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Author's personal copy
Environment International 37 (2011) 299–301

Contents lists available at ScienceDirect

Environment International
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / e n v i n t

Correspondence: Letter to the Editor
Comment on “Assessment of chemical screening outcomes based
on different partitioning property estimation methods”

In their article, Zhang et al. (2010) investigate several software
prediction methods for equilibrium partition coefficients between
octanol and water (Kow), air and water (Kaw), and octanol and air
(Koa) in the context of regulatory categorization methods for
persistence, bioaccumulation, toxicity, and long range transport
potential of various chemicals.
The authors use a database of 529 compounds selected from two
lists of substances previously identified by Brown and Wania (2008)
and Howard and Muir (2010). Our review of the Supplementary
materials in Zhang et al. (2010) shows that 18 compounds are
duplicate pair structures (given as the following CAS numbers):
2276906 and 13087531; 117964 and 131497 (diatrizoic acid);
20566352 and 77098078 (1,2-benzenedicarboxylic acid, 3,4,5,6tetrabromo-, 2-(2-hydroxyethoxy)ethyl 2-hydroxypropyl ester);
88722 and 1321126 (1-methyl-2-nitrobenzene); 58899 and 319846
(1,2,3,4,5,6-hexachlorocyclohexane); 2176627 and 68412408
(pentachloropyridine); 335671 and 72968388 (octanoic acid,
pentadecafluoro- [n-PFOA]); 68140181 and 68140192; and 678397
and 68391082 (1-decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10heptadecafluoro- [8:2-fluorotelomer alcohol]). One of each of these
pairs should be removed from the database. As we noted in our
previous comparative assessment of various Kow prediction methods
for compounds on the Canadian Domestic Substances List (DSL)
(Rayne and Forest, 2009), and our investigation into the potential for
corresponding false positives/negatives that are dependent on the
software employed in regulatory screening frameworks, such databases contain substantial numbers of structural errors and duplication, necessitating rigorous screening.
The database in Zhang et al. (2010) contains the following five acid
halides: CAS 98099 (benzenesulfonyl chloride); 98599 (p-toluenesulfonyl chloride); 719324; 69116730; and 52314677. Acid halides
are extremely reactive toward abiotic hydrolysis, giving the
corresponding parent acids in rapid and quantitative yields. Their
sensitivity towards atmospheric moisture is also well established
from work in synthetic organic chemistry. For example, the
International Programme on Chemical Safety (IPCS) Screening
Information Dataset (SIDS) document for p-toluenesulfonyl chloride
(CAS 98599) states that “[d]ue to the rapid hydrolysis [∼ 2 min at
pH 7] of 4-methylbenzenesulfonyl chloride, water solubility and
partition coefficient n-octanol/water cannot be measured.” (http://
www.inchem.org/documents/sids/sids/98599.pdf).
As we read the Supplementary materials in Zhang et al. (2010),
EPI Suite, SPARC, and ABSOLV flagged this compound as having long
range transport potential, and EPI Suite and COSMOtherm flagged it
as having bioaccumulation potential in the terrestrial environment.
It appears problematic that a regulatory screening system examines
compounds for persistency, bioaccumulation, and transport in the
environment using computationally generated properties when the
literature clearly indicates the compounds are so reactive that the
0160-4120/$ – see front matter © 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.envint.2010.06.005

corresponding experimental properties cannot be measured. Work
by Berti et al. (2006) on the rapid hydrolysis of terephthaloyl
chloride (TCl) and isophthaloyl chloride (ICl) should be used as a
regulatory screening context applied to all acid halides, where these
authors found that “TCl, ICl, and their respective half-acids will not
be persistent in aqueous systems for a time sufficient to have a
sustained toxicological effect on aquatic organisms (less than 1 h).
Performing additional aquatic toxicity studies, biodegradation
studies, and potentially mammalian studies on TCl and ICl are
unnecessary.”
The database in Zhang et al. (2010) also contains a number of
carboxylic acid esters. Compounds with this functional group are
expected to be susceptible to abiotic hydrolysis in environmental
systems and in vivo, severely restricting their potential for persistence, bioaccumulation, and/or long range transport potential. In
Table 1, we provide the SPARC (September 2009 release w4.5.1529s4.5.1529; http://ibmlc2.chem.uga.edu/sparc/) estimated hydrolytic
half-lives (t1/2,hyd) at 25 °C and pH 7 for 55 esters from the Zhang et al.
(2010) database. In addition to the in-house SPARC hydrolysis module
validation efforts (Hilal et al., 2003), we have also shown this module
to yield reasonably accurate t1/2,hyd for carboxylic acid esters and
carbonate esters having corresponding reliable experimental data
(Rayne et al., 2010a, 2010b).
A wide range of t1/2,hyd, from 5 min to more than a century, are
predicted by SPARC for these carboxylic acid esters. This variability is
not unexpected given the known structure-reactivity sensitivity of
these compounds to hydrolysis. However, a number of these
compounds are expected to hydrolyze fairly readily, on the order of
several days to less than a year. In addition, under more basic (i.e.,
marine systems) or acidic (i.e., precipitation and freshwaters near
populated areas, as well as regions of the gastrointestinal tract)
conditions, and in vivo with temperatures up to ∼39 °C, many of these
half-lives will be reduced significantly below the values given in
Table 1. As such, any carboxylic acid esters expected to hydrolyze
rapidly should potentially be excluded from lists investigating their
persistence, bioaccumulation, and/or long range transport potential.
Their hydrolysis products, where appropriate, however, may be of
regulatory concern.
Peroxides are included in this database (CAS 3457612, 2167239,
78637, and 25155253), even though they also hydrolyze very
readily (as would the peroxy esters; CAS 94360, 614459,
130097368, 133142, and 26748414). For example, the IPCS-SIDS
document for benzoyl peroxide (CAS 94360) notes that this
compound hydrolyzes in 5 h at pH 7 and 25 °C, and “the substance
is not bioaccumulated because of the rapid removal by hydrolysis …
and biodegradation.” (http://www.inchem.org/documents/sids/
sids/BENZOYLPER.pdf) We note that the four peroxy acids in the
database (CAS 3457612, 2167239, 78637, and 25155253) are
incorrectly classified by functional group; they are all peroxides
(R–O–O–R) rather than peroxy acids (R–O–O–H; which have acidic
O–H moieties). Isocyanates (CAS 329011, 104121, 102363,
34893920, and 4083641) are also reactive toward abiotic hydrolysis, as are epoxides (CAS 75150139 and 30171803), anhydrides

Author's personal copy
300

Correspondence: Letter to the Editor

Table 1
SPARC estimated acid-catalyzed (kA), neutral (kN), and base-catalyzed (kB) hydrolysis
rate constants at 25 °C in pure water for various carboxylic acid esters listed in the
database of Zhang et al. (2010).
CAS

log kA
(L mol− 1 s− 1)

log kN
(L mol− 1 s− 1)

log kB
(L mol− 1 s− 1)

t1/2,hyd
(pH 7)

120616
93583
51282496
99752
93890
84662
636533
840653
102090
136607
88415
64667330
1539044
20566352

− 6.40
− 6.38
− 7.03
− 6.51
− 6.55
− 7.01
− 6.57
− 6.40
− 5.03
− 6.61
− 4.68
− 6.69
− 6.88
− 8.00
− 7.94
− 4.28
− 4.96
− 7.82
− 7.83
− 7.59
− 8.88
− 6.36
− 7.50
− 7.43
− 8.23
− 4.83
− 5.01
− 6.94
− 6.98
− 7.46
− 7.09
− 7.57
− 7.56
− 7.56
− 7.77
− 5.80
− 6.84
− 4.51
− 7.21
− 6.17
− 7.22
− 7.22
− 7.22
− 7.22
− 6.11
− 6.11
− 6.11
− 6.12
− 6.67
− 7.35
− 7.43
− 7.44
− 7.44
− 7.44
− 6.33
− 6.34
− 6.71
− 5.82

− 14.00
− 13.75
− 11.55
− 13.66
− 14.03
− 13.33
− 13.78
− 14.46
− 16.51
− 13.99
− 12.65
− 11.97
− 11.50
− 10.91
− 11.08
− 8.90
− 6.20
− 10.92
− 10.71
− 14.18
− 11.30
− 10.61
− 12.09
− 12.11
− 11.93
− 10.46
− 10.85
− 12.05
− 12.07
− 11.18
− 14.65
− 14.14
− 14.16
− 14.16
− 13.92
− 8.96
− 9.40
− 10.71
− 13.53
− 13.33
− 13.53
− 13.53
− 13.53
− 13.53
− 12.85
− 12.85
− 12.85
− 12.85
− 13.08
− 13.56
− 13.59
− 13.59
− 13.59
− 13.59
− 12.91
− 12.91
− 13.06
− 5.81

− 1.55
− 1.63
− 0.04
− 2.09
− 1.78
− 1.55
− 1.55
− 1.67
1.26
− 1.83
− 1.54
− 2.93
− 0.43
0.12
− 0.01
0.47
2.12
− 0.32
− 0.23
− 2.74
− 1.28
− 1.52
− 0.72
− 0.57
− 1.23
0.10
− 0.05
− 3.03
− 3.08
− 0.25
− 2.11
− 2.55
− 2.52
− 2.55
− 2.14
0.39
− 0.56
− 0.93
− 1.87
− 0.81
− 1.88
− 1.88
− 1.88
− 1.88
− 0.66
− 0.66
− 0.66
− 0.66
− 1.17
− 2.05
− 2.11
− 2.12
− 2.12
− 2.12
− 0.90
− 0.90
− 1.24
4.31

7.8 y
9.5 y
88 d
27 y
13 y
7.8 y
7.7 y
10 y
4.4 d
15 y
7.5 y
125 y
215 d
61 d
81 d
22 d
4.0 h
165 d
134 d
120 y
4.0 y
5.0 y
1.1 y
298 d
3.7 y
63 d
90 d
155 y
169 y
142 d
29 y
77 y
72 y
77 y
30 y
26 d
161 d
1.7 y
16 y
1.4 y
17 y
17 y
17 y
17 y
364 d
364 d
364 d
370 d
3.2 y
24 y
29 y
29 y
29 y
29 y
1.7 y
1.8 y
3.8 y
5 min

50594779
50594440
6928672
24261196
70516415
34832887
1869778
68954018

60825265
60825276
55794202
67567231
65208346
1176745
15086949
12227780
15905325
13473262
1770805
4827558
61898951
17527296
7347195
27905459
17741605
34395249
34362497
67584558
67584569
67584570
68084628
383073
1799844
2144538
1996889
2144549
6014751
67584592
14650249
376147
75147205

aa
b

a
b
c

a
Lowercase letters for a particular CAS # designate different potential hydrolysis
pathways from multiple carboxylic acid ester functionalities in the parent compound.

(89327 and 19438610), some benzyl halides (CAS 5848931, 611198,
98873, 104836, 589151, 88664, 98077, 5216251, 68360, 73588428,
1929824, 69045789, 1817136, 69045836, 1201305, and 1134049),
and some phosphate (CAS 13674878, 125997208, 13674845,
76649155, 6145739, 25550985, 126636, 57583547, 78331,
68937406, and 68400793) and nitrate (CAS 3032551 and 78115)
esters.

Of concern regarding the Kow/Kaw classification schemes developed by these authors (and others) is the presence of acidic/basic
moieties in their databases with pKa values near the range of pH
values for precipitation, freshwater, and marine systems and in vivo
(i.e., composite range of ∼ 1 [gastrointestinal tract] to N8 [oceans]).
For example, the database in Zhang et al. (2010) contains carboxylic
acids (e.g., CAS 76051, 96991, 52270447, 375224, 3438162, 98737,
85563, 63734623, 72623779, and 335671), phosphoric acids (CAS
68412680), and sulfonic acids (CAS 1763231) under “neutral
organics”, even though these compounds have pKa values generally
b4 (∼ 0 for perfluoroalkyl carboxylic acids and bb0 for sulfonic
acids), and will be dominantly dissociated in most environmental and biological compartments. Similarly, phenols and thiols
with electron withdrawing groups (of which a number are in the
database; see, e.g., CAS 133493 [pKa,SPARC ∼ 1.9], 608719 [pKa,SPARC ∼
4.5], 88857 [pKa,SPARC ∼ 5.5], 15086949 [pKa,SPARC ∼ 5.7]) will be
substantially, dominantly, or effectively entirely dissociated under
ambient pH values. Primary and secondary imides (e.g., CAS 108805
[pKa,SPARC ∼ 7.0]) are also sufficiently acidic to warrant more
detailed examination.
For acids and bases with pKa values that give rise to partial or
substantial ionization at the pH of environmental and in vivo systems
under consideration, the octanol–water distribution coefficient
(log Dow) is the relevant partitioning parameter, not the traditional
octanol–water partition coefficient for the unionized molecular form
(log Kow, or log P). In many cases, the log Dow (which is pH
dependent) can vary substantially from the log Kow depending on the
size of the molecule and steric/electronic shielding of the acid/base
functionality. SPARC can estimate log Dow, EPI Suite cannot, and we
are unsure regarding the capabilities of COSMOtherm and ABSOLV.
Zhang et al. (2010) appear to have reported molecular form log Kow
values for all potential acids and bases in their list, which is not the
relevant physical property. In Fig. 1(a,b), we provide SPARC estimated
log Dow as a function of pH for 14 representative acids in the Zhang et
al. (2010) database. The difference between the molecular form log
Dow and the fully deprotonated log Dow ranges up to N7 units for some
compounds, and the difference between the molecular form log Dow
and the log Dow of the composite speciation present at pH 7 can range
up to 4 units. In several cases, compounds predicted to be significantly
lipophilic under strongly acidic conditions are predicted to be
significantly hydrophilic at near-neutral pH values, resulting in
potential regulatory misclassification if the molecular form log Kow
values are used.
Similarly, effective Kaw values are pH dependent for acids and
bases. Many software programs calculate the Kaw for the neutral
(unionized) form of a molecule, which is much more volatile than
the ionized form(s) (which are often approximated as nonvolatile in
many environmental modeling efforts). SPARC can estimate effective Kaw values as a function of pH by coupling its Kaw estimation
module for the unionized form with its pKa prediction module, and
likely assuming a Kaw of zero for any ionized forms. However, Zhang
et al. (2010) appear to report only Kaw for the unionized forms using
all software methods. Using the 14 representative acids discussed
above from Zhang et al. (2010), the SPARC estimated log Kaw as a
function of pH are given in Fig. 1(c,d). Differences in Kaw of up to 14
orders of magnitude are estimated between the molecular forms
and their fully deprotonated analogs, with corresponding Kaw
differences ranging up to nearly 7 orders of magnitude between
the speciation expected under strongly acidic conditions and that
present at near-neutral pH values. Consequently, all compounds
with possible acidic/basic functionalities in the database of Zhang et
al. (2010) must have octanol–water and air–water partitioning
frameworks constructed on their effective Dow/Kaw, respectively, at
the pH of interest, not their Kow/Kaw for the purely unionized form
which may not form any significant contribution in environmental
and biological systems.

Author's personal copy
Correspondence: Letter to the Editor

301

Fig. 1. SPARC estimated octanol–water distribution coefficients (log Dow) (a,b) and air-water partitioning coefficients (log Kaw) (c,d) as functions of pH for 14 representative acids
from Zhang et al. (2010).

References
Berti WR, Wolstenholme BW, Kozlowski JJ, Sobocinski RL, Freerksen RW. Hydrolytic
stability of terephthaloyl chloride and isophthaloyl chloride. Environ Sci Technol
2006;40:6330–5.
Brown TN, Wania F. Screening chemicals for the potential to the persistent organic
pollutants: a case study of Arctic contaminants. Environ Sci Technol 2008;42:
5202–9.
Hilal SH, Karickhoff SW, Carreira LA, Shrestha BP. Estimation of carboxylic ester
hydrolysis rate constants. QSAR Comb Sci 2003;22:917–25.
Howard PH, Muir DCG. Identifying new persistent and bioaccumulative organics among
chemicals in commerce. Environ Sci Technol 2010;44:2277–85.
Rayne S, Forest K. Performance of the ALOGPS 2.1 program for octanol–water partition
coefficient prediction with organic chemicals on the Canadian Domestic Substances
List. Nat Prec 2009. doi:10.1038/npre.2009.3882.1.
Rayne S, Forest K. Modeling the hydrolysis of perfluorinated compounds containing
carboxylic and phosphoric acid ester functions and sulfonamide groups. J Env Sci
Health A 2010a;45:432–46.
Rayne S, Forest K. Modeling the hydrolysis of the polymeric brominated flame
retardants BC-58 and FR-1025. Nat Prec 2010b. doi:10.1038/npre.2010.4160.1.

Zhang X, Brown TN, Wania F, Heimstad ES, Goss KU. Assessment of chemical screening
outcomes based on different partitioning property estimation methods. Environ Int
2010. doi:10.1016/j.envint.2010.03.010.

Sierra Rayne⁎
Ecologica Research, Penticton, British Columbia, Canada
⁎Corresponding author. Ecologica Research, 412-3311 Wilson Street,
Penticton, British Columbia, Canada V2A 8J3. Tel.: +1 250 487 0166.
E-mail address: rayne.sierra@gmail.com (S. Rayne).
Kaya Forest
Department of Chemistry, Okanagan College, Penticton,
British Columbia, Canada
11 May 2010


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