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Journal of Hazardous Materials 433 (2022) 128806

Contents lists available at ScienceDirect

Journal of Hazardous Materials


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

Research Paper

A mechanistic approach for toxicity and risk assessment of heavy metals,


hydroquinone and microorganisms in cosmetic creams
Muhammad Irfan a, Amir Shafeeq b, Umair Siddiq b, Farzana Bashir a, Tausif Ahmad c,
Muhammad Athar d, Muhammad Tahir Butt a, Sami Ullah e, Ahmad Mukhtar f,
Mohamed Hussien e, Su Shiung Lam g, h, *
a
Centre for Environmental Protection Studies, Pakistan Council of Scientific and Industrial Research (PCSIR), Laboratories Complex, Ferozepur Road, Lahore, Pakistan
b
Institute of Chemical Engineering and Technology, University of the Punjab, Lahore, Pakistan
c
Department of Chemical Engineering, Khwaja Fareed University of Engineering and Information Technology (KFUEIT), Abu Dhabi Road, Rahim Yar Khan 64200,
Pakistan
d
Department of Chemical Engineering, Muhammad Nawaz Sharif University of Engineering and Technology, BCG Chowk, Multan 60000, Pakistan
e
Department of Chemistry, College of Science, King Khalid University, Abha 61413, Saudi Arabia
f
Department of Chemical Engineering, NFC Institute of Engineering and Fertilizer Research, Faisalabad 38000, Pakistan
g
Pyrolysis Technology Research Group, Higher Institution Centre of Excellence (HICoE), Institute of Tropical Aquaculture and Fisheries (AKUATROP), Universiti
Malaysia Terengganu, 21030 Kuala Nerus, Terengganu, Malaysia
h
Henan Province Engineering Research Center for Biomass Value-added Products, School of Forestry, Henan Agricultural University, Zhengzhou 450002, China

H I G H L I G H T S G R A P H I C A L A B S T R A C T

• Comparative profiling of metals is


examined for local and imported fair­
ness creams.
• Quantitative analysis Cd, Cr, Ni, Pb, Zn
and Hg is performed.
• Zn and Hg were found the highest con­
centration at 138.06 mg/kg and 141
mg/kg.
• A significant presence of hydroquinone
is detected in the range of 0.12–7.2%.
• 44% of samples surpass 100 cfu/g, MoS,
HQ, HI tolerance limits by European
Union.

A R T I C L E I N F O A B S T R A C T

Editor: Dr. Rinklebe Jörg The demand and importance of fairness creams as a major cosmetic have increased significantly in recent years.
However, some of these cosmetics contain heavy metals, hydroquinone and microorganism that can cause
Keywords: various health problems. Therefore, the aim of this study is to determine and examine the concentration of metals
Facial cosmetics (i.e. Cd, Pb, Cr, Ni, Zn, Hg), hydroquinone and microorganisms in nine different fairness creams produced by
Heavy metals
local and international brands. The health risk assessment of the tested substances for consumers was accessed
Hydroquinone
through systemic exposure dosage (SED), margin of safety (MoS), lifetime cancer risk (LCR), hazard quotient
Microbiology
Toxicology (HQ) and hazard index (HI). The concentration of Zn and Hg were found the highest and measured in the range
Human health of 17.82–138.06 mg.kg− 1 and 2.3–141 mg.kg− 1, respectively. The concentrations of other metals were deter­
Risk assessment mined as 0.06–0.67 mg.kg− 1 of Cd, 0.43–1.55 mg.kg− 1 of Cr, 0.14–1.43 mg.kg− 1 of Ni and 0.3–1.34 mg.kg− 1 of

* Corresponding author at: Henan Province Engineering Research Center for Biomass Value-added Products, School of Forestry, Henan Agricultural University,
Zhengzhou 450002, China.
E-mail address: lam@umt.edu.my (S.S. Lam).

https://doi.org/10.1016/j.jhazmat.2022.128806
Received 6 February 2022; Received in revised form 13 March 2022; Accepted 25 March 2022
Available online 29 March 2022
0304-3894/© 2022 Elsevier B.V. All rights reserved.
M. Irfan et al. Journal of Hazardous Materials 433 (2022) 128806

Pb. HPLC results showed a significant presence of hydroquinone in the range of 0.12–7.2%. The total viable
counts of cosmetic samples showed the substantial presence of microorganisms, and 44% of the collected samples
surpassed the permissible limit of 100 cfu/g recommended by European Union. Many of the collected samples
exceeded the MoS, HQ and HI tolerance limits. However, the LCR value in all samples was significantly higher
than the acceptable limit. Therefore, it is advised to avoid overuse of these products in order to ensure human
safety and reduce the risks to skin health.

1. Introduction ability in skin creams. It is also called quinol due to the presence of
hydroxyl groups formed from the reduction of benzoquinone. This skin
Cosmetics is a generic term used for foundations, fairness creams, tone altering agent is notorious for its hepatotoxic and carcinogenic
lotions, sunscreens, lip glosses, eye shadows, emulsions, concealers, nature (Owolabi et al., 2020). Hydroquinone is added in fairness creams
soaps, blushes, lipsticks, deodorants, perfumes, and many other prod­ to suppress melanin formation and treat melisma. However, its use in
ucts. These products are used all over the world and their effectiveness fairness creams was rather controversial a few years ago due to its
for beautification and personal care cannot be repudiated. Moreover, the ambiguous efficacy as a safe ingredient. In recent years, the toxic effects
use of these beauty products has become increasingly popular with the of hydroquinone have been reviewed and it has been found that these
advancement of technology, fashion trends and the glamorous lifestyle compounds are extremely toxic to both the environment and humans,
of people. The global cosmetics industry was worth $532.43 and $675 even at very low concentrations (Tashkhourian et al., 2016). Continued
billion in 2017 and 2020 respectively and is expected to exceed $805.61 use of these products has been reported to lead to adverse effects,
billion in 2023 (Hall and de Sousa, 2019; Li et al., 2019). It is also including irritation, dermatitis, melanin destruction and ochronosis
attention-grabbing that since the inception of cosmetics industry, the (Chisvert et al., 2010; Moldovan et al., 2017).
demand for personal care products has been growing constantly and One of another possible risks associated with the use of cosmetics is
steadily and is developing even in an unstable economy. Therefore, the the presence of microorganisms. The presence of microorganisms could
global cosmetic products market is showing an average growth of about cause organoleptic alterations such as offensive and unpleasant odors
5% per year (Kazakova et al., 2021). Cosmetics manufacturers actively and changes in viscosity and color of the product and can also cause
encourage consumers to buy their products through electronic and print serious damage to the health of consumers due to the production of
media. As a result, consumers especially women are spending a lot of endotoxins or harmful metabolites. Although cosmetic creams are not
money on personal care products and supporting the development of the projected to be sterile, they should be free of infectious microbial
industry. According to a study, a lady could spend about 4% of house­ pathogens. The number of microorganisms per gram should be as low as
hold spending on cosmetic products (Khan et al., 2021). In recent years, possible. The presence of microorganisms in facial creams, regardless of
the use of fairness cream has increased considerably as they reduce the whether they are introduced during manufacturing process or passed on
melanin content to lighten the skin and increase a person’s complexion. to the product by the end user, can be detrimental to health. When the
It has been reported that more than 59% of women believe that lighter number of microorganisms exceeds the limit set by health organizations,
skin tones look prettier and fairness creams are more effective in their use can cause serious infections and health problems, such as those
achieving this goal (Khan et al., 2021; Majeed et al., 2021). associated with the skin comprising acne, scabies, dyschromia, and
Thousands of ingredients are used to make cosmetic products. eczema. The presence of microorganisms in cosmetic products such as
However, the common ingredients in cosmetics are preservatives, anti­ Clostridium tetani has been reported to have resulted in the death of four
oxidants, waxes, hydroquinone, moisturizers, colors and heavy metals babies in New Zealand (Behravan and Malaekeh P, 2005).
(Munir et al., 2020; Agorku et al., 2016). Some of these ingredients can Heavy Metals and hydroquinone are often present in whitening
be harmful and cause serious health problems if added in excess of the creams and their increased exposure to human body can lead to health
safe limits. In particular, flavors and preservatives are considered al­ problems, including neurotoxicity, carcinogenic health effects, oxidative
lergens despite being an essential part of cosmetics (Sharmeen et al., stress, skin allergies, and skin ulcer (Li et al., 2021; Ho et al., 2017;
2021). Metal composites are also deliberately used in cosmetics because Ghaderpoori et al., 2020). In addition, many studies measured only the
of their ability to cleanse and whiten the skin. For example, blends metal content of cosmetic products (Ababneh and Al-Momani, 2018;
containing lead carbonate and mercury chloride are used to whiten and Balarastaghi et al., 2018) while very little attention has been paid to the
cleanse the skin (Ababneh and Al-Momani, 2018). However, the use of dosage of systemic exposure and the risk assessment of the tested ele­
metal components is based on country-specific regulations. Several ments. Moreover, there is so far no study that fully compares not only
years before, it was believed that cosmetics only had superficial effects. the metals but also the hydroquinone and microorganisms with any
However, it has been feared in recent years that some of the ingredients national or international cosmetic standard and allows the end user to
present in cosmetics have the ability to penetrate deep into the skin and understand how much of these ingredients are added to these facial
further into organs. Even though the external stratum of the skin does products compared to their acceptable limit. There is also a need to focus
not permit much penetration, small amount of heavy metals in cosmetics on studies that fully compare and evaluate the risk and carcinogenic
can reach the circulatory system. Some metals tend to accumulate in the effects of the facial products, and also provide insight into the harmful
protecting layer of skin and cause allergic reactions, while others can effects caused by the uncontrolled addition of undesirable ingredients.
spread through sweat, tears and sebum and penetrate through append­ In this perspective, the present study was performed with emphasis
ages of the skin or through the intercellular and intracellular pathways on quantifying the health risks associated with heavy metals, hydro­
and enter the bloodstream of the human body (Arshad et al., 2020). quinone and microorganisms in facial cosmetic products. The presence
Consequently, the daily use of many cosmetic products can lead to an of microorganisms in collected samples was determined by measuring
increase in the exposure of the human body to heavy metals. There are the total bacterial counts at the time of opening and after one month to
many heavy metals that are considered lethal such as Pb, As, Hg, and Cd evaluate the product stability as a function of time. For a more thorough
(Buksh et al., 2020). Considering the potentially harmful effects of heavy assessment, the results of this study were compared with cosmetic
metals, most of them are strictly prohibited as essential components of standards of different countries such as Pakistan, Saudi Arabia, Europe
cosmetics, but some of the metals are still used or present in cosmetic and Canada. The risk assessment of the various metals present in the
products (Faruruwa and Bartholomew, 2014). selected cosmetic samples was also performed by measuring the sys­
Hydroquinone, a benzene derivative, is also added for its whitening temic exposure dosage (SED), margin of safety (MoS), hazard quotient

2
M. Irfan et al. Journal of Hazardous Materials 433 (2022) 128806

(HQ) and hazard index (HI). The carcinogenic effects of lethal metals Washing is considered an important step to ensure precise analysis
have also been assessed by estimating the lifetime cancer risk (LCR). for determination of heavy metals. Initially, the glassware was thor­
Thus, this study aims to capture the attention of end users so that they oughly washed with detergent followed by rinsing with tap water. They
are not prone to use low-quality and spurious cosmetics. It also draws were then soaked in 5% nitric acid for 24 h. These were then washed
the public’s attention to not buying national or international brands with distilled water (DW). The glassware were then dried at 80 ◦ C for
unless the ingredients have been properly printed on the product label. 48 h and placed in storage for later use.
In fact, this study not only provides end users with information about the Wet digestion technique was applied to digest all the cosmetic
health risks associated with the long-term use of beauty products, but samples as a step required for heavy metals analysis. About 1.0 g of each
also helps the consumer courts and government agencies to establish cosmetic sample was inserted into a 50 mL Erlenmeyer flask and 15 mL
that manufacturers of these beauty products are strictly enforced to of distilled water was added into it. A combination of concentrated nitric
display proper labels, with clear quantities of chemicals, updated con­ and hydrochloric acid i.e. HNO3 and HCL was prepared taking a ratio of
tact information, and clarification of the rules for advertising only 1–3.5 mL and poured into flasks together with the samples and DW. It
authorized cosmetic products. was kept at room temperature (25 ◦ C) for a night and then gradually
heated up to 90 ◦ C for 1–2 h for complete digestion until the solution
2. Materials and methods become completely clear. After digestion, the samples were brought to a
steady state for ambient conditions and filtered through Whatman filter
The comprehensive methodological configuration of the study is paper No. 41. DW was added to this mixture to achieve a final solution
shown in Fig. 1, which shows the identification of the risk of heavy volume of 50 mL. Blank samples were also prepared using similar pro­
metals, hydroquinone, microorganisms and associated health effects tocol. All of these digested solutions were placed in a refrigerator until
when using various skin whitening creams. At the first stage, the con­ required for analysis.
centration of metals, hydroquinone and microorganisms was measured
in the selected samples, followed by the identification of risk assessment
and carcinogenic effects by assessing parameters comprising the margin 2.2. Determination of heavy metals contents
of safety, systemic exposure dosage, hazardous quotient, hazard index,
and lifetime cancer risk. A detailed description of each parameter is Five metals including Pb, Cd, Cr, Ni, and Zn were characterized for
provided in the sections below. their quantification. The analysis was conducted using Atomic absorp­
tion spectrophotometer (Model: Perkin Elmer–AAanalyst 400). The
operating conditions of the instrument during the analysis were main­
2.1. Collection, washing and preparation of samples for analysis tained as; Air-Acetylene flame with variable flow rate, first 10 L/min
and then 2.5 L/min. Specific metal standard solutions at different con­
Samples of 9 different fair creams, including both local and inter­ centrations were passed through the instrument prior to analysis to
national brands, were purchased from the local market located in Lahore generate a calibration curve for each target metal.
city, Pakistan. These brands were selected due to their high sale and The concentration of Hg in whitening cream samples was estimated
demand among the population living in the city of Lahore (Siddiq, in accordance with a method as described in the Association of Official
2019). The collected samples were coded from 1 to 9. The ingredients of Analytical Chemists (AOAC), 2012 with minor modification. In sum­
the samples are listed in Table S1. The analysis was performed in trip­ mary, 1 g of sample was taken into a vessel along with addition of 20 mL
licates to obtain statistically reliable and reproducible data. of deionized water. Thereafter, 2 mL of concentrated HNO3 and 1 mL of

Fig. 1. Methodological lay-out of the study for identification of the risk of heavy metals, hydroquinone, and microorganisms in facial cosmetics using various
analytical approaches.

3
M. Irfan et al. Journal of Hazardous Materials 433 (2022) 128806

concentrated HCL were added. Each sample was placed on a digital hot Consumer Safety (SCCS) and assumed to be 1.54 g/day, 1425 (cm2) and
plate at 95 ◦ C till completely digestion. The sample was cooled by 2.14 per day, respectively (SCCS, 2018). RF indicates the retention
placing them in ice salt mixture water for 30 min and filtered. The same factor which is taken as 1.0 for leave-on cosmetic products. BF is the bio
methodology was adopted thrice for complete extraction and finally accessibility factor; 10− 3 (mg/kg) is used as unit conversion factor while
100 mL volume was prepared. The analysis was performed by using BW highlights the average weight of human body and is projected to be
Inductively Coupled Plasma Spectrophotometer ICP-OES (Optima DV 60 kg in this study.
5300). The exposure level at which no side effects are witnessed is called the
NOAEL and can be derived from dermal reference doses (RFD). The
latter represents "an estimate of the daily exposure of the human pop­
2.3. Determination of Hydroquinone, pH and total plate count (TPC)
ulation that is likely to have no discernible lifetime risk of harmful ef­
fects". NOAEL can be calculated using the following formula
For hydroquinone analysis, 2 g of each sample was taken with the
(Ghaderpoori et al., 2020),
addition of 25 mL of mobile phase (Water: Methanol, 40:60). A ther­
mostatic water bath (Julabo EM) was used to homogenize the mixture NOAEL = RfD × UF × MF (3)
for 45 min at 60 ◦ C followed by cooling to isolate the fats and waxes in − 1 − 1
the sample. Thereafter, the mixture was filtered and transferred into RfDs represents the dermal reference doses (in mg kg day ) and
Teflon vials. Approximately 20 μL of each sample was injected into taken as Cd (1 ×10− 3), Cr (3 ×10− 3), Ni (2 ×10− 2), Pb (4 ×10− 3), Zn
HPLC (Perkin Elmer, Series 200) with C18 column operating at 30 ◦ C (3.0 ×10− 1), Hg (3 ×10− 4) (Ho et al., 2017; Iwegbue et al., 2016).
with UV/Vis. Detector. Chromatograms were obtained from which Whereas, UF indicates the uncertainty factor (reflecting overall confi­
qualitative and quantitative analyzes were carried out to confirm the dence in different data sets) and MF is the modifying factor (based on the
presence of hydroquinone. The peak area was observed and compared to scientific judgment), respectively. The defaults values established for UF
the peak area of the hydroquinone standard solution. The retention time and MF are 100 and 1, respectively.
of the hydroquinone standard solution compared to the sample solution The World Health Organization (WHO) has recommended that the
was used to determine the presence of hydroquinone. minimum MoS value should be 100 to determine if a product can be
The pH of the samples was measured using pH meter, OHAUS ST20. considered marketable and safe. The SCCS distinguishes that various
Various standard buffer solutions with pH 4, 7 and 10 were used in order standard MoS calculations suggest an oral bioavailability of an element
to calibrate the pH meter prior to measurement. Distilled water was used is 100% when data on oral absorption are not accessible. Nevertheless, it
to wash and clean the pH meter rod after every reading and analysis. can be appreciated that no more than 50% of the orally administered
The TPC of cream samples was determined by pour plate method. For dose is systemically functional (SCCS, 2018).
this purpose, 10 g of sample was suspended in 90 mL of sterile water and
thoroughly mixed. This suspension was diluted 9-fold at aseptic condi­ 2.4.2. Hazardous quotient (HQ) and hazard index (HI)
tions. Hereafter, the pour plate technique was performed by taking a The hazard quotient (HQ) indicates the ratio of SED of a test sub­
1 mL aliquot and poured into Petri plates. Nutrient agar was added, stance to RfD of each metal. The value of HQ can be determined through
mixed completely and allowed to stand at room temperature to solidify. following formula,
Solidified agar Petri plates were incubated at 37 ◦ C for the next 72 h. HQ = SED/RfD (4)
Henceforth, the number of colonies was counted and the results were
expressed as a colony-forming unit (cfu/g). The Hazard Index (HI) is the sum of the HQ of each metal being
studied. It is used to assess the cumulative risk to human health posed by
metallic contaminants and can be determined using the following
2.4. Health risk assessment of facial cosmetic equation (Arshad et al., 2020).

2.4.1. Margin of safety (MoS) HI = HQ
The risks to human health associated with the occurrence of heavy = HQCd + HQCr + HQNi + HQPb + HQZn + HQHg (5)
metals present in cosmetics can be assessed using an uncertainty factor
called the Margin of Safety (MoS). It can be estimated by taking into
2.4.3. Lifetime cancer risk (LCR)
account of “no observed adverse effect level (NOAEL)” of an investiga­
The LCR value was determined to identify the risk of lifelong cancer
tional cosmetic material to its calculated systemic exposure dosage
due to the presence of carcinogenic metals in cosmetic creams and was
(SED) (SCCS, 2018).
measured using the following formula,
NOAEL
MoS = (1) LCR = SED × SF (6)
SED
The SED foresees the concentration of chemicals that move in the Where, SF is the coefficient of the slope of carcinogenicity and the
human body in a variety of ways. It is assessed considering the con­ transition to cancer risk for a unit dose of a cancer-causing substance
centration of the metal available in the test substances, the product that is consumed during a typical lifespan. Slope coefficient values for
quantity applied to the skin in a day, using rate or application frequency, Cd, Cr, Ni and Pb are 6.7, 0.5, 0.91 and 0.0085 (mg/kg/day)− 1,
the surface area of the applied skin and the value of the human body respectively, and are reported in the literature (Arshad et al., 2020). The
weight. The value of SED can be determined using the following LVR value for Hg and Zn was not calculated due to the lack of their slope
formula, coefficient in the literature (Ge et al., 2019).
⎛ ⎞
mg
⎜ kg ⎟ Cs × AA × SSA × F × RF × BF 2.4.4. Margin of safety (MoS) for hydroquinone
SED ⎝ ⎠= × 10− 3
(2) A cosmetic sample risk assessment for hydroquinone was also per­
d BW
formed in accordance with the SCCS guidelines notes. As previously
described in Section 2.4.1, the calculation of MoS requires two param­
In this equation, Cs expresses the concentration of heavy metal in the
eters, including NOAEL and SED. There are many studies which high­
cosmetic sample (mg/kg). AA is the concentration of the product to be
lighted the toxicological effects of hydroquinone, with the health-
applied in a day (g/cm2), SSA is the body surface area (cm2) and F shows
related NOAEL values ranging from 25 to 100 mg/kg/day. The risk
the frequency for product application per day. The values of these pa­
assessment was carried out using extreme values i.e. 25 and 100 mg/kg/
rameters are standard and established by the Scientific Committee on

4
M. Irfan et al. Journal of Hazardous Materials 433 (2022) 128806

day. cosmetic samples was found within the permissible limit (3 mg.kg− 1) by
the Canadian regulations for cosmetics. However, it must be noted that
3. Results and discussion Cd and its compounds have been classified as carcinogenic. Cd can
agglomerate into liver and kidneys after seeping through the skin and
3.1. Comparative profile of metals concentrations in facial creams may result in various diseases including kidney disorder, muscle short­
coming, bringing down bone mineral density, insensibility and lung
It is commonly accepted that heavy metals should not be used in damage (Balarastaghi et al., 2018). According to US cancer statistics, Cd
cosmetic and beauty products, as they are applied directly to the human exposure is a key risk factor for human carcinogenesis and is the 2nd
body and cause serious health problems for end users. However, trace leading cause of cancer death (Pal et al., 2017). Moreover, it could be
amounts of these metals may still be present in cosmetics due to their more damaging when it is absorbed or in contact with the skin in higher
persistent nature and easy availability in the natural environment. In concentration or for a longer time. Therefore, European Union (EU) has
general, there can be three main ways by which metals can enter cos­ strictly proscribed any presence of these types of metals and their
metics; (i) the deliberate addition of metallic compounds such as UV compounds in facial cosmetics. The results of the collected cosmetics
filters and pigments, (ii) the use of raw materials and water containing showed that, although the Cd concentration was within the acceptable
metallic elements as impurities, and (iii) the use of apparatus with metal limit of Canadian cosmetics regulations, it was in breach of the EU
coatings. In addition, if subsidiaries of crude oil such as paraffin and standard. Therefore, the presence of this heavy metal in facial creams
mineral oils containing metallic compounds are used as solvents during should be excluded to avoid carcinogenic risks and other health
the production phase of cosmetics, these can also act as additional problems.
source of metal contamination (Borowska and Brzóska, 2015). There­
fore, all samples were carefully analyzed for the presence of metallic 3.1.2. Chromium profile
impurities. The concentration of each metal in selected cosmetic sam­ The presence of Cr in eight cosmetic samples is shown in Fig. 2b. The
ples is shown in Fig. 2. overall concentration of Cr was observed in the range of 0.45–1.55 mg.
kg− 1. Tanzeela et al. also examined the presence of Cr in various skin
3.1.1. Cadmium profile whitening creams, and the results showed that the concentration of Cr
Cd was found in 56% of collected samples; Cd was present in 5 out of ranged from 1.0453 to 2.7455 ppm, which is almost similar as the
the 9 samples as shown in Fig. 2a. The highest concentration of Cd was current study (Ashraf et al., 2020). Cr and its compounds are often added
observed at 0.67 mg.kg− 1, while the lowest concentration was measured to personal care products as pigments to impart color (Achmad and
as 0.06 mg.kg− 1. It was observed that the Cd detected in the collected Ibrahim, 2017). Until now, all cosmetic standards, including those

Fig. 2. Comparative profile of heavy metals and their concentrations in facial cosmetics.

5
M. Irfan et al. Journal of Hazardous Materials 433 (2022) 128806

available in Canadian, Pakistan, Saudi Arabia and the US Food and Drug 3.1.5. Zinc profile
Administration (FDA), have not prescribed any limit on the use of Cr in Zn is an essential element for humans as it plays a vital role in the
cosmetic products. However, the presence of this metal could lead to body’s metabolism. On the contrary, the lack of Zn in the body can lead
skin redness, skin ulcers, swelling of the skin, lung cancer and even to multiple dysfunctions. Out of the 9 collected samples, the concen­
death (Ayenimo et al., 2010; Gondal et al., 2010). It may also be noted tration of Zn was observed in the seven samples as shown in the Fig. 2e.
that Cr in hexavalent form is significantly more toxic when compared The concentration of Zn was measured in the range of 17.82–138.06 mg.
with Cr+3 and could cause higher carcinogenic risks particularly at kg− 1. It should be noted that Zn is required for normal growth and
elevated concentration. Therefore, the International Agency for the metabolism from gametogenesis to old age and is extremely beneficial to
Research on Cancer has included Cr+6 as group 1 human carcinogenic human health. However, skin contact with zinc powders or concentrated
(AL-Azzawi and AL-Hilifi, 2017). Face is considered as the most sensitive solutions can cause corrosive effects including scarring, ulceration and
part of the human skin, especially for women who use numerous facial blistering of the skin (Nouioui et al., 2016). Therefore, the presence of
products for a radiant and beautiful face. Furthermore, facial skin has a Zn salts in cosmetic was allowed up to 1% (Świerczek et al., 2019). Zn
relatively thinner barrier with a high density of nerve endings. There­ and its salts are generally used in variety of different cosmetic products
fore, any presence of this heavy metal should be avoided, especially in including bath soaps, make up and beauty products, baby lotions and
facial creams. However, this study shows the presence of this heavy foot powders. The presence of Zn and its oxides is also found in skin
metal in almost all collected samples, which could lead to undesirable anti-inflammatory drugs such as ointments for diaper rash and sunblock
health effect. products due to their non-carcinogenic potential and low tendency to
penetrate the skin. Therefore, FDA has also allowed the use of ZnO in
3.1.3. Nickel profile cosmetic, sunblock and skin protection products at concentrations of up
Fig. 2c shows the presence of Ni in 66% samples, i.e. 6 of the 9 to 25%. A similar tolerance of 25% for the use of Zn in various cosmetic
collected samples showed the presence of Ni. The presence of Ni was products was also defined by the Korean cosmetic standard (Kim et al.,
measured in the range of 0.14–1.43 mg.kg− 1. Various regulatory bodies 2017). The Zn concentration in all samples in this study was within
for cosmetic products have not established any set limits for Ni content acceptable limits. This shows that by considering only the Zn metal,
in cosmetic products. This may be due to the lower toxicological prop­ these facial creams can be applied without causing much adverse effects.
erties and health hazards associated with Ni compared to Hg, Pb and Cd.
However, Ni-allergy was one of the most prevalent allergy around the 3.1.6. Mercury profile
world (Ahlström et al., 2019). Exposure of Ni to human skin can cause Mercury is available commercially as a liquid metal. The presence of
adverse health effects such as skin allergy, skin rash, cardiovascular Hg was found in six numbers of samples as shown in Fig. 2f. Although
diseases, kidney and respiratory tract cancer (Duda-Chodak and mercury was detected for up to 3.4 mg.kg− 1 in several samples, there
Blaszczyk, 2008). Nickel is transported in the body by binding metal ions were few samples that showed relatively high Hg concentrations and
to specific serum proteins and deposited in the kidneys, lungs, brain, and some even exceeded 100 mg.kg− 1. The massive presence of Hg in these
pancreas (Rizvi et al., 2020). As a result, 5 and 1 ppm limits have been samples is shocking as it could cause serious health risks. Hg is highly
proposed for some household products and detergents respectively, to volatile due to its high vapor pressure in ambient conditions and can be
prevent the development of allergic eczema on the hands caused by Ni. inhaled into the human body. Besides the possible poisoning by inges­
In this study, one sample showed the Ni concentration up to 1.43 mg. tion, these types of cosmetic products can affect the kidneys and the
kg− 1, which is in excess of 1 ppm. Consequently, the presence of this nervous system (Cheuk and Chan, 2006). This higher concentration of
metal can cause skin and respiratory problems, which can be hazardous Hg could also cause skin irritation, allergies and damaging effects on the
to the end user. Moreover, since the EU prohibits any presence of heavy nervous system. Chronic exposure to Hg can cause interstitial kidney
metals in cosmetics, this metal should be excluded in facial creams to disease, peripheral neuropathy, encephalopathy i.e. brain disease,
avoid health complications. malfunctioning or damage to brain (Soo et al., 2003). It may also be
noted that The FDA have approved the use of mercury as a preservative
3.1.4. Lead profile in cosmetics. However, it should not be used in the eye area and its
Lead poses significant health risks such as genotoxicity, organ dis­ concentration in the face product must be less than 65 ppm. In contrast,
ease, and carcinogenicity as seen in many parts of the world, especially the FDA does not allow more than 1 ppm to be present in cosmetic
in developing countries (Ghaderpoori et al., 2020). Even a small amount products under good manufacturing practice.
of it can have serious health consequences. Of the nine samples, Pb The results for concentration of Hg in this study are also consistent
concentration was observed in three samples, as shown in Fig. 2d. The with a recent study from Pakistan, which found that the concentration of
concentration of Pb was observed in the range of 0.30–1.34 mg.kg− 1. Pb mercury in various whitening creams ranges from 3.6 to 240 ppm
can be harmful to the nervous system of the fetus and baby. Therefore, (Majeed et al., 2021). In fact, in South Asia, mercury is found in high
people with sensitive skin, especially children, are specifically advised to concentrations in various beauty products and skin-whitening creams,
take special precautions when applying such products containing Pb to which are in fact top-selling brands (Khan et al., 2021). In this region,
faces (Bocca et al., 2014). Low-level exposure to Pb can reduce learning most women found it effective to use skin whitening creams for a lighter
and hearing capabilities. Other health impacts include kidneys mal­ complexion, and also agreed that the use of these products is closely
functioning, pain in the ankles and wrists, fluctuations in blood pressure, related to achieving a lighter complexion, which is considered more
anemia, nervous system abnormalities, even in some cases of brain beautiful. In many countries of the subcontinent, the liking for a milky
damage. In addition, products with higher Pb concentrations can lead to facial skin began with the successive incursions by the Aryans, Mughals
miscarriage and sperm-producing organs in pregnant women and men, and British. They were much fairer than the local community. Since all
respectively (Nourmoradi et al., 2013). In this study, the concentration three invaders had white skin and were influential, this supports the
of Pb in all collected samples was found within the allowable limits of notion of white as a sign of strength, better status, and wealth (Majeed
Canadian and Pakistan cosmetic standards. In addition, the FDA has also et al., 2021). The reason for adding Hg compounds to beauty creams is
allowed the presence of Pb and its derivatives in cosmetic products up to also to achieve a light complexion of skin. Hg attaches to the surface of
10 ppm. Therefore, it was observed that all collected samples complied the enzymes and inhibits their activity in the synthesis of the pigment
with the prescribed limits of FDA, Canadian and Pakistani cosmetic that colors the skin, i.e. melanin, and therefore gives the skin a lighter
standards. tone. Therefore, the use of skin whitening creams is higher in this region.
However, the presence of such a high concentration of Hg in these skin
whitening creams found in this study is alarming and can cause serious

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M. Irfan et al. Journal of Hazardous Materials 433 (2022) 128806

health issues as previously described. destruction of these body parts is relatively high. For example, it has
been reported that women have an increased risk of breast cancer due to
3.2. Comparison of metals concentrations with national and international overuse of underarm cosmetics (Linhart et al., 2017).
cosmetic standards Therefore, in recent years, with the massive use of cosmetic products,
many countries have developed and issued their own cosmetic standards
The report about the toxicity of metal is well documented since to control the concentration of heavy metals, especially the deliberate
ancient time i.e. 370 BCE when abdominal colic was diagnosed due to mixing of these elements in cosmetic products. The European Commu­
metal toxicity during the extraction of metal. Historically, many metals nity has developed strict and detailed guidelines for cosmetic products,
and their compounds have been used as essential cosmetic ingredients which clarify information on the safety of cosmetic products, safety
such as mercury sulfide in tattoo pigments and lead acetate in hair dyes. assessment, list of prohibited substances in cosmetics, list of substances
In a wide range of cosmetic products, most are applied to the face, neck with restricted use, suitable dyes, preservatives and UV filters in cos­
and underarm part of the human body. Therefore, the probability of metics. In addition, the presence of heavy metals, including Cd, Cr, Hg,

Fig. 3. Comparison of cosmetic samples with different cosmetic standards in Europe, Canada and Pakistan; the EU has set zero tolerance limits for all heavy metals,
whereas the Canadian cosmetic standard recommends limits for Cd, Pb, and Hg, and the Pakistani cosmetic standard recommends only Hg and Pb.

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M. Irfan et al. Journal of Hazardous Materials 433 (2022) 128806

Pb and Ni, is strictly prohibited in cosmetics. It was also observed that creams that is of concern for human health is to estimate the Margin of
there are minor differences in the permissible limits for metals recom­ Safety (MoS) which can be calculated by Eq. (1) as earlier described in
mended by various standards such as Pakistan, European, Canadian and section 2.9.1. The systemic exposure of a cosmetic product makes it
Saudi Arabian standards. It should be noted that, based on the Canadian possible to predict the amount of chemical substances that enter the
regulations for cosmetics, the limit value for heavy metals in cosmetics is human body through various routes of exposure. The calculated SED
10 mg.kg− 1 for Pb, 3 mg.kg− 1 for Cd and 1 mg.kg− 1 for Hg. However, an values at 50% and 100% bio-accessibility for selected heavy metals in
acceptable limit for the remaining metals was not defined in this study, cosmetic samples are shown in Table S2. From these values, MoS was
which may be due to the lower risk associated with them (Söğüt et al., calculated to evaluate the risk to human health due to exposure of
2016; Massadeh et al., 2017). Likewise, Pakistan Standards for skin metallic impurities present in cosmetic samples. The calculated MoS
creams have recommend a maximum limit for heavy metals as Pb; levels for heavy metals present in cosmetic samples at 50% and 100%
20 mg.kg− 1 and Hg; 1 mg.kg− 1. However, the limits for other heavy bioavailability are shown in Table 1. According to the WHO, the product
metals have not been suggested. The results of the current study showed is safe to use if the MoS content of the cosmetic product is 100 or more
that most of the samples violated Pakistani and Canadian cosmetic (Ghaderpoori et al., 2020). For most of the heavy metals in the samples
standards as shown in Fig. 3. The main problem with these samples was taken, MoS values were found to be in excess of 100, indicating that the
the higher Hg concentration. This is also in accordance with data samples assessed are safe to use. However, the MoS values for Hg in
released by the Sustainable Development Policy Institute (SDPI, Islam­ many of the collected samples were found significantly less than 100 and
abad, Pakistan) and the Ministry of Climate Change in 2018, where a this raises serious concerns about their safe use. The key problem with
quality assessment of 59 local and international brands disclosed that the collected cosmetic samples is the high Hg concentration, which is
only three manufacturers used standard amounts of mercury, while often used to suppress the melanin pigment, competing with copper in
others have used excessive amounts in their products and found up to tyrosinase, resulting in a lighter skin tone.
292 ppm against the allowable limit of 1 ppm (Khan et al., 2021). Un­ The value of HQ and HI was calculated to identify the risk analysis
fortunately, in Pakistan, whitening creams and other cosmetic products for the exposure level of a pollutant that is expected to cause side effects
are readily available in local stores, not just pharmacies or regular when used. If value of HQ for a test substance is less than 1, it is assumed
medical stores. Most of the production units are unauthorized and safe and risk-free. On the contrary, if it provides a value greater than 1, it
operated on a large scale illegally. Taking into account of the European is considered harmful to health and unsafe for humans (Xiao et al.,
cosmetic standards, all of the cosmetic samples also professed to violate 2019). However, several reports have favored HI, which provides an
this standard, due to the presence of heavy metals in every sample as appropriate approach for calculating the aggregate risk assessment of
shown in Fig. 3. chemicals and is measured as the sum of the HQ. The HQ and HI values
Even though the skin forms a shielding barrier, some components of the selected cosmetic samples were measured at 50% and 100%
and impurities can still penetrate and have a detrimental local or sys­ bio-accessibility levels and are shown in Fig. 4(a, b).
temic effect. In fact, when metal present in these face creams and beauty At 50% bio accessibility, the HQ values for Cd, Cr, Ni, Pb and Zn in
products are absorbed by the human body, it forms complexes with the each sample were less than one, indicating that these metals have a
amine (–NH2), carboxylic acid (–COOH) and thiol (–SH) proteins. This relatively low concentration and can be considered safe for human
can lead to malfunctioning or cell death, which subsequently becomes health. However, the HQ values for Hg were found to be 112, 163 and
the cause of many diseases. However, metals can be intoxicated using 184 for samples 2, 3 and 6, indicating a serious threat to human health.
any chelating agent which forms a complex with metal ions for easy The HQ values are even higher when the calculation took into account
exclusion from the body (Ullah et al., 2017). When heavy metals enter the factor of 100% bio accessibility. Similarly, HI values were measured,
the body, they are oxidized to various oxidative states that can readily which showed that most cosmetic samples had a value above 1, indi­
bind to biological molecules such as proteins and enzymes, creating cating that excessive use of these products could pose a health risk to the
stable and strong bonds. These metals can also inhibit protein folding. consumer as shown in Fig. 4(c, d). It has been reported that the toxi­
This was first observed when heavy metals such as Cd, Pb and Hg were cological effect of cosmetic creams poses a serious threat to human
shown to effectively interfere with the refolding of a chemically dena­ health. Recently, various cases have been reported in which females
tured protein (Hall and de Sousa, 2019). Thio groups are very common were diagnosed with fussiness, arthralgia and dysesthesias when using
to which heavy metals are attached and replace their hydrogen, thereby skin-whitening creams with a high content of mercury (Mudan et al.,
inhibiting protein function or enzyme activity. For example, Cd binds to 2019; Ori and Larsen, 2018).
a cystein-rich protein such as metallothionein which causes hepatotox­
icity in the liver. After that, it circulates in the kidneys and accumulates 3.3.2. Carcinogenic risk
in its tissue causing nephrotoxicity. Similarly, the reaction of Cr and The International Agency for Research on Cancer has listed Cd, Cr,
biological reducing agents such as thiols and ascorbate lead to the for­ Pb and Ni as carcinogens. These metals can enter the body in two main
mation of reactive oxygen species such as superoxide ion, hydrogen ways: by ingestion or penetration through the skin. These metals are not
peroxide, and -OH radical (Li et al., 2019). This eventually leads to biodegradable and they can accumulate in the body over a long period of
oxidative stress in the cell, which damages DNA and proteins. The effect time. As a result, these metals not only alter the functions of cells, but
of heavy metals on the cell and the balance between the production of also cause disruption of intracellular process. Hence, cancer-related
reactive oxygen species and the protection provided by subsequent an­ diseases are exacerbated by impurities that cause oxidative stress,
tioxidants that protect the cell from free radicals such as H2O2 is shown DNA damage, and cell death. Lifetime Cancer Risk (LCR) is an estimate
by Fig. S1. The small amount of heavy metals present in cosmetics after of the potential cancer risk for users when exposed to heavy metals
application can be absorbed through the epidermis, resulting in the present in cosmetic products. According to USEPA, the valid LCR range
accumulation of these impurities inside the skin. This can cause a variety is 1 × 10− 6 to 1 × 10− 4. USEPA considers a high cancer risk when the
of health problems depending on the nature of the impurities. However, LCR value is high enough, and any value below 1 × 10–4 is considered so
there is still no absolute information regarding the long-term use of face small as to be negligible. This means that a LCR value greater than 10–4
creams and other cosmetics and their health risks. is a reference value for gathering additional information and indicates
an increased risk of carcinogenicity and should be given priority as a
3.3. Health risk assessment of cosmetic public health concern. Therefore, LCR values were measured for cancer-
causing metals and found in the range of 8.81 × 10− 3 to 2.09 × 10− 1, as
3.3.1. Non-carcinogenic risk shown in Fig. 5. It has been shown that the total LCR values for all
One of the most important steps in the risk assessment of whitening cosmetic samples (Fig. 5 inset) exceed the acceptable limit, and the

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M. Irfan et al. Journal of Hazardous Materials 433 (2022) 128806

Table 1
Margin of Safety (MoS) of metals in selected samples of facial cosmetics using 50% and 100% bio accessibility.
MoS calculations using 50% bio accessibility

Cd Cr Ni Pb Zn Hg

1 15,030.85 6724.30 81,118.80 – 28,120.80 –


2 – 4945.65 268,972.75 – 43,017.55 8.90
3 – 7515.40 189,277.10 – 32,592.35 6.15
4 15,970.25 10,220.95 35,737.65 – 5552.45 333.30
5 – 17,034.95 – – 40,775.10 273.80
6 3813.79 11,273.12 91,258.60 – 24,617.00 5.45
7 – 5360.65 365,034.45 7627.60 – –
8 17,034.95 17,034.95 – 20,441.95 35,489.45 225.45
9 42,587.35 – – 34,069.90 – –
MoS calculations using 100% bio accessibility
Cd Cr Ni Pb Zn Hg
1 7515.40 3362.15 40,559.40 – 14,060.40 –
2 – 2472.80 134,486.40 – 21,508.75 4.45
3 – 3757.70 94,638.55 – 16,296.20 3.10
4 7985.15 5110.50 17,868.80 – 2776.25 166.65
5 – 8517.50 – – 20,387.55 136.90
6 1906.90 5636.55 45,629.30 – 12,308.50 2.70
7 – 2680.30 182,517.20 3813.80 – –
8 8517.50 8517.50 – 10,220.95 17,744.75 112.75
9 21,293.70 – – 17,034.95 – –

Fig. 4. Values of hazard quotient (HQ) and Hazard Index (HI) of metals in selected samples of cosmetic products using 50% and 100% bio accessibility.

collected cosmetic samples can have a lifetime risk of cancer when used 3.4. Hydroquinone content and its evaluation with cosmetic standards
for an extended period of time. However, this potential risk depends on
various factors, such as the amount of cosmetic applied per day, the Among the different skin whitening agents, hydroquinone is the most
surface area of the skin to which the sample is applied, the frequency of widely used in skin bleaching creams due to its known efficacy. It re­
product application and, in particular, the concentration of metals in the duces the formation of melanin in the skin, which usually gives the skin
sample. a brownish texture. Therefore, it is often used to lighten dark areas of the
skin such as aging, chloasma, hyperpigmentation, sun damage and acne
scars. The use of hydroquinone can cause temporary redness or dryness
in people, especially those with sensitive skin. Due to limited side

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M. Irfan et al. Journal of Hazardous Materials 433 (2022) 128806

Fig. 5. Lifetime Cancer Risk (LCR) of metals including Cd, Cr, Ni and Pb in selected samples of cosmetic products using bio accessibility levels of 100%.

effects, European Union initially allowed the use of hydroquinone up to national and international cosmetic standards. This value is actually too
2% in skin whitening creams by the Commission Directive 84/415/EEC. high to exceed the maximum limit originally stated for hair dyes. It was
Recently, its use has only been limited to hair dyes and artificial nail also interesting that none of the cosmetic brand showed any presence of
systems due to its known toxic potentials, including irritation, hyper­ hydroquinone in the ingredients mentioned on the labels of cosmetics
sensitivity, ochronosis and carcinogenicity (Chisvert et al., 2010). samples. This means that the manufacturers of these products mislead
Furthermore, its toxic potential becomes more severe in finding its consumers by referring to the incorrect composition of the samples when
presence in the body fluid of person using skin whitening creams con­ labeling the product. Gbetoh and Amyot (2016) also showed similar
taining hydroquinone. Therefore, EU countries have banned the sale of findings and witnessed higher concentrations of hydroquinone
any cosmetic products that contain hydroquinone as an ingredient. compared to the actual values on the product labels.
Likewise, the EU, Pakistan and Canada cosmetic standards have also
prohibited any addition of hydroquinone to cosmetics, particularly in
3.5. Comparison of pH values
facial creams (Gbetoh and Amyot, 2016; PSQC, 2017). However, a few
countries including the USA and West Africa have allowed its presence
The pH is another important factor that is imperative to measure
of up to 1.5–2% (Gbetoh and Amyot, 2016). In this study, analysis of
especially for end users having sensitive skin. The pH of facial creams
cosmetic samples showed a significant presence of hydroquinone in the
has an impact on skin and sometimes becomes a reason for skin irritation
range of 0.12–7.2% as shown in Fig. 6. This huge concentration is of
and redness. It has been observed that cosmetic manufacturers and
serious concern and exceeds the prevailing value recommended by
suppliers are not used to measure the pH values of the cosmetic prod­
ucts. Therefore, this factor is often found to be a missing parameter on
the product label. Consequently, the pH of all samples was measured,
and it remained within the range of 5.1–7.5 as shown in Fig. 7.
Saudi Arabian and Pakistan cosmetic standards have identified the
benign range of pH that has to be maintained for the preparation of
cosmetic products. According to Pakistan’s cosmetic standard, the pH of
skin creams was recommended to prepare within the range of 4–9
(PSQC, 2017). Likewise, the Saudi Arabian Standards Organization
(SASO) has endorsed the pH range as 5–9.5 (SASO, 1999). The pH of a
healthy human skin surface is slightly acidic and is in the range of
5.4–5.9. It has been found that using care products with high pH value
caused an increase in dehydrated effect, irritability, and alteration in
bacterial flora (Tarun et al., 2014). Therefore, all products which are to
be used on the skin should have pH closer to normal human skin pH
value. Unfortunately, in this study, most of the samples did not mention
any pH value on their label. However, the pH of all collected samples
was found within the allowable range recommended by national and
international standards.

3.6. Microbiological analysis of facial creams

Fig. 6. Concentration of Hydroquinone (%) in cosmetic samples. In this study, all of the cosmetic samples were well inspected at the

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M. Irfan et al. Journal of Hazardous Materials 433 (2022) 128806

Fig. 8. Microbiological analysis and evaluation of the selected sample of


facial creams.
Fig. 7. pH analysis of collected cosmetic samples.
there, and (iii) from consumer’s hands and body. This means that the
time of purchasing. All of these samples were found cleaned and un- consumer is also responsible for using the cosmetic products appropri­
tempered. Moreover, all samples were examined as homogenous with ately. However, this problem can be solved by adding potential pre­
any separation of emulsion, sedimentation, or discoloration. In accor­ servatives, which should be able to control microbes not only after
dance with Cosmetic Directive 2003/15/EC, the term PAO (period after production or packaging, but also during their application by the end
opening) was introduced that was based on microbiological criteria. user (Halla et al., 2018). In accordance with the US Food and Drug
This term explains the period of any cosmetic product from its first Administration (FDA) and EU legislation, it is mentioned that safety of
opening to the acceptable time during which it can be used without any the cosmetic products is the sole responsibility of a company or indi­
microbial contamination. However, all of these cream samples have not vidual who is responsible to sell the product (March et al., 2018). Pre­
mentioned PAO on their labels or descriptions. It was also reported that vious studies have identified the presence of microbes such as
cosmetic products including skin creams and lotions must contain less Pseudomonas Specie, Klebshialla Specie, Staphylococcus Specie and Bacillus
than 103 colony-forming units (cfu) mL− 1 or cfu g− 1 of bacteria before Specie etc. in different whitening creams (Aleem et al., 2020). In addi­
delivery to end users (Okeke and Lamikanra, 2001). Furthermore, this tion, it was also found that colored cosmetics are more prone to bacterial
quality level is expected to be retained during their use by the end user contamination in comparison with non-colored products (Periz et al.,
despite the inevitable contamination from the users by the addition of 2018). Therefore, additional efforts are required to pass legislation and
some specialty preservatives in the product. EU has specified the its further implementation for the production of high-quality cosmetic
guidelines on the microbiological quality of the finished cosmetic products. The data presented in this study can also be used as input to
product and classified the cosmetic products in two different categories. better evaluate cosmetic products, especially in Pakistan.
The first category was related to cosmetic products that are intended to
be used for children under three years of age or applications on the eye 4. Conclusion
area. The maximum allowable concentration for total viable counts was
recommended as 102 cfu mL− 1 or cfu g− 1. For other products, the The present study was performed to evaluate pH, hydroquinone,
allowable limit was set as 103 cfu mL− 1 or cfu g− 1 as suggested in the microorganism, and the presence of heavy metals in skin whitening
second category (March et al., 2018). However, these products should be creams. All collected cosmetic samples contained a minor fraction of
free of potentially pathogenic organisms. Therefore, all of these samples heavy metals. However, the presence of Hg in some samples were
were studied for their total viable count, and results are shown in Fig. 8. massively high exceeding the regulatory guidelines, recording up to
It was observed that at the time of sale, 55% of samples were free of 141 mg.kg− 1 and can pose serious health issues. The health risk
microbial contaminants. In addition, total viable counts for the rest of assessment showed that the MoS, HQ, and HI values of most samples
the products were also found less than 102 cfu g− 1 indicating these were were within the acceptable range, but significantly exceeded the
also in the permissible range. However, when cosmetic samples were acceptable range, especially for samples with higher Hg levels. The LCR
analyzed after one month, it was found a remarkable difference in the values of all samples also exceeded the permissible limit indicating their
total viable counts’ values. After passing 30 days, it was examined that carcinogenic effect. Likewise, few samples also showed a significant
44% of the cosmetic samples contained microbial counts above 102 cfu presence of hydroquinone and not complying with recommended stan­
g− 1. The reason for the presence of these microorganisms is that all dard limits set by various national and international cosmetic standards.
cosmetic products containing water, nutrients, vitamins and many other Few cosmetic brands also did not identify the complete ingredients list,
organic substances provide a healthy environment for microbial growth. concentration of metals, and hydroquinone on product labels that were
In addition, many other factors, such as oxygenation conditions, tem­ more problematic for end users. Similarly, collected samples have not
perature, pH, osmotic pressure, and the addition of flavoring in­ labeled any detail of stabilizers. Therefore, many samples showed an
gredients, can also facilitate microbial growth (March et al., 2018). The elevated concentration of microorganisms within four weeks after their
growth of microorganisms can occur in different phases, including (i) opening. Regardless of whether the heavy metals concentrations in most
during the manufacturing of these products where raw materials of the samples taken were within regulatory limits, daily exposure to
contribute a significant level of microbial contamination (ii) unsatis­ such products can cause cumulative effects such as a high risk of skin
factory hygienic conditions of manufacturing areas and persons working cancer and other chronic diseases. Therefore, end users are suggested to
avoid excessive or long-term usage of these types of cosmetic products

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M. Irfan et al. Journal of Hazardous Materials 433 (2022) 128806

for pursuit of beauty. In fact, it is critical to address key issues and Behravan, B.F., Malaekeh P, J., 2005. Survey of bacteriological contamination of
cosmetic creams in Iran (2000). Int. J. Dermatol. 44, 482–485.
carefully evaluate and regulate all personal care products in a country
Bocca, B., Pino, A., Alimonti, A., Forte, G., 2014. Toxic metals contained in cosmetics: a
before they are placed on the market. status report. Regul. Toxicol. Pharm. 68, 447–467.
Borowska, S., Brzóska, M.M., 2015. Metals in cosmetics: implications for human health.
J. Appl. Toxicol. 35, 551–572.
CRediT authorship contribution statement
Buksh, E., Naz, S.A., Zubair, A., Yasmeen, K., Shafique, M., Jabeen, N., 2020. Kohl: a
widely used eye cosmetic with hazardous biochemical composition. Biosci.
Muhammad Irfan: Experimentation, Original draft preparation. Biotechnol. Res. Asia 17, 621–628.
Amir Shafeeq: Supervision, Project administration. Umair Siddiq: Data Cheuk, A., Chan, H., 2006. Minimal change disease following exposure to mercury-
containing skin lightening cream. Hong. Kong Med. J. 12, 316–318.
analysis, Software. Farzana Bashir: Writing – review & editing. Tausif Chisvert, A., Sisternes, J., Balaguer, Á., Salvador, A., 2010. A gas chromatography–mass
Ahmad: Data analysis and Editing. Muhammad Tahir Butt: Data spectrometric method to determine skin-whitening agents in cosmetic products.
analysis, Methodology. Muhammad Ather: Writing – review & editing, Talanta 81, 530–536.
Duda-Chodak, A., Blaszczyk, U., 2008. The impact of nickel on human health. J. Elem.
Conceptualization. Ahmad Mukhtar: Resources, Validation. Sami 13, 685–693.
Ullah: Writing – review & editing, Investigation. Mohamad Hussein: Faruruwa, M., Bartholomew, S., 2014. Study of heavy metals content in facial cosmetics
Formal analysis, Methodology. Su Shiung Lam: Supervision, Writing – obtained from open markets and superstores within Kaduna metropolis, Nigeria. Am.
J. Chem. Appl. 1, 27–33.
review & editing, Resources. Gbetoh, M.H., Amyot, M., 2016. Mercury, hydroquinone and clobetasol propionate in
skin lightening products in West Africa and Canada. Environ. Res. 150, 403–410.
Declaration of Competing Interest Ge, M., Liu, G., Liu, H., Yuan, Z., Liu, Y., 2019. The distributions, contamination status,
and health risk assessments of mercury and arsenic in the soils from the Yellow River
Delta of China. Environ. Sci. Pollut. Res. 26, 35094–35106.
The authors declare that they have no known competing financial Ghaderpoori, M., Kamarehie, B., Jafari, A., Alinejad, A.A., Hashempour, Y., Saghi, M.H.,
interests or personal relationships that could have appeared to influence Yousefi, M., Conti, G.O., Mohammadi, A.A., Ghaderpoury, A., 2020. Health risk
assessment of heavy metals in cosmetic products sold in Iran: the Monte Carlo
the work reported in this paper. simulation. Environ. Sci. Pollut. Res. 27, 7588–7595.
Gondal, M., Seddigi, Z., Nasr, M., Gondal, B., 2010. Spectroscopic detection of health
Acknowledgment hazardous contaminants in lipstick using laser induced breakdown spectroscopy.
J. Hazard. Mater. 175, 726–732.
D. Hall, T. de Sousa Araújo, Digital Fashion Communication: The Influence of Instagram-
We are grateful to the Institute of Chemical Engineering (ICET) Queer-Makeup Artists and Their Future Developments on the Industry, in:
University of the Punjab and the Pakistan Council of Scientific Industrial International Conference on Fashion communication: between tradition and future
digital developments, Springer, 2019, pp. 21–45.
Research (PCSIR) for providing analytical research facilities and in­ Halla, N., Fernandes, I., Heleno, S., Costa, P., Boucherit-Otmani, Z., Boucherit, K.,
struments. The authors would like to acknowledge the King Khalid Rodrigues, A., Ferreira, I., Barreiro, M., 2018. Cosmetics preservation: a review on
University, Saudi Arabia (Deanship of Scientific Research) for providing present strategies. Molecules 23, 1571.
Ho, Y.B., Abdullah, N.H., Hamsan, H., Tan, E.S.S., 2017. Mercury contamination in facial
the facilities and financial support through the Research Groups Project
skin lightening creams and its health risks to user. Regul. Toxicol. Pharm. 88, 72–76.
under the grant number (R.G.P.2/169/42). The authors would also like Iwegbue, C.M., Bassey, F.I., Obi, G., Tesi, G.O., Martincigh, B.S., 2016. Concentrations
to thank Universiti Malaysia Terengganu under International Partner­ and exposure risks of some metals in facial cosmetics in Nigeria. Toxicol. Rep. 3,
ship Research Grant (UMT/CRIM/2-2/2/23 (23), Vot 55302), and the 464–472.
Kazakova, I., Lebedynets, V., Kovalenko, S., Kazakova, V., 2021. Research of the
Ministry of Higher Education, Malaysia under the Higher Institution Activities of the Enterprises of the Perfume ANd Cosmetic Industry of Ukraine, 2.
Centre of Excellence (HICoE), Institute of Tropical Aquaculture and Health Sci, EUREKA, pp. 44–55.
Fisheries (AKUATROP) program (Vot. No. 63933 & Vot. No. 56051, Khan, N.H., Ullah, F., Khan, T.A., Zafar, U., Khan, M.F.A., Mustaqeem, M., Shah, S.S.,
Wu, D.-D., Ji, X.-Y., 2021. Personal-care cosmetic practices in pakistan: current
UMT/CRIM/2-2/5 Jilid 2 (10)) for supporting Prof Lam to perform this perspectives and management. Clin. Cosmet. Invest. Dermatol. 14, 9.
joint project. Kim, K.-B., Kim, Y.W., Lim, S.K., Roh, T.H., Bang, D.Y., Choi, S.M., Lim, D.S., Kim, Y.J.,
Baek, S.-H., Kim, M.-K., 2017. Risk assessment of zinc oxide, a cosmetic ingredient
used as a UV filter of sunscreens. J. Toxicol. Environ. Health Part B 20, 155–182.
Appendix A. Supporting information Li, B.S., Cary, J.H., Maibach, H.I., 2019. Science behind cosmetics and skin care.
Nanocosmetics 3–15.
Supplementary data associated with this article can be found in the Li, Y., Liu, Z., Zhang, Y., Jiang, L., Cai, Y., Chen, X., Zhou, X., Li, H., Li, F., Zhang, J.,
2021. Investigation and probabilistic health risk assessment of trace elements in
online version at doi:10.1016/j.jhazmat.2022.128806. good sale lip cosmetics crawled by Python from Chinese e-commerce market.
J. Hazard. Mater. 405, 124279.
References Linhart, C., Talasz, H., Morandi, E.M., Exley, C., Lindner, H.H., Taucher, S., Egle, D.,
Hubalek, M., Concin, N., Ulmer, H., 2017. Use of underarm cosmetic products in
relation to risk of breast cancer: a case-control study. EBioMedicine 21, 79–85.
Ababneh, F.A., Al-Momani, I.F., 2018. Assessments of toxic heavy metals contamination
Majeed, T., Shah, S.H., Anjum, I., 2021. Estimation of mercury and hydroquinone
in cosmetic products. Environ. Forensics 19, 134–142.
content in skin whitening creams and the potential risks to the health of women in
Achmad, R.T., Ibrahim, E., 2017. Effects of chromium on human body. Annu. Res. Rev.
Lahore, Pakistan. J. Pak. Assoc. Dermatol. 31, 33–41.
Biol. 13, 33462 (ARRB).
March, G.A., Garcia-Loygorri, M.C., Eiros, J.M., Bratos, M.A., de Lejarazu, R.O., 2018.
Agorku, E.S., Kwaansa-Ansah, E.E., Voegborlo, R.B., Amegbletor, P., Opoku, F., 2016.
Microbiological quality in cosmetics. In: Analysis of Cosmetic Products. Elsevier,
Mercury and hydroquinone content of skin toning creams and cosmetic soaps, and
pp. 585–597.
the potential risks to the health of Ghanaian women. SpringerPlus 5, 1–5.
Massadeh, A., El-Khateeb, M., Ibrahim, S., 2017. Evaluation of Cd, Cr, Cu, Ni, and Pb in
Ahlström, M.G., Thyssen, J.P., Wennervaldt, M., Menné, T., Johansen, J.D., 2019. Nickel
selected cosmetic products from Jordanian, Sudanese, and Syrian markets. Public
allergy and allergic contact dermatitis: a clinical review of immunology,
Health 149, 130–137.
epidemiology, exposure, and treatment. Contact Derm. 81, 227–241.
Moldovan, Z., Popa, D.E., David, I.G., Buleandra, M., Badea, I.A., 2017. A derivative
AL-Azzawi, M.N.A., AL-Hilifi, H.T.A.-R., 2017. Detection of cadmium and chromium in
spectrometric method for hydroquinone determination in the presence of kojic acid,
some facial cosmetics. Iraqi J. Sci. 58, 408–416.
glycolic acid, and ascorbic acid. J. Spectro 2017.
Aleem, A., Khan, M., Abid, U., Ishfaq, M.F., Rouf, A., Jamshaid, T., 2020. Microbial
Mudan, A., Copan, L., Wang, R., Pugh, A., Lebin, J., Barreau, T., Jones, R.L., Ghosal, S.,
analysis of selected brands of whitening creams. Saudi J. Med. Pharm. Sci. 6,
Lee, M., Albertson, T., 2019. Notes from the field: methylmercury toxicity from a
178–182.
skin lightening cream obtained from Mexico—California, 2019. Morb. Mortal. Wkly.
Arshad, H., Mehmood, M.Z., Shah, M.H., Abbasi, A.M., 2020. Evaluation of heavy metals
Rep. 68, 1166.
in cosmetic products and their health risk assessment, Saudi. Pharm. J. 28, 779–790.
Munir, A., Hayyat, M.U., Shahzad, L., Sharif, F., Farhan, M., Ghafoor, G.Z., 2020.
Ashraf, T., Taneez, M., Kalsoom, S., Irfan, T., Shafique, M.A., 2020. Experimental
Assessment of heavy metals concentrations in commercially available lipsticks in
calculations of metals content in skin-whitening creams and theoretical investigation
Pakistan. Environ. Forensics 21, 259–266.
for their biological effect against tyrosinase enzyme. Biol. Trace Elem. Res. 1–8.
Nouioui, M.A., Mahjoubi, S., Ghorbel, A., Ben Haj Yahia, M., Amira, D., Ghorbel, H.,
Ayenimo, J., Yusuf, A., Adekunle, A., Makinde, O., 2010. Heavy metal exposure from
Hedhili, A., 2016. Health risk assessment of heavy metals in traditional cosmetics
personal care products. Bull. Environ. Contam. Toxicol. 84, 8–14.
sold in Tunisian local markets. Int. Sch. Res. Not. 2016.
Balarastaghi, S., Khashaiarmanesh, Z., Makhdoumi, P., Alavizadeh, S.H., Sameie
Nourmoradi, H., Foroghi, M., Farhadkhani, M., Vahid, M., 2013. Dastjerdi, Assessment of
Moghadam, Z., Shirani, K., Karimi, G., 2018. Determination of toxic element levels
lead and cadmium levels in frequently used cosmetic products in Iran. J. Environ.
(lead and cadmium) in commonly used cosmetic products in Iran. Toxin Rev. 37,
Public Health 2013.
117–122.

12
M. Irfan et al. Journal of Hazardous Materials 433 (2022) 128806

Okeke, I.N., Lamikanra, A., 2001. Bacteriological quality of skin-moisturizing creams and Sharmeen, J.B., Mahomoodally, F.M., Zengin, G., Maggi, F., 2021. Essential oils as
lotions distributed in a tropical developing country. J. Appl. Microbiol. 91, 922–928. natural sources of fragrance compounds for cosmetics and cosmeceuticals. Molecules
Ori, M.R., Larsen, J.B., 2018. Mercury poisoning in a toddler from home contamination 26, 666.
due to skin-lightening cream. J. Pediatr. 196 (e311), 314–317. Söğüt, Ö., Reyhanlıoğlu, H., Ezer, M., Baltaş, H., 2016. Elemental compositions of some
Owolabi, J.O., Fabiyi, O.S., Adelakin, L.A., Ekwerike, M.C., 2020. Effects of skin cosmetic products marketed in Turkey. Fresen. Environ. Bull. 25, 1068–1077.
lightening cream agents – hydroquinone and kojic acid, on the skin of adult female Soo, Y.O.-Y., Chow, K.-M., Lam, C.W.-K., Lai, F.M.-M., Szeto, C.-C., Chan, M.H.-M., Li, P.
experimental rats. Clin. Cosmet. Invest. Dermatol. 13, 283–289. K.-T., 2003. A whitened face woman with nephrotic syndrome. Am. J. Kidney Dis.
Pal, D., Suman, S., Kolluru, V., Sears, S., Das, T.P., Alatassi, H., Ankem, M.K., 41, 250–253.
Freedman, J.H., Damodaran, C., 2017. Inhibition of autophagy prevents cadmium- Świerczek, L., Cieślik, B., Matysiak, A., Konieczka, P., 2019. Determination of heavy
induced prostate carcinogenesis. Br. J. Cancer 117, 56. metals in eyeshadows from China. Mon. Chem. 150, 1675–1680.
Periz, G., Misock, J., Huang, M.C.J., Dewan, K., Sadrieh, N., 2018. FDA 2014 survey of Tarun, J., Susan, J., Jacob Suria, V.J.S., Criton, S., 2014. Evaluation of pH of bathing
eye area cosmetics for microbiological safety. Lett. Appl. Microbiol. 67, 32–38. soaps and shampoos for skin and hair care. Indian J. Dermatol 442.
PSQC, Pakistan Standards for Skin Creams, in: P.S.A.Q.C. AUTHORITY (Ed.), Pakistan, Tashkhourian, J., Daneshi, M., Nami-Ana, F., Behbahani, M., Bagheri, A., 2016.
2017. Simultaneous determination of hydroquinone and catechol at gold nanoparticles
Rizvi, A., Parveen, S., Khan, S., Naseem, I., 2020. Nickel toxicology with reference to mesoporous silica modified carbon paste electrode. J. Hazard. Mater. 318, 117–124.
male molecular reproductive physiology. Reprod. Biol. 20, 3–8. Ullah, H., Noreen, S., Rehman, A., Waseem, A., Zubair, S., Adnan, M., Ahmad, I., 2017.
SASO, Skin Cream Standard, in: S.A.S. Organization (Ed.), Saudia Arabia 1999. Comparative study of heavy metals content in cosmetic products of different
SCCS, The Scientific Committee on Consumer Safety: Notes of guidance for the testing of countries marketed in Khyber Pakhtunkhwa, Pakistan. Arab. J. Chem. 10, 10–18.
cosmetic substances and their safety evaluation–10th revision. SCCS/1602/18, Xiao, J., Xu, X., Wang, F., Ma, J., Liao, M., Shi, Y., Fang, Q., Cao, H., 2019. Analysis of
(2018). exposure to pesticide residues from Traditional Chinese Medicine. J. Hazard. Mater.
Umair Siddiq M.Sc. Thesis, “Comparative study of selected heavy metals in cosmetics” 365, 857–867.
2019 University of the Punjab, Lahore, Pakistan.

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