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Published in final edited form as: Int J Hyg Environ Health. 2014 Sep 6;218(1):91–98. doi: 10.1016/j.ijheh.2014.08.003

Ratio of cord to maternal serum PCB concentrations in relation to their congener-specific physicochemical properties

Kinga Lancz a, L’ubica Palkovičová a, Henrieta Patayová a, Beata Drobná a, Soňa Wimmerová a, Eva Šovčíková a, Ján Kováč b, Dana Farkašová a, Irva Hertz-Picciotto c, Todd A Jusko d, Tomáš Trnovec a
PMCID: PMC4256144  NIHMSID: NIHMS627127  PMID: 25277764

Abstract

The aim was to characterize placental transfer of some congeners of polychlorinated biphenyls (PCBs) and to relate human in utero exposure to these pollutants to their physicochemical properties. We included into the study 1134 births during the period 2002–2003 from two highly PCB contaminated districts in eastern Slovakia. Concentrations of 15 PCB congeners (IUPAC No. 28, 52, 101, 123+149, 118, 114, 153, 105, 138+163, 167, 156+171, 157, 180, 170, and 189) in umbilical cord (C) and maternal serum (M) were determined. The C/M ratios were significantly related, either positively or inversely depending on parameter, to the logarithm of partition coefficient octanol-water (KOW), to fusion enthalpy at the melting point, molecular weight, water solubility, total surface area of the molecule, solvent accessible surface area, melting point, molar volume, and molecular electronegativity distance vector. We found an inverse association between log KOW and lipid adjusted log C/M (const= 1.078, b1 = −0.179, p < 0.001, R2 = 0.039). Parameters evaluated were interrelated except fusion enthalpy at the melting point and electron affinity vs. solubility. We discuss the possible role of cholesterol as a transplacental transporter of PCBs.

Keywords: polychlorinated biphenyls, placenta, placental transfer, partition coefficient octanol water, physicochemical parameters

Introduction

The sensitivity of developing organism to the effects of environmental pollutants during the prenatal period has been amply documented (Fox et al., 2012; Winneke, 2011; Parent et al., 2011; Gore, 2010; Dickerson et al., 2011; Wigle et al., 2008; Sly and Flack, 2008). Polychlorinated biphenyls (PCBs) (ATSDR, 2000) are members of the group of persistent organic pollutants (POPs) and are important with respect to bioaccumulation in environmental media, persistence in the environment and toxic properties. They have been detected in fetuses (De Koning and Karmaus, 2000; Berg et al., 2010) where they can exert adverse effects (Ulbrich and Stahlmann, 2004; Boucher et al., 2009). To reach the fetus they must cross the placenta. PCBs, as a group, easily pass the placental barrier (Park et al., 2008; Linderholm et al., 2007; Correia Carreira et al., 2011; Bergonzi et al., 2009) by simple diffusion due to their electronegativity, high lipophilicity and moderate molecular weight. However PCBs in the environment are a mixture of congeners, each of which is characterized by its own physicochemical properties and toxicity. The knowledge of rules of transplacental transfer is important for protection of developing organism. The speed and the extent of compound-transfer from the maternal to fetal side depend on the physicochemical and structural characteristics of the chemical as well as the physical characteristics of the maternal–placental–embryonic-fetal unit (Giaginis et al., 2009; Giaginis et al., 2011; Myren et al., 2007). Pollutant properties such as molecular weight, lipid solubility and protein binding could also determine the transfer of pollutants from mother to fetus to a great extent (Myllynen et al., 2009). Kinetics of placental transfer of several POPs in humans have only recently been described (Needham et al., 2011; Suzuki et al., 2005; Tsukimori et al., 2013; Porpora et al., 2013), however we did not find any data on correlation of placental transfer of POPs to their physicochemical parameters. In a recent study on placental transfer of POPs any correlation between the maternal/cord serum concentration ratios and chemical properties of these pollutants such as molecular weight, molar volume, number of halogen substituents or log octanol water partition coefficient (Kow) were found (Vizcaino et al. 2014). A close relationship between the physicochemical properties encoded in the molecular structure and the ability of PCBs to mimic natural hormones may reflect toxic responses they elicit in biological systems (Puri et al., 2003). It is known that of these factors the lipophilicity, mostly expressed as the KOW, drives the kinetics of environmental pollutants in many biological systems (Hawker and Connell, 1988; Isnard and Lambert, 1988; Paasivirta et al., 1999; van Gestel et al., 1985; Woodburn et al., 1987). The aim of our study was to determine how is related the placental transfer of individual PCB congeners to their physicochemical properties. Besides transfer by simple diffusion, closely related to lipid solubility, transport of PCBs by carrier lipids was considered. In this connection we discussed which lipid components of serum may be involved in PCB transport across the placenta.

Materials and methods

We included into the study 1134 births during the period 2002–2003 from two districts (Michalovce and Svidnik) in eastern Slovakia highly contaminated by PCBs (Hertz-Picciotto et al., 2003). The characteristics of infants and mothers participating in the study have been described elsewhere (Hertz-Picciotto et al., 2003; Sonneborn et al., 2008; Sonneborn et al., 2008; Park et al., 2008). All women provided written informed consent, and the study protocol was approved by institutional review boards at the University of California-Davis and the Slovak Medical University, Bratislava. Concentrations of 15 PCB congeners (IUPAC No. 28, 52, 101, 105, 114, 118, 123+149, 138+163, 153, 156+171, 157, 167, 170, 180, and 189) in the umbilical cord and maternal serum were determined using solid phase extraction and high resolution gas chromatography with micro electron capture detection as already described (Conka et al., 2005; Petrík et al., 2006). For quality control, a solvent blank and recovery sample (fortified porcine serum) were analyzed with each batch of 10 human serum samples. Recovery was checked using PCB 174 as internal standard and PCB 103 served as a syringe standard. Certified reference material, Mackerel oil (CRM no. 350, Community bureau of reference, Brussels, Belgium) was used to verify the analytical procedure every 3 months as described earlier (Conka et al., 2005). LODs for individual PCB congeners and samples were evaluated using the ratio of noise/peak height in GC chromatogram and standardized for unit sample amount. We restricted our analyses to serum samples with PCB concentrations ≥ LOD. A useful marker of placental transfer of chemicals is the ratio between concentration in cord serum (C) to that in maternal serum (M) (Abballe et al., 2008; Covaci et al., 2002; Patayová et al., 2013; Vizcaino et al. 2014). C/M ratios were calculated for PCB congeners for which a sufficient number of pairs (>133) were available from samples with concentrations ≥ LOD. We considered this number satisfactory as concentrations of PCBs are strongly intercorrelated in maternal and cord serum (Ayotte et al., 2003).

We report both lipid adjusted and wet weight PCB concentrations. We estimated total serum lipids using the enzymatic summation method (Akins et al., 1989). Serum total cholesterol (TC), nonesterified cholesterol (FC), triglycerides (TG), and phospholipids (PL) were assayed by automated, enzymatic methods and total lipids (TL) were calculated from the expression TL = 1.677 * (TC − FC) + FC + TG + PL. We gathered data on physicochemical parameters of individual PCB congeners from available literature sources. We used linear regression to examine the association between log C/M ratio for PCB congeners and their physicochemical parameters (SPSS 16, Softonic International S.L.).

Results

We present information on the number of analyzed serum samples and number of samples with concentrations ≥ LOD and geometric means of lipid adjusted (ng/g lipid) and wet weight (ng/mL) concentrations of PCB congeners in cord and maternal blood serum in Table 1. It can be seen that at the low end of M values, with PCB congeners 28, 52, 101, and 189, the lipid adjusted C values > M values. On the other hand, at the high end of M values, C values < M values. The difference between the wet weight adjusted concentrations in cord blood and maternal blood serum reflects much lower lipid content in cord serum (median 2.46 g/L) compared to maternal serum (median 10.17 g/L). For PCB congeners 105, 114, 123, and 157 the percentage of samples with concentrations below the detection limit was unacceptably high and therefore these congeners were not considered for statistical treatment. For the remaining PCB congeners the geometric means of lipid and wet weight C and M concentrations, ranked in order of increasing values of M.

Table 1.

Numbers of analyzed serum samples from cord and maternal blood and numbers of serum samples with concentrations of PCB congeners ≥ LOD (limit of detection) and geometric means of concentration of PCB congeners in cord and maternal blood serum.

Mother Cord Mother Cord Mother Cord Mother Cord Mother Cord
PCB congener 28
52
101
105
114
Total number 1053 1063 1094 1065 1101 1078 1101 1076 1101 1079
Number ≥ LOD 409 136 159 133 212 212 207 77 146 47
Concentration ng/g lipids 9.69 9.86 5.23 7.31 6.05 8.71 6.23 5.31 4.36 5.8
Concentration ng/mL 0.1 0.02 0.06 0.02 0.06 0.02 0.06 0.01 0.05 0.01
PCB congener 118
123+149
138+163
153
156+171
Total number 1101 1080 1101 1079 1101 1080 1101 1081 1101 1080
Number ≥ LOD 920 750 154 133 1101 1074 1101 1079 1051 729
Concentration ng/g lipids 12.95 8.65 3.35 4.98 93.84 77.14 146.35 109.95 13.69 6.36
Concentration ng/mL 0.13 0.02 0.03 0.01 0.93 0.19 1.46 0.27 0.14 0.02
PCB congener 157
167
170
180
189
Total number 1101 1080 1101 1080 1101 1080 1101 1080 1101 1080
Number ≥ LOD 208 76 571 194 1099 1066 1101 1079 339 133
Concentration ng/g lipids 3.57 5.25 9.3 6.64 57.29 35.76 134.33 90.09 4.41 4.92
Concentration ng/mL 0.04 0.01 0.1 0.02 0.57 0.09 1.33 0.22 0.05 0.01
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When searching for the physicochemical parameters we have found data on KOW (Hawker and Connell, 1988; Woodburn et al., 1987; De Bruijn and Hermens, 1990; Li et al., 1992; Lü et al., 2007; Mackay et al., 1992), water solubility (Abramowitz and Yalkowsky, 1990; Dunnivant and Elzerman, 1988; Huang and Hong, 2002; Makino, 1998; Yalkowsky and Valvani, 1979; Yalkowsky et al., 1983), total surface area of the molecule (Hawker and Connell, 1988; De Bruijn and Hermens, 1990; Yalkowsky and Valvani, 1979), solvent accessible surface area (Makino, 1998), electron affinity (Makino, 1998), melting point (Abramowitz and Yalkowsky, 1990; Yalkowsky and Valvani, 1979), enthalpy of fusion at the melting point (Puri et al., 2003), molar volume (Yalkowsky and Valvani, 1979; Huang et al., 1993; Liu et al., 2008; Shiu et al., 1986) and molecular electronegativity distance vector (Liu et al., 2008; Qin et al., 2008) (Table 2).

Table 2.

The values of physicochemical parameters of 15 PCB congeners.

PCB congener Log octanol-water partition (Hawker and Connell, 1988) Solubility (Makino, 1998) Molecular weight Total surface area (Hawker and Connell, 1988) Solvent accessible surface area (Makino, 1998) Electron affinity (Makino, 1998) Melting point (Abramowitz and Yalkowsky, 1990) Fusion enthalpy at melting point (Puri et al., 2003) Molar volume (Shiu et al., 1986) Molecular electronegativity distance vector (Qin et al., 2008)
28 5.67 −6.22 257.54 230.83 121.44 −0.703 347 24.3 247.3 4.16
52 5.84 −7 291.99 235.84 130.98 −0.49 329 15.8 268.2 4.62
101 6.38 −7.8 326.43 251.62 139.72 −0.721 340 27 289.1 5.23
105 6.65 −7.52 326.43 259.41 137.6 −0.855 398 20.8 5.13
114 6.65 −7.5 326.43 259.41 137.87 −0.942 392 19.9 4.97
118 6.74 −7.33 326.43 262.04 139.3 −0.922 392 20.4 289.1 5.37
123+149 6.74 −7.42 326.43 262.04 137.6 −0.855 398 26 310 5.25
138+163 6.83 −8.38 360.90 264.76 146.86 −0.747 382 21 310 5.58
153 6.92 −8.49 360.88 267.39 148.61 −0.773 412 19.2 310 5.84
156+171 7.11 −8.64 395.32 273.15 153.14 −0.869 425 310 5.56
157 7.18 −8.25 360.88 275.01 146.79 −0.954 414 29.1 310 5.6
167 7.27 −8.21 360.88 277.64 148.25 −1.009 408 22.5 5.85
170 7.27 −8.9 395.32 277.74 154.41 −0.826 405 23.1 5.72
180 7.36 −9.1 395.32 280.37 155.95 −0.884 372 22.1 6
189 7.71 −8.72 395.32 290.61 156.02 −1.072 431 31.3 6.03
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We found by bivariate regression analysis (Table 3) that C/M values are statistically significantly related to the physicochemical parameters found, except electron affinity. We illustrate the relationship between lipid adjusted log C/M and log KOW in Figure 1 as this parameter is playing a central role in the behavior of many xenobiotics in biological systems (Hawker and Connell, 1988). It shows that the placental transfer of PCB congeners is decreasing with their increasing lipophilicity (const = 1.078, b1 = −0.179, p < 0.001, R2 = 0.039).

Table 3.

Regression analysis between cord/maternal serum PCB concentration ratios (C/M) and physicochemical parameters characteristic for individual PCB congeners. Included were serum samples with concentrations ≥ LOD (limit of detection) of 11 PCB congeners. R2 stands for coefficient of determination and p for statistical significance.

Physicochemical parameters C/M R2 Constant Slope p
Log octanol-water partition coefficient Wet weight 0.032 6.455 −0.126 <0.001
Lipid adjusted 0.014 6.425 −0.010 <0.001
Electron affinity Wet weight 0.026 −0.739 0.030 <0.001
Lipid adjusted 0.014 −0.732 0.003 <0.001
Fusion enthalpy at the melting point Wet weight 0.016 21.012 0.652 <0.001
Lipid adjusted 0.010 21.14 0.066 <0.001
Melting point Wet weight 0.062 371.635 −10.985 <0.001
Lipid adjusted 0.035 369.27 −1.047 <0.001
Total surface area Wet weight 0.032 253.787 −3.673 <0.001
Lipid adjusted 0.014 252.913 −0.305 <0.001
Molecular weight Wet weight 0.019 324.314 −7.361 <0.001
Lipid adjusted 0.007 322.445 −0.549 <0.001
Solubility Wet weight 0.011 −7.599 0.121 <0.001
Lipid adjusted 0.003 −7.566 0.008 <0.001
Molar volume Wet weight 0.019 287.812 −4.466 <0.001
Lipid adjusted 0.007 286.679 −0.333 <0.001
Solvent accessible surface area Wet weight 0.017 138.702 −1.773 <0.001
Lipid adjusted 0.006 138.245 −0.129 <0.001
Molecular electronegativity distance vector Wet weight 0.018 31.71 −0.509 <0.001
Lipid adjusted 0.007 31.594 −0.041 <0.001
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Figure 1.

Figure 1

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Relationship between the logarithm of the ratio of cord/maternal PCB congener lipid adjusted serum concentration (C/M) and log octanol-water partition coefficient (KOW). The numbers in the figure denote PCB congener. The relationship is characterized by slope = −0.179, p < 0.001, R2 = 0.039 and. R2 stands for coefficient of determination and p for significance.

Discussion

In the current study we have shown that the ratio of cord to maternal serum concentration of PCB congeners is inversely related to their lipophilicity expressed as KOW. We expected a positive relationship between these variables in agreement with rules governing passage of lipid soluble xenobiotics through lipid bilayer membranes (Balaz, 2009) and assumptions on placental transfer of lipophilic substances by diffusion (Suzuki et al., 2005; Tsukimori et al., 2013). We confirmed findings that the overall effect of the physicochemical properties on behavior in biological systems is difficult to predict (Needham et al., 2011) and transfer of PCB congeners from maternal to fetal side is more complex than the simple diffusion of the free fraction governed by parameters as molecular weight, pKa, protein binding and lipid solubility (Pacifici and Nottoli, 1995; Audus, 1999). The predictive potency of lipid solubility has already been questioned in human toxicokinetics (Tonnelier et al., 2012). A clue for explaining this controversy may be at least partly in a variety of transporters expressed in the placenta which can facilitate transfer of xenobiotics (Evseenko et al., 2006). Depending on the localization and function, transporters may either increase or decrease xenobiotic transfer towards fetal circulation (Myllynen and Vähäkangas, 2013; Vähäkangas and Myllynen, 2009). Due to structural resemblance of PCBs to thyroxin the most important candidates are transporters of thyroxin. Thyroid hormone can cross placenta and maternal thyroxin is crucial for normal development of fetal brain and other organs. To cross placenta thyroxin uses various transport mechanisms (Patel et al., 2011; Mortimer et al., 2012; Landers et al., 2013a; 2013b; Landers et al., 2009; Feldt-Rasmussen and Rasmussen, 2007; Richard et al., 2012). With regard to other potential transporters we found data on binding of PCBs to albumin (Han et al., 2013; Becker and Gamble, 1982), serum transport proteins-transthyretin and thyroid-binding globulin (Cheek et al., 1991; Marchesini et al., 2008) and plasma lipoproteins and proteins (Borlakoglu et al., 1990; Becker and Gamble, 1982). Fatty acids have been suggested as a transporter for structurally related dioxins and furans (Koppe et al., 1992). Lipid transport is complex, involves a variety of molecules present on the syncytiotrophoblast surface, and requires their coordinated interaction with other intracellular molecules in different placental cellular compartments. Currently, by far, all of the molecules and processes involved in transplacental lipid transfer have not been identified (Desoye et al., 2011; Larqué et al., 2013; Gil-Sánchez et al., 2012; Herrera et al., 2006). We discuss the hypothesis of transplacental transport by lipids carrying PCB molecules by analyzing behavior of concentration of serum lipid components in maternal and infant’s blood in Figure 2 and Table 4. From the lipid components only total cholesterol in cord serum significantly correlated with that in maternal serum (rs=0.045, p<0.001) and can thus be considered as transporter of PCBs.

Figure 2.

Figure 2

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Relationship between concentration (g/L) of main lipid components in cord blood serum and in maternal blood serum.

Table 4.

Descriptive statistics on concentration of main lipid components (g/L) in cord and mother serum.

Total cholesterol g/L Phospholipids g/L Free cholesterol g/L Triglycerides g/L Total lipids g/L
Cord Mother Cord Mother Cord Mother Cord Mother Cord Mother
Number 1075 1066 1075 1067 1075 1067 1075 1067 1065 1065
Mean 0.63 2.61 1.26 3.55 0.23 0.77 0.35 2.83 2.52 10.23
Standard Deviation 0.16 0.53 0.26 0.58 0.07 0.15 0.17 1.01 0.52 1.98
Median 0.62 2.57 1.23 3.54 0.22 0.76 0.31 2.70 2.46 10.17
Minimum 0.02 2.70 0.03 0.15 0.01 0.12 0.05 0.10 0.13 1.75
Maximum 1.61 4.71 2.87 5.72 0.60 1.36 2.02 11.05 5.34 20.17
Geometric Mean 0.62 2.54 1.23 3.49 0.23 0.76 0.32 2.65 2.47 10.03
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The C/M ratio, a marker of placental transfer of PCBs used in this study, suffers from potential disadvantage as inter-individual variations due to endogenous and/or exogenous factors. Indeed in our previous study (Patayová et al., 2013) we have shown that the anthropometric, socioeconomic, and maternal health factors are associated with functioning of the important part of the body system, the placenta. The strong interrelation between the different physicochemical parameters makes difficult the identification of a “primer” association between one of them and the measured outcomes (materno-fetal transfer rate). With this objective we analyzed our data with multiple linear regression. However interrelation between variables precluded to obtain valid results. Extremely high values of the Variance Inflation Factor (how2stats, 2011) confirmed multicollinearity. Lipophilicity determines the behavior of many chemicals in biological systems (Balaz, 2009) and in agreement bioconcentration of PCBs in environmental media is dependent on KOW values (Eisler and Belisle, 1996; Paasivirta et al., 1999; Hawker and Connell, 1985a; 1985b; Noegrohati and Hammers, 2008; Padmanabhan et al., 2006; Hope et al., 1998). The role of KOW in functioning of the blood-brain barrier, one of the most important and sophisticated biological systems, was confirmed in a recently published model relating transfer parameters across it to the physical chemical properties of 70 structurally diverse compounds (Zhang et al., 2010). For placenta a similar general model has not yet been published. Moreover, most modeling efforts have focused on placental drug transfer (Hutson, 2011; Hutson et al., 2011) with less attention to environmental toxins (Needham et al., 2011).

Our main finding that the transfer of PCB congeners across human placenta decreases with increasing KOW contrasts to enhanced passage of substances across the blood-brain barrier (Hou and Xu, 2003; Levin, 1980) with increasing KOW. It has to be noted however, that KOW of substances studied in blood brain barrier transfer were several orders of magnitude smaller than KOWs of PCB congeners evaluated currently.

There is an indication from our data that PCB congeners occurring in serum at low concentrations in a typically environmental PCB congener mixture have a C/M ratio >1 compared to more abundant congeners with a C/M ratio <1. However, the significance of this observation may be questioned due to detection limits in the current study. A similar greater exposure to offspring from lower than from higher doses has been described (Chen et al., 2001) for placental transfer of non-ortho substituted PCB congeners.

Our observation on inverse relationship between transfer of PCB congeners through the human placental barrier and lipophilicity, is in agreement with PCB mother fetus transfer data in marine mammals. In grey seal (Halichoerus grypus) the transfer from inner blubber to maternal serum was selective and strongly depended on the log Kow value of the compounds, with less lipophilic compounds being more efficiently released. These results indicate that compounds with a high log Kow and thus with a high lipophilicity are less easily transferred into the bloodstream (van den Berghe et al., 2012). In southern elephant seals (Mirounga leonina) lactational transfer rates were dependent on the log Kow values of the analytes measured, less lipophilic compounds being more readily transferred to the pups by the lactational route (Miranda Filho et al., 2009). In sea lions the fetus blubber to mother partition ratio of PCBs decreased with increasing KOW (Greig et al., 2007). In common dolphin the percentage of transfer declines inversely with the number of chlorines paralleled by increase of lipophilicity (Borrell and Aguilar, 2005). In a study on arctic beluga whales (Delphinapterus leucas) a single physicochemical parameter, log KOW, largely explained the transplacental transfer for PCBs with congeners having a log KOW <6.5 preferentially transferred to the fetus (Desforges et al., 2012). This parameter has also been examined in Zebrafish (Brachydanio rerio), in which a curvilinear relationship was observed between bioconcentration of PCBs and log KOW based upon data covering the log KOW range 5.06–8.18. Highest bioconcentration resulted at about a log KOW of 7.38, above which the degree of bioconcentration decreased (Fox et al., 1994). The physicochemical background to these events can be found in the diffusion limitation of the exchange between adipose and blood, which steeply decreased as a function of the KOW for the 13 PCBs studied (Levitt, 2010). In agreement with our findings was found a decrease of partition ratio between lipid-based concentrations of PCB congeners in milk and maternal serum in regard to the number of chlorine substitutions of each congener measured (Needham et al., 2011). A similar trend was observed with cord/maternal ratios (Vizcaino et al., 2014).

That PCB congener specific C/M values are related to several physicochemical parameters was expected as many physicochemical parameters of PCB congeners are interrelated (Hawker and Connel, 1988; De Bruijn and Hermens, 1990; Shiu and Mackay, 1986; Patil, 1991; Mackay et al., 1980; Inoue et al., 2006; Miller et al., 1985; Banerjee et al., 1980; Chiou et al., 2005; Opperhuizen et al., 1988; Silla et al., 1992). We confirmed this by pairwise Spearman rank correlation (Table 5) except electron affinity and fusion enthalpy at the melting point which were partly or completely unrelated to other parameters.

Table 5.

Pairwise Spearman rank correlation between physicochemical parameters characterizing 15 PCB congeners. N stands for number, rs for correlation coefficient and p for statistical significance.

Physico-chemical parameters Molecular weight Log octanol- water partition coefficient Solubility Total surface area Solvent accessible surface area Electron affinity Melting point Fusion enthalpy at the melting point Molar volume Molecular electronegativity distance vector
Molecular weight N 15 15 15 15 15 15 15 14 9 15
rs 0.908 −0.962 0.916 0.955 −0.446 0.607 0.284 0.862 0.855
p . <0.001 <0.001 <0.001 <0.001 0.095 0.016 0.326 0.003 <0.001
Log octanol-water partition coefficient N 15 15 15 15 15 15 14 9 15
rs −0.856 0.999 0.909 −0.667 0.683 0.320 0.880 0.956
p . <0.001 <0.001 <0.001 0.007 0.005 0.265 0.002 <0.001
Solubility N 15 15 15 15 15 14 9 15
rs −0.866 −0.951 0.336 −0.522 −0.244 −0.844 −0.839
p . <0.001 <0.001 0.221 0.046 0.401 0.004 <0.001
Total surface area N 15 15 15 15 14 9 15
rs 0.913 −0.652 0.681 0.322 0.880 0.952
p . <0.001 0.008 0.005 0.262 0.002 <0.001
Solvent accessible surface area N 15 15 15 14 9 15
rs −0.463 0.573 0.257 0.780 0.912
p . 0.082 0.026 0.374 0.013 <0.001
Electron affinity N 15 15 14 9 15
rs −0.659 −0.306 −0.633 −0.565
p . 0.008 0.288 0.067 0.028
Melting point N 15 14 9 15
rs 0.326 0.780 0.608
p . 0.255 0.013 0.016
Fusion enthalpy at the melting point N 14 8 14
rs 0.255 0.297
p . 0.542 0.303
Molar volume N 9 9
rs 0.844
p . 0.004
Molecular electronegativity distance vector N 15
rs
p .
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Acknowledgments

This project has been funded by the U.S. National Institutes of Health grants R01-CA96525 and K12-ES019852, the European Commission through the 7FP project OBELIX (No. 227391) and the project “Center of Excellence of Environmental Health”, ITMS No. 26240120033, based on the supporting Operational Research and Development Program financed from the European Regional Development Fund.

Footnotes

The authors declare no competing financial interest.

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