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Peripheral blood counts in workers exposed to

synthetic fibres
a a a a
Tiziana Caciari , Teodorico Casale , Beatrice Loreti , Maria P. Schifano , Assunta
a a a b a
Capozzella , Barbara Scala , Simone De Sio , Gianfranco Tomei , Maria V. Rosati &
a
Francesco Tomei
a
Department of Anatomy, Histology, Medical-Legal and the Orthopedics, Unit of
Occupational Medicine , Sapienza University of Rome , Rome , Italy
b
Department of Neurology and Psychiatry , Sapienza University of Rome , Rome , Italy
Published online: 30 Oct 2013.

To cite this article: Tiziana Caciari , Teodorico Casale , Beatrice Loreti , Maria P. Schifano , Assunta Capozzella , Barbara
Scala , Simone De Sio , Gianfranco Tomei , Maria V. Rosati & Francesco Tomei (2014) Peripheral blood counts in workers
exposed to synthetic fibres, Journal of Environmental Science and Health, Part A: Toxic/Hazardous Substances and
Environmental Engineering, 49:2, 146-152, DOI: 10.1080/10934529.2013.838839

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 Journal of Environmental Science and Health, Part A (2014) 49, 146–152
Copyright C Taylor & Francis Group, LLC

ISSN: 1093-4529 (Print); 1532-4117 (Online)

DOI: 10.1080/10934529.2013.838839

Peripheral blood counts in workers exposed to synthetic

fibres
TIZIANA CACIARI1, TEODORICO CASALE1, BEATRICE LORETI1, MARIA P. SCHIFANO1,
ASSUNTA CAPOZZELLA1, BARBARA SCALA1, SIMONE DE SIO1, GIANFRANCO TOMEI2,
MARIA V. ROSATI1 and FRANCESCO TOMEI1
1
Department of Anatomy, Histology, Medical-Legal and the Orthopedics, Unit of Occupational Medicine, Sapienza University
of Rome, Rome, Italy
2
Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
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Acrylonitrile is an intermediary with possible adverse health effects in the synthesis of organic products, such as acrylic fibres. This
investigation was undertaken to determine the possible changes in the peripheral blood counts in workers of a polyacrylic fibres plant.
The study involved 218 workers exposed to acrylonitrile at low doses and a control group of 200 unexposed workers. The chosen
subjects underwent blood tests in order to check their haematological parameters. There were no statistically significant differences
between the two groups in terms of the red blood cells, haemoglobin and total number of leukocytes. An increase in the neutrophils
associated with a reduction of lymphocytes, both statistically significant, was observed. The authors hypothesized that the neutrophils
are influenced by the exposure to acrylonitrile at low doses.
Keywords: Acrylonitrile, synthetic fibres, peripheral blood counts, neutrophilia.

Introduction nisms suggested is an increase of the oxidative stress, de-

In the last 30 years the textile industry has grown partic-
ularly with regard to the production of synthetic fibres,
the use of which has become more and more substan-
tial not only on its own, but also in combination with
other natural or artificial fibres. Among the synthetic fibres
the polyacrylic fibres are noteworthy for their adaptability
to new systems of textile production, and for the signifi-
cance and clear increase in their production in Italy. The
raw material for the production of the polyacrylic fibres
is acrylonitrile (AN); its polymer is the polyacrylonitrile
(PAN).[1–8]
In a PAN plant, the risks of occupational toxicity are
mainly linked to the absorption of acrylonitrile. The occu-
pational exposure to acrylonitrile occurs primarily through
the respiratory route, but the acrylonitrile can also be ab-
sorbed through skin contact and ingestion; metabolism
and the mechanism of toxic action have not yet been
fully elucidated.[1,3–5,7–12] One of several possible mecha-
Address correspondence to Maria V. Rosati, Department of
Anatomy, Histology, Medical-Legal and the Orthopedics, Unit
of Occupational Medicine, Sapienza University of Rome, Viale
Regina Elena 336, 00161 Rome, Italy; E-mail: siprosrl.spinoff@
gmail.com
Received April 26, 2013.
rived from depletion of glutathione (GSH) resulting, in
turn, by the ability of acrylonitrile and its metabolites—the
cianoetilene oxide (CNEO) and cyanide—to bind to
GSH.[3,4,11,13]
The effects on human health by the man-made organic
fibres (MMOFs), among which is PAN, are still studied
and current literary data may undergo further review, espe-
cially with regard to improvement of the production meth-
ods of such fibres and consequent reduction of their size
that makes them much more respirable.[6,14] The problem of
chronic toxicity, once denied by most authors, is currently
being revised. It has been suggested that a possible carcino-
genic role is likely, linked to the action of acrylonitrile, its
compounds and its metabolites.[6,13,14]
Over the last few years, different studies have been con-
ducted in order to verify the possible relationship between
exposure to acrylonitrile and its compounds and other syn-
thetic fibres, and the development of tumours in different
sites, for example renal cell carcinomas, lung carcinomas,
tumours of the central nervous system (in particular astro-
cytomas) and leukaemias.[1,3–5,7–9,11–13,15–19]
In the experimental field, histological lesions in the
central nervous system characterized by oedema and chro-
matolysis of the neurons, liver damage with hepatomegaly
and histological signs of degeneration, cardiovascular and
respiratory system damage and genitourinary apparatus
 Peripheral blood counts in synthetic fibre workers
damage have been observed. In workers chronically
exposed to low doses of acrylonitrile, symptoms such as
fatigue, headache, drowsiness, irritability, anorexia, nau-
sea, vomiting, heartburn, excessive sweating, dyspnoea and
objective signs such as low blood pressure, hepatomegaly,
reduction of ECG voltage and reduction of the vital
capacity (VC) have been reported.[1,4,12,20,21]
With regard to the peripheral blood counts, an influence
of the occupational exposure to acrylonitrile on the red
[20–23]
and white series, both for the number of the white
blood cells and the leukocyte formula,[2,16,17,19,23] has been
reported. The hematopoietic system is strongly influenced
by the action of many different environmental pollutants
to which workers may be exposed, as shown in some of our
previous studies.[24–31] Starting from these premises, this
research aims to analyse whether changes in the peripheral
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blood counts may occur in workers exposed to acrylonitrile
at low doses.
Materials and methods
The study was conducted on a sample of male workers
employed in a plant for the production of PAN. The pro-
duction cycle comprises the following steps: polymerization
(in cooled reactors), recovery of the unreacted monomers,
filtration (by means of rotary filters), and drying (in suit-
able dryers). In addition to acrylonitrile, other substances
are used: methacrylate, various additives and auxiliaries
(sodium metabisulphite, sodium nitrite, sulphuric acid,
soda) to reach the final product (polyacrylonitrile). After
drying, the PAN, now in the form of very fine powder, is
dissolved in the solvent dimethylacetamide (DMAC), in or-
der to obtain the viscose. For inclusion in the study, each
worker completed a clinical-anamnestic questionnaire in
the presence of a physician, investigating the following ar-
eas: age, work seniority, family history, physiological anam-
nesis, past and present pathological anamnesis and work
history.
Questions about diseases and/or disorders of the
hematopoietic system, collected through a binary system
(yes/no), were also raised. Each subject was asked: “have
you recently had bleeding disorders?”, “are you a blood
donor?”, and “have you ever been diagnosed with diseases
and/or disorders of the hematopoietic system?” An accu-
rate drug history was collected in order to verify any past
or present treatment for these diseases. The questionnaire
even focused on hobbies and/or other leisure activities that
could have exposed the subjects to one or more substances
acting on the blood counts (such as paint, pesticides, sol-
vents, etc.) and on any lifestyle habits (alcohol consumption
and smoking).
We excluded subjects with confounding factors: subjects
with past and/or present pathological history of diseases
and/or disorders of the hematopoietic system; subjects
147
with acute and chronic ongoing inflammatory processes;
subjects treated, in the past or at present, for the diseases
listed above; subjects potentially exposed to substances
acting on the blood counts for their hobbies and/or other
leisure activities; current smokers (a current smoker is
someone who has smoked at least 100 cigarettes in his
lifetime and currently smokes every day or almost every
day);[32] habitual consumers of alcohol who have exceeded
the threshold of moderate alcohol consumption (no more
than two units of alcohol per day for men and no more
than one alcoholic unit per day for women, where one unit
of alcohol corresponds to about 12 grams of ethanol).[33]
The workers exposed to acrylonitrile, who were included
in the study, were matched by age and work seniority to
a control group of subjects not exposed to acrylonitrile.
Among the initial 248 exposed workers, 218 were included
in the study; among the initial 800 not exposed subjects
working as clerks, 200 workers were included in the
study. The age of the 218 workers was between 25 and
50 years, mean age 37.84 and work seniority between
5 and 8 years with an average of 6.54 years. The age
of the 200 workers not exposed to acrylonitrile was
between 25 and 50 years, mean age 37.56 and work
seniority between 5 and 8 years with an average of
6.70 years.
After fasting and before the beginning of the work shift,
each worker and control underwent a blood test (10 mL)
so that the complete peripheral blood counts with leuko-
cyte formula could be performed. Samples were kept in
the workplace in a refrigerator at +4◦ C until they were
transferred, by means of a container at the same tempera-
ture, to the laboratory where the amount of red blood cells
(RBC), white blood cells (WBC), haemoglobin (HGB) and
percentages of neutrophils (Neutr), lymphocytes (Lymph),
eosinophils (Eos) and monocytes (Mono) were measured
by means of a haematological electronic analyser (Coulter
Counter Model S Plus IV, Hialeah, FL, USA).
All the subjects analysed worked regularly in places
where the levels of the chemical substances used were below
the threshold limit values (TLVs; TLV-TWA for acryloni-
trile <2 ppm, for the year 2011).[34] All the subjects agreed
to their personal data being available, declaring that they
had been made aware that these data were ranked as “sensi-
tive information,” and consented that the data arising from
the research protocol should be treated in an anonymous
and collective way, with scientific methods and for scientific
purposes in accordance with the principles of the Declara-
tion of Helsinki.
Statistical analysis of the data was based on the calcula-
tion of the mean, of the standard deviation, of the frequency
and of the minimum and maximum values, according to the
nature of the single variables. The differences between the
means were compared by using the Student’s t- test. Fre-
quencies of the single variables were compared using the χ 2
test. The differences were considered significant when the
P values were lower than 0.05.
 148
Results and discussion
The results observed are listed in Table 1. The table shows
that there are no statistically significant differences in the
values of RBC, HGB and WBC between the two groups
studied. A significant increase (P < 0.001) of the granulo-
cytic neutrophils associated with a significant reduction of
the lymphocytes is observed in the exposed subjects. There
are no significant differences between the two groups as to
the number of the eosinophils and of the monocytes. The
results show that in 28 exposed workers, that is, 12.84%
of cases, the granulocytic neutrophils are more than 70%,
while in the control group only 7 subjects, that is 3.5% of
cases, have a number of neutrophils higher than 70% (statis-
tically significant difference, P < 0.05). There are no statisti-
cally significant differences (the χ 2 test) among the exposed
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Caciari et al.
which must never be exceeded for a maximum time period
of 15 min and in any case for no more than four times a day
with intervals of at least 1 h between peak periods) have
been measured. For the same purpose, other possible con-
founding factors were eliminated: thus we excluded from
the case group and from the control group all subjects with
past or present pathological history of diseases and/or dis-
orders of the hematopoietic system; subjects with acute and
chronic ongoing inflammatory processes; subjects treated,
in the past or at present, for haematological diseases; sub-
jects who might have been exposed to substances acting
on the blood counts because of their hobbies and/or other
leisure activities; current smokers and habitual consumers
of alcohol who exceed the threshold of moderate alcohol
consumption.
In literature, a variable influence on the peripheral blood

subjects and the controls regarding the values outside the
reference range for the other haematological parameters.
The subjects were exposed to low doses of acrylonitrile
below the limits set by the TLVs.
To minimize the possible risk that the observed results
could be materially affected by the presence, in the work-
place, of one or more substances at high doses and with pos-
sible haematotoxic action, we proceeded to determine the
environmental concentrations of the other chemical agents
employed in the production cycle: methacrylate, sodium
metabisulphite, sodium nitrite, sulphuric acid and soda.
For all these substances, levels below the TLV-TWA
(time-weighted average concentration, on a conventional
working day of 8 h and for 5 days a week, of pollutants
in the workplace air to which nearly all workers may be
exposed without adverse effects occurring) and the TLV-
STEL (average concentration of the pollutants in the air
counts is reported, which may be dose-related; a compari-
son of our results with the results of other researchers for
similar studies is shown in Table 2. In a plastics plant three
groups of workers exposed to different doses (high doses:
hand laminators, medium doses: sprayers; low doses: main-
tenance workers) were compared with each other, and with
a control group of unexposed clerks. Red blood cells and
haematocrit were slightly reduced in subjects exposed to
high doses compared to controls; no alteration was ob-
served in haemoglobin and in the absolute number of white
blood cells, while there was a suppression of the prolif-
erative response of T-lymphocytes stimulated with con-
canavalin A in those exposed to high and medium doses
compared to controls.[23]
Also, a significant increase in the percentage of mono-
cytes in the differential white blood cell counts of the ex-
posed groups was observed.[23] Other authors found no

Table 1. Minimum and maximum values, mean, standard deviation (SD), Student t test and significance (p) in the peripheral blood
counts of the exposed (E) and not exposed (NE) subjects.
Normal Minimum Maximum Student
Variables range value value Mean SD t test Significance

HGB (E) (mmol/L) 8.07–10.86 7.7 11.6 9.746 0.698 −0.782 n.s.∗
HGB (NE) (mmol/L) 6.13 11.25 9.8 0.713
RBC (E) (104/mm3) 450–590 458 584 521.3 239.1 0.112 n.s.∗
RBC (NE) (104/mm3) 385 783 516.7 553.1
WBC (E) 102/mm3 40–100 39 108 71.6 13.58 0.583 n.s.∗
WBC (NE) 102/mm3 36 125 70.7 17.85
Neutr (E) (%) 50–70% 56 74 66.2 4.47 15.105 p < 0.001
Neutr (NE) (%) 39 76 58.6 5.78
Eos (E) (%) 1–4% 0 5 1.51 1.15 0.756 n.s.∗
Eos (NE) (%) 0 12 1.4 1.78
Lymph (E) (%) 20–45% 22 42 30.5 4.41 −14.885 p < 0.001
Lymph (NEx) (%) 20 54 37.7 5.46
Mono (E) (%) 3–7% 0 5 1.7 0.94 −1.284 n.s.∗
Mono (NE) (%) 0 4 1.8 0.60
∗
n.s. = no significance.
HGB = haemoglobin; RBC = red blood cells; WBC = white blood cells; Neutr = neutrophils; Eos = eosinophils; Lymph = lynphocytes; Mono =
monocytes.
 Peripheral blood counts in synthetic fibre workers
changes in the peripheral blood counts: a study was con-
ducted on workers with long-term exposure to acrylonitrile
(>5 years), compared to an unexposed control group. The
exposed workers belonged to seven plants classified accord-
ing to the time-weighted average concentration (TWAC) of
acrylonitrile as group A (TWAC < 0.3 ppm, concentration
of acrylonitrile equal to 0.27 ppm) and group B (TWAC ≥
0.3 ppm, concentration of acrylonitrile equal to 0.84 ppm).
The levels of exposure, estimated by the analysis of indi-
vidual samplings, were found to correspond to the levels of
exposure expressed by the TWAC.
Table 2. Comparison of results of this study with those reported by other researchers in the literature for similar studies.
Our results
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Red series No statistically significant differences in the values of
red blood cells and haemoglobin, between the
exposed (at low doses of acrylonitrile) and
unexposed subjects
White series No statistically significant differences in the values of
white blood cells, between the exposed (at low
doses of acrylonitrile) and unexposed subjects
Significant increase of the granulocytic neutrophils
in the exposed (at low doses of acrylonitrile)
subjects compared to controls
Significant reduction of the lymphocytes in the
exposed (at low doses of acrylonitrile) subjects
compared to controls
No significant differences in the number of the
eosinophils and of the monocytes between the
exposed (at low doses of acrylonitrile) and
unexposed subjects
Granulocytic neutrophils more than 70% in the
12.84% of the exposed (at low doses of
acrylonitrile) subjects versus the 3.5% of the
controls
149
The results observed showed no significant differences
between cases and controls with regard to the peripheral
blood counts.[21] The same results, that is peripheral blood
counts within reference range, were reported by Pimentel
et al.,[20] who described the cases of seven subjects occu-
pationally exposed to nylon and acrylic fibres (orlon) who
developed lung diseases. With regard to the white series, a
study was conducted on three groups of mice administered
with acrylonitrile once a day at a dose of 2.7 mg/kg for 5,
10 and 15 consecutive days, respectively. The results of the
study showed a reduction in the percentage of lymphocytes
Results of other researchers
Somorovská et al.[23] (study on humans) reported:
• a slightly reduction of red blood cells and of haematocrit
in subjects exposed to high doses compared to controls
• no alteration in haemoglobin in subjects exposed to
high doses compared to controls
Muto et al.[21] (study on humans) reported:
• no significant differences between cases and controls
with regard to the peripheral blood counts
(haemoglobin, haematocrit, red blood cells)
Pimentel et al.[20] (study on humans) reported:
• values of peripheral blood counts within reference range
in seven subjects occupationally exposed to nylon and
acrylic fibres
Somorovská et al.[23] (study on humans) reported:
• no alteration in the absolute number of white blood cells
in subjects exposed to high doses compared to controls
• a significant increase in the percentage of monocytes in
the differential white blood cell counts of the
exposed groups
Pimentel et al.[20] (study on humans) reported:
• values of peripheral blood counts within reference range
in seven subjects occupationally exposed to nylon and
acrylic fibresHamada et al.[2] (study on mice) reported:
• a reduction in the percentage of lymphocytes in a spleen
cell suspension in the exposed mice compared to a
control group
• a reduction of lymphocyte subsets (T and B cells) in the
exposed mice compared to a control group
• a marked reduction of T helper and T suppressor cells
in the exposed mice compared to a control group
Hamada et al.[2] (study on mice) reported:
• a reduction in the percentage of lymphocytes in a spleen
cell suspension in the exposed mice compared to a
control group
• a reduction of lymphocyte subsets (T and B cells) in the
exposed mice compared to a control group
• a marked reduction of T helper and T suppressor cells
in the exposed mice compared to a control group
Sathiakumar et al.[16,17] (study on humans) reported:
• a positive association between the development of
leukaemias and the work in synthetic rubber
industries for those workers exposed to relatively high
doses
 150
in a spleen cell suspension as well as a reduction of lym-
phocyte subsets (T and B cells) and a marked reduction
of T helper and T suppressor cells, compared to a control
group that only received distilled water for 10 days.[2] Some
authors demonstrated a positive association between the
development of leukaemias and the work in synthetic rub-
ber industries for those workers exposed to relatively high
doses.[16,17]
According to the results we obtained, it can be assumed
that the workers employed in the production of polyacrylic
fibres do not undergo toxic insults inducing changes of
the haemoglobin values or of the erythrocytes in a PAN
plant where the TLVs are not exceeded. These results are
similar to those observed in some previous studies where
no significant differences of the haemoglobin and red blood
cell values were observed.[20,21] As to the erythrocyte values,
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the discrepancy with a study by Somorovska et al.[23] could
depend on the difference in exposure dose, which was high
in the Somorovska et al.[23] study and lower than the TLVs
in our research.
In this study the influence of the exposure on the white
series was found: a significant increase of neutrophils as-
sociated with a significant reduction of lymphocytes was
observed in the group of exposed subjects. These changes
could be related to the occupational exposure to acryloni-
trile and its compounds, since the two groups of subjects
under examination (exposed and controls) were matched
by age and work seniority. The data observed could sug-
gest that in some workers, neutrophils are influenced by the
exposure to low doses in agreement with the fact that many
toxicants, at an early stage, may determine neutrophilia
associated or not to an increase of leukocytes, probably ex-
erting a transient irritative action on the leukopoietic line
of the bone marrow, generally a predictive condition of an
incipient leukopenia.[28,29]
As demonstrated for some metals (arsenic, copper, mer-
cury and cadmium), or micronutrients, vitamins, hormones
and various other substances (including pesticides, preser-
vatives, chemotherapeutic and other industrial chemicals),
it is also possible that the acrylonitrile has a hormetic ac-
tivity at low doses (that is stimulating neutrophils) with the
addiction of a mechanism of reverse hormesis (that is in-
hibiting lymphocytes).[26,35,36] Also we should note that the
majority of the literary studies that investigated the changes
in the peripheral blood counts as a result of exposure to
acrylonitrile was generally conducted using high doses of
this substance;[2,16,17,23] in our study, the observed changes
in the peripheral blood counts resulted from exposure to
low doses (far below the TLV-TWA). The interaction be-
tween two or more toxic substances with possible additive
or synergistic or antagonistic effects might be taken into
account.[37,38]
Toxicological interaction is the combination of two or
more chemical, biological, and/or physical agents that re-
sults in a qualitatively or quantitatively altered biological
response relative to the one predicted from the action of a
Caciari et al.
single chemical or agent; the interaction may be simultane-
ous or sequential, and the biological response may be in-
creased or decreased.[39] Toxicologic interactions may be of
different types: chemical substance vs chemical substance
interaction, chemical substance vs biological agent interac-
tion, chemical substance vs physical agent interaction, and
biological agent vs biological agent interaction.[39]
Humans are exposed simultaneously or sequentially to
a large variety of chemicals derived from different sources
such as environmental contaminants, voluntary exposure
(food, water, cigarette smoking) or work activity; despite
all this, most of the research investigates the effects of sin-
gle substance and less frequently the health effects resulting
from the exposure to two or more chemicals.[37,39–42] How-
ever there are some literary studies that have investigated
the effects of simultaneous or sequential exposure to two
or more chemical substances.[38,39,42–44]
Although in our study the occupational exposure to acry-
lonitrile and to the other chemicals of the production cycle
has occurred at levels below the corresponding TLVs, some
hypothesis could still be made: the effects on the periph-
eral blood counts attributed to the acrylonitrile may be the
result of potentiation linked to the presence of other sub-
stances or, on the contrary, the lack of involvement of the
red series could be due to the antagonism between acry-
lonitrile and one or more of the other substances in the
production cycle.
These results are interesting and could be the basis for
further research, even for the identification of strategies
for the improvement of the safety and/or of the risk
assessment from the combined exposure to chemicals.[41]
Moreover, considering the small number of subjects under
examination and the high number of confounding factors,
we suggest that this study should be carried out on other
plants with similar characteristics in order to confirm
on the one hand that at low doses the red series is not
altered and, on the other hand, that some changes in the
differential white blood cell count may occur indicating an
influence of the exposure to the acrylonitrile on the number
of neutrophils and lymphocytes in the peripheral blood.
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