<figure><img src="image_1.png" /></figure>

HAL
open science

# Lead abundances in bony fish from the world oceans: significance for contaminated marine habitats and environmental policies

A. Véron, Isabelle Bernier, Bruno Hamelin

► To cite this version:

A. Véron, Isabelle Bernier, Bruno Hamelin. Lead abundances in bony fish from the world oceans: significance for contaminated marine habitats and environmental policies. Comptes Rendus. Géoscience, 2021, 353 (1), pp.37-54. 10.5802/crgeos.49. hal-03199907

HAL Id: hal-03199907

https://hal.science/hal-03199907

Submitted on 16 Apr 2021

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_2.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
# Comptes Rendus
## Géoscience
### Sciences de la Planète

Alain Véron, Isabelle Bernier and Bruno Hamelin

Lead abundances in bony fish from the world oceans: significance for contaminated marine habitats and environmental policies

Volume 353, issue 1 (2021), p. 37-54.

<https://doi.org/10.5802/crgeos.49>

© Académie des sciences, Paris and the authors, 2021.

Some rights reserved.

<figure><img src="image_3.png" /></figure>

This article is licensed under the

CREATIVE COMMONS ATTRIBUTION 4.0 INTERNATIONAL LICENSE.

http://creativecommons.org/licenses/by/4.0/
Grandjean, 2010, Lanphear et al., 2005, Needleman, 2004, Tong et al., 1998). Likewise, pollutant Pb has pervaded all of the marine ecosystems [Boening, 1999, Dell'Anno et al., 2003, Durrieu de Madron et al., 2011, Halpern et al., 2008] and is widely distributed in fish tissues [Alves et al., 2006, Nussey et al., 2000, Rogers et al., 2003, Zhong et al., 2017]. Its toxicity is discernible in osteichthyes [Authman et al., 2015, Birge et al., 1981, Burger and Gochfeld, 2005, Danovaro, 2003, Demayo et al., 1982, Heath, 1987, Hodson et al., 1984, Jakimska et al., 2011a, Lee et al., 2019, Mallatt, 1985, Mason, 2013], also referred to as bony fish (about 95% of all fish population). Muscle and liver tissues are commonly used to characterize fish Pb accumulation [MacDonald et al., 2002, Ploetz et al., 2007, Velusamy et al., 2014] and risks of fish consumption for the human health [Castro-Gonzalez and Méndez-Armenta, 2008, Domingo et al., 2007, Falco et al., 2006, Han et al., 1998, Llobet et al., 2003, Viera et al., 2011]. Meanwhile, the metabolism and toxicokinetics of Pb in fish are affected by environmental (metal bioavailability, seawater physico-chemistry, regional productivity, anthropogenic stress) and biological (age, sex, size, trophic level, nutrition) factors [Burger et al., 2014, Erasmus, 2004, Jakimska et al., 2011a,b, Kojadinovic et al., 2007, Mathews and Fisher, 2009, Pourang, 1995]. Celik et al. [2004] investigated fish Pb content from the eastern Mediterranean (Turkish coast) and northeastern Atlantic fishing grounds (Faroe and Shetland Islands region) using 328 and 72 specimens for the Mediterranean and Atlantic cohorts, respectively (from 49 and 19 species in the Mediterranean and Atlantic). In spite of the limited number of specimens and the mixed species involved, they evidenced a 12 time increase in mean Cd and Pb contents from fish muscles collected in the eastern Mediterranean. In order to further investigate regional disparities in Pb content from bony fish tissues, and the effect of environmental policies on the health of the marine ecosystems, it is necessary to have access to multiple records with time from various marine locations, both at global and regional scales. As of 1974, there were merely 30 papers dealing with Pb burden and toxicity in all marine fauna [Corrill and Huff, 1976]. Growing evidences of Pb toxicity have prompted distinct reports on its accumulation in bony fish (see reference in Table S1) of which the few available recent reviews are either ge-

ographically circumscribed and/or limited to a single genus/species or to concentration exceeding the maximum allowable limits for consumption [Agusa et al., 2007, Ahmed et al., 2018, Bosch, 2015, Castro-Gonzalez and Méndez-Armenta, 2008, Cunningham et al., 2019, Hussain et al., 2014, Renieri et al., 2014]. One of the most comprehensive approach from the National contaminant biomonitoring program was conducted between 1965 and 1987 in the US on whole freshwater fish mostly [Schmitt and Brumbaugh, 1990]. Hitherto, there is no specific review of accumulated Pb in bony fish muscle and liver tissues that would include all of the main geographical marine areas and various species.

Our objective is to compile the most updated chronicle of Pb concentration from both muscle and liver in bony fish that could be used as pollution bioindicators in various areas and provide insights on intra- and interspecies Pb concentration differences. We expound the use of this cluster with case studies that include Pb accumulation levels and disparities in bony fish from various oceanic regions, its distribution between muscle and liver tissues, and the time transient shift of fish Pb burden in a Mediterranean coastal polluted hot spot.

## 2. Methodological approach

### 2.1. *The fish record*

Our literature review includes Pb analyses in bony fish muscle and liver tissues (Supplementary Table S1) from 203 publications that were searched using recent peer-reviewed publication from the Web of Science and references therein. In most cases, only papers published in English are considered, and listed in Table S1. Marine records are selected from the world oceans and some enclosed seas with the exception of closed bay or estuaries, coastal wetlands, mangroves, and ports to avoid the immediate proximity of polluted ecosystems that would significantly bias calculated means and medians within each marine area. Research studies are localized using the Food and Agricultural Organization of the United Nations (FAO-UN) major fishing areas, sub-areas, and divisions for the world oceans [FAO-UN, 2021], and the General Fisheries Commission [FAO GFCM, 2009] for the Mediterranean and the Black Sea. We provide further geographic references such
<table><caption>**Table 1a.** Descriptive statistics (Mean, Standard Deviation SD, Median, InterQuartile Range IQR, Skewness SKW) of Pb levels in bony fish muscles from various oceanic and Mediterranean basins</caption><thead><tr><th></th><th>ALL</th><th>ATL</th><th>PAC</th><th>IND</th><th>MED</th><th>MED<sub>1</sub></th><th>MED<sub>2</sub></th><th>MED<sub>3</sub></th><th>MED<sub>4</sub></th><th>MED<sub>5</sub></th><th>IND<sub>1</sub></th></tr></thead><tbody><tr><th><i>n</i></th><td>22190</td><td>4021</td><td>2894</td><td>3934</td><td>11341</td><td>3645</td><td>2410</td><td>3114</td><td>738</td><td>1434</td><td>1220</td></tr><tr><th>Mean<br>(SD)</th><td>0.26<br>(0.76)</td><td>0.06<br>(0.12)</td><td>0.14<br>(0.13)</td><td>0.21<br>(0.37)</td><td>0.39<br>(1.02)</td><td>0.09<br>(0.17)</td><td>0.20<br>(0.22)</td><td>0.23<br>(0.68)</td><td>0.82<br>(1.30)</td><td>1.40<br>(1.99)</td><td>0.41<br>(0.51)</td></tr><tr><th>Median</th><td>0.08</td><td>0.01</td><td>0.14</td><td>0.08</td><td>0.12</td><td>0.04</td><td>0.12</td><td>0.14</td><td>0.19</td><td>0.67</td><td>0.21</td></tr><tr><th>IQR</th><td>0.15</td><td>0.03</td><td>0.12</td><td>0.16</td><td>0.22</td><td>0.05</td><td>0.14</td><td>0.20</td><td>0.14</td><td>1.10</td><td>0.42</td></tr><tr><th>SKW</th><td>7.4</td><td>3.6</td><td>2.1</td><td>3.5</td><td>5.6</td><td>5.1</td><td>2.0</td><td>9.0</td><td>2.5</td><td>2.7</td><td>2.6</td></tr></tbody></table>

<table><caption>**Table 1b.** Descriptive statistics (Mean, Standard Deviation SD, Median, InterQuartile Range IQR, Skewness SKW) of Pb levels in bony fish livers from various oceanic and Mediterranean basins</caption><thead><tr><th></th><th>ALL</th><th>ATL</th><th>PAC</th><th>IND</th><th>MED</th><th>MED<sub>1</sub></th><th>MED<sub>2</sub></th><th>MED<sub>3</sub></th><th>MED<sub>4</sub></th><th>MED<sub>5</sub></th><th>IND<sub>1</sub></th></tr></thead><tbody><tr><th><i>n</i></th><td>5954</td><td>1143</td><td>689</td><td>2136</td><td>1986</td><td>204</td><td>207</td><td>257</td><td>260</td><td>1058</td><td>629</td></tr><tr><th>Mean<br>(SD)</th><td>1.21<br>(3.21)</td><td>0.10<br>(0.12)</td><td>0.27<br>(0.36)</td><td>0.51<br>(0.61)</td><td>2.90<br>(5.08)</td><td>0.15<br>(0.08)</td><td>1.84<br>(1.59)</td><td>0.45<br>(0.85)</td><td>0.49<br>(0.67)</td><td>4.83<br>(6.28)</td><td>0.75<br>(0.89)</td></tr><tr><th>Median</th><td>0.31</td><td>0.06</td><td>0.09</td><td>0.43</td><td>0.76</td><td>0.09</td><td>1.33</td><td>0.03</td><td>0.09</td><td>2.36</td><td>0.51</td></tr><tr><th>IQR</th><td>0.63</td><td>0.07</td><td>0.29</td><td>0.40</td><td>3.02</td><td>0.12</td><td>1.57</td><td>0.65</td><td>0.89</td><td>5.62</td><td>0.52</td></tr><tr><th>SKW</th><td>4.9</td><td>2.8</td><td>2.7</td><td>6.4</td><td>2.64</td><td>0.6</td><td>1.6</td><td>3.2</td><td>1.2</td><td>1.7</td><td>5.6</td></tr></tbody></table>

<table><caption>**Table 2.** Descriptive statistics (Median, InterQuartile Range IQR) of Pb levels in *n* paired bony fish muscle (MD<sub>M</sub>)–liver (MD<sub>L</sub>) from various oceanic and Mediterranean basins</caption><thead><tr><th></th><th>ATL</th><th>PAC</th><th>IND</th><th>MED</th><th>MED<sub>1</sub></th><th>MED<sub>2</sub></th><th>MED<sub>3</sub></th><th>MED<sub>4</sub></th><th>MED<sub>5</sub></th><th>IND<sub>1</sub></th></tr></thead><tbody><tr><th><i>n</i></th><td>735</td><td>632</td><td>2075</td><td>1952</td><td>182</td><td>197</td><td>248</td><td>267</td><td>1058</td><td>576</td></tr><tr><th>MD<sub>M</sub></th><td>0.01</td><td>0.06</td><td>0.08</td><td>0.27</td><td>0.05</td><td>0.51</td><td>0.01</td><td>0.02</td><td>0.86</td><td>0.15</td></tr><tr><th>IQR<sub>M</sub></th><td>0.01</td><td>0.22</td><td>0.11</td><td>1.10</td><td>0.09</td><td>0.5</td><td>0.18</td><td>0.33</td><td>1.19</td><td>0.11</td></tr><tr><th>MD<sub>L</sub></th><td>0.05</td><td>0.09</td><td>0.43</td><td>0.86</td><td>0.09</td><td>1.18</td><td>0.02</td><td>0.14</td><td>2.36</td><td>0.51</td></tr><tr><th>IQR<sub>L</sub></th><td>0.27</td><td>0.39</td><td>3.02</td><td>0.12</td><td>1.24</td><td>0.64</td><td>1.33</td><td>5.63</td><td>0.52</td><td>0.27</td></tr></tbody></table>

as regional seas, islands and/or countries when available. Means, sum of analyses and dates of sampling are reported for each fish cohort. The number of analyses is taken into account to ascertain statistical description of oceanic means and allow rational correlation thereof (as seen in Tables 1a, 1b, 2 and 3). In few occurrences when the cohort number is missing and cannot be reasonably estimated, it is assumed “1” by default. We do not take into account studies showing poor accuracy (based on international standards), concentration ranges or graphs only, absence of species names and whole-body analyses.

Data are also disregarded when fish sampling regions cannot be assessed on the basis of FAO-UN fishing areas. Individual or composite sample analyses are accepted from a single species. Because most of the fish concentration and associated international Maximum Permissible Limits (MPLs) for fish consumption) are reported in ppm fresh weight, we are compelled to convert dry mass concentrations for statistical analyses based on: $C_w = C_d \cdot [(100 - H)/100]$, where $C_d$ and $C_w$ are dry and wet mass concentration (ppm), and $H$ the percentage of humidity (%) in fish organs. The conversion factor (CF) is hence de-
<table><caption>**Table 3.** Liver and muscle medians (ppm) in pre- (PRE) and post- (POST) 2000 periods along with the number of analyses ($n_{pre}$, $n_{post}$)</caption><thead><tr><th></th><th>ALL<sub>M</sub></th><th>ATL<sub>M</sub></th><th>PAC<sub>M</sub></th><th>IND<sub>M</sub></th><th>MED<sub>M</sub></th><th>ALL<sub>L</sub></th><th>ATL<sub>L</sub></th><th>PAC<sub>L</sub></th><th>IND<sub>L</sub></th><th>MED<sub>L</sub></th></tr></thead><tbody><tr><td>n<sub>pre</sub></td><td>6886</td><td>1973</td><td>1935</td><td>1391</td><td>1587</td><td>1916</td><td>728</td><td>419</td><td>429</td><td>340</td></tr><tr><td>PRE</td><td>0.099</td><td>0.014</td><td>0.145</td><td>0.032</td><td>0.169</td><td>0.106</td><td>0.049</td><td>0.144</td><td>0.106</td><td>3.288</td></tr><tr><td>IQR</td><td>0.15</td><td>0.02</td><td>0.04</td><td>0.10</td><td>0.89</td><td>0.65</td><td>0.05</td><td>0.66</td><td>0.15</td><td>3.64</td></tr><tr><td>n<sub>post</sub></td><td>15304</td><td>2048</td><td>959</td><td>2543</td><td>9754</td><td>4038</td><td>415</td><td>270</td><td>1707</td><td>1646</td></tr><tr><td>POST</td><td>0.076</td><td>0.011</td><td>0.076</td><td>0.086</td><td>0.100</td><td>0.405</td><td>0.072</td><td>0.046</td><td>0.432</td><td>0.420</td></tr><tr><td>IQR</td><td>0.17</td><td>0.05</td><td>0.25</td><td>0.17</td><td>0.19</td><td>0.63</td><td>0.09</td><td>0.14</td><td>0.21</td><td>1.82</td></tr><tr><td>MW (p)</td><td>0.88</td><td>0.66</td><td>&lt;0.001</td><td>&lt;0.001</td><td>&lt;0.001</td><td>&lt;0.001</td><td>&lt;0.05</td><td>&lt;0.001</td><td>&lt;0.001</td><td>&lt;0.001</td></tr></tbody></table>

Mann-Whitney test ($MW_p$) are used to compare medians between the two periods.

fined as the ratio $C_d/C_w$. The CF is variable according to tissues and species [Harmelin-Vivien et al., 2009, Kojadinovic et al., 2007, Magalhaes et al., 2007, Mur-ray and Burt, 1969]. We have considered 1390 (muscle) and 87 (liver) CF measurements to infer mean CFs of 4.43 ± 0.24 and 2.64 ± 0.61 for fish muscle and liver, respectively [Bustamante et al., 2003, Cresson et al., 2017, Ergul and Aksan, 2013, Escobar-Sanchez et al., 2015, Hellou et al., 1992, Magalhaes et al., 2007, Oehlenschlager, 2009, Ong and Gan, 2017, Panichev and Panicheva, 2015, Siebenaller et al., 1982, Sell-ami et al., 2018, Tufan et al., 2013]. Our record comprises the Atlantic (ATL), Pacific (PAC), Indian (IND) oceans, and the Mediterranean Sea (MED) which are further divided when sufficient data are available. Hence, the MED area is divided into Western-Central ($MED_1$), Eastern ($MED_2$), Black Sea ($MED_3$), Marmara Sea ($MED_4$) and Iskenderun-Karatas Bay ($MED_5$). The eastern region ($MED_2$) data does not include $MED_{3,4,5}$ areas. The Indian Ocean (IND) also includes a subarea ($IND_1$) that corresponds to the Persian Gulf. These subregions were assigned on the basis of the available data owing to sufficient independent published studies. This data set will be available online as an open access database for each of the main world oceans, including the Mediterranean Sea and its surroundings along with new relevant biological information such as fish age, and trophic levels when available. Open share groups will be granted for identified users to allow inclusion of missing relevant publication and associated data. As of now, we provide excel sheets (Supplementary Table S1) that contain all of the pertinent data to investigate Pb burden on the basis of species, marine areas, and time trends.

## 2.2. Statistical approach

Statistical analyses are carried out using Past 4 statistical package software [Hammer et al., 2001]. We perform descriptive statistics (arithmetic mean, standard deviation, median, interquartile range, skewness, normality tests) and comparisons of bony fish Pb burden between oceanic regions. In order to assess the proper weight to each reported mean shown in Supplementary Table S1, we expand the data set to the total number of analyses for our statistical approach (i.e., 22,190 and 5954 Pb concentrations for muscle and liver, respectively for the complete record). The comparison of Pb levels between both tissues is carried out using paired analyses within the same cohorts and locations in order to avoid bias resulting from noncoupled Pb record. The choice of parametric and nonparametric tests is based on normality test (from Skewness index and Shapiro-Wilkinson test). Normality and comparison tests use the null hypothesis ($H_0$) with a given probability ($p$). Failing to reject the null hypothesis is dictated here by $p > 0.05$ (5% chance to detect a false positive). If $p < 0.05$, then we choose the alternative hypothesis, that is, mean/median differences, non-normal distribution or observed correlations are statistically significant. Statistics are applied to fish Pb concentration from the main and semienclosed marine regions (see all Tables and Figure 1a, b). None of the selected fish cohorts are normally distributed as shown by Skewness indices generally above 2 and Shapiro-Wilkinson test probability below 0.001. Therefore, medians rather than means are favored and concentration comparisons are performed using non-
<figure><img src="image_4.png" /><figcaption>**Figure 1.** (a) Median Pb levels in bony fish from the main marine basins with Maximum Permissible Limits (MPLs). (b) Median Pb levels in bony fish from the Mediterranean basins with Maximum Permissible Limits (MPLs).</figcaption></figure>

parametric Mann-Whitney test (MW). Data disper-
sion is assessed from interquartile range (IQR, dif-
ference between 75% and 25% percentiles) rather
than standard deviation owing to data skewed distri-
bution. Data variability is not easily appraised from
boxplot log scales (Figure 1a, b), and is more read-
ily assessed from IQR (see all Tables). Moreover, out-
liers have a lesser influence on both medians and

interquartile ranges than on arithmetic means and
associated variances.

3. Results and discussion

3.1. *Geographic distribution*

We use our database in order to explore the mag-
nitude of fish contamination in various oceanic
regions, and to what extent fish's geographic habitats
may explain Pb accumulation in tissues. Because
most fish are trawled in coastal regions, we expect
our geographic approach to reflect coastal rather
than open-sea contamination. Pollutant Pb invasion
of coastal marine ecosystems from atmospheric de-
position and local industrial (and urban) discharges
led to the establishment of MPLs for fish consump-
tion. Nowadays, MPLs (in ppm fresh weight) of Pb in
edible fish parts vary from 0.3 ppm in the European
Union and the FAO/WHO [CAC (Codex Alimentarius
Commission), 2011, EU, 2015] to 0.5 ppm in Canada,
Australia, and New-Zealand [CFIA (Canadian Food
Inspection Agency), 2014, FSANZ (Federal Register of
Legislation Australia/New Zealand Food Standards
Code), 2013]. These MPLs are compared to Pb medi-
ans calculated from our data set (Figure 1). All muscle
Pb medians are below the MPL with the exception of
MED₅ (Iskenderun–Karatas) (Figure 1a, b). Only liver
Pb medians from the Mediterranean (MED) and as-
sociated regional basins MED₂ (Eastern) and MED₅
(Iskenderun–Karatas) are above the MPL. Based
on the full record (from expanded Supplementary
Table S1), we infer that 16% and 10% of muscle Pb
analyses are above 0.3 and 0.5 ppm, respectively,
while it reaches 50% and 34% for liver Pb analyses.
These results emphasize both the preferential meta-
bolic accumulation of pollutant Pb in livers and the
anthropogenic insult to Mediterranean bony fish.

Lead medians in bony fish muscles from the world
ocean (Table 1a, Figure 1a) are significantly differ-
ent from each other (Mann-Whitney tests for medi-
ans *p* < 0.001). The lowest concentration, from far,
is encountered in the Atlantic (0.01 ppm) and the
highest in the Pacific (0.14 ppm). The Atlantic mus-
cle median is within the expected mean Pb content
(0.005 to 0.04 ppm) of 1225 fish muscles (C. *haren-
gus*, *S. sprattus*, *G. morhua*) from the Baltic Sea dur-
ing the 1994-2003 period [Polak-Juszczak, 2009]. A
more specific geographical approach in the Mediter-
ranean Sea endorses the role of habitat influence
in fish contamination with the western-central re-
gion (MED₁) showing the lowest muscle median (0.04
ppm), while the thoroughly investigated Turkish pol-
luted spot of Iskenderun-Karatas (Med₅) exhibits the
highest one (0.67 ppm) (Table 1a, Figure 1b). Me-
dian Pb levels in muscles increase from the western
to the eastern Mediterranean Sea with specific rises
in the more confined Black Sea (MED₃ 0.14 ppm)

and Marmara Sea (MED₄ 0.19 ppm). The Persian Gulf
region (IND₁) displays among the highest Pb me-
dian in bony fish muscles (0.21 ppm) (Table 1b) as
expected from the trend observed in other semien-
closed areas (MED₃,₄,₅). Lead medians in bony fish
livers are generally higher than those in muscles in
the main oceanic basins (Table 1a, Figure 1b). Mean-
while, such tissue comparison is best established on
the basis of coupled muscle–liver concentration from
the same cohorts in order to avoid biases, and is dis-
cussed in the next section. The lowest liver Pb me-
dian is again encountered in the Atlantic (0.06 ppm),
while the Indian Ocean and the Mediterranean Sea
display the highest ones (0.53 and 0.76 ppm, respec-
tively) (Table 1b, Figure 1a). The Atlantic liver me-
dian (0.06 ppm) is consistent with mean Pb content
in 1225 and 1343 fish livers (G. morhua, C. haren-
gus, S. sprattus, P platessa, M. Kitt, L. limanda) col-
lected from the southern Baltic Sea (0.004–0.05 ppm)
and the northeastern North Sea (0.03–0.17 ppm), re-
spectively, between the early 1990s and 2000s [Green
and Knutzen, 2003, Polak-Juszczak, 2009]. Lead lev-
els in livers are significantly different between each
oceanic basins (Mann–Whitney tests for medians *p* <
0.001). Liver Pb median in the Mediterranean regions
is at its lowest in the Black Sea (MED₃) (0.03 ppm)
where median's distribution is highly assymetrical
(Figure 1b), and, to a lesser extent, in the western–
central basin (MED₁) and Marmara Sea (MED₄)
(0.09 ppm) (Table 1b, Figure 1b). The highest Pb lev-
els in livers are found from far in the Iskenderun–
Karatas Bay (MED₅, 2.36 ppm), while the Persian Gulf
(IND₁, 0.51 ppm) exhibits Pb median close to IND
(0.43 ppm) (Table 1b). Statistical results in liver co-
horts for Mediterranean subbasins should be consid-
ered with caution owing to the fewer reported analy-
ses (less than 300 for MED₁,₂,₃,₄) and their larger data
dispersion (see IQRs in Table 1b).

Lead accumulation in fish tissues through water
exposure appears much more efficient than dietary
pathways [Alsop et al., 2016, Dural et al., 2007, Rozon-
Ramilo et al., 2011], although the latter may be en-
hanced for benthic foragers that may absorb contam-
inated particles in their alimentary tract [Dallinger
et al., 1987]. Different diet habits and trophic levels
also induce interspecific bioaccumulation disparities
(see review in Jakimska et al. [2011b]). We can ex-
plore this question using our database and examine
the capability of fish muscle Pb medians from mixed
species to mirror regional trends in surface seawater lead content (Pb<sub>ssw</sub>). We compare the Pb<sub>ssw</sub> yearly means between regional seas during the same periods, in offshore locations, away from the direct influence of populated enclosed bays and estuaries. The Yellow-China Sea (Korea, Pacific) display Pb<sub>ssw</sub> that are two to ten times higher than in the Ligurian Sea (France, western Mediterranean) and the Celtic Sea (GB, Northeast Atlantic) between the early 1980s and the mid 1990s [Brugmann et al., 1985, Cotté-Krief et al., 2002, Lee et al., 1998, Migon and Nicolas, 1998, Nicolas et al., 1994]. This pattern is consistent with Pb atmospheric emissions during the same period that decline by a factor 4–5 in Europe and increased by 10% in China in spite of the phasing out of leaded gasoline [Lee et al., 2014, Pacyna and Pacyna, 2000, Pacyna et al., 2007]. Pb<sub>ssw</sub> and atmospheric emissions differences are coherent with disparities in Pb muscle medians calculated from our database in the Atlantic (ATL), western-central Mediterranean (MED<sub>1</sub>), and Pacific (PAC) regions (0.01, 0.04, and 0.14 ppm, respectively). These temporal trends are further discussed in chapter 3.3 with the sorting of pre- and post-2000 fish records.

The geographic pattern of Pb accumulation in liver is slightly different than in muscle. While liver display the smallest median in the ATL region (Table 1b), still, the highest one is, from far, in the MED, and, to a lesser extent, the IND, rather than in the PAC that is close to the ATL (Table 1b). Like for muscle, the highest Mediterranean median is encountered in MED5 (Iskenderun-Karatas Bay). This discrepancy may be explained by the higher metabolic activity of liver that may prompt a more complex Pb median arrangement, not as reliable as muscle to proxy environmental contamination. Liver may exhibit more recent Pb contamination than muscles, and disparities in muscle and liver tissues may be emphasized from one species to another [Chouvelon et al., 2019, Hussain et al., 2014, Jakimska et al., 2011a,b, Renieri et al., 2014]. Differences may also partly rely on the lower number of specimens from the liver cohorts, most especially in the Pacific and the Mediterranean basins. This possible statistical bias is reinforced by significantly higher IQRs for liver than for muscle in each investigated region (Table 1a,1b). In order to best compare muscle and liver Pb accumulation, it is necessary to address paired tissues analyses within the same fish cohort.

## 3.2. *Comparison of paired muscle–liver*

Because of its detoxifying function and the production of metal-binding metallothioneins or lysosomes [Canli and Atli, 2003, Dunn et al., 1987, Fowler et al., 1981, Olsson, 1993, Roesijadi, 1992, Wang and Rainbow, 2010, Webb, 1979] fish liver is a target organ for Pb [Eroglu et al., 2015, Gingerich, 1982]. When excreted from liver with the bile, Pb passes into thetestine, where it can be reabsorbed or expelled with feces [Heath, 1987, Klaassen, 1986, Sures et al., 2003]. While the study of Pb in fish muscle is of prime interest for human consumption, and possibly to monitor environmental contamination, liver is a suitable proxy to assess fish intoxication in relation to metabolic activity [Jakimska et al., 2011b, Kalay et al., 1999, Kojadinovic et al., 2007]. Because Pb is poorly regulated and slowly excreted, we expect liver and muscle medians to display similar Pb geographical distribution patterns. We have evidenced differences between liver and muscle Pb median distribution in the main oceanic basins (Section 3.1). Meanwhile, Pb concentration in both tissues can only be appropriately compared to each other when it is measured from the same fish cohort collected together in the same region. Lead content in paired muscle–liver from the same fish cohort is presented in Table 2. Since Pb concentration from paired tissues are not normally distributed, only medians and IQRs are considered in descriptive statistics. When compared within each geographic area, livers always display significantly higher Pb median concentration than muscles (Mann–Whitney test *p* < 0.001). This geographic approach in various oceanic basins corroborates the role of liver as one of the prime tissues for Pb storage in bony fish [Agusa et al., 2007, Ahmed et al., 2018, Canli and Atli, 2003, El-Moselhy et al., 2014, Turkmen et al., 2009]. Overall, paired muscle and liver tissues display the same geographical patterns for the main marine basins, that is, ATL < PAC < IND < MED (Table 2), suggesting that both organs may be used as proxies to assess environmental marine pollution. It should be noticed that the Mediterranean Sea and associated subbasins display the largest distribution for paired muscle–liver (see IQR in Table 2). This statistical pattern, that is accented for livers, may be partly driven by the differentiate response of multiple species to the contrasted Mediterranean pollution imprints, that is, different abilities to induce
metal-binding proteins, various trophic levels and food habits [Jakimska et al., 2011b, Ruelas-Inzuza et al., 2014]. Moreover, the levels of fish metallothioneins is altered by gender, maturity, and natural environmental conditions [Olsson et al., 1998 and references therein] within a single species.

Muscle-liver response to anthropogenic Pb stress can be further examined with correlation plots (Figure 2). Overall, paired muscle and liver Pb levels are correlated (Spearman *r* = 0.85, *p* < 0.001). Meanwhile, this correlation appears to be driven by high Pb levels above 0.1 ppm in both muscle and liver as shown by a more detailed geographic investigation. Indeed, the MED area where most records are above 0.1 ppm in fish tissues displays a strong correlation (*r* = 0.92, *p* < 0.001), while there is no significant relation in the ATL area (*r* = 0.1, *p* = 0.1) where most of the data are below 0.1 ppm. The IND and PAC areas display moderate covariation factors owing to their larger data scattering. These various Pb burden distributions may signify a prevailing Pb accumulation in both fish organs for Pb content above 0.1 ppm, a threshold above which Pb excretion may be less efficient. As a consequence, fish tissues, and most particularly liver, may not be as proficient to proxy seawater Pb content in remote less contaminated environments. Further analyses are required within single species collected from various contaminated areas to examine these results and investigate the role of specific environmental settings. The metabolic accumulation and excretion of Pb seems to be driven by Pb concentration close to the EU and FAO/WHO MPLs for fish consumption, independently from the involved species or the considered regional habitat. The contamination of the latter depends on regional pollutant Pb emissions and associated regulation policies that vary from one country to another. Therefore, it is thus appealing to test whether it would be possible to discern the imprint of these policies and regulations of lessened Pb emissions with time in bony fish cohorts from various marine basins.

### 3.3. *Transient Pb concentration: global and regional experiences*

Atmospheric Pb trends are difficult to assess in seawater owing to the very few reliable Pb<sub>ssw</sub> time series and Pb content variability that may not be easily

associated to regional anthropogenic imprints only. Thanks to the most extensive case studies in the western North Atlantic (Bermuda), one can examine the response of surface seawater Pb content to Pb emission mitigation from Western Europe and North America between 1975 and 1995. Pb<sub>ssw</sub> in the vicinity of Bermuda have decreased by a factor 5–8 in the period 1979–2011 [Boyle et al., 2014, Noble et al., 2015 and references therein] as a result of about ten time decrease of Pb emissions in Western Europe and North America [Boyle et al., 2014, EMEP/EEA, 2016, Environment and Climate Change Canada, 2020, Lee et al., 2014, Nevin, 2017, Nriagu, 1990, Pacyna and Pacyna, 2000, 2001, Pacyna et al., 2007, Petit et al., 2015, Pirrone et al., 1999, Soto-Jimenez et al., 2006, U.S. EPA, 2018]. This mitigation experience was not as conclusive in neighboring India and south Asian countries, where the phasing out of leaded gasoline is counterweighted by rising industrial emissions such as coal burning [Lee et al., 2014]. Here, we explore our record to determine whether or not these atmospheric trends are recorded in bony fish, worldwide. To assess this issue, the data set is divided into pre- and post-2000 analyses. When grouped as such, all data median (ALL) remains unchanged for muscles (MW *p* > 0.05), while it significantly increases for liver (MW *p* < 0.001) from 0.11 ppm (PRE) to 0.41 ppm (POST) (Table 3). This shift can be examined by looking at the fraction of analyses above or below the MPL (from detailed Supplementary Table S1) for pre- and post-2000 data sets. As expected from ALL Pb medians, muscle analyses above the MPL remain unchanged, while livers reveal a significant increase from pre-2000 (33% above 0.3 ppm) to post-2000 (55% above 0.3 ppm) periods (MW *p* < 0.001). Meanwhile, this discrepancy relies mostly on the chosen MPL as it mostly applies to liver concentrations between 0.3 and 0.5 ppm. No significant change is being perceived for the liver's cohort above 0.5 ppm (29% and 27% in pre- and post-2000 periods, respectively). The rise in general liver Pb median (ALL<sub>L</sub>) in post-2000 is mostly driven by a significant increase of Pb median in liver from the Indian Ocean (IND<sub>L</sub>). On the contrary, liver medians from the Pacific (PAC<sub>L</sub>) and Mediterranean (MED<sub>L</sub>) basins substantially decrease from pre- to post-2000 periods. These latter results should be considered with caution since they often rely on less than 500 samples. Meanwhile, muscle Pb medians seem to com-
<figure><img src="image_5.png" /><figcaption>**Figure 2.** General and regional covariation of paired muscle–liver Pb levels.</figcaption></figure>

fort the observed trends for livers with a sharp decline of PAC<sub>M</sub> and MED<sub>M</sub>, and an increase of IND<sub>M</sub>, while ATL<sub>M</sub> does not exhibit any significant change. The increase of both IND<sub>L</sub> and IND<sub>M</sub> from pre- to post-2000 periods mimics patterns of Pb/Ca ratios in coral skeleton's Pb content in the northern Indian Ocean [Lee et al., 2014]. Indeed, the historical record of accumulated Pb in corals (Pb/Ca ratios) from the central and eastern Indian Ocean increased since the mid 1990s in spite of the phasing out of leaded gasoline during the same period in the neighboring heavily populated India and Indonesia [Lee et al., 2014]. This enhancement is mostly associated with the continuous rise of Pb emission from coal burning for the production of electricity in most surrounding countries since the mid 1980s [Lee et al., 2014]. The decrease of Pb in muscle and liver from the Mediterranean may result from the phasing out of leaded gasoline in European countries of which imprint is already apparent in the western basin surface seawater in the early 1990s [Nicolas et al., 1994]. The steadiness or slight increase of Pb medians in the Atlantic Ocean may appear at first intriguing as we would expect to observe a clear decrease of bony fish Pb medians in the Atlantic basin as for the Mediterranean basin between pre- and post-2000 data set. Indeed,

the neighboring North American and Western European countries were among the very first to initiate the phasing out of leaded gasoline in the 1970s and 1980s, respectively

[Thomas et al., 1999]. Considering the short residence time (i.e., about 10 days) of aerosol Pb in the marine atmosphere [Hussain et al., 1998, Poet et al., 1972, Settle et al., 1982], we may postulate that the outcome of these earliest policies materialized very rapidly in the northern Atlantic ecosystem, much before the years 2000s. This assumption is corroborated by seawater Pb concentration that had already significantly decreased into the North Atlantic thermocline between 1979 and the early 1990s [Véron et al., 1998, Wu and Boyle, 1997]. Afterward, Pb levels in North Atlantic surface seawater did not significantly vary between the late 1990s and the 2010s [Kelly et al., 2009, Noble et al., 2015] suggesting that most of the marine response occurred way before the 2000s. To test this hypothesis, we select the pre-1990 Atlantic record. ATL<sub>M</sub> in pre-1990 period (0.38 ppm, *n* = 279) is significantly higher (MW *p* < 0.001) than for the post-2000 cohort (0.011 ppm). ATL<sub>L</sub> displays the same pattern (0.13 ppm and 0.07 ppm in pre-1990 and post-2000 periods, respectively) with fewer data (*n* = 130 for pre-1990 period). These results corroborate our as-
<figure><img src="image_6.png" /><figcaption>**Figure 3.** Transient Pb levels in bony fish muscle and liver (Iskenderun–Karatas Bay, Turkey).</figcaption></figure>

sumption and reinforce the statistical evidence of en-
vironmental policies imprints in the Atlantic Ocean
for which most of the pre-1990 data are reported from
the North Atlantic basin.

Each geographic data set includes a large vari-
ety of sampling regions from which either muscle
and/or liver tissues are analyzed. These disparities
may distort time-trend monitoring based on dif-
ferent periods, most specially for smaller data co-
horts. This is why we favor local or regional surveys
where transient shifts may be best described. Here,
we venture into the eastern Mediterranean basin, in
the Turkish polluted hop spot of Iskenderun–Karatas
(MED5). Because of the release of untreated indus-
trial wastes and municipal sewage, this coastal area
has been categorized into one of the major Mediter-
ranean hop spot for metal contamination [Cogun
et al., 2005, Doygun and Alphan, 2006, Kargin, 1996,
UNEP (United Nations Environment Program), 2002,
Yilmaz, 2003, Yilmaz et al., 2010, Yilmaz and Son-
mez, 2018]. Our data set constitutes an opportunity
to investigate possible transient shifts owing to sev-
eral years of Pb analyses in fish tissues from this
area (Figure 3). Both muscle and liver Pb distribu-
tion with time show a significant decrease (r = 0.72
and 0.62, respectively; Spearman p < 0.001) in spite

of persistent records of Pb pollution in Iskenderun re-
gion [Cevik et al., 2010, Kara et al., 2019, Sert et al.,
2019, Tepe and Dogan, 2015], and regional PM10 an-
nual means that remain above the EU limit value of
50 µg·m⁻³ [Ministry of Environment and Urbaniza-
tion of Turkey, 2014, Tepe and Dogan, 2015]. These
are moderates but statistically significant correla-
tions that may reflect enforcement of European stan-
dards. Indeed, in the Iskenderun Bay region, most air
pollution indicators have ceased to increase during
the 2011–2015 period [Ministry of Environment and
Urbanization of Turkey, 2016]. This recovery is signi-
fied by an improvement of NOx and PM10 emissions
in the southern bay during the past few years [Akar
et al., 2020, Ministry of Environment and Urbaniza-
tion of Turkey, 2016]. Further, National policies and
clean air plans need to be implemented regarding the
development of renewable energy sources, monitor-
ing of industrial emissions, and industrial develop-
ment. Another mixed fish cohort from the more en-
closed Tagus Estuary (Portugal) displays the same 10–
100 time decrease of muscle Pb content during the
2000s as a response to a local reduction of industrial
inputs [Raimundo et al., 2011]. Similar decreases are
observed in the Baltic Sea between the early 1980s
and the 2010s (Bignert et al. [2016]; graphs and sta-
tistical trends available only). From this standpoint, we advocate the use of fish tissues as sensitive indicators to monitor the response of marine ecosystems to pluriannual modifications of the anthropogenic imprint within local polluted environments.

## 4. Conclusions

Fish biomonitoring of Pb pollution in coastal marine regions remains a challenge depending on fish's nutrition, age, size, trophic level and metabolism. Statistical examination of this toxic metal analyses in muscle and liver tissues features the usefulness of our literature review in order to demonstrate the sensitivity of fish response to distinct regional pollution status and governmental policies, in spite of expected interspecies disparities. While muscle appears less contaminated than liver within all marine basins, both tissues show covaried Pb enrichment for Pb levels above 0.1 ppm (wet weight) in coherence with EU and FAO/WHO MPLs for fish consumption. The latter suggests that above MPL, Pb uptake is not as efficiently excreted and readily accumulates in liver and muscle tissues. Our results suggest that fish fillets may be more efficient to biomonitoring anthropogenic transient trends than liver tissues, particularly in the least contaminated areas. Bony fish species and sizes are available from our record and may be dealt for to explore more thoroughly interspecies fish response to human pressure. The latter shall be facilitated with the computation of trophic level and ecological habitat for each considered species in the projected online version of the present database.

## Acknowledgments

All searches for references were performed with the online library services of Aix Marseille University. We thank D. Point, A. Lorrain (IRD Institute) and M. Harmelin-Vivien, D. Banaru (MIO, AMU) for sharing their biological expertises regarding metal records in fish database. We are grateful to Hélène Paquet for editorial revision of the references. Comments from two anonymous reviewers and the editors were very useful to improve the manuscript.

## Supplementary data

Supporting information for this article is available on the journal's website under https://doi.org/10.5802/crgeos.49 or from the author.

## References

Agusa, T., Kunito, T., Sudaryanto, A., Monirith, I., Kan-Atireklap, S., Iwata, H., Ismail, A., Sanguansin, J., Muchtar, M., Tana, T., and Tanabe, S. (2007). Exposure assessment for trace elements from consumption of marine fish in Southeast Asia. *Environ. Polut.*, 145, 766-777.

Ahmed, Q., Bat, L., Oztekin, A., and Mohammad Ali, Q. (2018). A review on studies of heavy metal determination in mackerel and tuna (family-scombridae) fishes. *J. Anatol. Environ. Anim. Sci.*, 3, 104-120.

Akar, O., Calisir, V., and Demerci, A. (2020). Determination of the amount and effects of ship fuel gas emissions in Iskenderun Bay. *Fresenius Environ. Bull.*, 07A, 6039-6045.

Alsop, D., Ng, T. Y. T., Chowdhury, M. J., and Wood, C. M. (2016). Interactions of waterborne and dietborne Pb in rainbow trout, Oncorhynchus mykiss: bioaccumulation, physiological responses, and chronic toxicity. *Aquat. Toxicol.*, 177, 343-354.

Alves, L. C., Glover, C. N., and Wood, C. M. (2006). Dietary Pb accumulation in juvenile freshwater rainbow trout (*Oncorhynchus mykiss*). *Arch. Environ. Contam. Toxicol.*, 51, 615-625.

Authman, M., Zaki, M. S., Khallaf, E. A., and Abbas, H. H. (2015). Use of fish as bio indicator of the effects of heavy metals pollution. *J. Aquac. Res. Dev.*, 6(4), 328-340.

Bignert, A., Danielsson, S., Faxneld, S., and Nyberg, E. (2016). Comments concerning the national Swedish contaminant monitoring program in Marine Biota, 2016. In *Report NV-01851-15/2213-15-007*, pages 86-95. Swedish Environmental Protection Agency, Environmental Monitoring Unit, Stockholm, Sweden.

Birge, W. J., Black, J. A., and Ramey, B. A. (1981). The reproductive toxicology of aquatic contaminants. *Haz. Assess. Chem.*, 1, 59-115.

Boening, D. W. (1999). An Evaluation of bivalves as biomonitors of heavy metals pollution in marine waters. *Environ. Monit. Assess.*, 55, 459-470.
Bosch, A. C. (2015). *Status of mercury and other heavy metals in South African marine fish species*. PhD thesis, Faculty of AgriSciences, Stellenbosch Univ., South Africa. 149 pages.

Boyle, E. A., Lee, J.-M., Echegoyen, Y., Noble, A., Moos, S., Carrasco, G., Zhao, N., Kayser, R., Zhang, J., Gams, T., Obata, H., and Nortsuye, K. (2014). Anthropogenic lead emissions in the ocean: The evolving global experiment. *Oceanography*, 27(1), 69–75.

Brugmann, L., Danielsson, L.-G., Magnusson, B., and Werstelung, S. (1985). Lead in the North Atlantic Ocean. *Mar. Chem.*, 16, 47–60.

Burger, J. and Gochfeld, M. (2005). Heavy metals in commercial fish in New Jersey. *Environ. Res.*, 99, 403–412.

Burger, J., Gochfeld, M., Jeitner, C., Pittfield, T., and Donio, M. (2014). Heavy metals in fish from the Aleutians: Interspecific and locational differences. *Environ. Res.*, 131, 119–130.

Bustamante, P., Bochet, P., Cherel, Y., Miramand, P., and Caurant, F. (2003). Distribution of trace elements in tissues of benthic and pelagic fish from the Kerguelen Islands. *Sci. Total Environ.*, 313, 25–39.

CAC (Codex Alimentarius Commission) (2011). Joint Food and Agriculture Organization of the United Nations/World Health Organization Food Standards Programme - Codex Committee on Contaminants in Foods. Fifth Session, The Hague, The Netherlands, March 21–25.

Canfield, R. L., Kreher, D. A., Cornwell, C., and Henderson, C. R. (2003). Low-level lead exposure, executive functioning, and learning in early childhood. *Child Neuropsychol.*, 9(1), 35–53.

Canli, M. and Atli, G. (2003). The relationships between heavy metal (Cd, Cr, Cu, Fe, Pb, Zn) levels and the size of six Mediterranean fish species. *Environ. Pollut.*, 121, 129–136.

Castro-Gonzalez, M. I. and Méndez-Armenta, M. (2008). Heavy metals: Implications associated to fish consumption. *Environ. Toxicol. Pharmacol.*, 26, 263–271.

Celik, U., Cakli, S., and Oehlenschlager, J. (2004). Determination of lead and cadmium burden in some northeastern Atlantic and Mediterranean fish species by DPSAV. *Eur. Food Res. Technol.*, 218, 298–305.

Cevik, U., Kozb, B., and Makarovskac, Y. (2010). Heavy

metal analysis around Iskenderun Bay in Turkey. *X-Ray Spectrom.*, 39, 202–207.

CFIA (Canadian Food Inspection Agency) (2014). Fish products standards. Appendix 3. In *Canadian Guidelines for Chemical Contaminants and Toxins in Fish and Fish Products*. amended August 2014.

Chouvelon, T., Strady, E., Harmelin-Vivien, M., Radakovitch, O., Brach-Papa, C., Crochet, S., Knoery, J., Rozuel, E., Thomas, B., Tronczynski, J., and Chiffoleau, J. (2019). Patterns of trace metal bioaccumulation and trophic transfer in a phytoplankton-zooplankton-small pelagic fish marine food web. *Mar. Pollut. Bull.*, 146, 1013–1030.

Cogun, H. Y., Yuzereroglu, T. A., Kargin, F., and Fırat, O. (2005). Seasonal variation and tissue distribution of heavy metals in shrimp and fish species from the Yumurtalik coast of Iskenderun Gulf, Mediterranean. *Environ. Contam. Toxicol.*, 75, 707–715.

Corrill, L. S. and Huff, J. E. (1976). Occurrence, physiologic effects, and toxicity of heavy metals - arsenic, cadmium, lead, mercury, and zinc - in marine biota: an annotated literature collection. *Environ. Health Persp.*, 18, 181–219.

Cotté-Krief, M.-H., Thomas, A. J., and Martin, J.-M. (2002). Trace metal (Cd, Cu, Ni and Pb) cycling in the upper water column near the shelf edge of the European continental margin (Celtic Sea). *Mar. Chem.*, 79, 1–26.

Cresson, P., Travers-Trolet, M., Rouquette, M., Timmerman, C. A., Giraldo, C., Lefebvre, S., and Emande, B. (2017). Underestimation of chemical contamination in marine fish muscle tissue can be reduced by considering variable wet:dry weight ratios. *Mar. Pollut. Bull.*, 123, 279–285.

Cunningham, P. A., Sullivan, E. E., Everett, K. H., Kovach, S. S., Rajan, A., and Barber, M. C. (2019). Assessment of metal contamination in Arabian/Persian Gulf fish: a review. *Mar. Pollut. Bull.*, 143, 264–283.

Dallinger, R., Prosi, F., Segner, H., and Back, H. (1987). Contaminated food and uptake of heavy Metals by fish: a review and a proposal for further research. *Oecologia*, 73, 91–98.

Danovaro, R. (2003). Pollution threats in the Mediterranean Sea: an overview. *Chem. Ecol.*, 19(1), 15–32.

Dell'Anno, A., Mei, M. L., Ianni, C., and Danovaro, R. (2003). Impact of bioavailable heavy metals
on bacterial activities in coastal marine sediments.
*World J. Microbiol. Biotechnol.*, 19, 93–100.

Demayo, A., Taylor, C. M., Taylor, K. W., Hodson, P. V., and Hammond, P. B. (1982). Toxic effects of lead and lead compounds on human health, aquatic life, wildlife plants, and livestock. *Crit. Rev. Environ. Control*, 12(4), 257–305.

Domingo, J. L., Bocio, A., Falco, G., and Llobet, J. M. (2007). Benefits and risks of fish consumption Part I. A quantitative analysis of the intake of omega-3 fatty acids and chemical contaminants. *Toxicology*, 230, 219–226.

Doygun, H. and Alphan, H. (2006). Monitoring urbanization of Iskenderun, Turkey, and its negative implications. *Environ. Monit. Assess.*, 114, 145–155.

Dunn, M. A., Blalock, T. L., and Cousins, R. J. (1987). Metallothionein. *Proc. Soc. Exp. Biol. Med.*, 185, 107–119.

Dural, M., Goksu, Z. L., and Ozak, A. A. (2007). Investigation of heavy metal levels in economically important fish species captured from the Tuzla lagoon. *Food Chem.*, 102, 415–421.

Durrieu de Madron, X., Guieu, C., Sempéré, R., Conan, P., Cossa, D., D'Ortenzio, F., Estournel, C., Gazeau, F., Rabouille, C., Sternmann, L., Bonnet, S., Diaz, F., Koubbi, P., Radakovitch, O., Babin, M., Baklouti, M., Bangon-Montigny, C., Belviso, S., Bensoussan, N., and Bonsang, B. (2011). Marine ecosystems responses to climatic and anthropogenic forcings in the Mediterranean. *Prog. Oceanogr.*, 91, 97–166.

El-Moselhy, K. M., Othman, A. I., El-Azem, H. A., and El-Metwally, M. E. A. (2014). Bioaccumulation of heavy metals in some tissues of fish in the Red Sea, Egypt. *Egypt. J. Basic. Appl. Sci.*, 1(2), 97–105.

EMEP/EEA (2016). Air pollutant emission inventory guidebook. In *Technical Guidance to Prepare National Emission Inventories*. European Environment Agency, Copenhagen, Denmark.

Environment and Climate Change Canada (2020). Canadian Environmental Sustainability Indicators: Emissions of harmful substances to air. www.canada.ca/en/environment-climate-change/services/environmental-indicators/emissions-harmful-substances-air.html.

Erasmus, C. P. (2004). *The concentration of ten metals in the tissues of shark species squalus magalops and mustelus mustelus (chondrichthyes) occurring along the southeastern coast of South Africa*. PhD

thesis, Faculty of Science, Port Elizabeth Univ., South Africa. 331 pages.

Ergul, H. A. and Aksan, S. (2013). Evaluation of non-essential element and micronutrient concentrations in seafood from the Marmara and Black Seas. *J. Black Sea/Med. Environ.*, 19(3), 312–330.

Eroglu, A., Dogan, Z., Kanak, E. G., Atli, G., and Canli, M. (2015). Effects of heavy metals (Cd, Cu, Cr, Pb, Zn) on fish glutathione metabolism. *Environ. Sci. Pollut. Res.*, 22, 3229–3237.

Escobar-Sanchez, O., Ruelas-Inzunza, J., Moreno-Sánchez, X. G., Romo-Piñera, A. K., and Frías-Espericueta, M. G. (2015). Mercury concentrations in Pacific angel sharks (*Squatinacalifornica*) and prey fishes from southern Gulf of California, Mexico. *Bull. Environ. Contam. Toxicol.*, 96(1), 15–19.

EU (2015). European Union Commission Regulation EU 2015/1005 of 25 June 2015, amending regulation EC 1881/2006 as regards maximum levels of lead in certain foods.

Falco, G., Llobet, J. M., Bocio, A., and Domingo, J. L. (2006). Daily intake of arsenic, cadmium, mercury and lead by consumption of edible marine species. *J. Agric. Food Chem.*, 54, 6106–6112.

FAO GFCM (2009). Resolution GFCM/33/2009/2 on the establishment of geographical subareas in the GFCM area of application.

FAO-UN (2021). *Major Fishing Areas*. Fisheries and Aquaculture Dept. International Council for the Exploration of the Seas, http://www.fao.org/fishery/area/search/en.

Flegal, A. R. and Smith, D. R. (1992). Current needs for increased accuracy and precision in measurements of low levels of lead in blood. *Environ. Res.*, 58, 125–133.

Flegal, A. R. and Smith, D. R. (1995). Measurements of environmental lead contamination and human exposure. *Rev. Environ. Contam. Toxicol.*, 143, 1–45.

Fowler, B. A., Carmichael, N. G., Squibb, K. S., and Engel, D. W. (1981). Factors affecting trace metal uptake and toxicity to estuarine organisms. II. Cellular mechanisms. In Vernberg, F. J., Calabrese, A., Thurberg, F. P., and Vernberg, W. B., editors, *Biological Monitoring of Marine Pollutants*, pages 145–164. Academic Press, New York, London.

FSANZ (Federal Register of Legislation Australia/New Zealand Food Standards Code) (2013). Australian Government Federal Register of Legislation Stan-
dard 1.4.1 - Contaminants and Natural Toxicants.

Gingerich, W. H. (1982). Hepatic toxicology of fishes. In Weber, L. T., editor, *Aquatic Toxicology*, pages 55–105. Raven Press, New York.

Grandjean, P. (2010). Even low-dose lead exposure is hazardous. *Lancet*, 376, 855–856.

Green, N. W. and Knutzen, J. (2003). Organohalogens and metals in marine fish and mussels and some relationships to biological variables at reference localities in Norway. *Mar. Pollut. Bull.*, 46, 362–377.

Halpern, B. S., Walbridge, S., Selkoe, K. A., Kappel, C. V., Micheli, F., D'Agrosa, K., Bruno, J.-F., Casey, K. S., Ebert, C., Fox, H. E., Fujita, R., Heinemann, D., Lenihan, H. S., Madin, E. M. P., Peray, M. T., Selig, C. R., Spalding, M., Stenek, R., and Watson, R. (2008). A global map of human impact on marine ecosystems. *Science*, 319, 948–952.

Hammer, O., Harper, D. A. T., and Ryan, P. D. (2001). PAST: Paleontological statistics software package for education and data analysis. *Palaeontol. Electron.*, 4(1), 9.

Han, B.-C., Jeng, W. L., Chen, R. Y., Fang, G. T., Hung, T. C., and Tseng, R. J. (1998). Estimation of target hazard quotients and potential risks for metals by consumption of seafood in Taiwan. *Arch. Environ. Contam. Toxicol.*, 35, 711–720.

Harmelin-Vivien, M., Cossa, D., Crochet, S., Barnaru, D., Letourneur, Y., and Mellon-Duval, C. (2009). Difference of mercury bioaccumulation in red mullets from the north-western Mediterranean and Black seas. *Mar. Pollut. Bull.*, 58, 679–685.

Heath, A. G. (1987). *Water Pollution and Fish Physiology*. CRC Press, Boca Roca, Florida.

Hellou, J., Warren, W. G., Payne, J. E., Belkhode, S., and Lobel, P. (1992). Heavy metals and other elements in three tissues of cod, *Gadus morhua* from the Northwest Atlantic. *Mar. Pollut. Bull.*, 24(9), 452–458.

Hodson, P. V., Blunt, B. R., and Whittle, D. M. (1984). Monitoring lead exposure of fish. In Cairns, V. W., Hodson, P. V., and Nriagu, J. O., editors, *Contaminant Effects of Fisheries*, pages 87–98. John Wiley, New York.

Hussain, M., Muhammad, S., Malik, R. N., Khan, M. U., and Farooq, U. (2014). Status of heavy metal residues in fish species of Pakistan. *Rev. Environ. Contam. Toxicol.*, 230, 111–132.

Hussain, N., Church, T. M., Véron, A., and Larson, R. E. (1998). Radon daughter desequilibria and lead

systematics in the western North Atlantic. *J. Geo-phys. Res.*, 103(13), 16059–16071.

Jakimska, A., Koniecka, P., Skora, K., and Namiesnik, J. (2011a). Bioaccumulation of metals in tissues of marine animals, part I: the role and impact of heavy metals on organisms. *Pol. J. Environ. Stud.*, 20(5), 1117–1125.

Jakimska, A., Koniecka, P., Skora, K., and Namiesnik, J. (2011b). Bioaccumulation of metals in tissues of marine animals, part II: metal concentrations in animal tissues. *Pol. J. Environ. Stud.*, 20(5), 1127–1146.

Janssens, M. and Dams, R. (1975). Man's impact on atmospheric lead concentrations - pollution sources and baseline levels in western Europe. *Water Air Soil Pollut.*, 5, 97–107.

Kalay, M., Ay, O., and Canli, M. (1999). Heavy metal concentrations in fish tissues from the Northeastern Mediterranean Sea. *Bull. Environ. Contam. Toxicol.*, 63, 673–681.

Kara, M., Odabasi, M., Dumanoglu, Y., and Falay, E. O. (2019). Investigation of atmospheric pollution by biomonitoring of major and trace elements in an industrial region. *J. Environ. Sci. Eng. Technol.*, 7, 16–25.

Kargin, F. (1996). Seasonal changes in levels of heavy metals in tissues of *Mullus barbatus* and *Sparus aurata* collected from Iskenderun Gulf (Turkey). *Water Air Soil Pollut.*, 90, 557–562.

Kelly, A. E., Reuer, M. K., Goodkin, N. F., and Boyle, E. A. (2009). Lead concentrations and isotopes in corals and water near Bermuda, 1780–2000. *Earth Planet. Sci. Lett.*, 283, 93–100.

Klaassen, C. D. (1986). Distribution, excretion, and absorption of toxicants. In Klaassen, C. D., Amdur, M. O., and Doull, J., editors, *Casarett and Doull's Toxicology: The Basic Science of Poisons*, pages 33–63. Macmillan Publishing Company, London, UK.

Kojadinovic, J., Potier, M., Le Corre, M., Cosson, R., and Bustamante, P. (2007). Bioaccumulation of trace elements in pelagic fish from the western Indian Ocean. *Pollut. Environ.*, 145(2), 548–566.

Lanphear, B. P., Hornung, R., Khoury, J., Yolton, K., Baghurst, P., Bellinger, D. C., Canfield, R. L., Dietrich, K. N., Bornschein, R., Greene, T., Rothenberg, J., Needleman, H. L., Schnaas, L., Wasserman, G., Graziano, J., and Roberts, R. (2005). Low-level environmental lead exposure and children's intellectual function: an international pooled analysis. *En-
*viron. Health Perspect.*, 113(7), 894–899.

Lee, J. M., Boyle, E. A., Nurhati, I. S., Pfeiffer, M., Meltzner, A. J., and Suwargadi, B. (2014). Coral-based history of lead and lead isotopes of the surface Indian Ocean since the mid-20th century. *Earth Planet. Sci. Lett.*, 398, 37–47.

Lee, J. W., Choi, H., Huang, U. K., Kang, J. C., Kang, Y. J., Kwang, K., and Kim, J. H. (2019). Toxic effects of lead exposure on bioaccumulation, oxidative stress, neurotoxicity, and immune responses in fish: A review. *Environ. Toxicol. Pharmacol.*, 68, 101–108.

Lee, K. W., Kang, H. S., and Lee, S. H. (1998). Trace elements in the Korean coastal environment. *Sci. Total Environ.*, 214, 11–19.

Llobet, J. M., Falco, G., Casas, C., Teixido, A., and Domingo, J. L. (2003). Concentrations of arsenic, cadmium, mercury and lead in common foods and estimated daily intake by children, adolescents, adults, and seniors of Catalonia, Spain. *J. Agric. Food Chem.*, 51, 838–842.

MacDonald, R., Mackay, D., and Hickie, B. (2002). A new approach suggests that phenomena, such as bioconcentration, biomagnification, and bioaccumulation, result from two fundamental processes. *Environ. Sci. Technol.*, 36(23), 458–462.

Magalhaes, M. C., Costa, V., Menezes, G. M., Pinho, M. R., Santos, R. S., and Monteiro, L. R. (2007). Intra- and inter-specific variability in total and methylmercury bioaccumulation by eight marine fish species from the Azores. *Mar. Pollut. Bull.*, 54, 1654–1662.

Mallatt, J. (1985). Fish gill structural changes induced by toxicants and other irritants: a statistical review. *Can. Fish. Aquat. Sci.*, 42, 630–648.

Mason, R. P. (2013). *Trace Metals in Aquatic Systems*. Blackwell Publishing Ltd., Oxford, UK.

Mathews, T. and Fisher, N. S. (2009). Dominance of dietary intake of metals in marine elasmobranch and teleost fish. *Sci. Total Environ.*, 407(18), 5156–5161.

Migon, C. and Nicolas, E. (1998). Effects of antipollution policy on anthropogenic lead transfers in the Ligurian Sea. *Mar. Pollut. Bull.*, 36, 775–779.

Ministry of Environment and Urbanization of Turkey (2014). Turkey's Environmental Problems and Priorities Assessment Report. Division for State of the Environment Reports, issue 23.

Ministry of Environment and Urbanization of Turkey

(2016). *State of the environmental report for Republic of Turkey*. General Directorate of Environmental Impact Assessment, Permit and Inspection, Ankara.

Murray, J. and Burt, J. R. (1969). *The Composition of Fish*, volume 38 of *Torry Advisory Note*. Torry Research Station.

Needleman, H. (2004). Lead poisoning. *Annu. Rev. Med.*, 55, 209–222.

Nevin, R. (2017). Understanding international crime trends: The legacy of preschool lead exposure. *Environ. Res.*, 104, 315–336.

Nicolas, E., Ruiz-Pino, D., Buat-Menard, P., and Bethoux, P. (1994). Abrupt decrease of lead concentration in the Mediterranean Sea: a response to antipollution policy. *Geophys. Res. Lett.*, 21, 2119–2122.

Noble, A. E., Echegoyen-Sanz, Y., Boyle, E. A., Ohnemus, C., Lam, P. J., Kayser, R., Reuer, M., Wu, J., and Smethie, W. (2015). Dynamic variability of dissolved Pb and Pb isotope composition from the U.S. North Atlantic GEOTRACES transect. *Deep Sea Res. II*, 116, 208–225.

NRC (1993). *Measuring Lead Exposure in Infants, Children, and Other Sensitive Populations*. National Research Council, Nat. Acad. Sci., Washington, DC.

Nriagu, J. O. (1990). The rise and fall of leaded gasoline. *Sci. Total Environ.*, 92, 13–28.

Nriagu, J. O. and Pacyna, J. M. (1988). Quantitative assessment of worldwide contamination of air, water and soils by trace metals. *Nature*, 333, 134–139.

Nussey, G., Van Vuren, J. H. J., and Du Preez, H. H. (2000). Bioaccumulation of chromium, manganese, nickel and lead in the tissues of the moggel, *Labeoum bratus* (Cyprinidae), from Witbank Dam, Mpumalanga. *Water SA*, 26, 269–284.

Oehlenschlager, J. (2009). Trace element concentrations in muscle tissue of the benthopelagic grenadier (*Coryphaeniodes armatus*) from the Iberian deep-sea. *Inf. Fishereiforsch.*, 56, 45–48.

Olsson, P., Kling, P., and Hogstrand, C. (1998). Mechanisms of heavy metal accumulation and toxicity in fish. In Langston, W. and Bebianno, M. J., editors, *Metal Metabolism in Aquatic Environments*. Chapman & Hall, London, UK.

Olsson, P.-E. (1993). Metallothionein gene expression and regulation in fish. In Hochachka, P. W. and Mommsen, T. P., editors, *Biochemistry and Molec-
*ular Biology of Fishes: Molecular Biology Frontiers*, pages 259–278. Elsevier Science Publishers BV, Amsterdam, NL.

Ong, M. C. and Gan, S. L. (2017). Assessment of metallic trace elements in the muscles and fins of four landed elasmobranchs from Kuala Terengganu waters, Malaysia. *Mar. Pollut. Bull.*, 124, 1001–1005.

Pacyna, E. G., Pacyna, J. M., Fudala, J., and Strzelecka-Jastrzab, E. (2007). Current and future emissions of selected heavy metals to the atmosphere from anthropogenic sources in Europe. *Atm. Environ.*, 41, 8557–8566.

Pacyna, J. M. and Pacyna, E. G. (2000). Atmospheric emissions of anthropogenic lead in Europe: improvements, updates, historical data and projections. *GKSS-Forschungszentrum Geesthacht GmbH Report*, GKSS 2000/31, Geesthacht.

Pacyna, J. M. and Pacyna, E. G. (2001). An assessment of global and regional emissions of trace metals to the atmosphere from anthropogenic sources worldwide. *Environ. Res.*, 9, 269–298.

Panichev, N. A. and Panicheva, S. E. (2015). Determination of total mercury in fish and sea products by direct thermal decomposition atomic absorption spectrometry. *Food Chem.*, 166, 432–441.

Patterson, C. C. (1980). An alternative perspective - lead pollution in the human environment: origin, extent, and significance. In *Lead in the Human Environment*, pages 265–342. Nat. Acad. Sci., Washington, DC.

Petit, D., Véron, A., Flament, P., Deboudt, K., and Poirier, A. (2015). Review of pollutant lead decline in urban air and human blood: a case study from northwestern Europe. *C. R. Geosci.*, 347, 247–256.

Pirrone, N., Costa, P., and Pacyna, J. M. (1999). Past, current and projected atmospheric emissions of trace elements in the Mediterranean region. *Water Sci. Technol.*, 39, 1–7.

Ploetz, D. M., Fitts, B. E., and Rice, T. M. (2007). Differential accumulation of heavy metals in muscle and liver of a marine fish, (King mackerel, Scomberomorus cavalla Cuvier) from the Northern Gulf of Mexico, USA. *Bull. Environ. Contam. Toxicol.*, 78, 134–137.

Poet, S. E., Moore, H. E., and Martell, E. A. (1972). Lead 210, bismuth 210, and polonium 210 in the atmosphere: accuracy ratio measurement and application to aerosol residence time determination.

*Geophys. Res.*, 77, 6515–6527.

Polak-Juszczak, L. (2009). Temporal trends in the bioaccumulation of trace metals in herring, sprat, and cod from the southern Baltic Sea in the 1994–2003 period. *Chemosphere*, 76, 1334–1339.

Pourang, N. (1995). Heavy metal bioaccumulation in different tissues of two fish species with regards to their feeding habits and trophic levels. *Environ. Monit. Assess.*, 35, 207–219.

Raimundo, J., Pereira, P., Caetano, M., Cabrita, M. T., and Vale, C. (2011). Decrease of Zn, Cd and Pb concentrations in marine fish species over a decade as response to reduction of anthropogenic inputs: The example of Tagus estuary. *Mar. Pollut.*, 62, 2854–2858.

Renieri, E. A., Alegakis, A. K., Kiriakakis, M., Vinceti, M., Ozcagli, E., Wicks, M. F., and Tsatsakis, A. M. (2014). Cd, Pb and Hg biomonitoring in fish of the Mediterranean region and risk estimations on fish consumption. *Toxics*, 2, 417–442.

Roesijadi, G. (1992). Metallothioneins in metal regulation and toxicity in aquatic animals. *Aquat. Toxicol.*, 22, 81–114.

Rogers, J. T. Richards, J. G., and Wood, C. M. (2003). Ionoregulatory disruption as the acute toxic mechanism for lead in the rainbow trout (*Oncorhynchus mykiss*). *Aquat. Toxicol.*, 64, 215–234.

Rozon-Ramilo, L. D., Dubé, M. G., Squires, A. J., and Niyogi, S. (2011). Examining waterborne and dietborne routes of exposure and their contribution to biological response patterns in fathead minnow (*Pimephales promelas*). *Aquat. Toxicol.*, 105, 466–481.

Ruelas-Inzuza, J., Soto-Jimenez, M. F., Ruiz-Fernadez, A. C., Ramos-Usuna, M., Mones-Saucedo, J., and Paez-Osuna, F. (2014). 210Po, Cd and Pb distribution and biomagnification in the yellowfin tuna *Thunnus albacores* and skipjack tuna *Katsuwonus pelamis* from the eastern Pacific. *Mar. Pollut. Bull.*, 87, 98–103.

Schmitt, C. J. and Brumbaugh, W. G. (1990). National contaminant biomonitoring program: concentrations of arsenic, cadmium, copper, lead, mercury, selenium and zinc in US Freshwater fish, 1976–1984. *Arch. Environ. Contam. Toxicol.*, 19, 731–747.

Sellami, M., Rebah, F. B., Gargouri, Y., and Miled, N. (2018). Lipid composition and antioxidant activity of liver oils from ray species living in Tunisian coasts. *Arabian J. Chem.*, 11, 233–239.
Sert, E. B., Turkmen, M., and Cetin, M. (2019). Heavy metal accumulation in rosemary leaves and stems exposed to traffic-related pollution near Adana-İskenderun Highway (Hatay, Turkey). *Environ. Monit. Assess.*, 19(1), article no. 553.

Settle, D. M., Patterson, C. C., Turekian, K. K., and Cochran, J. K. (1982). Lead precipitation fluxes at oceanic tropical sites determined from 210Pb measurements. *J. Geophys. Res.*, 87, 1239–1245.

Siebenaller, J. F., Somero, G. N., and Haedrich, L. (1982). Biochemical characteristics of marcourid fishes differing in their depths of distribution. *Biol. Bull.*, 163, 240–249.

Soto-Jimenez, M. F., Hibdon, S. A., Rankin, C. W., Aggarawi, J., Ruiz-Fernandez, A. C., Paez-Osuna, F., and Flegal, R. (2006). Chronicling a century of lead pollution in Mexico: stable lead isotopic composition analyses of dated sediment cores. *Environ. Sci. Technol.*, 40, 764–770.

Sures, B., Dezfuli, B. S., and Krug, H. (2003). The intestinal parasite *Pomphorhynchus laevis* (Acanthocephala) interferes with the uptake and accumulation of lead (210Pb) in its fish host chub (*Leuciscus cephalus*). *Int. J. Parasitol.*, 33, 1617–1622.

Tepe, A. M. and Dogan, G. (2015). Assessment of air pollution in Hatay. In Yipel, M., Kaya, A., and Tekeli, O., editors, *Environmental Problems of Hatay and Solution Suggestions Symposium Proceedings, 28–30 May 2015*, page 19, Turkey. Greater Municipality of Hatay and Mustafa Kemal University.

Thomas, V. M., Socolow, R. H., Fanelli, J. J., and Spiro, T. J. (1999). Effects of reducing lead in gasoline, an analysis of the international experience. *Environ. Sci. Technol.*, 33, 3942–3948.

Tong, S., Baghurst, P. A., Sawyer, M. G., Burns, J., and McMichael, A. J. (1998). Declining blood lead levels and changes in cognitive function during childhood: the Port Pirie cohort study. *JAMA*, 28(22), 1915–1919.

Tufan, B., Koral, S., and Kose, S. (2013). The variations in proximate chemical composition and fatty acid profile in different parts of the thornback ray (Raja clavata) caught from Black Sea, Turkey. *J. Aquat. Food Prod. Technol.*, 22(1), 83–95.

Turkmen, A., Tepe, Y., Turkmen, M., and Mutin, E. (2009). Heavy metal contaminations in tissues of the garfish, *Belone belone* L., 1761, and the bluefish, *Pomatomus saltatrix* L., 1766, from Turkey waters.

*Bull. Environ. Contam. Toxicol.*, 82, 70–74.

UNEP (United Nations Environment Program) (2002). Revision of pollution hot spots in the Mediterranean. MAP (Mediterranean Action Plan), UNEP(DEC)/MED/GEF/198/3, Athens, 29–29 January 2002.

U.S. EPA (2018). Data from the 2014 National Emissions Inventory, Version 2. https://www.epa.gov/air-emissions-inventories/2014-national-emissions-inventory-nei-data. Accessed 2018.

Velusamy, A., Kumar, P. S., Ram, A., and Chinnadurai, S. (2014). Bioaccumulation of heavy metals in commercially important marine fishes from Mumbai Harbor, India. *Mar. Pollut. Bull.*, 81, 218–224.

Véron, A. J., Church, T. M., and Flegal, A. R. (1998). Lead isotopes in the western North Atlantic: transient tracers of pollutant lead inputs. *Environ. Res.*, 78, 104–111.

Viera, C., Morais, S., Ramos, S., Delerue-Matos, C., and Oliveira, M. B. P. P. (2011). Mercury, cadmium, lead and arsenic levels in three pelagic fish species from the Atlantic Ocean: intra- and inter-specific variability and human health risks for consumption. *Food Chem. Toxicol.*, 49, 923–932.

Von Storch, H., Costa-Cabral, M., Hagner, C., Feser, F., Pacyna, J., Pacyna, E., and Kolb, S. (2003). Four decades of gasoline lead emissions and control policies in Europe: a retrospective assessment. *Sci. Total Environ.*, 311, 151–176.

Wang, W.-X. and Rainbow, P. S. (2010). Significance of metallothioneins in metal accumulation kinetics in marine animals. *Comp. Biochem. Physiol. C*, 152, 1–8.

Webb, M. (1979). The metallothioneins. In Webb, M., editor, *Chemical Biochemistry and Biology of Cadmium*, pages 195–266. Elsevier/North Holland Biomedical, New York.

Wu, J. and Boyle, E. A. (1997). Lead in the western North Atlantic ocean: completed response to leaded gasoline phaseout. *Geochim. Cosmochim. Acta*, 61, 3279–3283.

Yilmaz, A. B. (2003). Levels of heavy metals (Fe, Cu, Ni, Cr, Pb, and Zn) in tissue of *Mugil cephalus* and *Trachurus mediterraneus* from İskenderun Bay, Turkey. *Environ. Res.*, 92, 277–281.

Yilmaz, A. B., Sangun, M. K., Yaghoglu, D., and Turan, C. (2010). Metals (major, essential to non-essential) composition of the different tissues of three demer-
sal fish species from Iskenderun Bay, Turkey. *Food Chem.*, 123, 410–415.

Yilmaz, H. K. and Sonmez, H. (2018). Environmental problems and precautions of Iskenderun Gulf in eastern Mediterranean region. *Acta Biol. Turcica*, 31(3), 69–81.

Zhong, B., Wang, X., Mao, H., Wan, Y., Liu, Y., Zhang, T., and Hu, C. (2017). A mechanism underlies fish GRP78 protection against Pb2+ toxicity. *Fish Shell-fish Immunol.*, 66, 185–188.