The role of the bronchial provocation challenge tests in the diagnoisis of exercise-induced bronchoconstriction in elite swimmers
The role of the bronchial provocation challenge
tests in the diagnosis of exercise-induced
bronchoconstriction in elite swimmers
A Castricum, K Holzer, P Brukner, et al.
2010 44: 736-740 originally published online October 23,
Br J Sports Med
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British Journal of Sports Medicine
The role of the bronchial provocation challenge testsin the diagnosis of exercise-inducedbronchoconstriction in elite swimmers
A Castricum,1 K Holzer,1 P Brukner,2 L Irving2
a recognised incidence of EIB/asthma misdiagno-
Background The International Olympic Committee–
sis.6–8 Infrequently, the diagnosis was confirmed
Medical Commission (IOC-MC) accepts a number of
with a bronchial provocation challenge (BPC).
Royal Melbourne Hospital,Melbourne, Australia
bronchial provocation tests for the diagnosis of exercise-
Formalised testing for the confirmation of
induced bronchoconstriction (EIB) in elite athletes, none of
asthma and EIB was thus introduced by the IOC-
which have been studied in elite swimmers. With the
MC for the 2002 Winter Olympic Games in Salt
suggestion of a different pathogenesis involved in the
Lake City, and for subsequent Summer and Winter
Olympic Games. Although both airway reversibil-
development of EIB in swimmers, there is a possibility
that the recommended test for EIB in elite athletes, the
ity on spirometry and the presence of airway
eucapnic voluntary hyperpnoea (EVH) challenge, may be
hyperreactivity to a number of BPCs have been
missing the diagnosis in elite swimmers.
accepted by the IOC-MC, the eucapnic voluntary
Dr Adam Castricum, SportsPhysician, Olympic Park Sports
Objective The aim of this study was to assess the
hyperpnoea (EVH) challenge has been recognised
effectiveness of the EVH challenge, the field swim
as the gold standard challenge for the diagnosis of
challenge and the laboratory cycle challenge in the
EIB in elite athletes.9 This recommendation was
based on studies including winter athletes. The
Design 33 elite swimmers were evaluated on separate
EVH challenge has since been shown to be highly
days for the presence of EIB using 3 different bronchial
sensitive and specific for the diagnosis of EIB in
provocation challenge tests: an 8 minute field swim
challenge, a 6 minute laboratory EVH challenge, and an
It has been suggested that the high prevalence of
8 minute laboratory cycle challenge.
EIB in the various endurance athlete subgroups
Main outcome measurements Change in forced
may be due to different triggers of airway
hyperreactivity. In winter athletes, this may be a
result of airway inflammation secondary to airway
exposure of large volumes of cold air.11 In summer
Results Only 1 of the 33 subjects (3%) had a positive
athletes, the trigger is thought to be exposure to
large allergen loads.12 The prevalence of EIB in
baseline. 18 of the 33 subjects (55%) had a positive EVH
swimmers is remarkably high; up to 47% in some
elite swimming teams.5 This was initially thought
from baseline. 4 of the subjects (12%) had a positive
to occur as a consequence of people with asthma
laboratory cycle challenge, with a mean fall in FEV
being encouraged to swim.13 However, it is now
14.8 (4.7)% from baseline. Only 1 of the 33 subjects was
accepted that the high prevalence of EIB in
swimmers is due to injury of the airways as a
Conclusions These results suggest that the EVH
consequence of repetitive and prolonged exposure
challenge is a highly sensitive challenge for identifying EIB
to the gases of chlorine and their metabolites,
in elite swimmers, in contrast to the laboratory and field-
which accumulate at the water/gas interface on
based exercise challenge tests, which significantly
underdiagnose the condition. The EVH challenge, a well-
All but one of the diagnostic challenge tests
established and standardised test for EIB in elite winter
recommended by the IOC-MC fail to account for
and summer land-based athletes, should thus be used for
the exposure of the swimmer’s airways to chlorineand its metabolites, and through this omission may
the diagnosis of EIB in elite swimmers, as recommended
result in a significant number of missed diagnoses
of EIB in swimmers. The accepted field swimchallenge may account for these missed diagnoses.
Furthermore, none of the currently recommended
Currently the International Olympic Committee-
challenges have been studied in elite swimmers.
Medical Commission (IOC-MC) requires that all
The aim of this study is thus to assess the
athletes provide objective evidence of exercise-
effectiveness of the EVH challenge, the field swim
induced bronchoconstriction (EIB) or asthma to
challenge and the laboratory cycle challenge in the
obtain approval for the use of inhaled beta 2
Recent Olympic data suggests an increasing
prevalence of EIB/asthma amongst elite endurance
athletes,1–5 especially swimmers.1 Such data were
Thirty-three volunteer elite swimmers, defined as
obtained using various methodologies. These were
State Level or above, were recruited from
commonly based on clinical diagnoses, which have
swim clubs throughout Melbourne, Australia, to
Br J Sports Med
participate in this prospective study. All subjects were aged
average heart rate was recorded at the end of the challenge.
14 years and older and were required to have a baseline forced
Ambient conditions in the lab were 21 (0.8)uC and 60.5 (2.1)%
expiratory volume in 1 second (FEV1) greater than 60%
predicted for their age, height and gender to exclude anysubject with an active exacerbation of asthma. Subjects with a
past history of asthma were not excluded from the study.
Prechallenge values for percent predicted FEV1 were compared
Subjects were excluded if they had had a recent respiratory
with postchallenge values using a paired Student t test. The
infection or exacerbation of their asthma. The research protocol
maximum percent fall in FEV1 from baseline for each challenge
was approved by both the University of Melbourne and the
test was calculated by subtracting the lowest FEV1 value
Royal Melbourne Hospital Ethics Committees.
recorded post challenge from the best baseline value and
Once accepted into the study and having given informed
expressing it as a percentage of the baseline value. A fall in
consent, each subject completed a standardised Respiratory
FEV1 >10% from baseline was considered positive for EIB.20 A
Questionnaire adapted from the European Community
bronchodilator response of >12% rise in FEV1 from baseline was
considered positive for asthma.21 Within-subject comparisons
Each subject was evaluated for the presence of EIB using three
between the EVH and swim challenge tests, between the bike
different BPCs: a field swim challenge, an EVH challenge and a
and swim challenge tests, and between the EVH and bike
laboratory cycle challenge. Testing order was random, and
challenge tests were made using paired t tests. Differences
consecutive tests were separated by more than 24 h but less
between EIB-positive and EIB-negative subjects were examined
than 1 week. All testing occurred in the morning to control for
using independent t tests. A p value ,0.05 was considered
diurnal variation in airway calibre. The subjects were asked to
statistically significant for all analyses. All values are presented
refrain from caffeine and exercise on the days of the testing and
withhold their asthma medications for designated times as perHolzer et al.10
Baseline spirometry was performed prior to each challenge
All 33 subjects (23 male: age 19.3(5.3) years; 10 female: age 15.6
and the best of three values for FEV1 and forced vital capacity
(2.1) years) completed each of the challenges without complica-
(FVC) were recorded and used for subsequent calculations.
tion. Baseline spirometry and fall in FEV
Spirometry prior to and during the EVH and laboratory cycle
response to each of the challenges for the 33 subjects are
challenge was performed on the System 2310 Spirometer, Vmax
presented in table 1. Baseline spirometry exceeded the normal
series (Sensormedics BV) and for the field swim challenge on a
predictive values for age, gender and height and correlated well
portable MicroMedical Superspiro Spirometer (Rochester, Kent,
with existing resting values for elite athletes. There was no
significant difference in baseline values between those who
Spirometry was performed at 1, 3, 5, 7 and 10 minutes
were EIB-positive or negative, for any challenge.
following the cessation of each of the exercise/hyperpnoeastimuli. At each of these measurement times the better of two
values for FEV1 was recorded to be used in subsequentcalculations. Following the 10 minute measurement, or earlier
Thirteen of the 33 subjects (39%) had a previous clinical
diagnosis of asthma. Of these, three (23%) were regularly using
1 fell greater than 30%, 200 mg of salbutamol was
inhaled from a volumatic spacer; further spirometry was
an inhaled corticosteroid, three (23%) were regularly using an
performed 10 minutes following this.
inhaled corticosteroid/long-acting beta agonist combination,
The field swim challenge was conducted at the Melbourne
one (8%) was using an inhaled mast cell stabiliser prior to
Sports and Aquatic Centre, in a chlorine and ozone-filtered
exercise, four (44%) were only using an as-required inhaled beta
indoor 50 m competition pool used for national championships.
2 agonist, and two subjects (23%) were not using any asthma
The challenge required the subject to swim for 8 minutes at the
medication. One of the 13 (8%) subjects with a previous
highest intensity sustainable, aiming to maintain a heart rate of
diagnosis of asthma had a positive field swim challenge, 11
(85%) had a positive EVH challenge and three (23%) had a
max (HRmax = 220 2 age), for the duration of the
test. Subjects were fitted with a wireless Polar Heart Rate
positive laboratory cycle challenge. Only two (15%) of thosepreviously diagnosed with asthma showed a positive broncho-
Monitor (Polar Electro; Oy, Finland) and the average heart ratewas taken at the completion of the challenge. Ambient
dilator response for asthma. Two subjects (15%) with aprevious asthma diagnosis were negative for EIB on all three
conditions for the indoor pool were 30 (SD 2.7) uC and 82
BPCs and had negative bronchodilator responses. Both of these
(4.5)% relative humidity, with a pool temperature of 27 (0.3)uC.
subjects were using only an as-required inhaled beta 2 agonist.
The laboratory EVH challenge was conducted according to
the single-stepped protocol of Argyros and coworkers.18 Thischallenge required the subject to inhale a dry gas containing 5%
carbon dioxide, 21% oxygen and balance nitrogen (BOG Gases,
Of the 20 subjects with no previous diagnosis of asthma, seven
Melbourne, Australia) at room temperature for 6 minutes at a
(35%) had a positive EVH challenge with one (5%) of these also
target ventilation of 85% maximum voluntary ventilation
having a positive laboratory cycle challenge test diagnostic of
(MVV), equivalent to 30 times the resting FEV
EIB. None of these subjects had a positive field swim challenge.
conditions in the laboratory were 21 (0.8)uC and 60.5 (2.1)%
Further, one of these subjects had a positive bronchodilator
response for asthma, and negative EVH, swim and cycle tests
The laboratory cycle challenge used the stepped protocol
recommended by the American Thoracic Society.19 The 8 min-ute challenge was performed on the Ergometrics 800 (Ergoline,
Germany) cycle ergometer. A Polar Heart Rate Monitor Watch
Only one of the 33 subjects (3%) had a positive field swim test
(Polar Electro; Oy, Finland) was worn by the subject and the
with a fall in FEV1 of 16% from baseline compared with 3.0
Br J Sports Med
Table 1 Subject baseline spirometry and fall in FEV1 in response to the EVH, swim and cycle challengesSubject
EVH fall in FEV1 (%) Swim fall in FEV1 (%) Cycle fall in FEV1 (%)
EIB-positive swimmers identified in bold. pred, predicted.
*Subjects 1, 7 and 18 had a positive bronchodilator response for asthma
(2.4)% in the 32 (97%) who were negative. The swim-positive
challenge. This subject also had a positive bronchodilator
subject swam at 93% of his predicted HRmax and had a
response for asthma. This subject reported a mean symptom
postchallenge symptom score of 4/4, whilst the swim-negative
score of 4/4 following each challenge.
subjects swam at 87 (4)% their predicted HRmax (p.0.05), with
Of the 32 subjects negative to the swim challenge, 17 had a
positive EVH and three a positive cycle challenge, with mean
Eighteen of the 33 subjects (55%) had a positive EVH
falls in FEV1 from baseline of 19.1 (10.6)% and 14.8 (5.8)%
challenge test, with a mean fall in FEV1 of 20.4 (11.7)% from
baseline compared with a mean fall of 5.8 (2.3)% in the 15
Two subjects were negative to the swim and positive to both
subjects (45%) who were negative. The EVH-positive subjects
the EVH and cycle challenges, with a mean fall in FEV1 from
demonstrated a mean predicted MVV of 78 (11)% during the
baseline of 36 (2.8)% for the EVH and 17 (6.2)% for the cycle
challenge, compared with a mean predicted MVV of 75 (9)% in
challenge. One subject positive on the laboratory cycle challenge
the EVH-negative subjects (p,0.05). The EVH-positive subjects
had a mean number of 3.5/4 symptoms compared with 2/4symptoms in those subjects who were EVH-negative (p,0.01).
Four of the subjects (12%) had a positive laboratory cycle test,
The results of this study have shown a significant and
with a mean fall in FEV1 of 14.8 (4.7)% from baseline, compared
substantial discrepancy between the diagnostic results of three
with 2.4 (3.5)% in the 29 (88%) who were negative. The cycle-
BPCs commonly used for the diagnosis of asthma/EIB in elite
positive subjects exercised at 91 (3)% their predicted HRmax and
swimmers. The field swim challenge found that only one of the
had a mean symptom score of 3.5/4, whilst the cycle-negative
33 swimmers (3%) tested had a result consistent with the
subjects exercised at 91 (5)% their predicted HRmax (p.0.05)
presence of EIB. In contrast, the EVH challenge identified EIB in
and had a mean symptom score of 1.5/4.
18 of the 33 subjects (55%) tested. These results suggest thateither the EVH challenge is overdiagnosing the presence of EIB
in swimmers or the field swim challenge is significantly
Only one of the 33 subjects was positive to all three challenges,
with a fall in FEV1 from baseline values of 16% for the field
In this study to investigate the diagnostic efficacy of different
swim, 43% for the EVH and 15% for the laboratory cycle
BPCs for EIB in elite swimmers, we used challenges all
Br J Sports Med
considered acceptable by the IOC-MC for objective evidence ofEIB. In regards to the EVH challenge, Phillips et al22 demon-
strated that the airway response in asthmatics, as measured bychanges in FEV
EIB and asthma are common conditions in elite swimmers. The
1 and specific conductance, to hyperpnoea with
cause is thought to be the repeated exposure to ozone, chlorine
2 was similar to that provoked in the same asthmatic
subjects by exercise at the same ventilation. EVH has been
and their metabolites which accumulate at the pool/air interface.
reported to have a high specificity for active asthma, diagnosing
These conditions are commonly diagnosed and confirmed with a
number of objective bronchial provocation tests.
abnormal and 100% when a 15% fall is considered abnormal.23The symptoms provoked by EVH are very similar to those thatoccur following exercise. The major advantage in using EVH
over exercise is that subjects’ ventilation levels are monitoredand are able to be sustained at high enough levels to induce
This study shows a wide discrepancy between a number of
bronchial provocation tests accepted by the IOC-MC as objective
Few studies have been performed comparing the efficacy of
evidence of EIB in elite swimmers. It further shows that exposure
the EVH challenge with exercise challenges. Until recently,
to chlorine or its metabolite gases is not required to induce EIB at
these had only been performed in winter athletes and
the time of the challenge. It shows that the EVH challenge test is
concluded, similarly to our results, that the EVH challenge
highly sensitive at identifying EIB in elite swimmers.
was superior to both the field25 26 and laboratory27 exercisechallenges in the diagnosis of EIB. A recently published,concurrent study by Pedersen et al has suggested that the
unaccustomed exercise rather than ventilatory restriction.
EVH challenge is a BPC superior to the field swim, laboratory
During the EVH challenge, there was no such limitation.
exercise and the methacholine challenge in the diagnosis of EIB
Second, and perhaps more importantly, the air inhaled during
in 16 female non-asthmatic elite swimmers.28 Whilst it showed
the laboratory cycle challenge was the ambient room air, which
that the EVH challenge was the superior challenge for EIB
had an average relative humidity of 60%, greater than the
diagnosis, it did not show a significant difference over the
recommended 50% stated in the exercise guidelines.19 To
exercise challenges, perhaps a reflection of its smaller sample
overcome this, the subjects should have inspired dry air during
size and different exercise challenge protocols.
Although field exercise challenges are known to be highly
Perhaps the major limitation of this study relates to the
specific for EIB, the sensitivity of these in the detection of EIB is
humidity of the air inhaled during each of the challenges. The
only moderate.24 29 30 Unlike the EVH challenge, a number of
hypercapnic dry gas mixture used for the EVH challenge test has
variables may unknowingly influence the results of the exercise
a low enough water content to promote EIB, whereas the air
challenges. Although the subjects’ average HRmax exceeded 85%
inhaled during the field swim challenge was of such high water
for both the exercise challenges, we were unable to monitor
content that it was protective against EIB.32 The relative falls in
their ventilation rates. Rundell et al suggested that the exercise
FEV1 following each of these challenges, as well as the
challenge should be performed at race pace, or greater than 95%
postchallenge EIB symptom scores, reflects this.
HRmax, to achieve and maintain ventilations high enough to
In conclusion, the results of this study display the wide
induce bronchoconstriction.31 The Pedersen study, whilst not
discrepancy that occurs between the different BPCs in the
directly monitoring ventilation or heart rates, attempted to
diagnosis of EIB in swimmers. Importantly, it demonstrates
address this by asking subjects to exercise at the highest
that exposure to chlorine or its metabolite gases is not required
intensity possible until exhaustion, reflecting a higher preva-
to induce the airway hyperresponsiveness at the time of the
lence of positive field swim and laboratory treadmill challenges
challenge. Our study shows that the EVH challenge is highly
sensitive at identifying EIB in elite swimmers, whilst the
For the field swim challenge, difficulties in standardising the
exercise challenge tests may significantly underdiagnose the
environmental conditions at the pool surface may have affected
condition. As the EVH challenge test is a well-established and
the respiratory response to the swim challenge and thus the
standardised test for EIB in elite winter and summer land-based
results. Although the poolside ambient air conditions and pool
athletes, it supports the recommendations of the IOC-MC that
temperature were measured on each occasion, factors such as
the EVH challenge test should be used for the diagnosis of EIB in
the concentration of ozone, chlorine and its metabolite gases on
all elite athletes, including swimmers. However, where the EVH
the pool surface, pool chlorine and ozone concentrations and
challenge test is not available, a laboratory exercise challenge
poolside ventilation were not measured.
where the subject exercises until exhaustion whilst breathing
In both the laboratory-based challenges, despite standardisa-
dry air should be considered for identifying EIB in elite
tion of the environmental conditions, the athletes were not
exposed to the potential environmental triggers that are in thepool environment. This may have potentially reduced the
sensitivity of these challenges for EIB in swimmers. However,the results of this study, in particular the high prevalence of
positive EVH challenges, suggest that the airway hyperrespon-
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NCMIR METHODS FOR 3D EM: A NEW PROTOCOL FOR PREPARATION OF BIOLOGICAL SPECIMENS FOR SERIAL BLOCK FACE SCANNING ELECTRON MICROSCOPY Thomas J. Deerinck, Eric A. Bushong, Andrea Thor and Mark H. Ellisman Center for Research in Biological Systems and the National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA, USA Note: This protocol was desig
Sicherheitsdatenblatt gemäß 1907/2006/EG, Artikel 31 ABSCHNITT 1: Bezeichnung des Stoffs bzw. des Gemischs und des Unternehmens · Erstellungsdatum/Erstausgabe: 01.02.2012 · 1.1 Produktidentifikator · Handelsname: IBK 2012 · 1.2 Relevante identifizierte Verwendungen des Stoffs oder Gemischs und Verwendungen, von denen abgeraten wird keine Daten verfügb