Safety Concern and Regulatory Status of Chemicals Used in Cosmetics and Personal Care Products

: Cosmetics and personal care products (PCPs) are a few of the most commonly used products across the globe with a whopping market share of approximately USD 500 billion. These products are used for cleansing purposes and for improving the quality and beauty of the face, hair, and skin. There are many chemical substances involved in the manufacturing of cosmetics and PCPs. These chemical substances incorporated in cosmetics or PCPs are crucial to develop high-quality products with superior appearance, applicability, and stability; however, excessive use of such chemicals in cosmetics and PCPs has become a safety concern as many of these are reported to cause severe health complications. Overuse of cosmetics and PCPs with hazardous material should be minimized, especially by pregnant women and children. Gynecologists advise pregnant women not to use cosmetics and PCPs with hazardous chemicals. The implementation of a lawful framework is crucial to establish the safety of cosmetics and PCPs. Cosmetic companies/industries must be strictly regulated and made compliant to the guidelines in order to protect human health and minimize safety concerns. In this review, hazardous chemicals incorporated in the personal care products/cosmetics and their related risk and health complications have been discussed in detail. Additionally, regulatory status and clinical trials of chemical substances that involve toxicity and causing severe complications have also been discussed.


Introduction
According to Section 3(a) of the Drugs and Cosmetics Act, 1940 "Cosmetic can be explained as a product anticipated for coating, gushed, dispersed or sprayed on, or instigate into, or else dermally used on the humans or any part of the things just mentioned for cleansing, embellishing, enhancing attractiveness, or changing the looks, and includes any product intended for a component of cosmetic". The definitions of cosmetics as per different stringent regulatory agencies are presented in Table 1 [1,2]. It can be said that beauty products are the ones that help to clean and beautify human skin/hair or appearance. These products are also intended to repair damaged skin.
After globalization in 1980s, the cosmetic/PCPs industry boomed globally. These products are helping millions of people to improve their appearance, cleanliness, hydration, and moisturize the body. Some of the constituents in these products are toxic for human use and may cause serious health concerns [3,4]. Regularly, every culture of the world is known to apply their required cosmetic/PCPs that are mainly used for protection, cleaning, Table 1. Definition of cosmetics according to regulatory agencies.

Regulatory Agencies Definition of Cosmetics
USFDA "A product (except pure soap) that is used to be applied dermally for cleansing, whitening, and beautifying purposes" CDSCO (India) "An article anticipated for coating, pouring, and sprinkling or spraying on, or incorporated into, or otherwise applied on the human skin or any part thereof for cleansing, embellishing, enhancing attractiveness, or improve appearance, and includes any article used for a component of cosmetic." When these cosmetic products penetrate dermally after getting absorbed, they can cause severe complications such as endocrine disorders, cancer, neurological disorder, reproductive disorders, etc. There are more than 13,000 synthetic and other industrial chemicals that are incorporated in cosmetic products; however, only 20% of these chemicals are perceived as safe, and illustrated by the USFDA [10].
The threshold of toxicology concern (TTC) study of chemical compounds of cosmetics/PCPs has limited absorption data as functional barriers work on the stratum corneum. Quantitative study data of chemicals that have crossed the skin barriers are determined through in vitro studies. Absorption data of chemical constituents are expressed with the coefficient of dermal permeation (kp) and designated as steady-state flux via a concentration gradient [11,12].
Based on the report of the breast cancer fund, an average woman in the US applies more than twelve cosmetic products daily while men use six products. More than 10,000 chemicals are used in the manufacturing of these cosmetic products and ≤20% of chemicals or constituents are reported to be safe [13]. These active chemicals can transdermally penetrate the systemic circulation, which can adversely affect human health. High frequency and duration of application could enhance the risk of cancer, endocrine disorders, neurotoxicity, and reproductive disorders. Following the regulation for safe cosmetics/PCP, the United States has banned 11 chemicals while European Union has banned 1328 chemicals from use in cosmetics [14].
A large group of PCP such as skin whitening products, creams, and body oils contain around 9% of hydroquinone which is used in 30 times higher concentration than the maximum limit (0.3%). It can cause allergic reactions to the skin, ocular disorders, genetic disorders, and even cancer [15].
The high demand for cosmetics/PCP worldwide at all age groups has also elevated awareness associated with safety issues. In this review, a focus has been made on chemicals found in cosmetics/PCPs that are toxic and harmful to human health. This paper also highlights the regulatory issues and safety assessment of chemical ingredients and their related clinical trials. The search criteria of the key factors required in the given review have been mentioned in Figure 1. chemicals found in cosmetics/PCPs that are toxic and harmful to human health. This paper also highlights the regulatory issues and safety assessment of chemical ingredients and their related clinical trials. The search criteria of the key factors required in the given review have been mentioned in Figure 1.

Range of Personal Care or Topical Products
Personal care products include face wash, moisturizer, cotton swabs, eyeliner, lip balm, deodorant, cologne, sunscreen, etc. These are applied to improve or maintain the physical appearance of the user [16]. These products are either cleansers or dermally applied cream or lotion (sunscreen, moisturizer, etc.,) for different purposes to clean or to protect the skin from sunburn, dryness, and dust particles [17]. Additionally, they are used for facial makeovers are intended to beautify the look. In the modern lifestyle, consumers are diverting toward natural ingredient-based products with limited toxicity of natural compounds. However, herbal cosmetics also contain other synthetic chemicals such as parabens, artificial colorants, stabilizers, and emulsifiers, etc., [18]. These are not safe for humans and can cause serious health issues. Chemicals such as phenol, triclosan, parabens, ether could cause endocrine disorders, neurological disorders, and risk of other diseases [19]. The cosmetic industry is still growing and has some keys drivers for the growth areas.

Market Size and Growth
In 2019, world s beauty care industry had a capital of USD 532 billion [20]. In 2019, the biggest consumer was the United States (US) which occupies 20% of the overall market size; China occupied the second position and third position by Japan with a market percentage of 13% and 8%, respectively. The cosmetic industry is expected to reach USD 800 billion by the year 2025 with a CAGR (compound annual growth rate) of 5-7% [21]. The cosmetic industry is the largest sector under the beauty care industry. Top leading companies are L Oreal, Unilever, Estee Lauder, Coty, Proctor, and gamble. In the year 2018-2019, the Indian cosmetic market was valued at USD 6.5 billion. The top leading companies in India are Boutique, Lotus, Patanjali, Coach, Estee Lauder Companies Inc. [22] According to recent data, the market growth size of cosmetic industries increased through

Range of Personal Care or Topical Products
Personal care products include face wash, moisturizer, cotton swabs, eyeliner, lip balm, deodorant, cologne, sunscreen, etc. These are applied to improve or maintain the physical appearance of the user [16]. These products are either cleansers or dermally applied cream or lotion (sunscreen, moisturizer, etc.,) for different purposes to clean or to protect the skin from sunburn, dryness, and dust particles [17]. Additionally, they are used for facial makeovers are intended to beautify the look. In the modern lifestyle, consumers are diverting toward natural ingredient-based products with limited toxicity of natural compounds. However, herbal cosmetics also contain other synthetic chemicals such as parabens, artificial colorants, stabilizers, and emulsifiers, etc., [18]. These are not safe for humans and can cause serious health issues. Chemicals such as phenol, triclosan, parabens, ether could cause endocrine disorders, neurological disorders, and risk of other diseases [19]. The cosmetic industry is still growing and has some keys drivers for the growth areas.

Market Size and Growth
In 2019, world's beauty care industry had a capital of USD 532 billion [20]. In 2019, the biggest consumer was the United States (US) which occupies 20% of the overall market size; China occupied the second position and third position by Japan with a market percentage of 13% and 8%, respectively. The cosmetic industry is expected to reach USD 800 billion by the year 2025 with a CAGR (compound annual growth rate) of 5-7% [21]. The cosmetic industry is the largest sector under the beauty care industry. Top leading companies are L'Oreal, Unilever, Estee Lauder, Coty, Proctor, and gamble. In the year 2018-2019, the Indian cosmetic market was valued at USD 6.5 billion. The top leading companies in India are Boutique, Lotus, Patanjali, Coach, Estee Lauder Companies Inc. [22] According to recent data, the market growth size of cosmetic industries increased through the increment in consumer's income and urbanization, increment in consumer demand, lifestyle modification, rising interest in male grooming, and also increased demand for natural or bio-based products [23].

Harmful Chemicals Present in the Products
Despite all the positivitiess of cosmetics, we need to focus on safety measures of these hazards as it is a matter of human health. Chemicals and other ingredients present in these products can be hazardous [24]. A lot of these chemicals used as preservatives, UV filters, color additives, etc., can cause cancer, mutation, developmental and reproductive toxicity, endocrine disruption, etc., [25]. Most of the cosmetic products are applied on the skin, which results in the toxic/harmful chemicals penetrating the stratum corneum barrier and reaching the dermis of the human skin, and may further reach the systemic circulation [26]. Hence, it is capable of disrupting fertility during pregnancy and causing female reproductive disorders as shown in Figure 2. All the ingredients in the beauty products meet certain regulatory obligations, but some ingredients are allowed at low concentrations due to their toxicity at higher concentrations. Facial wash or cleansers might not be ideally safe for regular use on or around the delicate and specialized dermal layer of eyelids. These face wash/cleansers contain sodium lauryl sulfates that remove delicate natural oil/moisture on eyelids by evaporation [27]. Globally, lip care products are high-selling cosmetic products in the modern era used to enhance self-esteem and make attractiveness, and moisturize the lips. In lip care products, chemicals such as dye, mineral mica, colorant, and shiner are incorporated during manufacturing to develop high-quality products and boost its effect. These chemicals contain trace metals such as antimony, arsenic, copper, etc., [28] can cause severe adverse effects. Regular long-term use of lip care cosmetic reveal that when these trace metals are used in high quantity they can penetrate the systemic blood circulation causing damage of various organs [29].
Dermato 2023, 3, FOR PEER REVIEW 4 the increment in consumer s income and urbanization, increment in consumer demand, lifestyle modification, rising interest in male grooming, and also increased demand for natural or bio-based products [23].

Harmful Chemicals Present in the Products
Despite all the positivitiess of cosmetics, we need to focus on safety measures of these hazards as it is a matter of human health. Chemicals and other ingredients present in these products can be hazardous [24]. A lot of these chemicals used as preservatives, UV filters, color additives, etc., can cause cancer, mutation, developmental and reproductive toxicity, endocrine disruption, etc., [25]. Most of the cosmetic products are applied on the skin, which results in the toxic/harmful chemicals penetrating the stratum corneum barrier and reaching the dermis of the human skin, and may further reach the systemic circulation [26]. Hence, it is capable of disrupting fertility during pregnancy and causing female reproductive disorders as shown in Figure 2. All the ingredients in the beauty products meet certain regulatory obligations, but some ingredients are allowed at low concentrations due to their toxicity at higher concentrations. Facial wash or cleansers might not be ideally safe for regular use on or around the delicate and specialized dermal layer of eyelids. These face wash/cleansers contain sodium lauryl sulfates that remove delicate natural oil/moisture on eyelids by evaporation [27]. Globally, lip care products are high-selling cosmetic products in the modern era used to enhance self-esteem and make attractiveness, and moisturize the lips. In lip care products, chemicals such as dye, mineral mica, colorant, and shiner are incorporated during manufacturing to develop high-quality products and boost its effect. These chemicals contain trace metals such as antimony, arsenic, copper, etc., [28] can cause severe adverse effects. Regular long-term use of lip care cosmetic reveal that when these trace metals are used in high quantity they can penetrate the systemic blood circulation causing damage of various organs [29].

Cancer
Cancer is a disease in which aberrant cells divide with no control and conquer nearby cells and tissues. Chemicals that are used in beauty care products either directly show carcinogenic effects or have a risk of causing cancer [14]. Fluorene and phenanthrene (group 3) along with naphthalene (group 2B), chrysene (group 2A), and titanium dioxide (group 2B) are carcinogenic agents capable of inducing lung cancer; however, other chemicals such as naphthalene, N-nitrosodiethanolamine (group 2A) can develop liver cancer. Similarly, chemicals such as butylatedhydroxyanisole (group 2A) can cause stomach cancer [30]. Formaldehyde and formaldehyde-releasing preservatives (group1) can cause leukemia (blood cancer). Some chemicals such as avobenzone, hydroquinone, and PABA present in the sunscreens are not carcinogenic but can increase the risk of having skin cancer, while coal tar (group 1) is carcinogenic that can cause skin cancer as shown in Figure 3 [31]. 1,4-Dioxane (group 2A) present in hair products can cause breast cancer, while p-phenylenediamine present in hair dyes can increase the risk of skin cancer [28]. Arsenic (group 1) can cause bladder cancer, and acrylates (group 2B) in nail products can cause colorectal cancer [29].

Cancer
Cancer is a disease in which aberrant cells divide with no control and conquer nearby cells and tissues. Chemicals that are used in beauty care products either directly show carcinogenic effects or have a risk of causing cancer [14]. Fluorene and phenanthrene (group 3) along with naphthalene (group 2B), chrysene (group 2A), and titanium dioxide (group 2B) are carcinogenic agents capable of inducing lung cancer; however, other chemicals such as naphthalene, N-nitrosodiethanolamine (group 2A) can develop liver cancer. Similarly, chemicals such as butylatedhydroxyanisole (group 2A) can cause stomach cancer [30]. Formaldehyde and formaldehyde-releasing preservatives (group1) can cause leukemia (blood cancer). Some chemicals such as avobenzone, hydroquinone, and PABA present in the sunscreens are not carcinogenic but can increase the risk of having skin cancer, while coal tar (group 1) is carcinogenic that can cause skin cancer as shown in Figure 3 [31]. 1, 4-Dioxane (group 2A) present in hair products can cause breast cancer, while pphenylenediamine present in hair dyes can increase the risk of skin cancer [28]. Arsenic (group 1) can cause bladder cancer, and acrylates (group 2B) in nail products can cause colorectal cancer [29].

Organ System Toxicity
Harmful ingredients present in beauty care products can accumulate in our bodies and might cause organ system toxicity [32]. As can be seen in Table 2 and Figure 4, many ingredients can cause various types of organ system toxicity. Substances such as methylparaben, propylparaben, butylated hydroxy-toluene, acrylates, and octinoxate (present in shampoos, sunscreen, and nail products) can cause developmental toxicity [33]. Substances such as p-phenylenediamine, coal tar, and hydroquinone can cause skin toxicity. Butylated hydroxy-anisole and cadmium can cause renal toxicity [34]. Methylparaben, propylparaben, acrylates, and octinoxate can also cause reproductive toxicity. Ingredients such as ether, butylated hydroxy-anisole, and methylisothiazolinone

Organ System Toxicity
Harmful ingredients present in beauty care products can accumulate in our bodies and might cause organ system toxicity [32]. As can be seen in Table 2 and Figure 4, many ingredients can cause various types of organ system toxicity. Substances such as methylparaben, propylparaben, butylated hydroxy-toluene, acrylates, and octinoxate (present in shampoos, sunscreen, and nail products) can cause developmental toxicity [33]. Substances such as p-phenylenediamine, coal tar, and hydroquinone can cause skin toxicity. Butylated hydroxy-anisole and cadmium can cause renal toxicity [34]. Methylparaben, propylparaben, acrylates, and octinoxate can also cause reproductive toxicity. Ingredients such as ether, butylated hydroxy-anisole, and methylisothiazolinone (used in hair products) possess risk of causing lung toxicity while benzophenone can cause liver toxicity [35].
(used in hair products) possess risk of causing lung toxicity while benzophenone can cause liver toxicity [35].

Endocrine Disruption
Endocrine disruptors are chemical substances that are capable of disrupting hormonal signals thus affecting the reproductive and nervous systems. Various grades of phthalate can prevent the synthesis of testosterone, while antimicrobial agents (triclosan) cause hypothyroidism [36]. We can generalize endocrine disruptors present in beauty products in two parts namely reproductive health endocrine disruptor and thyroid endocrine disruptor, as shown in Figure 5. Ingredients such as avobenzone, butylparaben, methylparaben, octinoxate, and butylatedhydroxyanisole (present in sunscreen and hair products) are reproductive health endocrine disruptors and can cause fertility abnormalities, skewed sex ratio, and in females can also cause menstrual problems [37]. Chemicals such as PABA, padimate O, homosalate, triclosan, octinoxate, and resorcinol can disrupt the thyroid hormone and can cause hyperthyroidism or hypothyroidism. Generally, there are no metabolic disruptors present in any beauty care products [38]. In a a study on the examination of urine samples of a specified group of adults, in more than 96% of the samples methyl/propylparaben was obtained. Several other studies have also reported the high concentration of parabens in various products, dermal penetrability, and its toxic effects [39].

Endocrine Disruption
Endocrine disruptors are chemical substances that are capable of disrupting hormonal signals thus affecting the reproductive and nervous systems. Various grades of phthalate can prevent the synthesis of testosterone, while antimicrobial agents (triclosan) cause hypothyroidism [36]. We can generalize endocrine disruptors present in beauty products in two parts namely reproductive health endocrine disruptor and thyroid endocrine disruptor, as shown in Figure 5. Ingredients such as avobenzone, butylparaben, methylparaben, octinoxate, and butylatedhydroxyanisole (present in sunscreen and hair products) are reproductive health endocrine disruptors and can cause fertility abnormalities, skewed sex ratio, and in females can also cause menstrual problems [37]. Chemicals such as PABA, padimate O, homosalate, triclosan, octinoxate, and resorcinol can disrupt the thyroid hormone and can cause hyperthyroidism or hypothyroidism. Generally, there are no metabolic disruptors present in any beauty care products [38]. In a a study on the examination of urine samples of a specified group of adults, in more than 96% of the samples methyl/propylparaben was obtained. Several other studies have also reported the high concentration of parabens in various products, dermal penetrability, and its toxic effects [39]. Allergies are the body s immune system shows hypersensitive response to a foreign substance (harmful or harmless). Different people present different kinds of reactions to

Allergies, Irritation, and Asthma
Allergies are the body's immune system shows hypersensitive response to a foreign substance (harmful or harmless). Different people present different kinds of reactions to similar allergens. Skin allergies are one of the most common side effects of cosmetic or beauty care products. Allergic reactions could also be occurring by some chemicals that are common in cosmetics manufacturing, like alcohol (in shampoos, lotions), isothiazolinones (preservatives added in shampoos and body wash), butylated hydroxytoluene (preservative in hair products), and ether (as an impurity in hair products) [36].

Other (Cellular and Neurological Damage, Ochronosis, Sensitization)
Other health issue that can be caused by using beauty care products are ochronosis caused by hydroquinone (present in skin lightener and facial moisturizer), chemicals such as oxybenzone (present in sunscreen), diethanolamine (present in soap and shampoos), padimate-O (present in sunscreen), coal tar (present in shampoos and hair dyes) can cause bioaccumulation [40]. P-phenylenediamine and benzalkonium chloride are mutagenic, acrylates can cause cellular and neurological damage, mercury present in eye area products can cause mercury poisoning, and methylisothiazolinone (present in shampoos as preservatives) can cause neuroticism as mentioned in Figure 6 [23].

Regulatory Issues
In USA, cosmetics regulation comes under FDA and is authorized by the Federa Food, Drug, and Cosmetic Act (FD & C Act) and Fair Packaging and Labeling Act (FPLA Except for color additives, all the manufacturing items and excipients do not require an FDA premarket approval [31]. Manufacturers have the legal authority to guarantee th

Regulatory Issues
In USA, cosmetics regulation comes under FDA and is authorized by the Federal Food, Drug, and Cosmetic Act (FD & C Act) and Fair Packaging and Labeling Act (FPLA). Except for color additives, all the manufacturing items and excipients do not require any FDA premarket approval [31]. Manufacturers have the legal authority to guarantee the safety of products [41]. Based on the Safe Cosmetic and Personal Care Product Act, manufacturing brand holders in the USA have to register and renew annually and deposit actual data of excipients used in cosmetic products. In 2013, a subcommittee of workforce protection was referred by the secretary of health and human services [42,43]. Complete information on various chemicals used in cosmetics/personal care products including their major health concern and regulatory status are shown in Table 2.

Safety-Based Global Clinical Trials of Personal Care Products
In clinical trials, research is carried out on people to study the effect of new tests and treatments in order to observe and evaluate their effects on the human body. These trials include a test of new drugs, surgical treatment, biological products, etc., on people volunteering to take part in these clinical trials [44]. These clinical trials first have to be approved by the respective authorities of that country. Clinical trials have four phases: Phase (1) when the trial is carried out on healthy volunteers; phase (2) when the trial is carried out on a small population of the diseased patient; in the third and fourth phases, the test is approved for human use on a large populationto check its effect on the human body in a longer time frame [45]. Global data of clinical trials of cosmetics/PCPs are shown in Table 3a-c. Table 2. Range of chemicals used in cosmetics/personal care products and their major health concern and regulatory status.

S.No.
Category  The amount used in PCP: ≤5% in products applied for longer time (US) and ≤2.5% in non-rinse off products(EU) Major health concern: Carcinogenic/hepatocarcinogenic due to formation of nitrosamine on contamination [56,57] 8.
Ether: 1.4-dioxane Used in: Hair products Function: Impurity The amount use in PCP: There is no maximum potency as it is a by-product of the chemicals used Major health concern: Breast cancer, organ toxicity, irritation [60] 10.
Formaldehyde and formaldehyde-releasing preservatives (imidazolidinyl Urea) [59] Used in: Nail polish, hair gel, nail adhesive, shampoo for babies Function: Preservatives The amount used in PCP: 0.6% w/w (EU) and 0.28%w/w Amount used in other pharmaceutical products:
Phenol: Hydroquinone Used in: Skin lightener, facial moisturizer Function: Decreases melanine, make skin appear whiter The amount used in PCP: 2% w/w OTC, higher in prescription only products The amount used in other pharmaceutical products: Vaginal cream-0.02% w/w Major health concerns: Increase risk of skin cancer, ochronosis [76,77] 18.
Polyacrylic aromatic hydrocarbons: naphthalene, chrysene, fluorene, anthracene, phenanthrene and acenaphthene Used in: Lotions, cosmetics Function: Impurity in petrolatum a moisturizing agent The amount used: 5 ppm (US), petrolatum should be free of any carcinogenic impurities (EU) and 500 ppm as color additives (US) Major health concern: Cancer     Change from baseline in skin creepiness score, elasticity score, firmness score, sagging score, skin roughness (visual and tactile), overall photo damage score, evenness of skin tone score, evenness of skin redness score and in objective erythema parameters. Stephens

Safety Assessment of Excipient Used in Cosmetic/Personal Care Products
In the analysis of risk, safety margin (infertility factors) is determined in the last step of safety assessment. According to WHO, a minimum value of 100 is required for margin of safety (MoS) is required to accept the compound for minimum adverse effect/safety purpose and their equation is shown below [45].
Margin o f sa f ety = Non − observed adverse e f f ect Systemic exposure dose NOAEL is the maximum amount of dose from which no treatment-related side effects are observed. The SED of a personal care product is the predicted amount that enters into the blood circulation and is expressed as mg/kg BW/day. Whereas SED is expressed as % of component penetrating the skin as shown in the equation.

SED =
daily dermal exposure × DAp 60 kg o f bw Cosmetic ingredient review (CIR) was organized by the PCPC (Personal Care Product Council) Expert panel of CIR and constitutes industry representatives, toxicologists, dermatologists, and chemists [29]. The purpose of the meetings is to re-evaluate all the published and unpublished research, industry data, the literature on all chemicals of cosmetics being determined to check the safety of chemicals that are involved in the formulation of cosmetics [146]. Furthermore, based on the voting system, safety evaluations are finalized and concluded and then published in peer-reviewed journals. Documents of guidance are developed and followed for the cosmetics/ personal care products manufacturing and quality assurance unit [3].
The scientific committee on consumer safety is a self-governing body that is capable to suggest the European Commission. By risk assessment process, it also delivers the guidelines for characterizing and analyzing of the safety of cosmetics [147]. International Council of Chemical Associations is responsible to publish guidance on risk assessment of chemicals which govern the comprehensive strategy used to appraise risk factors of chemicals that are incorporated in cosmetics. Guidance documents are published to meet the criteria for the development of safe products and for the betterment of health worldwide [148]. Another framework, the International Fragrance Association (IFRA) was implemented to design and publish the standard safety guidelines for the use of fragrance ingredients and components in a wide range of cosmetic/personal care products. The standard of fragrance components is developed by IFRA with regard to risk assessment strategies that facilitate recently applied level, category of cosmetic item, and exposure potency during application along with scientists of Research Institute for Fragrance Materials [149]. Evaluation and conclusion are appraised by advisory experts including skin specialists, physicians, toxicologists, and other required scientists. Analyzed data that are published in peer review journals and standard criteria of IFRA for fragrance components are also uploaded on the website. The Flavor and Expert Manufacturers Association (FEMA) research scientists rely on a structurally similar group of chemicals as functional materials of its risk assessment strategies for food flavoring compounds [150].

Conclusions
The human body is exposed to various chemical substances. A substantial amount of hazardous chemicals are being used in the preparation of cosmetic products such as preservatives, perfumery, surfactant, colorant, and other excipients. Most of these chemicals possess toxicity and are known to cause various complications. For human grade products, there is a requirement to follow legal or regulatory guidelines and risk assessment to cover all possible aspects of using chemicals in cosmetics and PCPs. In some cases, if any ingredient exceeds the limits, especially in case of children or pregnant ladies, it can cause permanent damage to the skin, internal organs, as well as the brain. Many of these ingredients present in body care products can even cause cancer, neural damage, and permanent skin disorders.
According to the authors, the guidelines pertaining to safety should be made stringent and the compliance should be made mandatory. It is a general practice that products are granted marketing authorization on the basis of safety information or data of ingredients. However, there should also be a safety assessment of product as a whole. In the given point of view, the generation of preclinical data becomes mandatory but there are ethical concerns of using animals for the same. It can be addressed by using in vitro tools such as cell line studies, artificially generated skin models etc. The authors also suggest to put pharmacovigilance system in place for cosmetic products. The group is already working in this direction, and a survey study in this regard is also in process.