<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>Wheat and other
cereal flour dusts
Health-based recommendation on occupational exposure limits
To: the Minister of Social Affairs and Employment
No. 2017/10, The Hague, July 20, 2017
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<pre>                                                                               Wheat and other cereal flour dusts | page 2 of 26
contens
contents
   Samenvatting3                                               References                                                  14
   Executive summary                                       5   Annexes                                                     17
01 Scope                                                   7 A epidemiological data published since 2004                   18
   1.1  Background                                         7
   1.2  Committee and procedure                            7 B risk calculations                                           23
   1.3  Data                                               7
02 Previous evaluations                                    7
   2.1  DECOS (2004)                                       7
   2.2  SCOEL (2008)                                       9
03 Update quantitative hazard assessment                 10
   3.1  Literature published since 2004                  10
   3.2  Existing guidelines and standards                 11
   3.3  Quantitative assessment of risk of sensitisation  12
   3.4  Comparison with SCOEL                             13
   3.5  Groups at risk                                    14
   3.6  Conclusions and recommendation                    14
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<pre>                                                                                                    Wheat and other cereal flour dusts | page 3 of 26
samenvatting                                                                                        heid raakt, maar er nog geen of nauwelijks
                                                                                                    klachten optreden. De Gezondheidsraad
                                                                                                    hanteert bij advieswaarden voor allergenen het
Op verzoek van de minister van Sociale Zaken        Tarwemeelstof: gezondheidsrisico’s voor         uitgangspunt dat niet alleen de allergische
en Werkgelegenheid (SZW) actualiseert de            bakkers                                         klachten, maar ook de sensibilisatie voorkomen
Gezondheidsraad het advies over de beroeps-         Blootstelling aan meelstof afkomstig van tarwe  moet worden, zo ook voor tarwemeelstof.
matige blootstelling aan tarwemeelstof. Eerder      en aan tarwe verwante graansoorten waaronder    Voor allergenen die mensen inademen is het in
leidde de Gezondheidsraad een gezond-               haver, gerst en rogge (hierna aangeduid als     het algemeen niet mogelijk een concentratie
heidskundige advieswaarde af van 0,12 milli-        tarwemeelstof) kan leiden tot aandoeningen      vast te stellen waaronder sensibilisatie niet
gram (mg) inhaleerbaar tarwemeelstof per            zoals:                                          optreedt. In die gevallen schat de Gezond-
kubieke meter (m3) lucht (gemiddeld over een        • astma;                                        heidsraad een concentratie waarbij het extra
8-urige werkdag). In het huidige advies stelt de    • ontsteking van het neusslijmvlies;            risico op sensibilisatie door blootstelling op de
Gezondheidsraad de advieswaarde bij tot 0,2         • ontsteking van het oogslijmvlies.             werkvloer beperkt is tot 1%.
mg inhaleerbaar tarwemeelstof per m3 lucht.                                                         In de algemene bevolking raken 2 op de 100
Dit advies is tot stand gekomen in de commissie     Deze kunnen het gevolg zijn van een allergische mensen (2%) gesensibiliseerd voor tarwemeel-
Gezondheid en beroepsmatige blootstelling aan       reactie. Vooral mensen die werken in bakkerijen stof. Een extra risico van 1% betekent dat er in
stoffen (GBBS) – een vaste commissie van de         en de meelverwerkende industrie krijgen         een werkomgeving waar mensen worden bloot-
Gezondheidsraad.                                    hiermee te maken.                               gesteld aan tarwemeelstof niet 2, maar 3 op
De Gezondheidsraad heeft een vaste rol bij de                                                       100 mensen gesensibiliseerd raken. Die ‘1%
bescherming van werknemers tegen mogelijke          Advieswaarde op basis van 1% extra              extra’ geldt sinds 2009 als een uitgangspunt
schadelijke effecten van stoffen waar zij tijdens   risico op sensibilisatie                        voor het Nederlandse grens-waardenstelsel.
hun werk mee in aanraking kunnen komen.             Aan een allergische reactie op een stof gaat
Meer informatie over die rol staat op               sensibilisatie vooraf: het moment waarop het
www.gezondheidsraad.nl.                             immuunsysteem in verhoogde staat van paraat-
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<pre>                                                                                                        Wheat and other cereal flour dusts | page 4 of 26
Nieuwe berekening op basis van meer                  De commissie acht het waarschijnlijk dat het      heeft toegevoegd aan de oude gegevens
gegevens                                             verschil in risico tussen Nederlandse en Zuid-    (waarop het eerdere advies was gebaseerd),
In het vorige advies van de Gezondheidsraad          Afrikaanse bakkers het gevolg is van een relatief wat de betrouwbaarheid vergroot.
heeft de commissie een onderzoek gebruikt            groot aantal personen met een aanleg voor het
over risico’s op sensibilisatie door blootstelling   ontwikkelen van een allergie (atopie) in de Zuid- Advies aan de minister
aan tarwemeelstof bij Nederlandse bakkers. Op        Afrikaanse populatie. Ook wijst de commissie      Voor de beroepsmatige blootstelling aan tarwe-
basis van dit onderzoek is er een advieswaarde       erop dat de werkomstandigheden in Zuid-Afrika     meelstof komt de commissie tot een gezond-
van 0,12 mg per m3 lucht berekend, overeenko-        verschillen van die in Nederland. De commissie    heidskundige advieswaarde van 0,2 mg
mend met een extra risico op sensibilisatie van      is daarom van mening dat het onderzoek bij        inhaleerbaar tarwemeelstof per m3 lucht, als een
1%. Sindsdien zijn er twee nieuwe publicaties        Zuid-Afrikaanse bakkers niet representatief is    gemiddelde concentratie over een 8-urige
verschenen die zich lenen voor het afleiden van      voor de Nederlandse werknemers en dat het         werkdag. Bij deze concentratie hebben wer-
een advieswaarde. Het ene onderzoek is               risico het meest betrouwbaar kan worden           kenden ten opzichte van de algemene bevolking
uitgevoerd bij bakkers in Zuid-Afrika, het andere    geschat op basis van de onderzoeken bij Neder-    1% extra risico op sensibilisatie voor tarwemeel-
bij bakkers in Nederland – net als het onderzoek     landse bakkers.                                   stof.
dat voor het eerdere advies is gebruikt.             Uitgaande van de twee Nederlandse onder-
Op basis van het onderzoek bij Zuid-Afrikaanse       zoeken komt de commissie tot een
bakkers schat de commissie voor een extra            advieswaarde van 0,2 mg inhaleerbaar tarwe-
risico van 1% een blootstelling van 0,04 mg per      meelstof per m3 lucht. Dit is een hogere concen-
m3 lucht. Dit suggereert dat Zuid-Afrikaanse         tratie dan de aanbeveling uit een eerder advies
bakkers al bij een lagere blootstelling een          (0,12 mg/m3). Het verschil wordt verklaard
bepaald risico lopen.                                doordat de commissie de nieuwe gegevens
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<pre>                                                                                                       Wheat and other cereal flour dusts | page 5 of 26
executive summary                                                                                     Health Council calculates the concentration at
                                                                                                      which the extra risk of sensitisation by
                                                                                                      occupational exposure is limited to 1%.
At the request of the Minister of Social Affairs     • inflammation of the nasal mucous membrane;     In the general population – independently from
and Employment, the Dutch expert Committee           • inflammation of the conjunctiva.               occupational exposure – 2 out of 100 people
on Occupational Exposure Safety (DECOS),                                                              (2%) are sensitised for wheat flour dust. An
one of the permanent Committees of the Health        These can be the result of an allergic reaction. extra risk of 1% means that in a workplace
Council, has updated its recommendation on           In particular, the health effects concern people where people are exposed to wheat flour dust
occupational exposure to wheat flour dust and        who work in bakeries and the flour processing    not 2, but 3 out of 100 people are sensitised. For
the risk of sensitisation. Previously, the Health    industry.                                        allergens, this ‘1% extra’ is the starting point for
Council derived a health-based recommended                                                            the Dutch OEL-system.
occupational exposure limit of 0.12 milligram        Recommendation based on 1% extra risk of
(mg) inhalable wheat flour dust per cubic metre      sensitisation                                    New calculation based on additional
(m3) air (8-h mean for a working day). In the        A chemical-induced allergic reaction is preceded information
current report, the Health Council adjusts its       by sensitisation: the situation at which the     In the previous advice of the Health Council, the
advisory value to 0.2 mg inhalable wheat flour       immune system is triggered, but no (significant) Committee has used a study in Dutch bakery
dust per m3 air.                                     complaints have yet occured. For                 workers and the risk of sensitisation to wheat
                                                     recommendations on allergens, including wheat    flour dust. On the basis of this study an advisory
Wheat flour dust: health risks for bakers            flour dust, the Health Council applies the       value was derived of 0.12 mg per m3 air,
Exposure to flour dust from wheat and the            principle that not only the allergic complaints, corresponding with a 1% extra risk of
related cereal grains rye, barley and oats           but also the sensitisation should be prevented.  sensitisation. Since then, two new studies have
(hereafter referred to as wheat flour dust) can      For inhalatory allergens, it is generally not    been published that can be used to derive an
lead to diseases, including:                         possible to derive a concentration below which   advisory value. One study was done in bakery
• asthma;                                            no sensitisation occurs. In those cases, the     workers in South Africa, the other in Dutch
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<pre>                                                                                                    Wheat and other cereal flour dusts | page 6 of 26
bakery workers – similar to the study used for       higher than the previous recommendation (0.12
the previous recommendation.                         mg/m3). The difference can be explained by the
On basis of the study in South-African bakery        fact that the Committee has combined new data
workers, the Committee calculates an exposure        and data used previously, which increases the
level of 0.04 mg/m3, corresponding to an extra       reliability of the estimation.
risk of 1%. This suggests that at lower exposure
levels South-African bakery workers are already      Recommendation to the minister
at a certain risk.                                   For occupational exposure to wheat flour dust,
The Committee considers it likely that the           the Committee derives a health-based
differences in sensitisation risk between Dutch      recommended exposure level of 0,2 mg
and South-African bakery workers is the result       inhalable dust per m3 air, as a mean
of a relatively large number of people               concentration over a 8-h working day. At this
predisposed to allergies (atopy) in the South-       concentration, workers have a 1% extra risk of
African population. The Committee also notes         wheat flour dust sensitisation compared to the
that working conditions in South-Africa differ       general population.
from those in the Netherlands. The Committee
therefore considers the study in South-African
bakery workers not representative for the Dutch
workers and concludes that the most reliable
estimation of sensitisation risk can be made on
basis of the studies in Dutch bakery workers.
Based on the two Dutch studies, the Committee
derives an advisory value of 0.2 mg inhalable
wheat flour dust per m3 air. This concentration is
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<pre>                                                                                                        Wheat and other cereal flour dusts | page 7 of 26
01 scope                                                                    1.2 Committee and procedure
                                                                            The present document contains the evaluation of the DECOS, hereafter
1.1 Background                                                              called the Committee.
At request of the Minister of Social Affairs and Employment, the Dutch      The Committee has taken into account the published literature until
Expert Committee on Occupational Exposure Safety (DECOS), one of the        November 2016. In January 2017, DECOS released a draft version of the
permanent committees of the Health Council, proposes health-based           report for public review. The individuals and organisations that
recommended occupational exposure limits for chemical substances in         commented, the received comments, and the subsequent replies by the
the air at the workplace. These recommendations serve as basis in setting   Committee are publicly available on the website of the Health Council.
legally binding occupational exposure limits by the minister.
                                                                            1.3 Data
Workers in bakeries and flour mills may be exposed to wheat and cereal      The Committee’s recommendations are based on scientific data, which
flour dusts. The Committee has previously evaluated the consequences of     are publicly available. Published literature was retrieved from Pubmed
exposure to these dusts (2004).1 The recommendation of the Committee        using key words ‘wheat’ and ‘allerg*’. The final search was carried out in
then, has not been implemented in the Dutch occupational exposure limit     November 2016.
system. In 2008, the Scientific Committee on Occupational Exposure
Limits (SCOEL) also published a report on wheat flour dust, and the
related cereal grains rye, barley and oats.2                                02 previous evaluations
In the current evaluation, the Committee updates its quantitative hazard
assessment of specific sensitisation by exposure to wheat and other         2.1 DECOS (2004)
cereal flour dusts. For additional information, the Committee refers to its DECOS has evaluated the consequences of occupational exposure to
previous report.                                                            wheat and other cereal flour dusts, previously.1 In this Chapter, the
                                                                            Committee summarises the critical considerations and conclusions of this
                                                                            evaluation. For details, the Committee refers to the original report from
                                                                            2004.
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<pre>                                                                                                                                                Wheat and other cereal flour dusts | page 8 of 26
Definition                                                                                                         These complaints can also be caused by irritation. Typically, development
‘Wheat flour dust’ is specified as finely ground particles of taxonomically                                        of allergy involves an initial exposure by which the immune system is
related cereal grains of the subfamily Festucoideae and the tribes                                                 sensitised, usually without the occurrence of symptoms. At subsequent
Triticeae and Aveneae, such as wheat (Triticum sp.), rye (Secale cereale),                                         exposures, sensitised individuals can suffer from allergenic respiratory
barley (Hordeum sp.) and oats (Avenea sativa) produced by subjecting                                               effects.
these grains to milling or some other form of processing. This specification
includes these flour dusts as due to cross-reactivitya, exposure to one of                                         Risk calculation and recommendation
these cereal flour dusts could result in sensitisation towards another.                                            The Committee concluded that it was not possible to determine a
                                                                                                                   threshold for sensitisation by allergens in (wheat) flour dust. To enable
Monitoring                                                                                                         some protection for the large group of potentially exposed workers, the
For sampling the inhalable flour dust fraction, gravimetric techniques are                                         Committee calculated exposure levels corresponding with predefined risks
used. In the Netherlands, monitoring inhalable dust is usually done with                                           on sensitisation induced by wheat and other cereal flour dusts. The
the Dutch ‘PAS6’ sampling head; international equivalents are also                                                 Committee considered the study published by Heederik et al. (2001)3 most
available.                                                                                                         suitable for quantitative hazard assessment, as it includes a good quality
The allergen content of the dust can be evaluated by the use of                                                    data set on both exposure and response (i.e. data on amounts of
immunoassays. Most of these techniques, however, have not yet been                                                 inhalable dust and allergens, on cases of sensitisation and prevalence of
standardised for routine monitoring.                                                                               atopy), and extensive statistical analyses were performed. Importantly, of
                                                                                                                   all good quality studies, Heederik et al. measured concentrations in the
Effects                                                                                                            lowest exposure range. In line with the current Dutch regulations, the
Exposure to allergens from these flour dusts can lead to allergenic                                                Committee calculated the exposure level that corresponds to an extra risk
respiratory effects, such as cough, rhinitis, conjunctivitis and asthma.                                           of sensitisation of 1% (i.e. a risk of 1%, in addition to the background risk).
                                                                                                                   For this calculation, the Committee used the exposure metric (mg dust/m3)
                                                                                                                   since this metric, in contrast to the amount of airborne allergens, can be
a
  Data on cross-reactivity mainly consist of data on wheat and rye. Since co-exposure to other barley and oats is
  common and (some degree of) cross-reactivity highly likely, these cereal grains are also included as subject for measured by standardised and validated methods.
  recommendation.
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<pre>                                                                                                         Wheat and other cereal flour dusts | page 9 of 26
The Committee determined the best fit of the exposure-response               that should be prevented are related to disorders of the respiratory tract
relationship in the lower exposure range using linear regression, which      and the eyes, such as rhinitis, conjunctivitis and, especially, asthma.
was described by the function:                                               According to SCOEL, these symptoms are persistent when induced
                                                                             immunologically (primarily IgE-mediated), and reversible when caused by
    AR = D/0.124 (lineair model)                                             irritation. SCOEL defined sensitisation as the development of specific IgE
                                                                             antibodies to any of several wheat flour dust allergens, and considered
where AR is the additional risk (%) and D is the estimated mean              sensitisation as a sentinel event since it causes an increased risk of
concentration inhalable dust (in mg/m3).                                     developing respiratory symptoms.
In this model, an uncertainty factor of 2 was included for taking into       SCOEL concluded that the available literature does not demonstrate a
account the variation in amounts of allergens in inhalable dust. The model   trustworthy threshold for any of the wheat flour dust-induced effects.
was considered only valid for exposure concentrations up to 3 mg             Exposure levels exceeding 1 mg/m3 and 3 mg/m3 inhalable wheat flour
inhalable/m3, as only below this value the exposure-response relationship    dust were considered as levels at which the risk increased of nasal
is linear.                                                                   symptoms and asthma, respectively. Reference was made to studies on
On the basis of this model, the Committee derived a concentration of 0.12    dose-response relationships that according to SCOEL, indicated that
mg/m3 for inhalable dust, corresponding with an extra risk of sensitisation  symptoms (especially related to the lower respiratory tract, asthma, as
of 1% due to occupational exposure, in addition to the risk of 4% in the     well as sensitisation) are rare in the exposure range of 0.5-1.0 mg/m3.
general population of already being sensitised to allergens in wheat flour   Although SCOEL generally does not recommend health-based OELs for
dusts and other cereal flour dusts. This represents a mean concentration     sensitisers, it recommended one for wheat flour dust in view of the large
for 8 hours a day, 5 days a week, for life, under normal working conditions. number of workers exposed and the relatively large data base. SCOEL
                                                                             recognized that the majority of exposed workers would not develop onset
2.2 SCOEL (2008)                                                             of disease at exposures ≤ 1 mg/m3 of inhalable flour dust and that the
The European Scientific Committee on Occupational Exposure Limits            envisaged symptoms would be mild. However, SCOEL also noted that
(SCOEL) published a report on flour dust in 2008.2                           concentrations below 1 mg/m3 may trigger symptoms in already sensitised
SCOEL reasoned that the symptoms induced by cereal flour exposure            workers.
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<pre>                                                                                                      Wheat and other cereal flour dusts | page 10 of 26
03 update quantitative hazard                                              relationship between average exposure and sensitisation was obtained.
         assessment                                                        However, the relationship between allergic symptoms and probable
                                                                           occupational asthma followed a bell-shaped curve increasing up to 10-15
                                                                           µg/m3 wheat allergen concentration, which levelled off and decreased at
3.1 Literature published since 2004                                        higher exposure concentrations. This relationship was modified by atopic
Since the previous report of the Health Council1, several new studies on   status and IgG4 Ievels were strongly related to exposure.
the exposure to wheat flour dust and the induction of allergy have been    The authors also separately analysed bakers with and without atopy. The
published (see Annex B). The selection has been limited to publications    relationship exhibited a bell-shaped curve, i.e. with increasing exposures
involving both exposure measurements and effect assessment. Some of        the number of cases with allergy increased, but leveled off at the highest
these studies are particularly relevant for the calculation of risk of     exposures. This was most prominent for atopic bakers. Bell-shaped
sensitisation by wheat flour dust exposure, since these studies have       shaped curves are suggestive for a healthy worker effect. The Committee
addressed an exposure-response relationship. All studies involve cross-    notes a relatively high atopy prevalence of 42% – a major risk factor for
sectional studies, for which confounding by a healthy worker effect cannot occupational sensitisation – in the population studied by Baatjies. For
be excluded.                                                               further analysis, the Committee obtained the data set of this study (see
The relevant studies for quantitative risk assessment are summarised       Section 2.4). Interestingly, the atopy prevalence was particularly high in the
below and in Annex B.                                                      low exposure group, i.e. 48% compared to less than 40% in the high
                                                                           exposure group.
Baatjies et al. (2015) derived exposure-response relationships for wheat
flour dust exposure and the occurrence of asthma in a cross-sectional      In a study by Page et al. (2009 and 2010) performed in the US, 161
study, involving 466 supermarket bakery workers from 31 bakeries.4 The     workers from bakeries were divided in a low and a high exposure group,
exposure-response relationships were derived using questionnaires,         with mean inhalable wheat flour dust levels of 0.24 and 3 mg/m3,
specific serum-specific IgE and lgG4 measurements, methacholine            respectively.6,7 The fraction of cases with specific sensitisation for wheat
challenge testing, and exposure models developed previously5 to predict    flour dust allergens (based on IgE levels measured in serum) in the low
average personal exposure to wheat allergens. A linear exposure-response   exposure group was 24% and in the high exposure group 42%.
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<pre>                                                                                                          Wheat and other cereal flour dusts | page 11 of 26
Harris-Roberts et al. (2009) reported on an investigation in 225 bakery       allergen concentration instead of dust concentration, and specific
workers in the UK.8 Based on measurements derived by Elms et al. (2005;9      sensitisation.18 In this study, atopic bakers were distinguished from
in the same bakeries) these authors divided workers in 4 exposure             non-atopic bakers and an increase was found in cases of sensitisation at
categories: low, middle, middle-high and high (with mean inhalable            increasing exposure levels in both groups. In the group of atopics
exposure levels of 2.1 mg/m3, 3.6 mg/m3, 4.4 mg/m3 en 5.2 mg/m3,              however, this increase leveled off at higher concentrations, probably due
respectively).The fraction of cases of specific sensitisation (determined by  to the healthy worker effect.
serum IgE) was 9.7%, 5%, 0% and 11.1%, respectively. The fact that in the
middle-high group no cases were observed can be explained by the small        Other studies, included in Annex A, do not allow the calculation of a
group size (only 2 workers).                                                  health-based recommended occupational exposure level. In the
                                                                              publication of Droste et al. (2005) for instance, the cumulative exposure
In another British study, Brant et al. (2005) found one case of specific      was not measured and therefore the actual exposure in the study is not
sensitisation (specific IgE measured) in a group of 53 confectioners          completely clear.11 Storaas et al. (2005; 2007) has addressed other effects
exposed to 0.3 mg inhalable dust/m3 (geometric mean), and 18 cases in a       (i.e. chronic inflammation), at higher exposure levels.13-15 In the South-
group of 71 bakers exposed to 1.2 mg inhalable dust/m3.10 The Committee       African studies of Baatjies et al. (2009; 2010) exposure categories were
considers it likely that the wheat-allergen levels in the inhalable dust      distinguished based on tasks, but no exposure-response relationship can
differed between confectioners and bakers, since these groups use             be derived since the prevalence for each category was not given.5,16
different products. Usually, confectioners will be exposed to lower levels of
wheat flour dust compared to bakers and therefore hardly any                  3.2 Existing guidelines and standards
sensitisation has been observed among confectioners. With respect to the      Current occupational exposure limits of several countries are presented in
bakers, the number of cases of sensitisation was clearly increased            Table 1. In the Netherlands, no legally binding OEL has been set up to
compared to an unexposed control group.                                       now.
Jacobs et al. (2008) reported on a Dutch study with 860 bakers, in which
an extensive exposure-response relationship analysis was based on
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<pre>                                                                                                                         Wheat and other cereal flour dusts | page 12 of 26
Table 1. Occupational exposure limits applied word-wide. (source: Health Council
2004, unless specified otherwise)
                                                                                              be necessary, introducing a large uncertainty for the estimate. Noteworthy,
  Country (organisation)                Concentration TWA         Type of OEL Note
                                        (mg/m3)                                               although the study of Harris-Roberts et al. (2009)8 is not an appropriate
  The Netherlandsa                      -
                                                                                              starting point due to the high exposure levels involved, the observed
  European Union                        -
  Belgiumb                              0.5                                                   cases of sensitisation are, however, consistent with the exposure-
  Canada    c
                                        3                                     Total dust
                                                                                              response relationship derived previously by the Committee.
  Germany (DFG)                         -                                     Sa; wheat and
                                                                              rye flour dusts Furthermore, these studies have additional limitations. The study by Page
  The United Kingdom (HSE)              10             8-h        MEL         Sen; flour dust
                                        30             15 min     MEL                         et al. (2009; 2010)6,7 is based on a small number of subjects, with only two
  Spaind                                4                                                     exposure categories and a high response in the low exposure group,
  Sweden                                3              8-h        LLV         S
  USA (ACGIH)                           0.5            8-h        TLV         Sen; inhalable  which hampers a reliable exposure-response assessment. The report by
                                                                              dust fraction
                                                                                              Brant et al. (2005)10 also provides very limited information on a
a
   https://www.ser.nl/en/grenswaarden/meelstof.aspx
b
   http://www.werk.belgie.be/WorkArea/DownloadAsset.aspx?id=23914                             concentration-response relationship, since only the mean exposure was
c
   http://limitvalue.ifa.dguv.de/WebForm_ueliste2.aspx
d
   http://www.insht.es/                                                                       specified based on a limited number of bakery workers.
                                                                                              The Committee considers the study by Baatjies et al.(2015)4 of interest for
3.3 Quantitative assessment of risk of sensitisation                                          quantitative risk assessment purposes. This study is of high
                                                                                              methodological quality (i.e. a large population; reliable measurement
3.3.1 Assessment of relevant studies                                                          methods) and the endpoints studied are robust and clinically relevant (i.e.
The Committee concludes that most studies published since 2004, do not                        presence of non-specific bronchial hyper-responsiveness and
provide a reliable basis to calculate the risk of sensitisation due to                        sensitisation). The Committee notes that a relatively high prevalence of
exposure to wheat flour dust. The reason for this conclusion is that in most                  workers with an atopic status were included, which is a risk factor for the
studies, the measured exposure levels were relatively high.6-8,10 As a                        development of sensitisation, is observed (in particular in the low
consequence, these studies do not provide specific information on                             exposure group, i.e. 48%). The Committee considers it likely that this high
exposure levels that are associated with risk levels around 1%.                               prevalence of atopy is related to the atopic constitution since the
Extrapolation far outside the exposure range under study would therefore                      prevalence of atopic dermatitis, which could result in a higher risk for
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<pre>                                                                                                                  Wheat and other cereal flour dusts | page 13 of 26
allergic disease, is high in a population of African origin.17 The Committee  al. (2015)4 not representative for the Dutch working population. The
therefore considers the workers studied by Baatjies et al. not                Committee is of the opinion that the most reliable risk estimate is obtained
representative for the Dutch working population.                              by combining the data derived by Jacobs et al. (2008)18 and Houba et al.
Furthermore, the Committee considers the paper by Jacobs et al. (2008)18      (1998).20 The calculation based on both data sets results in an exposure
suitable for quantitative risk assessment. This is a well-performed study     level of 0.2 mg inhalable wheat flour dust/m3, corresponding to an 1%
which provides detailed information on the exposure-response relationship     extra risk of sensitisation by occupational exposure to wheat flour dust.
of wheat flour dust in a Dutch worker population.
                                                                              3.4 Comparison with SCOEL
3.3.2 Risk calculations                                                       Both the DECOS and SCOEL have concluded that no threshold can be
The Committee performed risk calculations on the data from the studies        determined below which no adverse health effects due to exposure to
by Jacobs et al. (2008)18 and, for comparison, Baatjies et al. (2015).4 For   wheat flour dust are expected to occur. In those cases, in analogy with
the risk calculation of the previous report, a linear regression analysis was stochastic genotoxic carcinogens, the Committee applies a risk-based
done on the dataset used by Heederik et al.3 (which involved data from        approach.21 This approach has been supported by the Social and
Houba et al.19) The Committee acknowledges that presently, more               Economic Councila and adopted by the Ministry of Social Affairs and
appropriate methodological approaches are applied for risk assessments        Employment that is responsible for the Dutch OEL-system. In this
using rates (e.g. Poisson regression instead of linear regression).           approach, the Committee uses sensitisation as primary endpoint and
Therefore, the Committee also did a re-calculation of the exposure-risk       calculates the exposure level that results in an extra risk of 1%. In
estimate based on the data of Houba et al. (1998)20, according to the         contrast, SCOEL mainly focuses on allergic complaints after exposure.
current scientific standards and using an updated sensitisation baseline      The SCOEL approach does not involve calculations of exposure
rate (for details, see Annex B).                                              concentrations that correspond to specific risks of developing health
The calculated exposures that correspond to an extra risk of 1% are 0.18      effects, but provides an exposure level based on an expert opinion without
mg inhalable wheat flour dust/m3 (Jacobs et al. (2008)18), 0.04 mg/m3         applying a specified guideline.
(Baatjies et al. (2015)4), and 0.20 mg/m3 (Houba et al. (1998)20). As
mentioned previously, the Committee considers the dataset of Baatjies et      a
                                                                                SER: Aanpak inhaleerbare allergene stoffen op de werkplek; Den Haag, 2008 (in Dutch).
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3.5 Groups at risk                                                             2004/02OSH.
In the previous report, the Committee identified three groups of workers     2
                                                                               Scientific Committee on Occupational Exposure Limits.
that have an increased risk of developing allergic respiratory symptoms        Recommendation from the Scientific Committee on Occupational
after exposure to wheat flour dust: 1) workers already sensitised; 2)          Exposure Limits for flour dust. 2008; SCOEL/SUM/123.
workers with an atopic status or an allergic constitution; and 3) workers    3
                                                                               Heederik D, Houba R. An exploratory quantitative risk assessment for
with pre-existing asthma.1 In addition, the Committee notes that the           high molecular weight sensitizers: wheat flour. Ann Occup Hyg 2001;
prevalence of an atopic status differs between ethnic subgroups (for           45(3): 175-85.
instance, the prevalence of atopic dermatitis is particularly high in people 4
                                                                               Baatjies R, Meijster T, Heederik D, Jeebhay MF. Exposure-response
of African descent).17 This suggests that the risk of sensitisation varies     relationships for inhalant wheat allergen exposure and asthma. Occup
between these populations correspondingly.                                     Environ Med 2015; 72(3): 200-7.
                                                                             5
                                                                               Baatjies R, Meijster T, Lopata A, Sander I, Raulf-Heimsoth M, Heederik
3.6 Conclusions and recommendation                                             D, et al. Exposure to flour dust in South African supermarket bakeries:
The Committee recommends a health-based occupational exposure level            modeling of baseline measurements of an intervention study. Ann
of 0.2 mg inhalable wheat flour dust/m3 (8h time-weighted average). This       Occup Hyg 2010; 54(3): 309-18.
exposure concentration corresponds to an extra sensitisation risk of 1%,     6
                                                                               Page EH, Dowell CH, Mueller CA, Biagini RE. Exposure to flour dust
compared to the general population, against wheat and other cereal flour       and sensitization among bakery employees. Washington, DC 200910,
dusts.                                                                         2009; Health Hazard Evaluation Report: HETA-2005-0248-3077, Sara
                                                                               Lee Bakery, Sacramento, California.
                                                                             7
                                                                               Page EH, Dowell CH, Mueller CA, Biagini RE, Heederik D. Exposure to
         references                                                            flour dust and sensitization among bakery employees. Am J Ind Med
                                                                               2010; 53(12): 1225-32.
1
   Health Council of the Netherlands. Wheat and other cereal flour dusts.    8
                                                                               Harris-Roberts J, Robinson E, Waterhouse JC, Billings CG, Proctor AR,
   An approach for evaluating health effects from occupational exposure.       Stocks-Greaves M, et al. Sensitization to wheat flour and enzymes and
   The Hague: Health Council of the Netherlands, 2004; publication no.         associated respiratory symptoms in British bakers. Am J Ind Med 2009;
        Health Council of the Netherlands | No. 2017/10
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<pre>                                                                                                       Wheat and other cereal flour dusts | page 15 of 26
   52(2): 133-40.                                                           15
                                                                               Storaas T, Ardal L, Van Do T, Florvaag E, Steinsvag SK, Irgens A, et al.
9
   Elms J, Robinson E, Rahman S, Garrod A. Exposure to flour dust in UK        Nasal indices of eosinophilic and exudative inflammation in bakery-
   bakeries: current use of control measures. Ann Occup Hyg 2005; 49(1):       workers. Clin Physiol Funct Imaging 2007; 27(1): 23-9.
   85-91.                                                                   16
                                                                               Baatjies R, Lopata AL, Sander I, Raulf-Heimsoth M, Bateman ED,
10
   Brant A, Berriman J, Sharp C, Welch J, Zekveld C, Nieuwenhuijsen M,         Meijster T, et al. Determinants of asthma phenotypes in supermarket
   et al. The changing distribution of occupational asthma: a survey of        bakery workers. Eur Respir J 2009; 34(4): 825-33.
   supermarket bakery workers. Eur Respir J 2005; 25(2): 203-8.             17
                                                                               Silverberg IJ. Racial and ethnic disparities in atopic dermatitis. Curr
11
   Droste J, Vermeire P, van SM, Bulat P, Braeckman L, Myny K, et al.          Derm Rep 2015; 4: 44-8.
   Occupational exposure among bakery workers: impact on the                18
                                                                               Jacobs JH, Meijster T, Meijer E, Suarthana E, Heederik D. Wheat
   occurrence of work-related symptoms as compared with allergic               allergen exposure and the prevalence of work-related sensitization and
   characteristics. J Occup Environ Med 2005; 47(5): 458-65.                   allergy in bakery workers. Allergy 2008; 63(12): 1597-604.
12
   Meijster T, Tielemans E, de PN, Heederik D. Modelling exposure in        19
                                                                               Houba R, van Run P, Heederik D, Doekes G. Wheat antigen exposure
   flour processing sectors in the Netherlands: a baseline measurement in      assessment for epidemiological studies in bakeries using personal dust
   the context of an intervention program. Ann Occup Hyg 2007; 51(3):          sampling and inhibition ELISA. Clin Exp Allergy 1996; 26(2): 154-63.
   293-304.                                                                 20
                                                                               Houba R, Heederik D, Doekes G. Wheat sensitization and work-related
13
   Storaas T, Steinsvag SK, Florvaag E, Irgens A, Aasen TB. Occupational       symptoms in the baking industry are preventable. An epidemiologic
   rhinitis: diagnostic criteria, relation to lower airway symptoms and IgE    study. Am J Respir Crit Care Med 1998; 158(5 Pt 1): 1499-503.
   sensitization in bakery workers. Acta Otolaryngol 2005; 125(11):         21
                                                                               Health Council of the Netherlands. Prevention of work-related
   1211-7.                                                                     respiratory allergies. Recommended occupational exposure limits and
14
   Storaas T, Irgens A, Florvaag E, Steinsvag SK, Ardal L, Van Do T, et al.    periodic screening. The Hague, 2008; 2008/03E.
   Bronchial responsiveness in bakery workers: relation to airway           22
                                                                               Khodadadi I, Abdi M, Aliabadi M, Mirmoeini ES. Exposure to respirable
   symptoms, IgE sensitization, nasal indices of inflammation, flour dust      flour dust and gliadin in wheat flour mills. J Occup Health 2011; 53(6):
   exposure and smoking. Clin Physiol Funct Imaging 2007; 27(5):               417-22.
   327-34.                                                                  23
                                                                               Ijadunola KT, Erhabor GE, Onayade AA, Ijadunola MY, Fatusi AO,
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<pre>                                                                          Wheat and other cereal flour dusts | page 16 of 26
   Asuzu MC. Pulmonary functions of wheat flour mill workers and
   controls in Ibadan, Nigeria. Am J Ind Med 2005; 48(4): 308-17.
24
   Wagh ND, Pachpande BG, Patel VS, Attarde SB, Ingle ST. The
   influence of workplace environment on lung function of flour mill
   workers in Jalgaon urban center. J Occup Health 2006; 48(5): 396-401.
25
   Health Council of the Netherlands. Fungal alpha-amylase (derived from
   the fungus Aspergillus oryzae) - Health-based recommended
   occupational exposure limit. The Hague: Health Council of the
   Netherlands, 2014; publication no. 2014/25.
26
   Health Council of the Netherlands. Flour dust from processed,
   de-hulled soybeans. Health-based recommendation on occupational
   exposure limits. The Hague: Health Council of the Netherlands, 2016;
   publication no. 2016/07.
27
   Gautrin D, Infante-Rivard C, Dao TV, Magnan-Larose M, Desjardins D,
   Malo JL. Specific IgE-dependent sensitization, atopy, and bronchial
   hyperresponsiveness in apprentices starting exposure to protein-
   derived agents. Am J Respir Crit Care Med 1997; 155(6): 1841-7.
28
   Bjornsson E, Janson C, Plaschke P, Norrman E, Sjoberg O. Prevalence
   of sensitization to food allergens in adult Swedes. Ann Allergy Asthma
   Immunol 1996; 77(4): 327-32.
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annexes
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A          epidemiological data published since 2004
Overview of studies with data on the relationship between exposure to wheat flour dust and the prevalence of sensitisation
Study design and       Exposure information                                     Health information                             Results sensitisation
population information
Cross-sectional: 1 US  Two categories: lower-exposure (not handling dough,      Self-administered questionnaire on job history Prevalence of sensitisation (Usually, specific IgE levels ≥ 0.35 kU/L are
bakery (n=186)         e.g. office, transportation, oven areas) and higher-     and work-related symptoms and smoking          considered to indicate sensitisation. For the method used in this study, the
                       exposure (handling raw materials and/or dough:           habits (n=161)                                 cut-off value for a positive test is 0.10 kU/L (FDA-approved)):
Page et al., 20096;    e.g. bread & bun production, distribution)                                                              flour dust exposure
Page et al., 20107                                                              Specific serum IgE antibodies to flour and     0.235 mg/m3: 24% (12/51)
                       Full-shift air sampling (IOM sampler with Teflon filter, wheat, and common allergens to assess          3.01 mg/m3: 42% (19/45)
                       pore size 1 µm): personal breathing zone (n=83) and      atopy (n=96). The method was a highly          PR 1.79 (95% CI 0.98-3.27)
                       general area (n=19)                                      sensitive enzyme-enhanced chemilumine-         wheat allergen exposure
                                                                                scent enzyme immune-assay, Immulite 2000. 0.433 µg/m3: 24% (12/51)
                       Inhalable flour dust                                     Traditionally, IgE levels ≥0.35 kU/L serum are 12.6 µg/m3: 36% (16/45)
                       lower-exposure:                                          considered positive for sensitisation. The     PR 1.51 (95% CI 0.80-2.84)
                       0.235 mg/m3 (ND-1.4)                                     threshold for this assay is 0.10 kU/L
                       higher-exposure:                                                                                        A number of employees working in lower-exposure group reported past work in
                       3.01 mg/m3 (trace-65)                                    There was no difference in prevalence of       higher exposure group; prevalence if these employees were included in the
                                                                                atopy between the two exposure groups          high-exposure group:
                       Wheat allergen concentration                                                                            flour dust exposure
                       lower-exposure:                                                                                         lower: 15% (5/33); current & past higher: 41% (26/63)
                       0.433 µg/m3 (0.14-3.6)                                                                                  PR 2.72 (95% CI 1.15-6.43)
                       higher-exposure:                                                                                        wheat allergen exposure
                       12.6 µg/m3 (0.18-900)                                                                                   lower: 15% (5/33); higher & past higher: 37% (23/63)
                                                                                                                               PR 2.41 (95% CI 1.01-5.75)
                                                                                                                               Prevalence of sensitisation (positive if IgE ≥ 0.35 kU/L):
                                                                                                                               flour dust exposure
                                                                                                                               lower: 6% (2/33); current & past higher: 21% (13/63)
                                                                                                                               PR 3.40 (95% CI 0.82-14.20)
                                                                                                                               wheat allergen exposure
                                                                                                                               lower: 6% (2/33); higher & past higher: 27% (17/63)
                                                                                                                               PR 4.45 (95% CI 1.09-18.12)
                                                                                                                               Atopics were significantly more likely to be sensitised to wheat and flour at
                                                                                                                               both cut-off values (p<0.01)
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Cross-sectional: bakers   Personal inhalable dust and wheat allergen            Self-administered questionnaire on                Prevalence of sensitisation:
(n=227) from 74 Belgian   concentrations measured (PAS-6, during shift 5-7 h).  respiratory, asthma and allergy-related           wheat allergen exposure
bakeries. Number of       Job/exposure categories (GM±GSD): low (industrial     symptoms, supplemented with questions on          2.81 ng/m3: 9.1%
workers in industrial     packers), medium (industrial bakers and traditional   smoking habits                                    8.13 ng/m3: 10.5%
packers n=34; industrial  pastry bakers) and high (traditional bread bakers and                                                   16.34 ng/m3: 16.5%
bakers n=49; traditional  traditional bread+pastry bakers)                      Skin prick testing on common and bakery-          Intergroup difference not statistically significant: medium vs. low OR 1.4
pastry bakers n=37;                                                             specific antigens (wheat flour, rye flour, fungal (95% CI 0.3-5.7); high vs. low OR 1.9 (95% CI 0.5-7.5)
traditional bread baker   Inhalable dust exposure (GM±SEM)                      alpha-amylase)
n=23; traditional         low: 0.53±1.14 mg/mL                                                                                    Sensitisation to bakers’ allergens (OR 5.9-95% CI 2.3-15.1) and atopy
bread+pastry n=84         medium: 1.05±1.15 mg/mL                               Lung function tests                               (OR 2.6-95% CI 1.2-5.5) were shown to be the best predictors of work-related
                          high: 2.09±1.07 mg/mL                                                                                   symptoms; current dust exposure levels (medium exposure OR 4.7-95% CI
Droste et al., 200511                                                                                                             0.9-24.6; high exposure OR 9.4-95% CI 1.8-49.1) add only little to their
                          Wheat allergen exposure (GM±SEM)                                                                        prediction
                          low: 2.81±1.15 ng/mL
                          medium: 8.13±1.23 ng/mL
                          high: 16.34±1.14 ng/mL
Cross-sectional: UK       Job categories for flour dust exposure were based on  Interviewer-led questionnaire on work-related     Prevalence (%) of wheat flour specific sensitisation
bakers (n=225) from 22    the job group median concentrations from personal     respiratory symptoms, demographic details,        low (others, 2.1 mg/m3): 9.7% (3/31)
bakeries: 140 general     breathing zone dust exposure measurements (IOM        work history and smoking habits; lung             medium (general bakers, 3.6 mg/m3): 5.0% (5/100); high (cleaners, 4.4
bakers, 31 mixer/siever/  samplers) in 208 workers from 55 bakeries in a        function assessment (n=225)                       mg/m3): 0% (0/2); high (flour mixer/weigher/sievers, 5.2 mg/m3): 11.1% (3/27)
weigher, 7 cleaner and    previous study (Elms et al., 2005)                                                                      Work-related upper respiratory symptoms were more common in atopic
47 other jobs                                                                   Specific serum IgE (RAST assay) to wheat          workers (OR 2.8, 95% CI 1.4-5.4) and in those sensitised to both wheat and
                          high exposure (flour mixers/weighers/sievers, n=59):  flour, enzymes and common allergens               enzyme (OR 13.9, 1.7-114.6) but not to wheat (OR 1.45, 0.42-4.99) or enzyme
Harris-Roberts et al.,    5.2 mg/m3 (ND-30.6)                                   (n=160). Workers were categorized in 4            only
20098; Elms et al., 20059 cleaners (n=6): 4.4 mg/m3 (0.4-14.3)                  groups: not sensitised, sensitised to wheat
                          medium exposure (general bakers, n=108):              flour only, sensitised to enzymes only,           Atopy was the most important risk factor for sensitisation to workplace
                          3.6 mg/m3 (ND-47.0)                                   sensitised to wheat flour and any enzyme          allergens (OR 18.4, 5.3-64.3). Correction for atopy was not feasible. Among
                          low exposure (others, n=35): 2.1 mg/m3 (ND-30.8)                                                        atopic workers smoking was a strong predictor of sensitisation to wheat or
                                                                                                                                  enzymes, corrected for duration of employment and current exposure category
                                                                                                                                  (OR 4.7, 1.1-20.8)
                                                                                                                                  Comment: The date of study conduct was not reported. Exposures were
                                                                                                                                  determined in 2002-2003 and may not be representative for later years
Cross-sectional: 197      Breathing zone personal dust samplers (n=58).         Interview focusing on occupational rhinitis       Prevalence of sensitisation to cereal allergens (skin prick test / specific serum
employees of bakeries in  Four exposure groups: <1.0 mg/m3 (packers, oven       (n=181) and self-administered question-naire      IgE):
Norway (n=6)              workers, administration); 1.0-1.9 mg/m3 (mainly       on work tasks, family history, occupation-al      wheat: 4% / 11%
                          confectionary workers, bread formers); 2.0-3.9 mg/m3  symptoms, smoking habits and prevalence of        rye: 1% / 10%
Storaas et al., 200513;   (mainly dough makers); >3.9 mg/m3 (mainly dough       allergy and atopic dermatitis/eczema (n=180)      barley: 3% / 8%
Storaas et al., 200714;   makers)                                                                                                 oats: 1% / 5%
Storaas et al., 200715                                                                                                            Prevalence of sensitisation to storage mites was 20% (37/183)
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                                                                             Allergy tests for occupational and common      Occupational rhinitis, IgE and non-IgE mediated, preceded lower airway
                                                                             allergens (skin prick, total and specific IgE  symptoms and was associated with asthma symptoms. Storage mite
                                                                             and histamine release, n=183)                  sensitisation was related to occupational rhinitis and exposure
                                                                             Spirometry, bronchial provocation test with    Bronchial hyperresponsiveness (BHR) was associated with smoking and
                                                                             metacholine, nasal challenge and lavage        work-related asthma. BHR, corrected for baseline lung function, was not
                                                                                                                            associated with occupation-al IgE sensitisation (defined as positive to wheat,
                                                                             Categorisation of workers in job titles: dough alpha-amylase, oats, barley, rye, soybean, storage mites, mold or cockroach).
                                                                             makers, bread formers, oven staff, packers,    It is con-cluded that IgE sensitisation is not the main causative factor for airway
                                                                             confectionary workers, administration and      hyperresponsiveness and occu-pational rhinitis in bakery workers.
                                                                             cleaning workers                               BHR was not associated with current flour dust exposure level, with number of
                                                                                                                            working hours in a bakery, or with a history of dough-making
                                                                                                                            A healthy worker effect cannot be excluded
Overview of studies with data on the relationship between exposure to wheat flour dust (expressed as concentration allergen) and the prevalence of sensitisation and
respiratory symptoms
Study design and        Exposure information                                 Health information                             Results sensitisation
population information
Cross-sectional: Dutch  A dataset of personal breathing zone exposure        Self-administered questionnaire on job         Prevalence (%) of sensitisation
bakers (n=860) from 341 assessments (full-shift, PAS-6 sampler) between 2000 history, history of respiratory, allergic, and wheat allergen exposure (GM) 12.8±3.5 µg/m3
traditional and 28      and 2005 (details in Meijster et al., 2007) was used work-related symptoms, symptoms                overall: 12% (107/859)
industrial bakeries     for estimating average and cumulative exposure to    suggesting bronchial hyper-responsiveness,     nonatopics: 7% (38/572)
                        dust and wheat allergens (GM and range)              medication use and smoking habits              atopics: 24% (69/288)
Jacobs et al., 200818;                                                                                                      Analyses included wheat allergen exposure only since the correlation between
Meijster et al., 200712 avg. dust exposure (GM): 1.8±1.7 mg/m3               Specific serum IgE antibodies to wheat and     dust and wheat allergen exposure was very high
                        (range 0.3-7.3)                                      common allergens to assess atopy
                        cum. dust exposure: 30.5 mg/m3 x yr (range 0.8-278)                                                 Prevalence (%) of work-related symptoms and asthma in non-sensitised/
                                                                                                                            sensitised persons:
                        avg. wheat allergen exposure (GM): 12.8±3.5                                                         Upper respiratory symptoms:
                        µg/m3 (range 0.3-95.6)                                                                              overall: 20/50; nonatopics: 16/42; atopics: 29/55. Lower respiratory
                        cum. wheat allergen exposure: 318.5 µg/m3 x yr                                                      symptoms: overall: 6/32; nonatopics: 5/26; atopics: 9/35. Asthma: overall:
                        (range 1.0-4492)                                                                                    6/35; nonatopics: 4/21; atopics: 11/42
                                                                                                                            Wheat sensitisation was strongest associated with lower respiratory symptoms
                                                                                                                            and asthma (3.8-5.8 times more sensitised individuals reported these
                                                                                                                            symptoms; 1.9-2.6 for lower respiratory symptoms). Atopics reported more
                                                                                                                            frequently respiratory health symptoms (factor 1.3-2.8), but the association
                                                                                                                            with sensitisation to wheat allergens was stronger than atopy
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                                                                                                                               Model calculations showed that in atopic workers, exposure to wheat allergens
                                                                                                                               was associated with a higher frequency of wheat sensitisation and respiratory
                                                                                                                               symptoms, increasing linearly up to an average wheat allergen concentration
                                                                                                                               of 25-30 µg/m3. At higher exposure levels, the exposure-response relation
                                                                                                                               flattened and decreased (bell-shaped curve). This decrease, which has been
                                                                                                                               explained as the “healthy worker effect”, was not observed in non-atopic
                                                                                                                               workers, who showed a very weak and not statistically significant exposure-
                                                                                                                               effect relation. The exposure-response relation was strongest for the
                                                                                                                               cumulative exposure, indicating that duration of exposure is also an important
                                                                                                                               determinant
Cross-sectional (baseline Full-shift personal airborne dust was sampled (PAS6)  Self-administered questionnaire (n=517) on     Prevalence of sensitisation to wheat flour allergen (IgE-positive):
measurements):            in 18 bakeries on 2 days (n=211).                     respiratory symptoms, employment history       all: 26% (134/513)
517 employees of 31       Analysis for total mass and wheat and rye allergens   and job title, degrees of exposure to flour    atopics: 42% (90/213)
supermarket bakeries in   by polyclonal AB-EIA                                  dust, baking activities at home and smoking    nonatopics: 15% (44/294)
South-Africa                                                                    habits                                         atopic/nonatopic significant
                          Inhalable dust in each job category (GM±GSD):
Baatjies et al., 2009 ,
                     16
                          bread baker (n=112): .33±2.25 mg/m3; confectioner     Skin prick tests (n=507) to common and         Prevalence of sensitisation to rye flour allergen (IgE-positive):
20105, 20154              (n=38): 0.65±2.08 mg/m3; supervisor (n=13):           work-related allergens, including cereal flour all: 24% (123/513)
                          0.56±2.05 mg/m3; manager (n=13): 0.51±2.34            allergens                                      atopics: 38% (81/213)
                          mg/m3; counterhand (serving customers, n=35):                                                        nonatopics: 14% (42/294)
                          0.28±1.89 mg/m3                                       Wheat and rye specific serum IgE was           atopic/nonatopic significant
                                                                                measured by fluorescence EIA (n=513). A
                          Wheat allergen in each job category (GM±GSD):         result >0.35 kU/L was considered positive      The authors did not present job-title specific prevalences for sensitisation.
                          bread baker (n=112): 13.66±2.66 µg/m3; confectioner                                                  Exposure-response relations can therefore not be established. Relevant in this
                          (n=38): 5.82±2.25 µg/m3; supervisor (n=13):           Pulmonary function testing (spirometry and     respect is that exposure assessment was done in 18 of the 31 bakeries
                          4.99±1.93 µg/m3; manager (n=13): 3.41±4.01 µg/m3;     methacholine challenge, n=517). FEV1/FVC
                          counterhand (serving customers, n=35): 1.16±4.81      and PD20 metacholine dose (≥20% decrease Atopy prevalence was 42%, comparable with Brant et al., 200510
                          µg/m3                                                 of FEV1 during challenge test) were
                                                                                determined                                     Correlation between long function and sensitisation to wheat flour
                          Rye allergen in each job category (GM±GSD): bread                                                    (IgE-positive) was not very strong:
                          baker (n=112): 5.14±2.89 µg/m ; confectioner (n=38):
                                                          3
                                                                                                                               PD20: Spearman r=-0.30 (p<0.001), independent of atopy status
                          2.04±2.41 µg/m3; supervisor (n=13): 1.74±1.97 µg/m3;                                                 FEV1/FVC: r: r=-0.15 (p=0.001)
                          manager (n=13): 1.99±4.06 µg/m ; counterhand
                                                             3
                                                                                                                               FEV1: r=-0.07 (p=0.090)
                          (serving customers, n=35): 0.39±4.57 µg/m3
                                                                                                                               The prevalence of probable occupational asthma (defined as bronchial
                          Note: inhalable dust concentrations were strongly                                                    hyperresponsiveness and sensitisation to bakery dust allergens) was 13%
                          correlated with wheat and rye allergen concentrations                                                (60/457). Among atopics and nonatopics, the prevalence was 22% and 7%,
                          (Pearson r=0.84 and 0.86, respectively, p<0.001)                                                     respectively. By including ex-bakers, the healthy worker effect was partially
                                                                                                                               avoided in this study
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<pre>                                                                                                                                                Wheat and other cereal flour dusts | page 22 of 26
                                                                                                                                    In the 2015 paper, Baatjies et al. was submitted on the exposure-response
                                                                                                                                    relationships for average current wheat allergen exposure, specific
                                                                                                                                    sensitisation and respiratory symptoms. The authors found a bell-shaped
                                                                                                                                    relationship for symptoms, which they explained mainly to a healthy-worker
                                                                                                                                    effect. The prevalence reached a maximum up to 10 to 15 μg/m3, after which it
                                                                                                                                    levelled-off and decreased at higher exposure levels. Atopy modified the
                                                                                                                                    relationship, in that atopic workers showed highest effects
Overview of studies with data on the relationship between exposure to wheat flour dust (expressed as concentration dust) and the prevalence of sensitisation and respiratory
symptoms
Study design and population information             Exposure information                          Health information                       Results sensitisation
Cross-sectional:                                    Whole-shift personal inhalable dust exposure  Self-administered questionnaire on       Prevalence of wheat flour specific sensitisation:
239 employees of in-store bakeries in UK            measurement (10 stores): bakers (GM): 1.2     employment history and work-             bakers (1.2 mg/m3): 27% (18/66)
super-markets (n=20)                                mg/m3 (n=27); managers (GM): 0.5 mg/m3        related respiratory symptoms             managers (0.5 mg/m3): 7% (2/28)
                                                    (n=8); confectioners (GM): 0.3 mg/m3 (n=21);  (n=239)                                  confectioners (0.3 mg/m3): 2% (1/45)
Brant et al., 200510                                assistants (GM): 0.3 mg/m3 (n=33); total                                               assistants (0.3 mg/m3): 4% (3/71)
                                                    (GM): 0.5 mg/m3 (n=89) (Instead of a range    Skin prick tests to common allergens total (0.5 mg/m3): 11% (24/210)
                                                    of measured exposures, 2GSD values are        (n=233) and RAST assay for
                                                    reported)                                     determining specific serum IgE to        Prevalence of atopy was 41%, comparable with Baatjies et al., 200923
                                                                                                  wheat flour and alpha-amylase
                                                    Job title was used as a surrogate for flour   (n=210)
                                                    and amylase exposure in exposure-response
                                                    analyses                                      Atopy was evenly spread across the
                                                                                                  work groups.
Cross-sectional/case-control: workers (n=95) and    Breathing zone personal samplers for 8-h      Total serum IgE and anti-gliadin-        Total serum IgE: exposed workers (n=95): 146.26±132.46 IU/mL;
unexposed office workers (n=95) from 8 wheat        sampling of respirable dust (n=64)            specific IgA and IgG. The report         control subjects (n=95): 67.49±81.92 IU/mL
flour mills in Iran. Excluded were: smokers,        flour packing: 3.50±1.80 mg/m3 (n=26); husk   does not contain health information
workers employed less than 1 year, and subjects     packing: 2.53±1.18 mg/m3 (n=19); flour        of the workers
with previous lung and/or immune-deficiency         production: 1.72±0.92 mg/m3 (n=9); wheat
disease history                                     unloading: 2.33±1.00 mg/m3 (n=10)
Khodadadi et al., 201122
Cross-sectional/case control: production workers    Static breathing zone area samplers for total Interviewer-administered                 Prevalence (%) of long function abnormalities (FEV1, FVC, FEV1/FVC)
at 3 flour mills in Nigeria (n=91), other employees floor dust at two locations:                  questionnaire and lung function          non-smokers):
(internal control, n=30) and external control       shop-floor (production unit): 2.4±2.0 mg/m3   assessment (spirometer)                  production (n=75): 20%, 9%, 20%
subjects (n=121), all males. Excluded were          (range 0.6-4.7)                                                                        internal control (n=19): 0%, 0%, 11%
subjects with a history of chronic respiratory      maintenance workshop (internal controls):                                              external control (n=109): 7%, 2%, 2%
problems before current employment. Controls        0.4±0.3 mg/m3 (range 0.1-0.6)
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<pre>                                                                                                                                                            Wheat and other cereal flour dusts | page 23 of 26
 were of a similar socio-economic class and were                                                                                                       ex-smokers:
 matched for age, length and weight                                                                                                                    production (n=12): 25%, 8%, 17%
                                                                                                                                                       internal control (n=7): 14%, 0%, 14%
 Ijadunola et al., 200523                                                                                                                              external control (n=10): 20%, 10%, 10%
                                                                                                                                                       Only the differences between non-smoking production workers and
                                                                                                                                                       external control subjects were statistically significant
 Cross-sectional: Indian flour mill workers (n=59)      Personal dust samplers (8-h PM10                    Recording (undefined) of general           Prevalence of respiratory symptoms
 and a non-employee control group (n=54). All           sampling):                                          characteristics (age, length, weight)      controls (n=54): 5-16%
 non-smoking                                            624±190 µg/m3 (430-814)                             and respiratory symptoms.                  flour mill workers (n=59): 19-42% (RR 2.3-3.6, AR 0.11-0.24)
                                                                                                            Pulmonary function testing
 Wagh et al., 200624                                                                                                                                   Prevalence (%) of long function abnormalities (FEV1, FVC, FEV1/FVC)
                                                                                                                                                       control (n=54): 20%, 16%, 17%
                                                                                                                                                       flour mill workers (n=59): 43%, 40%, 68%
Abbreviations: PD20: the administered dose of a substance in the inhaled aerosol which causes the FEV1 to fall by 20%; PR: prevalence ration; FEV1: forced expiratory volume in 1 second; FVC: forced vital capacity.
B           risk calculations                                                                                        Analysis using data from Houba et al. (1998)20
                                                                                                                     The data of Houba et al. has previously been used by the Committee for
Additional analysis by the Netherlands Health Council DECOS, based on                                                estimation of the risk of sensitisation by wheat flour dust. The Committee
the papers by Houba et al. (1998)20, Jacobs et al. (2008)18 and Baatjies et                                          applied linear regression for that analysis. Here, the Committee
al. (2015)4                                                                                                          reanalyzed the data using Poisson regression. In this study exposure-
The Health Council previously1 used exposure-response relationships                                                  response relations were calculated for cumulative exposure, and based on
based on sensitisation and dust exposure from a study by Houba et al.                                                duration of exposure recalculated to average exposure in the different
(1998).20 Since the publication of this study, two new studies were                                                  exposure groups. The number of sensitised individuals per exposure
published which describe exposure-response relations. Exposure-                                                      group was estimated based on calculated prevalence ratio, in combination
response analyses are presented here and compared with updated                                                       with the total number of participants in the study (n=246) and “equal group
analysis of Houba et al.20                                                                                           size” as reported by Heederik et al. (2001).3
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<pre>                                                                                                                         Wheat and other cereal flour dusts | page 24 of 26
Data used for Poisson regression analysis
 Number of subjects      Sensitised          Estimated average dust exposure mg/m3
                                                                                   information on sensitisation, atopy and respiratory symptoms were
 68                        4 (5.9%)          0.13
 69                        5 (7.2%)          0.46                                  available. In addition, exposure assessment surveys were conducted which
 70                        5 (7.1%)          1.03
                                                                                   made it possible to characterize dust and allergen exposure of participants.
 69                      10 (14.5%)          2.50
 69                      12 (17.4            7                                     For this analysis, results from the study by Jacobs et al. were produced by
                                                                                   the first author with information on dust exposure instead of wheat allergen
Analysis using data from Baatjies et al. (2015)4                                   exposure (as used in the original publication). Exposure levels in this study
The paper describes exposure-response analyses for supermarket bakery              at the low end of the distribution are higher than for the Houba study
workers of wheat allergen levels and different endpoints (wheat                    because of the inclusion of a higher number of traditional bakery workers.
sensitisation, allergic chest symptoms, probable occupational asthma,
etc.). For the purpose of this analysis the dataset from Baatjies was              Data used for Poisson regression analysis
                                                                                     Number of subjects             Sensitised                   Estimated average dust exposure mg/m3
obtained with permission of the authors. Exposure response analyses                  207                            23 (11%)                     1.2
were evaluated for estimated average exposure in each exposure                       210                            23 (11%)                     1.5
                                                                                     210                            28 (13%)                     1.8
category. The average exposure was measured on the job title level and               209                            33 (16%)                     2.6
average job title levels were assigned to all individuals in the study.
                                                                                   Comparison of risk estimates
Data used for Poisson regression analysis                                          The information from the tables above was analyzed by the Committee, as
 Number of subjects    Sensitised           Estimated average dust exposure mg/m3
  43                    4 (9.3%)            0.23
                                                                                   done earlier for other allergens,25,26 in a Poisson regression analysis (see
 106                   19 (17.9%)           0.33                                   Figure 1). A baseline rate of 2.8% has been useda, based on the studies
 111                   33 (29.7%)           0.66
 203                   59 (29.1%)           1.41
                                                                                   by Houba et al. (1996)19, Gautrin et al. (1997)27, and Björnsson et al.
                                                                                   (1996)28 with in total 2,239 controls without known occupational wheat
Analysis using data from Jacobs et al. (2008)18                                    flour dust exposure of whom 62 were sensitised to wheat allergens.
The study by Jacobs was undertaken as part of a health surveillance
programme in the Dutch baking industry. A large population survey was
included as a validation of the surveillance approach. For this population,        a
                                                                                      In 2004, the Committee used a background prevalence of 4%.
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<pre>                                                                                                                                          Wheat and other cereal flour dusts | page 25 of 26
                                                                                                                                 Slope estimate   Standard error   p-value    1% excess risk
                                                                                                             All three studies   3                0.24             <0.0001    0.12
Of these exposure-response relationships, the slope estimates were                                           Houba & Jacobs      1.97             0.22             <0.0001    0.18
obtained and subsequently used to calculate the exposure that                                                Baatjies            8.9              0.95              0.0007    0.04
                                                                                                             Houba               1.8              0.42              0.0077    0.20
corresponds to an extra risk of sensitisation of 1% using the formula:                                       Jacobs              2.03             0.25              0.0013    0.18
                          RR = 1 + [slope x average exposure]
                                                                                                             The steeper exposure-response slope of the Baatjies study could be
                                                                                                             explained by the high proportion of atopics in the study relative to the
                                          Exposure response relation dust wheat sensitisation                other two studies. Atopy is known to be more common in westernised
                                 35
                                                                                                             native African and Asian communities. Because exposure-response
                                                                         Baatjies et al., 2015               relations are not linear in these studies, particularly in atopics (bell shape,
                                 30                                      Houba et al., 1998
                                                                                                             see original papers), and not fully comparable (probably because of
Wheat sensitisation prevalence
                                                                         Jacobs et al., 2005
                                 25                                      background prevalence
                                                                                                             differences in the local context (healthy worker effect, job mobility)), a
                                                                         Baatjies et al., 2015
                                 20                                      Houba et al., 1998                  detailed comparison of exposure response relationships in atopics is not
                                                                         Jacobs et al., 2008
                                                                                                             possible. However, in all three populations, the sensitisation risk is higher
                                 15
                                                                                                             in atopics and ranges from 20-30%, dependent on the exposure level.
                                 10
                                 5
                                 0
                                      0        1       2         3         4         5           6   7   8
                                                           Wheat flour dust exposure in mg/m 3
Figure 1 Derived exposure-response relationships for wheat sensitisation, based on
the studies by Houba et al. (1998)20, Baatjies et al. (2015)4 and Jacobs et al. (2008)18
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<pre>The Health Council of the Netherlands, established in 1902, is an independent scientific advisory body. Its remit is “to advise the government and
Parliament on the current level of knowledge with respect to public health issues and health (services) research...” (Section 22, Health Act).
The Health Council receives most requests for advice from the Ministers of Health, Welfare and Sport, Infrastructure and the Environment, Social Affairs
and Employment, and Economic Affairs. The Council can publish advisory reports on its own initiative. It usually does this in order to ask attention for
developments or trends that are thought to be relevant to government policy.
Most Health Council reports are prepared by multidisciplinary committees of Dutch or, sometimes, foreign experts, appointed in a personal capacity.
The reports are available to the public.
This report can be downloaded from www.healthcouncil.nl.
Preferred citation:
Health Council of the Netherlands. Wheat and other cereal flour dusts. Health-based
recommendation on occupational exposure limits The Hague: Health Council of the
Netherlands, 2017; publication no. 2017/10.
All rights reserved
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