A Bibliometric and Hot Topics Analysis of Organophosphate
Non-Cholinergic Toxicity Based on Web of Science
Zhenmin Liu
1#
, Jiangtao Liu
1#
, Hexi Li
1
, Xu Zhang
2
, Bo Zhou
3
, Fei Liu
1
and Xiaoguang Zhao
1*
1
The Institute of NBC Defense PLA Army, Beijing 102205, China
2
Tianjin University Department of Management and economics, Tianjin, 300072, China
3
Chaoyang Hospital Affiliated to the Capital University of Medical Science, Beijing, 100020, China
#
Co-first authors
Zhenmin Liu and Jiangtao Liu contributed equally to this work
Keyword:
Organophosphorus Pesticides, Organophosphorus Flame Retardants, Non-Cholinergic Toxicity, Bibliometrics.
Abstract:
The toxicity of most organophosphorus compounds cannot be explained only by cholinergic toxicity
mechanism, indicating that non-cholinergic toxicity of organophosphorus compounds has a great impact on
their comprehensive toxicity. Bibliometric analysis related to non-cholinergic toxicity of organophosphorus
can provide data reference for researchers to understand key research directions and explore hot topics. This
paper selected the web of science core collection database to obtain and sort out the documents data related
to non-cholinergic toxicity of organophosphorus compounds in the recent 30 years. CiteSpace 5.8 R3 and
origin 2019b software were utilized to analyze the annual publication amount and annual citation amount,
countries, journals, authors and documents co-citation analysis and burst documents. It was found that the
annual publication amount in this field was increasing, and the annual citation amount was increasing
exponentially. The United States was the country with the largest number of documents published, and the
US military attached great importance to the research on the non-cholinergic treatment of organophosphorus
compounds poisoning. "PESTIC BIOCHEM PHYS" magazine ranked No. 1 in the number of documents
published. The most influential authors were ELLMAN GL and VAN DER VEEN I. The research mainly
covered the effects of organophosphorus pesticides and organophosphorus flame retardants on life. The effect
of organophosphorus flame retardants on gene expression and non-cholinergic prevention and treatment of
organophosphorus pesticide poisoning may be the future research hotspots.
1 INTRODUCTION
Organophosphorus compounds (OP) are ubiquitous
in the environment (WANG, 2020). In agriculture, it
has been used worldwide in insecticides, herbicides
and mosquito repellents (KAUSHAL J, 2021). In
industry, it is used as flame retardants and plasticizers
for various materials in daily life (FARKHONDEH
T, 2020). People are exposed to OP by a variety of
routes (CHEN, 2020), causing acute effects (such as
headache, dizziness, nausea, etc.) and chronic effects
(such as cancer, asthma, diabetes, etc.) (JI, 2021;
HUSSAIN T, 2021). The current studies on the
toxicity of organophosphorus compounds mainly
focus on the inhibition of acetylcholinesterase in the
nerve center, which cannot fully explain all the
adverse biological effects of OP. It is worth
researching the potential non-cholinergic toxicity of
organophosphorus compounds. With the deepening
and expansion of the research, it is difficult for
researchers to clarify the implied complex
relationship between the various research directions.
Bibliometrics is a way to analyze the research
dynamics and development trends in the field, which
can quickly explore the research directions and
hotspots (YAO, 2020). To fully understand the
research status of non-cholinergic toxicity of OP, this
paper used the bibliometric method to analyze the
documents related, to provide data reference for
researchers to understand this field.
26
Liu, Z., Liu, J., Li, H., Zhang, X., Zhou, B., Liu, F. and Zhao, X.
A Bibliometric and Hot Topics Analysis of Organophosphate Non-Cholinergic Toxicity Based on Web of Science.
DOI: 10.5220/0012001000003625
In Proceedings of the 1st International Conference on Food Science and Biotechnology (FSB 2022), pages 26-33
ISBN: 978-989-758-638-5
Copyright
c
2023 by SCITEPRESS Science and Technology Publications, Lda. Under CC license (CC BY-NC-ND 4.0)
2 MATERIALS & METHODS
2.1
Data Collection and Processing
Documents on non-cholinergic toxicity of OP
between 1990 and 2021 were collected from the Web
of Science Core Collection (WOSCC) Database,
which is regarded as the most frequently used and
most authoritative scientific database in many
research fields. Boolean operation terms included the
following: TS (Topic Search)=((organophosphate
OR organophosphorus) AND ((toxicity of non-
cholinergic) OR (toxicity of metabolic) OR (toxicity
of immune)OR (toxicity of neurodevelopment) OR
(toxicity of antioxidant system))) AND Language:
(English). A total of 575 published documents were
retrieved for initial screening, and saved as text files
in the format of "abstract, full record (including cited
references)", completed on December 11, 2021. To
prevent the deviation of results, we presented an
analysis of 491 articles only. All document types and
proportions are shown in Figure 1.
Figure 1: Document type and proportion.
2.2
Bibliometrics Analysis Methods
CiteSpace is one of the bibliometric analysis tools
used for knowledge mapping and bibliometric
research, developed by Dr. Chaomei Chen (CHEN,
2006). The nodes of the knowledge map represent
one item such as journals, authors and articles, and
the connecting lines of these nodes show their co-
citation or co-occurrence. A series of tree rings in
different colors are used to depict each node, where
gray indicates the oldest and red indicates the newest.
The warmer the color means the closer to the current
time. The same applies to the color representation of
the connecting lines. In this paper, CiteSpace 5.8 R3
software was utilized for all publication
characteristics, including journals, authors, literature
co-citation cluster analysis and burst literature
analysis. Origin 2019b software was utilized to
process data such as annual publication amount and
annual citation amount. The process of bibliometric
analysis is shown in Figure 2.
Figure 2: Flowchart of bibliometric analysis.
3 RESULTS
The annual publication amount, annual citation
amount (1990-2021) and its trend are shown in
Figure 3. In the past five years, more than 38% of the
total number of documents has been published, and
the largest number of documents (47 articles)
published in 2021. The annual citation amount
increased exponentially (R2=0.9687), indicating that
researchers have paid great attention to this field in
recent years.
Figure 3: The annual publication amount, annual citation
amount and its trend (1990-2021).
3.1
Contributed Countries and
Institutions
The document data in this field were further analyzed
using Citespace based on the contributed countries
and institutions. A total of 59 countries weere
involved in the non-cholinergic toxicity research of
organophosphate. The United States, China and India
have the largest number of published articles in this
A Bibliometric and Hot Topics Analysis of Organophosphate Non-Cholinergic Toxicity Based on Web of Science
27
field, with 141(28.7%), 77(15.7%) and 57(11.6%)
respectively. The top 10 countries with the largest
number of published articles are shown in Table S1.
A total of 713 scientific research institutions were
involved in this field. Duke University, the Chinese
Academy of Sciences, and UC Berkeley have the
largest number of published articles, with 14(2.95%),
12(2.44%) and 8(2.04%) respectively. There are six
scientific research institutions in America, two in
China, one in Turkey and one in Iran. The top 10
institutes with the largest number of published
articles are shown in Table S2.
The number of articles funded by the institute is
positively correlated with the degree of its attention.
The American Department of Health's Institute of
Human Services, the National Institutes of Health,
and the National Institutes of Health Sciences has the
largest number of funded articles, with 74(15.07%),
68(13.85%) and 55(11.20%). There are five funding
institutes in the United States, two in China, and one
in India, the European Union and Brazil. The top 10
institutes with the largest number of funded articles
are shown in Table S3.
3.2
The Amount of Articles Published
and Co-Citation In Journals
A total of 199 journals were involved in this field.
“Pesticide Biochemistry and Physiology” and
“Chemosphere” published the largest amount of
articles, with 26 (5.27%) and 20 (4.05%)
respectively. The top 10 journals with the largest
number of published articles are shown in Table S4.
The journal co-citation reflects the quality and the
influence of the journals. “Toxicology and Applied
Pharmacology”, “Toxicology” and “Pesticide
Biochemistry and Physiology” had the largest
number of co-citations, 240 times, 234 times and 195
times respectively. The top 10 journals with the
largest number of co-citations are shown in Table S5.
We imported all the document data into CiteSpace,
and selected the "Cited Journal" module to analyze
the journal co-citation. The results were obtained by
using the Minimum Spanning Tree (MST) algorithm
and described in a journal co-cited graph composed
of 595 nodes and 1762 lines, as shown in Figure 4.
3.3
The Amount of Articles Published
and Co-Citation of Authors
A total of 2196 authors involved in the field of
organophosphate non-cholinergic toxicity. Seidler FJ
and Slotkin TA have the largest number of published
articles, both of which are 10 (2.04%). The top 5
authors with the largest number of published articles
are shown in Table S6.
The author co-citation relationship reflects the
influence of the author in this field. Ellman GL,
Lowry OH and Costa LG were cited the most times,
109 times, 59 times and 42 times respectively. The
top 5 authors with the largest number of co-citations
are shown in Table S7.
Figure 4: The journal co-cited map.
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28
Figure 5: Author co-citation map (1990-2021).
Figure 6: Document co-citation cluster map.
We imported all the document data into
CiteSpace, and selected the "Cited Author" module
to analyze the author's co-citation. The author's co-
citation graph was generated and composed of 887
nodes and 1133 links, as shown in Figure 5.
3.4
Literature Co-Citation Clustering
We imported the data of 491 documents and their
19605 references into CiteSpace to perform
document co-citation cluster analysis by using the
Log-Likelihood Ratio (LLR) algorithm. The time
span is set to 1990-2021, and the time slice option is
set to 1 year. The document co-citation graph was
generated and composed of 469 nodes, 1657 lines and
8 clusters, as shown in Figure 6.
The average publication year of clustering
reflects the dynamic state and current development
trend of research in this field. The earliest three
clusters of average publication year were #5
protective effect (2005), #5 high-fat diet (2006) and
#3 Norway mice (2008). Clusters over the past
decade were #1 organophosphate flame retardants
(2011), #4 agricultural pesticide use (2011), #6 non-
target metabonomics (2014) and #7 intestinal
microbiomics (2014). The average publication year
of cluster #0 organophosphate ester flame retardants
is closest to the current time. The cluster results of
literature co-citation are shown in Table 1.
A Bibliometric and Hot Topics Analysis of Organophosphate Non-Cholinergic Toxicity Based on Web of Science
29
Table 1: The cluster results of literature co-citation.
Cluster Size Silhouette Means (Year) Top Terms (LLR)
0 54 0.906 2016 Organophosphate ester flame retardant
1 49 0.898 2011 Organophosphate flame retardant
2 46 0.949 2005 Protective effect
3 35 1 2008 Norway rat
4 29 0.908 2011 Agricultural pesticide use
5 26 0.976 2006 High-fat diet
6 26 0.933 2014 Untargeted metabolomics
7 20 0.995 2014 Gut microbiome
Note: The closer the contour coefficient value is to 1, the higher the credibility of clustering.
Table 2: Documents with co-citation burst characteristics in the past 5 years.
Ran
k
Be
g
in En
d
Stren
g
th References
1 2016 2021 6.31 Van der Veen I, 2012, CHEMOSPHERE, V88, P1119
2 2018 2021 4.12 Liu X, 2012, AQUAT TOXICOL, V114, P173
3 2016 2019 5.37 Colovic MB, 2013, CURR NEUROPHARMACOL, V11, P315
4 2017 2019 4.38 Grube A, 2011, PESTICIDES IND SALES, V0, P0
5 2018 2019 3.6 Su GY, 2014, ENVIRON SCI TECHNOL, V48, P13511
6 2018 2019 3.6 Du ZK, 2016, SCI REP-UK, V6, P0
7 2015 2018 4.2 Dishaw LV, 2011, TOXICOL APPL PHARM, V256, P281
3.5 Burst Literature
Based on the cluster results of literature co-citation,
29 burst documents were obtained by using the burst
document detection tool “burstness”. There were a
total of 7 documents with burst characteristics in the
past 5 years. Two articles still had strong co-citation
burst until 2021. Among them, the article published
by Van der Veen I in “Chemosphere” in 2012 had the
strongest co-citation burst. Documents with co-
citation burst characteristics in the past 5 years are
shown in Table 2.
4 DISCUSSION
The research in the field of non-cholinergic toxicity
of organophosphorus compounds can be divided into
two stages (1990-2009, 2010-2021). The first phase
was the primary stage, the annual publication amount
is less than 20. There was no significant increase and
the growth rate of the document citation amount was
also low. The second stage was the rapid
development stage. The number of articles published
has increased sharply, and the annual number of
articles published is more than 30 in the recent 5
years. The growth rate of document citation amount
has accelerated significantly. The annual publications
amount was increasing steadily, and the annual
citation amount was increasing exponentially. It
showed that this field has received extensive attention
from researchers. The United States is ranked No. 1
in the number of publications, and had more than
50% of the top 10 institutes with the largest published
articles.
A total of 7 journals were ranked in the top 10 of
published article amount and co-citation amount at
the same time, including “Pesticide Biochemistry and
Physiology”, “Chemosphere”, “Toxicology and
Applied Pharmacology”, “Toxicology”, “Toxicology
Letters”, “Ecotoxicology and Environmental Safety”
and “Toxicological Sciences”. These journals have
great influence in this field.
Two authors were ranked in the top 10 of
publication amount and co-citation amount at the
same time, including Slotkin TA and Abdollahi M,
indicating that they have contributed a lot. In the
initial stage and rapid development stage in this field,
the influential authors were Ellman GL and Van der
FSB 2022 - The International Conference on Food Science and Biotechnology
30
Veen I respectively. Ellman GL mainly studied the
toxicity of organophosphorus pesticides, while Van
der Veen I mainly studied the toxicity of
organophosphorus flame retardants.
Eight literature clusters were obtained by the LLR
algorithm. According to different research objects, all
clusters can be divided into two main research
directions. One is the study on the non-cholinergic
toxicity of organophosphorus pesticides, which
includes six clusters (ID: #2, #3, #4, #5, #6, #7). The
second is the study on the non-cholinergic toxicity of
organophosphorus flame retardants, including two
clusters (ID: #0, #1).
4.1 The Non-Cholinergic Toxicity of
Organophosphorus Pesticides
Includes Neurodevelopmental
Toxicity, Lipid Metabolic Toxicity
and Antioxidant Toxicity.
4.1.1 Neurodevelopmental Toxicity
Continuous exposure to low concentrations of
organophosphorus pesticides can lead to autism in
pregnant women (FURLONG M A, 2017); fetal
neurodevelopmental disorders (GUNIER R B, 2017),
birth defects and death in fetuses (ROBERTS J R,
2010); and abnormal peripheral axon diffraction
during fetal development (JACOBSON S M, 2010).
Organophosphorus pesticides affect axonal transport
by regulating intestinal bacterial population
composition and functional gene expression (GAO,
BIAN, MAHBUB R, 2017; Gao, NAUGHTON S X,
BECK W D, 2017), and hinder neuronal development
and mature neuronal function (GAO, BIAN, CHI,
2017).
4.1.2 Lipid Metabolic Toxicity
Organophosphorus pesticides aggravate oxidative
stress by inhibiting the activity of antioxidant
enzymes in the body, leading to lipid peroxidation
(ULLAH S, 2018). Thereby sperm function was
affected (LEONG C T, 2013), and cancer and
neurodegenerative diseases were caused (LÓPEZ O,
2007). Also, OP can destroy cell signal transduction
mediated by cyclic adenosine monophosphate,
resulting in impaired metabolic function, increased
glucose metabolism and imbalance in lipid
metabolism, thereby causing metabolic symptoms
similar to early diabetes (ADIGUN A A, WRENCH
N, LEVIN E D, 2010; ADIGUN A A, WRENCH N,
SEIDLER F J, 2010).
4.1.3 Antioxidant Toxicity
Organophosphorus pesticides reduce the
concentration of paraoxonase (PON1), glutathione
peroxidase (GSH-Px) and catalase (CAT) by
affecting the expression of key genes in the
hepatocyte antioxidant system (HASSANI S, 2021).
It can also significantly reduce the plasma antioxidant
capacity while reaching the peak plasma level, which
has potential acute toxic effects (BIRDANE Y O,
2021).
4.2 The Non-Cholinergic Toxicity of
Organophosphorus Flame
Retardants Includes Mouse Fetal
Development Toxicity, Liver
Toxicity and Dopaminergic
Nervous System Toxicity.
4.2.1 Mouse Fetal Developmental Toxicity
Organophosphorus flame retardants disrupt the
placental nerve signal transduction by affecting the
expression of endocrine and inflammation-related
genes in the placenta, which causes placental
dysfunction and fetal forebrain dysplasia (ROCK K
D, 2021). These compounds can also cause an
excessive stress response in the endoplasmic
reticulum, endochondral ossification and
chondrodysplasia in limb buds (YAN H, 2021).
4.2.2 Liver Toxicity
Organophosphorus flame retardants cause
mitochondrial dysfunction and lipid accumulation by
affecting gene expression in human hepatocytes,
which is the reason for non-alcoholic fatty liver and
other diseases (NEGI C K, 2021). This kind of
compound also can induce metabolic reprogramming
of mesenchymal stem cells, reduce bone mineral
density and cause obesity (MACARI S, 2020).
4.2.3 Dopaminergic Nervous System Toxicity
Organophosphorus flame retardants can change the
transcriptional profiles of adenylate cyclase signal
transduction components by affecting the signal
cascade of adenylate cyclase and its connection with
G-protein coupled receptor, which destroy the
dopaminergic system (OLIVERI A N, 2018). Those
compounds can also accumulate in the body and
cause the level of dopamine and serotonin in the brain
to decrease, and affect the function of the dopamine
nervous system (WANG, 2015).
A Bibliometric and Hot Topics Analysis of Organophosphate Non-Cholinergic Toxicity Based on Web of Science
31
Burst literature that has a sharp increase in
citations in a certain period, is widely concerned by
researchers (CHEN, 2021). There are seven
documents with burst characteristics in the past five
years. According to the research content, they can be
divided into two main research directions, which may
become research hotspots in the future. One is the
study on the gene expression effect of
organophosphorus flame retardants.
Organophosphorus flame retardants affect the
function of related pathways such as
glycosphingolipid biosynthesis and fatty acid
elongation by affecting DNA replication, base
excision repair and other ways of destroying gene
expression (
GRUBE A, 2021)
, which interfere with
carbohydrate and lipid metabolism (DU, 2016) and
cause neurodevelopmental toxicity (DISHAW L V,
2011). Those compounds can also lead to endocrine
disorders by changing the transcription of genes
related to the synthesis of sex hormones and steroids
(Liu, 2012). Metabolites of organophosphorus flame
retardants accumulate in the liver, which causes
cancer (VAN DER VEEN I, 2012) and more genetic
changes in the embryo. The toxicity of metabolites is
greater (SU, 2014).
The second is to study the non-cholinergic
prevention and treatment of organophosphorus
pesticide poisoning. By injecting phosphatase or
carboxylesterase, the pesticide can be hydrolyzed or
oxidized before it reaches the target, so as to achieve
the purpose of detoxification. (COLOVIC M B,
2013)
5 CONCLUSIONS
The toxicity of most organophosphorus compounds
is unexplained only by the cholinergic toxicity
mechanism. And the research on the non-cholinergic
toxicity mechanisms has attracted great attention. In
this paper, bibliometric analysis was carried out to
clearly understand the research progress of non-
cholinergic toxicity of organophosphorus
compounds, which has been proved that
bibliometrics can provide valuable information for
researchers. The United States is the most influential
country in this field, and the U.S. military attaches
great importance to the research on the non-
cholinergic treatment of organophosphate poisoning.
The research mainly covers the effects of
organophosphorus pesticides and organophosphorus
flame retardants on organisms. The future research
focus may be the effect of organophosphorus flame
retardants on gene expression and the non-
cholinergic prevention and treatment of
organophosphorus pesticide poisoning.
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