Regulatory Toxicology and Pharmacology 104 (2019) 56–58

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Regulatory Toxicology and Pharmacology

journal homepage: www.elsevier.com/locate/yrtph

Evaluation of the efficacy in cosmetic products safety: Comparison with T

biochemical substrates
Yaşar Demira,∗, Meryem Uckayab, Nazan Demirb
a
Ataturk University, Faculty of K.K Education, Department of Chemistry Education, 25200, Erzurum, Turkey
b
Mugla Sitki Kocman University, Faculty of Science, Department of Chemistry, 48000, Kotekli-Mugla, Turkey

A R T I C LE I N FO A B S T R A C T

Keywords: Chemicals used in cosmetics must interact with the enzymes for their consumption after entering our bodies. The
Cosmetic area at which the interaction realizes on the enzyme is known as the active center. This center is three di-
Safety mensional and optically active. Considering the properties of the active regions, it is believed that the de-
HATKO rules termination of the geometric properties of the chemicals may contribute to the safety evaluation of the chemical
Biochemical substrate
products. Obtainment of toxicological data of chemicals is a long and difficult process. It is an impossible process
Enzyme
as the animal experiments have been prohibited. Since there are large number of chemical compounds available,
it is not possible to conduct toxicological evaluation on all of them. Therefore, it is important to estimate
whether chemicals are toxic through using molecular formulas. In this study, the similarities and differences
between the unwanted chemicals used in cosmetic products and the geometric structures of the chemicals used
in metabolism were determined by using Group Theory. The aim of the study is to estimate whether the che-
micals will be toxic by taking advantage of point-group determinations. Molecular formulae of chemicals pro-
hibited in cosmetics and substrates used in biological systems were used as materials. The point groups of the
molecules were determined using these formulas. ChemDraw Professional 17 chemical drawing program was
used to draw the formula structures of the molecules. Campus Licensed version of the program provided by
Atatürk University was utilized. An Excel application which was developed to examine the molecules ac-
cording to the Group Theory was also used.

1. Introduction epidermis, hair system, nails, lips, and external genital organs or with
the teeth and the mucous membranes of the oral cavity with a view
Group theory explains the spectroscopic properties and molecular exclusively or mainly cleaning them, perfuming them changing their
orbitals of the compounds by using the structures of molecules. Group appearance, protecting them, keeping them in good condition or cor-
Theory is used to explain the experimental results rather than revealing recting body odors (Cosmetics Directive, 2009). Cosmetic product
unknown properties. components are any synthetic or natural substance or mixture used in
The catalytic centers of enzymes that catalyze chemical reactions in the structure of cosmetic product other than perfume and aromatic
living systems are three-dimensional. Therefore, molecules with ap- substances (Sağlık Bakanlığı, 2005a). The safety assessment is an as-
propriate geometries may approach to active centers and each enzyme sessment report that must be made on the finished product, considering
has effects on certain functional groups (David L. Nelson, 2013). The the toxicological properties, chemical structure and exposure levels of
chemicals used in cosmetics interact with enzymes after entering our the components of a cosmetic product, the specific exposure char-
body, in order to be used or destroyed. acteristics of the target audience or the area for which the product is to
Reactions catalyzed by enzymes occur in these active centers. The be applied. (Sağlık Bakanlığı, 2005b).
active center is a special region of the enzyme with substrate binding Toxicology is a branch of science that studies the negative effects of
feature. Knowing the geometric characteristics of active centers and chemicals on living organisms. All foreign substances i.e. xenobiotics,
chemicals can contribute to the safety assessment of cosmetics. which are not required for the normal metabolism of the organism ra-
Cosmetic product includes any substance or mixture intended to be ther taken from outside through various ways, are included in the area
placed in contact with the external parts of the human body such as of interest of toxicology. Toxicity is toxic effect of xenobiotics (Vural,

∗
Corresponding author.
E-mail address: yasdemir@atauni.edu.tr (Y. Demir).

https://doi.org/10.1016/j.yrtph.2019.03.001
Received 2 October 2018; Received in revised form 14 February 2019; Accepted 1 March 2019
Available online 08 March 2019
0273-2300/ © 2019 Elsevier Inc. All rights reserved.
Y. Demir, et al. Regulatory Toxicology and Pharmacology 104 (2019) 56–58

Table 1 2.1. Selection of molecules

Quantity and availability percentage of point groups in the prohibited and non-
prohibited chemicals, as analyzed according to Group Theory. In the selection of chemicals that are forbidden to use, the list of
Group Prohibited Non-prohibited substances that should not be included in Cosmetic Products is used. Of
the 1233 chemicals in this list, 621 chemicals which are not polymeric
Count % Count % and inorganic were selected.
In order to make a comparison (non-harmful molecular model), 81
C1 252 40.51 18 21.95
Cs 196 31.51 molecules used in living systems were selected. These molecules are
C∞V 139 22.35 61 74.39 amino acids, carbohydrates (straight chain structures, α- and β-
D∞V 30 4.82 2 2.44 Haworth structures), fatty acids, citric acid cycle molecules, glycolysis
Ci 4 0.64
pathway molecules and compounds used in other metabolic ways.

2.2. Drawing of molecular structures

Table 2
Appearance Frequencies of the determined point groups according
to Group theory (GSx). Molecules selected for analyses were drawn with ChemDraw
Professional 17 program and recorded with JPEG extension. JPEG
Point Group Appearance Prevalence (GSx)
image files were used in the studies conducted according to Group
C1 0.542 Theory.
Cs 0.000
C∞v 3.328 2.3. Rules concerning the examination of molecules
D∞v 0.506
Ci 0.000
While the molecules were analyzed according to Group Theory, a set
of rules known as HATKO rules was used to provide standardization
2005). It determines the amount of toxicity of a chemical entering the (Uçkaya et al., 2016).
living system, that is to say, the main factor determining the toxicity is
the dosage (Borzelleca, 2000). The term LD50 is used as an acute toxi- 2.4. Programs used in the analysis of molecular structures
city unit to indicate how toxic a substance is. NO(A)EL, LO(A)EL, SED,
LC50 and MoS are other toxicity units. 2.4.1. Molecular analysis according to group theory used in excel
The pharmacological effects, toxicities and pharmacokinetic prop- applications
erties of the chemical substances that are synthesized or isolated from The Excel application used in the analysis was developed by
natural sources should be examined in appropriate experimental ani- Yaşar Demir and used to analyze whether there are inversion point,
mals. The basic concept as the basis for these tests and experiments is axes, planes and reflection-rotation points available in the molecules.
that the drug would cause the same effects it caused in the experimental
animals (Büken Ö., 2000). 2.5. Determination of point groups of molecules
According to the eighth article of the Universal Declaration of
Animal Rights, which was promulgated in Paris on 15 October 1978, In defining the point groups, point group determination table in-
conducting experiments causing physical or psychological suffering on cluded in Inorganic Chemistry books is used. (Shriver et al., 1994).
animals are violation(s) of animal rights. This shall apply for any and all
medical, scientific, commercial and etc. experiments. 3. Results and discussion
After 11 March 2013, the sale of any cosmetic and personal care
products tested on animals was prohibited in the European Union. This As a result of the investigations and researches, the point groups of
also applies to products imported from the non-member countries the molecules according to Group Theory were determined separately
(Universal Declaration of Animal Rights, 2016). and the results obtained were discussed.
In our opinion, since these chemicals are forbidden to be tested on
animals, these experiments are carried out on humans, especially on 3.1. Point group analysis
women being the main consumers. Therefore, the development of
toxicological estimation techniques for human and community health A total of 702 molecules were analyzed, 621 of which were pro-
will be very beneficial for public health in the longer term. hibited molecules and 81 of them were not prohibited ones. At the end
Cosmetic products became widespread in 1900s. The conscious use of these studies, the following data have been obtained.
cycle of these products started after the Second World War. The green In a review of this table to see the difference between the groups, it
movement, started in Western Europe in the late 1960s, has led to the is seen that the prohibited molecules are clustered in five different point
tendency of natural origin cosmetics in the cosmetic industry. Due to groups and the non-prohibited molecules are clustered in three dif-
this trend, natural raw materials and finished products were developed. ferent point groups. Cs and Ci groups are seen as groups unique to the
Then, it was seen that natural raw materials or finished products could prohibited molecules. C1, C∞V and D∞V point groups are seen in both
be harmful to human health. Therefore, it was concluded that safety the prohibited and non-prohibited groups.
and efficacy assessment must be performed for all cosmetic products of According to intra-group analysis, the most covalent group of mo-
natural or synthetic origin (Bergişadi et al., 2014; Alğın Yapar and İnal, lecules in the prohibited group is the C1 group while it is C∞V group in
2012; Kaymak and Tırnaksız, 2007). the non-prohibited group.
Cs point groups have never been found in non-prohibited molecules.
This result indicates that there are no intramolecular symmetries of the
2. Materials and methods substrates. Substrate molecules do not have mirror planes. The absence
of the point group Ci indicates that the non-prohibited molecules do not
In this study, 621 molecular formulae which are prohibited to be have symmetry points in the molecule.
used in cosmetic products and 81 formulae of chemical substances used The fact that the C1 point group was present in both clusters in-
in living metabolism have been used. Structures of these formulas are dicates that all the molecules examined have at least one axis of rota-
drawn and point groups are determined according to Group theory. tion.

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Y. Demir, et al. Regulatory Toxicology and Pharmacology 104 (2019) 56–58

The fact that the D∞v element is available in both groups shows that order to determine the point groups.
some of the prohibited and non-prohibited molecules have one main
axis, one horizontal axis and one horizontal plane perpendicular to the Transparency document
main axis.
Other point groups were never seen in both the prohibited and non- Transparency document related to this article can be found online at
prohibited groups. https://doi.org/10.1016/j.yrtph.2019.03.001.
When we compare the presence quantity of these point groups to
each other (Prohibited/Non-Prohibited), we get the Prevalence of References
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micals. In this determination, it made sense to compare the harmful
chemicals with the chemicals (substrates) used in the living systems in

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