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Neurotoxicology: B. Hilt, K. Svendsen, T. Syversen, O. Aas, T. Qvenild, H. Sletvold, I. Melø
Neurotoxicology: B. Hilt, K. Svendsen, T. Syversen, O. Aas, T. Qvenild, H. Sletvold, I. Melø
NeuroToxicology
A R T I C L E I N F O A B S T R A C T
Article history: Previous investigations have presented evidence for an increased prevalence of late cognitive effects in
Received 25 November 2008 dental personnel exposed to metallic mercury. We wanted to examine if there was a correlation between
Accepted 29 April 2009 mercury exposure and cognitive effects in a Norwegian population of dental workers, and if so, to
Available online 7 May 2009
quantify the occurrence.
The study group consisted of 608 female dental assistants from central Norway and 425 female
Keywords: controls from the general population, all under the age of 70. They had responded to a standardized
Cognitive function
postal questionnaire (Euroquest) inquiring about seven symptoms in regard to neurology, psychoso-
Dental work
Occupation
matics, memory, concentration, mood, sleep disturbances, and fatigue. A score was calculated for each
Metallic mercury symptom based on 4–15 single questions graded on a scale from 1 (seldom or never) to 4 (very often).
Euroquest Dental assistants and controls had a participation rate of 56.4% and 42.9% respectively. Dental
assistants reported more cognitive symptoms than the controls, but on average they reported having
each of the symptoms ‘‘now and then’’ or less frequently. There were 4.4% of the dental assistants and
2.8% of the controls who reported having three or more of the seven symptoms ‘‘often’’ or more
frequently. The corresponding figures for five or more of the seven symptoms were 1.0% and 0.5%
respectively.
The occurrence of cognitive malfunction may be moderately increased in dental assistants. For dental
assistants there was a relative risk of 1.6 of having three or more symptoms ‘‘often’’ or more frequently,
and a relative risk of 2.0 of having five or more symptoms as frequently. It can be assumed from our
results that the prevalence of possibly work-related cognitive malfunction in dental assistants is
between 0.4% and 2.8%, dependent on the applied severity.
ß 2009 Elsevier Inc. All rights reserved.
0161-813X/$ – see front matter ß 2009 Elsevier Inc. All rights reserved.
doi:10.1016/j.neuro.2009.04.012
B. Hilt et al. / NeuroToxicology 30 (2009) 1202–1206 1203
with urine levels above 500 nmol/l can lead to chronic cognitive To form a control group, the Norwegian Central Bureau of
effects, while there is more doubt as to whether exposures below Statistics randomly chose 1062 women from the same counties
this level can lead to similar long term effects (Meyer-Baron et al., with a categorical matching for age within 5-year groups. To be
2004; Rohling and Demakis, 2006). During the last 25 years, several included in the study, the control subjects had not to have been
studies have given indications which raised concern, by showing engaged in dental health care, and had to have worked outside
that both dentists and other dental personnel have had an their homes for more than 5 years after 1960. The control group
increased prevalence of symptoms of cognitive malfunction, and/ was invited and asked to fill out and submit the primary
or have shown cognitive impairments in neuropsychological questionnaire in the same way as the dental assistants.
investigations (Shapiro et al., 1982; Uzzell and Oler, 1986; Nilsson In addition to inquiring about some general information such as
et al., 1990; Ngim et al., 1992; Ibarra Fernandez de la Vega et al., age, education, some life style issues, and a few health questions,
1992; Echeverria et al., 1995; Langworth et al., 1997; Ritchie et al., the first questionnaire comprised a Norwegian version of the
2002; Aydin et al., 2003; Moen et al., 2008). standardized European questionnaire called ‘‘Euroquest’’ which
The toxic mechanism in the nervous tissue after metallic has been designed to monitor cognitive symptoms in subjects
mercury exposure has not been completely worked out. When exposed to neurotoxic substances (Carter et al., 2002). We used the
metallic mercury vapour is inhaled and absorbed in the form of Hg0 parts of that questionnaire inquiring about mood, memory, ability
it is transported in the blood stream and deposited throughout the to concentrate, sleep disturbances, neurological symptoms,
body. Hg0 is oxidised to form mercuric mercury, Hg2+ in different psychosomatic symptoms, and fatigue. For each of these symp-
organs, and there is a dynamic equilibrium between Hg0 and Hg2+ toms there are 5–15 different questions. Each of these can be
in blood. It is believed that mercury deposited in the brain after Hg0 answered with the alternatives ‘‘seldom or never’’, ‘‘now and then’’,
exposure is taken up as the metallic form and not as the oxidised ‘‘often’’ or ‘‘very often’’ with designated values from 1 to 4
form Hg2+. Once mercury has passed the blood–brain barrier as respectively. In order to have a valid answer for each symptom, it
Hg0, some of it will be intracellularly oxidised to Hg2+, most was required that two thirds of the questions included in that
probably in the astrocytes. It has repeatedly been suggested that particular symptom had been answered. A score was calculated for
exposure to metallic mercury may result in both short term and each symptom as the mean of the values for the questions
long term psychological and cognitive effects. The milder form of included.
these effects, characterized by weakness, fatigue, psychological By comparing the occurrence of cognitive symptoms with
disturbances, and asthenia, is termed micromercurialism, while increasing levels of severity between the group of dental assistants
the more severe form of intoxication, which entails psychotic and the control group, we were able to calculate a range of
symptoms, is termed erethism (Clarkson and Magos, 2006; Berlin corresponding etiological fractions that could be used to assess the
et al., 2007). share of dental assistants with different levels of cognitive
In Norway, the preliminary publication of the results from a symptoms that could possibly be attributed to their occupational
small study of cognitive problems in 41 dental assistants (Moen exposure to mercury.
et al., 2008), and a television programme broadcasted in 2005
raised considerable public concern by indicating that chronic 2.1. Statistical analysis
metallic mercury intoxication and cognitive injuries were common
in dental personnel. After that, the Ministry responsible for labour Data were registered and analysed with the data program
protection initiated research on the topic. Statistical Package for Social Science version 14.0 (SPSS) (SPSS Inc.,
The aim of this study was to see whether dental assistants have Chicago, IL, USA). The differences between the dental assistants
an increased prevalence of symptoms consistent with cognitive and the controls in scores for each symptom group was analysed by
malfunction, and, if so, to quantify the occurrence of such general linear modelling controlling for age and educational level.
complaints. A 5% level was chosen for statistical significance, and all p-values
were calculated as two-sided.
2. Subjects and methods
2.2. Ethical considerations
We asked the public dental health care system and some dentists
in private practice in three counties in Central Norway for lists of all The study was approved by the ethical committee for medical
employees who had ever worked as dental assistants. In this way we research in Central Norway, and had a licence for personal
identified 1224 females who had probably worked as dental registrations from the Norwegian Social Science Data Services. The
assistants and thus were candidates to be included in the study. authors declare that there are no conflicts of interest.
All the identified women were invited to participate in the
study by filling out a posted primary questionnaire and to answer a 3. Results
second questionnaire relating to their work career and working
conditions while working in the dental health care system. We Out of the 1224 presumed dental assistants who were asked to
asked them to submit both questionnaires in a prepaid envelope. participate, 690 (56.4%) responded and 655 of them confirmed that
More details on our inquiry about working conditions in they had worked as a dental assistant. Of these, 47 were excluded
Norwegian dental health care and the results thereof are described because they were over the age of 69, leaving us with 608 dental
at more length in another publication (Svendsen et al., submitted assistants for the analysis. From the 1062 women who had been
for publication). In addition, all the identified dental assistants selected for the control group, 456 (42.9%) participated. Of the
were asked for written permission to access any results on urine controls, 31 were excluded because they had not been occupa-
mercury levels held at the National Institute of Occupational tionally active for at least 5 years, had worked in the dental health
Health. Norwegian dental personnel had throughout the years care themselves, and/or were older than 69 years of age. Table 1
been invited to submit urinary samples to this central institute shows background variables and some information on life style
where the samples were analysed as they came in by cold vapour issues for the participating dental assistants and the control group.
flameless atomic absorption spectrophotometry and the results The groups were rather similar in regard to most variables, apart
were given in nmol/l (Gundersen and Mowé, 1977; Lenvik et al., from the control group having a somewhat higher level of formal
2006). education than the dental assistants.
1204 B. Hilt et al. / NeuroToxicology 30 (2009) 1202–1206
Table 1
Background variables for the participating dental assistants and controls.
Table 2
Mean scores for seven symptom groups from the Euroquest questionnaire reported by 608 dental assistants and 425 controls.
Number of valid answers Mean symptom score (SD) Number of valid answers Mean symptom score (SD)
Table 3 the general population, where we find small, but yet, some
Percent of the dental assistants and the controls who had answered that they had
statistically significant differences.
three, four or five of the seven symptoms often (value 3) or more frequently.
As the symptoms scores reported were low, and mostly in the
Dental assistants Controls Relative range from ‘‘never/seldom’’ to ‘‘now and then’’ for both dental
n = 608 n = 425 risk
assistants and controls, this did not say much about a possible
Three or more symptoms 4.4 2.8 1.6 health injury. We therefore tried to refine the results by elucidating
Four or more symptoms 2.5 0.9 2.8 how many of the participants who had a certain amount of the
Five or more symptoms 1.0 0.5 2.0
seven symptom groups ‘‘often’’ or more frequently, and thus could
be disabled by their symptoms to some extent. In the dental
assistants we found three, four or five of the symptom groups to be
mercury have an increased prevalence of symptoms consistent present ‘‘often’’ or more frequently in 4.4%, 2.5% and 1%
with cognitive malfunction. When compared to a control group respectively. When comparing with the control group, the rate
from the general population, we found that some dental assistants ratios were 1.6, 2.8, and 2 respectively. Thus, depending on what
may suffer from long term cognitive effects, mainly reflected by degree of symptom severity we chose, we found the prevalence of
problems with their memory, ability to concentrate, neurological cognitive complaints in dental assistants to be probably some-
symptoms, and fatigue. where below 5%, with an etiological fraction between 38% and 64%.
Both for dental assistants and the control group, the results may In this analysis we did not attempt to relate the occurrence of
be hampered by a low participation rate. This could entail bias in symptoms to exposure. This might be difficult anyway in this kind
both directions because it might be that the non-responders from of low dose, long term toxicological effect where many factors,
both groups, as often is the case, were less healthy than the including a probable individual susceptibility may play a role in
responders, and, thus, the real occurrence of symptoms in both determining the effects (Echeverria et al., 2006). We do, however,
groups has been underscored. The present study was carried out find it worth mentioning, and which is also to some degree relief,
about a year after a television programme which brought the issue that in dental assistants who had started to work after 1990 when
of mercury exposure in dental offices and possible injuries from amalgam was gradually phased out of Norwegian dental health
that into the public agenda. This may influence both the quantity care, our results showed the same symptom scores as in the
and quality of the response to our questionnaire. A possible bias controls.
might be that dental assistants who believe that their health In conclusion, some of the dental assistants who were exposed
problems are related to previous exposure will be more likely to to mercury from dental amalgam during earlier years may suffer
respond—and that they are inclined to report symptoms in a more from long term cognitive effects. We must, however, in light of the
aggressive manner. This would, in both cases, have biased the methodological difficulties and limitation that we faced, be
results in the direction of enhanced differences between the cautious to interpret this as causality. Even so, when applying
groups. One feature which is an argument against a serious bias in our criteria for the graveness of symptoms and an etiological
our material, is that the dental assistants did not report more of the fraction between 38% and 64%, it can be assessed from our material
other health complaints that had also been mentioned in the media that the prevalence of possibly work-related cognitive malfunction
as possible effects of mercury exposure. Moreover, our results were in dental assistants is between 0.4% and 2.8%, dependent on the
in line with the other Norwegian study (Moen et al., 2008) which severity.
was conducted before the media attention about the health of
dental assistants emerged. Thus, neither selection, nor recall bias Conflicts of interest
can be ruled out, but we do not think that the possible effects
thereof have been decisive in the results in regard to cognitive The authors declare that there are no conflicts of interest.
symptoms.
Uncontrolled confounding may also have had impact on the Acknowledgement
results of the present study. The group of dental assistants and the
controls were fairly similar in regard to smoking habits, alcohol Cordial thanks to Prof. Bente Moen at the University of Bergen
consumption, and amalgam fillings in their own teeth, while we for providing us with a correctly translated Norwegian version of
lacked information on other potential confounders such as drug the Euroquest questionnaire, to Patricia Flor for linguistic help, to
abuse, mental illness, cardiovascular diseases, and previous head the Norwegian Ministry of Labour and Inclusion for initiating and
injuries. At least age turned out to play a role when we used general financing the study, and not least to all the participants for their
linear modelling to look at possible impacts of urine mercury great patience when answering a lengthy questionnaire.
values and length of employment as a dental assistant.
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