Human Health Assessment of Sixteen Priority Polycyclic Aromatic Hydrocarbons in Contaminated Soils of Northwestern Algeria

Background. Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental organic contaminants generated by incomplete combustion of organic materials that are widely distributed in soils. Objectives. This study represents the first attempt to examine the health toxicity of 16 detected PAHs in contaminated soil, via different exposure pathways to populations in northwestern Algeria. Methods. The toxicity equivalency quotients (TEQ) of PAHs were evaluated. The carcinogenic risk assessment of incremental lifetime cancer risk (ILCR) from ingestion, inhalation, and dermal exposure pathways to each PAH in soil are described. Results. Incremental lifetime cancer risk values were in the upper limit of the tolerable range (10−6–10−4) for adults and children. The total cancer risk of PAH-contaminated soils for children, adolescents and adults was 2.48×10−5, 2.04×10−5 and 3.12×10−5mg.kg−1d−1, respectively. The highest potential cancer risks were identified for adults and children, with adolescents having the lowest risks. Across exposure pathways, the dermal contact and ingestion pathways had the greatest contributions to the carcinogenic risk of human exposure to PAHs. Conclusions. Further research and guidelines are needed for risk assessments of PAHs in agricultural, residential/urban, and industrial areas, and further risk assessments should include risks posed by exposure through air. Competing Interests. The authors declare no competing financial interests.


Introduction
Polycyclic aromatic hydrocarbons (PAHs) are a class of organic molecules that contain more than two fused aromatic benzene rings. 1 The majority of PAHs present in the environment are due to incomplete combustion and pyrolysis of organic matter. 2,3 Recently, toxicity studies of 16 PAHs listed as priority pollutants by the United States Environmental Protection Agency (USEPA) have received considerable attention. 4-6 These PAHs are of particular interest due to their mutagenic activities as some are classified as probable human carcinogens and others are potentially carcinogenic. 7 Furthermore, benzo[a]pyrene (BaP) has been characterized as having a local and systemic carcinogenic effect, as well as widespread persistence in diverse environmental matrices such as soil, dust, sediments, and water due to its lipophilic and hydrophobic properties. 8 The International Agency for Research on Cancer (IARC) classified benzo(a) pyrene as carcinogenic to humans, along with seven PAHs: Group I, benzo(a)anthracene, dibenzo(a,l) pyrene, and dibenzo(a,h)anthracene as probable carcinogens; and Group II, naphthalene, chrysene, benzo(b) fluoranthene, benzo(j)fluoranthene, benzo(k)fluoranthene and indeno(1,2,3-c,d)pyrene as possible carcinogens. 9 These PAHs have been shown to have toxic effects on human reproductive, developmental, cardiorespiratory, and immune systems. 9 Most of the questions Research about the toxicological effects of PAHs on humans are related to their carcinogenesis, mutagenesis, and endocrine disruption. 10 Furthermore, PAH toxicity may have estrogen and antiestrogen effects, which may influence the risk of breast cancer, stomach cancer, dermatitis, gastroenteritis, and pneumonia. 11,12 The soil system is considered to be a good reservoir of organic contaminants, including PAH compounds, owing to their ubiquity, stability, and longterm enrichment in soils. A high concentration of PAHs has been found in many surface soils around the world, among the numerous environmental matrices (water, dust, soil, plant, and sediments). 13 However, PAH-contaminated surface soil can directly or indirectly expose humans, so it is critical to assess the risk of PAH-contaminated soils to protect human health. 9 Health and cancer risk evaluations focused on various methods of specific exposure criteria and age ranges have been extensively described for populations in various locations around the world, but there are only a few cases of studies recorded for the African community in this context. 10,14-17 It is therefore necessary to assess the potentially harmful effects of PAHs in soils in order to inform future remediation decisions. 18 Polyaromatic hydrocarbons are widespread in the studied area of northwestern Algeria as a result of industrial, commercial and transportation activities, and cereal cultivation. 19,20 This research represents the first evaluation of the cancer risk for three population groups: children (2 to 12 years old), adolescents (13 to 20 years old), and adults (over 20 years old) who were exposed to 16 PAHs through contaminated surface soils via three different exposure pathways: ingestion, inhalation, and dermal contact in northwestern Algeria.

Methods
The population of Algeria's northwestern region is concentrated in five cities (Tlemcen, Sidi Bel Abbes, Ain Temouchent, Mascara, and Oran) (Figure 1), which covers an area of 33 030 km 2  where, BaPeq is a toxic equivalent concentration, Ci is a concentration of PAHi, and TEFi is a toxicity equivalence factor for each PAH.

Risk assessment of polyaromatic hydrocarbon models
In this research, chronic daily intakes (CDIs) associated with PAH exposure in the soil through the three pathways (ingestion, inhalation, and dermal contact) were evaluated by the formulae reported by the USEPA (1991) 25 , following Equation 3-5:

Equation 3
Equation 4 Equation 5 where CDI ingestion is the chronic daily intake related to soil particle ingestion (mg/kg/day). The CDI of PAHs in other mediums was not considered as this study only addresses the PAHs carried by soil dust particles. CS soil is the concentration of PAHs in soil (mg/kg), IRsoil is the ingestion rate of soils (mg/day), EF is the exposure frequency (d. year -1 ), ED denotes exposure duration (years), BW is the bodyweight of the exposed individual (kg), 26,27 LT is a lifetime (WHO 2006), AT is the average time (days) for lifetime exposure of cancer risk (AT=LTx365), CF is a conversion factor (1. 10 -6 kg/mg), CDI inhalation is the chronic daily intake via inhalation of soil particles (mg kg -1 d -1 ), HR is the air inhalation rate (m 3 /d), PEF soil is the soil particle emission factor, CDI dermal contact is the chronic daily intake for dermal contact of soil (mg/kg/d), SA is the skin surface area available for contact soil (cm 2 /day), AF is the relative skin adherence factor for soil (mg/cm -2 ), and ABS is the dermal absorption fraction. The values of all variables are reported in Table 2.

Human health risk assessment
According to the USEPA's Exposure Factor Handbook, 28 the incremental lifetime cancer risk (ILCR) model was used to evaluate the risk to residents exposed to PAHs in soil. The ILCRs for each of the three contact pathways resulting from intake of daily contact products (CDIs) to oral slope factor cancer (CSFs) is shown in Equation 6: ILCR = CDI × Cancer oral slope factor (CSF)

Equation 6
Where CSF is the carcinogenic slope factor (mg/kg/day). CSF ingestion , CSF dermal , and CSF inhalation of BaP were considered to be 7.3, 25, and 3.85 (mg/ kg/day) −1 , respectively, based on the cancer-causing ability of BaP. 29,30 R represents the total risk of cancer resulting from the sum of the ILRC associated with each exposure contact as follows in Equation 7:

Equation 7
Where Cs is the PAH concentration of soil samples (mg/kg), other variables are shown in Table 1, and the cancer risks for children (2 to 12 years), adolescents (13 to 20 years), and adults ( >20 years) were calculated separately.
According to the USEPA and regulatory programs, an ILCR of ≤10 −6 denotes the level of risk considered acceptable or inconsequential, an ILCR of ≥10 −4 is considered a serious risk requiring high priority attention, and an ILCR from < 10 −6 to <10 −4 reflects a potential risk to human health. 28,31-33 A cancer risk (R) value greater than 10 −6 is considered unacceptable according to the USEPA. 34,35

Results
Only benzo(a)pyrene, from of the 16 PAHs considered in the present study, has toxicity data that can be used to  Tables 3-5 and Supplemental Material  Table S2.
In the present assessment of human health exposure to PAH-contaminated soils, the ILCR was chosen to assess and diagnose the potential cancer risk (R) for different age groups via three pathway exposures, based on the CSF and CDI. The results of ILCRs and R values (min, max and mean) for three population groups: children (2-12 years of age), adolescents (13-20 Halfadji et al

Table 2 -Exposure Variables for the Health Risk Assessment for Children, Adolescents and Adults via Ingestion, Inhalation and Dermal Exposure Pathways
Research years of age), and adults (>20 years of age), via different exposure pathways (inhalation, ingestion, and dermal contact) are presented in Tables 3-6.

Discussion
The present study revealed that BaPeq values for 16 PAHs in the study area averaged 280.28 g/kg, which is less than 300 g/kg and much lower than the Canadian Soil Quality Guideline recommendation of TEQ < 600 g/kg. 37 However, the BaPeq levels for surface soils in the study area exceeded the Dutch target value of 33 g. kg -1 . 38 In addition, the TEQ values also reflect the relative carcinogenic potential of all 16 PAHs to BaP in soil samples ( Table 1).

Health risk assessment and contribution of individual polyaromatic hydrocarbons
To date, no environmental guidelines have yet been established in Algeria for PAH-contaminated soils. According to most regulatory programs and guidelines around the world, an ILCR less than or equal to 10 -6 denote a negligible risk, ILCRs of 10 -6 to 10 -4 indicate potential risk, and ILCRs greater than 10 -4 indicate potential high risk. 25,51,52 The chronic daily intakes (CDIs) of the sum of low molecular weight (LMW) ∑ LMW -PAHs (5.39 x 10 -12 -1.53 x 10 -7 mg/kg/d) for all age groups are less than those of high molecular weight In addition, the risks from individual PAH exposure pathways were summarized to determine the key exposure pathway for each PAH compound contaminant surface soil in the study area. The results presented in Tables 3-5 clearly show a large difference between cancer risks for all 16 PAHs detected in soils via the inhalation route with a magnitude of (10 -13~1 0 -10 ), and the dermal contact and ingestion routes with a magnitude of (10 -8~1 0 -6 ) and (10 -9~1 0 -6 ), respectively.
The results indicate that the dermal contact and ingestion pathways greatly contribute to the carcinogenic risk of human exposure to each PAH. Thus, higher dermal exposure contact can be explained by the emission of PAHs during traffic road, industrial and agricultural activities, which can be transferred to the surface of tools and clothing to the skin. 54 In summary, the carcinogenicity of each PAH depends on its chemical structure and physical-chemical properties. The HMW PAHs are more potent carcinogens, and many studies have reported that exposure to HMW PAHs is linked to increased incidences of leukemia, bone, brain, bladder and scrotal cancers, and adverse pregnancy outcomes. 55

Cancer risk
In the present study, the cancer risk (R) of a total of 16 PAHs for children, adolescents, and adults had means Table 6

-Cancer Risk and Corresponding Incremental Lifetime Cancer Risk Across Age Groups via Different Exposure Routes to Contaminated Soil
Research of 2.48 x 10 -5 , 2.04 x 10 -5 , and 3.12 x 10 -5 mg/kg/d, respectively (Table 6). These values are in the unacceptable range (10 -6 ~10 -4 ) an indicate a potential cancer risk to human health. In addition, the results showed that the ILCRs through the ingestion and dermal contact pathways ranged from 10 -7 and 10 -5 in soil samples, while the cancer risk through inhalation was 10 -12 to 10 -9 , about 10 4 to 10 5 times lower than that through ingestion and dermal exposures. As shown in For children and adults, the cancer risk levels via dermal contact were in the same order of magnitude (10 -5 ), showing that both dermal contact and ingestion had a significant contribution to the cancer risk in children and adults. Nevertheless, the risk of ingestion for adolescents (< 10 -6 ) was lower than for children and adults, because children are more likely to be exposed to environmental pollutants and considered the most sensitive group age with frequent hand-to-mouth or object-to-mouth activities which facilitates ingestion of contaminated soils. 56 For adults, a longer exposure time to the indoor/ outdoor environment, greater body weight and greater skin surface area can also lead to a higher potential cancer risk. 57 In the present study, the cancer risk for adults via dermal contact (1.99 x10 -05 ) was higher than for children and adolescents. This result is similar to the human cancer risk resulting from PAH exposure to surface soil in China cities (Beijing, Guangzhou, and Lanzhou), due to the larger dermal exposure with a long exposure period for adults. 34 However, for adults, although the ingestion rate for soil (IRsoil) was relatively small, the longer exposure time may result in increased cancer risk, where can be similar to the risk of soil ingestion for children.
For adolescents, (13 to 20 years), the ILCRs for adolescents were lower due to lower soil ingestion rates and shorter exposure time. As shown in Table 3, the risk of cancer in children exposed to PAHs via dermal contact was significantly higher than that reported for adolescents. Furthermore, the risk of cancer in children from ingestion was equivalent to that of adults but higher than that of adolescents (Table 4).
Based on national and international regulatory agencies' delineated ILCR values, ≤ 10 −6 , 10 −6 to 10 −4 , and >10 −4 correspond to negligible risk, potential risk, and high risk of cancer, respectively. 14, 58 The ILCRs reported in the present study for children, adolescents, and adults due to PAH exposure (  65 Guangzhou, China (adults, 2.08 x 10 -4 -1.13 x 10 -2 ; children, 2.26 x 10 -5 -1.23 x 10 -3 ), 66 and higher than in Kobra, India (adults, 5.6 x 10 -8 ; children, 2.9 x 10 -7 ). 40 The R level for adults in the present study was higher than for children, while adolescents had the lowest risk ( possibly due to fact that IR soil and EF in children and adults were higher than in adolescents.
In addition, the R for children and adults in the study area was greater than the acceptable value of 1 x 10 -6 , indicating that the study area has the potential for human carcinogenic risk. Compared to other studies, the obtained results show that the total R values were in agreement with those reported in contaminated soils from Hong Kong metropolitan soils and urban soil from Nigeria. 59,67 In general, preliminary health assessment results from the study area indicate that PAH-contaminated soils present a cancer risk to the resident population via cumulative ingestion and through dermal contact routes. The R for the three age groups in the present study indicate a potential health risk for adults and children, indicating that special attention should be paid to the health risks of children.

Study limitations
Benarba et al. found a high incidence of liver cancer in the province, the highest in Algeria, suggesting a high prevalence of risk factors. 68 Therefore, evaluation of PAH levels in soil and air, as well as other organic pollutants in specific sites with diverse activities (industrial, urban/residential) is recommended to better understand the potential effects on human health in this area.

Conclusions
The present study represents the first health risk assessment from PAHcontaminated soils in northwestern Algeria. Total cancer risks of 16 PAHs for children, adolescents and adults were 2.48 x 10 -5 , 2.04 x 10 -5 and 3.12 x 10 -5 mg/kg/d. The risk of cancer for adolescents was within the acceptable range, with no potential risk of cancer, but there was a higher risk of moderate to severe cancer in children and adults in the study area. Among different exposure pathways, the observed cancer risks through dermal contact had the highest contribution to total cancer risks in the study area. Further research should focus on risk assessment of PAHs in specific areas as agricultural, residential/urban, and industrial, and should include exposure through air.