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

-------
                           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

-------
                                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

-------
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.
                                  178

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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)

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                                                  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)

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                                                  •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)

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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

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               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

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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

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          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 
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   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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