
When age of the lio*ei was con-
sidered, both groups were found
to have the same distribution
of IICIIO levels (levels decrease
with Increasing sge). So the
two groups were analyzed as
one. Twenty-three different
adverse symptoms arc reported.
The most common (> 251) being:
eye and nose irritation, cough-
ing, dry/sore throat, headache,
and burning eyes. Prevalence
of symptoms was lower in the
random group, and the only
symptom which was significantly
associated with IICHO concentra-
tion was burning eyes. A model
is developed predicting that
20% of adults would experience
burning eyes at 0.2 ppm, which
the authors recommend as the
indoor IICIIO standard.
A mixed survey of 65 complain-
ing mobile tione owners and an
attempted cross-sect tuna I study
of 208 randomly selected mobile
homes. "Complaint cases" were
added to the cross-sectional
study when only 50% of those
contacted agreed to participate:
- 65 allowed air measurements to
be taken.
- 40/65 (60%) of thc»e allowed
clinical information to be
recorded.
Thus, a heavy self-selection
bias is present both for the
"complaint" cases and the
"random" series. There are
essentially no controls (whe-
ther or not the two groups art:
lumped together or compared).
Twenty-eight percunt or 16 of
the "random" group met the
clinical criteria of the "com-
plaint" series. It is diffi-
cult to interpret this In view
of the selection bias due to
the poor response rate. Only
acute symptoms are evaluated
and long-term exposures cannot
be estimated from this study.
The threshold recommended as a
standard from this study is
simply an "educated guess."
The study does correlate IICIIO
levels to age of roimtrucllon
Materials and this will be use-
lul in note well-controlled
studies. For further < oronionta,
BCC Appendix A.
llanrahuii
rt nl.
(1980?)
D-6
(l nut ilinril)
-------
Compound(s) and
Conceulrat ion(s)
in Big/ra1 (|>|>ro)
TABLE V-2 (continued)
Pojiu Ration ?roi'l!
Description Exposed
Controls
Klfeels
Kcm.iiks
Itafi'rrncr
mid
Kill ii>|>
IICIIO
avg. ~ 1.38;
range 0.38-3.88
(avg. -1.1;
range 0.3-3.I)
Ln
00
IICIIO 3.75
(3.0)
IICIIO 3.75
(3)
The maximum
level measured
Tenants, employees, Not given None
and customers of a
shopping center which
used urea-formaldehyde
foam insulation and
had been open 6 mo.
Residents of a home
with urea-formalde-
hyde foam insulation.
Residents of apart-
ment complex where
urea-formaldehyde
foam had been in-
stalled.
Not
given
None
None
Complaints of eye (with occa-
sional lacrimation), nose, and
throat irritation. No skin ir-
ritation. These effects were
enhanced on hot-humid days.
Complaints of eye and upper
respiratory irritation,
stomach cramps, fatigue,
and odor were reported.
Eye irritation.
An environmental survey of a
shopping center requested by
the tenants. No information
on exposed persons. Only 3
sentences on subjective symp-
toms, which increased on hot-
liumid days. The survey was
performed 2 wk after the loam
was removed, so that the IICIIO
levels are not meaningful. A
new ton chromatographic system
for IICIIO analysis was utilized
(charcoal-packed tubes).
See entry for 1.13-1.19
mg/ma (CI'SC, 1978).
See entry for 1.13-1.19
mg/m3 (CPSC, 1978).
Ta'n
(1980)
C-2
CI'SC
(1078)
B-2
CI'SC
(1978)
B-2
IICIIO 2.5
(2.0)
Residents of homes
with urea-formalde-
hyde foam insulation.
4 adults None
Headaches and eye and upper
respiratory tract irritation
were reported. Odor was
detected, especially on
humid days.
See entry for 1.13-1.19
rng/ra3 (CI'SC, 1978).
CI'SC
(1978)
B-2
(continued)
-------
TABLE V-2 (conliiiiK'.l)
Compoimd(s) and
Concentratlon(s)
ill rng/w1 (ppn)
Population Groiu)
Description Exposed
Controls Rffecls
He Terence
and
Kemarka Haling
Ln
vo
IICIIO
0.04-2.21
(0.03-1.77)
Sixty-six
percent of
the samples
were between
0.13 an
-------
TABLE V-2 (conlinurd)
Com|)oiiiiil(s) and
Concentralion(s)
in mg/m3 (ppm)
_Popul]il_io_n Croup _
Description Exposed
Controls
Effects
Kemarks
Reference
ami
Bating
IICIIO
~ 0.25— 1.25
(~ 0.2-~ 1.0)
Cases of possible
IICIIO exposure in the
home, reported to
the Minnesota De-
partment of Health.
168 None Eye, nose, and throat irrita-
(93 H tion was reported more often
+ 75 F; in adults. Coughing, wheezing,
36 new- and skin rash were reported
born to more often in the < 13-y-old
2-y-olds, groups. Diarrhea, nausea, and
30 3 to vomiting were reported more
13-y-olds, often in babies. Other symp-
102 > 13- tonis included respiratory
y-olds) problems arid headache. The
mean IICIIO concentration in
the homes of persons reporting
the index symptoms (eye, nose,
and throat irritation) was
significantly higher than the
concentration in non-symptoma-
tic individuals' homes. Per-
sons with history of asthma
reported effects at a lower
dose.
Descriptive survey of com-
plaints of possible exposures
to IICIIO and in-home ambient air
levels. No controls. Symptoms
are riot correlated to exposure
levels, except to slate that
mean levels were higher in
homes with a person reporting
index symptoms (eye, nose, and
throat irritation). Therefore
not useful for deriving a range
of concern. Few data arc given.
The most useful information is
the documentation of changes in
home IICIIO with changing seasons
and age of home. Only acute
effects were examined, and a
potential for selection bias
exists.
Carry ct al,
(I9BO)
Ii-7
(continued)
-------
TAIU.K V-2 (continued)
Compound's) and
ConrentniUonU)
In mg/M1 (ppm)
Population Croup
Description Exposed'
Controls
Effects
Hi-murks
Reference
ami
Knling
IICIIO 0.10-1.21
(0.08-0.97)
Teacher* *nd pupils
in 3 scliools with
IICHO-e»itUng chip-
board in the panel-
ing and acoustic
ceilings. Duration
of exposure not
given
1,594 497, I torn Test group had significantly
schools higher frequency of complaints
without for: headaches, disorders of
chipboard concentration ability, dizzi-
ness, nausea, irritation of
the aucosa of the nose and
throat, cough, and irritation
of the conjunctiva. An in-
crease in recurrent upper
respiratory tract infec-
tions also reported. In
a follow-up study of 328
people, 8 no after chip-
boards had been removed
frost the school, a de-
crease in all symptoms
was found (30-100%)
A poorly controlled CTOBS-
sectional study of the acute
effects of low levels of IICIIO.
Controls comprised only 1/3
the no. of cases. Compara-
bility of the groups is not
described. Controls were
not utilized in the follow-up
portion of the study. IICIIO
measurements were not made.
The canes were heavily biased
by the complaints from teachers
and students which initialed
the atudy. Subjective "func-
tional" outcome would be
heavily influenced by this
type of bias. This study
needs more objective mea-
sures (i.e., absenteeism).
Duration of exposure not
evaluated.
Strengths of the study include
the following:
(1) total number of cases
(2) diminished symptoms were
reported after the removal
of the chipboards (but
environmental measurements
of IICIIO were not repeated)
(3) respiratory complaints at
low levels of IICIIO were re-
ported, arid so may be use-
ful for determining a range
of concern.
Dunbili and
Wechsclberg
(1980)
B-9
(continued)
-------
TAIII.E V-2 (rout inur.l)
Coinpound(s) and
Concenlration(s)
in mg/m1 (ppm)
Population Group
Description Exposed
Controls
Effects
Hi-marks
Reference
a ml
K.it Ing
IICIIO 1.13-1.19
(0.0-0.95)
Tlie max i mum
level measured
IICIIO 1.13
(0.09)
IICIIO
1.0
(0.8)
Residents and tenants
of buildings, imme-
diately after urea-
formaldehyde loan
insulation was in-
stalled
None
Resident of a home
with urea-formalde-
hyde foam insulation
Eye and upper respiratory
tract irritation.
1 adult
Resident of a home 1 F,
with urea-formalde- 51 y
hyde foam insulation
None
None
Eye and upper respiratory
tract irritation. No odor
after initial installation.
Eye irritation.
A scries of case reports of
persons complaining of IICIIO
exposure. Exposure measure-
ments were made, but:
(1) no controls
(2) biased sample (of complain-
ing persons)
(3) symptoms only generally
described
(4) other irritants were not
considered
The report is useful to i;ain an
appreciation of the uniformity
of complaints and the breadth
of the problem.
See entry for 1.13-1.19 mg/m3
(CPSC, 1978).
See entry for 1.13-1.19 mg/m3
(CPSC, 1978)
Cl'SC
(1978)
B-2
Cl'SC
(1978)
B-2
CPSC
(1978)
B-2
(continued)
-------
TABLE V-2 (continued)
Compountl(s) and
Concentration(s)
in mg/m1 (ppn)
Description
Population Croup
Exposed Controls
Remarks
Deference
nuil
Mating
IICIIO 0-0.98
(0-0.78)
Residents of 55
homes with urea-
formaldehyde foa«
insulation, who
voluntarily reported
health problems to
the New Jersey State
Dept. of Health;
1-40 mo after instal-
lation
153 None 111/153 complained of SOUP ad-
verse health effect. The aiain
complaints were burning or
tearing of eyes, sore throat,
cough, runny nose, wheezing or
breathing difficulty, head-
aches, sleeping problem,
and skin rashes. Avg. IICIIO
concentration generally de-
creased with increasing lime
since foam installation. Of
the 15 homes sampled i 4 mo
after installation, 9 (60*)
had IICIIO levels £ 0.01 \>\m.
ON
u>
Descriptive, uncontrolled Niir-
vcy of persons complaining due (1980)
to recently installed urea- B-6
formaldehyde foam insulation.
Only 22 of 55 homes had air
samples taken, and despite
reported symptoms 5 were nega-
tive. Problems with these data:
(I) only those who complained
were surveyed (biased sample)
(2) no controls (symptoms may
vary with age, sex, race,
sociocconomic status, smoking
history, season, etc.)
(3) limited, crude measurements
of exposure. No search for
other possible irritants
(4) only acute effects were
evaluated.
(5) symptoms not correlated to
exposure levels.
(6) in one of the cases where
Measurements were made before,
air sampling showed 1.5 ppb
before and negative results
2 d after installation. This
highlights the need for con-
trols of these measurement
procedures.
The report shows that IICIIO levels
diminish with time, ventilation,
snd the removal of foam. For
further comments, sec Appendix A.
(continued)
-------
TAIII.K V-2 (continued)
COIII|IOIIIII|(H) anil
Concentration(s)
in mg/m1 (ppm)
Population Croug
Description Exposed
Controls
Effects
Remarks
Reference
and
Hat ing
IICIIO £ 0.88
(S 0.7)
IICIIO 0.75
(0.6)
The maximum
level measured
IICIIO
0.25-0.75
(0.2-0.6)
Residents of build-
ings with urea-
formaldehyde foam
insulation
Residents of a home
where urea-formalde-
hyde foam insulation
had been installed
Residents of an
apartment building
built with chipboard
containing formalde-
hyde resins
Not
given
adults
None Eye and upper respiratory
tract irritation and head-
aches. Some complained of
odor, lasting a few days or
a couple of months. Others
noticed no odor. 2/9 had no
symptoms (in a home with no
odor).
None Eye irritation.
None Complained of burning of eyes,
tearing, and coughing. After
7-h exposure to 0.78 mg/m3,
between 2.3 and 6.7 mg%
formic acid (IICOOII) and
between 0.06 and 0.07 mg%
IICIIO were found in the urine.
During a 17*1) recovery period,
between 2.3 and 4.1 mgl IICOOII
and between 0.007 and 0.12 mg%
IICIIO were found iir the urine.
See enlry for 1.13-1.19
mg/m3 (CPSC, 1978)
See entry for 1.13-1.19
mg/m3 (CPSC, 1978)
Cl'SC
(1978)
B-2
CPSC
(1978)
B-2
An experimental study where
subjects served as their own
controls to evaluate biologic
measurement of IICIIO and formic
acid excretion after varying ex-
posures. The study design is
weak and only limited conclu-
sions can be drawn due to:
(1) too few subjects to measure
individual variation.
(2) no baseline measurements
were made when subjects were
totally unexposed.
(3) acute symptoms are not well
correlated to biologic mea-
surements .
(4) the proposed threshold level
(0.1-0.5) is derived on the
basis of the sensitivity of
the tests used, not on care-
ful measurements of liealtli
or disease outcome.
Ki nli rod I and
Prajsnar
(1978)
11-6
(continued)
-------
TAIII.K V-2 (continued)
Cnm|>ouii(l(u) and
ConcentraIion(s)
in mg/»* (ppm)
Population
Description Exposed
Controls
Effects
Remarks
Reference
nnil
Kntiiig
IICIIO S 0.63
(S 0.5)
Ui
IICIIO
avg. 0.211
wax. 0.578
IICIIO
0.36-0.46
(0.29-0.37)
IICIIO
0.09-0.13
(0.07-0.10)
Resident! of build-
ings wilh urea-
formaldehyde foasi
insulation
57 adults
and chil-
dren
None
Residents living 52
- 250 si from a
plant producing
formalin
Residents of a hone Not
with urea-formalde- given
hyde foan insulation
Residents of an 4
apartment building
constructed of for-
maldehyde resin
chipboard.
None
None
None
Eye and upper respiratory
tract irritation, headaches,
sore throat, muscle aches,
lung congestion, skin rash,
and nausea. Each incident
generally caused only I or
2 of the symptoms. Some
noticed an odor only \ A
after foan installation.
Others reported an inter-
mittent odor lasting 5 SKI.
Some had complaints, but
swelled no odor. A few
family members had no
symptoms. One family
was driven from the home
by the odor and symptoms.
The IICIIO level at that
lime was 18.8 mg/m3.
9/52 complained of irritation
of the upper respiratory tract,
eyes, and throat. Odor was
clearly perceived by the leih-
nI clans taking the air samples.
Eye and upper respiratory
tract irritation.
Had complained of eye and
throat irritation at 0.25-0.75
mg/m3 (see entry for those
levels, Einbrodt and Prajsnar,
1978). No (symptoms at these
levels.
See entry for 1.13-1.19 mg/m3
(CI'SC, 1978)
This account is just a
brief section in an
article on experisiental
exposure.
Sec entry for 1.13-1.19 mg/ma
(CFSC, 1978)
CI'SC
(1978)
11-2
Melekhina
(1964)
A-9
CI'SC
(1978)
B-2
Einbroilt and
Prajsnar
(1978)
IJ-6
(continued)
-------
TAIJI.K V-2 (continue.!)
Compound(a) ami
Concent rat ion(s)
in me/in1 (ppm)
I'onu 1 a t i on _
Description Exposed
Controls
KII.M tfi
Kcmarks
Referent <•
anil
Hating
IICIIO
~ 0.08- ~ 0.13
(0.06-0.10)
Children in a school
built with chipboard
ceilings and some fur-
niture and walls pre-
sumably made of 1IC110-
containing materials.
There was constant
ventilation.
37 None No complaints were received,
nnd there was no increase in
absenteeism compared to other
schools in the district.
17/37 were exposed to ~ 0.13
ing/in3, and between l.B and 5.2
mg% IICOOII and up to 0.05 niftX
IICIIO were found In their urine.
20/37 were exposed to ~ 0.07
mg/m3, and between 1.5 and
5.9 mg% IICOOII, and up to 0.07
mg% IICIIO were found in their
urine. During 24-h elimina-
tion, both groups had similar
values: 17.8 ing HCOOH/24-h
urine for those exposed to
0.12 mg/m3, and 15.7 rng IICOOII/
24-ti urine for those exposed
to 0.07 mg/m3. Authors con-
clude that exposure to £ 0.1
ppm IICIIO cannot be biologically
traced.
See comments for the 0.25-0.75
mg/m3 entry (lUnhrodt and
liajsnai, 1'JVft). This utudy
is uncuntrolled, but the re-
port of similar absenteeism
rates suggests that few acute
problems may be present. This
descriptive study simply sets
the limits of sensitivity of
of the analytical measurements.
Kinbrodt and
Prajsnar
O'J78)
11-6
(continued)
-------
TAI1I.K V-2 (continued)
Compound(a) and
Concent ra11on(•)
in mg/rn1 (ppm)
Population Croup
Description Kxpnsed
Controli
Kffocls
Kumar kit
Reference
anil
Knling
IICIIO unt given
Resident* of homea 1,396
1 mill a Led with urea- (395
formaldehyde (OF) liotise-
fo«m in the year holds)
preceding the ft inly.
1,395 124/395 delected an odor after
(400 the installation of the foam,
lioiiae- lasting < 1 wit- > I mo. from
holds the prevalence data for the
without entire study period, only
UF foam) asthma, wheezing or breath-
ing difficulty, and burning
skin were higher in the ex-
posed group. Only wheezing
was statistically significant.
Incidence data for new sysiptosis
occurring in the study period
was significant for asthma,
breathing difficulty, and
burning skin. The rate of
acquisition of new Symplons
in the post-UK installation
population wns significantly
(slightly) above that of the
control population. There
was a dose-response effect
between the presence and
duration of odor and an in-
crease in the rale of new
symptom acquisition. Overall
rates of seeking medical at-
tention were aliont the same
in both groups. The persis-
tent odor group was higher,
post-insulation. 64.3X of
the Insulated households de-
nied any problems which they
associated with the foam.
Essentially a cross-sectional Thiiii el al.
study which correlates ex- (1480)
posure to urea-formaldehyde C-lli
foam insulation to the pre-
valence of symptoms deter-
mined by telephone interview.
Unfortunately, no environmental
measurements of IICIIO were made
to correlate with odor percep-
tion and symptoms. Control
households were we 11-matdied by
geographic location and appeared
similar in socioeconomic status,
family size, and percentage of
smokers in the households. This
study could have been designed
and analyzed as a concurrent
prospective study and morbidity
rates determined. Unfortunately,
this was not done and only
simple differences in proportion
of symptoms were evaluated (i.e.,
there was no stratification by
smoking status vs. exposure to
IICIIO). Selective recall bias
may he present in the cases due
to the nature of the publicity
and the telephone interviews.
For further comments, see Appen-
dix A.
(rout i lined)
-------
TABLE V-2 (concluded)
Compound(s) and
Concentratioii(s)
in nig/m3 (|ipm)
Population Croup
Description Exposed
Controls
Effects
Remarks
Reference
and
K.i ting
IICIIO Occupants of hones
Nut given insulated with urea-
fa rnaldehyde foan.
24 H, None The major symptoms were: dys-
24 F, pnea, headache, rhinitis, eye
6-mo to irritation, cough, and fre-
75-y-old quenl colds. Other symptoms
were: rani), malaise, sore
throat, and vomiting in in-
fants < 1-y-old. Symptoms
lasted at least 1 mo, and up
to 4, y. Only 38% could de-
tect the odor of IICIIO, Indi-
cating olfactory accommodation.
Descriptive survey of com-
plaints of persons contacting
the Rocky Mountain I'oison
Center after homes had been
newly insulated with IICIIO
foam. The lack of exposure
measurements made, the brief
review of acute symptoms,
lack of controls, the limited
nos., and the selection bias
all limit the usefulness of
this study. Mainly a review
of other studies.
Harris el a I.
(198!)
00
-------
SECTION VI
SUMMARY OF HEALTH EFFECTS INFORMATION
This chapter provides background information on the toxicity and metab-
olism of HCHO and reviews the most relevant studies that were described in
tabular format in Chapters II through V.
BACKGROUND
Toxicity
HCHO is a well-known toxic gas, covered in such standard works as Gosselin
et al. (1976). The generally acknowledged effects of gaseous HCHO are irrita-
tion of the eyes and upper respiratory tract with edema and/or laryngospasm
in severe cases. It is generally believed that the high reactivity of HCHO
with amines and formation of methylol adducts with nucleic acids, histones,
proteins, and amino acids account for many of the adverse effects of high
concentrations such as coagulation necrosis and mutagenicity.
Systemically, HCHO decreases blood pressure and causes irregular respir-
ation. Thus, i.v doses of £ 5 mg HCHO/kg produce primarily pressor effects
in anesthetized rats; at 10 mg/kg, both pressor and depressor effects are
manifested about equally; but at 20 mg/kg, only depressor effects such as
marked bradycardia and occasional transient cardiac arrest are seen. The
pressor effect is thought to be due to the release of catecholamine from
the sympathetic nerve endings and the adrenal medulla (Kitchens et al.,
1976).
Metabolism
Although HCHO metabolically produced at the site of damage is generally
believed to be the cause of methanol-induced retinal lesions, the only eye
lesion reported from exogenous HCHO is superficial irritation and burns.
The metabolism of HCHO in mammals has been summarized by Akabane et al. (1970)
Kitchens et al. (1976), Griesemer et al. (1980), and, most recently, by Brooks
and Reinhart (1981) in the National Research Council/National Academy of
Sciences publication Formaldehyde and Other Aldehydes.
Formaldehyde is a normal metabolite along with formic acid (HC02H),
its metabolic oxidation product, in the tetrahydrofolic acid-dependent one-
carbon pool. This pool is a synthetic pathway for the addition of a single
carbon group to a substrate molecule. The interconversions of labile methyl
169
-------
(CH3) groups from degradation of 0-, N-, and S-methyl compounds (primarily
araino acids), formic acid (as its sodium salt), and HCHO are depicted in
Figure VI-1.
HCHO may be utilized in the one-carbon pool (tetrahydrofolic acid path-
way) , but to a greater extent is converted to S-formyl glutathione, which
is oxidized by NAD. Cleavage by a thiol esterase releases formic acid and
glutathione. HCHO may also be oxidized to formic acid by a nonspecific alde-
hyde dehydrogenase (Griesemer et al., 1980). The major pathway for formate
oxidation to C02 is via the tetrahydrofolic acid pathway (at least in rats)
(Palese and Tephly, 1975; Makar and Tephly, 1977).
Proteins and * Labile CH3 groups
nucleic acids ^>^* and one - carbon
metabolism
I
HCHO " HCO2H
1
HCO2Na
in urine
Figure VI-1. Formaldehyde Metabolism by the Tetrahydrofolic Acid-
Dependent Pathway (adapted from Griesemer et al.,
1980; and Kitchens et al., 1976).
HCHO is so rapidly oxidized to formate that when measurements of the
two in blood and urine are attempted after intake of HCHO or methanol, for-
mate concentrations are always higher than those of HCHO. Sometimes HCHO
is not even detected, although this may be due to a problem of analytical
sensitivity. The blood half-life of HCHO in cynomolg'us monkeys was esti-
mated to be 1.5 min by McMartin et al. (1979), which agrees well with values
observed in rats, guinea pigs, rabbits, and cats. However, the human data
of Einbrodt et al. (1976) leads to a half-life of HCHO in blood of ~ 85 h
(Dost, 1980). The plasma half-life of formate is 80-90 min (Griesemer et
al., 1980).
170
-------
In vitro, HCHO interferes with adenosine triphosphate (ATP) generation,
uncouples oxidative phosphorylation, and possibly inhibits anaerobic glycol-
ysis. Because the retina has a greater oxygen consumption via aerobic gly-
colysis in proportion to its iron content than any other tissue, HCHO is
the generally accepted cause of the visual symptoms and signs observed in
methanol-poisoned primates (Schneck, 1979). Perhaps the reason ocular
toxicity has never been found in HCHO poisoning is because there have been
far fewer cases of HCHO ingestion, or, as Gosselin et al. (1976) suggest,
perhaps HCHO must be generated metabolically in the sensitive ganglion cells
of the retina from methanol, never being able to reach that site when taken
into the body as HCHO.
Martin-Amat et al. (cited as "to be published" by McMartin et al., 1979)
have shown that formate produces ocular toxicity in the intact monkey identi-
cal to that produced by methanol. This finding, coupled with the finding
that formic acid accumulation accounts for the metabolic acidosis seen in
methanol poisoning, suggests that HCHO is not a major factor in methanol
poisoning, at least in the monkey (McMartin et al., 1979).
The biochemical mechanisms for the differences in the toxicities of
HCHO and methanol are not completely clear due to species differences, other
metabolic pathways, and a variety of other complications. Regardless of
the reasons why, the retinal toxicity of methanol is irrelevant to the toxic-
ity of low levels of formaldehyde.
BIOASSAY TESTS
In vitro tests show that HCHO inhibits ciliary movement in respiratory
tissue and is a weak mutagen. Only studies on respiratory tissue effects
were tabulated in Chapter II. The mutagenicity of HCHO is briefly discussed
here.
In vitro tests on respiratory tissues
Most of the in vitro tests evaluated toxic affects of HCHO and cogeners
(acrolein was often compared) on respiratory tissues, the site of greatest
cellular toxicity in whole-animal exposure (see Table II-l). Ciliary activ-
ity of the rabbit trachea and the clam gill was often used to quantitate
effects of HCHO vapors (Cralley, 1942; Kensler and Battista, 1963; Kensler
and Battista, 1966; Wynder et al., 1965). Measures were made on either the
dose required to produce ciliary paralysis or on the transport rate of micro-
scopic particles by ciliary movement in the in vitro preparation, before
and after HCHO exposure.
Cilia of rabbit tracheas were paralyzed rapidly after HCHO exposure.
Some representative doses are: 50 ppm (Dalhamn and Rosengren, 1971); 30 ppm
in air or 60 ppm in buffer for 5 min (Cralley, 1942). HCHO given in eight
12-s doses, 150 mg/m3 in each dose, produced a 50% reduction of the movement
of particles in a rabbit trachea bioassay (Kensler and Battista, 1963).
Kensler and Battista (1966) found HCHO was inhibitory to ciliary transport
activity, but that (unlike acrolein and HCN) the effects of formaldehyde
171
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were rapidly reversible. Wynder et al. (1965) noted that HCHO had the most
rapid ciliostatic effect of several aldehydes tested in a clam gill bioassay—
stasis at 0.05% (500 ppm) in water—but that recovery of spontaneous activity
occurred. Dalhamn and Rosengren (1971) did not look at recovery in the rabbit
trachea bioassay; HCHO produced ciliostasis at 60 mg/m3 (50 ppm). Other
aldehydes were less toxic; acrolein produced ciliostasis at five times the
HCHO level, and acetaldehyde effects were seen with 100 times the HCHO dose.
Other bioassays
The Formaldehyde Panel (Griesemer et al., 1980) summarized most of the
available literature on the mutagenicity of HCHO, usually in the form of
HCHO-food or aqueous -solutions. Auerbach et al. (1977) reviewed in-depth
tests with fruit flies (Drosophila), grasshoppers, fungi, and bacteria, and
possible mechanisms of HCHO's action on DNA. HCHO vapors have seldom been
tested for mutagenic effect. Drosophila adults exposed for ^ 1 h and larvae
exposed for S 2 h to sublethal concentrations of HCHO gas showed no mutations
(Auerbach, 1949; cited by Griesemer et al., 1980).
The DNA single-strand breaks and DNA-protein crosslinks in bacteria
and yeast cells are the only lesions found that have been rather well char-
acterized for HCHO. In yeast cells, the HCHO-induced single-strand breaks
seem to be reparable. In both bacteria and yeast, the excision-resynthesis
repair system appears to be involved in at least a fraction of formaldehyde-
induced lesions (Chanet et al., 1976). In yeast, HCHO induces mitotic re-
combinations and a cell-cycle dependence which was demonstrated for both
lethality and induction of recombination (Chanet and Von Borstel, 1979).
Effects found in cultured mammalian cells include an 8- to 10-fold in-
crease in forward mutation frequency at the thymidine kinase locus in mouse
lymphoma cells; a 1.5- to 3-fold increase in the frequency of sister chromatid
exchanges in Chinese hamster ovary cells (however, Hsie et al., 1978, who
were not cited by the Formaldehyde Panel, reported in a brief abstract that
HCHO gave a possible false negative in the Chinese Hamster Ovary CHO/HGPRT
system); and induction of unscheduled DNA synthesis in HeLa (human cervical
cancer) cells by 10"8 to 10~6 M solutions of HCHO (Griesemer et al., 1980).
A current study is attempting to correlate blood levels of HCHO with changes
in human chromosomal material in cultured human lymphocytes (Anonymous, 1980c).
Griesemer et al. (1980) concluded that HCHO can be classified as a weak
mutagen. Although it causes gene mutations and chromosome aberrations such
as deficiencies, duplications, inversions, and translocations, dose-response
relations have been poorly demonstrated. They suggested use of certain mam-
malian tests that would aid in the prediction of .possible human genetic
effects. These were the in vitro mammalian spot test to determine whether
HCHO vapors or solutions would cause gene mutations in somatic cells that
affect coat color, the heritable translocation test, and the morphological
specific locus test. The latter two tests detect genetic effects in male
germ cells.
Other in vitro test models of HCHO effects included the chorioallantoic
membrane of~~the hen's egg, where 0.625 to 10 MS HCHO/jjL (625 - 10,000 ppm
172
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or 0.0625 - 1.0%) produced hyperplasia. Comber and Grasso (1973) measured
the effects of a series of chemicals on the 10-day incubated egg model, com-
paring toxic effects of the chemicals to that of croton oil, a potent tumor
inducer. HCHO rated 3,000 on an arbitrary scale rating croton oil at 6,500.
In comparison, cigarette smoke condensate rated 200; phenol, 50; and silica,
< 10. Gibson (as cited in Anonymous, 1981a) speculated on HCHO's role as a
promoter in his cited discussion of recent rat carcinogenicity data on the
chemical.
ANIMAL EXPOSURE STUDIES
Animal studies of the effects of HCHO are detailed in a serie's of tables
given in Chapter III and discussed below. A complete summary table is given
in Chapter III, and the portion of that table concerned with levels < 6 mg/m
(which is twice the threshold limit value [TLV]) is reproduced in Table S-l
in the Summary of the whole report.
Practically all the acute mouse studies (Table III-l) were 10-min expo-
sures by Kane and Alarie (1977 and 1978). They used respiratory rate as a
measure of toxic effect. HCHO, even at the lowest dose (0.41 mg/m3), caused
a decrease in rate. However, there was a threshold of sorts, in that concen-
trations of < 1.54 mg/m3 caused rate decreases of only 14 to 30%, with poor
dose-response relationship, while doses of > 1.89 mg/m3 caused decreases of
41% or more in a dose-related fashion. Adding acrolein (another irritating
aldehyde) increased the effect in a more or less additive fashion.
Kane and Alarie (1977) also did most of the repeated dose mouse studies
(Table III-2). Repeated 10-min exposures (usually 4 consecutive days) pro-
duced no evidence of sensitization. However, longer exposures (3 h/d for
4 d) did provide evidence of accumulative effects. The peak decrease in
respiratory rate increased on successive days and the recovery toward pre-
exposure level (during the continued exposure) was slower each day.
Additional repeated dose and chronic studies (Table III-3) were done
by Horton et al. (1963). Mice tolerated 100 mg/m3 for 35 wk (given 1 h/d,
3 d/wk), and 35 wk at 50 mg/m3 followed by 33 wk at 150 mg/m3 (same schedule),
with no grossly apparent toxicity, such as decreased weight gain. However,
tracheobronchial epithelia showed numerous changes, especially hyperplasia
and metaplasia. These potentially cancerous changes with no grossly apparent
effects are disturbing. The Chemical Industry Institute of Technology (CUT)
study of rats and mice has yielded no formal publication for mice data.
However, Anonymous (1981a) reported that after 24 mo at 15 ppm HCHO for 6 h/d
5 d/wk, 2 of 85 mice had developed nasal squamous cell carcinomas.
Kilburn and McKenzie (1978) gave hamsters 4-h exposures to HCHO and
HCHO-coated carbon particles (Table III-4). They were looking for damage
to the airway cells and defense mechanisms. The lowest dose of HCHO alone
(8 mg/m3) was damaging to the cells. Interestingly, even 712 mg HCHO/tn
did not cause recruitment of polymorphonucleocytes, while 4 mg HCHO/m° with
131 mg C/m3 did cause such a response. Apparently the particulates (e.g.,
173
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carbon soot) and the irritants activate distinct defense mechanisms. A
single exposure to 12.5 mg/m3 for 5 h caused little cell damage in nasal
turbinates, trachea, or lungs, as measured by 3H-thymidine incorporation
(Dalbey, 1981).
In repeated dose exposure of hamsters (Table III-5), Schreiber et al.
(1979) found that up to 15 1-h exposures to 312.5 mg HCHO/m3 caused severe
cytologic changes in the tracheobronchial epithelium. These changes were
reversible with complete recovery within 2 to 6 weeks. A single exposure
to 31.2 mg/m3 for 5 h caused cell damage in nasal turbinates and, to a lesser
degree the trachea. A second exposure a week later indicated some adaptation
to the irritant effects (Dalbey, 1981).
In the single chronic hamster exposure study, no adverse effects were
reported after 6-mo exposures to 0.25, 1.25, or 3.75 mg/m3 (Clary, 1980).
There are more data from rats than from any other species. For acute expo-
sures (Table III-6) there were a number of more or less routine toxicology
studies. Skog (1950) found a 30-min LD50 of 1,000 mg/m3, with deaths hours
to weeks after exposure due to excessive respiratory tract secretions and
pulmonary edema.
Nagornyi et al. (1979) considered 18 mg/m3 .for an unstated exposure
period the "acceptable limit" for pulmonary function (measured by oxygen
uptake). If one relied on standard clinical chemistry parameters (e.g.,
SGPT), then the much higher dose of 63 mg/m3 would be defined as the "accept-
able limit." Zaeva et al. (1968) found some toxic effects (decreased blood
pressure, leukocyte effects, irritation) at 5 mg/m3, but no effects at
1-2 mg/m3.
Two groups studied more unusual end points. Katz and Laskin (1977)
studied the in vitro phagocytic activity of macrophages exposed to HCHO in
vivo; their results are difficult to interpret. Kulle and Copper (1975T"
looked at nasal sensory response and found decreased response even at their
lowest doses, but partial recovery within an hour. The mechanism is not
known, but may involve the excessive secretions as well as direct effects
of HCHO on receptors.
There are many repeated dose studies on rats (Table III-7); only the
more significant are discussed.
Dubreuil et al. (1976) found that continuous exposure for 3 mo to 2 mg
HCHO/m3 caused only progressive yellowing of the fur. It is not known if
this represents dyeing (non-toxic effect) or a failure to groom (a toxic
effect). Higher doses produced decreased weight.gain, sneezing, nasal and
eye discharges, and other effects.
Fel'dman and Bonashevskaya (1971) studied electrophysiological effects
as well as the classical toxicological parameters. They found no effects
after 3 mo at 0.012 or 0.035 mg/m3. However, exposure to 1 mg/m3 produced
electrophysiological effects by the end of the second month and a variety
of mild to moderate lesions, mostly pulmonary (desquamation of bronchial
epithelium, inflammatory reactions). A higher dose (3.0 mg/ra3) produced
more severe effects faster.
174
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Sheveleva (19*71) did a teratology study. She found negligible effects
at 0.5 mg/m3 and definite maternal toxicity at 5 mg/m3. The study was not
a complete, standard protocol, so some possible effects may have been over-
looked.
The most significant study of the chronic exposures (Table III-8) is
the excellent report of Swenberg et al. (1980)*, with rats exposed 6 h/d,
5 d/wk for 18 mo of a 24-mo study. The low dose (2.6 mg/m3) was toxic, with
decreased body weight, discolored hair, and epithelial dysplasia and/or
squamous metaplasia of the nasal turbinates. The middle dose (7.0 mg/m )
was similar, with a small incidence of rhinitis. (At 24 mo, two rats had
developed squamous cell carcinomas of the nasal turbinates [NIOSH/OSHA, 1980J).
The high dose of 17.6 mg/m3 was much more toxic. Most rats had acute suppura-
tive or seropurulent rhinitis. Squamous cell carcinomas were found in 64%
of rats dying at unscheduled times (mostly after month 12) and 20% of those
killed at 18 mo. (By the end of 24 mo, 95 rats exposed to the highest dose
had developed nasal squamous cell carcinomas.) In recent brief reports, a
study at NYU has found nasal cancers in only 10% of rats exposed to 17.5 mg/m
for 382 six-hour periods (Anonymous, 1981c; Anonymous, 1981d). In contrast
to these two studies, Dalbey (1981) found no evidence of carcinogenicity in
hamsters exposed 5 times/wk to 12.5 mg/m3 for a "lifetime" (10-26 mo).
Gibson (as cited in Anonymous, 1981a) suggested that the nasal tumors
were promoted by the tremendous cell death caused by HCHO irritation. The
nature of this reaction makes the "one hit" linear model incorrect, according
to Dr. Gibson. Other risk estimation techniques postulate a 1-2 ppm exposure
for a 1 in 100,000 risk.
After 6 mo exposure to 0.25, 1.25, or 3.75 mg/m3, the only adverse effect
reported in rats was decreased weight gain in the highest exposure group
(Clary, 1980). Nagornyi et al. (1979) found only minor (probably negligible)
adverse effects in rats exposed to 0.5 mg/m3, 5 h/d, 6 d/wk for 6 mo. Some
Russian studies found small changes in various biochemical parameters after
6 mo of 3 h/d exposure to 0.035 mg/m3 (Basmadzhieva et al., 1974), or 6 mo
of 8 h/d exposure to 0.035 mg/m3 (Davidkova and Basmadzhieva, 1979), or 4 mo
of 4 h/d exposure to 0.5 mg/m3 (Pod1'yacheva, 1977). Pod"yacheva (1977)
found that the effects of HCHO and phenol were additive, but the onset from
combined small doses was faster.
Amdur (1960) performed many acute studies of respiratory mechanical
parameters with guinea pigs breathing HCHO for 1 h (Table III-9). The low-
est dose (0.06 mg/m3) had no significant effects. The next dose (0.39 mg/m )
caused increases in lung resistance and decreases in lung compliance with
5The study, sponsored by the Chemical Industry Institute of Technology
(CUT), was performed by Battelle Columbus Laboratories. An Inter-
agency Regulatory Liaison Group (IRLG) task force including patholo-
gists from CPSC, DOE, EPA, NCI, and NIEHS visited CUT in January 1980
to verify the findings. The group oi pathologists in a February 1980
report concurred in general with the CUT observations, diagnoses, and
interpretations (CPSC, 1981).
175
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recovery in 1 h. An increase to 1.43 mg/m3 increased breathing work and
caused small, but statistically significant, increases in lung resistance
1 h after exposure. As even greater doses were used, additional parameters
were affected.
Repeated dose guinea pig studies (Table 111-10) varied widely in quality
and relevance. Coon et al. (1970) found that 90-d continuous exposure to
4.6 mg HCHO/m3 was toxic with interstitial inflammation of the lungs and
chronic inflammation of visceral organs. Nagornyi et al. (1979) dosed guinea
pigs 5 h/d, 6 d/wk for 1 mo at 0.5 mg/m3 and found no toxicologically signifi-
cant effects.
A useful rabbit study was a repeated dose study by Coon et al. (1970)
(Table 111-12). They found pulmonary interstitial inflammation, but no other
adverse effects, in rabbits continuously exposed to 4.6 mg HCHO/m3 for 90 d.
In the large animal studies (Tables 111-13 to 111-16), the most notable
results were in the multi-species study of Coon et al. (1970). Beagle dogs
and squirrel monkeys exposed continuously for 90 d to 4.6 mg HCHO/m3 had
varying degrees of pulmonary interstitial inflammation, like the other species
they tested. In the study by Clary (1980), 6-mo exposures (22 h/d) of monkeys
to 0.25, 1.25, or 3.75 mg/m3 caused nasal discharge in the highest exposure
group.
There is good evidence that the animal organism can recover from moder-
ately irritating doses of inhaled HCHO. However, there is a limit to this
recovery as shown by the progressively increasing time to recovery in studies
like that of Kane and Alarie (1977) and the squamous cell carcinomas found
by Swenberg et al. (1980).
There were very few interspecies studies. Nevertheless, there is no
evidence of major differences.
There is a moderate amount of evidence for simple additivity with other
irritants and with air pollutants having different effects.
The minimal adverse effects seem to be local irritation and subsequent
tissue reactions, especially in the pulmonary system. From these studies,
it appears that adverse effects appear at levels at or above 1 mg/m3.
HUMAN EXPOSURE STUDIES
Experimental studies
Only acute inhalation studies have been reported. These are fully de-
scribed in Chapter IV, Table IV-1, and summarized in Table S-2 of the report
Summary.
The lowest dose at which effects have been reported is 0.0024 mg/m3.
Van Ven'-yan' as cited in Zaeva et al. (1968) stated that this level had an
effect on the mood of human subjects. The same source reported 0.0075 mg/m3
176
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as the threshold of respiratory irritation, 0.016 mg/ra3 as the threshold of
nervous system irritation, and 0.029 mg/m3 as the threshold of salivary
action. The value (if any) of these data is unknown. Other studies
(Fel'dman, 1974; Takhirov, 1974) have reported on the effects of mixtures
of formaldehyde with other chemicals, including nitrogen dioxide (N02) and
hydrogen chloride (HC1). Results on odor threshold, etc., were simply addi-
tive.
A number of studies found minimal effects at about 0.05-0.08 mg/m3 for
several minutes. Russian studies (Makeicheva, 1978; Fel'dman, 1974) found
that 0.046 or 0.053 mg/m3 was sufficient to affect the electroencephalographic
(EEC) response to a flashing light.
Reported odor thresholds for the most sensitive individuals include
0.05 mg/m3 (Petterson and Rehn, 1977; as cited in Andersen, 1979), 0.065 mg/m3
(Takhirov, 1974), 0.07 mg/m3 (Melekhina, 1964), 0.073 mg/m3 (Fel'dman, 1974),
0.077 mg/m3 (Makeicheva, 1978), and 0.080 mg/m3 (Fel'dman and Bonashevskaya,
1971). Sgibnev (1968), however, found that three of six subjects could not
perceive HCHO odor at 0.3-0.4 mg/m3.
Some electrophysiological effects have been seen at HCHO levels near
0.1 mg/m3. Specifically, Melekhina (1964) found the threshold for affecting
the optical chronaxy as 0.084 mg/m3 and an increase in light sensitivity
at 0.2 mg/m3. However, these studies only involved 3 subjects.
Irritation thresholds are higher. Okawada et al. (1979) found an eye
irritation threshold of 0.25 mg/m3. Sgibnev (1968) found respiratory-tract
irritation, distortions in breathing rhythm, and other effects at 1.0 mg/m3.
Andersen (1979) reported slight discomfort and slight airway resistance
changes during 5-h exposures to 0.3, 0.5, 1.0, and 2.0 mg HCHO/m3. Irrita-
tion effects increase considerably in the range of 1 to 5 mg/m3 (Stephens
et al., 1961; Weber-Tschopp et al., 1977; Renzetti and Schuck, 1961). Con-
centrations of 5 mg/m3 or more rapidly become unbearable, but recovery occurs
5-10 min after cessation of formaldehyde exposure (Sim and Pattle, 1957;
Weber-Tschopp et al., 1977). There is evidence (Einbrodt et al., 1976)
that this rapid recovery is due to rapid oxidation of the formaldehyde to
formic acid.
Environmental exposures
A discussion of completed studies follows. A discussion of on-going
studies is contained in Appendix A.
Occupational exposure—
Studies of occupational exposures to HCHO are fully described in Chap-
ter V, Table V-l. The A- and B-rated studies are summarized in Table S-3
of the Summary. As is often the case, many studies are confounded by expo-
sure to other agents, including acrolein and phenol (which have similar
irritating effects). Controls generally range from poor to non-existent.
In one of the better studies, Efremov (1970) found increased prevalence
of upper respiratory tract disease in workers exposed to urea-formaldehyde
177
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vapors, generally at less than the maximum allowable concentration, with
reasonable dose and duration of exposure effects. Parallel effects were
seen in respiratory physiology.
Because of recent reports of respiratory tumors in animals, a number
of human occupational exposure studies are in progress (see Appendix A).
These include mortuary workers and histotechnologists, who can have cutane-
ous as well as inhalation exposure. No definitive results are yet avail-
able.
Epidemiological studies--
A number of epidemiological studies have been done, primarily on the
inhabitants of homes and schools with urea-HCHO insulation. These are
listed in Chapter V, Table V-2. Most studies listed are defective due to
no (or poor) controls, no reasonable estimates of HCHO exposure, and selec-
tion bias. Each study has been critically assessed in the Remarks column
of Table V-2. The results of the better studies are given in Table S-3 of
the Summary. Eye, nose, and upper respiratory tract irritation was observed
for exposures to 0.211 mg HCHO/m3 (Melekhina, 1964), but no symptoms were
seen in adults or schoolchildren exposed to 0.08-0.13 mg/m3. The most tech-
nically acceptable methodology is that of Thun et al. (1980), who surveyed
homes with recently installed insulation. Although a majority of the test
homes had no problems, there was an increase in wheezing and other breathing
difficulties, especially in the homes and times where odors were noted.
Unfortunately, no environmental measures of HCHO were made.
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SECTION VII
HUMAN EXPOSURES TO FORMALDEHYDE AND RECOMMENDATIONS
FOR A RANGE OF CONCERN
HUMAN EXPOSURES
Metabolic formaldehyde
Besides the normal endogenous metabolic sources of ECHO mentioned in
Chapter VI, formate and ECHO can arise as metabolic products of other exoge-
nous compounds such as acetone or methanol. In addition, N-demethylation
of drugs such as aminopyrine or ethylmorphine or metabolism of dihalo-
methanes can lead to in vivo formation of HCHO and formate. Enzymatic hydro-
lysis of 5-methyltetrahydrofolate in the presence of biogenic amines and
the action of mixed function oxidases on the N-methyl groups of various
xenobiotics also produce HCHO (Griesemer et al., 1980).
Public exposures to HCHO
Many researchers have found HCHO at detectable levels in the atmosphere
both indoors and outdoors (see Table VII-1). Reported indoor levels range
from "not detected" to 8.7 mg HCHO/m3. The higher levels, > 1 mg/m3, gener-
ally are due to the use of urea-HCHO foam for insulation or polymeric mate-
rials and chipboard for construction. Energy-efficient construction
(0.035-0.261 mg/m3), use of gas stoves (0.035-0.4 mg/m3), nearness to heavy
traffic (0.051-0.106 mg/m3), and hot, humid weather conditions (0.155 mg/m3)
all contribute to elevated indoor HCHO levels.
The highest outdoor levels (~ 0.08-2.6 mg HCHO/m3) were generally re-
ported near highways during rush-hour traffic (0.01-2.6) or in large cities
with heavy air pollution and traffic problems, such as Los Angeles (0.04-
0.16 mg/m3) and Tokyo (0.001-0.091 mg/m3). The lowest levels were usually
reported in small towns (< 0.009 mg/m3) and during cold weather (0.008-
0.01 mg/m3).
The level of total aldehydes in human breath has been measured: "not
detected" to 0.09 mg/m3 in smokers; "not detected" to 0.12 mg/m3 in non-
smokers (Nefedov et al., 1969).
179
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Location
Indoor
Concentration
in mg/m3 (ppm)
Description
Reference
00
o
< 0.6 - 8.7
(< 0.5 - 7.0)
< 0.012-2.38
(< 0.01-1.90)
0.08-2.24
not detected-0.97
(not detected-0.78)
0.4
0.080-0.261
0.035-0.156
(0.028-0.125)
0.06-0.155
(0.048-0.124)
0.106
(0.085)
0.066
(0.053)
U.S. residences with urea-HCHO foam
insulation
Interior of a new school building in West
Germany, the higher levels during summer
months.
23 Danish dwellings using chipboard
U.S. residences with urea-HCHO foam in-
stalled l->24 mo previously.
Kitchen (in the U.S.) with a new gas
stove in use, no ventilation or hood
Inside an energy-efficient house in
Mission Viejo, California. Levels
varied with occupancy arid presence
of furniture.
Inside an Energy Research Building in
Ames, Iowa (see Outdoor, < 0.009, below).
Living room in the summer.
First floor office, in a "traffic
canyon."
Suburban apartment.
CPSC (1978)
Deimel (1978)
Andersen et al. (1975)
Marshall (1980)
Hollowell et al. (1979a)
Hollowell et al. (1980)
Hollowell et al. (1979b)
Berk et al. (1979)
Wanner (1978)
Wanner et al. (1977)
Wanner et al. (1977)
-------
TABLE VI1-1 (continued)
Location
00
Outdoor
Concentration
in mg/m3 (ppm)
Description
Reference
0.051
(0.041)
0.04
(0.032)
0.035
0.008-0.032
0.006-0.016
avg. 2.6
0.1 - 1.2
0-0.16
(0-0.13)
0.06-0.15
(0.05-0.12)
0.005 - 0.15
0.001 - 0.091
(0.001 - 0.073)
A "store and dispatch" in a residential
area.
Living room in the winter.
Kitchen (in the U.S.) with new gas
stove and high-speed ventilation.
Interior of school in the USSR built
with polymeric materials.
School in the USSR built with non-
polymeric materials.
Sic. jlk and 1-2 m from road in Moscow
during maximum traffic, at twilight.
Along two USSR highways.
Downtown Los Angeles.
Urban polluted air.
A distance of 10 to 15 m from two
USSR highways.
Range of hourly values in Tokyo, during
1968 to 1976. The mean for the 9-year
period was 0.009 mg/m3.
Wanner et al. (1977)
Wanner et al. (1977)
Hollowell et al. (1979a)
Trubitskaya et al. (1978)
Trubitskaya et al. (1978)
Melekhina (1964)
Prigoda (1973)
Renzetti and Bryan (1961)
Stupfel (1976)
Prigoda (1973)
Matsumura and Higuchi
(1979)
-------
•rAJJL.I£ VI 1-1 C«--o«ii--| ut
Location
oo
NJ
Concentration
in mg/m3 (ppm)
0.01-0.09
(0.01-0.07)
0.04-0.08
(0.03-0.066)
0.004 - 0.025
(0.003-0.020)
0.016-0.019
(0.013-0.015)
0.009 - 0.018
0.012-0.015
(0.0093-0.012)
Description
South Pasadena, California.
Downtown Los Angeles and suburbs,
Range during the summers of 1972 to
1974 in four cities in New Jersey.
Summer air.
Reference
Renzetti and Bryan (1961)
Altshuller (1978)
Cleveland et al. (1977)
Wanner (1978)
Ohtsu area of Japan in October 1976. Suga et al. (1978)
Near roads with varying traffic density. Wanner et al. (1977)
0.0062-0.0145
0.008-0.010
(0.006-0.008)
< 0.009
(< 0.007)
0.001-0.0068
Sofia, Bulgaria
Winter air.
Outdoor air in Ames, Iowa (see Indoor,
0.035-0.156, above)
Levels generally detected 7 to 8 m
from a road in Moscow witli heavy
traffic at twilight. Max. of 0.017 mg/m3,
Kalpazanov et al. (1976)
Wanner et al. (1978)
Hollowell et al. (I979b)
Berk et al. (1979)
Melekhina (1964)
-------
Cigarette smoking
The level of ECHO found in cigarette smoke has varied with the investi-
gator and the type of cigarette. Stupfel (1976) reported 150 mg/m3 (120 ppm*
in unspecified smoke. Newsome et al. (1965) reported 90 mg/m3 (3.6 yg/bQ nil
puff) in the smoke of filtered cigarettes and 103 mg/m3 (4.1 M8/40 ml puff)
in the smoke of unfiltered cigarettes. NIOSH/OSHA (1980) reports < 50 mg/m0
(£ 40 ppm). NIOSH uses this figure to calculate that an individual smoking
a pack of cigarettes a day would inhale 0.38 mg HCHO, whereas occupational
exposure to formaldehyde at 3 ppm could result in a daily intake of 29.0 mg
HCHO. From Stupfel1 s data it can he estimated that after each 40 ml puff
containing 3.6-4.1 pg HCHO, the lung will be exposed momentarily to air con-
taining ~ 5.1-5.8 mg HCHO/m3 (3.6-4.1 pg/0.7 L tidal volume). This is 170-
190% of the TLV (3 mg/m3).
INTERNATIONAL STANDARDS AND RECOMMENDATIONS
A summary of regulations and recommendations is given in Table VII-2.
Most of the recommendations were made by individual researchers, not regula-
tory or advisory agencies. The standards for occupational exposure range
from 0.5 to 10 mg HCHO/m3, for 8-h to 30-min intervals. Standards for out-
door air range from 0.01 to 0.075 mg/m3. The American Industrial Hygiene
Association (AIHA) recommended 0.12 mg/m3 for the U.S. standard for outdoor
air. Recommendations for indoor air exposure range from 0.025 to 0.62 mg/m3.
The Committee on Toxicology of the National Research Council (NRC, 1980)
concluded that "there is no population threshold for the irritant effects
of formaldehyde in humans" and advised "maintaining formaldehyde at the low-
est practical concentration to minimize adverse effects on public health."
NIOSH/OSHA (1980), in a Current Intelligence Bulletin, recommended that
"formaldehyde be handled in the workplace as a potential occupational car-
cinogen." However, under orders from the Office of Health and Human Ser-
vices Secretary Richard Schweiker, NIOSH has halted further distribution of
that bulletin (Anonymous, 1981c).
RECOMMENDED RANGE OF CONCERN
The EPA Work Directive for this Task 6 suggested 0.03-3.0 mg HCHO/m3
as a preliminary range of uncertainty with regard to health effects of in-
haled HCHO. The threshold limit value in the United States for occupational
exposures is 3.0 mg/m3.
Experimental animals show obvious adverse effects at HCHO concentrations
> 1 mg/m3 whether acutely or chronically exposed. In chronic studies, bio-
chemical and inflammatory changes are seen at concentrations as low as 0.035;
and 8-12 wk exposures of rats to 0.012 mg HCHO/m3 produced such changes.
Thus, a range of concern, based on animal studies would be from 0.012 to
about 1 mg/m3.
183
-------
TABLE VI1-2. SUMMARY OF REGULATIONS AND RECOMMENDATIONS FOR HUMAN FORMALDEHYDE EXPOSDKK
oo
HC1IO Level
in
mg/m3 (ppm)
12.5*
(10)
6.3
(5)
5.9
(4.7)
(4)
3.8
(3)
3.1
(2.5)
3.
(2)
2.5*
(2)
Recommendation/Regulation
Type of Exp_osjjj[e_
Outdoor Indoor Occupational
Air Air Air
Promulgated ceiling exposure
limit in Great Britain. Max.
acceptable peak level for a
total of no more than 30 min
during an 8-h shift in the U.S.
Promulgated ceiling exposure
limit in Japan, Finland, and U.S.
Promulgated ceiling exposure
limit in Italy and Poland
Promulgated ceiling exposure
limit in Czechoslovakia (short,
single exposure) and Bulgaria
Time-weighted avg. (TWA)
promulgated by OS1IA; TLV in
Australia
Promulgated ceiling exposure
limit in Sweden and Rumania
Ceiling threshold limit value
(TLV) recommended by ACGIH; TLV
in The Netherlands
Promulgated TLV (ceiling) in
Great Britain
X
X
Reference
NRC (1980)
NIOSH/OSHA (1980)
NRC (1980)
NIOSH/OSHA (1980)
NRC (1980)
NRC (1980)
ILO (1970)
NRC (1980)
NIOSH/OSHA (1980)
Hewlett (1980)
NRC (1980)
NRC (1980)
ACGIH (1980)
Hewlett (1980)
Lynne (1979)
* Note the discrepancy between the two entries.
(Continued)
-------
TABLE VII-2 (continued)
HC1IO Level
in
mg/m3 (ppm)
Recommendation/Regulation
Type of Exposure
Outdoor Indoor Occupational
Air Air Air
Reference
CX)
Lfl
<2.5 Recommended a TLV
(<2) below this level
2.1 Promulgated TWA (8-h) in
(1-7) Czechoslovakia arid East Germany
1.9 Proposed TLV in Italy
(1.5)
1.2 Ceiling exposure limit recom-
(1) mended by NI OSII
1.2 Promulgated TWA (8-h) in Denmark
(1) and West Germany. MAC in West
Germany. TLV in Poland and
Yogoslavia
I'O Promulgated ceiling exposure
(0.8) limit in Hungary
0.62 Recommended exposure limit
(0.5) in residences
6.62 Standard in The Netherlands
(0.5) for levels 2 wk after in-
stallation of urea-IICHO foam
insulation
0.12-0.62 Recommended exposure limit
(0.1-0.5) for schools and living areas
0.12-0.5 Recommended ceiling exposure
(0.1-0.4) limit in Sweden
Weber-Tschopp et al
(1977)
NRC (1980)
ILO (1970)
Hewlett (1980)
NRC (1980)
NIOSH/OSHA (1980)
NRC (1980)
Helwig (1977)
Hewlett (1980)
NRC (1980)
Timm and Smith
(1979)
Rumack (1978)
Einbrodt and Prajsaar
(1978)
NRC (1980)
(Continued)
-------
TABLE VIJL-Z Ccontinued}
00
IICHO Level
in
ing/m3 (ppm)
0.5
(0.4)
0.4
0.038-0.38
(0.03-0.3)
0.25
(0.2)
0.15
(0.12)
0.12
(0.1)
0.12
(0.1)
0.075
(0.06)
Type of Exposure
Outdoor Indoor Occupational
Recommendation/Regulation Air Air Air
Promulgated ceiling exposure X
limit in the USSR
Proposed preliminary standard
for continuous exposure, in
Denmark
Recommended TLV X
Recommended exposure limit X
Recommended ceiling exposure X
limit in Denmark
Ceiling exposure limit recom- X
mended by the AIHA
Ceiling exposure limit prom- X
ulgated in The Netherlands
and recommended in West
Germany
Standard for the maximum X
immission concentration (MIC)
Reference
NRC (1980)
USSR (1972)
Andersen
(1979)
Kane and Alarie
(1977)
Hanrahan et al.
(1980)
NRC (1980)
Andersen (1979)
NRC (1980)
NRC (1980)
Andersen (1979)
Helwig (1977)
0.035
for short-term exposures in
West Germany
Standard for maximum one-
time exposure in populated
places in the USSR
USSR (1972)
(Continued)
-------
HCHO Level
in
mg/n>3 (PP»0
0.025
(0.02)
0.025
(0.02)
Recojimiendation/Kegulation
Standard for the MIC for
long-term exposure in
West Germany
Standard in The Netherlands
for levels 2 mo after in-
Type of Exposure
Outdoor Indoor Occupational
Air Air Air
X
X
Reference
Helwig (1977)
NRC (1980)
Rumack (1978)
0.012
0.01
(0.008)
0.004
(0.003)
stallatioti of urea-UCHO foam
insulation
Standard for maximum avg.
exposure in populated places
in the USSR
Promulgated ceiling exposure
limit in the USSR
Recommended highest concen-
tration for Air Quality
Standard
X
X
USSR (1972)
NRC (1980)
Kane et al. (1979)
-------
The upper limit of a range of concern for nonoccupationally exposed
humans based on short-term experimental exposures should be 0.95-1.0 mg
HCHO/m3, where eye irritation is slight, the odor is perceived, and other
effects occur (changes in breathing rhythm and a-rhythms). The lower level
should be at least 0.2-0.25 mg/m3, which is the threshold for eye irritation.
Perhaps the lower level should be 0.05 mg/m3, the lowest reported odor thresh-
old.
From occupational, epidemiological, and similar public exposure reports,
a level of concern of 0.211 mg HCHO/m3 may be recommended. This concentra-
tion produced eye and upper respiratory tract irritation in moderately long-
term exposures whereas no such symptoms were observed in adult or school
children exposed to 0.08-0.13 mg/m3.
Thus, the human studies indicate that the range of concern in long-term
or acute exposures to HCHO should be 0.06 or 0.2 to ~ 1 mg/m3. If animal
studies were directly extrapolatable to humans, it would appear prudent to
make the lower limit of the range of concern 0.01-0.04 mg/m3.
The value of 0.2 mg/m3 may be the most defensible choice since both
nonsmoking and smoking humans sometimes contain aldehydes in the breath at
levels as high as ~ 0.1 mg/m3, HCHO being a normal metabolite and a metab-
olite of exogenous substances. This value is frequently the maximum value
reported for urban polluted air. However, various authorities have recom-
mended or promulgated standards for HCHO in outdoor air as low as 0.01 mg/m .
188
-------
ANNOTATED BIBLIOGRAPHY
189
-------
5-175* ACGIH, American Conference of Governmental Industrial Hygienists.
1971. Documentation of the Threshold Limit Values for Substances
in Workroom Air. ACGIH, Cincinnati, Ohio. pp. 118-119.
C— .** ACGIH recommended a ceiling limit for HCHO in workplace
air of 2 ppm; ANSI in 1967, 3; the USSR in 1966, 0.8; and Czechoslo-
vakia in 1969, 1.6 ppm. The ACGIH limit was set to avoid upper
respiratory tract irritation in most workers. A limit of 5 ppm
would be low enough to prevent respiratory injury.
5-421 ACGIH, American Conference of Governmental Industrial Hygienists
TLV Airborne Contaminants Committee. 1980. TLVs Threshold Limit
Values for Chemical Substances and Physical Agents in the Work-
room Environment with Intended Changes for 1980. ACGIfl Cincinnati,
Ohio. p. 19.
A—. The time-weighted-average TLV for HCHO is 3 mg/m3 (2 ppm).
5-179 Ahmad, I., and T. Whitson. 1973. Formaldehyde: How Much of a
Hazard? Ind. Med. Surg. 42(8):26-27.
C-4. Employees of an industrial garment'company lost conscious-
ness after short exposure to at least 2.5-12.5 mg HCHO/m3. Con-
tinued headache, dizziness, nausea, and some tremors. Other em-
ployees seemed unaffected, when observed later in the day.
5-407 AIHA, American Industrial Hygiene Association. 1978. Hygiene
Guide Series; Formaldehyde. American Industrial Hygiene Asso-
ciation, Akron, Ohio. 5 pp.
C—. Review.
5-218 Alabert, N., J. Godin, C. Boudene, and A. Roussel. 1971. The
Effect of Aldehyde Atmospheric Pollutants on the NAD-NADH System
of the Liver, Lungs, and Encephalon in Rats. C. R. Hebd. Seances
Acad. Sci., Ser. D. 272(26):3363-3366 (Fre).
D-6. After 3-h exposure to 140 ppm HCHO, the rats were immediately
sacrificed and the levels of NAD and NADH in the brain, liver,
and lungs were determined. Only the level of NAD in the brain
decreased significantly. Few details of the methodology are given.
Other aldehydes were studied, leading to the suggestion that after
passing the respiratory barrier, aldehydes may have a specific
toxic action at the cellular level.
5Numbers in the left margin are MRI document acquisition numbers.
** MRI rating. See full explanation in Chapter I.
190
-------
5-219 Alarie, Y. 1973. Sensory Irritation by Airborne Chemicals.
C.R.C. Crit. Rev. Toxicol. 2(3):299-363.
D--. Extensive review of respiratory tract sensory receptors,
the reflux reactions evoked following their stimulation by in-
haled chemicals, the nature of chemicals eliciting sensory irrita-
tion, and the mechanisms of their interactions with nerve endings.
Concerned primarily with acute exposures. Concludes that measure-
ments of decrease in respiration rate in animals is a reliable
predictor that an airborne chemical will evoke sensory irritation
in humans.
5-217 Akabane, J. 1970. Aldehydes and Related Compounds. Int. Encycl.
Phannacol. Ther. Sect. 20, Vol. II, pp. 544-560.
C—. A review of the metabolism, toxicity, and pharmacological
effects of lower aliphatic aldehydes, especially formaldehyde and
acetaldehyde. 190 literature references.
'5-022 Altshuller, A. P. 1978. Assessment of the Contribution of Chem-
ical Species to the Eye Irritation Potential of Photochemical Smog.
J. Air Pollut. Control Assoc. 28(6)-.594-598.
D-8. A review and discussion of the results of several studies
on atmospheric samples or irradiated auto exhaust and hydrocarbon-
nitrogen oxide mixtures. The eye irritation on a moderately smoggy
day may be due 40% to HCHO and 25% to acrolein. Atmospheric sam-
ples collected in California contained 30-66 ppb HCHO and 6-7 ppb
acrolein.
5-001 Amdur, M. 0. I960. The Response of Guinea Pigs to Inhalation of
Formaldehyde and Formic Acid Alone and With a Sodium Chloride Aero-
sol. Intern. J. Air Pollut. 3(4):201-220.
B-13. Guinea pigs were exposed to HCHO at 0.05-50 ppra alone and
in combination with Nad aerosol. Upper vs. lower respiratory
effects are compared through use of normal and tracheotomized
animals.
5-204 Amdur, M. 0. 1966. The Respiratory Response of Guinea Pigs to
Histamine Aerosol. Arch. Environ. Health 13(l):29-37.
D—. Study of guinea pigs' response to histamine aerosols com-
pared to responses to HCHO determined earlier. Same HCHO data as
in Amdur (I960).
5-024 Amdur, M. 0. 1978. Respiratory Response to Iodine Vapor Alone
and with Sodium Chloride Aerosol. J. Toxicol. Environ. Health
4(4):619-630.
D--. Study of guinea pig responses to I vapor and NaCl aerosol
as compared to responses to HCHO determined earlier. Same HCHO
data as in Amdur (1960).
191
-------
5-310 Andersen, I. 1979. Formaldehyde in the Indoor Environment— Health
Implications and the Setting of Standards. In: Indoor Climate,
Effects on Human Comfort, Performance, and Health in Residential,
Commercial, and Light- Indus try Buildings., Proc. of the First Int.
Indoor Climate Symp., Copenhagen, Denmark. August 30-September 1,
1978. P. 0. Fanger and 0. Valbjorn, Eds. Danish Building Research
Institute, Copenhagen, Denmark, pp. 65-87.
A-14. Literature review with 16 references. Results of a human
experimental study exposing 16 people to 0.3, 0.5, 1.0, and 2.0 mg
HCHO/m3 for 5 h each on consecutive days. No changes in airway
resistance, small decrease in nasal mucus flow except at 1.0 mg/ra3,
eye irritation and dryness in nose and throat at all levels, and
no change in performance tests were reported. Suggest a standard
for continuous exposure to HCHO of < 0.15 mg/m3 . Panel discussion
of the paper included the information that the Netherlands recom-
mended and Germany published an indoor air standard of 0.12 mg/m3.
5-205 Andersen, I., G. R. Lundqvist, and L. Molhave. 1975. Indoor Air
Pollution Due to Chipboard Used as a Construction Material. Atmos.
Environ. 9(12): 1121-1127.
C— . HCHO concentrations in 25 rooms in 23 Danish homes using
chipboard construction materials were 0.08-2.24 mg/m3 (avg. 0.62
mg/m3). The West German limit for outdoor ambient air (0.03 mg/m3)
was exceeded in all cases. (The West German workplace limit is
1.2 mg/m3.)
5-025 Anderson, R. , and Y. Alarie. 1978. Respiratory Toxicity of Ther-
al Decomposition Products of Urea Formaldehyde and Phenol Formal-
dehyde. Pharmacologist 20(3): 197.
D — . Abstract of work completely described in Anderson et al.
(1979) [5-026].
5-026 Anderson, R. C., M. F. Stock, R. Sawin, and Y. Alarie. 1979.
Toxicity of Thermal Decomposition Products of Urea Formaldehyde
and Phenol Formaldehyde Foams. Toxicol. Appl. Pharmacol.
D-7. Mice were exposed to thermal decomposition products of urea
and phenol-formaldehyde foams. Study too confounded to be useful
Authors stated HCHO was not the cause of acute mortality from
either foam.
5-027 Anonymous (Editorial). 1979. Formaldehyde Toxicity. Lancet
2(8143) :620-621.
192
-------
C—. This editorial cites only a few references on the inhala-
tion toxicity of HCHO, yet one of its citations was one we were
not aware of. (Ozhiganova et al., 1977 [5-377]). Three mechanisms
are enumerated by which HCHO vapors may cause chest disease:
immunological reaction, direct histamine release from mast cells,
and stimulation of bronchial irritant receptors.
5-415 Anonymous. 1980a. Dr. Selikoff Expresses Reservations about Form-
aldehyde Study. Occup. Health Safety Lett. 10(11):2.
D--. The reservations were: no verification of the contention
that plants producing HCHO or HCHO-based resins are the most prom-
ising resources for cohort mortality studies; voluntary participa-
tion of workers and companies would introduce selection bias; con-
fidentiality of the data; the need for an "exemplary professional
input," a full-time epidemiologist; and the possible problem of a
cohort of insufficent size and duration from onset for meaningful
results.
5-416 Anonymous. 1980b. Westat Awarded Data Collection Contract for
Formaldehyde Study. Occup. Health Safety Lett. 10(12):2-3.
D—. A response to some of Dr. Selikoff's reservations (Anonymous,
1980a).
5-422 Anonymous. 1980c. Clinical Approach to Quantitating Formaldehyde
Effects in Human Blood. In: Workshop on Indoor Air Quality Re-
search Needs. Interagency Research Group on Indoor Air Quality.
Washington, D.C. p. H-15.
D—. Very brief description of a project attempting to correlate
blood levels of HCHO with changes in human chromasomal material
in cultured human lymphocytes.
5-401 Anonymous. 198la. Formaldehyde, Cadmium Highlighted in Toxicology
Forum Sessions. Pest. Toxic Chem. News 9(21):12-13.
C—. Article summarizes the 24-mo results of the CIIT-sponsored
study in rats and mice that found a high incidence of nasal car-
cinomas in rats exposed to 15 ppm HCHO.
5-414 Anonymous. 1981b. Support Services for a Mortality Study of
Workers Exposed to Formaldehyde. Commerce Bus. Dly. April 17.
p. 1.
D—. Announcement of a request-for-proposal, the study sponsored
by the Formaldehyde Institute and the National Cancer Institute.
193
-------
Anonymous. 1981c. Formaldehyde Institute Disputes NYU's Dr. Upton
in Letter to OSHA. Occup. Health Safety Lett. 11(17)[September 8]:1-2,
C~. Includes a brief description of study by NYU, finding "grossly1
visible nasal tumors in 10% of rats exposed to 14 ppm HCHO for 382
6-h periods. Formaldehyde Institute contends that the animal data
are inconclusive, that what data there are suggest a possible
threshold for carcinogenicity, and that human data are negative.
Anonymous. 1981d. Study shows Formaldehyde is Carcinogenic.
Science 213(11):1232.
C—. Includes a brief mention of a study by NYU, finding nasal
cancers in 10% of rats exposed to 10.6 and 14.6 ppm HCHO.
6-116 Apol, A. G., 1973. Health Hazard Evaluation/Toxicity Determina-
tion Report 72-32-42; Union Pacific Railroad, Pocatello, Idaho.
PB 229 161, National Technical Information Service, U.S. Depart-
ment of Commerce, Springfield, VA. 23 pp.
D—. 117 workers were exposed to acrolein (0.014-0.04 ppm), HCHO
(0.015-0.07 ppm), CO (< 1-15 ppm),. NO (0.03-0.26 ppm), S02
(< 0.01 ppm), and particulates (0.09-0?26 mg/m3). No excess of
chronic respiratory disease. Eye irritation and headaches reported.
5-221 Apol, A. G. 1976. Health Hazard Evaluation Determination Report
Number 76-38-326, Rycraft, Inc., Corvallis, Oregon. PB-273748,
National Technical Information Service, U.S. Department of Commerce,
Springfield, VA. 11 pp.
D—. Although the metals Co, Pb, Mn, Sn, and V and phenols were
not detected in the workplace samples, the employees suffered
slight nose and throat irritation ("expected responses at the
concentrations found and are not considered detrimental") from
exposure to £ 0.16 ppm HCHO and £0.4 ppm S02.
5-002 Auerbach, C., M. Moutschen-Dahmen, and J. Moutschen. 1977. Gene-
tic and Cyto-genetical Effect of Formaldehyde and Related Compounds.
Mutat. Res. 39:317-362.
D—. Review. Pages 326-343 deal with the effects of a "formalde-
hyde food" - a Drosophila melanogaster diet of unknown composition
containing sublethal levels of formalin. The authors reviews the
speculations of other authors using this mixture as to the biochem-
ical mechanisms of effects seen in the test animals (fruit flies).
Respiratory exposures and effects on mammals are not discussed.
5-029 Avdeeva, I. A., V. P. Agudin, L. M. Barysheva, B. I. Karpunin,
and I. Ya. Saidasheva. 1980. Physiological-Hygienic Evaluation
of the Work of Women in Plywood Production. No. 2:30-32 (Russ).
194
-------
D-4. Workers exposed to ~ 1.5-2.5 mg HCHO/m3 and wood dust at
1.5-2x the MAC, and had > 5 y service. Complained of muscle
fatigue in the hands and feet, general weakness, headache, and
eye fatigue. The highest morbidity was due to colds and flu.
Women had higher frequency of loss of work capacity and cardio-
vascular illness. The results of this uncontrolled study probably
reflect the nature of the work (heavy labor) more than the HCHO
exposure.
5-329 Barnes, E. C., and H. W. Speicher. 1942. The Determination of
Formaldehyde in Air. J. Ind. Hyg. 24:10-17.
C-3. Primarily a discussion of the methods for taking HCHO meas-
urements, and their efficiencies. Exposure to 20 ppm HCHO while
testing caused immediate and strong eye, nose, and throat irrita-
tion. Workers in industrial areas sampled didn't seem to object
to HCHO levels < 5 ppm.
5-322 Basmadzhieva, K., T. Burkova, M. Argirova, St. Milanov, and E.
Davidkova. 1974. Biological Effect of Threshold Concentrations-
of Hydrochloric Acid and Formaldehyde Inhaled into the Organism.
Khig. Zdraveopaz. 17(5):480-486 (Bulg).
B-9. Chronic exposure of rats to 0.035 rag/m3 of HCHO resulted in
. 20-30% decrease in bioenergetic metabolism processes in mitochondrial
fraction of liver from 1st mo through 6 mo exposure.
5-336 Batulin, Yu M., A. L. Klyashchitskaya, and N. K. Kulagina. 1972.
Toxicology of an FM-1322 Organosilicon Heat-Transfer Agent. Gig.
Tr. Prof. Zabol. l6(3):56-58 (Russ).
D-9. Female rats exposed to the gases evolved from the heating
of poly(methylphenylsiloxane) (^ 20 mg CO/m3, £ 0.635 mg HCHO/m3,
0.005 vol. % C02, and ^ 20 mg C6H6/m3) did not show any signifi-
cant differences from the controls with respect to the summation
threshold, 02 consumption, morphological condition of the blood,
and growth dynamics.
5-031 Baur, X., and G. Fruhmann. 1979. Bronchial Asthma of Allergic
or Irritative Origin as an Occupational Disease. Prax. Klin.
Pneumol. 33(Suppl. 1):317-322 (Ger).
C-8. A 47-y-old female chemical plant worker complained of eye
watering, head cold, coughing, and asthma when exposed to formalin
vapors (no concentrations given). There was a slight decrease of
IgG (0.8 g/L) and a negative reaction to skin tests with formalin
and the usual inhalation allergens. A 5-min provocation inhalation
test with vapors from a 25% formalin so'lution produced severe
bronchoconstriction, running nose, and watering eyes. Dry cough
appeared 3-5 h later. After being away from work for 2 wk, the
responses required a 25-min exposure and a slight bronchial reac-
tion occurred after 5 h.
195
-------
6-005 Beckner, J.S., P. M. Hudgins, and J. L. Egle, Jr. 1974. Effects
of Acetaldehyde, Propionaldehyde, Formaldehyde, and Acrolein on
Contractility, Carbon-14-Labelled Norepinephrine and Calcium-45
Binding in Isolated Smooth Muscles. Res. Commun. Chem. Pathol.
Pharmacol. 9(3):471-488.
D-16. Good, well-done pharmacology. Mechanisms of structural
congeners on isolated rat vas deferens and rabbit aorta (smooth
muscle). Does not help define inhalation exposure levels. 10 M
HCHO and 10 M acrolein gave similar responses.
5-032 Berk, J. V., C. D. Hollowell, and C. I. Lin. 1979. Indoor Air
Quality Measurements in Energy-Efficient Houses. LBL-8894, National
Technical Information Service, U.S. Dept. of Commerce, Springfield,
VA. 27 pp.
C—. An Energy Research House in Ames, Iowa, contained 28-61 ppb
HCHO (avg. 42 ppb) in the indoor air compared to < 7 ppb outdoors.
5-427 Blackwell, M., H. Rang, A. Thomas, and P. Infante. 1981. Formaldehyde:
Evidence of Carcinogenicity. Am. Ind. Hyg. Assoc. J. 42(7):A34, A36,
A38, A40, A42, A44, A46; NIOSH Current Intelligence Bulletin #34.
C—. Review. NIOSH recommends that HCHO be handled as a potential
occupational carcinogen. Doesn't necessarily represent the official
evaluation of OSHA.
5-123 Blejer, H. P., and B. H. Miller. 1966. Occupational Health Report
of Formaldehyde Concentrations and Effects on Workers at the Bayly
Manufacturing Company, Visalia, California. Study Report No. S-1806
of California Health and Welfare Agency, Dept. of Public Health,
Bureau of Occupational Health, Los Angeles, California. 6 pp.
C-3. The manufacture of permanently pressed pants released HCHO
into the workplace atmosphere, causing levels of 1.1-3.4 mg/m3.
Eye, nose, and throat irritation was intense for ~ 20 min, then
some apparent habituation occurred. Wasn't considered a systemic
health hazard.
5-003 Bokina, A., and N. Eksler. 1973. Electrophysiological Analysis
of the Action of Certain Atmbspheric Pollutants on the Central
Nervous System. Gig. Sanit. No. 12. 11-16 (Russ).
B-7. EEG's of rabbits exposed to HCHO in concentrations from
0.035 to 6.5 mg/m3 for 10 s to 1.5 mo showed detrimental effects
except for the lowest level used for 20 min. Stress such as noise
or flashing light accompanied some of the exposures.
5-222 Bokina, A. I., N. D. Eksler, A. D. Semenenko, and R. V.Merkur'yeva.
1976. Investigation of the Mechanisms of Action of Atmospheric
Pollutants on the Central Nervous System and Comparative Evalu-
ation of Methods of Study. Environ. Health Perspect. 13:37-42.
196
-------
B-2. There is little experimental detail on HCHO in this English-
language article, but it does give some of the results of the
studies by Bokina and Eksler (1973) [5-003] and Fel'dman and Eksler
(1975) [5-184] and helps in the translation of the Russian terms
used. The overall electrical activity of various brain structures
of rabbits was studied in response to 03, HCHO, and CS2. The brain
structures that account for the sensory response to olfactory stim-
uli are the olfactory bulb and piriform complex [the amygdaloid
nucleus ?]. Those that organize adaptive-behavioral reactions
are the hippocampus, amygdala, and reticular formation of the
brain stem.
5-224 Bonashevskaya, T. I. 1973. Amygdaloid Lesions after Exposure to
Formaldehyde. Arkh. Anat., Gistol. Embriol. 65(12):56-59 (Russ).
B-8. Rats exposed for 3 mo to 3 mg HCHO/m3 showed definite struc-
tural and cytological shifts in their amygdaloid complexes compared
to those of the controls. Changes in the relation of the chronaxy
of the muscles-antagonists were seen by the 2nd wk and 2nd mo in
rats exposed to 3 and 1 mg HCHO/m3, respectively. Cholinesterase
activity was lowered significantly in rats exposed to 3 but not
to 1, 0.035, or 0.012 mg HCHO/m3.
5-223 Bonashevskaya, T. I. 1975. Barrier Function of the Nasal Mucosa
During Action of Atmospheric Pollutions. Gig. Sanit. No. 9:14-17
(Russ).
C-5. Rats exposed to 0.12 mg HCHO/m3 for 3 mo showed morphological
degenerative and proliferative changes in the nasal mucosa not
seen with 0.012 mg HCHO/'m3 (the ambient air MAC). However, the
same changes were ascribed to benzene, toluene, xylene, m- and
£-chlorophenyl isocyanate, chlorophos, hexane, and pentane also
at 10 X their ambient air MAC's but not at the MAC levels.
5-126 Bourne, H. G., and S. Seferian. 1959. Formaldehyde in Wrinkle-
Proof Apparel Produces—Tears for Milady. Ind. Med. Surg. 28:
232-235.
C-3. Uncombined HCHO from the treatment process is emitted, re-
sulting in levels in dress stores of 0.16-0.56 mg HCHO/m3. Cus-
tomers and employees complained of strong odor and eye and throat
irritation.
5-311 Breysse, P. A. ed. 1977. Formaldehyde in Mobile and Conventional
Homes. Environ. Health Saf. News 25(1-6): 20 pp.
B-6. A review of HCHO toxicity, case reports of some HCHO exposure
incidents, and the early results of a mobile and conventional homes
studv for HCHO exposure. More extensive results are discussed in
Breysse (1978) [5-357], Breysse (1979a) [5-355], Breysse (1979b)
[5-356], and Breysse (1980b) [5-354].
197
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5-357 Breysse, P. A. 1978. Formaldehyde Exposure Following Urea Formal-
dehyde Insulation. Environ. Health Saf. News. 26(1-12): 13 pp.
B-6. Several case reports, and the results of a study of HCHO
exposure. In 39 conventional homes with UF insulation, HCHO levels
ranged from 0.05 to 3.40 ppm, with 80% of the samples < 0.5 ppm.
Eye, nose, and respiratory tract irritation and headaches were
the most frequent complaints.
5-355 Breysse, P. A. 1979a. Formaldehyde Exposure in Mobile Homes and
Conventional Homes. In: Proc. 43rd Ann. Educational Conference
of the National Environmental Health Association, June 23-28, 1979.
16 pp.
B-6. A less detailed discussion of the same study described in
Breysse (1978) [5-357], Breysse (1977) [5-311], Breysse (1979b)
[5-356], and Breysse (1980b) [5-354].
5-356 Breysse, P. A. 1979b. Formaldehyde Exposure In Mobile Homes.
In: Proc. 39th Ann. AMA Congress on Occupational Health, Uni-
versity of North Carolina, October, 1979. 17 pp.
B-7. The same report as Breysse (1980b) [5-354], and a continu-
ation of the study described in more detail (although of fewer
homes) in Breysse (1977) [5-311].
5-354 Breysse, P. A. 1980b. Small Plants and Their Medical Problems--
The Furniture Industry. The Environmental Problems of Urea-For-
maldehyde Structures—Formaldehyde Exposure In Mobile Homes. In:
Occupational Safety and Health Symposia, 1979. Publication No.
(NIOSH) 80-139. U.S. Dept. of Health and Human Services, Cincinnati,
Ohio. pp. 56-64.
B-7. The same report as Breysse (1979b) [5-356]. Residents of
334 mobile homes were exposed to HCHO levels from 0.04 to 2.21
mg/m3, with 66% between 0.13 and 0.61 mg/m3. Irritation of the
eyes, nose, and throat were the primary symptoms. Differences
between adults and children were considered. No control or com-
parison group.
5-425 Brooks, S. M., and C. F. Reinhart. 1981. Health Effects of For-
maldehyde. In: Formaldehyde and Other Aldehydes. Committee on
Aldehydes, National Research Council. National Academy Press.
Washington, D.C. pp. 175-220.
C—. This authoritative review of the health effects of HCHO is
organized by type of toxic effect rather than by route and dose.
5-128 Brunnthaler, J. 1913. The Toxic Effects of Formaldehyde. Aerztl.
Sachverstaendigen-Zeitung. 19(7):142-146 (Ger).
198
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C--. A good review of early reports on the toxic effects of oral
and inhalation exposures to formaldehyde.
5-035 Burdach, S., and K. Wechselberg. 1980. Damages to Health in
Schools. Complaints Caused by the Use of Formaldehyde-Emitting
Materials in School Buildings. Fortsch. Med. 98(11) :379-384
(Gcr).
B-9. Teachers and pupils in school buildings with atmospheric
levels of 0.1-1.21 mg HCHO/m3 complained of mucous membrane irri-
tation and loss of concentration. Fewer symptoms were reported
8 mo after the removal of the HCHO-emitting chipboard.
5-374 Burian, K. 1960. Histological Changes in the Nasal Mucosa After
Formalin Adaptation and Increased Crossed Resistance. Acta
Otolaryngol. 52:429-437 (Ger).
D—. Rats were exposed 1 h/d for £ 7 wk to vapors from 2.5, 3.75,
or 5% formalin solutions. The HCHO concentration in the air was
not measured. Metaplastic epithelial cells were observed after
healing of the initial epithelial damage.
5-225 Cali, G. 1965. Modifications Induced by Irritating Vapors on
Mast Cells of Nasal Mucosa of the Rat. Clin. Otorinolaringoiatr.
17(2):117-128 (Ital).
D-5. Study of the effect of exposure of rats to 20% HCHO vapors
for 3-5 min/d for 2-20 exposures. Damage to epithelium and the
inflammation of nasal passages, more pronounced in rats exposed
10-20 times, but not present in rats restrained from rubbing their
noses. In rats with only 2 exposures, mast cells of nasal mucosa
were modified by increase in number, greater variety in shapes,
increased tint affinity, and pronounced degranulation tendency.
In rats exposed 10-20 times, same types of changes were reported,
but less pronounced, particularly those concerning the degranula-
tion phenomena.
5-129 Carpenter, C. P., H. F. Smyth, and U. C. Pozzani. 1949. The Assay
of Acute Vapor Toxicity and the Grading and Interpretation of Re-
sults on 96 Chemical Compounds. J. Ind. Hyg. Toxicol. 31:343-346.
D-5. Study to develop a toxicity screening method. HCHO at 250
ppm or 8 ppm acrolein killed 2-4 of 6 albino rats exposed for 4 h.
6-118 Carson, S., R. Goldhamer, and M. S. Weinberg. 1966. Characterization
of Physical, Chemical, and Biological Properties of Mucus in the
Intact Animal. Ann. N.Y. Acad. Sci. 130:935-943.
D—. Primarily a discussion of the effects of cigarette smoke.
Brief mention of HCHO as an irritant. Acrolein was the most
effective in reducing mucus flow rates in cats after short-terra
inhalation exposures.
199
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5-378 Chaigneau, M. 1980. ClassificatioQ of Harmful Gases. Ann.
Anesthesiol. Fr. 21(6):683-688 (Fre.).
D—. Very brief reviews (with no references) of the toxicity of
several gases, including ECHO. Acrolein is mentioned as being
lethal in < 10 min at 30-100 ppm.
5-038 Chanet, R., and R. C. Von Borstel. 1979. Genetic Effects of
Formaldehyde in Yeast. 3. Nuclear and Cytoplasmic Mutagenic Ef-
fects. Mutat. Res. 62:239-253.
C-10. In yeast cells, Saccaromyces cerevisiae, HCHO was a weak
mutagen. (Much detail about strain/allele specificities/repair
processes that is probably relevant to genetic researchers but
not our task).
5-037 Chanet, R., C. Izard,-andE. Moustacchi. 1976. Genetic Effects
of Formaldehyde in Yeast. II. Influence of Ploidy and of Muta-
tions Affecting Radiosensitivity on its Lethal Effect. Mutat.
Res. 35:29-38.
C-12. Important in that this assay demonstrates that the HCHO-
induced single strand DNA breaks appear to be repaired. This has
ramifications in overall long-term effects if these principles
apply to mammalian systems.
7-008 Chernomorskii, A. R. , L. N. Zimont, R. A. Druz, L. N. Sigalova,
E. F. Drigo, and G. G. Antipova. 1978. Study of Respiratory
System Function in Workers Involved in a New Casting Process Us-
ing Cold-Hardening Molding Sands (based on the Resin BS-40).
Gig. Tr. Prof. Zabol. No. 5:47-49 (Russ).
D-9. Workers were exposed to 2 mg HCHO/m3, dust at lOx the MAC,
phenol, aldehydes, methanol, cyanides, and CO (the last 5 at
< MAC's) for up to 3 y. Respiratory pathology and functional
changes were reported. Teplyakov et al. (1980) reported on ap-
parently same group (1976 results), giving slightly lower HCHO
levels (0.1-1.2 mg/m3). They concluded that exposure had not
caused expressed pathological changes.
5-226 Chizhikov, V. A. 1970. On the Use of Animals with a Simulated
Disease in Studies of Hygienic Standards. Hyg. Sanit. 35(5):
182-186.
C-6. Exposure of hormonally deficient (castrated) male rats to
0.9 to 5 mg/L HCHO for 4 h. Test animals exhibited considerably
less resistance, their mortality was higher, and survival time
shorter than in controls.
5-428 Clary, J. J. 1980. A Review of the Health Effects of Formaldehyde
In: Proc. 14th Wash. State Univ. Int. Symp. Particleboard. pp. 125-
136.
200
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B--. A review of animal and human data, pointing out problems in
protocol and interpretation. Argues that rats are not a
good model for human cancer, and that the carcinogenicity found
in the CUT study may have been due to the severe irritation and
tissue damage, and that there is a threshold for this, and thus
for possible carcinogenicity. Includes a brief presentation of a
study conducted by the Formaldehyde Institute, in which monkeys,
rats, and hamsters were exposed to 0.2, 1, or 3 ppm HCHO for 6 mo.
No adverse effects were found at the lowest levels; slight effects,
at 3 ppm.
5-419 Cleveland, W. W. , T. E. Graedel, and B. Kleiner. 1977. Urban
Formaldehyde: Observed Correlation with Source Emissions and Photo-
chemistry. Atmos. Environ. 11:357-360.
C--. HCHO levels were measured during the summer months of 1972,
1973, and 1974 in four different New Jersey cities: Bayonne, 3-12
ppb; Newark, 4-14 ppb; Camden,.avg. 3.8 ppb; and Elizabeth, avg.
5.5 ppb. Levels varied during the day and the week with amount
of automobile traffic and photochemical formation.
5-319 Comber, R., and P. Grasso. 1973. The Effects of Chemical Irri-
tants and Tobacco Smoke Condensate on the Chorioallantoic Membrane
of the Fertile Hen's Egg. Chem.-Biol. Interactions. 6:25-34.
C—. Development of a test system. HCHO (0.625-10 |Jg/(Jl) was
applied to the chorioallantoic membrane of fertile hen's eggs.
After 72 h, a dose-related hyperplasia (increased thickening of
the membrane) was observed. Hyperplasia may be a necessary step
in tumor promotion.
5-359 CPSC, Consumer Product Safety Commission. 1978. Summary of
In-Depth Investigations: Urea-Formaldehyde Foam Home Insulation.
Directorate for Communication, U.S. Consumer Product Safety Com-
mission, Washington, D.C. 15 pp.
B-2. Brief summaries of 118 complaints and studies of adverse
health effects following the installation of urea-formaldehyde
foam insulation. HCHO levels ranged from < 0.5 to 7.0 ppm.
Symptoms were primarily headache, eye and upper respiratory
tract irritation, and nausea.
5-116 CPSC, Consumer Product Safety Commission. 1980a. Evaluation
of Health Risks of Formaldehyde by Government Scientists. Fed.
Regist. 45 (100):34031-34033.
C--. This is the announcement of the formation of the Formalde-
hyde Panel and the questions to be addressed by their November
1980 report, which see: Griesemer et al. (1980). The bibliogra-
phy was consulted for additional references.
201
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5-309 CPSC, Consumer Product Safety Commission. 1980b. Urea-Formal-
dehyde Foam Insulation; Proposed Notice to Purchasers. Fed.
Regist. 45(113):39434-39444.
C—. The proposed written notice to prospective purchasers and
first purchasers of insulation products made of urea-formaldehyde
foam is to include the following statements: "This product may
release formaldehyde gas into your home over a long period of time.
Formaldehyde gas may cause eye, nose, and throat irritation, cough-
ing, shortness of breath, skin irritation, nausea, headaches and
dizziness. People with respiratory problems or allergies may suf-
fer more serious reactions, especially persons allergic to formal-
dehyde." This publication summarizes actions by state and local
governments and other federal agencies concerning urea-HCHO foam
insulation. It describes the agency's investigation of consumer
complaints and among symptoms of chronic impairment includes "loss
of visual acuity." Numerous medical and scientific literature
references cited were acquired for this task.
5-420 CPSC, Consumer Product Safety Commission. 1981. Urea-Formaldehyde
Foam Insulation; Proposed Ban. Fed. Regist. 46(24):11888-11211.
C—. The discusion supporting the proposal reviews the report of
the Formaldehyde Panel, the CUT rat and mice studies showing nasal
cancers, and numerous other primary literature reports. The Com-
mission staff estimated that "any person living in a U.S. foam
insulation home for seven years after the product is installed
would have, as an upper estimate, an 85 in a million additional
risk of developing cancer from the formaldehyde released by the
insulation. The Commission has concluded "Based on the report of
the Federal Panel as well as additional research by Mantel and
Schneiderman, the risks to laboratory rats of developing cancer
should be considered to apply directly to humans breathing the ^
same concentration of formaldehyde (in ppm) as the test animals."
The Commission had requested the National Academy of Sciences
(NAS) to determine whether there is a tolerable level of HCHO in
residential indoor air. The NAS committee of expert toxicologists
concluded that "there is no population threshold for the acute
irritant effects of formaldehyde in humans."
5-176 Coon, R. A., R. A. Jones, L. J. Jenkins, Jr., and J. Siegel. 1970.
Animal Inhalation Studies on Ammonia, Ethylene Glycol, Formalde-
hyde, Dimethylamine, and Ethanol. Toxicol. Appl. Pharmacol. 16(3):
646-655.
B-12. Chronic exposure of 5 animal species to 4.6 mg HCHO/m3 for
90 d produced one rat death and inflammatory changes in lungs,
heart, and kidneys.
5-365 Cooper, P. 1979. Genetic Effects of Formaldehyde. Food Cosmet.
Toxicol. 17:300-301.
202
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C--. A review with selective points of view presented from several
authors. These include: (1) action of HCHO on bacterial DNA is
through products of reaction of HCHO with amino-containing com-
pounds or the free amino acids present in the bacterial cells,
not directly by HCHO; (2) radiation and HCHO appear to share a
common step in damage/repair of the breaks which occur in
Saccfaaromyces cerevisiae (yeast) pyrimidine dimers.
5-333 Cralley, L. V. 1942. The Effect of Irritant Gases Upon the Rate
of Ciliary Activity. J. Ind. Hyg. Toxicol. 24:193-198.
C-10. Exposure of rabbit tracheal preparations to 30-60 ppm HCHO
for 10 min or 60-100 ppm for 5 min caused cessation of ciliary
activity without recovery in Ringer's solution. Exposure to 18-20
ppm for 10 min or 30 ppm for 5 min caused cessation of activity
without recovery in air.
5-220 Criteria for Community Air Quality Committee. 1968. Community
Air Quality Guides. Aldehydes. Am. Ind. Hyg. Assoc. J. 29(5):
505-512.
C—. The toxicology and ambient concentrations of specific alde-
hydes including HCHO and acrolein are reviewed. In automobile
exhaust, ~ 70 mol-% of the carbonyl compounds, which are mainly
aldehydes, is HCHO. Acrolein and acetaldehyde comprise 3-10 mol-%.
Avg. U.S. urban air concentrations are 0.06 ppm HCHO (~ 0.09 mg/m3)
and 0.006 ppm acrolein (~ 0.015 mg/m3). Recommended levels (caus-
ing no sensory irritation) are 0.1 ppm HCHO, 0.01 ppm acrolein,
and 0.2 ppm total aldehyde as HCHO.
5-429 Dalbey, W. E. 1981. Effects of Formaldehyde or Nitrogen Dioxide on
Tumors in Hamster Respiratory Trace. Submitted to Toxicology for
publication; draft copy sent to Midwest Research Institute by author.
B-12. Exposure of hamsters to 10 ppm HCHO five times/wk for lifetime
caused no tumors or adverse effects on nasal epithelium.
Concurrent exposure of 30 ppm HCHO and subcutaneous injuections of
diethylnitrosamine (DEN) increased the number of tumors per tumor-
bearing animal above that of DEN alone.
3-027 Dalhamn, T. 1956. Mucous Flow and Ciliary Activity in the Trachea
of Healthy Rats and Rats Exposed to Respiratory Irritant Gases
(S02, H3N, HCHO). VIII. The Reaction of the Tracheal Ciliary
Activity to Single Exposure to Respiratory Irritant Gases and
Studies of the pH. Acta Physiol. Scand. 36(Suppl. 123):93-105.
C-6. Tracheal ciliary movement was observed in rats apparently
opened and exposed in situ to 0.5, 3, 10, or 22 ppm HCHO. Move-
ment was stopped in 2.5 min and 10 s for the lowest and highest
exposures, respectively. Recovery occurred in 30 s after the
lowest exposure stopped.
203
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5-228 Dalhamn, T., and A. Rosengren. 1971. Effect of Different Alde-
hydes on Trachea! Mucosa. Arch. Otolaryngol. 93(5):496-500.
C-5. A study of rabbit tracheal tissue showed that formaldehyde
appeared to be the most ciliotoxic, followed by acetaldehyde and
acrolein. Their experiments largely confirmed the results of other
authors. Data for HCHO indicated that ciliotoxicity increased
rapidly for small increases in the concentration of vapor, 61.7
mg/m3 causing immediate cessation of ciliary activity.
5-229 Danilin, V. A., and V. P. Meshcheriakov. 1968. On the Aspects
of Acute Formaldehyde and Dimethyldioxane Poisoning. Gig. Tr
Prof. Zabol. 12(7):45-46 (Russ).
D-3. The course of acute HCHO poisoning in workers is described,
but no HCHO concentrations are given. Exposure is confounded by
the presence of dimethyldioxane. Respiratory and skin symptoms
disappeared in 2-3 d if there was no further contact with HCHO.
5-044 Davidkova, E., and E. Basmadzhieva. 1979. Changes in Protein
and Nucleic Acid Metabolism as a Method for Assessing Gonadotoxic
Effects. Probl. Khig. 4:101-109 (Bui).
B-7. Chronic exposure of male rats to 0.035 mg HCHO/m3 decreased
RNA content, deoxyribonuclease activity, and protein content in
testicular homogenate. DNA content was increased. Sperm mobil-
ity was decreased.
5-230 Davis, T. R. A., S. P. Battista, and C. J. Kensler. 1965. Effect
of Cigarette Smoke, Acrolein and Formaldehyde on Pulmonary Func-
tion. Fed. Proc. 24(2, Part I):518.
C-5. Exposure of both tracheotomized and intact guinea pigs with
effect on lung function only in intact animals.
5-131 Davis, T. R. A., S. P. Battista, and C. Kensler. 1967. Mechanism
of Respiratory Effects During Exposure of Guinea Pigs to Irritants.
Arch. Environ. Health 15:412-419.
C-6. Exposure of guinea pigs to HCHO and acrolein using both tra-
cheotomized and intact animals. Effect on lung function only in
intact animals.
5-302 Deimel, M. 1978. Experience on the Formaldehyde Concentrations
in Room Air of a New School Building. In: Urg. Verunreinig.
Umwelt: Erkennen, Bewerten, Vermidern, [Tag.]. K. Aurand, U.
Haesselbarth, E. Lahmann, G. Muller, and W. Niemitz, Eds. Erich
Schmidt Verlag, Berlin, Germany, pp. 416-427 (Ger).
C—. The ambient air of new school buildings contained < 0.01 to
1.90 ppm HCHO with concentrations £ 0.31 ppm in the hot summer
months.
204
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5-231 Diamant-Berger, 0. 1970. Forensic Evaluation of the Sequelae of
Toxic Pulmonary Aggressions. Poumon Coeur 26(9):1013-1016 (Fre).
D-6. Case histories of exposures to several different gases, only
two for HCHO. In one case an existing asthmatic condition was
aggravated. In the other, a one-time asthma-like attack occurred
witn no sequelae. Following a second exposure 3 y later, a char-
acteristic, long-term asthma evolved. No HCHO levels or exposure
times given.
5-045 Dost, F. N. 1979. Assessment of Potential Toxic Hazards of For-
maldehyde. Proc. Wash. State Univ. Symp. Particleboard 13:317-327.
C--. A good review of the health effects of HCHO by a toxicologist.
5-341 Drobysheva, R. A., Y. V. Mitin, and A. M. Eskin. 1972. Experi-
mental Study of the Combined Effect of Dimethyldioxane and Formal-
dehyde on the Air Passages. Gig. Tr. Prof. Zabol. 16(6):52-53
(Russ).
D—. Rats (20 per group) were exposed to a mixture of dimethyl-
dioxane and HCHO in the concentrations 360 mg/m3 plus 23 mg/m3 or
544 mg/m3 plus 29.7 mg/m3, respectively, for 2 h/d, 5 d/wk for 9
wk. These values were ~ 36-60x the MAC's. Destructive changes
were observed in the upper respiratory tract mucosa.
5-232 Dubreuil, A., G. Bouley, J. Godin, and C. Boudene. 1976. Contin-
uous Inhalation of Low Levels of Formaldehyde: Experimental Study
in Rats. Eur. J. Toxicol. Environ. Hyg. 9(4):245-250 (Fre); English
translation available from John Crerar Library, Chicago, Illinois
Order No. 79-12804-06T.
B-10. Chronic exposu e of rats to 3 levels of HCHO. No effect
from ~ 2 to 5.7 mg/n, , respiratory effects seen at ~ 10 mg/m3
level.
5-234 Dubrovskaya, F. I., V. P. Levkin, and L. L. Zabudnyak. 1976a.
Effect of Low Concentrations of Formaldehyde in a Chronic Inhal-
ation Experiment. Gig. Aspekty Okhr. Okruzhayushchei Sredv
pp. 115-122 (Russ).
B-8. Exposing rats for 98 d to 0.012 or 0.031 mg HCHO/m3 caused
a fine focal pneumonia in the lungs, heart changes such as an in-
crease of rhythm frequency and a decrease of electrical activity,
and lowering of the function of the nerve cells of the brain.
5-233 Dubrovskaya, F. I., M. S. Katsenelenbaum, Y. K. Yushko, S. A.
Ipatova, and P. P. Vlasov. 1976b. Hygienic Evaluation of Air
Protection Measures at the Volga Industrial Complex. Gig.
Aspekty Okhr. Ozkruzhayushchei Sredy. pp. 123-127 (Russ).
205
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D—. Exposure of children living in the vicinity of the Volga
industrial complex to HCHO, S02, aldehydes, H2S, and NH3 led to
increased morbidity. Effects were not ascribed to particular
substances and levels of the compounds were not stated except
that they exceeded their limits.
5-171 Efremov, G. G. 1970. State of the Upper Respiratory Tract in
Formaldehyde Production Workers. (Data of a Special Study). Zh.
Ushn. Nos. Gorl. Bolez 30(5):11-15 (Russ).
A-10. Diseases of the upper respiratory tract were at least twice
as prevalent in 278 workers of 2 wood-processing plants using urea-
HCHO resins as in 200 age-matched, unexposed controls. Besides
observable pathology, the nasal membranes showed functional dis-
turbances as judged from the motility of the cilia, the absorp-
tive capacity, and odor threshold measurements. Workers appar-
ently became inured to the hazard with increasing length of ser-
vice. Griesemer et al. (1980) [5-361], p. 43, concluded that if
the controls were appropriate, the report supports the hypothesis
that HCHO exposure may lead to chronic respiratory disease.
5-005 Egle, J. L. 1972. Retention of Inhaled Formaldehyde, Propionalde-
hyde, and Acrolein in the Dog. Arch. Environ. Health 25:119-124.
D-9. Anesthetized dogs were exposed to 0.15 to 0.35 (Jg/mL of HCHO
or 0.4 to 0.6 Mg/ml- acrolein. Retention of HCHO in the total resp-
iratory tract was nearly 100%, upper tract retention alone exceeded
95%. Retention of acrolein in the total respiratory tract was 81
to 84%, upper tract retention was 75 to 80%. Variations in con-
centration, ventilatery rate, or tidal volume had little effect
on retention of the chemicals.
5-183 Egle, J. L., and P. M. Hudgins. 1974. Dose Dependent Sympatho-
mimetic and Cardioinhibitory Effect of Acrolein and Formaldehyde
in the Anesthetized Rat. Toxicol. Appl. Pharmacol. 28:358-366.
D-6. Primarily a study of i.v. exposure. Anesthetized rats were
exposed by inhalation for 1 min to 0.01 to 5.00 M8 acrolein/mL.
As concentration increased a pressor effect of increasing magni-
tude was observed. Cardioinhibitory effect occurred at 2.50 and
5.00 pg/mL. HCHO concentrations up to 2.0 \ig/mL did not produce
any significant cardiovascular effects.
5-301 Einbrodt, H. J., and D. Prajsnar. 1978. Effect of Formaldehyde
Exposure in School and Living Areas on People. In: Org. Verun-
reinig. Umwelt: Erkennen, Bewerten, Vermidern [Tag.]. K. Aurand,
U. Haesselbarth, and E. Lahmann, Eds. Erich Schmidt Verlag, Berlin,
Germany, pp. 428-435 (Ger).
206
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B-6. Studies of 2 groups exposed to ECHO: school children (0.08-
0.13 mg HCHO/m3) and adults (0.25-0.75 mg HCHO/m3). Complaints
were reported only by adults exposed to the highest levels. By
measuring HCHO and HCOOH levels in the urine, the authors conclude
that exposure to S~0.01 mg HCHO/m3 cannot be traced biologically.
They recommend that the threshold value for schools and living
areas snould be between 0.1 and 0.5 ppm to avoid annoyance due to
HCHO.
5-006 Einbrodt, H. J., D. Prajsnar, and J. Erpenbeck. 1976. The Formal-
dehyde and Formic Acid Levels in Blood and Urine in Man After Ex-
posure to Formaldehyde. Zentralbl. Arbeitsmed. Arbeitsschultz
Prophyl. 26:154-158 (Ger).
C-6. Exposure of humans to 0.78 mg HCHO/m3 or avg. 1.28 mg HCHO/m3
for 3 or 8 h, respectively. Levels of HCHO and HCOOH were mea-
sured in the blood and urine after exposure and after a recovery-
period. Weak experimental design due to lack of appropriate controls
and smoking histories.
5-244 Elinek, R. 1974. Precancerous Laryngeal Diseases and Their Rela-
tion to Carcinoma. Acta Univ. Palacki. Olomuc. Fac. Med. 70:245-316
(Russ).
D-3. Exposure of 20 rats to formalin vapors (no HCHO concentra-
tions given) for from 0.5 h to 32 d. Preparation of larynx
histological sections from animals killed after 71 d from last
exposure showed hypersecretory changes in 17 rats, significant
chronic inflammatory infiltration in the membrane itself of 12 rats,
dilation of the channels of the serous-mucous glands in 8 rats,
and squamous cell metaplasia of the pseudostratified epithelia
in 4.
5-134 Ettinger, L. , and M. Jeremias. 1955. A Study of the Health
Hazards Involved in Working with Flameproofed Fabrics. N. Y.
State Dep. Labor Div. Ind. Hyg. Mon. Rev. 34(7):25-27.
C-4. Garment industry workers exposed to 1.25-13.75 mg HCHO/m3
complained of eye, nose, and throat irritation. A brief, anecdotal
account of the toxicity. A longer discussion of the treatment
process, problems with it, and possible solutions.
5-174 Fassett, D. W. 1963. Aldehydes and Acetals. In: Industrial
Hygiene and Toxicology, 2nd revised ed., F. A. Patty, D. W. Fassett,
and D. D. Irish, Eds. Interscience Publishers, New York, New York.
Vol. 2, pp. 1959-1989.
C—. Includes a specific review of the toxicity of HCHO: very
mild eye and nose irritation at 2-3 ppm; increased irritation and
lacrimation at 4-5 ppm, tolerated for 10-30 rain; profuse lacrima-
tion and barely tolerable irritation at 10 ppm; coughing, lacrima-
tion, and difficulty breathing at 10-20 ppm, irritation lasting
207
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up to 1 h after exposure stops; and very serious injury following
5-10 min exposure to 50-100 ppm. The 30-min LC$Q for acrolein in
rats is 130 ppm.
5-236 Fel'dman, Yu. G. 1971. An Answer to K. K. Sidorov, Medical
Science Candidate. Hyg. Sanit. 36(12):435-436.
D—. Reply to the criticisms of Sidorov (1971) [5-270]. Agrees
that the workplace MFC for HCHO is 0.5 mg/m3, but maintains that
the one-time MPC for atmospheric air is 0.035 mg/m3 and the mean
diurnal MFC for atmospheric air is 0.012 mg/m3. These figures
are supported by U.S.S.R. (1972) [3-094].
5-007 Fel'dman, Yu. G. 1972. Biological Action of Certain Products
from Atmospheric Photochemical Reactions. Gig. Sanit. 37(1):6-9
(Russ).
D-7 (animal). B-7 (human). For HCHO, the human odor threshold
was 0.073 mg/m3 and the threshold for effect on brain electrical
activity was 0.053 mg/m3. The bulk of the report considers the
effect of mixtures of 0s, NC-2, and HCHO on humans and rats, the
results indicating simple summation effects.
5-008 Fel'dman, Yu. G. 1974. Combined Action on the Human Organism of
a Mixture of the Major Components of Automobile Exhaust Gases
(Carbon Monoxide, Nitrogen Dioxide, Formaldehyde, and Hexane).
Gig. Sanit. No. 10: 7-10 (Russ); English translation by Joint
Publications Research Service, JPRS-65836, National Technical In-
formation Service, U.S. Department of Commerce, Springfield, Va.
A-9. For HCHO, the subthreshold odor value was 0.054 mg/m3 and
the subthreshold EEG activity value was 0.04 mg/m3. A good inter-
action study: a mixture of low concentrations of HCHO, N02, CO,
and hexane was found to be simply additive in effect. The signi-
ficance of the EEG effects is dubious.
5-048 Fel'dman, Yu. G., and T. I. Bonashevskaya. 1971. On the Effects
of Low Concentrations of Formaldehyde. Hyg. Sanit. 36(5):174-80.
A-10. The human odor threshold was found to be 0.073 mg/m3. EEG
changes were induced by 0.053 mg/m3. The recommended one-time
maximum permissible concentration for atmospheric air was 0.04 mg/m3.
Chronic exposure of rats to 0.012-3 mg/m3 caused mild functional
and morphological changes at the higher levels, but no changes at
0.012 mg/m3.
5-184 Fel'dman, Yu. G., and N. D. Eksler. 1975. Assessment of the Action
of Atmospheric Pollution on the Electric Activity of the Brain.
Gig. Sanit. No. 9:11-14 (Russ).
208
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B-7. The EEC's of rabbits exposed to 0.65 mg HCHO/m3 + flashing
light for 20 min showed detrimental effects such as deterioration
of the reactions of rearrangement of rhythm of all studied brain
structures. In the same conditions, rabbits exposed to 0.035 mg
HCHO/m3 did not show any EEC changes. These tests are mentioned
in Bokina and Eksler (1973) [5-003].
5-330 Fischer, M. H. 1905. The Toxic Effects of Formaldehyde and Forma-
lin. J. Exp. Med. 6:487-518.
C-7. Inflammatory lung changes are described for animals (small
numbers of various small and medium-size laboratory species) ex-
posed to unquantitated HCHO levels (but apparently high; generated
by common methods used for disinfection). These results contradict
those of 9 earlier reports by workers who found no serious ill
effects upon exposure of animals to disinfection levels of HCHO.
5-325 Freeman, H. G., and W. C. Grendon. 1971. Formaldehyde Detection
and Control in the Wood Industry. For. Prod. J. 21(9):54-57.
D-3. A test for monitoring HCHO in the workplace and for checking
the relative amounts of HCHO given off by different adhesives,
was developed. Workers complained when levels were >1 ppm. HCHO
was felt to be a contributor to increased accidents.
5-049 Frey, G. , K.-H. Bock, H. Meister, H.-U. Haug, J. Kilian, and
F. W. Ahnefeld. 1979. Effects of Ventilation with Defined For-
maldehyde Concentrations on Lung Function and Lung Structures:
Animal Experiments on the Noxiousness of Formaldehyde Residues
after Disinfection in the Aseptor. Anesthesist 28(6):271-278.
B-12. Exposure of pigs to 0.03 to 2.5 mg HCHO/m3 for 6 h. Similar
respiratory effects at all three levels.
5-051 Gadzhiev, G. P., V. G. Deinega, V. V. Sukhanov, I. M. Levshina,
N. T. Yarym-Agaeva, and G. A. Petrenko. 1977. Hygienic Evalua-
tion of a New Technology of Methane and Dust Control in Coal Mines.
D-4. The physical conditions of miners in mines treated with urea-
HCHO resin did not differ after several months from that of miners
in untreated mines. In treated mines, the air contained 0.02-0.13 mg
HCHO/m3 and 0.14-0.8 mg MeOH/ra3 during cleaning operations. Rats
given an intratracheal dose of treated or untreated dust showed
more severe bronchial changes if the dust was followed by a 6-mo
exposure to 0.5-0.6 mg HCHO/m3 and 5.0-6.0 mg MeOH/m3.
5-017 Galibin, G. P. 1963. Action of Hardened (meaning three-dimensional
or cured) Synthetic Resins on Animal Systems. Toksikol. Nov. Prom.
Khim. Veshchestv 5:45-50 (Russ).
209
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D-7. Rats were exposed for 2 h/d for 12 d to decomposition products
generated when various hardened synthetic resins were heated at
60°C; e.g., phenol-HCHO resin gave 0.5 mg phenol/m3 and 0.2 mg
HCHO/m3. Behavior, threshold of excitability, and morphological
composition of the blood showed no differences from those of the
controls.
5-315 Gamble, J. F., A. J. McMichael, T. Williams, and M. Battigelli.
1976. Respiratory Function and Symptoms. An Environmental-Epidemi-
ological Study of Rubber Workers Exposed to Phenol-Formaldehyde
Type Resin. Am. Ind. Hyg. Assoc. J. 37:499-513.
C-9. The title workers were exposed to ECHO (mean 0.047 mg/m3),
NH3 (mean 0.052 mg/m3), resorcinol (mean 0.295 mg/m3), and respir-
able particulates (<0.5 mg/m3). There was an excess of self-reported
symptoms of eye and respiratory tract irritation, but no difference
in baseline lung function tests. Some acute, temporary "small
airways" effects occurred after the workday.
5-284 Garry, V. F., L. Oatman, R. Pleus, and D. Gray. 1980. Formalde-
hyde in the Home. Some Environmental Disease Perspectives. Minn.
Med. 63(2):107-111.
B-7. A study of 168 people exposed in their homes to 0.2-1.0 ppm
HCHO, with no control or comparison group. Data are stratified
by age of subject. Symptoms include respiratory problems, mucous
membrane irritation, skin rash, and gastrointestinal complaints.
5-426 Geomet, Inc., and Technology and Economics, Inc. 1980. Mobile
Home Evaluation of Formaldehyde Problems in Residential Mobile
Home. Final Task 1 Report. PB81-175499, National Technical
Information Service, U.S. Department of Commerce, Springfield,
Virginia. 154 pp.
C—. Extensive review of HCHO properties, monitoring techniques,
sources and emissions in mobile homes (0-4.2 ppm), human health
effects, international standards, and abatement techniques.
5-295a Giulietti, M. A. 1980. Connecticut Department of Health Services,
Preventable Diseases Division, Toxic Hazards Section, July 14,
1980 Summary Report [Urea Formaldehyde Insulation Investigations];
transmitted to MRI by M. A. Giulietti, Product Safety, Department
of Consumer Protection, State of Connecticut. 5 pp.
B-6 The results of a study of 282 cases complaining of adverse
health effects and living in buildings with urea-formaldehyde in-
sulation (a total of 847 people questioned). Detectable HCHO
levels ranged from 0.5 to 10 ppm. Symptoms included eye, nose,
throat, and skin irritation, nausea, headache, and if^S"6-
Symptoms were reported (including odor perception) in buildings
with nondetectable (<0.5 ppm) HCHO levels.
210
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5-052 Gofmekler, V. A. 1968. Effect on Embryonic Development of Benzene
and Formaldehyde in Inhalation Experiments. Hyg. Sanit 33(3):327-
332.
D-5. Same study as Pushkina et al. (1968) [5-012] and Gofmekler
et al. (1968) [5-238] on rats and progeny. Data on effect of
exposure on fetal organ weights.
5-237 Gofmekler, V. A. 1974. Embryotropic Action of Chemical Atmospheric
Pollution. Gig. Sanit. 39(9):7-10 (Russ); English translation
available from John Crerar Library, Chicago, Illinois. Order No.
13535-06J.
D—. Review of teratology study of albino rats exposed continuously
during pregnancy to 0.01 and 1.0 mg HCHO/m3. Data tabulated from
original article for this report.
5-185 Gofmekler, V. A., and T. I. Bonashevskaya. 1969. Experimental
Studies of Teratogenic Properties of Formaldehyde, Based on Pathol-
ogical Investigations. Gig. Sanit. 34(5):92-94 (Russ); Hyg. Sanit.
34(5):266-268.
D-5. Same study as Pushkina et al. (1968) [5-012], Gofmekler et
al. (1968) [5-238], and Gofmekler (1968) [5-052] on rats and progeny.
Data on histological and histochemical changes.
5-238 Gofmekler, V. A., N. N. Pushkina, and G. N. Klevtsova. 1968. Some
Biochemical Aspects of the Embryotropic Effect of Benzene and For-
maldehyde. Gig. Sanit. 33(7):96-98 (Russ); Hyg. Sanit. 33(7):112-116.
D-6. Same data on effect of HCHO exposure on ascorbic and nucleic
acid levels in rats as Pushkina et al. (1968) [5-012].
5-054 Goloshchapov, 0. D. 1979. Protein Metabolism in Experimental
Formaldehyde Poisoning. Khim. Prom-st., Ser.: Toksikol. Sanit.
Khim. Plastmass. No. 3:11 (Russ).
C-5. Rats exposed to 20 mg HCHO/m3 for 6 wk were protected by a
diet with 32% protein from the ensuing disturbances of protein met-
abolism seen in rats fed a normal ration with 18% protein. Compare
Goloshchapov and Agranovskii (1976) [5-239].
5-239 Goloshchapov, 0. D., and M. Z. Agranovskii. 1976. Lipoamide as a
Component of a Prophylactic Diet in Exposure to Formaldehyde. Gig.
Sanit. No. 3:25-28 (Russ).
C-ll. Rats exposed to 20 mg HCHO/m3 for 3 h/d for 6 wk were protec-
ted by a diet containing 5 mg lipoamide/kg from the disturbances seen
in serum proteins and amino acids, ascorbic acid in the liver, behav-
ior changes, depression in weight gain, dystrophic and necrotic chan-
ges in the liver, etc., in rats fed a diet with 18% protein without
additional lipoamide.
211
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5-403 Gosselia, R. E., H. C. Hodge, R. P. Smith, aad M. N. Gleason. 1976.
Formaldehyde. In: Clinical Toxicology of Commercial Products—Acute
Poisoning. Fourth Edition. The Williams and Wilkins Co., Baltimore,
Maryland, pp. 166-168.
D—. Brief review.
5-057 Granati, A., R. Lenzi, and E. Monaco. 1978. Environmental Health
Problems in the Clothing Industry in Relation to Formaldehyde-Treated
Fabrics. Riv. Med. Lav. Ig. Ind. 2(July-Sept.):221-232 (Ita) .
B-9. Study of garment factory workers exposed to levels of HCHO up
to ~ 0.5 mg/m3. Of 3034 workers, 30.3% reported cutaneous and mucous
membrane irritations. During the exposure period, there was an ~ 800%
increase in symptoms and seriousness of irritation compared to pre-
vious period when different fabric (the source of the HCHO) was used.
5-240 Green, G. M., and D. Carolin. 1967. The Depressant Effect of Cig-
aret Smoke on the in vitro Antibacterial Activity of Alveolar Macro-
phages. N. Engl. J. Med. 276(8):421-427.
D--. HCHO at 1.6-163 Mg/mL (levels above those found in cigarette
smoke) did not inhibit the in vitro phagocytic ability of rabbit
pulmonary alveolar macrophages. Whole cigarette smoke did.
5-361 Griesemer, R. A., A. G. Ulsamer, J. C. Arcos, J. R. Beall, et al.*
1980. Report of the Federal Panel on Formaldehyde. National Toxi-
cology Program, Public Health Service, Department of Health and Human
Services, Research Triangle Park, North Carolina. 64 pp.
A—. A very extensive and authoritative review and evaluation of
animal and human exposure to try to determine the potential health
risks to humans from chronic exposure to HCHO. The Panel concludes
that " it is prudent to regard formaldehyde as posing a carcino-
genic risk to humans." Conclusions on other topics such as terato-
genicity/reproductive effects and animal-to-man data extrapolation
are not made.
5-241 Guseva, V. A. 1972. Gonadotropic Effect of Formaldehyde on Male
Rats During Its Simultaneous Introduction with Air and Water. Gig.
Sanit. No. 10: 102-103 (Russ).
8-6. Male rats exposed for 6 mo to 0.5 mg HCHO/m3 air and 0.1 mg
HCHO/L orally for 4 h, 5x/wk produced normal nos. of normal off-
spring, but the content of nucleic acids in their testicles was sig-
nificantly reduced.
5-186 Guseva, V. A. 1973. Effect of Formaldehyde During its Joint Respir-
atory and Oral Administration. Gig. Sanit. No. 5:7-11 (Russ).
^ See page A-4 for a complete listing of the panel members and their
affiliations.
212
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C-8. Exposure of rats simultaneously by inhalation (0.12, 0.25, or
0.5 mg/m3) and ingestion (0.1, 0.01, or 0.005 rag/L) for 4 h/d, 5 d/wk,
for 7 mo. Effects on CNS, conditioned reflex, biochemistry, pathomor-
phology, and neurohistology were studied. No effects seen at the com-
bination of lowest doses.
5-394 Guzeev, Yu. M., and I. V. Bachinskii. 1980. Upper Airway Damage
and Methods for Reducing the Worker Morbidity in the Woodworking
Industry. Zh. Ushn., Nos. Gorl. Bolezn. No. 5:47-54 (Russ).
D—. Woodworking industry workers (512) were exposed to wood dusts,
HCHO, toluene, xylene, abrasive dusts, and/or electrowelding dusts.
Workers (185) exposed to the highest concentrations of HCHO (2.7 mg/m3)
but lower levels of wood dust (7.0 mg/m3), abrasive dust (11.8 mg/m3),
and electrowelding aerosols (0.46 mg/m3) had the lowest incidence of
upper respiratory tract problems (7.0%). Of these patients, 30.7%
showed hypertrophy of the mucous membranes, a higher incidence than
in the other groups of workers exposed to less HCHO but more solvents
and dusts.
5-363 Hanrahan, L. P., K. A. Dally, and H. A. Anderson. 1980. A Random
Sample Survey of Wisconsin Mobile Homes: Formaldehyde Concentra-
tions and Health Effects. Wisconsin Division of Health, Department
of Health and Social Services, Madison, Wisconsin. 29 pp.
B-6. Two groups of mobile home residents (105 total) were studied.
23 different symptoms are reported, but only burning eyes was sta-
tistically associated with HCHO. Levels measured ranged from < 0.14
to 1.01 mg/m3. An indoor HCHO standard of 0.2 ppm is recommended.
5-058 Harper, C., and J. M. Patel. 1978. Inactivation of Pulmonary Cyto-
chrome P-450 by Aldehydes. Fed. Proc. 37(3):767.
D—. An abstract only, so no experimental details (levels and mode
of exposure) are given. Formaldehyde caused destruction of liver
microsomal P450 and pulmonary cytochrome P450 with no requirement
for NADPH.
5-137 Harris, D. K. 1953. Health Problems in the Manufacture and Use of
Plastics. Br. J. Ind. Med. 10:255-268.
D-7. Clinical examination of 25 men exposed to HCHO in a factory
making urea-HCHO and phenol-HCHO resins and employed for > 5 y re-
vealed abnormalities in blood counts in 13 and dyspnea in 4. Only
4 had been affected by dermatitis.
5-360 Harris, J. C. , B. H. Rumack, and F. D. Aldrich. 1981. Toxicology
of Urea Formaldehyde and Polyurethane Foam Insulation. J. Am. Med.
Assoc. 245(3):243-246.
213
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D-3. Review of the use and toxicity of urea-formaldehyde foam.
Includes the results of questionnaires filled out by occupants of
homes insulated with the foam, reporting dyspnea, headache, rhin-
itis, eye irritation, cough, and frequent colds. No HCHO levels
given.
5-313 Helwig, N. 1977. How Safe Is Formaldehyde. Dtsch. Med. Woch.
102:1612-1613 (Ger); English translation available from John Crerar
Library, Chicago, Illinois. Order No. 810412-06T.
C-4. Young school children exposed to ~ 5 ppm HCHO from HCHO-con-
taiaing fiberboard for ~ 8 mo complained of irritation, nausea,
and apathy. Habituation and individual variability in sensitivity
were seen.
5-242 Hendrick, D. J., and D. J. Lane. 1975. Formalin Asthma in Hospital
Staff. Br. Med. J. 1:607-608.
C-8. Inhalation provocation tests confirmed that exposure to forma-
lin vapors was the cause of the delayed asthmatic symptoms in one
hospital staff member but not the cause of change in ventilatory
function of another member who had suffered from asthma as a child
and hay fever since age 19.
5-060 Hendrick, D. J., and D. J. Lane 1977. Occupational Formalin Asthma.
Br. J. Ind. Med. 34(1):11-18.
C-6. 8 cases of occupational asthma developed among 28 members
of nursing staff at Hemodialysis Unit in which formalin was used
to sterilize dialysis machine, over a 3-y period. 2 of 5 persons
had positive responses to formalin provocation tests. No air sample
measurements were requested, and no control or comparison group
was studied.
5-061 Hollowell, C. D., J. V. Berk, C. Lin, W. W. Nazaroff, and G. W.
Traynor. 1979a. Impact of Energy Conservation in Buildings on
Health. LBL-9379, National Technical Information Service, Spring-
field, VA. 11 pp.
C—. At low ventilation rates, HCHO concentrations in indoor air
are frequently > 0.1 mg/m3 when outdoor concentrations are typically
0.02 mg/m3. Indoor and outdoor HCHO concentrations and the health
effects of HCHO are briefly reviewed.
5-062 Hollowell, C. G., J. V. Berk, C. I. Lin, and I. Turiel. 1979b.
Indoor Air Quality in Energy-Efficient Buildings. Conf. 79052j-z,
National Technical Information Service, U.S. Dept. of Commerce,
Springfield, VA. 12 pp.
C—. HCHO concentrations in an Energy Research House in Ames, Iowa,
were 51-125 ppb indoors compared to < 5 ppb outdoors.
214
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5-349 Hollowell, C. D. , J. V. Berk, M. L. Boegel, R. R. Miksch, W. W.
Nazaroff, and G. W. Traynor. 1980. Building Ventilation and In-
door Air Quality. Stud. Environ. Sci. 8(Atmos. Pollut.):387-396.
C—. Indoor air concentrations of HCHO reported from the U.S.,
Denmark, Sweden, and Vest Germany are ".aquently > 0.120 mg/m3,
which is the limit set for indoor air by the Netherlands in July
1978. HCHO concentrations in a test kitchen with a new gas stove
ranged from 0.040 mg/m3 when a hood vent with a fan was used at
high speed to 0.460 mg/m3 when no stove vent or hood was used.
(The values reported for this study by Hollowell et al., 1979a
[5-061] were 0.035 and 0.400 mg/m3, respectively.) Typical out-
door HCHO concentration during the test was 0.005 mg/m3.
5-009 Horton, A. W. , R. Tye, and K. Stemmer. 1963. Experimental Carcino-
genesis of the Lung. Inhalation of Gaseous Formaldehyde or an
Aerosol of Coal Tar by C3H Mice. J. Natl. Cancer Inst. 30:31-43.
B-10. Acute and chronic exposure of mice to 50-900 mg HCHO/m3
produced death and at lower levels tracheobronchial epithelium
changes but no. carcinomas. No mention of effects on nasal cavity.
5-140 Hovding, G. 1969. Occupational Dermatitis from Pyrolysis Products
of Polythene. Acta Derm. Venereol. 49:147-149.
D-4. Case report of exposure to small amounts of smoke (presumably
containing HCHO and acrolein) from cutting polyethylene bags.
Symptoms of the skin and the mucous membranes of the eyes and upper
respiratory tract were described. No measurements and no follow-up
after changes in the ventilation system. All five workers gave a
positive response to a patch test with a 4% aqueous HCHO solution.
Hewlett, C. T., Jr. 1980. An Assessment of the Regulation of
Indoor Air Quality. In: Proc. 14th Wash. State Univ. Int. Symp.
Particleboard, Pullman, Washington, April 1980. pp. 145-158.
D—. General review. Includes some international regulations
and recommendations for allowable HCHO levels.
5-065 Hsie, A. W. , J. P. O'Neill, J. R. San Sebastian, D. B. Couch, J. C.
Fusco, W. N. C. Sun, P. A. Brimer, R. Machanoff, J. C. Riddle,
N. L. Forbes, and M. H. Hsie. 1978. Mutagenicity of Carcinogens:
Study of 101 Agents in a Quantitative Mammalian Cell Mutation Sys-
tem, CHO/HGPRT. Fed. Proc. 37(6):1384.
B--. A standard Chinese hamser ovary-bioassay for mutagenicity
(CHO/HGPT) showed formaldehyde negative. The abstract called the
result a "possible FALSE negative: with no data furnished.
215
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5-366 Ikeda, A., Y. Horiguchi,'and K. Koyoshi. 1980. Research on the
Effect of Air Pollution. 2. Studies on Biological Effects of
Carbohydrates. On Aldehydes. Kanagawa-ken Taiki Osen Chosa Kenkyu
Hokoku 22:193-196 (Japan).
C-7. Exposure of rabbits to 6.3 mg/m3 for 3-4 min caused decreased
heart rate and respiratory HCHO movement and changes in blood
pressure.
1-0172 ILO. 1970. Permissible Levels of Toxic Substances in the Working
Environment. Occupational Safety and Health Series 20, International
Labour Office, Geneva, pp. 194-198.
C—. Maximum acceptable concentrations in Czechoslovakia:
Short
Normal Single Exposure
MAC (mg/m3) MAC (mg/m3)
Acrolein 0.5 1.0
NH3 40 80
HCHO 2 5
HCN 3 15
MeOH 100 500
H2S 30
5-141 ILO/WHO Committee. 1970. Permissible Levels of Toxic Substances
in the Working Environment—Sixth Session of the Joint ILO/WHO
Committee, Occupational Health and Safety Series, Title 20. Inter-
national Labor Office, Geneva, pp. 190, 201, 213, 242, 288, 290,
292, 295, 296, 306, 333, and 348.
C--. International values ranged from 0.5-20 ppm HCHO, with 5 ppm
the most frequent standard for occupational exposure.
5-066 lonescu, J., D. Marinescu, V. Tapu, and A. Eskenasy. 1978. Experi-
mental Chronic Obstructive Lung Disease. I. Bronchopulmonary
Changes Induced in Rabbits by Prolonged Exposure to Formaldehyde.
Morphol. Embryol. (Bucur). 24(3):233-242.
C-5. Male rabbits exposed to aerosol of 3% of HCHO for 3 h/d for
up to 50 d. No dose level given. In-depth discussion of changes
induced in the respiratory system by the exposure.
5-067 Ishchenko, V. N., and I. K. Pushkina. 1978. Evaluation of the
Working Conditions in the Manufacture and Processing of Phenol-For-
maldehyde Resins. Gig. Sanit. No. 11:98-100 (Russ).
C-8. The workers were exposed to < 0.5 mg HCHO/m3, phenol usually
at > 5 mg/m3 (its MAC), cresol (< MAC), high temperatures, and high
humidity, and were involved in strenuous physical activities. Only
the exposed women workers showed significant increases in morbidity,
216
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especially in respiratory diseases, musculoskeletal afflictions, and
diseases of the urogenital system compared to the exposed men or the
control men and women. Sleep disturbances were also more frequent
in the exposed women. Domestic burdens were probably a contributing
factor to the illnesses of the exposed women.
5-142 Iwanoff, N. 1911. On Some Aldehydes of Practical Importance. Arch.
Hyg. 73:307-340 (Ger).
C-8. Acute exposure of cats to ECHO and acrolein. Study is of
interest but of limited value because of high dose levels used
U 260 mg HCHO/m3 and £ 25 mg acrolein/m3).
6-024 Jermini, C. , and A. Weber. 1975. Air Pollution by Cigarette Smoke.
Soz.-Praeventivmed. 20(5):213 (Ger).
C—. Smoking 10 tobacco cigarettes in a 30 m3 room produced the
following concentrations of irritating substances: acrolein, 0.120
ppm; HCHO, 0.450 ppm; CO, 24 ppm; and NO, 0.678 ppm. The corres-
ponding MAC's are 0.1, 2, 50, and 25 ppm, respectively.
5-208 Jermini, C., A..Weber, and E. Grandjean. 1976. Quantitative Deter-
mination of Various Gas-Phase Components of the Side-Stream Smoke
of Cigarettes in the Room Air as a Contribution to the Problem of
Passive-Smoking. Int. Arch. Occup. Environ. Health 36(3):169-181
(Ger).
D--. An unventilated 30 m3 room in which 30 cigarettes were smoked
contained 0.37 ppm acrolein. The unpolluted air in the room con-
tained 0.036 ppm HCHO, and 0.06 ppm HCHO after one cigarette was
smoked. Other components were also measured.
5-246 Jordeczka, S., B. Basa, and S. Basa. 1973. The Incidence of Chro-
nic Nonspecific Respiratory Disease Among the Workers of Furrier
Industry. Abstr. Congr. Pol. Phthisjopneumonol. Soc. 18:100-101.
D—. Occupational study is confounded by exposures to NH3, naph-
thalene, trichloroethylene, and acetic acid esters as well as HCHO
and smoking. The respiratory disease was significantly correlated
with duration of smoking habit but not with the number of cigarettes
smoked daily.
5-209 Kabe, J. 1971. Bronchial Asthma and Asthma-Like Dyspnea Caused
by Inhalation of Simple Chemicals. J. Allergol. 20(6):444-450
(Jap).
D—. Kabe defined four types of allergologic patterns caused by
inhalation of low-molecular-weight compounds--immediate type, de-
layed type, non-allergic, and irritative type, as well as undeter-
mined type reactions. When Kabe (1969) [Shonikagaku 10:513] ad-
ministered dilute solutions of formalin to guinea pigs over long
217
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periods, a delayed increase in respiratory frequency was not in-
duced as was observed when they inhaled other respiratory
antigens.
5-247 Kalpazanov, Y., M. Stamenova, and G. Kurchatova. 1976. Air Pollu-
tion and the 1974-1975 Influenza Epidemic in Sofia: A Statistical
Study. Environ. Res. 12(1):1-8.
D-5. Multiple regression analysis is used to study the influence
of meteorological conditions and air pollutants on the number of
influenza cases. Several pollutants were considered: dust, NO ,
oxidants, phenol, S02 and HCHO (0.0107-0.0145 mg/m3). A statis-
tically significant dependence was found between the number of ill
during a given day and the concentration of HCHO 2 days earlier.
Other relationships were seen for the other pollutants.
5-143 Kamchatnov, V. P., and S. S. Gayazova. 1971. Temperature Asymmetry
in Workers Exposed to Formaldehyde Vapor. Hyg. Sanit. 86(1) -.286-287
C-8. Exposure to 5-78 mg HCHO/m3 for 5-20 y caused a pathological
skin thermal asymmetry (0.6-2.2°C) which existed before a workday
began in 48.4% of the workers and increased to 60% by the end of
the workday. The authors consider this evidence of adverse CNS
effects. Headache, vertigo, and irritability were also reported.
5-010 Kane, L., and Y. Alarie. 1977. Sensory Irritation to Formaldehyde
and Acrolein During Single and Repeated Exposures in Mice. Am. Ind.
Hyg. Assoc. J. 38:509-522.
B-12. Mice exposed to low levels of HCHO and acrolein in single
and repeated acute exposures with decreases in respiration rate.
Kane and Alarie recommend a TLV of 0.03 to 0.3 ppm HCHO.
6-069 Kane, L. E., and Y. Alarie. 1978. Evaluation of Sensory Irrita-
tion from Acrolein-Formaldehyde Mixtures. Am. Ind. Hyg. Assoc. J.
39(4):270-274.
B-10. A mathematical model applied to the data on the effects of
acrolein and HCHO alone and in 11 combinations on the respiratory
rate of mice indicates that competitive agonism exists between
acrolein and HCHO when both are present.
3-134 Kane, L. E., C. S. Barrow, and Y. Alarie. 1979. A Short-Term Test
to Predict Acceptable Levels of Exposure to Airborne Sensory Irri-
tants. Am. Ind. Hyg. Assoc. J. 40(3):207-229.
D—. Review of short-term exposure studies with mice, involving
HCHO, acrolein, and 9 other chemicals. Recommended highest concen-
tration for an Air Quality Standard was 0.003 ppm HCHO.
218
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5-071 Katz, G. V., and S. Laskin. 1977. Effect of Irritant Atmospheres
on Macrophage Behavior. In: E.R.D.A. Symp. Ser. 43(Pulm. Macro-
phage Epithelial Cells):358-373. C. L. Sander, G. E. Dagle, and
H. A. Ragan, Eds. Order No. Conf. 760927, Energy Research and Devel-
opment Administration, National Technical Information Service, U.S.
Department of Commerce, Springfield, VA.
C-7. Pulmonary alveolar macrophage activity of cells collected
from rats pre-exposed to ~ 12.5 and ~ 25 mg HCHO/m3. Higher level
only decreased phagocytic activity.
5-190 Kensler, C., and S. P. Battista. 1963. Components of Cigarette
Smoke with Ciliary-Depressant Activity. Their Selective Removal
by Filters Containing Activated Charcoal. New Engl. J. Med.
296:1161-1166.
B-13. Technique described in minute detail - controls include
points not addressed in other papers. Their 1966 article [5-248]
that discussed recovery is important addition to this line of bio-
assay tests. Method of quantitating effect is hard to follow:
what number of micrograms of gas per 1.2 liter "puff" of air (when
8 puffs are administered) is needed to produce 50% inhibition of
tracer particles' movement of 5 mm on isolated rabbit trachea.
For HCHO, this value was 6 (Jg, about three times the HCHO level
in each puff of cigarette smoke.
5-248 Kensler, C. J., and S. P. Battista. 1966. Chemical and Physical
Factors Affecting Mammalian Ciliary Activity. Amer. Rev. Resp.
Dis. 93(3):93-102.
C-12. HCHO tested on isolated rabbit tracheal preparations pro-
duced reversible inhibition of ciliary activity, following 12-s
exposures to unknown concentrations. The in vitro bioassay may
have applicability to in vivo mammalian ciliary transport.
5-390 Kerfoot, E. J. 1972. Formaldehyde Vapor Emission Study in Embalm-
ing Rooms. The Director 42:6-7.
C-4. A summary of the information given in Kerfoot and Mooney
(1975) [5-145].
5-145 Kerfoot, E. J. , and T. F. Mooney, Jr. 1975. Formaldehyde and
Paraformaldehyde Study in Funeral Homes. Am. Ind. Hyg. Assoc. J.
36:533-537.
B-4. Embalmers exposed to 0.11-6.58 mg HCHO/m3 complained of eye
and upper respiratory tract irritation. Some sinus problems and
asthma reported. The necessity for adequate ventilation is demon-
strated. No comparison group.
219
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5-367 Kettner, H. 1978. Indoor Contamination by Chemical Substances
and Their Hygienic Significance. In: Org. Verunreinig. Umwelt:
Erkennen, Bewerten, Vennindern. K. Aurand, V. Haesselbarth, E.
Lahmann, G. Muller, and W. Niemitz, Eds. Erich Schmidt Verlag,
Berlin, Germany, pp. 448-453 (Ger).
C—. Maximum allowable indoor air concentrations in the USSR:
Acrolein 0.1 mg/m3
NH3 0.2
HCN 0.002
ECHO 0.01
MeOH 0.5
5-072 Kilburn, K. H., and W. N. McKenzie. 1978. Leukocyte Recruitment
to Airways by Aldehyde-Carbon Combinations that Mimic Cigarette
Smoke. Lab. Invest. 38(2):134-142.
B-ll. Exposure of hamsters to HCHO and acrolein alone and with
carbon particles. Effect only from combination of two and very
high level HCHO. Significant in relation to exhaust mixture,
especially diesel.
5-249 Kilburn, K. H., W. N. McKenzie, and R. J. Thurston. 1976. Effects
of Formaldehyde, as Vapor and Absorbed [sic] on Carbon on Hamster
Airways. Am. Rev. Respir. Dis. 113(4):238.
D—. Appears to be preliminary data on effect of HCHO alone and
with carbon particle. Full study reported in Kilburn and McKenzie
(1978) [5-072].
5-250 Kitchens, J. F., R. E. Casner, G. S. Edwards, W. E. Harward, II,
and B. J. Macri. 1976. Investigation of Selected Potential Envir-
onmental Contaminants: Formaldehyde. PB-256839, National Tech-
nical Information Service, U.S. Dept. of Commerce, Springfield,
VA. 217 pp.
C—. The authors review the potential environmental hazards of
HCHO resulting from its manufacture, use, inadvertent production
from combustion and other sources, and nascent sources such as
paraformaldehyde, trioxane, and hexamethylenetetramine. Early
literature on aldehyde (as HCHO) emissions from mobile sources
reported values for automobiles of 3.3 to 18.7 lb/1,000 gal.
(6,250 lb) gasoline. Diesel engines emit aldehydes at approx.
the same rate and aircraft engines at about half their rate.
This report pointed out that the automobile is the primary source
of outdoor air pollution but that stationary combustion is also a
main source of atmospheric HCHO. Irradiating the hydrocarbon-
nitrogen oxide mixtures in auto exhaust leads to a threefold in-
crease in the HCHO content.
220
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5-433 Koivusalo, M. 1956. Studies on the Metabolism of Methanol and
Formaldehyde in the Animal Organism. Acta. Physiol. Scand.
Suppl. 131.39:1-103.
D—- A review of early literature plus several in vivo and in vitro
experiments on the metabolism of MeOH and HCHO. So much work has
been done in the past 25 years on the topic, it was not used as
a reference.
5-074 Kok, G. L. 1979. Analytical Instrumentation for the Determina-
tion of Formaldehyde in the Ambient Atmosphere. Abstract No. 9.0672
Toxicology Research Projects Directory 4(9):1-75.
C—. Since current methods for determining HCHO in ambient air
at its usual concentrations (~ 10 ppb, which is ~ 0.015 mg/m3)
are not sensitive enough, this research project is developing a
new method based on the chemiluminescent reaction of gallic acid
with HCHO.
5-075 Kopylova, L. S., S. E. Gle'iberman, T. V. Likhtman, T. F. Semenova,
and M. I. Alekseeva. 1980. Safety Study of a Method for Disinfect-
ing Artificial Pulmonary Ventilation Apparatus with Aerosols Con-
taining Formaldehyde. Anesteziol. Reanimatol. No. 2:33-37 (Russ).
D—. Aerosols of a sterilizing mixture containing 20% HCHO, 30%
ethanol, and 50% chaladone-12 (CC12F2) at concentrations 2-74 g/m3
irritated the mucosae of the upper respiratory tract of albino
rats exposed for 45-90 min. Guinea pigs exposed to the mixture
at 2 mg/m3 for 2 mo were sensitized to HCHO. Rats were exposed
to the residual gases (+ NH3) [^0.2 mg/m 3] in the artificial
ventilation apparatus for up to 30 d, but no hematological or mor-
phological changes were observed compared to the controls.
5-147 Krans, E. W. 1935. Effects of Fumes during the Moulding of Cer-
tain Types of Plastics. Ind. Med. Surg. 4:10-11.
D-6. A 29-y-old workman exposed to fumes in the unmolding of art-
icles produced from a formaldehyde-based resin developed a typical
bronchial cough after a few mo. Three years later, he developed
pneumonia, from which he recovered within ~ 3 mo. Krans suggested
that lung infections are likely when the membranes have been har-
dened due to continual HCHO inhalation exposure.
5-343 Krasevac, J. 1972. Influence of Anatomical and Occupational Fac-
tors on Respiratory Allergy of the Upper Respiratory Organs. Med.
Glas. 26(6):138-141 (Serbo-Croat).
D—. Workers in the wood-forming industry were exposed to wood
dust, lye, and nitro dyes as well as HCHO. No exposure levels
given.
221
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5-148 Kratochvil, I. 1971. The Effect of Formaldehyde on the Health
of Workers Employed in the Production of Crease Resistant Ready
Made Dresses. Pr. Lek. 23:374-375. (Cze).
D-5. A description of symptoms following suspected exposure to
ECHO (no measurements were made) for up to 7 y: light conjunctiv-
itis in 72%, rhinopharyngitis in 28%, and chronic bronchitis in
22%. The small number of workers (18) further limits the useful-
ness of this study.
5-252 Kulle, T. J., and G. P. Copper. 1975. Effects of Formaldehyde
and Ozone on the Trigeminal Nasal Sensory System. Arch. Environ.
Health 30(5) -.237-243.
C-ll. Study of nasal sensory response in guinea pigs exposed to
- 0.6 to 3.2 mg/m3 HCHO. Sensory response decreased with HCHO
exposure and only partially recovered after exposure.
5-321 Kuz'menko, N. M., A. I. Buslenko, S. E. Kataeva, T. I. Kravchenko,
and R. S. Asatryan. 1975. Sensitizing Effect of Formaldehyde
During Production of Plastics. Vrach. Delo No. 6:131-134 (Russ).
C-4. Workers were exposed to 0.025-0.22 rag HCHO/m3 and dust and
had direct contact with phenol-HCHO powders. Half had 4-5 y and
half > 5 y of service. 8% had clinical changes in the skin. 22%
were sensitized by skin applications of aqueous HCHO. Some cases
had a general reaction of headaches, weakness, and poor health
2-3 d following HCHO application to the skin. Lack of controls
greatly reduces the usefulness of this study.
5-353 LaBelle, C. W., J. E. Long, and E. E. Christofano. 1955. Syner-
gistic Effects of Aerosols. Particulates as Carriers of Toxic
Vapors. A.M.A. Arch. Ind. Health 11:297-304.
C-6. Acute exposure of mice to HCHO and acrolein in combination
with various aerosols. In general, aerosols increased the toxic-
ity of HCHO and had no effect on acrolein.
5-149 Leonardos, G., D. Kendall, and N. Barnard. 1969. Odor Threshold
Determinations of 53 Odorant Chemicals. J. Air Pollut. Control
Assoc. 19(2): 91-95. Data also appear in A.D. Little, Inc.,
Research on Chemical Odors, Manufacturing Chemists Association,
Washington, D.C. 1968.
A-ll. Definitive paper. The odor recognition thresholds for
various compounds were:
NH3 46.8 ppm
H2S 0.00047 ppm
H2S (from Na2S) 0.0047 ppm
HCHO 1.0 ppm
Acrolein 0.21 ppm
Methanol 100 ppm
222
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5-400 Lin, C., R. N. Anaclerio, D. W. Anthon, L. Z. Fanning, and C. D.
Hollowell. 1979. Indoor/Outdoor Measuremtns of Formaldehyde and
Total Aldehydes. LBL-9397, Conf-790917-10, or EEB-Vent-79-7, Na-
tional Technical Information Service, U.S. Department of Commerce,
Springfield, VA. 14 pp.
C--. Analytical methods are described, and information given in
earlier report of this series is repeated.
5-382 Long, K. 1979. Problems Associated with the Use of Urea-Formal-
dehyde Foam for Residential Use. Department of Energy Publication
No. ORNL/SUB-7559/1, U.S. Department of Energy Information Center
Complex, U.S. Department of Energy, Oak Ridge, Tennessee. 86 pp.
D—. Foams samples were tested in chambers for HCHO emissions.
Increases were found for higher temperatures (7°C vs. 33°C) and
higher humidities (> 80% vs. < 75%). Emission decreased with time
(1-43 d). The entire range of values detected was 0.15-13.69 ppm.
5-078 Loomis, T. A. 1979. Formaldehyde Toxicity. Arch. Pathol. Lab.
Med. 103(7):321-324.
C--. Good basic review of acute actions (primary irritant effect
and the immunogenic-mediated response). The authors suggest that,
based on the insufficient data available, exposure to ^ 0.5 ppm
for several hours is a dose without detectable toxic effects.
5-316 Ludwig, H. 1935. Acute Formaldehyde Bronchiolitis in Workman
Handling Artificial Resin. Samml. Vergiftungsfallen. 6:227-230
(Ger).
C-4. This paper describes the onset and course of the acute bronchi-
olitis (asthma, slimy sputum, etc.) with eczema and fever observed
in a 38-y-old chemically sensitive workman who had been exposed to
urea-HCHO resin powder while unloading drums containing the resin.
The inhaled resin particles may have released HCHO in the lungs and
probably exacerbated the response due to HCHO by producing mechanical
irritation of the bronchi.
5-079 Lyne, A. R. 1979. Inhalation of Formaldehyde Vapor (letter). Br.
Med. J. 2(6204):1589.
C-. The TLV (ceiling) for HCHO in workplace air in Great Britain
is 2 ppm (same as that of the ACGIH in the U.S.A.).
7-071 Makar, A. B., and T. R. Tephly. 1977. Methanol Poisoning VI:
Role of Folic Acid in the Production of Methanol Poisoning in the
Rat. J. Toxicol. Environ. Health. 2(5) -.1201-1209.
D--. Rats placed on a folate-deficient diet for 10-12 wk showed
a marked sensitivity to methanol poisoning. Formate oxidation
was inhibited so that high blood formate and acidosis occurred.
HCHO did not accumulate appreciably, however, in the acidotic rats.
223
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5-080 Makeicheva, N. A. 1978. Data for the Hygienic Standardization
of a Mixture of Furfural, Formaldehyde, Phenol and Acteone, in the
Atmosphere. Gig. Sanit. No. 9:3-7 (Russ).
B-9. Human odor threshold (0.077 mg/m3) and electrocortical condi-
tioned reflex threshold (0.034 mg/m3) for HCHO were determined.
Recommended a one-time MAC of 0.035 mg HCHO/m3 in the atmospheric
air.
5-253 Markova, Z. S., and A. I. Sautin. 1975. Hygienic Evaluation of
Textile Products According to Questionnaire Data. Gig. Sanit.
7:118-119 (Russ).
A-7. The numbers of complaints decreased and their character changed
in 627 of 1,000 salespersons exposed to fabrics finished with HCHO
resins with increasing length of service. The aging factor may
have influenced the results. Complaints independent of length of
service were pains in the heart, mucus discharge, sleep disturbance,
dyspnea, angina, and nausea. Sales persons contacting unfinished
linen fabrics registered far fewer complaints.
5-327 Marshall, F. J. 1980. New Jersey State Department of Health.
Special Epidemiology Project. Health Investigations of Urea-For-
maldehyde Foam December 1977 to January 1980. New Jersey State
Health Department, Trenton, New Jersey. 11 pp.
B-6. Residents of homes with urea-formaldehyde foam installed
1-40 mo earlier complained of odor, mucous membrane and skin irrita-
tion, and problems sleeping. Ambient air levels ranged from 0 to
0.98 mg HCHO/m3.
5-290 Matanoski, G. M. 1980. Epidemiologic Study of Mortality in Pathol-
ogists. From an annotated list of epidemiologic and formaldehyde
monitoring studies prepared by the Epidemiology Branch, Health
Review Division, Environmental Protection Agency.
D—. Very brief description of a current research project. Data
to date show increased mortality due to kidney and liver cancer,
and decreased oral pharyngeal carcinomas. No HCHO levels.
5-082 Matsumura, T., and E. Higuchi. 1979. Concentration of Formaldehyde
in Urban Air. Kogai To Taisaku. 15(12):1547-1550 (Japan).
C-9. Levels of HCHO in air over Tokyo were measured continuously
for 9 y. Reports incident on June 28, 1971, in which HCHO levels
ranged from ~ 10 to ~ 40 ppb with - 12 h above 20 ppb. (Mean value
of 9-y period was 7.1 ppb). Thousands reported eye irritation
that day. The hourly values over the 9 y ranged from 1 to 73 ppb,
with 45.8% of the total hourly measurements £ 5 ppb. Fluctuations
during the day, wk, mo, and year are discussed.
224
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5-083 Matsushima, T., D. Mizoguchi, and R. Soejima. 1978. Experimental
Mouse Pneumonia Following Lung Injury with One Percent Formaldehyde.
Kawasaki Med. J. 4(l):35-46.
C-ll. Study of bacterial pneumonia, caused by Serratia marcescens,
in'albino mice. ECHO was used to injure the respiratory tract to
make the mice susceptible to infection. All mice exposed to 1%
(10,000 ppm) HCHO developed pneumonia when exposed to bacteria
whereas few mice unexposed to HCHO did.
7-074 McMartin, K. E., G. Martin-Amat, P. E. Noker, and T. R. Tephly.
1979. Lack of a Role for Formaldehyde in Methanol Poisoning in
the Monkey. Biochem. Pharmacol. 28(5):645-650.
D—. Formic acid appears to be the major metabolic agent respons-
ible for methanol toxicity in the monkey since formic acid accounts
for the acidosis and the ocular symptoms.
5-085 Mecler, F. J. 1978. Biochemical Changes Seen in Guinea Pigs after
Inhalation of Formaldehyde and Nitrogen Dioxide. Toxicol. Appl.
Pharmacol. 45(1):298-299.
D-4. Repeated dose study of effect of ~ 12.5 mg HCHO/m3 exposure
on lung, liver, and kidney glutathione and glutathione reductase
levels.
5-192 Melekhina, V. P. 1960. Maximum Permissible Concentration of For-
maldehyde in Atmospheric Air. USSR Literature on Air Pollution and
Related Occupational Diseases 3:135-140.
A-9. Same data as Melekhina (1964) [5-193] in a more condensed
form, with some of the experimental details not given, but also
containing some not in the other article.
5-193 Melekhina, V. P. 1964. Hygienic Evaluation of Formaldehyde as
an Atmospheric Air Pollutant. In: USSR Literature on Air Pollu-
tion and Related Occupational Diseases-A Survey. NTIS TT64-11574,
National Technical Information Service, U.S. Department of Commerce,
Springfield, VA. 9 pp.
A-9. Human odor threshold (0.07 mg/m3), light sensitivity threshold
(0.098 mg/m3), and respiratory frequency threshold (< 2.5 mg/m )
were determined. Atmospheric levels near a formalin production
plant were 0.0055-1.5 mg HCHO/m3 and caused some irritation. The
exhaust gases of gasoline engines contained 6-9 mg HCHO/m . Air
samples collected 1-2 m from street during max. evening traffic
contained 2-10 mg HCHO/m,3 avg. 2.6 mg/m3. 24-h samples collected
7-8 m from heavily travelled streets generally contained 0.001-
0.0068 mg HCHO/m3, with a max. of 0.017 mg/m3.
225
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5-155 Miller, B. H., and H. P. Blejer. 1966. Report of an Occupational
Health Study of Formaldehyde Concentrations at Maximes, 400 E.
Colorado Street, Pasadena, California. Report No. S-1838, State
of California Health and Welfare Agency, Dept. of Public Health,
Bureau of Occupational Health, Los Angeles, California. 5 pp.
C-3. HCHO levels in a dress store, due to treated fabrics, ranged
from 1.1 to 4.1 mg/m3. Odor and mild eye irritation reported.
Possible additive effect with smog.
5-086 Misiakiewicz, Z., G. Szulinska, A. Chyba, and E. Czyz. 1977.
Effect of Formaldehyde on the Development of Rats During Long-Terra
Continuous Exposure. Rocz. Panstw. Zakl. Hig. 28(1):99-106 (Pol).
C-7. Two-generation study on effects of 1.0 mg HCHO/m3 on rats
exposed continuously for 8 mo (including during pregnancy) and on
offspring also exposed continuously for 8 mo. No changes in blood
parameters, smaller increase in body wt. increase in second gener-
ation and of relative liver wt. Upper respiratory tract morpholog-
ical changes in exposed rats.
5-156 Morrill, E. E. 1961. Formaldehyde Exposure from Paper Process
Solved by Air Sampling and Current Studies. Air Cond. Heat Vent.
58(7):94-95.
C-4. Workers exposed to 0.9-1.6 ppm HCHO and a trace of NH3 com-
plained of itching eyes, dry and sore throats, disturbed sleep,
and unusual thirst upon first awakening.
5-388 Most, R. S., G. R. Curry, A. V. Sardinas, and J. S. Marks. 1981.
Persistence of Symptoms Associated with Urea-Formaldehyde Foam
Insulation. J. Environ. Health 43(5):251-253.
B-5. A follow-up to the study by Giuletti (1980). Of the house-
holds originally complaining of adverse health effects, 72 still
had symptoms at least as severe as ~ 2 y earlier. The avg. foam-age
in these homes was 2.3 y. No new HCHO measurements were made.
38 no longer had any symptoms, for a variety of reasons. No con-
trol group.
5-158 Murphy, S.D., and C. E. Ulrich. 1964. Multi-Animal Test System
for Measuring Effects of Irritant Gases and Vapors on Respiratory
Function of Guinea Pigs. Am. Ind. Hyg. Assoc. J. 25:28-36.
D-5. Methods development study reporting limited data on effect
of 5.9 and 18.8 mg HCHO/m3 on guinea pig respiration.
5-157 Murphy, S. D., H. V. Davis, and V. L. Zaratzian. 1964. Bio-
chemical Effects in Rats from Irritating Air Contaminants. Toxicol.
Appl. Pharmacol. 6:520-528.
226
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C-8. Study of effect of acrolein (1-4 ppm, 20-81 h) and 18-h, 35
ppra HCHO exposure on rat organ weights and alkaline phosphatase
activity. The same values for concentration x time for acrolein
had different effects, the continuous exposures to the higher con-
centrations causing increased liver wt. and enzyme activity.
5-213 Nagornyi, P. A. 1971. Evaluation of a Combined Effect Exerted
by Several Factors by the Method of Multiple Regression. Farmakol.
Toksikol. 34(3):366-369 (Russ).
D-8. Nagornyi used multiple regression to process the results of
2-h lethality studies in mice with 13 different mixtures of phenol,
toluene, anthracene, and HCHO (resulting from thermo-oxidative
decomposition of a resin based on the constituents). The results
indicated that the mixture was synergistic, the mixture being many
times more toxic than the separate components. By eliminating
HCHO from the mixture, N. calculated that its LC50 in mice would
be 91 mg/m3.
5-254 Nagornyi, P. A. 1973. Combined Action of Several Factors Studied
by Regression Analysis. Gig. Sanit. No. 7:76-82 (Russ).
D-8. Nagornyi (1973) continues the work of Nagornyi (1971) with
tests of 20 new mixtures with and without HCHO. The results here
from its elimination from mixtures indicate that the LCso of HCHO
is 155 mg/m3.
5-091 Nagornyi, P. A. 1977. Hygienic Evaluation of Working Conditions
and Health Status of Workers in the Production of Phenol-Formalde-
hyde Polymers. Gig. Tr. Resp. Mezhved. Sb. No. 13:48-52 (Russ).
C-5. Workers were exposed to phenol and HCHO in concentrations
of 0.9-43 mg/m3 and 0.9-11.5 mg/m3 respectively, as well as to
aerosols of lead (0.006-0.06 mg/m3) and resin dust (2.1-9.0; MAC
= 6 mg/m3) Morbidity among the plant workers, studied for 12 y,
was mostly due to respiratory illnesses, which was significantly
more elevated in years of grippe epidemics and was higher than
the sick rate seen in mine and metal workers. The incidences of
women showing complications of pregnancy, labor, and the post-natal
period were not reported although incidences were reported for
practically every other sickness or symptom.
5-090 Nagornyi, P. A. 1978. Harmful Action of Formaldehyde in Low Con-
centrations (a Review of the Literature). Gig. Tr. Prof. Zabol.
No. 6:42-44 (Russ).
C—. Review of Russian human and animal studies.
5-089 Nagornyi, P. A. 1979. Comparative Evaluation of Some Methods
for Studying the Characteristics of the Combined Effect of Mix-
tures of'Chemical Substances in Critical Tests. Deposited Doc.
VINITI 836-79. 15 pp (Russ).
227
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C-8. Two mathematical treatments were used to process data obtained
from acute exposures of mice to 53 mixtures of phenol plus HCHO.
Pure HCHO at £ 120 mg/m3 and pure phenol at S 75 mg/m3 did not
kill any mice during a 2-h dynamic poisoning test. Calculated
LC50's and LC100's were 505 + 64 and 1,030 mg/m3 for HCHO and 177
+ 11 and 278 mg/m3 for phenol. The mixtures had a synergistic
action being 1.03-2.2x more toxic than equal concentrations of
phenol or HCHO alone.
Nagornyi, P. A., R. K. Mel'nichenko, Zh. A. Sudakova, and L. L.
Filipchenko. 1975. Toxicity and Maximum Permissible Concentra-
tion of a Complex Set of the Neoleucorite (Phenol-Formaldehyde)
Resin Volatile Products. Gig. Tr. Prof. Zabol: No. *:from TOXLINE
abstract.
D—. Animals exposed to 0.75 mg HCH/m3 plus 0.26 mg phenol/m3
and to 0.13 ing HCHO/m3 plus 0.11 mg phenol/m3 showed functional
and morphological changes in the internal organs and systems, some
of which had not been reversed after a 1-mo recovery period. A
• mixture of 0.05 mg HCHO/m3 plus 0.06 mg phenol/m3 produced insig-
nificant, fully reversible changes in the test animals. N. recom-
mends 0.01 mg/m3 each HCHO and phenol as the MACs when present
together in the workplace.
5-092 Nagornyi, P. A., Z. A. Sudakova, and S. M. Shchablenko. 1979.
General Toxic and Allergenic Action of Formaldehyde. Gig. Tr.
Prof. Zabol. No. 1:27-30 (Russ); English translation available
from John Crerar Library, Chicago, Illinois. Order No. 79-127-
93-06J.
B-9. Chronic exposure of albino rats and guinea pigs to 0.5 mg/m3
of ECHO. General health unaffected, some blood and urine para-
meters affected.
5-323 Nefedov, Yu. G., V. P. Savina, N. L. Sokolov, and V. E. Ryzhkova.
1969. Contaminants in the Air Exhaled by Man. Kosm. Biol. Med.
3(5):71-77 (Russ).
D—. Total aldehyde concentrations in exhaled breath of 10
smokers ranged from not detected to 0.09 mg/m3 and in the breath
of 11 nonsmokers, from not detected to 0.12 mg/m3. The people
were healthy and were aged 25 to 35 years.
5-376 Nelson, N. 1979. Written Communication from New York University
Medical Center, Institute of Environmental Medicine to NIOSH,
Rockville, Maryland; cited in NIOSH/OSHA (1980). p. 5.
B-7. Of 100 rats exposed for 6 h/d for 544 d to - 12.5 mg HCHO/m3
along with 10.6 ppm HC1, 25% developed squamous cell carcinomas
of the nasal cavity within 814 d of the 1st exposure. These can-
cers are not typically produced by bis(chloromethyl) ether, the
reaction product of HCHO and HC1.
228
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5-255 Neshkov, N. S., and A. M. Nosko. 1976. Effect of Toxic Components
of Fiber Glass-Reinforced Plastics on the Higher Nervous Activity
and Sexual Function of Males. Gig. Tr. 12:92-94 (Russ).
D-.-. Fifty-eight of 143 workers exposed to phenol, HCHO, aniline,
styrene, and other contaminants at 1.5x the MAC complained of
sexual and pyschoneurological disorders. See the discussion of
this paper by Griesemer et al. (1980), p. 44. They concluded,
"It is impossible to determine how much of the sexual dysfunction
might be attributable to formaldehyde since appropriate control
groups were not included and these workers were exposed to a vari-
ety of toxic chemicals in addition to formaldehyde."
6-124 Newsome, J. R. , V. Norman, and V. L. Zaratzian. 1965. Vapor Phase
Analysis of Cigarette Smoke. Tob. Sci. 9:102-110; or Tobacco 161(4):
24-32.
D—. Levels in tobacco smoke (pg/40 ml puff):
Unfiltered Filtered
methanol 13 10
HCHO 4.1 3.6
acrolein 8.2 7.9
HCN 32 29
H2S 3.4 3.1
NH3 12 13
5-375 NIOSH/OSHA, National Institute for Occupational Safety and Health/
Occupational Safety and Health Administration. 1980. Current Intel-
ligence Bulletin 34. Formaldehyde: Evidence of Carcinogenicity.
National Institute for Occupational Safety and Health, U.S. Depart-
ment of Health and Human Services, and Occupational Safety and Health
Administration, U.S. Department of Labor.
C—. Recent animal work on the carcinogenicity of HCHO is reviewed
with 27 references, some of them unpublished. NIOSH and OSHA recom-
mend that HCHO be handled as a potential occupational carcinogen.
5-318 Nova, M. M., and R. G. Touraine. 1957. Asthma from Formalde-
hyde. Arch. Mai. Prof. 18:293-294 (Fre).
D-7. Case history of a North African man working for 2 y in a
factory handling fatty acids, HCHO, and various other aldehydes.
After 1 y, he had skin eruptions attributed to the acids. After
1-2 mo working in a room with HCHO vapors, he suffered from vomit-
ing, headache, and respiratory difficulty typical of pulmonary
edema lasting ~ 1 wk. In the following days, he developed dyspnea,
and then the characteristics of chronic, recurrent asthma. No
HCHO levels given. Includes a brief review of other occupational
exposures, distinguishing between those causing irritation and
edema, isolated asthma crises after each exposure, and chronic
asthma even after all exposure stops.
229
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5-352 NRC, National Research Council Panel on Vapor-Phase Organic Pol-
lutants. 1976. Vapor-Phase Organic Pollutants. Volatile Hydro-
carbons and Oxidation Products. Printing and Publishing Office,
National Academy of Sciences, Washington, B.C. 417 pp
C—. An authoritative, but brief, review of various aspects of
acrolein and HCHO health effects literature is included in appro-
priate chapters of this book, which was used as a source of addi-
tional pertinent original papers.
5-331 NRC, National Research Council; Committee on Toxicology. 1980.
Formaldehyde - An Assessment of Its Health Effects. AD-A087854,
National Technical Information Service, U.S. Department of Com-
merce, Springfield, VA. 45 pp.
A—. Extensive review of animal and human exposure to HCHO, through
all routes. From the results of 2 controlled human experimental
studies, the Committee predicts that at < 0.25 ppm HCHO, < 20% of
the population will experience minimal to slight eye, nose, and
throat irritation, and recommends "...maintaining formaldehyde at
the lowest practical concentration to minimize adverse effects on
public health." Includes a list of world-wide recommended and
promulgated HCHO exposure limits for outdoor ambient air (0.008-0.1
ppm), indoor air (0.1-0.4 ppm), and occupational air (0.4-10 ppm).
5-093 Okawada, N., I. Mizoguchi, and T. Ishiguro. 1979. Effects of
Photochemical Air Pollution on the Human Eye - Concerning Eye Irri-
tation, Tear Lysozyme and Tear pH. Nagoya J. Med. Sci. 41(1-4):9-20.
A-ll. 0.2 ppm HCHO was the threshold for eye irritation during
300 s exposures. Moderate to severe irritation was caused by 0.5-1.0
ppm.
5-194 Ostapovich, I. K. 1975. Characteristics of the Sensitizing Action
of Sulfur Dioxide and Formaldehyde in Various Regimes of Their
Inhalation. Gig. Sanit. No. 2:9-13 (Russ).
B-6. Rats and guinea pigs were continuously exposed to HCHO at
2, 7, and 15 mg/m3. Guinea pigs were also exposed intermittently
to 7 mg/m3. The time to toxic effects and to allergic effects,
if any, increased with decreasing concentration. At higher levels,
the toxic effects superceded the allergic effects, but allergic
effects appeared sooner at a continuous level of 2 mg HCHO/m3 or
when the avg. concn. was 2.3 mg/m3 due to the intermittency of
the 7 mg/m3 exposures.
5-391 Ostapovich, I. K. 1978. Some Methodical Approaches to Regula-
ting the Content of Chemical Allergens in the Air. Gig. Aspekty
Okhrany Okruzh. Sredy, (Moskva) No. 6:84-85 (Russ).
230
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B-6. The experimental results presumably of Ostapovich (1975)
[5-199] (although another, lower concentration--0.5 mg HCHO/m3--
is mentioned here) with respect to the allergic effects on rats
and guinea pigs gave a straight line on a log scale grid. By ex-
trapolation and the use of a nomogram (no figures given), Ostapo-
vich calculated an inactive concentration for HCHO of 0.003 mg/m3.
5-256 Otte, W. , and K. Kroepelin. 1973. Histological Changes in Guinea
Pig Lungs after Formaldehyde Inhalation and x-Radiation and the
Effect of Dexamethasone 21-isonicotinat.e Thereon. Arzneim.-Forsch.
23(3):420-424 (Ger).
D-6. Study of guinea pigs exposed to HCHO and x-radiation to irri-
tate the lungs. Dexamethasone 21-isonicotinate reduced inflamma-
tion of lungs
5-257 Ozhiganova, V. N. , L. A. Dueva, and N. G. Popova. 1976. Clinical
Picture and Diagnosis of Occupational Bronchial Asthma Caused by
Formaldehyde-Containing Polymers. Gig. Tr. Prof. Zabol. No. 11:17-
20 (Russ).
C-10. The incidence of bronchial asthma, 34 of 972, in workers
engaged in the production and processing of HCHO-containing poly-
mers, was no higher than that in the general population. Various
diagnostic methods differentiated those whose bronchial asthma
was and was not due to HCHO. Most appeared to be sensitized in
varying degrees to HCHO as were those showing disorders of bron-
chial potency (9). All should be removed from HCHO contact.
5-377 Ozhiganova, V. N., I. S. Ivanova, and L. A. Deuva. 1977. Bronchial
Asthma in Radio Equipment Assemblers. Sov. Med. (Moscow) No. 4:
139-141 (Russ).
C-8. Bronchial asthma in radio equipment assemblers was usually
due to the occupational exposure to HCHO (no concentration deter-
mined) , a thermal destruction product of the rosin used in the
lead soldering process. Methods are described to distinguish occu-
pational from nonoccupational bronchial asthma.
7-076 Palese, M. , and T. R. Tephly. 1975. Metabolism of Formate in
the Rat. J. Toxicol. Environ. Health 1(1):13-24.
D—. The folate-dependent one-carbon pool plays a major role in
the metabolism of formate to C02. Folate-def icient rats rely on
the catalase-peroxidative system.
5-314 Paliard, F., L. Roche, C. Exbrayat, and E. Sprunck. 1949. Chronic
Asthma Due to Formaldehyde. Arch. Mai. Prof. 10:528-530 (Fre).
D—. Case history of a man developing severe asthma-like symptoms
after working 25 y in a tannery, which included continuous exposure
to formaldehyde vapors. Irritation of the upper airways and con-
junctiva, coughing, tramitis, loss of sense of smell, and dyspnea
231
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and cyanosis even at rest were observed. Some symptoms were not
characteristic of asthma, and the authors attribute the problems
to formaldehyde. Other facts, such as an apparent lack of sensi-
tivity to HCHO, argue against this. No levels were given.
5-258 Pankova, V. B. 1976. Cytological Profile of the Lower Nasal
Cavity Mucosa Under the Effect of Different Chemical Allergens.
Deposited Doc. No. VINITI 2969-76:20-22 (Russ).
D—. Formalin was directly applied to the mucosa of the lower
nasal cavity.
5-259 Patterson, R. M., M. I. Bornstein, and E. Garshick. 1976. Assess-
ment of Formaldehyde as a Potential Air Pollution Problem. PB-258360,
National Technical Information Service, Springfield, VA. 29 pp.
D—. The document contains a 5-page uncritical review of health
effects literature on HCHO.
5-260 Pavlenko, S. M., and V. A. Guseva. 1973a. Dynamics of the De-
velopment of Adaptive Reactions Under the Long-Terra Effect of In-
dustrial Poisons Entering an Organism by Different Means. Itogi
Nauki Tekh. Farmakol., Khimioter. Sredstva, Toksikol., Probl.
Toksikol. 5:110-119 (Russ).
D—. The elaborate set of tests performed on rats exposed to low
levels of HCHO, C2H5OH, CH3OH, CC14, or cyclohexanone given by
inhalation and/or by mouth does not distinguish the effects caused
by each poison, i.e., they each elicit the same responses at nearly
the same times.
7-042 Pavlenko, S. M., and V. A. Guseva. 1973b. Development of Adap-
tive Shifts after Complex Administrations of Nonelectrolyte Poisons.
Gig. Sanit. No. 1:15-20 (Russ).
D—. This is a slightly different version of Pavlenko and Guseva
(1973a) [5-260].
5-261 Pavlenko, S. M., T. V. Yudina, and V. A. Guseva. 1975. Methodolo-
gical Approaches to an Evaluation of Latent Reactions of Certain
Regulatory Systems of the Body in the Case of Different Ways of
Intake of Toxic Substances. Gig. Sanit. No. 10:55-60 (Russ).
D—. Another abstruse study much like Pavlenko and Guseva (1973a)
[5-260], wherein the effects of oral or inhaled HCHO are not espe-
cially different from those seen from low levels of C2H5OH, CH3OH,
CC14, or cyclohexanone.
232
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5-399 Pendergast, H. 1979. Formaldehyde. A Basic Building Block of
Industry. Formaldehyde Institute, Scarsdale, New York. 13pp.
C—. This brief report summarizes work on HCHO recently done or
begun by OSHA, NIOSH, EPA, the Dept. of Housing and Development,
CPSC, and DOE and summarizes that "no valid scientific evidence
was found to suggest that HCHO poses significant risk to human
health or the environment." The report also describes the com-
mittees of the Formaldehyde Institute (Medical, Technical, Regu-
latory Action, and Information Resources and Communications) as
well as the initiation of the HCHO inhalation carcinogenicity test-
ing with rats and mice by the Chemical Industry Institute of Toxi-
cology (CUT).
5-095 Plunkett, E. R., and T. Barbela. 1977. Are Embalmer's at Risk?
Am. J. Hyg. 38(l):6l-62.
C-4. Embalmers exposed to unknown levels of HCHO reported eye,
skin, and upper respiratory tract irritation. Some had acute bron-
chitis and others chronic bronchitis. Those without bronchitis
had longer work histories. No control group.
5-096 Pod"yacheva, N. A. 1977. Generally Toxic Effect of Low Concentra-
tions of Phenol and Formaldehyde During their Separate and Combined
Effect on Experimental Animals. Gig. Aspekty Okhr. Zdorov'ya Nasel-
eniya. p. 131 (Russ).
C-9. Exposing female rats to either HCHO or phenol at 0.5 mg/m3
for 4 h/d for 4 mo increased the activities of cholinesterase,
oxidase, and glutaminoaspartic aminotransferase and lowered the
nucleic acid and total protein content of the serum while increas-
ing SGOT and lowering the activities of cholinesterase and aspartic
transferase in liver homogenates. These changes apparent within
2-3.4 mo, but when a mixture of 0.25 mg/m3 of each compound was
used, the changes appeared within 15-30 d.
5-159 Porter, J. A. H. 1975. Acute Respiratory Distress Following For-
malin Inhalation. Lancet 2(7935):603-604.
C-8. A 27-y-old neurology resident during his second stint of
preparing brain specimens using formalin noted irritation of the
conjunctiva and nasal mucosa and became progressively dyspneic
even at rest within 15 h after the exposure to a "high concentra-
tion of formaldehyde vapor." Chest x-ray showed increased inter-
stitial markings with early edema. The clinical picture was that
of acute pneumonitis that required treatment by aminophylline and
steroids before recovery by 5 wk after the onset. The reaction
may have been due to hypersensitivity, since the man experienced
allergic rhinitis on exposure to common inhalation allergens.
5-262 Prave, V. E., M. M. Prupis, L. G. Cherniakova, B. L. Litvak, and
A. P. Beliaeva. 1972. Health Evaluation of the Atmosphere in
Working Premises of Disinfection Chambers. Gig. Sanit. 37(l):96-98
(Russ).
233
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C-7. The subjects were exposed only to HCHO at concentrations of
0.33-42.0 mg/m3. The incidences of various diseases of the respir-
atory system, skin, nervous system, liver, etc., as well as of
cholinesterase inhibition are given but not compared to exposure
levels or to the corresponding incidences among a control group.
5-404 Prigoda, Yu. G. 1973. Hygienic Characteristics of Air Conditions
on Some Types of Automobile Highways. Aktual. Vopr. Gig. Naselennykh
Mest, Mater. Vses. Konf. Molodykh Uchenykh. pp. 108-110 (Russ);
Chem. Abstr. 1975. 82:076650a.
C—. HCHO concentrations along two USSR highways were 0.1-1.2
mg/m3, whereas at a distance of 10-15 m from the highways the val-
ues were 0.005-0.15 mg/m3.
6-115 Protsenko, G. A., V. I. Danilov, A. N. Timchenko, A. V. Nenartovich,
V. I. Trubilko, and V. A. Sauchenkov. 1973. Working Conditions
When Metals to which Primer has been Applied are Welded Evaluated
from the Health and Hygiene Aspect. Avt. Svarka 26(2):65-68.
D--. Levels of many gases were determined under several different
welding conditions: acrolein, 0.11-1.04 mg/m3; and HCHO, 0.31-0.83
mg/m3.
5-098 Pruett, J. J., H. Scheuenstuhl, D. Michaeli, and Z. Nevo. 1980.
The Incorporation and Localization of Aldehydes (Highly Reactive
Cigarette Smoke Components) into Cellular Fractions of Cultured
Human Lung Cells. Arch. Environ. Health 35(1):15-20.
C—. Human fetal lung fibroblasts were incubated with trace amounts
of 14C-labeled HCHO for 10 min. The HCHO migrated into the nucleus,
where the RNA fraction had the highest amount of HCHO.
5-012 Pushkina, N. N. , V. A. Gofmekler, and G. N. Klevtsova. 1968.
Changes in Content of Ascorbic Acid and Nucleic Acids Produced
by Benzene and Formaldehyde. Bull. Exp. Biol. Med. 66:868-870.
D-6. Study of exposure of 0.012 and 1.0 mg/m3 of HCHO on female
rats and their fetuses caused decreased ascorbic acid levels.
5-195 Renzetti, N., and R. Bryan. 1961. Atmospheric Sampling for Alde-
hydes and Eye Irritation in Los Angeles Smog. J. Air Pollut. Con-
trol Assoc. ll(9):421-424 and 427.
D-10. An attempt at correlating eye irritation and aldehyde levels
in smog. Total aldehydes ranged from 0.02 to 0.40 ppm; formaldehyde
from 0 to 0.13 ppm. Good correlation was found for a log-probit
relationship with total aldehydes, but the fit for HCHO wasn't as
good.
234
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5-196 Renzetti, N. , and E. A. Schuck. 1961. Preliminary Observations
on the Relationship Between Eye Irritation in Synthetic Systems and
in the Atmosphere. J. Air Pollut. Control Assoc. 11(3):121-124.
C-8. Moderate to very severe (lacrimation in > 50% of the subjects)
eye irritation was caused by 5-min exposure to 3 ppm HCHO. Compar-
isons are made to irritation caused by irradiated hydrocarbon/N02
mixtures and to outdoor smog conditions, in an attempt to show
that HCHO and acrolein are the primary irritants in smog.
5-099 Rosenkranz, H. S. 1972. Formaldehyde as a Possible Carcinogen.
Bull. Environ. Contain. Toxicol. 8(4) :242-244.
C-2. In addition to the fact that formaldehyde has been known,
from literature citations, to be a mutagen, the author now believes
it to be a potential carcinogen. He used a microbial assay method
with an E. coli strain that lacks DNA polymerase (involved in DNA
repair) ."After the addition of an unknown amount of HCHO, to cul-
tures grown in petri dishes, the zone of growth inhibition was 62
mm vs. 59 mm for the normal strain. Article lacks details, numbers
of tests, ranges of results, and control information.
5-335 Rumack, B. H. 1978. Position Paper: Urea-Formaldehyde Foam.
Rocky Mountain Poison Center, Denver, Colorado. 30 pp.
C—. This paper reviews toxicity problems, and consumer complaints
related to urea-HCHO foam insulation as well as current standards
and criteria for HCHO in workplace and ambient air. Other domestic
sources of HCHO are enumerated: particle board, chipboard, wood
panels, curtain and rug backings, auto exhaust, wood preservatives,
smoking, fireplaces, possibly gas furnaces and appliances, glues,
and permanent press fabrics. The Netherlands has promulgated a
standard for homes insulated with urea-HCHO foam products -- i
0.5 ppm at 2 wk after foaming and 0.02 ppm after 2 mo. •
5-344 Ryzhik, L. A. 1970. Hygienic Characterization of Foliated
Hetinax Production. Gig. Tr. Prof. Zabol. 14(5):12-15 (Russ).
D—. Workers were exposed to cresol and HCHO in concentrations
less than the maximum allowable concentration (MAC) as well as
acetone (S 20 x > MAC), NH3 (^ 3 mg/m3; MAC = 20 mg/m3), and phenol
(^ 3 x > MAC). The health of the workers was not discussed.
5-160 Sachs, 0. 1921. On Acute Dermatitis Caused by Vapors of Carbolic
Acid, Formaldehyde and Ammonia in the Production of Synthetic Resins.
Wien. Klin. Wochenschr. No. 29:356 (Ger).
D-3. Case reports of 8 workers with acute dermatitis of the face,
forearms, and hands. Some conjunctivitis, bronchitis, and irrita-
tion of the nose. Problems are attributed to carbolic acid, NH3,
and HCHO, 3 of several compounds used in production. No air samp-
ling done, or concentrations reported.
235
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5-264 Saindelle, A., F. Ruff, N. Flavian, and J. L. Parrot. 1968. His-
tamine Release by Short-Chain Aldehydes. C. R. Hebd. Seances Acad.
Sci., Ser. D. 266(2):139-140 (Fre).
D-3. Guinea pig lung fragments were incubated for 15 min in a
solution containing 0.1 mg HCHO/mL, and 0-2.3 Mg histamine/g was
released. Other short-chain aldehydes were studied, with acetal-
dehyde being the most active in causing the release of histamine.
5-265 Sakula, A. 1975. Formalin Asthma in Hospital Laboratory Staff.
Lancet 2:816.
D-6. Formalin vapor caused bronchial asthma in a 57-y-old hospital
laboratory technician who prepared pathological specimens and hist-
ological sections.
5-161 Salem, H., and H. Cullumbine. 1960. Inhalation Toxicities
of Some Aldehydes. Toxicol. Appl. Pharmacol. 2:183-187.
C-6. Exposure of mice, guinea pigs and rabbits to HCHO and acrolein
in both vapor and aerosol form for up to 10 h HCHO concentrations
of 19-20 mg/m3 caused few deaths during exposure but a number of
the animals died later. Acrolein at mean concentration of 4,624
to 5,225 mg/m3 was lethal to all the animals in < 1 h. Mice were
more susceptible to both HCHO and acrolein than other animals.
5-389 Samitova, R. Sh., Yu. P. Gracheva, and F. M. Gaynutdinov. 1973.
Physiological-Hygienic Evaluation of Work Conditions and Gynecol-
ogical Morbidity of Polishers of Formalin Departments of Fur Pro-
duction. Nauchn. Trudy Kazansk. Med. In-ta. 42:37-42 (Russ).
C-10. By the end of the shifts, workers exposed to 2.0-7.5 mg
HCHO/m3, dust, methanol, ethanol, and formic acid (the last 3 at
< MAC's) had complaints of vertigo, stimulation, noise in the eata,
and decreased endurance. Small increases in some gynecological
complaints were reported.
5-266 Sanotskii, I. V., V. N. Fomenko, G. A. Sheveleva, L. S. Sal'nikova,
M. V. Nakoryakova, and T. E. Pavlova. 1976. A Study on the Effects
of Pregnancy on the Sensitivity of Animals to Chemical Agents.
Gig. Tr. Prof. Zabol No. 1:25-28 (Russ); English translation avail-
able from John Crerar Library, Chicago, Illinois. Order No.
80-11975-06J.
B-8. Study of the effect of pregnancy on the sensitivity of rats
to HCHO. Levels of 0.4 to 6 mg/m3 effected blood hemoglobin and
liver and kidney functioning.
5-100 Sanotskii, I. V., V. N. Fomenko, L. S. Sal'nikova, and G. A.
Sheveleva. 1977. Some Problems Related to Experimental Research
of the Embryotropic Action of Industrial Chemical Compounds. Gig.
Tr. Prof. Zabol. No. 2:27-30 (Russ).
236
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C—. A review without full citations of work done at the Institute
of Industrial Hygiene and Occupational Diseases of the Academy of
Medical Science of the USSR. It is reported here without attribu-
tion that ECHO at levels up to and at the MAC were without effect
on. human embryogenesis of pregnancy whether exposure was at the
1st or 2nd month or the entire course.
5-312 Sardinas, A. V., R. S. Most, M. A. Giulietti, and P. Honchar.
1979. Health Effects Associated with Urea-Formaldehyde Foam In-
sulation in Connecticut. J. Environ. Health 41:270-272.
C-6. A preliminary report (of 69 complaints) of the full study
discussed in Giulietti (1980) [5-295a]. Attempted to show dif-
ferences in symptoms between those exposed to < 0.5 ppm and those
exposed to 0.5-10 ppm: skin and miscellaneous symptoms were higher
in the less exposed group, eye irritation and headache were higher
in the high exposure group, and nose, throat, lung, and gastroin-
testinal tract irritation were about equal. These ratios changed
in the full report, with the high exposure group reporting slightly
higher symptoms in all categories.
5-162 Saury, A., M. P. Ravault, and V. Vincent. 1965. Optic Atrophy
Due to Exposure to Formol Vapors. Bull. Med. Tox. Med. Leg. 8:
466-469 (Fre).
D—. Case history of a man suffering from optical neuritis, in-
cluding blurriness and loss of vision. Because of the lack of
any other findings, the authors attribute it to the man's exposure
on the job while handling fabrics treated with a formaldehyde-
containing mixture to prevent wrinkling. Mo levels are given and
the cause-effect relationship is not definitely established.
7-501 Schneck, S. A. 1979. Methyl Aclohol. In: Handbook of Clinical
Neurology, Vol. 36, Intoxications of the Nervous System, Part I.
P. J. Vinken, and C. W. Bruyn, Eds. Elsevier/North-Holland, Inc.
New York, New York. pp. 351-360.
D—. A good review of methanol poisoning and the presumed role of
HCHO.
5-013 Schoenberg, J. B. , and C. A. Mitchell. 1975. Airway Disease
Caused by Phenolic (Phenol-Formaldehyde) Resin Exposure. Arch.
Environ. Health 30:574-577.
C-9. Employees were exposed to phenol (7-10 mg/m3) and HCHO (0.5-
16.3 mg/m3). A high proportion reported acute respiratory symptoms,
but only small decreases in pulmonary functions during the work
week were found. Employment for > 5 y caused lower pulmonary func-
tions than shorter employment but those employees also had greater
cigarette consumption (in pack-years).
237
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5-101 Schreiber, H., M. Bibbo, G. L. Wied, G. Saccomanno, and P. Nettesheim.
1979. Bronchial Metaplasia as a Benign or Premalignant Lesion.
I. Cytologic and Ultrastructural Discrimination Between Acute
Carcinogen Effects and Toxin-Induced Changes. Acta Cytol. (Baltimore)
23(6):496-503.
C-8. Study of cytologic and histologic changes in tracheobron-
chial epithelium of hamster exposure to 312.5 mg/m3. HCHO effects
compared to changes in hamsters exposed to known carcinogens.
Results indicated that HCHO is non-carcinogenic.
5-328 Schuck, E. A., and G. J. Doyle. 1959. Photooxidation of Hydro-
carbons in Mixtures Containing Oxides of Nitrogen and Sulfur Dio-
xide. Report No. 29. Air Pollution Foundation. San Marino,
California, pp. 41-46.
C-8. Same data as Schuck and Renzetti (1960) [5-307].
5-307 Schuck, E., and N. Renzetti. 1960. Eye Irritants Formed During
Photooxidation of Hydrocarbons in the Presence of Oxides of Nitro-
gen. Air Pollut. Control Assoc. J. 10:389-392.
C-8. Moderate to severe eye irritation was caused by 5-min ex-
posure to 1.5 ppm acrolein or 4 ppm HCHO. These 2 irritants ac-
counted for most of the observed eye irritation caused by the prod-
ucts of the photooxidation of hydrocarbons with oxides of nitrogen.
3 ppm propionaldehyde and 10 ppm acetaldehyde caused no eye irri-
tation.
5-163 Schuck, E. A., E. R. Stephens, and J. T. Middleton. 1966. Eye
Irritation Response at Low Concentrations of Irritants. Arch.
Environ. Health 13:570-575.
D-10. Exposure to the products of the irradiation of hydrocarbons/
N02 mixtures caused eye irritation. Good correlation was seen
with HCHO when it was present at £ 0.3 ppm, but not when it was <
0.3 ppm.
5-418 Selikoff, I. J., and E. C. Hammond. 1981. Carcinogenicity of
Formaldehyde. Final Report. Report to the American Cancer Society
by the Environmental Cancer Information Unit, Environmental Sciences
Laboratory, Mt. Sinai School of Medicine, City University of New
York, New York, New York.
C—. This 9-page report is bound with full copies of Griesemer
et al. (1980) [Report of the Federal Panel on Formaldehyde] and
NIOSH/OSHA (1980) [Formaldehyde: Evidence of Carcinogenicity].
In an earlier report the authors had raised the question of whether
the nasal cancers seen in the CUT study (Swenberg et al., 1980)
were due to the combined effects of a viral infection and HCHO.
In this report, they decide on the basis of the 24-mo results that
238
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"HCHO exposure and not the viral infection appears to be the cru-
cial factor in development of nasal carcinomas in the CUT study."
They recommend that since "cancer occurred in animals at levels
not unlike those which can be found in some human exposures that
"effective controls should be initiated to reduce or eliminate
human exposures to HCHO."
5-198 Sgibnev, A. K. 1968. Influence of Small Concentrations of Formal-
dehyde Vapors on the Human Organism. Gig. Tr. Prof. Zabol. 12(7):
20-25 (Russ); English translation available from John Crerar Li-
brary, Chicago, Illinois. Order No. 74-13624-06J.
A-7. Exposure of humans to 0.3-0.4 or 1.0 mg/m3 for 10 rain caused
slight respiratory and skin changes at the lower level and more
extensive changes at the upper level. 1 mg/m3 is recommended as
the maximum permissible concentration.
5-014 Shafaiziev, U., and G. Shipovskikh. 1972. Working Conditions
and Health of Workers Employed in Processing of Plastic Resins in
Uzbekistan. Vop. Sanit. Gig. Usloviyakh Zharkaogo Klimata Usb.
1972:136-138 (Russ).
C-6. Workers were exposed to ^ 2-15.6 mg phenol/m3 and 0.6-3.1
mg HCHO/m3 as well as phenol-HCHO resin dust. Disturbances were
seen more often in the pressmen, who were exposed to the higher
resin dust concentrations, than in the polishers. Disturbances
observed included chronic rhinopharyngitis (5 pressmen), skin ir-
ritations, stabbing-constricting pain in the heart region,^muffling
of heart tones at the tip, a tendency toward hypotonia (50%), gas-
tritis and colitis, liver function disturbances, and nervous system
disturbances in 24 of the 30 pressmen.
5-337 Sheveleva, G. A. 1971. Specific Action of Formaldehyde on the
Embryogeny and Progeny of White Rats. Toksikol. Nov. Prom. Khim.
Veschestv. 12:78-86; English translation available from John Crerar
Library, Chicago, Illinois. Order No. 73-13539-06P.
B-ll. Study of the effect of 0.5 to 5 mg HCHO/m3 on pregnant rats
and development and health of progeny.
5-164 Shipkovitz, H. D., 1968. Formaldehyde Vapor Emissions in the
Permanent-Press Fabrics Industry. Report No. TR-52, Environmental
Control Administration, Consumer Protection and Environmental
Health Service, Public Health Service, U.S. Department of Health,
Education and Welfare, Cincinnati, Ohio. 20 pp.
C-5 Formaldehyde concentrations during cutting, sewing, pressing,
and storing of permanent press fabrics ranged in eight plants from
not detected to 2.7 ppm. In two plants with good ventilation and
two with fair ventilation, 5-15% of the employees showed respiratory
and other complaints. In the four other plants with fair ventila-
tion, such complaints came from > 15% of the employees.
239
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5-018 Shumilina, A. V. 1975. Menstrual and Reproductive Functions in
Workers with Occupational Exposure to Formaldehyde. Gig. Tr. Prof.
Zabol. 75(12):18-21 (Russ); English translation available from
John Crerar Library, Chicago, Illinois. Order No. 78-12467-06J.
B-8. Chronic exposure to 1.5-4.5 mg HCHO/m3 or to 0.05-0.70 mg
HCHO/ m3 caused increased numbers of menstrual problems, genital
diseases, problems during pregnancy and birth, and lower neonatal
weights.
5-345 Sidorenko, G. I., F. F. Lampert, I. A. Pinigina, V. A. Klebanova,
V. P. Osintseva, and A. F. Nazarenko. 1972. Experimental Sub-
stantiation of Air Sanitation Measures in Gas Supplied Apartments.
Gig. Sanit. 37 (7)-.24-28 (Russ).
D-8. Male rats exposed for 3 or 6 h/d for 125 d to 0.043 mg HCHO/
m3, 0.07 mg C6H6/n»3, 0.44 mg N02/m3, and 0.60 mg NO/m3 (products
of incomplete combustion of gas from a cooking stove) showed
absence of weight gain, leukocytosis, increase in carboxyhemoglobin,
CNS disturbance, and changes in the parenchymatous organs that
were probably due to chronic CO poisoning. The emphysematous
changes with atelectasis in the lungs were probably due to poisoning
by the N oxides.
5-270 Sidorov, K. K. 1971. Letter to the Editor: Effect of Low Con-
centrations of Formaldehyde on the Organism. Hyg. Sanit. 36(12):
435.
D—. Corrections of the official standards given in the text of
Fel'dman and Bonashevskaya (1971) [5-048]. The maximum permissible
concentration of HCHO in a work zone was 0.5 mg/m3.
5-178 Sim, V. M., and R. E. Pattle. 1957. Effect of Possible Smog Ir-
ritants on Human Subjects. J. Am. Med. Assoc. 165:1908-1913.
B-9. A study of acute (S 30 min) human exposure to several com-
pounds of interest: HCHO at 17.3 mg/m3 was slightly irritating;
acrolein at 1.88 or 2.80 mg/m3 was extremely irritating; acetalde-
hyde at 240 mg/m3 was mildly irritating; and propionaldehyde at
324 mg/m3 was mildly irritating. A more complex study of H2S04
exposure was done.
5-165 Skog, E. 1950. A Toxicological Investigation of Lower Aliphatic
Aldehydes—I. Toxicity of Formaldehyde, Acetaldehyde, Propional-
dehyde, and Butyraldehyde, as well as of Acrolein and Crotonalde-
hyde. Acta Pharmacol. Toxicol. 6:299-318.
B-10. Acute exposure of rats to 600-1,700 mg HCHO/m3 led to an
LDso of 1,000 mg/m3. Rats exposed to 100 to 700 mg acrolein/m3
showed an LDso of 300 mg/m3. This is a solid acute, lethal dose
study.
240
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5-392 Skvortsova, R. I., V. M. Puznyakovskii, and S. A. Rudakov. 1980.
State of Some Metabolic Functions in Workers Manufacturing Phenol-
Formaldehyde Resins. Gig. Sanit. No. 8:69-71 (Russ).
C—. This appears to be a fairly good occupational study, but
because the end point studied (lowering of the acetylation of
sulfanilaraide by CoA) is not clearly a toxic effect, it was not
rated by a pharmacologist or epidemiologist or tabulated. The
authors ascribe the effect to phenol's blocking of the SH
group of CoA (the site where the Ac group is attached), but the
blocking action could arguably be attributed more to HCHO on the
basis of their ordinary chemistry. Interestingly, the lowering of
acetylation activity was most marked in 25-30-y-old female instrument
workers (female "apparatchiks" were the most sensitive of phenol-HCHO
resin workers in the study by Ishchenko and Pushkina, 1978 [5-067])
and press foremen.
5-272 Smirnova, N. A., and N. P. Granik. 1971. Remote After-Effects
of Acute Occupational Lesions of the Respiratory Tract Caused by
Irritating Gases. Gig. Tr. Prof. Zabol. 15(11):16-19 (Russ).
D—. Nothing specific is related about the four workers who were
acutely poisoned by HCHO. Pneumosclerosis, bronchitis, and emphysema
were seen as late effects in 35 of the 88 chemical plant workers,
who were variously exposed to Cl2-(46), HC1 (2), COC12 (9), NO
(11), Ni(CO)4 (14), HCHO (4), and NH3 (2).
5-104 Sprince, H., C. M. Parker, and G. G. Smith. 1979. Comparison of
Protection by L-Ascorbic Acid, L-Cysteine, and Adrenergic-Blocking
Agents against Acetaldehyde, Acrolein, and Formaldehyde Toxicity:
Implications in Smoking. Agents Actions 9(4):407-4l4.
D-12. Rats were orally intubated with - 90% of the 24-h LD50 of
HCHO or acrolein. Both groups gradually showed lethargy, tremors,
respiratory distress, and death, which suggested that the primary
toxic effect even through oral dosing was on the respiratory sys-
tem. Lung congestion and pulmonary edema at death, are mentioned
but there is no description of histopathology or even gross necropsy.
5-306 Stephens, E., E. Barley, 0. Taylor, and C. Scott. 1961. Photo-
chemical Reaction Products in Air Pollution. Int. J. Air Water
Pollut. 4:79-100.
A-9. Eye exposure only to 1-5 ppm HCHO for 5 or 12 rain caused
moderate to severe irritation, the percentage of people affected
varying with concentration, exposure time/ and exposure conditions.
5-286 Stofft, E., I. Nitsche, and A. Mayet. 1971. Formaldehyde Content
of the Air in Dissecting Rooms. Zentralbl. Bakteriol. Parasitenkd.
Infektionskr. Hyg. Erste. Abt. Orig. Reihe. B. Hyg. Praev. Med.
155(2) -.131-141 (Ger).
241
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D—. In dissection rooms, concentrations of HCHO over the fixed
dead bodies were as high as 20 mg/m3. Concentrations of S 10-100
mg/m3 were typical in the area where the dead bodies were stored
in conserving tubs.
5-338 Stupfel, M. 1976. Recent Advances in Investigations of Toxicity
of Automotive Exhaust. Environ. Health Perspect. 17:253-285.
D—. Summary of levels of various components of exhaust: HCHO
in gasoline exhaust (10-300 ppm), HCHO in diesel exhaust (5-30
ppm), HCHO in urban polluted air (0.05-0.12 ppm), HCHO in tobacco
smoke (120 ppm), acrolein in urban polluted air (0.01 ppm), acrolein
in tobacco smoke (60 ppm), and HCN in tobacco smoke (300-1,500
ppm). Extensive review of epidemiology and human and animal ex-
perimental results of exposure to exhaust.
5-405 Styazhkin, V. M., G. M. Kuzuetsova, and T. P. Soldatchenkova.
1976. Hygienic-Chemical Study of an Experimental Mobile Home
Made with the Extensive Use of Plastics. Gig. Aspekty Okhr.
Okruzhayushchei Sredy. pp. 62-64 (Russ); Chem. Abstr. 1978.
89:203319w.
C—. The interior air concentrations of HCHO, NH3, phthalate
esters, and phenol (0.3, 1.1, 3.8, and 0.03 mg/m3, respectively)
in this mobile home made it unsuitable for human habitation.
5-106 Suga, K., S. Aoki, Y. Yasufuku, J. Nishikawa, and K. Yoshikawa.
1978. Survey of Ambient Air in Ohtsu Area in 1976. Shigakenritsu
Eisei Kenkyusho Ho 12:162-173 (Japan).
C—. Ambient air samples in October 1976 from the Ohtsu area of
Japan contained 0.009-0.018 mg HCHO/m3, 0.0085 mg NH3/m3, and
0.0007-0.0015 og H2S/m3.
5-362 Swenberg, J. A., W. D. Kerns, R. I. Mitchell, E. J. Gralla, and
K. L. Pavkov. 1980. Induction of Squamous Cell Carcinoma of the
Rat Masai Cavity by Inhalation Exposure to Formaldehyde Vapor.
Cancer Res. 40:3398-3402.
B-15. Rats were exposed to 2.1, 5.6, and 14.1 ppm HCHO for 6 h/d,
5 d/wk for 18 mo of a 24-mo study. Exposure to 14.1 ppm for up
to 18 mo resulted in nasal cavity carcinomas. No tumors at lower
levels. This is the experiment sponsored by the Chemical Industry
Institute of Toxicology.
5-351 Taft, R. M. 1980. Hazard Evaluation and Technical Assistance
Report Mo. TA 78-46, Potomac Village Shopping Center, Potomac,
Maryland. PB80-150717, National Technical Information Service,
U. S. Department of Commerce, Springfield, VA. 17 pp.
242
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C-2. The tenants, employees, and customers of the shopping center
complained of eye, nose, and throat irritation (no skin irritation)
during 7 mo. Formaldehyde levels averaged ~ 1.4 mg/m3, and probably
emanated from urea-formaldehyde foam insulation, which had been
removed 2 wk before.
5-215 Takhirov, M. T. 1974. Combined Action of Six Air Pollutants on
the Human Body. Gig. Sanit. No. 5:100-102 (Russ); Chem. Abstr.
1974. 81:110854.
B-8. The odor threshold of HCHO was 0.065 mg/m3. In studies of
mixtures of HCHO, AcOH, Ac20, HC1, acetone, and phenol, simple
summation effect was observed at low concentration, suggesting
that during their simultaneous presence their total concentra-
tions expressed in fractions of existing standards of each iso-
lated substance should not exceed 1.
7-058 Teplyakov, S. D., V. A. Sokolova, G. G. Antipova, L. N. Zimont
and R. A. Druz. 1980. Complex Assessment of Working Conditions
in the Use of Cold-Setting Mixes with Urea-Furan Binder BS-40.
Liteinoe Proizvod. No. 6:27-28 (Russ).
D-9. Workers were exposed to 0.1-1.2 mg HCHO/m3, dust, and benzo-
pyrene. Clinical examination in 1976 did not reveal any expressed
pathological changes. A study published earlier of presumably
the same workers by Chernomorskii et al. (1978) found respiratory
pathology and functional changes. That study found slightly higher
HCHO levels (2 mg/m3), dust (lOx the MAC), phenol, methanol, alde-
hydes, cyanides, and CO.
5-326 Thun, M. J., M. F. Lakat, and R. Altman. 1980. New Jersey Urea
Formaldehyde Foam Insulation Study. New Jersey State Health De-
partment, Trenton, New Jersey (currently undergoing revisions for
publication).
C-13. A study of 395 households with recently installed urea-form-
aldehyde foam insulation. There was no excess of increased overall
morbidity, although there was for 2 specific symptoms (skin burning
and wheezing or breathing difficulty). Those households reporting
persistent odor problems also reported the most health problems.
Evidence of acute health effects is suggestive rather than conclusive.
No HCHO levels given.
5-285 Timm, W., and P. M. Smith. 1979. Formaldehyde Odor and Health
Problems Within Residences. Proc. Int. Conf. Therm. Insul. 1:223-248.
D— _ £ review attempting to refute the evidence that formaldehyde
from foam insulation and particle board causes adverse health ef-
fects. It considers: lack of methods given for HCHO testing,
the low incidence of complaints compared to the no. of homes in-
sulated, over-reaction by the media and the public, other sources
of HCHO exposure, and studies showing no evidence of toxicity at
243
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low HCHO levels. A threshold level for HCHO in residences' of 0.5
ppm is recommended as being well below the safe toxic limit.
5-274 Tiunov, L. A., and V. A. Ivanova. 1976. The Effect of Some Indus-
trial Poisons on DNAse Activity. Gig. Tr. Prof. Zabol. No. 1:29-34
(Russ).
B-8. DNA-ase levels in the liver were significantly increased
when rats were exposed to 0.1, 0.7, or 3.9 mg HCHO/m3 for 60 d.
Levels in the spleen, however, were increased only for the highest
HCHO concentration and decreased at 0.1 or 0.7 mg/m3.
5-402- Tremer, H. M., H. L. Falk, and P. Kotin. 1959. Effect of Air
Pollutants on Ciliated Mucous-Secreting Epithelium. J. Nat. Cancer
Inst. 23(5):979-997.
D-8. Methods developments for measuring effect of various atmos-
pheric contaminants on respiratory epithelium in vitro. Sections
of the ciliated epithelium of the esophageal tract of the leopard
frog were exposed to 1.1-3.3 mg HCHO or 0.4-1.4 mg MeOH in aerosols.
Mucus flow was inhibited by HCHO and accelerated by MeOH.
5-324 Trinkler, H. 1968. Working with Formaldehyde. Med. Lab. 21(12):
283-290 (Ger).
D-4. Medical technicians, cleaning personnel, and textile workers
having contact with HCHO (presumably formalin solutions as well
as vapors) reported eczema, throat pains, coughing, and asthma-like
diseases. No HCHO levels or length of employment given.
5-108 Trubitskaya, G. P. 1978. Chemical Air Pollution in Furniture
Stores. Kazan. Md. Zh. 59(l):81-82 (Russ).
C-5 Furniture store workers and the persons living in apartments
above the store were exposed to 0.116-0.324 mg HCHO/m3 and 0.007-
0.046 mg HCHO/m3 respectively. Complained of headaches, difficulty
breathing, and irritation of the mucous membrane of the eye. Essen-
tially a small, uncontrolled, descriptive study.
5-109 Trubitskaya, G. P., A. N. Boiko, R. F. Komarova, and N. P.
Cherednichenko. 1978. Effect of a Low-Intensity Chemical Factor
on Children Under Conditions of the Use of Polymeric Materials in
Construction. Pediatriya (Moscow) No. 8:26-29.
D—. Children, 2- to 7-y-old, in a school constructed of nonpoly-
meric materials where the concentrations of HCHO, phthalates, and
NH3 were 0.006-0.016 (avg. 0.010), trace, and 0.046-0.129 (avg
0.092) mg/m3, respectively, suffered significantly fewer cases of
allergic reactions and sicknesses such as exudative diathesis,
nettle rash, and reactions to medicine than similarly aged chil-
dren in two schools constructed of polymeric materials. In the
latter two schools, the concentrations were HCHO, 0.008-0.02/
244
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(avg. 0.010) and 0.009-0.032 (avg. 0.017) mg/m3; phthalates, trace
and 0.048-0.079 (avg. 0.055) mg/m3; and NH3, 0.046-0.268 (avg.
0.124) and 0.057-0.224 (avg. 0.134) mg/m3.
5-110 Tuazon, E. C. , R. A. Graham, A. M. Winer, R. R. Easton, J. N.
Pitts, Jr., and P. L. Hanst. 1978. A Kilometer Pathlength Fourier-
Transform Infrared System for the Study of Trace Pollutants in
Ambient and Synthetic Atmospheres. Atmos. Environ. 12(4):865-876.
C—. Ambient air at Riverside, California, during August-October
1976 contained ppb concentrations of HCHO, HC02H, NH3, and other
trace contaminants.
5-424 Urban, C. M. , and R. J. Garbe. 1980. Exhaust Emissions from Mal-
functioning Three-way Catalyst-equipped Automobiles. SAE Tech.
Pap. Ser. 800511. 11 pp.
C—. Maximum emission rates (mg/m3) in 4 malfunctioning, 3-way
catalyst-equipped automobiles:
NH3 254
CN- 67
H2S 8
HCHO 3
5-167 USA Standards Committee on Acceptable Concentrations of Toxic Dusts
and Gases, Z237. 1967. USA Standard Acceptable Concentrations
of Formaldehyde. USAS Z37.16-1967, United States of America
Standards Institute, New York, New York. 8 pp.
C—. The acceptable workplace concentration selected to avoid
discomfort is 3 ppm (TWA) with 5 ppm as an acceptable ceiling limit.
5-304 USDA, U.S. Department of Agriculture, Forest Service. 1977. The
Formaldehyde Problem in Wood-Based Products—An Annotated Bibli-
ography. USDA Forest Service Gen. Tech. Rep. FPL-8, Forest Pro-
ducts Laboratory, Madison, Wisconsin, pp. 47-57.
C--. The section on the toxicology of HCHO contains ~ 45 cita-
tions, not all of which are annotated.
3-094 U.S.S.R. State Committee of the Council of Ministers for Construc-
tion. 1972. Sanitary Norms for Industrial Enterprise Design.
Publishing House of Literature on Construction, Moscow. 96 pp.
(Russ).
C--. In the U.S.S.R., the MAC for HCHO in workplaces was 0.5 mg/m3,
and'in populated places was 0.035 mg/m3 for a one-time and 0.012
mg/m3 for a mean diurnal level.
245
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5-413 Van Gemert, L. J., and A. H. Nettenbreijer. 1977. Compilation
of Odour Threshould Values in Air and Water. National Institute
for Water Supply. Leidschendam, The Netherlands, and Central In-
stitute for Nutrition and Food Research, TNO, Zeist, The Netherlands.
A—. Compilation of odor threshold values reported by different
researchers, for many compounds, including:
NH3 0.03-37 mg/m3
HCN < 1.1 - 6
H2S 0.001 - 2
ECHO 0.033 - 2.2
Methanol 4.3 - 11,700
Acrolein 0.05 - 4.1
5-384 Vernon, T. M., S. W. Ferguson, and T. A. Edell. 1978. Formaldehyde
Vapors Create Health Problems. Colorado Bull. 6(51):1.
C—. This bulletin recommends that elderly persons and those with
chronic respiratory disease be warned that HCHO vapors may be haz-
ardous to their health, that persons with allergies should be warned
that HCHO exposure may aggravate existing symptoms and/or precipitate
new allergies. Avoidance of HCHO exposure is recommended for pregnant
women, infants, and children. The report states that chronic nausea,
vomiting, and diarrhea in infants and young children living in
homes insulated with urea-HCHO have been reported.
5-276 Vinogradov, G. I., and M. I. Rudnev. 1976. Immunological Reactiv-
ity to the Effect of Carbon Monoxide and Formaldehyde in the Air.
Gig. Sanit. No. 9:9-12 (Russ).
B-7. HCHO poisoning (0.011 mg/m3 for 21 d) led to an increase in
the immunobiological reactivity of the exposed guinea pigs. However,
subsequent stress, in the form of hypoxia, caused a sharp depression
of all the studied indexes in contrast to the controls, revealing
the inferior resistance of the test animals.
5-275 Vinogradov, G. I., I. A. Chernichenko, and E. M. Makarenko. 1974.
Allergic Activity of the Motor Traffic Exhaust Gas. Gig. Sanit.
No. 8:10-13 (Russ).
B-7. Exposure of guinea pigs to HCHO at 0.011', 0.038, or 0.38
mg/m3 for 21 d was accompanied by injury to the neutrophils, degran-
ulation of the basophiles, and increase in the titer of antibodies
in bound complement. The results confirm the sensitizing action
of HCHO.
5-015 Volkova, Z., and E. Sidorova. 1971. Formaldehyde Content in Blood
of Persons Working in Contact with Urea-Formaldehyde Resins. Gig.
Tr. Prof. Zabol. 15:44-46 (Russ).
246
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C-9. Concentrations of HCHO in the blood of workers was positively
correlated with the degree of exposure via inhalation and skin
contact. By the start of the next day, only the most heavily ex-
posed workers contained HCHO in the blood, and this may have been
due to contamination of the clothing they wore home. HCHO con-
centrations in the workplace air ranged from 0.31 to 8.8 mg/m ;
in the blood of exposed workers at the end of the day, from
< 0.06 to 0.70 mg %.
5-387 Von Oettingen, W. F. 1958. Poisoning. A Guide to Clinical Diag-
nosis and Treatment. 2nd ed., W. B. Saunders Co., Philadelphia,
Pennsylvania, p. 365.
C—. This very brief summary of HCHO toxicity by inhalation, der-
mal, or oral routes mentions that following ingestion of HCHO and
its expected direct action on the gastrointestinal tract, there
may be diarrhea, tenesmus, anuria, and injury of the liver.
5-277 Wallenstein, G. , and E. Rebohle. 1971. Results of Experiments
on Allergic and Irritative Effects of Formaldehyde on the Resp-
iratory Tract. Z. Erkr. Atmungsorgane 135(3):359 (Ger).
C-7. Of 78 patients exposed to HCHO-containing resins on their
jobs who exhibited respiratory sensitivity to HCHO—vasomotor
rhinitis, chronic bronchitis, and obstructive respiratory problems—
only 17% showed a positive reaction to epicutaneous exposure and
5% showed a positive late reaction to the intracutaneous test.
Sixty-two percent showed a nonspecific bronchial hyperactivity
(positive acetylcholine test). No inhalation provocation tests
were done. There were workplace exposure values for only 7
cases—5-25 mg/m3, which exceeded the MAC of 3 mg/m3.
5-27F Wallenstein, G., and E. Rebohle. 1976. Sensitization to Formaldehyde
in Occupational Exposure by Inhalation. Allerg. Immunol. 22(3):287-290
(Ger).
D-5. Determinations of skin test sensitivity to HCHO of workers
in various industries with HCHO exposure. 22/180 (12.2%) showed
positive sensitization. Of these, none showed a clear positive
response to provocative tests (nasal and inhalation application).
No environmental sampling was done to correlate exposure to test
results.
5-303 Wanner, H. U. 1978. Hygienic Evaluation of the Pollutants from
Living Room Air. In: Org. Verunreinig. Umwelt: Erkennen, Bewerten,
Vermidern, [Tag.]. K. Aurand, V. Haesselbarth, E. Lanmann, G.
Muller, and W. Niemitz, Eds. Erich Schmidt Verlag, Berlin, Germany.
pp. 405-415 (Ger).
C--. A review of CO, HCHO, acrolein, and N oxides in indoor air.
In 1978, Satish and Wanner found HCHO concentrations of 32-46 ppb
in indoor air in the winter (6-8 ppb outdoors) and 48-124 ppb in
indoor air in the summer (13-15 ppb outdoors).
247
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5-115 Wanner, H. U., A. Deuber, J. Satish, M. Meier, and H. Sommer. 1977.
Evaluation of Air Quality in Streets. Proc. Int. Clean Air Congr.,
4th, Tokyo, Japan, pp. 551-554.
C—. HCHO concentrations in ambient air at outdoor sites varied
little with wide differences in traffic density (9.3-12 ppb), but
indoor air concentrations were considerably higher: traffic canyon
first floor office, 85 ppb; suburban apartment, 53 ppb; and resi-
dential area "store and dispatch," 41 ppb.
5-016 Wayne, L. G., R. J. Bryan, and K. Ziedman. 1976. Irritant Effects
of Industrial Chemicals: Formaldehyde. Publ. No. 77-117. National
Institute for Occupational Safety and Health, Center for Disease
Control, Public Health Service, U.S. Dept. of Health, Education,
and Welfare, Cincinnati, Ohio. 135 pp.
B-9. HCHO levels were determined in garment apparel workshops
and wood products plants, but health effects were evaluated in
only one—a large wood products plant. No significant relations
between HCHO exposure and eye disorders, irritation symptoms, or
visual function were observed.
5-348 Weber, A., C. Jermini, and E. Grandjean. I976a. Irritating Ef-
fects on Man of Air Pollution Due to Cigarette Smoke. Am. J.
Public Health 66(7):672-676.
D-ll. Exposure is confounded for the purposes of this task, but
worth a mention as an interaction study with HCHO and acrolein as
probably the primary irritants. The sidestream smoke from 30
cigarettes added to a 30 m3 room for 26 min resulted in ~ 71 ppm
CO, - 1.32 ppm HCHO, and ~ 0.30 ppm acrolein. The results of self-
rated intensity of eye irritation paralleled the increases in ir-
ritants with time. Nose and throat irritatation, respiratory and
general complaints, and poor air quality judgements also increased
with time, although weaker and less obviously paralleling irritant
concentration. Nonsmokers were slightly more sensitive.
5-280 Weber, A., T. Fischer, E. Sancin, and E. Grandjean. 1976b. Air
Pollution Due to Cigarette Smoke: Physiological and Irritating
Effects. Soz.-Praeventivmed. 21(4):130-132 (Fre.).
D-4. A group of 33 subjects was exposed to an increasing concen-
tration of cigarette sidestream smoke for 28 min. (containing 0.03-
0.64 ppm HCHO, 1-43 ppm CO, 0.08-1.5 ppm NO, and 0-0.2 ppm acrolein)
Eye irritation and subjective annoyance (the more sensitive cri-
terion) increased with time, smokers and nonsmokers apparently
equally sensitive. No significant differences in lung function
were observed.
5-281 Weber-Tschopp, A., C. Jermini, and E. Grandjean. 1976c. Air Pol-
lution and Irritation Due to Cigarette Smoke. Soz.-Praeventivmed.
21(2-3):101-106 (Ger).
248
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D-ll. The same data are reported in Weber et al. (1976a) [5-348].
5-279 Weber-Tschopp, A., T. Fischer, and E. Grandjean. 1976d. Physiolog-
ical and Psychological Effects of Passive Smoking. Int. Arch.
Occup. Environ. Health 37(4):277-288.
D-ll. Apparently the same study as Weber et al. (1976b) [5-280],
but with more experimental detail given. Superseded by Weber et
al. (1976a) [5-348], a larger study with more subjects.
5-117 Weber-Tschopp, A., T. Fischer, and E. Grandjean. 1977. Irritating
Effects of Formaldehyde (HCHO) on Men. Int. Arch. Occup. Environ.
Health 39(4):207-218 (Ger); English translation by M. Tandy, Health
and Safety Executive Library and Information Service.
A-15. Comparison of exposure to continuously increasing HCHO levels
(0-3.2 ppm) for 37 min and repeated 1.5-min exposures to 1, 2, 3,
or 4 ppm. Adaptation occurred in the 1st instance, and all values
of irritation and distress were lower than those for repeated expo-
sures to 2-4 ppm. Overall, the avg. threshold of irritation for
HCHO was 1-2 ppra. Therefore, the authors recommend a TLV of < 2
ppra.
5-298 Weiss, H., M. A. Woodbury, and W. Taylor. 1981. Risk Factors
and Infant Mortality; A County Study with an Emphasis on Dwelling
Type. Abstract of Paper Submitted March 5, 1981, to the American
Public Health Association 109th Annual Meeting, Los Angeles,
California, November 1981; and personal communication from H. Weiss
to B. L. Carson, March 19, 1981.
D-6. This study, based on analysis of death certificates, confirms
a preliminary report that there is an increased risk of infant
mortality among mobile home residents (23.4% mortality) vs. non-
mobile home residents (13.3%) in Eau Clair County, Wisconsin.
However, the results tend to show only that mothers living in
mobile homes are younger and less educated so that the twofold
greater incidence of infant mortality is merely that expected from
mothers of a lower socioeconomic class. The study does not look
specifically at newer mobile homes where HCHO emanations would be
expected. In fact, there are no HCHO measurements at all.
5-203 Williams, J. E., and C. D. Gordon. 1970. The Hatchability of
Chicken Eggs Fumigated With Increasing Levels of Formaldehyde Gas
Before Incubaton. Poultry Sci. 49(2):560-564.
D-ll. Exposure of eggs before incubation to ~ 0.5 to 2.5 mg HCHO/m3
for 20 min. Number of chicks hatched was reduced slightly, more
so in brown eggs and eggs from older hens.
5-282 Wynder, E. L., D. A. Goodman, and D. Hoffmann. 1965. Ciliatoxic
Components in Cigarette Smoke. II. Carboxylic Acids and Aldehydes.
Cancer (Philadelphia) 18(4):505-509.
249
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C-8. The methods of this clam gill cilia study are not fully des-
cribed. The lowest level of HCHO tested was 0.05% (500 ppm) and
this produced almost immediate complete stasis of ciliary activity
with eventual recovery. 0.1-1.0% (1,000-10,000 ppm) acrolein caused
immediate and complete ciliastasis, while 0.05% (500 ppm) caused
immediate loss of metachronic wave in the lateral cilia and partial
stasis at ~ 1 min with no further effect.
5-119 Yamate, N., T. Matsumura, T. Inoue, and E. Higuchi. 1978. Summary
of Air Pollutant Levels at Three National Auto Exhaust Monitoring
Stations in Tokyo in 1977. Eisei Shikensho Hokoku No. 96, 119-123
(Japan); Chem. Abstr. 1979. 91:111832w.
C—. HCHO concentrations measured at the gas monitoring stations
declined from 0.01 ppm in 1969 to 0.006 ppm in 1977.
5-172 Zaeva, G. N., I. P. Ulanova, and L. A. Dueva. 1968. Materials
[Information] for Revision of the Maximal Permissible Concentra-
tions of Formaldehyde in the Interior Atmosphere of Industrial
Premises. Gig. Tr. Prof. Zabol. 12(7):16-20 (Russ); English trans-
lation available from John Crerar Library, Chicago, Illinois.
Order No. 74-13625-06J. .
B-5. A review of the Russian literature, the authors recommend-
ing a maximum permissible concentration in the air of workplaces
of 0.5 mg HCHO/m3.
5-173 Zannini, D., and L. Russo. 1957. Consequences of Acute Intoxi-
cations Due to Gaseous Irritants of the Respiratory System. Lav.
Urn. 9:241-253 (Ita); English translation available from John Crerar
Library, Chicago, Illinois. Order No. 75-21078.
C-5. Of 18 persons acutely poisoned by gaseous irritants, only
one had been exposed to HCHO (no concentrations given). This 40-y-
old person complained of dyspnea on exertion, asthma attacks, weight
loss, and nervousness. Chest showed harsh respiration and dissem-
inated rhonchii. The left side of the heart was enlarged. There
was accentuation of the 2nd pulmonary tone on the pulmonary focus,
and the thyroid was hypertrophic. Vital capacity and max. pulmonary
ventilation had decreased 40 and 45%, respectively. The decrease
in diaphragm motility may have been attributable to loss of gen-
eral condition due to rest at home as well as to bronchopulmonary
lesions.
5-121 Zitting, A., and H. Savolainen. 1979. Neurotoxic Effects of the
Oxidative Thermal Degradation Products from Low Density Polyethylene.
Fire Mater. 3(2):80-83.
C-10. Repeated exposure of rats to polyethylene combustion products
containing 1.4 ppm HCHO, 0.5 ppm acrolein, ash, CO, and mixed alde-
hydes for 6 h/d, 5 d/wk for 2-5 wk led to undesirable neural effects
250
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APPENDIX A
HUMAN STUDIES IN PROGRESS
A "Review of Planned and On-Going Epidemiological Studies of
Formaldehyde," excerpted from the Report of the Federal Panel on Formalde-
hyde (Griesemer et. al., 1980) is included in this Appendix.
MRI contacted by letter many of the principal investigators of
these on-going studies, and those complete or near-complete reports received
in reply were included in the preceding chapters. To correlate the informa-
tion received with the remarks concerning each study by Griesemer et al.
(1980), we have identified each study by the numbering system u-sed in the
excerpt.
"II.a)" This is presumably the report by Giulietti (1980), which is in-
cluded in Table V-2.
"Il.b)" The report of Marshall (1980) is included in Table V-2.
"II.c)" No response.
"III.a)" Following written and telephone inquiries, MRI was told that infor-
mation on Dr. Levine's studies was not available.
"Ill.b)" The report of Thun et al. (1980) is included in Table V-2.
"III.c)" No data are available yet for Woodbury and Zenz's study of new
mobile home owners. The last samples were to have been col-
lected in May 1981 (personal communication to B. L. Carson from
Mary Ann Woodbury of the Wisconsin Department of Health and
Social Services, January 1981). The results on the retrospec-
tive study of 65 mobile home residents are discussed in Hanrahan
et al. (1980?) and the data given in Table V-2.
"Ill.d)" Dr. Williams' study, "Survey of Mobile Home Residents in Two Dif-
ferent Coastal Regions: Coastal and Inland," had obtained an-
swered questionnaires but no funding for data analysis. Formal-
dehyde measurements were not made (personal communication to
Dr. H. V. Ellis, III, from Dr. L. P. Williams of the Office
of State Health Division, Department of Disease Monitoring and
Control, Oregon, December 1980).
"IV.a)" No letter sent.
A-l
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"IV.b)" Data collection for Dr. Grauman's study of medical technologists
was not scheduled to begin until March 1981. The report was
estimated to be completed in mid-1982. Dr. Graumann is work-
ing on a similar study of 5,000 histotechnologists, with
greater exposure levels. A preliminary report may be ready by
October 1981, to be given at the National Histotechnologists
meeting (personal communication to Dr. Ellis from Dr. Dan
Grauman, National Cancer Institute, December 1980).
"IV.c)D" Results of Dr. Walrath's study are given in a paper presented at
the C.I.I.T. Conference on Toxicology: Formaldehyde Toxicity
(received from Dr. Walrath in January 1981), and described in
Table V-l.
"IV.c)2)" A protocol for the California embalmers study was received from
Dr. Walrath in January 1981, but no data have been collected.
"IV.c)3)" Following written and telephone inquiries, MRI was told that in-
formation on Dr. Levine's studies was not available.
"IV.d)" The first phase of finding a suitable cohort has apparently been
undertaken by Westat, Inc. (Anonymous 1980b). Several reserva-
tions about the proposed course of study have been made by
Dr. Irving Selikoff of Mt. Sinai Medical Center (Anonymous,
1980a). A request-for-proposal has been issued for a mor-
tality study of the 5,000-10,000 worker cohort (Anonymous,
198lb).
Two additional on-going studies were found which are not discussed
in Griesemer et al. (1980). Dr. Genevieve M. Matanoski is conducting a study
of pathologists, originally investigating the virological risk but later
broadened to consider the possible influence of past formaldehyde exposure
on mortality. To date, the data indicate a significant increase in mortality
due to liver cancer, some excess of kidney cancer, and a lower relative risk
of oral pharyngeal carcinoma (Matanoski, 1980). Richard Dailey is the pro-
ject officer for a study entitled, "Integrated Risk Assessment of Formaldehyde,
sponsored by the Interagency Regulatory Liaison Group.
A-2
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The following pages in this Appendix were copied directly
from the Report of the Federal Panel on Formaldehyde (Griesemer et. al.,
1980). This page lists all of the panel members and their affiliations.
Panel Members
Richard A. Griesemer*, D.V.M., Ph.D. (Chairman)
National Cancer Institute
Andrew G. Ulsamer, Ph.D. (CPSC Liaison)
Consumer Product Safety Commission
Joseph C. Arcos, Ph.D.
Environmental Protection Agency
James R. Beall, Ph.D.
Department of Energy
Aaron E. Blair, Ph.D.
National Cancer Institute
Thomas F. X. Collins, Ph.D.
Food and Drug Administration
Federick J. de Serres, Ph.D.
National Institute of Environmental
Health Sciences
Richard B. Everson, M.D.
National Institute of Environmental
Health Sciences
John F. Gamble, Ph.D.
National Institute for Occupational
Safety and Health.
David W. Gaylor, Ph. D.
National Center for Toxicological
Research
David H. Groth, M.D.
National Institute for Occupational
Safety and Health
Han K. Kang, Dr. P.H.
Occupational Safety and Health
Administration
Richard A. Keenlyside, M.B., B.S.,
M.R.C.P.
National Institute for Occupational
Safety and Health
J. William Lloyd, Sc.D.
Occupational Safety and Health
Administration
Paul Nettesheim, M.D.
National Institute for Environmental
Health Sciences
Umberto Saffiotti, M.D.
National Cancer Institute
Elizabeth K. Weisburger, Ph.D.
National Cancer Institute
Now at the Oak Ridge National Laboratory.
A-3
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Review of Planned and On-Going Spidemiological Studies of Formaldehyde
Planned and on-going investigations related to formaldehyde exposure include
one study of a new technique of measuring formaldehyde, three studies investigating
complaints, four epidemiologicai studies of morbidity (cross-sectional and prospective)
and six mortality studies (cohort, proportionate mortality, and case-control). The
questions being addressed and an evaluation of each group of studies follows.
I. Measurement Technique
The use of solid absorbent surfaces for collecting personal samples of
vapor and particulate foraaldehyde is being examined. This method should
be aore sensitive and efficient than the present iapinger aethod, thereby
permitting aore accurate assessment of environmental exposures. An occu-
pational study (cross-sectional morbidity) is planned, but details have not
yet been provided.
II. Investigation of Complaints Relating to Formaldehyde
The results from three states are being compiled:
a) In Connecticut persons complaining of health problems due to uraa-
fsraaldenyde insulation completed a questionnaire concerning their
symptoms and air levels of formaldehyde were measured in their homes.
Occupants 489/794 of 262 residences presented complaints, the aost
common symptoms being eye, nose, and throat irritation, and headaches.
Formaldehyde concentrations ranged from 0 to 10 pom (aean of 1.5 ppc;.
About 1/2 of the complaints were associated with levels of I/I to 10 ??m.
b) F. Marshall of the Mew__Jersey. Department.of Health obtained aedical
histories, ail available information on insulation, and patterns of
health effects from residents with recently installed urea-formaldehyde
foam insulation who complained of formaldehyde odor, irritation, or
increased pre-existing illness patterns. In 40/55 hoses investigated,
the most common symptoms were tearing of the ayes, sora throat, cough,
and runny nose. Air samples were collected in 22 homes. In 14 homes
vher* formaldehyde was detected, levels ranged from .01 to O.T3 pen.
c) In Mew Hampshire, the Bureau of Occupational Health (M. Eilgemeier)
administered a standard questionaire to residents with complaints
associated with formaldehyde exposure. Standard XICSH techniques
-were used to collect formaldehyde samples. About $G" of the samples
•j*r« below 0.5 ?pm; 10/77 dwellings were sofaila homes.
The above studies on formaldehyde complaints are all similar and
suffer the same deficiencies. Sotie of then can be used to estimate
prevalence of symptoms aor can they be used to establish dose-response
ra_ations. These shortcomings include: 1. The surveys ara conducted
only acong those who complain, and although the pravalar.ca of 5yr.ptor:s
should be high, it is a biased sample; 2. There are r.o controls ar.c
10 measurement of other irritants that could causa health ccarolair.ts. -
Thus, these studies are only suggestive of possible ?roale=s and by
themselves provide little evider.ca cf cause and a'ffact relatior.s'r.irs.
A-4
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III. Morbidity
The following studies are underway:
a) 3.. Levine of the Cheaicai Industry Institute of Toxicology studied
approximately 100 West Virginia morticians in a cross-sectional study
of lung function (spirooetry) and respiratory symptoms. Employment
and smoking histories «ere also obtained. Industrial hygiene measurements
made in the mortality study of Ontario emfaalmers along vith symptoms
during embalming, number of bodies embalaed, subjective assessment of
severity of fumes, and length of employment will be used to assist in the
estimation of exposure in this study. Spironetry will be compared to
predicted values from SCnudson, and internal comparisons will be related
to exposure after age, height, and smoking adjustments.
Data from this study are being analyzed in terms of the prevalence of
respiratory symptoms (cough, phlegm, dyspnea) and the relation of percent-
age of predicted pulmonary function to employment (formaldehyde exposure)
after adjustment for confounding variables. There is no assessment af
skin effects. It is not clear if acute symptoms related to exposure are
to be evaluated.
Although there is a good rationale far studying this occupational
group, an inability to detect a significant response in this study could
be due to low cumulative exposure (probably less that 3 hours/day).
Length of exposure (years worked or latency) should be adequate. If
we assume 30 persons each (smoking groups combined) in a high and low
exposure group (the optimal situation) there is an 35Z chance of
correctly rejecting the null hypothesis of no difference in FZT
between exposure groups, if the true difference is 0.5 liters and^.
•level is 5J. If the symptom rate is 20* in the low exposure group,
there is less than a 502 chance of correctly rejecting the hypothesis
of ao difference if the true difference is 20" at the 5" ^ level (tvo-
tailed test). As in all cross-sectional studies, estimates of exposure
are only a crude indicator of actual exposure. This is, however, one
of the few studies to attempt to assess long ten effects of formaldehyde
on lung function. Although embalming fluid contains 1-2Z formaldehyde,
other pulmonary irritants are also present (e.g., phenol) but these ray
be at low enough concentrations to have a ainimal affect, A comparison
group (e.g., funeral directors) would have provided raore confidence in
the results and more power in the analysis.
The remaining three morbidity studies ara of residents in homes
with urea-formaldehyde (U~) foam insulation.
b) M. Thun of the New Jersey Department of Health identified about ^00 homes
that had been insulated with U? foam and an equal number of control homes.
Information zathered by telephone interview included type of home and in-
sulation, formaldehyde odor, health symptoms and ether redical data,
demographic data OR the occupants, and the period prevalence of asthmatic
attacks, vheesing, chest pain, stir.zir.g or burning skin,
A-5
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or tsaring ays. Except for vheezing, the controls raportad
a higher prevalence of symptoms than did T? foam households. There
no detectable diffarance in the overall incidence of new symptoms during
the year. Thera vas, however, an association of increased symptoms and
formaldehyde odor; the incidence of new symptoms following installation
of the insulation vas 2.7 times higher than in the souths preceding the
insulation. About $*Z of the residents of the Ts foam homes raportad no
problems at all related to the foam insulation. There is the possibility
of selective recall in the remaining 362 of the study group because of the
possible publicity relating to acbila homes and the specific questions
relating to insulation. Despite this potential bias, there vas littla
overall difference becvaen study and comparison populations. There vas
however, a dose-response relation (dose vas based on odor). Cnfcrtunatalj,
there vera no environmental measurements to correlate vith odor percaption
and symptoms, and appararently no control of other potentially confounding
irritants other than formaldehyde. The added insulation nay have also
incraased other respiratory irritants chat touli have raised the symptom
raw. Is is not claar how the formaldehyde odor vas described to :ha
subjects. This study has been completed recently and should be available
far'review shortly. The summary given the Panel suggests littla iiffaranca
betveen the issulatsd and control homes except vhen odor occurred.
M. "^oodbury and C. I*nz of the Visconsin department of Health and social
Studies are proposing to study 110 sew tofaila home swners. Ispcsura
measurements ara to be aade tvica sonthly for ? months.
It is difficult to evaluate this prospective study because of the
lack, of detail provided. Some of the questions that seed answering ara:
- «hat are the health paraseters that vill be determined and how
oftan ara they being monitorad?
- Are there formaldehyde controls for the mobila homes? If
so, how are they selected? If so controls ara planned, the
studv vill have limitad
--an
*
- Are other respiratory irritants beinz teasurad -'e.g., NC, ?
About 50*o f the homes ara newer horses vith higher forraldahyda lavels
the older hoses vhich are serving as controls and have seasuracls rut -"-
**ve:s of forsaldecyde. Assuaing a 20Z symptom rata and 130 reopla in aacn
Irsosur* group CHigh and ;ow formaldehyde) . there is about an 35^ =r.anca a:
-or-ectly ra'ectisg the hypothesis =f so iiffarancas in sy=?t=ss vr.en :r.e
-~e diffarance is ^' at'the 5^* lavel. and about a ?« shaace =: carrac-..;-
-a^ec-ing the hypothesis af =o diffaraaca is 7TT. vr.an the true ;i;:aranca is
500 =L at the 5 ', ok lw«i (two-tailed :•«} . Thi af facts of long-carm csrsnis
asposura cannot re astiaated by this srady.
~-ase investigators also cerforred a ratrospective pilot study c: 63
=o=ila has* residents. The iata vill be rainly useful is ".e pjaaisg anc
axacution rf :he prospective study.
A-6
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d) L. Williams of the Oregon Department of Disease Monitoring
and Control is planning to study 300 mobile hone residents who
responded to a health questionnaire. The volunteers were fron
two regions, coastal and island. The purpose of the study is
to ascertain the effect of humidity, temperature, and wind
ventilation, on "health effects to potential formaldehyde exposure."
Inasmuch as the participants in the study are volunteers, however,
it is noc a random sample. Apparently, environmental measures
are planned, but it is not known what other information on insulation,
demography, other pulmonary irritants, humidity, temperature, etc., will
be collected. Although the details are unknown, tS4s study design does
not promise to add very much to our knowledge. The power in this study
is similar to the study fay Woodbury and Zenz when the following assumptions
are made:
1) the two exposure groups to low and high formaldehyde
are of equal size (<*— L50) ;
2) the prevalence of symptoms is about 30* in low exposure
group.
IV. Mortality
a) H. Weiss of the Wisconsin Department of Health and Social Sciences
conducted a case—control study of infant mortality by type of residence
and found an increased risk for mobile home residents. Socioeconomic
status is only one of many sources of potential bias in this study. The
completed study should be reviewed, but the short description available
suggests that the data will provide little, if any, useful information on
the effect of formaldehyde.
b) D. Grauman of the National Cancer Institute proposes to evaluate the
mortality experience (using standardized mortality ratios [SMS] of a
cohort of about 11,000 medical technologists. This group is exposed
to other chemicals in addition to formaldehyde (e.g., chloroform and
benzidine). No environmental data are available, so there cannot be
a good estimate of exposure—response relationships. A positive
association will not be conclusive because of the nixed exposure.
A negative association will not be conclusive because of 'the lack
of exposure information and the possibility of low exposures. The
control group is to be the U.S. population. If 15* of the cohort
are dead (n - 1650 cases) and if 20 5 of the deaths in the control
population were from cancer, there would be better than a 95* chance
of correctly rejecting the hypothesis of no difference between
exposed and controls if the true differences-were SZ at the 5Z^ level.
Assuming 1/4 of all cancers were lung cancer, there is about an^SO"
chance of correctly rejecting the hypothesis of no difference if the
true differences were 52 at the 102 •* level (two-tailed test).
c) There are three mortality studies of ambaimers.
A-7
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1) J. '-alrath La conducting a proportionate aortality
ratio analysis of about 1500 norticians from Saw York. The
purpose is to deterraiaa wiether there Is an excess proportion
of deaths due to specific salignant neoplasms compared to the
general population. Besides having the problems inherent in
a ?MS analysis '--here che populatian-at-risk is act available
there is little exposure data (length of exposure is estimated
on the basis of the year first licensed). Assuming the rate
of long cancer is 52, there is batter than a 992 chance of
correctly rejecting the hypothesis of no difference is lung
cancer rates «hen the true difference is 52 at the 12 dt
level (tso-talied test).
2) Or. Hairath is conducting another ?*S study on about 1200
ilaers from California. This study is very siailar to the one in
Tork, except there will be =ore information an length of exposure
wnich can be evaluated. There is, however, ao direct asti=ate of sxposura
or snaklsg history or other confounding exposures. If IC2 of the deaths
wire fron cancer, chere vould be a better than 902 chance of correctly
rejecting the hypothesis of ao difference is cancer rates beevean exposed
and controls if the true diffemcas were 52 at the 102 oi, lave! (re-
tailed test).
3) 1. Levine of the Chemical Industry Institute of Toxicology is
also studying eafaalaers using an SXR retrospective sortality design. The
cohort is composed of Ontario's funeral service professionals licensed
during 1914-1967. Date of birth, date of first licensure, type of license,
years licensed, and place of employment are available for each person.
Observed aortality rates will be compared to Canadian aational and provincial
aortality data, itortaiity will also be analyzed as a function of exposure
(years worked ?). A retrospective industrial hygiene assessment will consist
of inquiring about changes in funeral practices uith :i=e, surveying several
selected funeral establishments. The survey vill include air sampling far
agents of potential health concern (e.g., foraaldehyda, phenol) and exam-
ination of purchase records to deteraine aaount and kind of cheaicals -ased.
?resuaably these data are to be used in evaluating dose—casuoosa relation-
ships. Assuming the study population comprises 130 deaths (132 of the
estiaated cohort) and a 202 cancer rare there is about a 502 chance of
correctly rejecting the hypothesis of ao difference if :he true difference
is 102 at 32 "* level (or an 352 chance if the true difference is IJZ at
the 52 * level).
As a group, these three studies of esbalsers should provide a good
*stiaate of potential risk from formaldehyde exposure.
d) A. 31air at MCI and che Foraaldehyde Institute are colliborating
on a proposed ccoort mortality srady to develop age, race, and sex-aaecific
sortaliry rates among corsaldeovde-exaosed Barkers. Jatas vill be comcarac
viix those ia the -J.S. populatian and local or regional populations whera
appropriate.
The first phase of the investigation is to determine if -here is a
suitable cohort for study. Suitability will be based an representatives
3f the participating companies, range of exposure, availability ^c a cohort
A-8
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of at least 3,000 workers with a -rf.n-fw™ 13-year latent period, suitable
age distribution, and sufficient information for adequate follow-up. If
the requirements for a scientifically sound study are met, the study will
proceed. Formaldehyde exposure for each individual will be estizaiad
using job titles, work locations, past environmental measurements, years
of employment, and the presence of potentially confounding exposures. The
exposed group will be stratified^by intensity and duration of exposure,
age and year of first exposure, susceptibility, and latency.
The cohort should be large enough to engender confidence in the
differences in mortaliry experience of study aad comparison populations.
Although exposures are unlikely to be to pure formaldehyde, because of the
varied occupational exposures and size of the cohort, it may be possible
to assess the individual contribution of formaldehyde. Although the
assessment of exposure is retrospective, it can still be at least seai-
quantitative. This is a very important part of this study and should
employ a full-time industrial hygieaist following methods similar to
those of Emsden at the University of Pittsburgh. It is important chat all
companies participate in the study, as the results may be seriously
biased if some do not.
Conclusions
Of ai"! Ejjg mortality studies proposed, those examining the nedical techno-
logists, embalaers, and formaldehyde workers are the only ones that can assess
the carcinogenic risk among those individuals exposed. Although single epidem-
iologic studies usually cannot adequately assess an occupational risk, or the
risk of exposure to a chemical agent, taken together these studies should help
clarify the situation. There are, however, a number of concerns about these
studies including:
a) Are exposures to formaldehyde high enough in these populations
to assess possible effects? For example, are emhainers exposed
8 hours/day, 5 days/week, or is their exposure much less?
b) Can exposure history be adequately documented?
- Are individuals with little or no embalming experience
distinguishable from those with considerable exposure?
- Since few if any of the -workers are exposed only co
formaldehyde, what is" the effect of exposure to these
other agents?
c) Is exposure to formaldehyde in the same range as for other
populations?
The confidence -we place ia the findings from these studies depends largely
on the ability to retrospectively estimate exposure. If exposure in these
occupational zroups is representative of other exposed populations, the
conclusions aay be indicative of potential risk to ail exposed populations.
re these studies do not adequately address the above questions, then further
investigation aay be required. Such investigation say be pursued within the
existing data set, or new populations may need to be investigated.
A- 9
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Secaanendations for Zpidg^olagjc Research
There is a need for carefully designed apideaiologic studies to evaluate
the role formaldehyde say play is the origin of certain chronic diseases.
Specific research areas identified by the Panel include:
1. Additional studies of chronic respiratory systea disorders chat
include environmental measurements to allow a sore precise estimate
of risk at various exposure levels. These should include industrial.
as veil as aobila horse populations.
2. Projects designed to canfiza ar deny the association of menstrual
and reproductive disorders and foraaldehyde ^xsosura reaortad by
Shuailiaa (1975).
3. Mere complete epideaioiogic studies to evaluate the carcisoganicity of
foraaldehyde is huama populations. Although several projects are
under «*y, there is a seed to be alert for resources for additional
research, the widespread use of foraaldehyde is industry and its
occurrence ia a variety of consumer products say provide opportunities
for other studies. The aany us«s of foraaldehyde are sucaarized in the
5IOSH Criteria Document (1975) and viil aot be itemized here. It is
sufficient to say that the chemical is of importance is achesires
for particle board and plywood production; resins to sold a variety
of plastic parts for automobiles, appliances and hardvare; vriskls-
resistance ia textile aanufacraring; strengthening of various paper
products (grocery bags, wax paper, aapkiss and tissues, and filter
paper); speciaen preservation; aildaw prevention; insulation;
and protective coatings.
It xay be possible to Identify other foraaldehyde-«3pos«d cohorts for
study, tse aajor difficulty is that, for
-------
Heavy construction 3.7
Plastering-and lathing 5.4
Textiles
Finishing plants (synthetics) 11.6
Coated fabrics 14.0
Hats and caps • 47.0
Fabricated textile products 3.3
Voad and Paper
7eneer and plywood 21.0
Voad products 3.5
Upholstered furniture 12.2
Paper mills 3.3
Paper coating and glazes 9.0
Sags (except taxrilas) 11.1
Paints and allied products 15.9
Fabricated rubber products 29.0
Abrasive products _ 11.0
This survey confirms an impression given '37 published reports that
exposura to formaldehyde is ssore common in medical and laboratory anviron—
aents and in certain parts of the textile, --ood, and paper industries..
In certain industries, however, :he dumber of work places and workers
studied ~J3.s small and the survey aay act have included those vhera
significant exposure to formaldehyde occurs (e.g., the chemical manu-
facturing industry).
The Industry-wide Studies Branch of MIOSH is carrying out an industrial
hygiene study of formaldehyde exposure in several industries in search of
a suitable cohort far a mortality study of formaldehyde exposed workers.
Measurements vili be made in industries concerned --ith formaldehyde manufacture,
textile and clothing production, waod famiturs and vocd and paper product man-
ufacture, "iftaen site visits are planned and these vill :e complacad ever the
next sis months.
The aajor difficulty of the mortality studies of individuals exposed
to formaldehyde is the limited ability of such studies to detect -axcass risk
for rare causes of death. Since the known carcinogenic action of formaldehyde
is limited co che sasal sinuses in rats, there is a. aeed to evaluate the risk
for this site in an, although it is claar that carcinogens ray sot affect the
same tissues in. humans as in laboratory animals. It is 'inlikel1/ that a cohort
of sufficient size can be assembled to accomplish this task; however, a carefully
designed case-control study might. The Panel suggests that the feasibility of
performing a case-csntrol study of cancer of the oasal sinuses in araas vhera
there is heaw production or use of formaldehyde as a vapor should be axplorad.
A-11
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