See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/352100694

Standardized experimental model for cement dust exposure; tissue heavy

metal bioaccumulation and pulmonary pathological changes in rats

Article  in  Toxicology Reports · June 2021

DOI: 10.1016/j.toxrep.2021.06.001

CITATIONS READS

0 37

3 authors:

Mathew Owonikoko Benjamin Emikpe

Igbinedion University University of Ibadan
12 PUBLICATIONS   11 CITATIONS    379 PUBLICATIONS   2,067 CITATIONS   

SEE PROFILE SEE PROFILE

Samuel Olaleye
University of Ibadan
117 PUBLICATIONS   1,127 CITATIONS   

SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Use of phytogenic extracts in control and management of listeriosis in farm raised Clarias gariepinus in Oyo State, Nigeria View project

Cadmium Exacerbates Acetic Acid Induced Experimental Colitis in Rats View project

All content following this page was uploaded by Benjamin Emikpe on 09 June 2021.

The user has requested enhancement of the downloaded file.

 Toxicology Reports 8 (2021) 1169–1178

Contents lists available at ScienceDirect

Toxicology Reports
journal homepage: www.elsevier.com/locate/toxrep

Standardized experimental model for cement dust exposure; tissue heavy

metal bioaccumulation and pulmonary pathological changes in rats
M.W. Owonikoko a, B.O. Emikpe b, S.B. Olaleye a, *
a
Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria
b
Department of Veterinary Pathology, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria

A R T I C L E I N F O A B S T R A C T

Edited by DR. A.M Tsatsakis A controlled experimental model of exposure to aerosols particularly for cement dust was recently invented in a
study from the laboratory that found high serum levels of heavy metals, decrease gastrointestinal motility, and
Keywords: altered hematological variables in cement dust exposed rats. However, reproducibility was not considered. This
Exposure chamber work aims at standardizing the model and investigating preliminary toxicological indicators. Thirty male rats
Heavy metals
used in this study were divided into 3 groups (n = 10). Group 1; control, while groups 2 and 3 were exposed to
Cement dust
cement dust for 14 days and 28 days respectively. We assessed clinical signs of toxicity, tissue heavy metal
Histopathology
Bioaccumulation concentration, histopathological, and body weight (BW) changes. We observed poor movement coordination,
Pulmonary toxicity abnormal posture, cephalic fur loss. Evidence of ischemia and fibrotic pneumoconiosis were grossly observed in
the lungs of the exposed groups. There was a significant increase in tissue level of heavy metals with pulmonary
and gastric heavy metal content showing a trendy relationship during the period of the exposure as the value of
Lead, Chromium, Cadmium, Iron, Calcium, and Nickel increased by nearly similar percentages in both tissues.
Organs weights increased; the 14-day exposed (198 ± 31; 168 ± 22) and 28-day exposed (198 ± 22; 187 ± 26)
groups had significantly reduced body weight at the first and second weeks of exposure compared to the control
group (265 ± 26; 357 ± 40) respectively. Exposure to cement dust induced low bone density in the exposed rats
(p < 0.05). Histopathological alterations include necrosis, inflammatory cellular infiltration, and alveolar hy­
perplasia suggestive of the proliferative response of pulmonary tissue to the dust. The operation of the stan­
dardized apparatus mimics a typical occupational exposure and the findings show that cement dust induces
systemic toxicity via respiratory perturbation and body/organ weight discordance mediated by heavy metal
bioaccumulation.

1. Introduction considered to be toxic to the body system. Deleterious health effects of

cement production at host communities such as Kashmir valley and
Cement industries constitute a notable source of environmental Krew in India [8,9]; Ewekoro in Nigeria [10] and Oromia, Addis Ababa
toxicants [1,2] encountered during the manufacturing, distribution, and in Ethiopia [11] have been severally reported. These reports have
utilization of cement product. Occupational and environmental expo­ attracted the attention of researchers to cement dust studies.
sure to cement dust has been known to precede a number of systemic Increased level of consciousness on the adverse health effects of
injuries with particular reference to the respiratory, gastrointestinal, cement dust culminates in scientific research since over two decades
and integumentary systems characterized by fibrosis, emphysema, ago; an intervention which has been overtly impeded by the dearth of a
cough, cancer, inflammation, and liver diseases among workers and host known model of experimental exposure. Data hitherto analyzed stem­
community residents of cement factories [3,4]. Cement product which med basically from questionnaires [12–17,9], examination of health/­
has wide application in the construction industry is a homogenous medical records [18,19], interviews [16,20,21] and case report [22].
mixture of hazardous heavy metals such as Cobalt (Co), Iron (Fe), lead Toxicosis of cement dust is still poorly understood because, hitherto,
(Pb), cadmium (Cd), Chromium (Cr), Nickel (Ni), Manganese (Mn), and empirical investigations have been achieved only by the deployment of
arsenic (As) at different relative proportions [5–7] which have been crude experimental procedures of merely placing experimental animals

* Corresponding author.
E-mail addresses: [email protected] (M.W. Owonikoko), [email protected] (S.B. Olaleye).

https://doi.org/10.1016/j.toxrep.2021.06.001
Received 21 October 2020; Received in revised form 31 May 2021; Accepted 1 June 2021
Available online 3 June 2021
2214-7500/© 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
M.W. Owonikoko et al. Toxicology Reports 8 (2021) 1169–1178

in proxy distance to cement factories [10,23]. Meanwhile, this method laboratory chow ad libitum.
of exposure gives wide room for controversies as a number of other Following two weeks of acclimatization, they were exposed to
confounding environmental factors could be responsible for the reported cement dust with the aid of an exposure chamber fabricated according to
pathologies considering the appreciable physical distance between the the specifications below (Fig. 1A and B). This study was conducted in
location of the experimental animals and the actual cement factory. The accordance with the current Animal Care Regulations and standards
need for experimental research on the pathophysiological mechanisms approved by the Institute for Laboratory Animal Research [25] and the
involved in the reported effects of cement dust is required for validation experimental protocol was approved by the Animal Care and Use
and further investigation of its toxicosis. Therefore, an exper­ Research Ethics Committee, University of Ibadan, Ibadan, Nigeria hav­
imental/laboratory method of exposure characterized by simplicity and ing been assigned the approval number UI-ACUREC/18/0129.
reproducibility is required. Recently, our laboratory developed a model
for regulated exposure which has been deployed in a preliminary study
to access the effect of cement dust on some hematological variables and 2.2. Standardized design and operation of the Exposure Apparatus
indices with interesting outcomes. Emanating data suggest that an in­
crease in serum concentration of some heavy metals including the The dust exposure was carried out with the use of a fabricated non-
alteration of hematological variables accompany the exposure to cement mobile apparatus designed to simulate a cement factory environment for
dust [24]. Although the results from this study mimic earlier reports in the exposure of experimental animals to particulate matters. Unlike the
the literature on human subjects, however, the efficacy and reproduc­ previous report [24], the method was standardized by modifying it into
ibility of the model cannot be guaranteed. The initial generation and a perfect square of 60 cm in height, breadth, and width, made of
distribution of dust by the chamber is characterized by significant en­ transparent plexiglass. An internal subchamber of height 20 cm, breadth
tropy, a condition that may be substantially different from the instan­ 26 cm, and diameter of 32.8 cm is specifically designed to house the
taneous distribution. These provisions make the effusion rate of the dust. Made of plexiglass, the subchamber is designed to contain cement
chamber dust generation unquantifiable. Also, some important param­ dust with its walls adequately perforated to ensure constant effusion of
eters of the chamber such as the diameter were not taken into cogni­ cement dust-laden air into the portion of the chamber housing the rats.
zance which further precipitates the challenge of reproducibility. Hence, There is no available entrance to the subchamber from the internal
the rationale for this study is to standardize the chamber and since portion of the apparatus. This is with the intention to prevent the
inhalation is one of the three major routes of exposure to respirable explorative animals from mechanical injury, to prevent the interruption
particulate matters from the external environment, we set to investigate of the dispensing circuitry of the chamber to ensure sustained; main­
the attendant effect of cement dust exposure on the pulmonary taining constant effusion rate, and to prevent direct ingestion of the dust.
cytoarchitecture and the probable accompanying heavy metal accu­ The apparatus which is particularly designed to avail the experimental
mulation tendency particularly in the visceral tissues. animals a wide range of movement consists of a manipulative chimney
of 30 cm by 10 cm dimension located on the apparatus lid (dorsally) and
2. Materials and methodology diagonally to the internal subchamber, perpendicularly to the internal
subchamber and opened during operational periods but closed
2.1. Animals thereafter.
The subchamber houses two miniature metallic quadri-bladded
Thirty (30), 3-month-old male Wistar rats weighing between aerators situated at an anterodorsal right angle to each other. The aer­
150− 180 g were purchased from the animal house of the college of ators are heavy duty type of model CNS-3− 20/620 (serial number
Medicine, University of Ibadan, and were kept in plastic cages with S40141392) running in main alternating current of 220 V, power of
wood shavings. They were housed under standard conditions of tem­ 27 W, current of 0.25A, and frequency of 50/60 Hz. They are capable of
perature (23 ± 2 ◦ C), humidity (55 ± 15 %), and natural 12 h light and moving with a speed of 2400/3400 rpm. When connected to a power
dark cycle in the Animal house of Department of Physiology, University source, sufficient torque equips the aerators as they synergistically
of Ibadan, Ibadan. They were allowed access to water and standard generate, propel and deliver the dust in inhalable form from the sub­
chamber to the internal portion of the apparatus housing the

Fig. 1. A: The Description of the apparatus. B: The apparatus in operation (Advancement and modifications stated in Table 2).

1170
M.W. Owonikoko et al. Toxicology Reports 8 (2021) 1169–1178

experimental animals. The specificity of the aerators enables the gen­ 2.7. Digestion of tissue and heavy metal analysis
eration and dispensation of about 0.2 g/h of the dust.
Heavy metal level in the lungs, brain, stomach and spleen of the
2.3. Cement material and exposure exposed animals were investigated according to [26]. Nitric acid (1 mL)
followed by perchloric acid (1 mL) was added to 100 mg of the tissues
A full intact and freshly supplied bag of Nigeria Portland cement was each in a clean sample bottle. The mixtures were then digested over a
purchased from an accredited depot in Ibadan, Oyo state, Nigeria. The sand bath until the solution becomes clear and yellow in colour. In the
exposure began daily by introducing 100 g of cement dust into the instance of the outcome of brown-coloured digest, the above process was
subchamber. Old and remnant dust were evacuated prior to exposure repeated. The digests were aliquoted after being made up to known
every other day. This routine practice was maintained on daily basis. volume of ionized water and read using Atomic Absorption spectro­
Exposure was 5 h daily for periods of 14 days and 28 days using the photometer model (Buck Scientific AAS Model 210/211 VGP, Con­
exposure chamber. The control rats received sham exposure to normal necticut, USA) at various wavelengths according to the standard
atmospheric oxygen. They were all sacrificed thereafter. working parameters stated in Table 1 below. Results of accumulated
heavy metals were recorded in mg/L and presented as mean ± SEM.
2.4. Experimental rats grouping Radiation source were the hollow cathode lamp of Lead (Pb), Chromium
(Cr), Cadmium (Cd), Nickel (Ni), Iron (Fe), Manganese (Mn), Cobalt
There were three (3) groups in this study each with 10 animals. The (Co) and Calcium (Ca) while the fuel was air acetylene.
first group (Group 1) of rats were the control group. The second group
(Group 2) received cement dust exposure for 14 days (14-day group) 2.8. Macroscopy and histomorphological investigation
while the last group (Group 3) were exposed to cement dust for 28 days
(28-day group). Exposure was carried out 5 h daily. The control Group Following the sacrifice of the animals, the lungs were excised and
animals were allowed to thrive in completely dust-free environment. carefully examined for any macroscopic pathology before fixing in 10 %
The experimental animals were all allowed free access to standard lab­ formalin for histological examinations. They were thereafter embedded
oratory chow and water. in paraffin wax; sectioned at 5 μm and were stained with haematoxylin
and eosin before viewing under light microscope (PEC MEDICAL USA;
2.5. Body and organ weights X400 Mag) for any pneumopathological alterations according to [27].
The histological and pathological evaluations were carried out by a
The weekly weight changes of the animals in the groups each were blinded pathologist.
determined using Acculab® USA, Model-vic-303 electronic analytical
weighing balance and recorded while weekly percentage change in 2.9. Statistical analysis
weight throughout the study was calculated as:

[(B – A)/A x 100] (1) Statistical analyses were done using Graphpad prism 5.0® and data
presented as mean ± SEM for n = 5 per group while One-way ANOVA
Where “A” represents the “initial weight”, “B” is the “final weight”. and Dunnette post-hoc test were used for mean comparison between the
During sacrifice, visceral organs including the stomach, lungs, heart, different groups with p < 0.05 considered significant as stated at each
spleen and brain were collected. The relative organ weight was calcu­ case.
lated by using the formula;
3. Results
(X/ Y) x100 g (2)

Where “x” represents the “Absolute Organ Weight”; the raw weight of The chamber as modified and standardized is pictorially represented
the organ as obtained from the weighing balance while “y” is the above in Fig. 1A and B. The major discrepancies and the standardizing
“Terminal Body Weight (TBW)”; the instantaneous weight of the animal factors are analysed in Table 2 below.
at the point of sacrifice. The width of the chamber and the subchamber had been slightly
Mean Femoral Weight (MFW) is the sum of the weight of the femur adjusted to suit that of a perfect square. Although the height of the
divided by “n” per group while Relative Femoral Weight (RFW) was chamber remains the same but that of the subchamber was slightly
calculated from the equation below reduced. The diameter and the dust effusion rate were determined. This
is expected not only to increase the internal space of the major part of
(FW/TBW) g (3) the chamber but also to modify the aerosolized dust. Overall, the
Mean Relative Femoral Weight (MRFW) is the sum of the RFW modifications ensured effective and calculable dust effusion rate.
divided by “n” per group
The same as above was applicable to the femur after collecting and 3.1. Clinical signs
the attached muscles carefully trimmed off.
One rat died after two weeks of exposure out of the 28-day exposed
2.6. Clinical observations animals (Group 3) while the period of exposure lasted. A number of
clinical signs of toxicities such as mortality, laboured breathing,
Each animal in the different groups were carefully examined on daily
basis before and after experimental exposure for possible clinical signs of Table 1
cement dust-induced toxicity in the respiratory and behavioural pat­ Operational parameters of atomic absorption spectrophotometer.
terns, skin, fur, eyes and other mucous areas while morbidity/mortality S/NO METAL WAVELENGTH (nm) SLIT WIDTH
case was equally noted. At the end of the experiment, the animals were
1 Lead 283.3 0.7
fasted overnight but were allowed access to water. All visceral organs 2 Chromium 357.9 0.7
including the stomach, spleen, lungs and brain were excised, carefully 3 Cadmium 228.9 0.7
examined before weighing and thereafter digested for heavy metal 4 Cobalt 352.7 0.7
analysis except the lungs tissue that was divided into two and part of it 5 Manganese 279.5 0.7
6 Iron 248.3 0.7
was fixed in 10 % formalin for histopathology.

1171
M.W. Owonikoko et al. Toxicology Reports 8 (2021) 1169–1178

Table 2 increased fur lability and cephalic fur loss. Other signs were frequent
Modifications entrenched to standardize the earlier model of cement dust sneezing, abnormal posture and hypoactivity. There was evidence of
exposure. poor nervous coordination resembling that of hemiballism and tremor. It
PARTS SPECIFICATIONS MODIFICATIONS FUNCTIONAL was equally observed that the vigor and boisterous tendencies exhibited
ALLOWANCES by the exposed animals at the beginning of the experiment gave way for
DUST 1Plastic and 1 iron 2 iron bladed docility, weakness and anorexia occasioned by restricted movement
GENERATOR bladed industrial fan aerators before the end of the experiment Fig. 2B. The exposed animals also show
CHAMBER
59.9cm 60 cm sign of drastic weight loss than the control. During sacrifice, there were
WIDTH
grossly observable conditions of fibrotic pneumoconiosis at the caudal
CHAMBER
HEIGHT
60 cm 60 cm lobe alongside with being pus-gorged portions (black arrows in Fig. 2D,
CHAMBER E and F) near the deep respiratory zone. There was also evidence of
Unknown 84.9cm
DIAMETER pulmonary ischemia with grossly observable pale red patches at the
SUBCHAMBER serosal surface of the anterior lobes (yellow arrow in Fig. 2F) in the 14-
26.1cm 26 cm
WIDTH
SUBCHAMBER
and 28-days exposed animals.
19.6 cm 20 cm
HEIGHT
SUBCHAMBER
Not stated 32.8 cm 3.2. Body and organ weight changes
DIAMETER
CHIMNEY AREA 10.6cm × 9.9cm 30cm × 10cm
Table 4 shows that the 14-day exposed group and 28-day exposed
group had significantly reduced body weight at the first and second
weeks of exposure (Week 1 – week 4 in the table) compared to the
FAN SPEED 2400− 3000rpm 2400− 3000rpm control group. The rate of body weight gain in the test groups (14-day
and 28-day exposed) was significantly reduced in the weeks of exposure
when compared with the control. Also, the TBW and weight changes of
the femur present an interesting statistic with the 14-day group showing
DUST EFFUSION marginal difference and 28-day showing a significant difference when
Unknown 0.2 g/hr Reproducible
RATE compared with the control group. For instance, TBW of the 14-day
exposed groups decreased by 10.67 % while the 28-day group
decreased by 16.42 % when compared with the control. The MFW of the
14-day exposed group present 9.34 % while the 28-day exposed group
present 31.78 %. MRFW shows the same trend with the 28- and 14-days
exposed group showing 27.14 % and 8.57 % respectively. The foregoing

Fig. 2. A-F: Observed clinical signs of toxicity

among cement dust exposed animals; A: Ce­
phalic fur loss (black arrow) and abnormal
posture following 28-day cement dust exposure.
B: Docility and hypoactivity of exposed animals
showing maintenance of stationary position. D,
E and F: pulmonary emphysema and haemor­
rhages of caudal lobe of the lungs in the 14- and
28-days exposed animals. E and F: pus-gorged
and pulmonary ischemia of the caudal lobes
respectively (black arrows) and pale red
patches on the anterior lobe of the lungs (yel­
low arrow); all compared with C: A normal
lungs (from the control group) showing normal
appearance and intact gross morphology. (For
interpretation of the references to colour in this
figure legend, the reader is referred to the web
version of this article.)

1172
M.W. Owonikoko et al. Toxicology Reports 8 (2021) 1169–1178

shows that the body weight of the 28-day exposed group is more affected the distribution and severity of the pulmonary histopathological
than the 14-day group. changes observed in this study with hyperplasia of histiocytes, mono­
nuclear cell infiltration in alveoli, medial hypertrophy of muscular ar­
3.3. Histoarchitectural alterations teries and fibrinoid necrosis being the most predominant pathologies
while presence of eosinophilic substance, fibroblast proliferation,
Fig. 3A-F, represent the photomicrographs of experimental animals oedema and alveolar septal thickening were the least observed which
from the control, 14-day and 28-day exposed groups respectively. The were all completely absent in the control animals.
control animals (Fig. 3A and B) show normal lungs cytoarchitecture Fig. 4A-F represent the relative weights of the stomach, spleen, lungs,
while the treated groups (3C-F) had an array of pathological manifes­ heart, brain and femur respectively while Table 3 shows femoral bone
tations including fibrinoid necrosis, evidence of emphysema and in­ weight changes. The relative weight of the lungs (F-value = 16.25, p-
flammatory response of the tissue marked by mononuclear cell Value = 0.0010), stomach (F-value = 5.307, p-Value = 0.0223), and
infiltration. Alveolar type II pneumocyte hyperplasia was observed in spleen (F-value = 27.64, p-Value = 0.009) were significantly higher in
addition to those alterations at the 28-day exposed group. Table 6 shows 14-day and 28-day groups when compared to the control. However, the

Fig. 3. A and B: Lung tissue showing normal

architecture of control animals. C and D: Lung
tissue showing alveolar congestion and hemor­
rhage (Fig. 3C brown arrow), Alveolar septal
thickening with congestion, hemorrhages,
diffuse mild type II pneumocyte proliferation
and infiltration of mononuclear cell infiltration
(Fig. 3D; black arrow) of 14-day Exposed ani­
mal. E and F: Lungs showing effect of cement
dust on pulmonary tissue with evidence of se­
vere alveolar type II pneumocyte cell hyper­
plasia (Fig. 3E green arrow) and mononuclear
cell infiltration (Fig. 3F black arrow) and
medial hypertrophy of muscular arteries and
fibrinoid necrosis of 28-day exposed animals.
Mag: X400. (For interpretation of the references
to colour in this figure legend, the reader is
referred to the web version of this article.)

1173
M.W. Owonikoko et al. Toxicology Reports 8 (2021) 1169–1178

Fig. 4. A Effect of cement dust on relative

lungs weight. ** Significant when compared
with the control. B: Effect of cement dust on
relative stomach weight. ** Significant when
compared with the control. C: Effect of cement
dust on relative heart weight. ** Significant
when compared with the control. D: Effect of
cement dust on relative spleen weight. ** Sig­
nificant when compared with the control. E:
Effect of cement dust on relative brain weight.
** Significant when compared with the control.
F: Effect of cement dust on femoral weight and
mean femoral weight. ** Significant when
compared with the control.

relative weights of the brain (F-value = 5.323, p-Value = 0.0298) and Fig. 4A, B and E respectively depicted a persistent increase in weight
femur (F-value = 50.33, p-Value = 0.0002) was significantly higher only from the 14-day to the 28-day.
in the 28-day group while that of the heart increased significantly only
in the 14-day exposed group when compared with the control at 3.4. Heavy metals analysis
p < 0.05. Lung, stomach and brain tissues shows somewhat similar
pattern of response to cement dust exposure. While other organs (Heart Heavy metals analysis as found in Table 5 above represents a
and Spleen) show a mithridatic reduction in the 28-day group when considerable output. Analysis of the heavy metal content of the various
compared with the 14-day group, stomach, lungs and brain tissues in visceral organs shows that the lung tissue has a significantly high level of

1174
M.W. Owonikoko et al. Toxicology Reports 8 (2021) 1169–1178

Table 3 consistent with all the assessed organs. Values of Ca in the test groups
Mean relative femoral weight of experimental animal following exposure to (14- and 28-day) in the respective organs are significantly higher than in
cement dust. the control. However, the 28-day group produced multiple folds of value
GROUPS TBW(g) MFW(g) MRFW as found in the 14-day except for the stomach sample where the 14-day
CONTROL 168.7 ± 4.1 1.07 ± 0.03 0.7 ± 0.03
is approximately half. Values of Pb and Cr are also significantly higher in
14-DAY 150.7 ± 2.4* 0.97 ± 0.03* 0.64 ± 0.01 the test group when compared with the control. Similarly, almost none
28-DAY 141.0 ± 5.51* 0.73 ± 0.13* 0.51 ± 0.07* of the values presents a double or multiple fold of the other. The 28-day
Only values of the MRFW are presented in mean ± SEM.
group only show a marginal increase when compared with the 14-day
TBW- Terminal body weight; MFW; mean Femoral Weight; MRFW; mean group. With respect to the data from the lungs, Pb and Cr show a mar­
Relative Femoral Weight. ginal increase over time as found in the comparison between the 14-day
*
p < 0.05 are significant when compared with control. and the 28-day groups, Cd decreased, Co and Mn increased in multiple
(5 and 7 times respectively). Only, Fe and Ni doubly increased in line
with what might be expected considering the double length of exposure.
In the brain tissue, only Fe increased doubly while other metals appear
Table 4 about the same level at both the 14- and 28-day groups. In the spleen,
Weekly percentage mean body weight change induced by 4 weeks exposure to however, Pb and Cr increase are similar to the findings in the lungs,
cement dust.
whereas Cd, Co, Mn, Fe, and Ni all increased 5, 3, 4, 2, and 3 times
GROUPS WEEK 1 WEEK 2 WEEK3 WEEK 4 respectively, showing substantial accumulation from 14 to 28 day of
CONTROL 165 ± 26 257 ± 40 373 ± 50 463 ± 58 exposure. Available data at the 14- and 28-day exposed groups partic­
14-DAY 98 ± 31* 68 ± 22* ularly for the lungs and stomach are interesting when compared with the
28-DAY 96 ± 22* 87 ± 26* 152 ± 45* 166 ± 52*

Values are presented in percentages.

* Table 6
p < 0.05 is significant when compared to the control.
Observed pulmonary histomorphometry of rats exposed to cement dust.
ALTERATIONS/GROUPS CONTROL 14 DAY 28 DAY

Ni at 14-day and 28-day groups, Cr and Co showed significantly high Alveolar type II Pneumocyte Hyperplasia ̶ þþ þþþ
Alveolar mononuclear cell infiltration
level only at 28-day while Cd was significant only at the 14-day exposed ̶ þþ þþþ
Focal Hemorrhage ̶ þþ þþ
group when compared with the control. The stomach tissue has signif­ Alveolar Septal thickening ̶ þ ̶ þþ
icantly high Pb, Fe at both exposed groups (14-day and 28-day expo­ Emphysema ̶ þþ þþ
sure), while Cr and Ni were significantly high only at the 28-day exposed Periarteitis ̶ þþ þþ
group when compared with the control. The brain tissue as shown by the Medial hypertrophy of muscular arteries ̶ þ ̶ þþþ
Eosinophilic Substance
14-day and 28-day groups had significantly high levels of Pb, Cd, Mn,
̶ þ ̶ þþ
Fibroblast tissue proliferation ̶ þ ̶ þþ
and Ni while Cr and Fe were only significantly higher in the 28-day Fibrinoid Necrosis of blood vessels ̶ þþ þþþ
group compared to the control. The spleen at both 14-day and 28-day Oedema ̶ þ ̶ þþ
groups depicted a significantly high level of Pb, Cr, Co, Ni while Cd
The observed morphological alteration of the erythrocyte was assessed using the
and Mn were only significantly high at the 28-day group when compared grade below:
with the control. ̶: morphological change absent in animals in a group.
The values of Fe in the respective organs (brain, spleen, lungs, and + ̶: morphological change rarely found in animals in a group.
stomach) are significantly higher in the test groups when compared with +: morphological change found in some animals in a group.
the control. Moreover, values of this metal in the 14-day exposed group ++: morphological change common to all animals of a particular group.
approximately twice as found in the 28-day exposed group. This is +++: morphological change common to most animals in the exposed groups.

Table 5
Heavy metal analysis of the various tissues (mg/L) of experimental animals exposed to cement dust.
PARAMETERS ORGANS

HEAVY METAL GROUPS LUNGS BRAIN SPLEEN STOMACH

CONTROL 0.03 ± 0.00 0.05 ± 0.01 0.04 ± 0.00 0.03 ± 0.01

Pb 14-DAY 0.95 ± 0.07* 1.05 ± 0.06* 1.29 ± 0.14* 1.02 ± 0.04*
28-DAY 1.02 ± 0.07* 1.08 ± 0.33* 1.43 ± 0.24* 1.10 ± 0.03*
CONTROL 0.02 ± 0.00 0.06 ± 0.03 0.07 ± 0.01 0.03 ± 0.01
Cr 14-DAY 0.17 ± 0.04* 0.11 ± 0.00 0.12 ± 0.01* 0.12 ± 0.00*
28-DAY 0.26 ± 0.08* 0.15 ± 0.00* 0.17 ± 0.01* 0.35 ± 0.12*
CONTROL 0.04 ± 0.01 0.01 ± 0.00 0.01 ± 0.00 0.02 ± 0.01
Cd 14-DAY 0.35 ± 0.05* 0.05 ± 0.02* 0.05 ± 0.01* 0.06 ± 0.01
28-DAY 0.12 ± 0.07* 0.05 ± 0.01* 0.27 ± 0.03* 0.05 ± 0.01
CONTROL 0.02 ± 0.00 0.05 ± 0.00 0.01 ± 0.00 0.11 ± 0.01
Co 14-DAY 0.16 ± 0.05* 0.44 ± 0.17* 0.20 ± 0.07* 0.39 ± 0.02*
28-DAY 0.84 ± 0.15* 0.45 ± 0.13* 0.74 ± 0.13* 0.30 ± 0.03*
CONTROL 0.05 ± 0.01 0.00 ± 0.00 0.02 ± 0.01 0.07 ± 0.01
Mn 14-DAY 0.13 ± 0.01* 0.06 ± 0.00 0.04 ± 0.01 0.06 ± 0.01
28-DAY 0.98 ± 0.00* 0.08 ± 0.0* 0.18 ± 0.08* 0.06 ± 0.01
CONTROL 0.02 ± 0.00 0.16 ± 0.02 0.04 ± 0.00 0.06 ± 0.01
Fe 14-DAY 0.59 ± 0.07* 1.18 ± 0.13* 0.14 ± 0.01* 1.81 ± 0.27*
28-DAY 1.15 ± 0.00* 2.52 ± 0.22* 0.25 ± 0.02* 3.76 ± 0.33*
CONTROL 0.05 ± 0.01 0.02 ± 0.00 0.00 ± 0.00 0.02 ± 0.00
Ni 14-DAY 0.14 ± 0.01* 0.14 ± 0.01* 0.05 ± 0.02* 0.06 ± 0.01
28-DAY 0.24 ± 0.01* 0.18 ± 0.01* 0.15 ± 0.02* 0.40 ± 0.08*

Values are presented as mean ± SEM; *p < 0.05 are significant when compared with control.

1175
M.W. Owonikoko et al. Toxicology Reports 8 (2021) 1169–1178

control. There was a substantially significant difference between the in most intracellular activities such as oxidative phosphorylation,
treated and control groups. A more interesting difference is observable enzymatic activities, nucleic acid, and protein synthesis, membrane
between the 14-day and 28-day groups. Asides from Co and Mn, all other stabilization, and transport. However, regulation of their relative bio­
heavy metals assessed in this study follow a similar pattern of bio­ logical abundance and bioavailability is a requirement for the effective
accumulation in the two tissues. functioning of the cell. Asides from the sole toxicities of heavy metals,
their influx into the cell as typified by cement dust exposure is delete­
4. Discussion rious as they compete for transporters with essential trace elements
especially when they exceed the homeostatically tolerable limit [39,40];
This study presents a standardized form of the earlier presented and thereby leading to loss of function as a result of deficiencies of essential
deployed exposure model [24]. The morphology, operation, and modi­ minerals [41].
fication of the model were presented in Fig. 1A, B, and Table 2. It meets Clinical presentations are often indicators of systemic toxicity. The
the need to simplify, substantiate and normalize the suitability of the observed clinical signs following exposure in this study confirm the
model in the assessment of the systemic effect of inhalable/particulate systemic toxicity of cement dust. The animals exhibited vigour at the
matters. It was deployed in this study to assess the effect of cement dust initial stage of the study exploring every accessible point within the
on the respiratory tract; the foremost points of call for investigation in apparatus including the top of the subchamber. The fabricated chamber
aerosol-mediated toxicity. The primitive exposure chamber was fabri­ differs significantly in internal morphology and space from the plastic
cated and immediately deployed for use. Initially, it was not clear if the cages they were housed. This answers for the rambunctious behavior
chamber would fill the gap of the experimental toxicological evaluation initially exhibited by the animals. However, towards the end of the
model particularly with respect to occupational/residential scale of experiment, they appeared docile, hypoactive, and anorexic constantly
exposure or not. However, subsequent results emanating from the study maintaining a stationary position. This could be due to the stress accu­
featured a number of pathological manifestations that closely mimic mulation occasioned by the exposure to the dust or perhaps due to
those earlier reported in the literature on human subjects in many anorexia. The mortality of one animal which occurred while the expo­
conditions of case reports, questionnaires, interviews, etc. hence, the sure was ongoing may be due to multi-organ failure caused by the acute
need to standardize the exposure chamber became overtly expedient. effect of the heavy metal in the dust. The observed laboured breathing
The “modification” column of Table 2 outlines the advancement of the and frequent sneezing are suggestive of respiratory distress induced by
chamber with a view to standardizing it. For the present study, the dust cement dust.
generation rate was stabilized at 0.2 g/hr. The source of bodily functions, regulation, and integration is the
Cement particles have been reported to consist of toxic metals in central nervous system (CNS) being principally composed of the brain
varied proportions [28,29] depending particularly on the raw materials and the spinal cord. It gathers information from far and near extremities
used. Nigeria cement dust particles contain very high concentrations of for coordination and control. Maintenance of gait, posture, and coor­
heavy metals known to be lethal even at small doses such as Cd, Pb, and dination of movement right from thought to execution are all the
mercury (Hg) [30]. The significantly high levels of Pb, Cd, Cr, Co, Ni, functions of the CNS. Dyskinesia and other poor movement coordination
Mn, and Fe observed in the stomach, lungs, heart, and brain tissues of resembling hemiballism, abnormal posture, and hypoactivity as
the exposed animals confirm intoxication with heavy metallic compo­ observed in this study following the exposure to cement dust indicate a
nents of the dust. There is a considerable siamese relationship between central nervous disorder. The dermal route is one of the major routes of
the pattern of heavy metals deposition at the lungs and stomach tissues exposure to cement aerosol; others being inhalation and gastrointestinal
as shown by Table 5. Almost all the heavy metals show a similar trend of routes. Since cement dust is an airborne toxicant, the skin, by virtue of
bioaccumulation, particularly when the test groups are compared. This its large surface area remains the most affected. It quickly settles on the
similarity is probably borne out of the anatomical relationship between skin and exerts topical effects with toxicoses yet to be studied in detail.
the lungs and the gastrointestinal tract (GIT) as established by the In this study, exposure to cement dust may be responsible for the
mucociliary escalator. The GIT is susceptible to the toxicosis of any integumentary degradation as marked by increased fur lability. It was
toxicant found within the upper respiratory tract. Germs, particles, dust, evident that more than one animal showed signs of loss of fur at the
and other pollutants in the inspired air are trapped by mucus before the cephalic region at different times during the study.
mucociliary escalator moves them up and out of the lungs. These ma­ Abnormal body weight change is considered a veritable toxicity
terials can then be removed from the body via coughing or swallowing. index [42–44]. Similarly, organ weight is an indicator of the physio­
The latter makes the GIT become vulnerable to the debris moved out of logical or pathological condition of experimental animals [45,46]. There
the lungs. In the case of this study, the heavy metal-loaded dust removed was a significant reduction in weekly body weight gain which is in
from the lungs may have found its way to the GIT where they stimulate contrast with an increase in the relative visceral organs (stomach,
similar pathophysiological mechanisms. Similar evidence was recently spleen, lungs, and brain) weights of the exposed groups when compared
reported by [31] who found significantly high levels of heavy metal in with the control (Fig. 4A-F). Although daily food intake was not
visceral organs of rats co-exposed to cadmium and lead, and [32] who assessed, the exposed and the control were equally allowed free access to
similarly found significantly high levels of heavy metals in various tis­ food and water. The weight discrepancies observed in this study may
sues of snails picked around cement factory. Also, in plant physiology, either be due to anorexia or the direct systemic toxicity induced by the
similar evidence has been reported where heavy metallic constituents of dust. The foregoing is expected since visceral organs are directly
cement dust have been demonstrated to leach into the soil around exposed to the deleterious effect of toxicants [47]. Most organs have the
cement factory site causing a significantly higher proportion of toxic ability to sequester heavy metals following entry into the body [35].
metal within the factory neighborhood [2,33,34]. Recently, our labo­ This finding is in concert with several other findings [48–50]. Also, [51]
ratory reported an increase in plasma concentration of heavy metals in their study involving exposure of experimental animals to silica found
following exposure to cement particles [24]. The present study provides significantly higher lung weight of the exposed animals when compared
the first evidence using experimental animals that cement dust could with the control. The condition of organomegaly observed in this study
trigger heavy metal bioaccumulation in living tissues. After heavy metal is an indication that the exposed rats bioaccumulated the heavy metals.
intoxication; sequestration and bioaccumulation precede a number of The latter which is a condition typical of heavy metal toxicity remains an
pathological manifestations [35] as they are not easily metabolized or inevitable precursor to pathological manifestations especially during
excreted [36]. Apart from Cd, Pb, and Hg that are known to elicit sys­ carcinogenesis [52].
temic toxicities even at low concentrations [37,38], most divalent cat­ Bone density changes have been shown to inversely correlate with
ions have been implicated in effective cytophysiology as they participate heavy metal toxicity (Hee-Sook et al., 2016). Bone has been regarded as

1176
M.W. Owonikoko et al. Toxicology Reports 8 (2021) 1169–1178

one of the major target sites for heavy metal toxicosis [53–55]. Heavy enlargement is an early sign of emphysema.
metals such as Pb and (Cd) which accumulate in the bone matrix can
store up significantly and displaced calcium, leading to bone deminer­ 5. Conclusion
alization, and in the process makes the bone susceptible to osteoporosis.
Even though the comprehensive and holistic explanation is not yet This study provides a standardized laboratory-based experimental
available in the literature, exposure to a higher concentration of Cd model of exposure for investigation on cement dust toxicity. It generally
alone has been strongly linked to lower bone densities, decrease revealed heavy metal bioaccumulation and histoarchitectural alteration
trabecular number and decrease thickness [53,55,56]. Co-exposure to as organ damaging mechanisms with respect to the respiratory system.
Pd and Cd stimulates bone histopathological damage [57]. As the largest The exposure apparatus has been modified and standardized to mimic
bone in the body, the decrease in femoral density observed in this study the cement factory environment and host communities of cement fac­
suggests the possibility of chelation of essential minerals like calcium tories alike who are equally vulnerable to cement dust toxicities as
from the bone matrix causing mineral imbalance which may eventually occupationally exposed individuals. The results from this study add to
predispose the bone to osteoporosis. Low bone density observed in this the relatively few experimental-based data available on cement dust and
study does not only corroborate but is also suspected to be responsible therefore advance the existing claims of its toxicity. The pathogenesis of
for the low body weight gain observed in the exposed groups. cement dust-induced toxicities is not limited to bioaccumulation of the
Pulmonary tissue reaction to dust particles is known to be dependent heavy metal content of cement dust but also includes organomegaly and
on a number of factors such as the composition of the dust, the length of pneumopathological alterations. Further studies on the toxicosis of
exposure, and the immunological status of the exposed [58]. Of more cement dust are hereby encouraged in order to validate the epidemio­
significance is the composition of cement dust owing to its multi-heavy logical reports in the literature on cement dust-induced pathologies and
metallic composition. Pneumoconiosis was grossly observed in the lung to incite policies geared towards the protection of occupationally and
tissue of the exposed groups (Fig. 2D-F) when compared to the control geographically exposed individuals.
(Fig. 2C). The topical pulmonary effect of the dust culminates the
observed pneumoconiosis; the fibrogenic tendency of the dust is thereby Authors’ agreement
suspected. The onset of the pneumopathology may be the stimulus for
the respiratory distress observed in some of the exposed animals as they We the authors of this manuscript write to clearly state that there is
show irregular and laboured breathing. The clinical signs of toxicity no conflict of interest whatsoever in in the conception, design and
observed in this study show a wide range of semblance with the path­ writing of this work.
ological manifestations that accompany occupational exposure to
cement dust [12,16,59,60]. In addition, the serosal surface of the lungs Declaration of Competing Interest
shows signs of infarction (Fig. 2F). This is suggestive that exposure to
cement dust may significantly affect blood supply at the organ level. The authors report no declarations of interest.
Cytoarchitectural investigations play a significant role in establishing
pathological alterations at the tissue level following exposure to toxi­ References
cants. It gives reliable information about the extent of degradation in
exposed tissues difficult to be observed macroscopically, cellularly, or [1] N.O. Olatunbosun, B.A. Sawa, A. Jibrin, A.E. Ilori, Assessment of effect of cement
dust from cement factory on elemental properties of some cultivated crops,
even with the aid of subcellular biomarkers [61]. Pulmonary histo­ Obajana, Kogi State, Nigeria, J. Geogr. Environ. Earth Sci. Int. 24 (1) (2020) 63–69.
pathological disruptions after exposure to cement dust had been earlier [2] R.E. Lamare, O.P. Singh, Effect of cement dust on soil physico-chemical properties
reported by a study of in-situ exposure [10] where inflammation, dis­ around cement plants in Jaintia Hills, Meghalaya, Environ. Eng. Res. 25 (3) (2020)
409–417, https://doi.org/10.4491/eer.2019.099.
rupted bronchiole and bronchus, and degenerated the epithelial lining
[3] M.D. Adak, S. Adak, K.M. Purohit, Ambient air quality and health hazards near
were observed. Fig. 3A–F shows an array of histopathological alterations min-cement plants, Poll. Res. 26 (3) (2007) 361–364.
while Table 6 shows the frequency and severity of the observed alter­ [4] Mehraj, Bhat, Cement Factories, Air Pollution and Consequences [Online], pp.
12.03.2016.Available from:, 2013 http://www.sciencepub.net/book/00065_book
ations secondary to cement dust exposure. The black arrow in Fig. 3D
_1_65.pdf.
shows infiltration of inflammatory cells. Inflammatory cells play sig­ [5] S. Fairhurst, A. Phillips, Health & Safety Executive (Great Britain). Portland
nificant roles in the development and healing of either chemical or Cement Dust. Criteria for an Occupational Exposure Limit. Sudbury: HSE Books,
topical injuries. Analogous to any condition of heavy metal intoxication, 1994. ISBN 071760767631.
[6] R. Schemback, Burning Our Health: Hazardous Waste Incineration in Cement Kilns
infiltration of inflammatory cells is considered a reliable yardstick for in Mexico, Available at: http://tecascenter.orgpublications/kiln.htm (accessed 20
the assessment of the pathogenesis of heavy metal-induced toxicosis as April 2021), 1998.
they are known to produce and release pro-inflammatory cytokines, [7] S.K. Gupta, J. Singh, Evaluation of mollusc as sensitive indicator of heavy metal
pollution in aquatic system: a review, IIOAB J. 2 (1) (2011) 49–57.
proteolytic enzymes, reactive oxygen, and nitrogen species [62]. [8] S. Tak, G.A. Bhat, Assessment of epigeal invertebrate community in cement
Neutrophilic infiltration is known to precede the cascade of mechanisms polluted and non - polluted areas, J. Res. Dev. 9 (2009) 45–52.
that herald injuries on tissues. Hence, the histopathological changes [9] S.S. Mehraj, G.A. Bhat, H.B. Mehraj, T. Gul, Health risks for population living in the
neighborhood of a cement factory, Afr. J. Environ. Sci. Tech. 7 (12) (2013)
observed in this study which feature inflammatory cell and mononuclear 1044–1052.
cell infiltration are indicators of the pro-inflammatory tendency of the [10] Y. Tajudeen, J. Okpuzor, T.F. Adedayo, Investigation of general effects of cement
dust. Meanwhile, according to Balduzzi and colleagues, crystalline silica dust to clear the controversy surrounding its toxicity, Asian J. Sci. Res. 4 (2011)
315–325.
elicits inflammatory cell production which ultimately leads to free
[11] A. Fortune, Ethiopia: Cement Factory’s Reign of Pollution, Addis Fortune, Addis
radical generation [63]. The respiratory distress observed in the exposed Ababa, Ethiopia, 2011. http://allafrica.com/stories/201104121072.html.
animals may be due to the free radicals generated via the topical pul­ [12] J. Vestbo, F.V. Rasmussen, Long-term exposure to cement dust and later
hospitalization due to respiratory disease, Int. Arch. Occup. Environ. Health 62
monary effect of crystalline silica, a major compound constituent of
(1990) 217–220, https://doi.org/10.1007/BF00379436.
cement dust, or by the inflammatory cell infiltration observed in the [13] J. Mwaiselage, B. Moen, M. Bratveit, Acute respiratory health effects among
histoarchitectural alteration above. The “black arrow” in Fig. 4B depicts cement factory workersin Tanzania: an evaluation of a simple health surveillance
alveolar hyperplasia in the lung tissues. This condition is suggestive of tool, Int. Arch. Occup. Environ. Health 79 (2008) 49–56, https://doi.org/10.1007/
s00420-005-0019-x.
the proliferative reaction of pulmonary tissue to the dust; a notable [14] L. Coppeta, A. Pietroiusti, A. Magrini, G. Somma, A. Bergamaschi, Prevalence and
characteristic of the onset of carcinogenesis. Howbeit, [64] and [65] had characteristics of functional dyspepsia among workers exposed to cement dust,
established the positive correlations between cancer of the respiratory Scand. J. Work Environ. Health 34 (5) (2008) 396–402.
[15] S. Peters, Y. Thomassen, E. Fechter-Rink, H. Kromhout, Personal exposure to
system and the length of cement dust exposure period, the literature has inhalable cement dust among construction workers, J. Environ. Monit. 11 (1)
been devoid of laboratory-based support for the claim. Air space (2009) 174–180.

1177
M.W. Owonikoko et al. Toxicology Reports 8 (2021) 1169–1178

[16] Z. Zeleke, B. Moen, M. Bratveit, Cement dust exposure and acute lung function: a [42] S. Teo, D. Stirling, S. Thomas, A. Hoberman, A. Kiorpes, K. Vikram, A 90-days oral
cross shift study, BMC Pulm. Med. 10 (1) (2010) 19–26. gavage toxicity study of D-methylphenidate and D, L- methylphenidate in sprague-
[17] J.O. Ogunbileje, O.M. Akinosun, Biochemical and haematological profile in Nigeria dawley rats, Toxicology 179 (2002) 183–196.
cement factory workers, Res. J. Environ. Toxicol. (2011), https://doi.org/10.3923/ [43] C.D.S. Tomlin, The Pesticide Manual: a World Compendium, 14th ed., British Crop
rjet.2011. ISSN 1819-3420. Production Council, Alton, 2006, p. 2006.
[18] B. Isıklı, T.A. Demir, T. Akar, Cadmium exposure from the cement dust emissions: a [44] K. Toynton, B. Luukinen, K. Buhl, D. Stone, Permethirn Technical Fact Sheet,
field study in a rural residence, Chemosphere 63 (2006) (2006) 1546–1552. Available from:, National Pesticide Information Center, Oregon State University
[19] O. Oguntoke, A.E. Awanu, H.J. Annegarn, Impact of cement factory operations on Extension Services, 2009 http://npic.orst.edu/factsheets/Permtech.
air quality and human health in Ewekoro Local Government Area, South-Western [45] Y.K. Vaghasiya, V.J. Shukla, S.V. Chanda, Acute oral toxicity study of Pluchea
Nigeria, Int. J. Environ. Stud. 2012 (2012) 1–12, https://doi.org/10.1080/ arguta Boiss Extract in Mice, J. Pharmacol. Toxicol. 6 (2) (2011) 113–123, https://
00207233.2012.732751, iFirst Article. doi.org/10.3923/JPT.2011.113.123. ISSN 1816-496X.
[20] J. Vestbo, K.M. Knudsen, E. Raffn, B. Korsgaard, F.V. Rasmussen, Exposure to [46] K. Dwivedi, D.K. Gupta, Concomitant influence of heavy metal intoxication on size
cement dust at a portland cement factory and the risk of cancer, Br. J. Ind. Med. 48 of organs and body weight in albino rats, IJPSR 11 (3) (2020) 1417–1424.
(12) (1991) 803–807. [47] E. Dybing, J. Doe, J. Groten, J. Kleiner, J. O’Brien, A.G. Renwick, J. Schlatter,
[21] S.A. Meo, A.A. Muhammad, A.A. Qureshi, G.M. Ghori, A.M. Al-Drees, M.M. A. Tritscher, R. Walker, M. Younes, Hazard characterization of chemicals in food
F. Subhan, Dose response effect of cement dust on respiratory muscles competence and diet: dose response, mechanism and extrapolation issues, Food Chem. Toxicol.
in cement mill workers, Int. J. Environ. Health Res. 16 (6) (2006) 439–447. 42 (2002) 237–282.
[22] V. Karkhanis, J.M. Joshi, Cement dust exposure-related emphysema in a [48] H. Li, M. Han, L. Hou, G. Li, N. Sang, Landfill leachate inges-tions induced protein
construction worker, Lung Ind. 28 (2011) 294–296. oxidation and DNA–protein crosslinks in mouse viscera, J. Haz Mat. 2010 (174)
[23] T. Bamidele, B. Atolaye, Antioxidant status and hepatic lipid Peroxidation in Wistar (2010) 54–58.
rats exposed to cement dust, Transnat. J. Sci. Technol. 2 (4) (2011). May edition. [49] C.G. Alimba, A.A. Bakare, O.O. Aina, Liver and kidney dysfunction in wistar rats
[24] P.C. Nwafor, O.A. Odukanmi, A.T. Salami, M. Owonikoko, S.B. Olaleye, Evaluation exposed to municipal landfill leachate, Resour. Environ. 2 (4) (2012) 150–163,
of a Cement Dust Generation and Exposure Chamber for Rodents: Blood Heavy https://doi.org/10.5923/j.re.20120204.04.
Metal Status, Haematological Variables and Gastrointestinal Motility in Rats, Afr. [50] S.S.F. Kenston, H. Su, Z. Li, L. Kong, Y. Wang, X. Song, Y. Gu, T. Barber, J. Aldinger,
J. Biomed. Res. 22 (2019) (2019) 79–87. Q. Hua, Z. Li, M. Ding, J. Zhao, X. Lin, The systemic toxicity of heavy metal
[25] J. Ilar, Guide for the Care and Use of Laboratory Animals, 8th edition, 1996. mixtures in rats, Toxicol. Res. 7 (2018) 396–407.
[26] S. Akram, N. Rahila, H.R. Ghazala, S.A. Abbas, Determination of heavy metal [51] D.W. Porter, A.F. Hubbs, R. Mercer, V.A. Robinson, D. Ramsey, J. McLaurin,
contents by atomic absorption spectroscopy (AAS) in some medicinal plants from A. Khan, L. Battelli, K. Brumbaugh, A. Teass, V. Castranova, Progression of lung
Pakistani and Malaysian origin, Pak. J. Pharm. Sci. 28 (5) (2015) 1781–1787. inflammation and damage in rats after cessation of silica inhalation, Toxicol. Sci.
[27] M.M. Haber, I. Lopez, Gastric histologic findings in patients with nonsteroidal anti- 79 (2004) 370–380, https://doi.org/10.1093/toxsci/kfh110.
inflammatory drug-associated gastric ulcer, Mod. Pathol. 12 (1999) 592–598. [52] N.P. Okolie, A.U. Osagie, Liver and kidney lesions and associated enzyme changes
[28] A. Dietz, H. Ramroth, T. Urban, W. Ahrens, H. Becher, Exposure to cement dust, induced in rabbits by chronic cyanide exposure, Food Chem. Toxicol. 37 (7) (1999)
related occupational groups and laryngeal cancer risk: results of a population- 745–750.
based case-control study, Int. J. Cancer 108 (2004) 907–911. [53] R. Honda, I. Tsuritani, Y. Noborisaka, H. Suzuki, M. Ishizaki, Urinary cadmium
[29] J.S. Swaran, P. Vidhu, Chelation in metal intoxication, Int. J. Environ. Res. Public excretion is correlated with calcaneal bone mass in Japanese women living in an
Health 7 (7) (2010) 2745–2788. urban area, Environ. Res. 91 (2003) 63–70.
[30] J.O. Ogunbileje, V.M. Sadagoparamanujam, J.I. Anetor, E.O. Farombi, O. [54] K. Theppeang, T.A. Glass, K. Bandeen-Roche, A.C. Todd, C.A. Rohde, J.M. Links, B.
M. Akinosun, A.O. Okorodudu, Lead, mercury, cadmium, chromium, nickel, S. Schwartz, Associations of bone mineral density and lead levels in blood, tibia,
copper, zinc, calcium, iron, manganese and chromium (VI) levels in Nigeria and and Patella in urban-dwelling women, Environ. Health Perspect. 116 (2008)
United States of America cement dust, Chemosphere 90 (2013) (2013) 2743–2749. 784–790.
[31] M. Andjelkovic, A.B. Djordjevic, E. Antonijevic, B. Antonijevic, M. Stanic, J. Kotur- [55] X. Chen, G.Y. Zhu, C.L. Shao, T.Y. Jin, M.G. Tan, S.Z. Gu, Y.Y. Zhang, H.F. Xiao,
Stevuljevic, V. Spasojevic-Kalimanovska, M. Jovanovic, N. Boricic, D. Wallace, Effects of cadmium on bone microstructure and serum tartrate-resistant acid
Z. Bulat, Toxic effect of acute cadmium and lead exposure in rat blood, liver, and phosphatase 5b in male rats, Exp. Biol. Med. 9 (2011) 1–8.
kidney, Int. J. Environ. Res. Public Health 2019 (16) (2019) 274. [56] J.A. Staessen, H.A. Roels, D. Emelianov, T. Kuznetsova, L. Thijs, J. Vangronsveld,
[32] R.N. Ugbaja, M.A. Enilolobo, A.S. James, T.F. Akinhanmi, A.J. Akamo, D. R. Fagard, Environmental exposure to cadmium, forearm bone density, and risk of
O. Babayemi, O. Ademuyiwa, Bioaccumulation of heavy metals, lipid profiles, and fractures: prospective population study. Public Health and Environmental
antioxidant status of snails (Achatina achatina) around cement factory vicinities, Exposure to Cadmium (PheeCad) Study Group, Lancet 353 (1999) 1140–1144.
Toxicol. Ind. Health 36 (11) (2020) 863–875. [57] H. Lu, G. Yuan, Z. Yin, S. Dai, R. Jia, J. Xu, X. Song, L. Li, C. Lv, Effects of
[33] A.F. Abimbola, O.O. Kehinde-Phillips, A.S. Olatunji, The sagamu cement factory, S. subchronic exposure to lead acetate and cadmium chloride on rat’s bone: Ca and Pi
W. Nigeria: is the dust generated a potential health hazard? Environ. Geochem. contents, bone density, and histopathological evaluation, Int. J. Clin. Exp. Pathol. 7
Health 29 (2007) 163–167. (2) (2014) 640–647. /ISSN:1936-2625/IJCEP1311073, www.ijcep.com.
[34] R. Devarajan, K.R. Hanumappa, N. Kuppan, The Study of change in physico- [58] D.E. Gardner, H.A. Wallace, A. John, in: Donald E. Gardner (Ed.), Toxicology of the
chemical properties of soil due to cement dust pollution-an hazardous terrorization Lung, 4th ed, Taylor and Francis, 2006.
to ecosystem, Canadian J. Pure Appl. Sci. 9 (1) (2015) 3193–3200. ISSN: 1920- [59] A.S. Laney, E.L. Petsonk, M.D. Attfield, Pneumoconiosis among underground
3853; Print ISSN: 1715-9997 Available online at www.cjpas.net. bituminous coal miners in the United States: is silicosis becoming more frequent?
[35] B. Olivier, J. Gregory, T. Michel, C. Marc, Effect of heavy metals on, and handling Occup. Environ. Med. 67 (2010) 652–656.
by, the kidney, Nephron Physiol. 99 (2005) 105–110. [60] S. Aydin, S. Aydin, G. Croteau, I. Sahin, C. Citil, Ghrelin, nitrite and Paraoxonase/
[36] Z. Cooper, R. Bringolf, R. Cooper, K. Loftis, A.L. Bryan, J.A. Martin, Heavy metal Arylesterase concentrations in cement plant workers, J. Med. Biochem. 29 (2)
bioaccumulation in two passerines with differing migration strategies, Sci. Total (2010) 78–83.
Environ. 592 (2017) 25–32, https://doi.org/10.1016/j.scitotenv.2017.03.055. [61] L.L. Lanning, D.M. Creasy, R.E. Chapin, P.C. Mann, N.J. Barlow, K.S. Regan, D.
[37] J. Millichap, Lead neurotoxicity, Pediatr. Neurol. Briefs 9 (1995) 42. G. Goodman, Recommended approaches for the evaluation of testicular and
[38] B.O. Anyanwu, A.N. Ezejiofor, Z.N. Igweze, O.E. Orisakwe, Heavy metal mixture epididymal toxicity, Toxicol. Pathol. 2002 (30) (2002) 507–520.
exposure and effects in developing nations: an update, Toxics 2018 (6) (2018) 65, [62] T. Watanabe, K. Higuchi, K. Tominaga, Y. Fujiwara, T. Arakawa, Role of
https://doi.org/10.3390/toxics6040065. neutrophils in development, healing and recurrence of gastric ulcer in rats.
[39] A.D. Dayan, A.J. Paine, Mechanism of chromium toxicity, carcinogenicity Oxidative Stress and Digestive Diseases, Karger, Basel, 2001, pp. 41–50.
andallergencity: review of the literature from 1985 to 2000, Human Exp. Toxicol. [63] M. Balduzzi, M. Diociaiuti, B. De Berardis, S. Paradisi, L. Paoletti, In vitro effects on
20 (2001) 439–451. macrophages induced by noncytotoxic doses of silica particles possibly relevant to
[40] J. Liu, R.A. Goyer, M.P. Waalkes, Toxic effects of metals, in: C.D. Klaassen (Ed.), ambient exposure, Environ. Res. 96 (2004) 62–71.
Casarett and Doull’s Toxicology: The Basic Science of Poisons, seventh ed., The [64] H. Maier, U. Gewelke, A. Dietz, H. Thamm, W.D. Heller, H. Weidauer, Laryngeal
McGraw Inc., New York, 2008, pp. 931–979. cancer and occupation: results of the Heidelberg laryngeal cancer study, H N O. 40
[41] R. Singh, G. Neetu, M. Anurag, G. Rajiv, Heavy metals and living systems: an (1992) 44–51.
overview, Indian J. Pharmacol. 43 (3) (2011) 246–253. [65] H. Maier, M. Tisch, A. Dietz, C. Conradt, Construction workers as an extreme risk
group for head and neck cancer, HNO 47 (1999) 730–736.

1178

View publication stats