Phenols - Sources and
Phenols - Sources and
Phenols - Sources and
3 (2007), 347-362
Review
Phenols – Sources and Toxicity
J. Michałowicz*, W. Duda
University of Łódź, Faculty of Biology and Environment Protection,
Banacha 12/16 str., 90-237 Łódź, Poland
Abstract
Phenols and their derivatives commonly exist in the environment. These compounds are used as the
components of dyes, polymers, drugs and other organic substances. The presence of phenols in the ecosys-
tems is also related with production and degradation of numerous pesticides and the generation of industrial
and municipal sewages. Some phenols are also formed during natural processes. These compounds may be
substituted with chlorine atoms, may be nitrated, methylated or alkylated. Both phenols and catechols are
harmful ecotoxins. Toxic action of these compounds stems from unspecified toxicity related to hydrophob-
ocity and also to the generation of organic radicals and reactive oxygen species. Phenols and catechols re-
veal peroxidative capacity, they are hematotoxic and hepatotoxic, provoke mutagenesis and carcinogenesis
toward humans and other living organisms.
Keywords: phenols, catechol, natural origin of phenols, anthropogenic sources of phenols, toxicity of
phenols
phenols most commonly present in the environment and pork the content of phenol was 7 and 28.6 µg/kg, respec-
human surroundings that reveal toxic influence towards tively [19]. Other authors have found phenol in the outer
living organisms, including human. layer of smoked meat in concentrations of 37-70 mg/kg.
The exposure data are inadequate to determine the degree
of exposure of the general population to phenol. However,
Anthropogenic and Natural Sources of Phenols persons exposed to phenol through inhalation of air from
strongly industrialized areas or with frequent consump-
Phenol tion of smoked food with high phenol content may ac-
cept toxic doses of phenol about 4 mg and 2 mg per day,
Phenol (hydroxybenzene) is a colourless, crystalline respectively. It also has been estimated that 0.3–0.4 mg of
substance of characteristic odour, soluble in water and phenol per cigarette is released during its burning. Expo-
organic solvents. Phenol was one of the first compounds sure to phenol may also be accidental. Delfino and Dube
inscribed into The List of Priority Pollutants by the US described the case of contamination of ground water with
Environmental Protection Agency (US EPA). Phenol is phenol that was then used for drinking purposes. The au-
synthesized on an industrial scale by extraction from coal thors evaluated the daily exposure to be 10-240 mg of
tar as it is formed by transformation of high quantities of phenol per person. The result was statistically significant
cumene present in plants that were used for tar produc- increases of diarrhoea, mouth sores, dark urine and burn-
tion. Phenol is also obtained in a reaction between chlo- ing pain in mouth [20].
robenzene and sodium hydroxide, toluene oxidation and
synthesis from benzene and propylene. It is commonly
used in different branches of industry including chemical Chlorophenols
– production of alkylphenols, cresols, xylenols, phenolic
resins, aniline and other compounds [8], oil, coal process- Chlorophenols are the most widespread and the larg-
ing and metallurgic [9]. Phenol is also used in pesticides, est group of phenols. Chlorophenols are formed in the
explosives, dyes and textiles production [10]. environment by chlorination of mono and polyaromatic
Phenol also penetrates the environment through vehi- compounds present in soil and water. Synthesis of chlo-
cle exhaust, and it is used as a disinfectant and reagent in rophenols proceeds at the participation of chloroperoxi-
chemical analysis. In the United States alone, are 580,000 dases contained in plants and microorganisms in the pres-
people occupationally exposed to phenol influence [9]. ence of hydrogen peroxide and inorganic chlorine [21].
Phenol is also formed as the result of chemical reactions The example is synthesis of chlorinated phenols by fungi
that occurred in the atmosphere in condensed water va- from Hypholoma genera [5, 22]. The concentrations of
pour that forms clouds. Hydroxybenzene is also formed chlorophenols in oceanic waters are of 5-10 ng/L. The
during natural processes like biosynthesis by plants or highest concentrations are noted for river waters and are
decomposition of organic matter [11]. This compound is in the range of 2-2000 µg/L. Chlorophenols are also pres-
also formed from aminoacids contained in plants’ hemi- ent in drinking water due to substitution of organic matter
celluloses under the influence of UV irradiation (sunlight) and low molecular weight compounds (present in puri-
[12] and tyrosine transformation in mammalian (includ- fied water) with chlorine atoms derived from inorganic
ing human) digestive tract [13]. The concentrations of chlorine oxidants. The investigations of drinking water
phenol in surface water are different. In natural waters its of Warsaw and Łódź (Poland) revealed the presence of
amounts are between 0.01 – 2.0 µg/L [14]. Relative fast 2,4,5-trichlorophenol and tetrachlorophenol in concentra-
degradation of phenol causes its concentration in waters tions of 0.2 – 0.3 µg/L [23]. The highest concentrations
exposed to strong anthropogenic pollution may be compa- of phenols are noted in industrial sewages and may reach
rable. Concentration of phenol in surface water of Neth- (for pentachlorophenol) 0.1-10 mg/L. Atmospheric con-
erlands were of 2.6 – 5.6 µg/L. River water polluted with centrations of chlorinated phenols are usually contained
sewage derived from petrol processing plants contained in low concentrations of 0.25 to 7.8 ng/m3; however, in
the concentration of phenol over 40 mg/L [9]. Phenol was urbanized areas of Holland the concentration may reach
also found in domestic water supply in the USA at a level even 1 µg/m3 [24]. The concentrations of chlorophenols in
of 1 µg/L. Background levels of phenol in air are expected soils that are not exposed to anthropogenic pollution are
to be low, at about 1 ng/m3 [15]. In high concentrations rather low. However, Garrett has reported that soil sam-
phenol is determined near factories that impregnate wood ples from the farmer site of pesticide plant in Richmond
and its value reaches 9.7µg/m3 [16]. Phenol is also present (British Columbia) contained 2 mg of TeCP and 0.18 mg
in food. Moderate quantities of this compound (5 µg/kg) of TCP per kg of soil. Soils situated within sawmills are
were determined in honey [17], also in coffee, in which usually heavily contaminated with chlorophenols. Ki-
is formed from ferulic acid. In this process ferulic acid it tunen and co-workers determinated the concentrations
the natural compound present in corn-undergoes conver- of chlorophenols near preserving facilities at 4 different
sion to vinyl-guaiacol, guaiacol and finally to phenol [18]. sawmills in the range of 500 to 3500 µg/kg [25]. Both
Phenol concentration in processed food may reach alarm- tetrachlorophenol and pentachlorophenol were identified
ing concentrations. For example, in grilled sausage and in agricultural products like carrots, potatoes and turnips
Phenols – Sources... 349
to the formation of nitrophenols in the atmosphere. The The highest concentrations of methylphenols are noted in
reaction of phenol, nitrite ions and hydroxyl radical leads waters situated near plants that produce coal tar (creosote)
to the formation of 2-nitrophenol and other nitrated com- – determined concentration of 4-methylphenol in ground
pounds [44]. Nitration of phenols substituted mainly in water exceeded 2 mg/L. There are some reports concern-
ortho and para positions also proceeds at the participation ing atmospheric concentrations of methylated phenols.
of enzymes present in plant tissues. Peroxidases and li- The analysis of air samples obtained from eleven areas of
pooxygenases in the presence of nitric ions and hydrogen California (with different levels of industrial emissions)
peroxide catalyze phenol nitration to form nitrophenols. revealed the range of the concentrations of methylphenols
It is considered that this phenomenon may considerably of 0.07 to 4.6 µg/m3. The median air concentration of cre-
effect the presence of nitrophenols in soil environment sols was 1.58 µg/m3 for 32 source sites in the USA. Rain-
[45]. Nitrophenols in the atmosphere are usually deter- water concentrations for o-cresol were determined at 0.24
mined in low concentrations of some ng/dm3, however to 2.8 µg/L. These results may lead to the conclusion that
strong pollution of air due to industrial emissions lead to methylphenols exist in the air in higher amounts than oth-
increase of nitrophenols concentrations up to 320 ng/dm3 er phenolic compounds. Discussing xenobiotics are also
[46]. In water nitrophenols exist in concentrations that formed due to pesticide degradation. The environmental
seldom exceeded some µg/L. Analysis of the Ebro river transformation of 4-chloro-2-methylphenoxyacetic acid
(Spain) revealed the presence of 2-nitrophenol, 4-nitro- (MCPA) lead to the formation of 2-methylphenol [31].
phenol and 2,4-dinitrophenol in the range of 0.1 – 5.0 Methylphenols are contained in high concentrations (up
µg/L of individual compound. 2-nitrophenol and 4-nitro- to several grams per kilogram) in coal tar used for asphalt
phenol were detected in 177 samples of river waters of production and wood impregnation. The commonness of
Japan. The concentrations were of 0.04 to 10 µg/L. 2-ni- creosote usage is the reason for releasing considerable
trophenol levels in rainwater and snow are between 0.03 concentrations of methylphenols, in particular 4-methyl-
to 5.7 µg/L. Nitrophenols are formed by man during pro- phenol, to the natural environment. The representatives of
duction and degradation of pesticides like 2-buthyl-4,6- methylphenols are cresols that form three isomers – ortho,
dinitrophenol (Dinoseb) and 4,6-dinitro-2-methylphenol meta and para-cresol. Chlorinated and nitrated form of o-
(DNOC). Those compounds are also used as components cresol is used as a compound of herbicide and pesticide
and precursors in polymers and drug production [47], and properties. It is also used for epoxy-resins, dyes and drug
employed as photographic developers and preservatives. production [52]. Both cresols, dimethylphenol and 2,4,6-
Moreover, nitrated phenols are used in dyes, solvents, trimethylphenol are formed during coal and gasoline com-
plastics and explosives production [48] and formed due bustion [53]. The presence of p-cresol is also related to the
to electric, electronic and metallurgic industrial activity production of sewage by the petrochemical industry. The
[19]. Mononitrophenols, 3-methyl-4-nitrophenol and 4- occurrence of m-cresol in the environment is mainly relat-
nitro-3-phenylphenol reach the environment in regards to ed to use this compound in cosmetic, fragrance, disinfec-
vehicular emissions [49]. In the United States exposure tant, explosive and pesticide production [52]. The mixture
to nitrophenols related with exceeded and illegal use of of m-cresol and p-cresol is used in insecticide synthesis.
methylparathion has led to the accumulation of the main The solution of cresols in potassium soap is known as li-
metabolite of this pesticide (4-nitrophenol) in tissues. sole and is used in medicine as it reveals strong disinfect-
The analysis of samples obtained from 16,000 people ing activity. Cresols at concentrations normally found in
revealed the increased concentration of 4-nitrophenol the environment do not pose any significant risk for the
and its concentration was correlated with the amount and general population. However, the potential for adverse
frequency of methylparathion usage in homes [50]. Ex- health effects exists for specific subpopulations living on
posure of the general population to nitrophenol isomers the industrialized regions and under conditions of expo-
is mainly through ambient air and drinking water. A daily sure. For example, significant concentrations of cresols
uptake by inhalation of nitrophenols was calculated to be (0.01 – 0.2 mg/L) have been noted in beverages. More-
of 0.06 µg/kg per body weight. The uptake via drinking over, the incineration of one cigarette leads to inhalation
water for 2- and 4-nitrophenols is calculated to be about of 75 µg of p-cresol.
0.02 µg/kg body weight [51]. Workers are usually ex-
posed to high (toxic) concentrations of nitrophenols via
inhalation and skin contact during production and pro- Alkylphenols
cessing (mainly in the manufacturing of pesticides).
Alkylphenols of low molecular weight commonly exist
in rock-oil and shale oils. The sources of these compounds
Methylphenols in particular substituted in para position are geochemical
processes like methylation, buthylation and alkylation that
Methylphenols commonly exist in the environment, proceed in geological structures [54]. These compounds
often in considerable concentrations. High amounts of 4- are also produced in some technological processes. For
methylphenol – 204 µg/L were noted in Hayashida river example, nonylphenols are derived from nonylphenol
in Tatsuno town (Japan) polluted from industrial effluents. ethoxylates – the surfactants produced for industrial and
Phenols – Sources... 351
urine is the marker of paracetamol and aniline influence to 1.22µg/L [57]. The concentrations of chlorophenols in
of human organism. People of highest occupational expo- soils that are not exposed to anthropogenic pollution are
sure to aniline are workers employed in rubber production rather low. The investigations that concerned the presence
and processing [80]. of chlorophenols in forest soils of Tucholski Landscape
Park (northwest Poland) did not exceed several µg/kg of
soil. Generally, phenols occur in low concentrations in air
Buthylhydroxytoluene and Buthylhydroxyanisole in Poland; however, high concentrations of phenol are re-
lated to urban areas. Ambient air levels of phenol were in-
Buthylhydroxytoluene (BHT) and buthylhydroxyani- vestigated in strongly industrialized and urbanized upper
sole (BHA) are antioxidants that are capable of scaveng- Silesia region of Poland were from 3.8 to 26.6 µg/m3.
ing reactive oxygen species and preventing their forma-
tion [81]. The world production of BHT is about 62,000
tons per year [82]. Both compounds are commonly used Exposure of Population
in food-stuffs given to animals. BHT is commonly used in
gasoline, lubricants, oils, waxes, synthetics, rubber, plas- Occupational exposure to phenols is related to pro-
tics and elastomers as it prevents those materials from ox- duction of phenolic resins that belong to plastic materi-
idation during storage. BHT is also used in edibles – oils, als used in Poland to produce glue, vitreous fibre, dyes
vitamins, cosmetics and fragrances [83]. Sources of BHT and products of common applications. During processing
also include industrial sewages and wastes combustion. (induration) of resins at high temperatures, some phenols
The concentrations of BHT in the environment are usu- (like phenol and m-cresol) are emitted. Exposure of work-
ally low, the analysis of the content of BHT in samples ers to benzene is also related to the influence of phenol
collected from rivers of Germany revealed the concentra- on their organisms as it is formed as the main metabolite
tions of the compounds of 0.02-0.16µg/L. during benzene metabolism. It has been determined that
about 8,000 workers in Poland are chronically exposed
to benzene influence. In regard to the presence of ben-
The Presence of Phenols in Poland and zene in gasoline and vehicle exhausts and also in cigarette
Exposition of the Polish Population to Their fumes exposure of the general population to phenol is
Influence considerable [85]. Exposure to biocyde – o-phenylphenol
mainly concerns health service workers, and in particular
Phenols in the Environment assistant personnel. This compound is also used in disin-
fections of medical equipment and hospital waste. Other
The concentrations of phenols in surface water are examples are trichlorophenol and p-chloro-m-cresol used
different. Investigations in the water of the drainage of as the impregnants of leather and textiles to protect them
the Dzierżązna river (Central Poland) revealed concentra- from microbes [86]. Exposure of the general population in
tions of this compound between 0.01 and 2.0 µg/L [14]. Poland is also related to strongly industrialized areas, for
The investigations of strongly polluted water of the Ner example Silesia, which is characterized by high emissions
river (Central Poland) revealed the concentrations of phe- of toxic compounds, including phenols.
nol only for 1.7 µg/L; however, considerable concentra-
tions of chlorophenols (above 2 µg/L) were determined in
this ecosystem [9]. The concentrations of chlorophenols Noxious Activity of Phenols
in water are related to its pollution. In lakes and rivers
of the Tucholski Landscape Park the total concentrations Toxic influence of organic compounds depends on
of chlorophenols were low and did not exceed 1 µg/L. many factors. Penetration of phenol to organisms is re-
On the other hand, polluted water of the Vistula River lated with diffusion of the compound across a cell’s mem-
contained about 6 µg/L of 2,4-dichlorophenol [84]. The brane. The factor that strongly affects diffusion is hydro-
similar total concentration of chlorophenols (0.1-6.0 µg/ phobocity of the individual compound. The increase of
L) were determined in water of the Gulf of Gdańsk. Chlo- hydrophobocity affects the more effective penetration of
rocatechols in regard to anthropogenic origin more com- a cell’s membrane by phenol and thus enhances the toxic-
monly occur in polluted waters. The analysis of samples ity of xenobiotics. When comparing toxic effects of phe-
of water obtained from the polluted Ner River (Central nols one cannot omit such important parameters as pKa
Poland) revealed considerable amounts of chlorocate- (where Ka is the compound dissociation constant) and log
chols, including very toxic tetrachlorocatechol in concen- P (where P is the octanol-water partition coefficient of the
trations of 2 µg/L. The investigation performed after four undissociated acids). The increase of hydrophobocity and
years revealed that the quality of water of the discussed the value of logP, and the decrease of pKa value result in
river has improved as only trace concentrations of these more effective membrane penetration by xenobiotics and,
compounds were detected. Analysis of samples of water thus, enhance their toxicity [86]. The example is 2.4-chlo-
obtained from the Odra River (Poland) showed inconsid- rophenol which has (in comparision to other phenols) the
erable concentrations of nonylphenol estimated for 0.028 highest value of log P and the lowest pka value.
Phenols – Sources... 353
and buthylhydroxyanisole reveal histopathological ac- xenobiotics. Chromosome aberrations and other structural
tivity. Those compounds cause damage of adrenal gland changes within chromosomes were also induced by pen-
and increase brain and liver weight [81]. The results of tachlorophenol and proceeded even at low concentrations
clinical investigation also describe mass poison with chlo- of PCP [112]. Damage of DNA was provoked by the for-
rophenols. The example is pollution of water and fish in mation of the PCP product – tetrachlorohydroquinone and
reservoir in Jarrela locality in south Finland with a mix- also harmful intermediate form –tetrachlorosemiquinone
ture of 2,4,6-trichlorophenol, 2,3,4,6-tetrachlorophenol radical (TCSQ) that degraded DNA and handicaped the
and pentachlorophenol derived from a wood processing mechanisms responsible for its repair [113].
plant. As the result of poison of about 2000 people – the Mutagenic influence was also exerted by nitrophenols
consummates of water and fish increase morbidity on the and nitrated aminophenols. In the test with the use of Sal-
side of digestive tract. Also, the increase of infections of monella typhimurium mutagenic activity was observed
respiratory system, strong exhaustion, headaches and de- for 2,3-dinitrophenol, 2,5-dinitrophenol, 3,4-dinitrophe-
pression were observed [107]. nol, 2,4,6-trinitrophenol and 2-nitro-5-aminophenol. In
another experiment performed on Salmonella typhimuri-
um and Eschericha coli, mutagenic activity was noted
Mutagenicity for bisphenol F. This compound induced the increase of
frequency of sister chromatyde exchange and decreased
The investigations of hamster fibroblasts revealed mu- the number of micronucleus in human lymphocytes [114].
tagenic activity of phenol. This compound also inhibited 4-aminophenol is capable of interacting with genetic ma-
synthesis and replication of DNA in HeLa cells [108]. terial at the presence of Fe3+ and thus damages DNA con-
Moreover, phenol stopped reparation of DNA in diploid tained in mouse and human lymphocytes. The process
human fibroblasts. Hydroquinone (1.4-dihydroxyphenol) was related with action of free radicals that were formed
induced damages of chromosomes in human lymphocytes, in the reaction of iron ions and hydrogen peroxide [115].
increasing deletion ratio in 7. chromosome, which may Some BHA and BHT metabolites also reveal genotoxic
lead to leukemia development [109]. In another experi- capacity toward DNA. Tert-butylhydroquinone (TBHQ)
ment phenol, catechol and hydroquinone induced morpho- is formed in cells from buthylhydroxyanisole in oxidative
logical changes in cells of hamster embryos. In another demethylation reaction and reveals genotoxic, cytotoxic,
experiment catechol and hyroquinone inhibited rybonu- clastogenic and mutagenic capacities. 2,5-di-tert-buth-
cleotide reductase activity (the enzyme that participates in ylhydroquinone (DTBHQ) is formed from 2,5-di-tert-
DNA synthesis) and thus stopped activation and prolifera- buthylhydroxyanisole (DTBHA), the compound that con-
tion of T lymphocytes. Those compounds also inhibited taminates commercial preparations of BHA. In performed
the proliferation cycle of lymphocytes in G1 phase [110]. experiment both DTBHQ and DTBHA unplaited DNA
Catechol in the presence of NADPH and Cu2+ was able to helix by cleavage of single and double hydrogen bonds.
modify guanine and tymine residues and induce gene mu- TBHQ revealed stronger activity – 92.5% of DNA struc-
tations and chromosome aberrations. Catechol and hydro- ture was damaged. As free radical scavengers like gluta-
quinone damaged chromatides and induced incorrect DNA thione were activated in this process, it was considered
synthesis. The similar changes were provoked by pyrogal- that DNA cleavage was induced by free radicals gener-
lol, which induced the strongest (among hydoxybenzenes) ated by describing metabolites [116]. BHT metabolism is
chromosome aberrations. Pyrogallol and hydroquinone ex- related with hydroxylation of alkyl substitutents, and also
pressed their toxicity by forming a reactive oxygen species with oxidation of aromatic ring. In the experiment some
that included a hydroxy radical that caused deprotonation buthylhydroxyanisole metabolites like 2,6-ditertbuthyl-4-
of the substrates and thus degraded deoxyrybose [111]. It hydroxyl-4-methyl-2 cyclohexadienone (BHT-OOH) and
was also observed that semiquinone and quinone radicals 2,6-ditertbutyl-4-benzoquinone (BHT-quinone) caused
are involved in damage of DNA structure by discussed damage to DNA in the presence of Cu2+ by cleavage of
Fig. 9. Pentachlorophenol (PCP) oxidation yields tetrachlorosemiquinone (TCHQ) radical and tetrachlorohydroquinone (TCHQ) formation.
356 Michałowicz J., Duda W.
hydrogen bounds. These compounds also induced charac- and additionally generated reactive oxygen species [121].
teristics of apoptosis endonucleosomal DNA fragmenta- Occupational exposure of workers to phenoxyherbicides
tion. The mechanism of action of both metabolites was is related to an increase of death incidents. The observed
different: BHT-OOH indirectly damaged genetic material increase of mortality was linked to morbidity on cancer of
and BHT-quinone interacted by the formation of hydro- respiratory system, lymphoma and myocardial ischaema
gen peroxide [117]. [122]. The positive correlation was also noted between
non-Hodgekins lymphoma appearance among children
and documented frequency of using pesticides and their
Carcinogenicity effect on the organism of birth child [123]. The investiga-
tions of 10,000 workers employed in vinyl chloride pro-
Clinical data have shown that people exposed to chlo- duction factories revealed that they suffered from liver and
rophenols influence fall ill with of tumours, sarcoma and lung cancer [124]. Chlorophenols are the main by-prod-
lung cancer. According to literature data the mixture of ucts that are formed during vinyl chloride production. The
chlorophenols or sodium salts of these compounds is exposure of people to chlorophenol influence appears also
probably carcinogenic for animals [35]. An admissible in factories that produce chloroorganic pesticides, mainly
daily dose of individual chlorophenol that may be taken phenolic biocides. The main compound that is formed in
by a man that does not induce carcinogenic changes is this process is pentachlorophenol that was classified by
5µg/kg of body weight for 2-chlorophenol, and 3µg/kg of the U.S. EPA as a probable carcinogen. The workers that
body weight for 2,4-dichlorophenol, 2,4,6-trichlorophe- are employed in pesticides production suffer from non-
nol and pentachlorophenol [118]. Catechol also reveals Hodgekins lymphoma and sarcoma [125]. Carcinogenic
carcinogenic activity. The U.S. Environmental Protec- properties are also characteristic for 4-methylcatechol
tion Agency classified this compound as a carcinogen and 4-methoxyphenol that are responsible for skin can-
and the World Health Organization classified catechol cer and epithelium cancer development. In an experiment
in 2B group as a compound of possible carcinogenicity catechol, 4-methoxyphenol and buthylhydroxyanisole
[35]. Para-cresol was classified as probable carcinogenic individually and particularly in mixture induced papillo-
for human [119] and 2,4-dimethylphenol was considered mas in stomach of rats [126]. Carcinogenic activities of
as the compound responsible for carcinogenic influence catechol were also confirmed in investigations of mice,
[120]. Chronic exposure of skin rats to 2,4-dimethylphe- the compound given in a dose of 85 µg/kg of body weight
nol caused the formation of skin tumours (31% towards in a few weeks caused skin cancer development. In other
control). In the experiment an additional application of investigations 4-nonylphenol in concentrations of 25 and
3% dimethyl-benzanthracene caused the formation of 250 ppm given in food to rats by 28 weeks provoked pro-
skin tumours (50% towards control) and 18% of skin liferation of cancer cells in lungs. In the experiment 8-hy-
cancer. These changes were induced by o-quinones, in droxy-2’-deoksyguanosine as a marker of DNA damage
particular quinones methide that revealed high toxicity was determined [127].
The cancer development in people exposed to phenols and humans. The examples are alkylphenols, bisphenol
is related with microsomal activation of cytochrome P450. A, 2,4-dichlorophenol and pentachlorophenol [131, 132].
The oxidation reactions lead to conversion of some xeno- Those compounds express their activity by binding with
biotics to electrophilic forms that actively interact with a ER receptors. There are some places within a receptor that
cell’s structures. For example, pentachlorophenol activa- may bind not only 17-β-hydroxyl groups of hormones but
tion leads to the formation of tetrachloro-1.4-benzoqui- also hydroxyl residues of phenols as well. Moreover, it is
none and tetrachloro-1,2-benzoquinone by intermediate considered that core of alkylphenols imitates a ring A in
steps with formation of respective semiquinone radicals. E2 estrogens and thus reveal estrogenic activity [133]. In
Formation of the above-mentioned compounds is also re- another experiment bisphenol A caused protein expres-
lated to liver cancer development in mice. The essential is sions in TM4 cells in mice, which play a key role in sper-
that cancer development is also correlated with the level matogenesis. It was noted that viability of cells decreased
(strength) of microsomal activation of cytochrome P450 10 to 70% after exposure to doses of 50-250 µM/kg of
of hepatocytes. Much lower activation of this cytochrome body weight over 16 hours. Obtained results showed that
by PCP in rats does not lead to cancer development in bisphenol A may induce infertility in mice.
spite of the identical pentachlorophenol metabolism in Phenols also modulate the activity of ion channels in the
this species [128]. nervous system. It was noted that simple phenols and in par-
ticular trichlorophenols, trijodophenols and butylphenol may
block ion channels in a micromolar concentrations range.
Other Toxic Influence of Phenols The conclusion of investigation was that phenol and hydro-
phobic residues – alkyl chains or additional phenyl rings sub-
4-octylphenol and 4-nonylphenol induce immuno- stituted in third, fourth and fifth positions are responsible for
toxicity by inhibition of lymphocytes proliferation. The the above-described kind of toxic activity [134].
second compound revealed stronger toxic activity and Some phenols like phenol and p-cresole may be
induced this process even in a concentration of 1 µM/kg formed from non-toxic compounds like tyrosine in di-
of body weight [129]. Administration of 4-nonylphenol gestive tract of mammals, including humans. P-cresol is
to rats in doses of 125-375 mg/kg of body weight caused also a marker of organism exposure to toluene. This com-
changes in the activity of the immunological system. The pound in the presence of hydrogen peroxide caused DNA
mechanism of action was related to modulation of genes adducts formation in HL-60 cells. Researchers revealed
expression that are responsible for mRNA synthesis in ty- that DNA damages were induced by a metabolite of 4-
mocythes. Decrease of mRNA synthesis led to apoptosis methylphenol – quinone methide of p-cresol (PCQM) that
and finally inhibited thymocyte proliferation [130]. also may be used as biomarker of organism exposure to
Phenols also affect the function of the hormonal system. toluene influence [135]. Damages caused by aminophe-
Some phenols are capable of disturbing sexual hormones nols are related to fast oxidation of these compounds in
function, which finally may lead to sterility of animals physiological conditions to benzosemiquinoimines that
358 Michałowicz J., Duda W.
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