<b>Bijsluiter</b>. De hyperlink naar het originele document werkt niet meer. Daarom laat Woogle de tekst zien die in dat document stond. Deze tekst kan vreemde foutieve woorden of zinnen bevatten en de opmaak kan verdwenen of veranderd zijn. Dit komt door het zwartlakken van vertrouwelijke informatie of doordat de tekst niet digitaal beschikbaar was en dus ingescand en vervolgens via OCR weer ingelezen is. Voor het originele document, neem contact op met de Woo-contactpersoon van het bestuursorgaan.<br><br>====================================================================== Pagina 1 ======================================================================

<pre>Gezondheidsraad
P.O.Box 1052
2500BB Den Haag
The Netherlands
Dear Lady/Sir,
                             qitoser,                                162      5
Re: Draft Document on Formaldehyde
Thank you for the possibility to comment on this. The document has cited many articles, but still
many - possibly relevant ones - have been omitted, too. In our national document for formaldehyde
limit value from 1997 we had only 27 citations, and your document covers 9 (33%) of these. Lately,
new interesting articles have been published. I will not deal in length with these older publications,
however. .
In 3.2 you give the vapour pressure of 0,2 kPa at 20 C. I wonder if this one is- for a water solution of
formaldehyde. At flash point you mention flammable gas, and to my knowledge the vapour pressure
of the gas is several decades higher.
As for sensory irritation in animal experiments, you mention the Kane and Alarie study for RD50.
Many more exist, like Chang, 1981 (4,9 ppm) and DeCeaurritz,1981 (5,3 ppm).
The existing guidelines for working population tend to be outdated. This draft is no exception. In
table 3, Sweden has also a note of carcinogenicity, and ACGIH a note of sensitisation. The Iceland
standard is presently 0,3 ppm (Vinnueftirlit Rikisins, 1999).
The present Finnish limit values are 0,3 ppm (8 hr) and 1 ppm- (ceiling). The year of adoption was
 1998., and the present literature reference is 'Sosiaali-ja terveysministerio, HTP-aryot 2000,
Tyosuojelus'aadoksia 3, 2000'.
I would like to point out few recent publications that might have relevance to limit value setting.
An article from Australia (Allergy 1999,54,330) pointed out that the risk of atopy was increased by
40% , if the formaldehyde concentration of bedrooms was at least 135 micrograms per cubic metre
or the concentration of the whole apartment at least 145 micrograms per cubic metre.
An American study on nasopharyngeal carcinoma supported the hypothesis that formaldehyde but
not wood dust increases the risk on NPC (Vaughan et al (2000): Occupational Exposure to
Formaldehyde and Wood Dust and Nasopharyngeal Carcinoma, Occup. Environ. Med. 57, 376-
,384). There was a statistically significant risk for people exposed to more than 1,1-0 ppm -years. For
40 years this would mean 0,0275 ppm as 8 nr - if I calculate right.
 Short- term effects of formaldehyde on peak,expiratory flow and irritant symptoms of students
dissecting cadavers was studied by Kriebel et al (Archives of Environmental Health 2001, 56, 11-
 18).
</pre>

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<pre>  French researches reported recently on their study of ten workers exposed to formaldehyde. Using
  the micronucleus assay they reached results t^hlt suggested that exposure to formaldehyde induces
  chromosome aberrations on lymphocytes ( Sari- Minodier et al (2001); le Test des Micronoyaux
  dans l'Evaluation du Risque Mutagene:Etude aupres de 10 Salaries Exposes au Formaldehyde,
. Arch. Mai. Prof. 62, 75-82).
  Sincerely,
</pre>

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<pre>Gezondheidsraad
Health Council of the Netherlands
mr A Aalto
Ministry of Labour
Occupational Safety and Health Division
PO Box 536
FIN-33101 Tampere
Finland
Subject             : Comments on public draft'Formaldehyde'
Your reference      : August 6, 2001
Our reference       : 1625/AvdB/459^g™^
Enclosure(s)        :1
Date                : January 27, 2003
Dear mr Aalto,
In 2001, the Dutch Expert Committee on Occupational Standards (DECOS) published
a draft report on formaldehyde for public review. Your organisation used the opportu-
nity to comment on the draft, report. The committee thanks you for your comments,
which were used in finalising the report. On behalf of the President of the Health
Council of the Netherlands I herewith present you the D E C O S ' reaction to your
comments.
The committee has updated the existing guidelines for the working population from
other countries.
     You suggested to include several additional studies, in the report. The committee
has reviewed all these studies and decided, however, not to include the animal studies
of Chang and DeCeauritz because the H B R O E L is based on human data only, fn addi-
tion, the human study of Kriebel et al is not added to the report because the differences
between the exposed groups and the controls is (although relevant and significant)
limited.
     The committee considered the human studies of Garret et al and Vaughan et al as
important and of sufficient quality and these studies are therefore described in the final
 report. However, the committee concluded that, although a small number of studies
produce limited evidence on nasal cancer, the total body of data doesnot support a cau-
sal relationship for a nasal cancer risk at the experienced exposure levels.
P.O Box 16052                                                         Visiting Address
NL-2500 B B Den Haag                                   '              Parnassusplein 5
Telephone +31 (70)'340 75 '20                                         NL - 251'1 V X Den Haag
                     1
Telefax+31 (70) 340 75 23                                             email GR@gr.nl
</pre>

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<pre>Gezondheidsraad
Health Council of the Netherlands
Subject              Comments on public draft 'Formaldehyde'
Our reference        3113/AvdB/459-N38
Page                 2
Date                 January 27, 2003  '
The final report was published on January 27, 2003. Enclosed you will find a copy.
                 an der Burght
  lentific seefetary DECOS
P.O Box 16052                                                    Visiting Address
NL-2500 BB Den Haag                                              Parnassusplein 5
Telephone +31 (70) 340 75 20                                     NL - 2511 V X Den Haag
Telefax +31 (70) 340 75 23                                       email: GR@gr.nl
</pre>

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<pre>       SENATSKOMMISSION.                                        Kommissionssekretariat
          DER DEUTSCHEN                                         HohenbachernstrafJe 15-17
  FORSCHUNGSGEMEINSCHAFT                                        D-85350 Freising-Weihenstephan
               ZURRRUFUNG
 GESUNDHEItfSSCHADLICHER'.ARBEITSSTOFEE         TECHNISCHE Telefon-.08161/71-5601
     VORSITZ PROF DR MED H< GREIM               UNIVERSITAT Telefax: 08161./71-5618
            Dr. Heidrun Greim                   M D N C H E N E-mail:, heidrun.greim@lrz.tum.de
Dutch Expert Committee on
Occupational Exposure Standards (DECOS)
Health Council of the Netherlands
PO Box 16052
NL-2500 BB Den Haag
                                                           , Weihenstephan, 26. Juli 2001
                                                                     (7/mak/DECO2307.doc HG/nk)
 Formaldehyde
 Draft May 1, 2001
 Dear Madam and Sirs,
The description of the MAK carcinogen category 4 in your draft document is
 not correct.
 My suggestion would be to replace the second sentence of paragraph 3 on
 pagina 59 with :
"Formaldehyde is classified* in carcinogen category 4, which contains
substances with carcinogenic potential, for which genotoxicity plays no or at
most a .minpr part. No significant contribution to human cancer risk is
expected provided the MAK value is observed. The classification is
supported especially by evidence that increases,in cellular proliferation or
changes in cellular differentiation are important in the mode of action. To
characterize the cancer risk, the manifold mechanisms contributing to
carcinogenesis and their characteristic dose-time-response relationships are
taken into consideration."
                                                        rd
i. would* also suggest replacing the last line in the 3 paragraph of pagina 5
with:,
"and classified formaldehyde into carcinogen category 4 (genotoxicity playing
 no or at most,a minor,part)".
 Further more, I would like to inform you that our commission has classified
formaldehyde into germ cell mutagenicity category 5.
Yours sincerely
Dr. Heidrun Greim
      . .          .              •                   cr.,
         . . .                    ,                  ho .
                                                     o
</pre>

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<pre>Gezondheidsraad
 Health Council of the Netherlands
 Senatskommission der Deutschen Forschungsgemeinschaft
Kommissionsekretariat
Hohenbachernstrasse 15-17
D-85350 Freising-Weihenstephan
Deutschland
 Subject                       Comments on draft 'Formaldehyde'
Your reference                 7/mak/DECO2307.doc HG/nk
 Our reference                 01526/AvdB/459g^p
Enclosure                      1
Date                           January 27, 2003
Dear dr Greim,
In 2001, the Dutch Expert Committee on Occupational Standards (DECOS) published
 a draft report on formaldehyde for public review. Your organisation used' the opportu-
nity to comment on the draft report. On behalf of the President of the Health Council of
                                                            1
the Netherlands I herewith present you the DECOS 'answers to your comments.
                                                    rd
DECOS has corrected the last line of the 3 paragraph of page 5 according to your
comments. Ih addition, the committee adjusted the desciption of carcinogen category 4
on page 59 as you suggested and added the classification of formaldehyde into germ
cell mutagenicity category 5.
The final report was published on January 27, 2003. Enclosed you will find a copy.
Y-o1|i|^sjncerely^
Mw^dj>ASA^d van der Burght
-Scientific Secretary DECOS
Bezoekadres                                                                  Postadres
Parnassusplein 5                                                             Postbus 16052
2511 V X Den Haag                                                            2500 BB Den Haag
Telefoon (070), 340 75 20                                                    Telefax (070)' 340 75 23
                        -
email: G R @ g r . n l ' ' " '
</pre>

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<pre> Corporate Safety, Health, Environment &
 Manufacturing
 Milieu & Productveiligheid                                             GR.
 Het Overloon 1, 6411 TE Heerlen                                        Nr.
'Postbus 6500, 6401 JH ,Heerlen
 Phone (045) 5782075, Fax (045) 5787112, Internetwww dsm.nl
                                                                             20               »
                                                                                         HS
                                                                       vv
Dutch- Expert Committee on Occupational
 Exposure Standards,
 Health Council of the Netherlands
 P O; Box 16052,
 2500 BB Den Haag                                    0 1 5 0 4 I 4Arebtef£                      ~2±-
 Your reference                Our reference*         Dealt'with'by               Direct line
                               WB034/CVM'7404         W . F , ten Berge           +31 45 5787128
                               DMM        •
 Subject                                              E-mail'
 Formaldehyde                  t 9 July 2001          wil-berge-ten@dsrri.com
 Dear Madam, Sir,
 Herewith I send you as attachment my comments to the D E C O S proposal for a Health-based
 recommended occupational exposure limit.                                   . . .
 I look forward to your final evaluation,, .
 Kind regan
Enclosure: Comment to the proposal.
DSM N V , Handelsregister Heerlen 22069                                                              1/&
</pre>

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<pre>Corporate Safety, Health, Environment &
Manufacturing
Milieu & Productveiligheid
Your reference             Our reference            Direct line              Date
                           WB034/CVM 7404           +31 45 5787128            19 July 2001
                           DMM
Comment to the proposal of the Dutch Expert Committee on Occupational Standards for
a Health Based Recommended Occupational Exposure Limit of Formaldehyde
Author: W.F. ten Berge, D S M Heerlen, NL
Introduction
The Dutch Expert Committee on Occupational Standards has issued a draft health-based
recommended occupational exposure limit for formaldehyde. The basis for the
recommendation of 0.15 mg/m3 is based on cytotoxicity of formaldehyde of the nasal
epithelium in rats and on eye irritation in volunteers. Both toxicological end points in relation
to formaldehyde exposure and other environmental factors are considered in the text below in
order to provide the complete information on the studies used by D E C O S for setting an
occupational standard for formaldehyde.
Cytotoxicity studies in rat nasal epithelium of rats
Zwart et al. (1988) exposed Wistar rats to 0, 0.3, 1 and 3 ppm formaldehyde vapour for 6
hours per day, 5 days per week during 3 days or 13 weeks, using in vivo [3H]thymidine
labeling for cell proliferation studies and light and electron microscopy for detecting
morphological effects. No difference in the nasal epithelium were found at 0, 0.3 and 1 ppm
exposure by means of light and electron microscopy. Clear effects were seen at 3 ppm as
loss of the cilia of the epithelial cells After 3 days a dose related increase in cell proliferation
was observed in the posterior part of the incisor teeth region, which had disappeared after 13
weeks. This indicates an adaptation after prolonged exposure to formaldehyde for 13 weeks.
In the anterior part of the incisor teeth region an increase of cell proliferation was seen only at
3 ppm. Three ppm was definitely an adverse effect level. The No Observed Adverse Effect
Level appeared to be 1 ppm.
Reuzel et al. (1990) studied the interactive effects of ozone and formaldehyde on the nasal
repiratory lining epithelium in rats. This study is interesting because of the exposure to only
formaldehyde at levels of 0, 0.3, 1 and 3 ppm for 22 hours per day for 3 consecutive days.
The pathology of nasal epithelium was studied by means of light microscopy and the cell
proliferation was measured by counting by [3H-methyl] thymidine labeled cells at epithelium
of the incisor teeth region. Treatment related histopathological changes and increased cell
proliferation were only found at 3 ppm formaldehyde. The No Observed'Adverse Effect Level
was estimated to be 1 ppm.
Kamata et al. (1997) exposed groups of 32 male F-344 rats to formaldehyde levels of 0, 0.3,
2 and 15 ppm for 6 hours per day, for 5 days perweek for 28 months. Nasal tumours were
                                                                th
microscopically evident in the 15 ppm group from the 14 month and 8 of 32 rats bore such
                     th
tumours at the 24 month. Histopathological examination revealed both squamous cell
papillomas and carcinomas. No nasal tumours were observed in the lower exposure groups
(0.3 and 2 ppm groups).
</pre>

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<pre>Corporate Safety, Health, Environment &
 Manufacturing
                                  1
Milieu & Productveiligheid
Your reference'             Our reference   • ,   Directhne       •       "Date
                            WB034/CVM.7404 •      +31,45.5787128           19July2001
                          , DMM •
Cell infiltration, erosion and edema of the epithelium was observed' in all groups. This .points
to a chronic inflammation of the upper respiratory tract.. Epithelial hyperplasia with squamous
cell metaplasia, was found at the level' of 0.3 ppm after 24 months and one isolated squamous
metaplasia was seen after 18 months At 2 ppm. 5 rats developed squamous metaplasia
without, hyperplasia and 7 rats developed'epithelial cell hyperplasia with squamous
metaplasia after month 18. One rat showed epithelial cell hyperkeratosis at spontaneous
death in the'2 ppm group.              .
Interspecies variation in nasal epithelium cell proliferation due to formaldehyde exposure
Morgan, (1997) has shown, that the effects in the monkey and the rat are more or less
comparable at 6 ppm,formaldehyde except thatthe extent of DNA-protein cross-linking due to
formaldehyde is considerably higher in rats. He made'his comparison only for one dose level,
6 ppm formaldehyde. He emphasises the need, of exploring interspecies differences in nasal •
dosimetry and local metabolism oyer the full dose range. He states, that, low concentration (<
2 ppm) extrapolation, where no tissue damage is observed', should'be uncoupled from the
responses at high concentration (> 6 ppm), where epithelial degeneration! regenerative cell
replication and inflammation appear to be essential driving forces in formaldehyde
carcinogenesis
Heck and Casanova (1999) studied, the cytotoxicity of formaldehyde to the nasal'epithelium
on the basis of D N A replication, at low formaldehyde exposure levels. D N A replication was
measured by radioactive thymidine incorporation. On the basis of the data in both species it
was concluded', that inhibition of DNA replication was less than 1 % after 6 hours exposure to
1 ppm of formaldehyde for the rat and 2 ppm formaldehyde in rhesus monkeys.
Interpretation of the cytotoxicity of formaldehyde for nasal epithelium
The study of Zwart et al.. indicate a NOAEL: of T ppm after 3 days and 3 weeks for 6 hours
per day, 5 days per week under all conditions. The N O A E L was established via light
microscopy, electron microscopy and measuring of cell proliferation in the most susceptible
part of the rat nasal epithelium..
Rats exposed'to 0:3 ppm and',1 ppm for 22 hours per day on three consecutive days did not
show a clear effect on pell proliferation or changes in the nasal epithelium The nasal
epithelium was slightly affected'at 0.3 and 1 ppm formaldehyde compared to the control
group, but there was no difference between the 0.3 and 1 ppm exposure groep. The effects
observed were minimal to slight hyper/metaplasia in 1 of 10 rats at 0.3 ppm and in 2 of 10
rats at 1 ppm and minimal to slight rhinitis in 2 of 9 rats at 0.3 ppm and in 1. of 9,rats at T
ppm. These are slight effects .above background, not significantly different from the control
group..
In the study of Kamata (1997) epithelial cell hyperplasia, with squamous cell metaplasia was
observed in the most susceptible region of the nasal epithelium, in 4 of 32 to rats after 24
months of exposure to 0'.3<ppm of formaldehyde Epithelial cell hyperkeratosis, a further
degeneration of the epithelium', was not observed, at 0 3 ppm, but only in 1 rat, dying
</pre>

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<pre>Corporate Safety, Health, Environment &
Manufacturing
Milieu & Productveiligheid
Your reference             Our reference            Direct line             Date
                           WB034/CVM 7404           +31 45 5787128          19 July 2001
                            DMM
spontaneously, of the 2 ppm group. It is surprising, that the effect of squamous metaplasia
with hyperplasia occurred so late in the study and that it was not earlier detected like in the
studies of Zwart et al.(1988) and Reuzel et al. (1990). However, it might be that the
susceptibility of the nasal epithelium was enhanced by chronic inflammation of the hasai
epithelium. Ceil infiltration, erosion and edema in the nasal epithelium were evident in all
groups, including the 0 ppm group and the Room Control group. This points to some
widespread upper respiratory tract infection, which might have made the nasal epithelium
more susceptible for the irritant action of formaldehyde. So the results of Kamata et al. (1997)
might be flawed by the occurrence of chronic infection of the upper respiratory tract. An other
shortcoming is the monitoring of the formaldehyde during the study. It was measured only
twice per day by means of the acetyiacetone method, a method presently hardly used. This
method'was also not mentioned in section 3.3 of the D E C O S report.
A few words should be spent to the severity of nasal metaplasia as a toxic effect of irritants. In
the human population squamous metaplasia and hyperplasia are common findings in nasal
epithelium due to virus infections or allergic rhinitis. With increasing age there is an increase
in squamous epithlium of the nasal mucosa. In persons more than 40 years of age squamous
epithelium was observed in more than one third (Boysen 1982). So squamous metaplasia
and'epithelial cell hyperplasia itself does not mean being predisposed to get nasal cancer.
In addition, one should consider that rats are obligate nose breathers. Man and monkey can,
change to mouth breathing in case of irritant vapours and this will diminish the deposition of
formaldehyde in the nasal epithelium and so also damage of the nasal epithelium becomes
less probable.
The study of Heck and Casanova (1999) indicates that at low exposure levels (1-2 ppm
formaldehyde) monkeys are a factor 2 less sensitive than rats concerning increased cell
proliferation in the nasal epithelium due to exposure to formaldehyde. Monkey is generally
assumed to be a better model for man than the rat.
Our conclusion from the results of the studies presented is, that exposure of man up to 1
 ppm formaldehyde for 8 hours per day is not expected to result in increased damage of the
 nasal epithelium of healthyworkers. This is based on the following considerations:
• The studies of Zwart et al. (1988) and of Reuzel et al (1990) indicate, that exposure levels
     of 0.3 and 1.0 ppm do not result into histopathological damage of the nasal epithelium..
• Heck and Casanova (1999) showed that rhesus monkeys were a factor 2 less sensitive
     than rats concerning slight inhibition of cell proliferation. Monkeys are assumed to be a
      better model for nasal pathology than the rat.
 • The study of Kamata is seriously flawed by upper respiratory tract infection and is not in
     agreement with the findings of Zwart et al. (1988) and Reuzel et al. (1990)
                                                                                                4/8
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<pre>  Corporate Safety, Health, Environment &
  Manufacturing
 .Milieu & Productveiligheid '               "    .
 Your reference              Our reference.                Direct line              Date
                             W B 0 3 4 / C V M 7404        +31 45 5787128.          19 July 2001
                             DMM
  Human experience- eye irritation inworkers; and volunteers;
  Eye irritation is the most sensitive toxicological endpoint related, to formaldehyde exposure in
 volunteers.
                        1
  DECOS, discussed' the study of Wilhemssori and Holmstrom (.1992) in one paragraph with
 that of Andersen et al (1983) as a 'basis for discomfort. This is not well possible. Wilhelmsson'
 and Holmstrom (1992) carried out monitoring, during the time>of the study but in their
 questionnaires they asked'for symptoms over the last years. S o t h e effects reported cannot
be related to the measured exposure. In, addition, the .average exposure, levels over the day
 hide the short term higher fluctuations of exposure levels over the day, which increase the
 irritation experience.
 D E C O S considers the study of Bender et al. ,(1983) as a key study for setting an upper limit
for eye irritation over a' short exposure, period. In fact it is not well possible to draw a firm
 conclusion from this study. This study has been characterised by a;strong selection .of the
 volunteers. About half of the original' volunteers reported eye irritation from clean air or were
 unresponsive to levels of 1.3 to 2.2 ppm formaldehyde in 6 minutes and therefore these
 volunteers were unacceptable according, to.the authors. Only volunteers were included, who
 responded, to 1.3 to ,2.2 ppm formaldehyde in 6 minutes with increased eye irritation. So the
 volunteers were a 50% selection'of the staff members of the Battellfe Memorial Institute,'
 Columbus Ohio. Bender et al. (1983) conclude,, that only at 1 ppm a significant difference in.,
 median response time for'eye, irritatipnrwas.observed, but at all, other Jeveils this difference
                                                                     l
was not significant. In addition, the severity index of irritation when,first rioted, was not
 different from 0.35 to 0.9 ppm and was about 0.8 in a scate from 0 to 3 (0=none, 1=slight,
,2=moderate and 3=severe). In addition,, the severity index decreased during exposure
 indicating a decrease of response in time. The only clear result from this study is, that at 1
 ppm formaldehyde and higher the eye irritation response i s increasing from slight to
moderate.                       •            ,,                   •
In the, study of Andersen, (1983)' 16. volunteers wereexposed'fo formaldehyde at levels of 0.3',
0.5i i 0 and 2.0 mg/m3. After 2 and a half hour respectively 3 2 , 7'and 9 persons of 16
                                                                              ;
volunteers experienced some discomfort: The. average scale of experienced discomfort was
respectively 2, 1, 7 and 18., The average discomfort values while not exposed, to
formaldehyde were between 1 and 3. The highest individual scale scores were 30, 20,, 40. and
50.scale*units respectively at 0 3, 0.5, 1 0 and 2 0.mg/m3 After 3 hours of exposure the
discomfort decreased strongly andl after 5'. hours o f exposure/the average scale of discomfort-
was 8.5, 5, 9.5 arid 1;0.'5, respectively. , ;'•                    ' ,
The explanation of the scale of discomfort is in'.the table below
            . Type of discomfort                                 Scale score .
              Intolerable discomfort                                    100 '
            ..'Strong discomfort        •     •  • • ,-     •       . 67.-99    • ;
              Discomfort            .               .' ' ;             34-66
              Slight discomfort                                         1.33
              No discomfort                                            ' o •
                                                                                                  5/8
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<pre>Corporate Safety, Health, Environment &
Manufacturing
Milieu & Productveiligheid
Your reference             Our reference              Direct line                  Date
                           WB034/CVM 7404             +31 45 5787128               19 July 2001
                           DMM
Benchmark dose analysis of the data after 2.5 hours of exposure showed that an increase of
the background response or background score with a factor of 2 is to be expected at a dose
level of about 0.5 ppm. After 5 hours of exposure this benchmark level changed into 1.2 ppm
due to the decrease of sensitivity for the discomfort of formaldehyde
The DECOS-report states, that at a level of 0.3 mg/m3, 19% of the volunteers showed
discomfort. This is half the truth. At an even higher level of 0.5 mg/m3, only 12.5% showed
discomfort, fully comparable with exposure to clean air. This is consistent with the study of
Bender et al. (1983), who could not observe a statistically significant increase in eye irritation
in the range from 0.35 to 0.9 ppm formaldehyde.
Weber-Tschopp et al (1977) studied the eye irritation by steadily increasing the exposure
level over a period of 37 minutes. Every 5 minutes the volunteers completed a questionnaire
and in addition, the eye blinking rate of the volunteers was measured. The same procedure
was carried out with exposure to clean air. An eye irritation index was developed on the basis
of questions with a 5 grade scale The following grades were discerned: 1=none, 2=slight,
3=moderate, 4=strong and 5=very strong. In the table below the score of Weber-Tschopp et
al. (1977) in volunteers exposed to formaldehyde is presented.
               Formaldehyde exposure level ppm                  eye irritation index
                                 0 03                                     1.2
                                  0.5                                     1.3
                                  1.2                                    1.75
                                  1.7                                    2.1
                                  2.1                                    2.3
                                  2 5                                    2.5
                                  2.8                                    2.8
                                  3 2                                    2.9
It is clear from this table, that the eye irritation index hardly increases going from 0.03 to 0.5
ppm. The authors state, that below 1.2 ppm the eye irritation index did not increase
significantly. Also the eye-blinking rate (measure of eye irritation) did not increase at levels
between 0.03 and 1.2 ppm formaldehyde, but significantly increased at levels above 1.2 ppm
On the basis of the study of Weber-Tschopp (1977) the formaldehyde level should not exceed
1 2 ppm in the workroom in order to prevent eye irritation.
Kulle (1993) exposed 19 healthy non-smoking volunteers to formaldehyde in order to explore
eye irritation Nineteen volunteers were exposed for 3 hours to 0, 1 and 2 ppm formaldehyde
at rest and to 2 0 ppm formaldehyde with intermittent moderate exercise for 8 minutes each
half hour. Ten subjects were also exposed to 0.5 ppm in the same way and 9 subjects to 3.0
ppm only at rest. Symptom questionnaires were completed directly before and immediately
after each exposure. The following severity levels were assigned: 0=none, 1=mild (present
but not annoying); 2=moderate (annoying), and 3=severe (debilitating).
                                                                                                  6/8
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<pre>  Corporate Safety, Health, Environment &
   Manufacturing
  Milieu & Productveiligheid
  Yourrreference              Our reference              'Direct line          Date.
                              WB034/CVM 7404              +31 45 5787128       19 July 2001
                              DMM'
  The results are presented in the table below;
        Formaldehyde level
                                       1
                                         ., Mild eye irritation        • Moderate eye irritation
                   0.0                            1. of 1,9                      Oof 19
;             •    0.5                           Oof 10                    •     Oof 10
                   1.0                           5 of 19                         1 of 19
                  .2.0                           10 of 19                        4-of 19- ,
                 , 3,0                             9 of 9                         4 of'9
  Benchmark analysis according to a Weibull model provided the following estimates of the
  exposure level, of an increase of 5 % response:
   • 0.7 ppm for a .5% increase of the'response for mild, eye irritation!
  •• 1.0 ppm for .a response of 5% fdf.'rripdferate'eye irritation.,
  The experiments of Kulle (T993); are qualitatively and quantitatively well described.-Also Kulle
  observed., that it was not possible with a panel' of 19 volunteers to make a distinction between
  air with 0.5 ,ppm formaldehyde, and clean air It is riot clear, why D E C O S did not consider the
  study of Kulle (1993) for standard settirig of eye'irritation.         '
  Conclusions
  The studies in volunteers show clearly, that up to 0.5 ppm exposure to formaldehyde
  perceptions of eye irritation are comparable-in exposed and non exposed volunteers. The
                       j
  best data for dose response modelling are those from Kulle (1993). The Benchmark dose for
  a 5% increase of slight eye irritation was estimated to be- 0.7 ppm in- the volunteers, studied
  by Kulle (1993). An occupational'standard of 0.3 ppm formaldehyde for 8 hours time weighted
  average and a short term exposure standard of 1 ppm for 15 minutes is more than sufficient
  to avoid, a significant increase of eye irritation in workers.
  Occupational Hygiene monitoring
  D E C O S proposes a very low occupational exposure limit. Not all methods bf industrial
  hygiene monitoring of/orrhaldehyde are comparable concerning their detection limit.
  Therefore D E C O S is urgently requested'to indicate their preference fbr a personal sampling
  and-monitoring methodi for formaldehyde at,a level of 0.15 mg/m3'.
  References                .                          ' ' • • ' , ' ' • •
  Andersen I-. • and. Molhave- L , 1983. .Controlled human studies with formaldehyde:              In
  Formaldehyde toxicity, ed.' J E Gibson,pp 154--1'65 Washington DC Hemisphere,, 1983-.
                                                                                                   7/8
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<pre>Corporate Safety, Health, Environment &
Manufacturing
Milieu & Productveiligheid
Your reference            Our reference          Direct line           . Date
                          WB034/CVM 7404         +31 45 5787128          19 July 2001
                          DMM
Bender J.R., Mullin L S , Graepel G . J . and Wilson W.E., 1983. Eye irritation response of
humans to formaldehyde. American Industrial Hygiene Association Journal 44: 463-465,
1983
Boysen M , 1982. The surface structure of the human nasal mucosa. I. Ciliated and
metaplastic epithelium in normal individuals. A correlated study by scanning/transmission
electron and light microscopy. Virchows Archiv B [cell Pathology], 40, 279-294, 1982.
Heck H ; Casanova M ; 1999. Pharmacodynamics of formaldehyde: applications of a model for
the arrest of D N A replication by DNA-protein cross-links. Toxicology and Applied
Pharmacology, 160(1), 86-100, 1999.
Kamata E; Nakadate M ; Uchida O; Ogawa Y ; Suzuki S; Kaneko T; Saito M ; Kurokawa Y ,
 1997. Results of a 28-month chronic inhalation toxicity study of formaldehyde in male Fisher-
344 rats. Journal of Toxicological Sciences, 22 (3), 239-254, 1997.
Kulle T.J., 1993. Acute odour and irritation response in healthy              non-smokers with
formaldehyde exposure. Inhalation Toxicology 5: 323-332, 1993.
Morgan KT, 1997. A brief review of formaldehyde carcinogenesis in relation to rat nasal
pathology and human health risk assessment. Toxicological Pathology, 25(3), 291-307, 1997.
Reuzel P G J , Wilmer J W G M , Woutersen RA, Zwart A , Rombout PJA.and Feron V J , 1990.
 Interactive effects of ozone and formaldehyde on the nasal respiratory lining epithlium in rats.
Journal'of Toxicology and Environmental Health 29, 279-292, 1990.
Weber-Tschopp A , Fischer T and Grandjean E., 1977. Irritating effects of formaldehyde in
humans. Int. Arch. Occup. Environ Health 39: 207-218, 1977.
Zwart A, Woutersen RA, Wilmer J W G M , Spit B J and Feron V J , 1988 Cytotoxic and adaptive-
effects in rat nasal epithelium after 3 day and 13 week exposure to low concentrations of
formaldehyde vapour. Toxicology 51, 87-99, 1988
                                                                                              8/8
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<pre>Gezondheidsraad
Health Council of the Netherlands
mr dr W ten Berge
Corporate Safety, Health, Environment and Manufacturing
Milieu & Productveiligheid
Postbus 6500
 6401 J H Heerlen
 Subject
Your reference
 Our reference
Enclosure(s)          1
Date                  January 27, 2003
Dear dr Ten Berge,
In 2001, the Dutch Expert Committee on Occupational Standards (DECOS) published
a draft report on formaldehyde for public review. Your organisation used the opportu-
nity to comment on the draft report. The committee thanks you for your comments,
which were used in finalising the report. On behalf of the President of the Health
Council of the Netherlands I herewith present you the DECOS' reaction to your
comments.
You are of the opinion that several animal studies (Zwart et al 1988, Reuzel et al 1990
and Kamata et al 1997) show that a concentration of 1 ppm appears to be the No Ob-
served Adverse Effect Level for formaldehyde. Taking the interspecies variation in na-
sal cell epithelium proliferation into account as well, you suggested a H B R O E L of 0.3
                  3                                                      3
ppm (0.3 6 mg/m ) in stead of the H B R O E L o f 0.12 ppm (0.15 mg/m ) that the commit-
tee recommended. You concluded that the study of Wilhelmsson and Holmstrom
(1992) cannot be* the basis of deriving a H B R O E L because the exposure levels were
not measured at the time the sympoms were studied and thus cannot be related. The
committtee is however of the opinion that based on the review of Paustenbach etal
(1997) and the studies of Anderson et al (1983) and Wilhelmsson (1993), it can be con-
                                                                                        3
cluded that (minimal) effects are found in humans at an exposure level of 0.3 mg/m .
The committee therefore considered this level as a L O A E L . The committee concluded
that a factor of 2 (instead of 3) should be sufficient for the extrapolation from L O A E L
to N A E L because the incidence of the effect is low, the effects are not systemic and
'accomodation' might occur at low exposure levels.
P.O Box 16052                                                          Visiting Address
NL-2500 BB Den Haag                                                    Parnassusplein 5
Telephone +31 (70) 340 75 20                                           NL - 2511 V X Den Haag
Telefax +31 (70) 340 75 23                                             email: GR@gr.nl
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<pre>Gezondheidsraad
Health Council of .the Netherlands
Subject               Comments in public draft 'Formaldehyde'
Our reference         1957/AvdB/459-P38
Page                  2
Date                  January 27, 2003
Moreover, you commented that the study of Bender et al has been characterised by a
strong selection of the volunteers. Only volunteers were included in the study who res-
ponded to 1.3-2.2 ppm formaldehyde within 6 minutes. The committee agrees with
your comment on this study and concluded that this study can not be used for deriving
a STEL. Therefore, the committee is of the opinion that the total body of acute studies
(Paustenbach et al, 1997, Bender et al, 1983) indicate that at an exposure level of 1.0 to
           3
 1.2 mg/m sensory irritation will still be present. The committee considered an safety
factor of 2 sufficient for the extrapolation from L O A E L to N A E L . Therefore, DECOS
                                     3
recommends a STEL of 0.5 mg/m .
The final report was published on January 27, .2003. Enclosed you will find a copy.
Yqurs^siscerely,
P.O Box 16052                                                            Visiting Address
NL-2500 BB Den Haag                                                      Parnassusplein 5
Telephone +31 (70) 340 75 20                                             NL - 2511 V X Den Haag
Telefax +31 (70) 340 75 23                                               email. GR@gr.nl
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<pre>       DEPARTMENT O F H E A L T H A N DH U M A N SERVICES                          Public Health Service
4                                                                                  National Institute for Occupational
                                                                                      Safety and Health
                                                                                   Robert A. Taft Laboratories
                                                                                   4676 Columbia Parkway
                                                                                   Cincinnati OH 45226-1998
                                                                                   September 5,2001
                                                                         'jii... _     k5BX£&             I
                                                                   5 / ;
 Health Council of the Netherlands                              ^         ^ 3       OKT, 2001             1
 c/o Dr. ASAM van der Burght
 Scientific Secretary
                                                                         •i                J > A S _ J
 DECOS/Committee on Compounds Toxic to Reproduction
 P.O. Box 16052                                                          ±                | % f c £ i a J
 2500 BB Den Haag
 THE NETHERLANDS
 Dear Dr. Van der Burght:
 Thank you for the opportunity to review the draft DECOS document on formaldehyde and the
 draft documents on toluene, styrene, and xylene prepared by the Committee on Compounds Toxic
 to Reproduction. We apologize for not getting these comments to you,at an earlier date.
 If you have any questions regarding these reviews, please contact me at: 513/533-8320 (telephone)
 or email: RDZl@CDC.gov.
                                                     ;erely yours,
                                                          3
                                                 Ralph D^zjafiwalde
                                                 Senior Scientist
                                                 Document Development Branch
                                                 Education and Information Division
 Enclosures (4)
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<pre>         Formaldehyde—-Health-based Recommended Occupational Exposure Limit
                                 DECOS/NEG Draft Document
         Comments of the National Institute for Occupational Safety and Health (NIOSH)
 General Comment
 The conclusion made in the document appears to have been significantly influenced by the meta-
 analysis by Collins et al. [JOEM, 39(7): 639-651]. This industry sponsored meta-analysis did
 find, as did the previous meta-analyses, a significantly elevated relative risk estimate for
 nasopharyngeal cancer (NPC). This excess risk was not apparent in the cohort studies once it
 was corrected for the missing information from studies that did not report findings for NPC. In
 this regard, the meta-analysis by Collins et al. study is superior to the earlier reported meta-
 analyses. However, an excess of NPC was still observed among the case-control studies, which
 was borderline significant (p=0.06). The analysis performed by Collins et al. dismisses the
 findings from the case-control studies on the basis that these studies had substantial potential for
misclassification of exposures. Although this is undoubtably true, the fact is that this kind of
non-differential exposure misclassification is well known to lead to bias towards the null (i.e.,
towards not seeing an effect). Thus, if anything, the results from the case-control studies would
be expected to be stronger than observed if this bias could be eliminated. Furthermore, another
NPC case-control study has been recently published, which was not included in the meta-analysis
by Collins et al. or cited in the draft document. This study by Vaughan et al. [Occ. Environ. Med
2000; 57(6):376-384] found a significant association between formaldehyde exposure and NPC
risk that increased with both duration of exposure and cumulative exposure. If this study were
included in an updated meta-analysis it would most likely make the results for NPC statistically
significant particularly for the case-control studies.
Given the results from the 3 meta-analyses and the study by Vaughan et al.,, there is evidence to
suggest that occupational exposure to formaldehyde is causally related to NPC. In addition, there
is an incomplete review of many existing epidemiologic and other human studies that could
collectively provide more evidence of a potential adverse effect from formaldehyde, exposure. If
there was a reason for omitting these studies, it, should be- stated. Consideration, may also want
to be given to including a statement about the in vivo generation of formaldehyde from the
metabolism of some chemicals that can be consumed or used for therapeutic purposes. For
example, one ofthe metabolites of cyclophosphamide is formaldehyde.
Specific Comments
Page 5, Current limit values: the National Institute for Occupational Safety and Health (NIOSH)
recommended exposure limit (REL) for formaldehyde is: 0.016 ppm TWA and 0.1 ppmceiling
limit (15-minutes); the U.S. Occupational Safety and.Health Administration (OSHA) permissible
exposure limit is: 0.75 ppm TWA and 2 ppm STEL.
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<pre>           Continued-NIOSH comments on draft Formaldehyde DECOS/NEG document
 Section 7
                                                             3
 In section 7, exposure concentrations are expressed in mg/m (ppm) whereas earlier in the
                                                         3
 document concentrations were expressed in ppm (mg/m ). Some concentrations are expressed in
        3
 mg/m only. Readability would be enhanced by using the same units for concentration (e.g., ppm
          3
 (mg/m )) throughout the document.
Page 27, first paragraph, last sentence
Unclear whether this refers to IgE, IgG, or both IgE and IgG antibody titers.
             nd
Page 27, 2 paragraph
The summary of this study refers to "formaldehyde sensitivity", but the definition of
                                                   th
 formaldehyde sensitivity isn't indicated. In the 4 sentence, formaldehyde sensitivity appears to
be based on self-reported information whereas elsewhere in the document the phrase may refer to
the presence of formaldehyde-specific IgE. It's unclear if formaldehyde sensitivity in the 5*
sentence of this paragraph is based on self-report information or the results of allergen-specific
IgE results.
Section 7.1.4, Effects on pulmonary function in. healthy and asthmatic subjects
The discussion of pulmonary effects is inconsistent. Of the studies discussed in section 7.1.4,
only one found an association between pulmonary function and formaldehyde exposure (i.e.,
Her94). In contrast, Table 1 on page 30-31 includes several: studies in which a difference in lung
function was observed (i.e., Her94, Akb94, Kil89, and Kri93). It's not clear why only Her94 was
discussed in section 7.1.4.
In the summary of cross-sectional studies of workers occupationally exposed to formaldehyde on
page 29, the document states that "after exposure for a few hours decreases of the FEV1 and
FVC have been observed". In contrast, in the summary of human studies of pulmonary function
on page 52, the document states that "no changes in pulmonary function have been found in
                                                                  3
humans exposed to formaldehyde concentrations up to 3.6 mg/m (3 ppm).
The discussion of pulmonary effects also appears to be incomplete. A literature search revealed
a number of other studies evaluating pulmonary function among individuals exposed to
formaldehyde. These studies included:
Abkar-Khanzadeh F, Mlynek JS. Changes in respiratory function after one and three hours of
exposure to formaldehyde in non-smoking subjects. Occup Environ Med 1997; 54(5):296-300.
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<pre>            Continued-NIOSH comments on draft Formaldehyde DECOS/NEG document
   MalakaT. Kodama AM. Respiratory health of plywood workers occupationally exposed to
   formaldehyde. Arch Environ Health 1990;45(5);288-294.
   Alexandersson R, Hedenstiema G. Pulmonary function in wood workers exposed to
   formaldehyde: a prospective study. Arch Environ Health 1989;44:(1):5-11.
   Holness DL, Nethercott JR. Health status of funeral service workers exposed to formaldehyde.
   Arch Environ Health 1989;44(4);222-228.
   Horvath EP, Anderson H, Pierce WE, et al. Effects of formaldehyde on the mucous membranes
., and lungs: a study of an industrial population. J Amer Med Assoc 1988; 259(5):701-707.
   Green DJ, Sauder LR, Kulle TJ, Bascom R. Acute response to 3,0 ppm formaldehyde in
   exercising healthy nonsmokers and asthmatics. Am Rev Respir Dis 1987;135(6):1261-1266.
   More recent (i.e., after 1997) studies include Kriebel D, Myers, D, Cheng M, et al. Short-term
   effects of formaldehyde on peak expiratory flow and irritant symptoms. Arch Environ Health
   2001; 56(1): 11-18.
   Section 7.1.7
               nd
   Page 32,, 2 paragraph-The percentage of exposed workers with dyspasia is reported to be 18%,
  but what was the percentage of dyspasia in the non-exposed? Were the differences in dyspasia
   significant? If so, then this study should not have been dismissed for its having too small
  numbers. Small sample size would be, a concern if the findings were negative, but shouldn't be a
   concern if the findings are positive.
  The text and table headings imply that the table in this section (and similar tables in other
   sections) is a comprehensive summary of the studies. But, the tables only contain selected
  studies. The basis for including (or omitting) a study is unclear.
  In addition, some studies are discussed in the text ofthe document but not in the appropriate
  tables (e.g., Sal91) and others are mentioned in the, tables but not, in the text.
  Retrospective cohort mortality/morbidity studies, page 33-37
  Only 3 retrospective cohort mortality studies (and related fbllow-up/related studies) are included
  in Table 2, which summarizes the retrospective cohort mortality studies of workers occupationally
  exposed to formaldehyde. Only the cohort mortality study by Blair and colleagues and the re-
  analyses and follow-up studies of this study are discussed in the text. Yet, there have been many
  mortality studies of formaldehyde-exposed individuals. The document should either include a
  more comprehensive review ofthe studies of clearly state why only selected studies are
  discussed.
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<pre>          Continued-NIOSH comments on draft Formaldehyde DECOS/NEG document
 Case-control studies, page 37-39
 Again, only selected studies are presented, but this is not clearly stated and the reason for
 focusing on these studies is not discussed. Then, on page 39, the committees appear to make a
 conclusion about the relationship between occupational exposure to formaldehyde and cancer
 based on only these selected studies.
 Meta-analysis, page 39-40
 If the committee is going to rely on the results of one or more ofthe meta-analysis papers,
instead of providing a comprehensive review ofthe individual studies, the document should
 include a comprehensive critique ofthe meta-analysis papers. Currently, the committees point
 out that the meta-analysis by Collins and colleagues included more studies than the previous
 meta-analyses and an evaluation of the exposure potential for jobs in the general population case-
 control studies, but they do not provide a thorough critique of the three meta-analysis papers and
 adequately justify their reliance on the meta-analysis by Collins and colleagues.
 The meta-analysis by Collins and colleagues included 47 epidemiologic studies. Yet, only a few
 of these studies are discussed in the document. No rationale for discussing only selected papers
 is given. Thus, it is unclear whether the document accurately reflects what is known about the
 carcinogenic effects of formaldehyde. In addition, the document does not clearly state that only a
 few ofthe many studies evaluating the carcinogenicity of formaldehyde are presented. Instead,
the initial impression is that the document provides a comprehensive review of all studies.
             th
Page 50, 5 line- The statement "Clearly, for tumour formation drastic conditions, seem to be
required" doesn't seem to be appropriate given the range of exposure concentrations used in
animal studies. This section fails to point out that there was one study where a significant
increase in tumors was observed at 2 ppm (Ker83), and another where it was observed at 0.3 ppm
(Kam97). Thus the exposures producing effects in the animal studies are at least within ,a order
of magnitude, and perhaps within a, factor of 2 of those found in the workplace.
Page 54, carcinogenic effects in man
The summary appropriately focuses on respiratory and nasopharyngeal cancers. However, the
summary of the carcinogenic effects in man' should also include a brief statement about what is
known about the relationship between formaldehyde exposure and other cancers.
Genotoxicity, page 55
The draft document states that there are no adequate data available on genetic effects .of
formaldehyde in humans. If the committee feels that the studies of genetic effects are inadequate,
this needs to be discussed in the document. Three studies were mentioned that suggested effects
of formaldehyde exposure (J3al92, Boy90, Sur93). The rationale for discounting the findings of
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<pre>        Continued-NIOSH comments on draft Formaldehyde DECOS/NEG document
the study by Boysen and colleagues should be strengthened. The rationale for not discussing
other studies and/or discounting the findings of other studies also needs to be discussed. The
following articles should be considered for inclusion in the document:
Ying CJ, Ye XL, Xie H. et al. Lymphocyte subsets and sister-chromatid exchanges in, the
students exposed to formaldehyde vapor. Biomed Environ Sci 1999<12(2):88-94.
He J. Jin Lf, Jin H Y. Detection of cytogenetic effects in peripheral lymphocytes of students
exposed to formaldehyde with cytokinesis-blocked micronucleus assay. Biomed Environ Sci
 1998;ll(l):87-92.
Ying CJ, Yan WS, Zhao MY, et al. Micronuclei in nasal mucosa, oral mucosa and lymphocytes
in students exposed to formaldehyde vapor in anatomy class.. Biomed Environ Sci
 1997';10(4):451-455,
Vasudeva N, Anand C. Cytogenetic evaluation of medical students exposed to formaldehyde
vapor in the gross anatomy dissection laboratory. J Am Coll Health 1996;44(4): 177-179.
           nd              st
Page 63, 2 paragraph, 1 sentence-This statement isn't consistent with the fact that at least one
study found a significant excess of tumors at 3 ppm, which is close to the exposure
concentrations experienced by some workers.
Editorial Comments
Page 6 paragraph 5 line 4: Replace the word "auteurs" with the word "authors". The word
"auteurs" appears in several places in the text. Please make similar corrections in other places as
well.
Page 6 paragraph 6 line 7: rewrite "hyper/metaplasia" as hyperplasia and metaplasia as
separate entities
Page 7 paragraph 2 line 1: Replace the word " inhalatory" with the word "inhalation."
Page 9 paragraph 3 line 5: Word "auteurs". See above.
Page 11 Item 1.1 line 9: "In the.latter case on ..." Replace "on" with the word "an"
Page 12 Item 1.3 line 2: "... DECOS in, respectively, 1981 and 1987 (WGD, RA 4/81: RA 3/87).
Rewrite this as " ... DECOS in 1981 (WGD RA 4/81) and 1987 (RA 3/87), respectively.
Page 13- Item 2 line 2: " ... protect occupational exposed     Rewrite as "... protect
occupationally exposed ..."
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<pre>         Continued-NIOSH comments on the draft Formaldehyde DECOS/NEG document
 Page 14 Item 3.1: "Identity and properties". Replace with "Identification and Chemical
 Properties".
 Page 16 Item 4.2.2 line 4: replace the word "fibreboard" with "fiberboard"
 Page 16 Item 4.2.2 line 6: The words "auto applications" does not make .sense. Probably it
 should be "automobile applications" or "automobile manufacturing".
 Page 17 Item 5.1 last line: "... formaldehyde are potentiated by...." The exact toxicological
 definition of "potentiation" does not apply here. Perhaps the word " increased" should replace
 the word "potentiated".
 Page 18 Item 5.2 paragraph 1 line last: Replace the word "Annex" with "appendix".
 Page 18 Item 5.2 paragraph 2 line 1: "The following data... date." Rewrite this sentence as " The
 following represents more recent occupational exposure data"
 Page 22 Item 7.1.2 paragraph 2 line 4: "(during of exposure not described)". Rewrite as "
 (duration of exposure not described).
 Page 26 paragraph 2 line 2: "... The reference group existed      Replace the word existed with
 the word "consisted."
Page 31 Table 1 continued reference Kri93 under effects line 3: Replace the word "rares" with
 "rates."
Page 32 paragraph 2 line 4: "... 37 age-matched referents." Replace the word referents with the
word "controls."
Page 36 paragraph 1 lines 2 and 7: Replace the word " significant" in both places with the word
"significantly".
Page 37 paragraph 2 line 5: Replace the word " referents" with the word "controls"
Page 40 paragraph 1 line 17: replace the word "auteurs" with the word "authors."
Page 43 paragraph 1 line 1: "... middle mates). Replace the word mates with the word "meatus."
Page 47 paragraph 1 line 2: replace Annex with "appendix"
Page 47 paragraph 3 line 4: "... formaldehyde during 6 hours...." Replace the word "during" with
the word "for"
Page 48 Item 7.2.8 paragraph 2 line 3: "... following exposure by inhalation ..." Rewrite as "...
following inhalation exposure..."
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<pre>        Continued-NIOSH comments on draft Formaldehyde DECOS/NEG document
Page 49 paragraph 2 lines 5 and 12: Replace the words "hyper- and metaplasia" with "
hyperplasia and metaplasia" in each case
Page 49 paragraph 2 line 6: Replace the word "precize" with the word "precise"
Page 49 paragraph 2 line 16: Delete the period between the words "non-exposure" and
"observation"
Page 50 Item 7.2.9: "Reproduction toxicity" should read as "Reproductive toxicity"
Page 50 Item 7.2.9 paragraph 1 line 1: "... concluded in her..." Should read as "... concluded in
its..."
Page 50 Item 7.2.9 paragraph 1 line 8: "... of the embryo being ..." Should read as "... ofthe
embryo, it being..."
Page 50 Item 7.2.9 paragraph 2 line 1: "... the reproduction toxicity..." Should read as     the
reproductive toxicity..."
Page 51 Item 7.2.10 paragraph 1 line 3: " ... during 28 days...." Shouldread "... for 28 days..."
Page 52 Item 7.3 paragraph 3 line 1: "Transient rhinitis have been ..." Should read as,"Transient
rhinitis has been..„"
                                                                          1
Page 53 paragraph 3 line 18: "... same collection of data... Should read as "... same data..."
Page 53 paragraph 4 lines 4 and 5: " ...population and confounding by..." Should read as "...
population confounded by ..."
Page 54 paragraph 2 line 6: Replace "auteurs" with "authors"
Page 54 paragraph 4- short term exposure line 6: "hyper/metaplasia" Rewrite as hyperplasia and
metaplasia or - hyperplasia or metaplasia. I think the former is the correct way.
Page 59 under Sweden line 2: "... was dated from ..." Delete the word "from"
Page: 62 paragraph 1 last line: " Both ... conclusion". Put a period after the word "conclusion"
Page 62 paragraph 2 line 6; "maldehyde than humans...." Delete the words "than humans"
Page 63 paragraph 2 lines 6 and 7: " ... has meanwhile been.... and thus should be       Rewrite as
" and has meanwhile been .... Thus should be ..."
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<pre>        Continued-NIOSH comments on the draft Formaldehyde DECOS/NEG document
Page 63 paragraph 3 lines 2 and 3: "... experimental animals reveals a NOAEL ... while in all..."
Rewrite as "...experimental animals reveal a NOAEL .... However in all..." (delete the word
"while.")
Page 63 paragraph 3 lines 9 and 11:"... formaldehyde ... with respect to ... damaging or not
                                                                    3
damaging the nasal.." Rewrite as "... formaldehyde {1.2 mg/m (lppm)}... with respect to its
effects on the nasal..."
Page; 64, paragraph 1 lines 6 and 11: "... auteurs". Replace it with the word "authors" in each
ease.
Page 65 paragraph 1 line 5: "committee consideres a factor          Rewrite as "committee
considers a factor..."
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<pre>Gezondheidsraad
Health Council of the Netherlands
mr dr R D Zumwalde
National Institute for Occupational Safety and Health
Robert A Taft Laboratories
4676 Columbia Parkway
Cincinnati O H 45226-199.8
United States of America
Subject                : Comments in public draft 'Formaldehyde'
Your reference         : September 5,, 2001
                                                                      1
Our reference          : 1957/AvdB/459|p8>^
Enclosure(s)          ,: 1
Date                   : January 27, 2003'
Dear dr Zumwalde,
In 2001, the Dutch Expert Committee on Occupational Standards. (DECOS) published
a draft report on formaldehyde for public review. Your organisation used the opportu-
nity to comment on the draft report. The committee thanks you for your comments,
which were used in finalising the report. On behalf of the President of the Health
Council of the Netherlands I herewith present you the DECOS' reaction to your
comments.
You commented'that the metaanalysis of Collins et al (JOEM, 39(7):639-651) would
most likely have found a statistically'.significant association between exposure to for-
maldehyde and nasopharyngeal cancer (NPC) i f the study of Vaughan et al was inclu-
ded. Therefore you concluded that there is evidence to suggest that occupational expo-
sure to formaldehyde is causally related to nasopharyngeal cancer. Although, the com-
mittee is of the opinion that there is no concvincing evidence for a positive association
between exposure and NPC, she decided to. adjusted her conclusions to: 'The committees
conclude that although a.small number of studies .produce limited .evidence for the association between,
nasopharyngeal cancer and' exposure to formaldehyde, the'overall total body of epidemiological data does
not support a causal relationship for a nasal, cancer risk at the experienced exposure levels (see last ali-
nea par 7.1.7). Moreover, the commitee is. of the opinion that i f sensory irritation is
prevented, as a consequence workers will be protected against to potential risk of nasal
cancer.
     Your comments concerning the current limit values are incorporated in the final re-
port. In addition, you suggested to include several studies discussing pulmonary ef-
fects. The committee did not include the human studies of Akbar-Khanzadeh, Mlynek,
P.O Box 16052                                                                       Visiting Address
NL-2500 BB Den Haag                                                                 Parnassusplein 5
Telephone +31 (70), 340 75 20                                                        NL - 2511 V X Oen Haag
Telefax+31 (70). 340 75 23                                                          email GR@gr.nl
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<pre>Gezondheidsraad
Health Council of the Netherlands
                                                                                             ( «
Subject              Comments in public draft 'Formaldehyde'
Our reference        1957/AvdB/4'59-R38
Page                 2
Date                 January 27, 2003
Malaka, Alexander et al, Holness et al, and Green et al in the final report because the
exposure levels in these studies were highland there were no new additional' effects we-
re found. Moreover; the human study of Kriebel et al is not added to the report either
because the differences between the exposed groups and the controls is (although rele-
vant and significant) limited. The study of Horvath et al is included in the report. The
results of this study confirm the presence of irritation after exposure to formaldehyde
but not the effects on the pulmonary function.
     The genotoxic studies you mentioned in your commented are derscribed in the f i -
nal report.
Finally, DECOS appreciated very much your general comments on the quality of the
report. Based on these comments, several editorial corrections have been made. Be-
cause of your extended and detailed .comments, DECOS is of the opinion that the quali-
ty and clearness of the report is improved, and hopes that the report is easier to follow.
 The final report was published on January 27, 2003. Enclosed you will find, a copy.
P.O Box 16052                                                         Visiting Address
NL-2500 BB Den Haag                                                   Parnassusplein* 5
Telephone +31 (70) 340 75 20                                          NL - 2511 V X Den Haag
Telefax +31 (70) 340 75 23                                            email: GR@gr.nl
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<pre>              VERENIGING                  ACADEMISCHE                        ZIEKENHUIZEN
                                                                  ! Hr.
                                                                 i           11 JULI
               Gezondheidsraad
               t.a.v. mevr. dr. A.S.A..M. van der Burghri '*°
                                                                 r  vv
                                                                                      HB
                                                                                                                     AZ
               Secretaris Commissie W G D                        j 1.
               Postbus 16052                                    j"
               2500 BB Den Haag,                                 J
                                                                                                                   014 6 8
                                                                    Arebief
        Datum  10 juli 2001                                         Bijlagen
-.oUw kenmerk
C^)ns kenmerk  012555/JL/sas
    Onderwerp  Openbaar concept-rapport over beroepsmatige blootstelling aan formaldehyde, 2001/19OSH, d.d. 18 mei 2001
CM
co
 O
 co
               Geachte mevrouw van der Burght,
CM
              Naar aanleiding van uw brief van 18 mei j.l. (kenmerk: U 972/AvdB/mj/459-N33),
              zend ik u hierbij het commentaar van de Vereniging Academische Ziekenhuizen (VAZ)
              op het openbaar concept.
              De V A Z onderschrijft het belang van het nemen van maatregelen om de blootstelling
              aan formaldehyde zoveel mogelijk te beperken. Regelgeving is een goed middel om
              adequate maatregelen landelijk voor te schrijven, De V A Z wil zich inzetten om mee te
              denken over de inhoud van deze regelgeving, zodat deze doeltreffend zijn, effect
              sorteren en werkbaar zijn. Tegen dat licht is het openbaar concept door ons beoordeeld.
              Navraag bij een van de academische ziekenhuizen leverde het volgende beeld op:
              Een investering voor afzuigtafels voor de uitsnijkamers, kasten voor opslag van
              formaline en bouwkundige infcastpuctuur heeft circa / 500.000,— gekost. De- extra,
              afzuiging is aangebrachtin een bestaande situatie, waarbij aangesloten is op het
              bestaande ventilatiesysteem. De ruimteventilatie in het laboratorium is 10x en is ruim
              voldoende. Het laboratorium voldoet aan de normen.
              De eerste metingen na oplevering in 1997 gaven, een gemiddelde waarde van 0,1 ppm
              formaldehyde boven de uitsnijtafel (de werkplekken). De metingen in 2000 bij de
              uitsnijtafels gaven een gemiddelde waarde aan van 0,2 - 0,225 ppm. Met ander woorden:
              de nieuwe MAC-waarde van 0,12 ppm is in deze meest optimale situatie niet haalbaar
              tenzij er opnieuw een forse investering gedaan wordt; Daarnaast zal een verdere sub-
              optimalisatie voor andere arbo-technische problemen, zoals tooht zorgen. Voomoemde
              situatie betreft een zeer moderne uitgeruste werksituatie, hetgeen landelijk gezien
              geenszins overal het geval zal zijn.
              Daarom zijn wij tot de conclusie gekomen dat de door u voorgestelde verlaging van de
              MAC-waarden tot giganusche bouwkundige en technische investeringen zullen gaan
              leiden en ernstige problemen zullen geven bij de naleving van de door u voorgestelde
              waarden.
              Wij. vertrouwen er dan ook op datu onze opmerkingen bij het opstellen van de
              definitieve rapport mee zult wegen.
              Namens de Vereniging Academische Ziekenhuizen
              Hoogachtend,                                                                                     fWvb     r?<?f w€/"?.
                        ^andman,
                      ieen secretaris
              Postbus 9696 3506. GR Utrecht Oudlaan4 telefoon (030) 2739880 fax (030) 2739532 email.vaz@vaz.nl'
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<pre>Gezondheidsraad
Health Council of the Netherlands
Aan mr J Landman
Algemeen Secretaris Vereniging Academische Ziekenhuizen (VAZ)
Postbus 9696
3506 G R Utrecht
Onderwerp
Uw kenmerk
Ons kenmerk
Bijlagen
Datum
Geachte heer Landman,
In 2001 maakte de Voorzitter van de Gezondheidsraad een concept-rapport van de
Commissie W G D van de Raad openbaar over formaldehyde. Belangstellenden werden
in de gelegenheid gesteld commentaar te leveren op het rapport. U maakte van die gele-
genheid gebruik. Op verzoek van de Voorzitter van de Raad doe ik u hierbij de reactie
van de commissie op uw commentaar toekomen.
Uw commentaar heeft voornamelijk betrekking op de haalbaarheid van de voorgestelde
gezondheidskundige advieswaarde. De Commissie W G D betrekt echter alleen inhoude-
lijk commentaar bij het afronden van het advies. Voor commentaar met betrekking tot
de haalbaarheid van de advieswaarde verwijst de commissie u naar de Subcommissie
MAC-waarden van de Sociaal Economische Raad (SER): Deze commissie stelt, reke-
ning houdend met de haalbaarheid van de gezondheidskundige advieswaarde, in een
tweede fase aan het Ministerie van SZW een MAC-waarde voor. Ik zal uw brief daar-
om ook doorsturen aan deze commissie.
Het rapport is op 27 januari 2003 gepubliceerd; bijgaand vindt u een exemplaar.
cc de heer mr JJ Brokamp, Subcommissie MAC-waarden, SER
Bezoekadres                                                               Postadres
Parnassusplein 5                                                          Postbus 16052
2511 VX Den Haag                                                          2500 BB Den Haag
Telefoon (070) 340 75 20                                                  Telefax (070) 340 75 23.
email: GR@gr.nl
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