• Login
    • Join
  • Subscribe Free
    • Magazine
    • eNewsletter
    Checkout
    • Magazine
    • News
    • Formulary
    • Exclusives
    • Top Companies
    • Raw Materials
    • End-User
    • Packaging
    • Directories
    • Events
    • Jobs
    • More
  • Magazine
  • News
  • Formulary
  • Exclusives
  • Top Companies
  • Raw Materials
  • End-User
  • Packaging
  • Directories
  • Events
  • Jobs
  • Current / Back Issues
    Features
    Columns
    Editorial
    Digital Edition
    eNewsletter Archive
    Our Team
    Editorial Guidelines
    Subscribe Now
    Advertise Now
    Top Features
    Help for Indies

    The Future Has Arrived

    Shape It Up

    Stepping into the Spotlight for 2021

    The Independent Beauty Association Supports Sensible Reform
    Online Exclusives
    Association News
    Breaking News
    Financial News
    Industry News
    International
    Marketing News
    New Products
    News Front
    Packaging News
    Patents
    Personnel
    Regulations
    Snapshots
    Top News
    Live From Shows
    Top News
    ACI Urges Senate to Approve Regan as EPA Administrator

    Estée Lauder Signs Actress Ana de Armas

    GUM Recalls Oral Spray

    Sephora To Open More Stores in 2021

    Clean Beauty Collective Supports Earth Day Initiative
    Blog
    Online Exclusives
    Infographics
    Podcasts
    Whitepapers
    Videos
    Expert's Opinion
    HappiTV
    eBook
    Surveys
    International Top 30 Report
    Top 50 Report
    Top Companies
    4. Estée Lauder

    48. State Industrial Products

    12. Church & Dwight

    6. LVMH

    30. Fancl
    Actives
    Functional Ingredients
    Pigments
    Polymers
    Preservatives
    Surfactants

    Freckle Pens Are Spot On!

    Are Chemists the Rock Stars of Beauty?

    Sales More Than Double at Madison Reed

    Eucerin Launches Sun Protection Formula

    What You're Reading on Happi.com
    Air Care/Environmental Fragrance
    AP/Deo
    Color Cosmetics
    Disinfectants
    Fine Fragrance
    Hair Care
    Household Cleaning
    I&I Marketplace
    Laundry Care
    Oral Care
    OTC/Medicated
    Packaging
    Personal Cleansers
    Skin Care
    Sun Care
    Testing

    ACI Urges Senate to Approve Regan as EPA Administrator

    Estée Lauder Signs Actress Ana de Armas

    Shelf Present

    GUM Recalls Oral Spray

    Sephora To Open More Stores in 2021
    Lab Equipment
    Mixing
    Packaging
    Testing

    Burt’s Bees Outlines New Sustainability Goals

    Secret, Old Spice Add Refillable Deo Packaging

    Estée Lauder Travel Retail's Sustainability Goals

    Ross Introduces Double Cone Tumble Blender

    Happi Talks: Overnight Labels
    Contract Manufacturing / Private Label Directory
    Buyer's Guide
    Add New Company
    Corporate Profiles
    International Buyers Guide Companies
    Siltech Corporation

    Ashland

    Vantage Specialty Ingredients

    Croda

    Centerchem Inc
    Live From Shows
    Meetings
    Webinars
    Snapshots
    • Magazine
      • Current / Back Issues
      • Features
      • Editorial
      • Columns
      • Digital Edition
      • eNewsletter Archive
      • Subscribe Now
      • Advertise Now
    • Breaking News
    • Formulary
    • Directories
      • Buyer's Guide
      • Contract Manufacturing / Private Label Directory
      • Corporate Profiles
      • Add Your Company
    • Raw Materials
      • Actives
      • Functional Ingredients
      • Pigments
      • Polymers
      • Preservatives
      • Surfactants
    • End-User
      • Air Care/Environmental Fragrance
      • AP/Deo
      • Color Cosmetics
      • Disinfectants
      • Fine Fragrance
      • Hair Care
      • Household Cleaning
      • I&I Marketplace
      • Laundry Care
      • Oral Care
      • OTC/Medicated
      • Packaging
      • Personal Cleansers
      • Skin Care
      • Sun Care
      • Testing
    • Packaging
      • Lab Equipment
      • Mixing
      • Packaging
      • Testing
    • Top Companies
      • International Top 30 Report
      • Top 50 Report
    • Online Exclusives
    • Experts Opinion
    • Slideshows
    • HappiTV
    • Videos
    • Podcasts
    • eBook
    • Infographics
    • Blog
    • Whitepapers
    • Surveys
      • R & D Salary Survey
      • Sales & Marketing Salary Survey
    • Job Banks
    • Events
      • Industry Events
      • Live from show Events
      • Webinars
    • About Us
      • About Us
      • Contact Us
      • Advertise With Us
      • Privacy Policy
      • Terms of Use
    Safety Assessment In Skin Care

    Physical Chemical Properties in Safety Assessment

    ...

    Nava Dayan, Dr. Nava Dayan LLC01.06.15
    The first section on the guidelines published in October 2012 by The Organization for Economic Co-operation and Development (OECD) for testing of chemicals includes a list of relevant physical-chemical properties.1 Identification of the composition of interest is the first step in any chemistry-body interaction assessment since it equips the assessor with tools for prediction and drafting a plan for valuation.

    Properties that do not change the chemical nature of a matter are termed “physical” while properties that do change the chemical nature of matter are termed “chemical.” The more detailed the information obtained at this early stage the better one can identify a substance and the better the knowledge of its characteristics. These properties can help formulators understand how it may behave under different conditions.

    Assessing Safety
    The essence in safety evaluation of compounds we use on a daily basis, such as personal care and cosmetics, lies in the interaction and impact of the composition on the body. The assessment is based on the postulation that at a given concentration, route of exposure and intensity, the chemistry (composition applied) introduced to biology (skin) may be recognized by the body as foreign or harmful and therefore may generate an unfavorable reaction. The assessor, therefore, should strive to outline the risks associated with predicted exposure and determine whether the predicted risk is acceptable and the benefit of use justifies the risk.

    The skin is the largest and most complicated immune organ in the human body. It fills multiple roles, acquiring signals from the environment that are communicated via sophisticated cascades to the circulation and vice versa. Its structure and composition provides a very sensitive responsive flow of stimuli inside and out. In approximately 30 days, a normal healthy skin is completely renewed. This means that abundance of stems cells supplemented by nutrients, trace elements and specific peptides are synthesized de novo to comply with the constantly generated barrier. Nourished by the blood in the vasculated dermis, accompanied with environmental indicators and factors that are secreted, compartmentalized and affecting its acquired immunity cells, this process holds the premise for the difference between health and disease. 

    To add to this complexity, the skin hosts an abundance of biota that is an essential contributor to its maintenance, as well as to the prevention of proliferation and pathogenicity of opportunistic bacteria and fungi. Certain treatments and practices foster biota imbalance leading to impaired biological barrier, potential disease and abnormal sensitivity.

    Compound Characterization
    The first and most important step in safety assessment of skin care ingredients and compositions is the characterization of the compound/s applied; i.e., their chemistry, physics, stability and overall nature. The collection of such information at the early stage of product development is essential to the project path and its success. The safety assessment of skin care products is determined by their detailed compositions; i.e. the individual raw materials it contains. Raw materials should be characterized for the following:
    • Chemical structure molecular weight and its innate stability under a variety of conditions;
    • Physical properties such as appearance, color, density, particles size, electrical charge, light absorption and, when relevant, melting point, boiling point, freezing point, flash point and minimum ignition temperature. When determining particle size it should be highlighted that the average particle size is not sufficient for the understanding of particulate properties and a size distribution should be established so one can assess what is the size of the particles composing the majority of the batch; and
    • Level and nature of purity. These are of key importance since impurities, although usually at lower concentration than the central ingredient, can impart a toxicological effect that is irrelevant to the core compound and can be minimized or eliminated if purity is higher. A validated analytical method should be developed and utilized to determine purity and impurities levels to ensure batch-to-batch consistency.
    Tracing Impurities
    According to the EU Commission guidelines published in November, 2013 “when chemically well-defined substances are present, their quantity and molecular formula should be given together with their analytical specifications (degree of purity, identification of major impurities, criteria and test methods used).”2 Further in this document it is outlined that “traces can originate from the following sources: impurities in the raw materials/substances; the manufacturing process; potential chemical evolution/interaction and/or migration of substances in the product that could occur under normal storage conditions and/or through contact with the packaging material.”
    • With compounds that are extracted with solvents, levels of residual solvents should be determined;
    • Heavy metals nature and contents should be specified;
    • Solubility in a variety of relevant solvents; and
    • The pH in water should be determined and recorded. The skin’s normal pH is around 5.5. If the pH generated by the compound is 2 or lower or 11.5 or higher the compound is considered as a skin corrosive and cannot be used in a formulation or should be neutralized.
    The interplay between the varieties of physical-chemical properties may allow, in part, predicting the interaction of the compound with the skin and hence its toxic potential. This assessment, of course, does not release one from the need to conduct empirically a battery of customized safety assessment studies but should be part of the overall assessment and justification of theorized risk.
    Composed of keratin-filled corneocytes surrounded by highly organized lamellar structures, a healthy intact upper skin layer (stratum corneum) is lipophilic and relatively dry (composed of 15% water). Therefore it is generally assumed that lipophilic compounds will partition easier into the stratum corneum. This means that a lipophilic compound, depending on other relevant properties such as molecular weight and electric charge, may either remain in the skin’s upper layer, generating a reservoir, or further partition or absorb into deeper layers, the live epidermis, the dermis and the blood circulation.

    The lipophilicity of a compound is determined by its octanol/water partition coefficient or Log P. This value reflects the ratio of concentrations of a compound in a mixture of octanol and water that are immiscible at equilibrium. The coefficient reflects the measure of the difference in solubility in the two phases; e.g., the higher the solubility in octanol, the higher the lipophilicity and vice versa.

    Penetration Levels
    The general view for the threshold of molecular weight associated with penetration to the skin is 500 dalton. This means that compounds that are high in molecular weight such as polymers will remain on top of the skin and not penetrate. This, however, does not mean that they will not impart a biological effect, but that this effect will not be directly associated with the polymer chemistry. For example, hyaluronic acid with molecular weight of 2×106 dalton will not penetrate unbroken skin. It may, however, elevate the stratum corneum water content by capturing water that attempts to leave the body through the skin to the environment thereby reducing trans epidermal water loss (TEWL). Long term, such an effect can change the skin biota population and also allow higher solubility and skin partitioning of water soluble compounds in the base applied.

    If the compound applied to the skin generates a reservoir in the stratum corneum and remains there for sufficient time not further partitioning into the epidermis, it is most likely to be removed with cells naturally exfoliated from the skin. If it does penetrate beyond the epidermis into the vasculated dermis, it is reasonable to assume that certain amounts will be absorbed into the blood system to be distributed into internal organs.

    Since the skin is negatively charged, cationic molecules, may exhibit better adherence onto the stratum corneum. Here too, depending on other properties, cationic compounds may remain at the upper layer or partition deeper.

    The solubility of the compound in the base applied to skin is a crucial aspect to study. Skin absorption is highly dependent on the concentration presented to it, as molecules will penetrate the skin following Fick’s law of simple diffusion. According to Fick’s law, flux of molecules will travel from regions of high concentration to regions of low concentration, with a magnitude that is proportional to the concentration gradient. Since the maximal concentration is directly associated to the solubility, the higher the solubility, the higher the penetration and therefore, the higher the potential exposure and risk. This law is applied only to compounds at their molecular form and not to compounds in their particulate form such as powders. The interaction of particles with the skin will be discussed in future column that will also address safety aspects of nanoparticles.

    Phototoxicity Issues
    If a compound absorbs at the UV or visible spectra it may exhibit a potential to be photo-toxic (photo-irritating, photo-sensitizing or photo-genotoxic). This means that by absorbing radiation, its structure and therefore interaction with the skin may change and impart a toxic effect. Photo-toxicity will be discussed in details in a future column but this is an example of the implications of a physical property on potential safety. Since photo-toxicity by definition required radiation absorption, a compound with no such property cannot be photo-toxic; therefore such effect is not of concern and should not be part of the testing battery.

    When it comes to natural compounds extraction in which total composition characterization can be difficult and sometimes impossible, the approach should be to focus on the following:
    • The main compound with the highest percentage in the composition;
    • Identification of key chemistries that are thought or known to impart the biological activity, their nature and percentage;
    • Residual solvents;
    • Heavy metals;
    • Microbiological contamination; and
    • Batch to batch consistency of the above.
    Finally, outlining and documenting the physical-chemical properties of the compound or composition of interest should serve for the utilization of in silico approaches to elucidate safety. Such is for example, structure-activity relationships (SAR). In silico methods are virtual screening and evaluations composed by computerized methods that use information embedded into software to compare new or unknown chemistries to an existing pool and drawing correlation and relevancy. Such tools are used for predicting toxic effects using a special algorithm.

    It should be acknowledged that such systems may sometimes provide false information since the algorithm used may not be relevant or when biological or physical effects, such as metabolism or degradation respectively, are not taken into consideration.

    In summary, whether it is a raw material, blend, natural extract, composition or formulations, the understanding and collection of physical chemical properties is the first and most essential part in product development in general and safety assessment in particular. This information should be utilized in the overall evaluation and be part of the product information package (PIF).
    It should pave the path and drive sequence study decisions, starting from highest concern based on these properties, level of exposure and population of choice. 

    References:
    1. OECD http://www.oecd.org/chemicalsafety/testing/TG%20List%20EN%20Aug%202012.pdf
    2. Annex  I EU Commission http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32013D0674&qid=1395764232390&from=FR:PDF

    Nava Dayan
    President
    Dr. Nava Dayan LLC

    Nava Dayan Ph.D. is the owner of Dr. Nava Dayan L.L.C, a skin science and research consultancy and serving the pharmaceutical, cosmetic, and personal care industries. She has 25 years of experience in the skin care segment, and more than 150 publication credits.
    Tel: 201-206-7341
    E-mail: nava.dayan@verizon.net
    Related Searches
    • care
    • collection
    • chemicals
    • color
    Related Knowledge Center
    • Functional Ingredients
    • Skin Care
    • OTC/Medicated

    Related Safety Assessment In Skin Care

    • Actives | Functional Ingredients | Skin Care | Testing

      The Metabolism of Skin and How To Test It

      ...
      Nava Dayan, Dr. Nava Dayan LLC 09.01.16

    • Actives | Functional Ingredients | Skin Care | Testing

      Endocrine Disruption & Cosmetic Ingredients

      ...
      Nava Dayan, Dr. Nava Dayan LLC 07.01.16

    • Actives | Functional Ingredients | OTC/Medicated | Polymers | Preservatives | Skin Care | Surfactants | Testing

      Assessment of Potential Skin Sensitization

      Anaphylaxis to skin care products is possible.
      Nava Dayan, Dr. Nava Dayan LLC 01.04.16


    Trending
    • When The FTC Comes Calling...
    • Eucerin Launches Sun Protection Formula
    • Planting Roots
    • MAC Appoints SVP, Global Marketing
    • Are Chemists The Rock Stars Of Beauty?
    Breaking News
    • ACI Urges Senate to Approve Regan as EPA Administrator
    • Estée Lauder Signs Actress Ana de Armas
    • GUM Recalls Oral Spray
    • Sephora To Open More Stores in 2021
    • Clean Beauty Collective Supports Earth Day Initiative
    View Breaking News >
    CURRENT ISSUE

    February 2021

    • Help for Indies
    • Trade Association Directory 2021
    • The Future Has Arrived
    • Shape It Up
    • View More >

    Cookies help us to provide you with an excellent service. By using our website, you declare yourself in agreement with our use of cookies.
    You can obtain detailed information about the use of cookies on our website by clicking on "More information”.

    • About Us
    • Privacy Policy
    • Terms And Conditions
    • Contact Us

    follow us

    Subscribe
    Nutraceuticals World

    Latest Breaking News From Nutraceuticals World

    Preliminary Study Links Markers of Impaired Bone Health to Vegan Diet
    Refined Grains Linked to Heart Attack Risk, Early Death
    Kappa Bioscience Extends Research Partnership For COVID-19 Research
    Coatings World

    Latest Breaking News From Coatings World

    Nippon Paint Marine Wins Korea Export Award
    Universal Display Corporation, PPG Expand Global Production of UniversalPHOLED Materials
    PPG Introduces Premium Iso-free Primer Surfacer, Catalyst
    Medical Product Outsourcing

    Latest Breaking News From Medical Product Outsourcing

    January AI Raises $8.8 Million in New Funding
    FDA Clears Ava Fertility Tracking Wearable Device
    First Patient in Europe Treated With Diamondback 360 Coronary Orbital Atherectomy System
    Contract Pharma

    Latest Breaking News From Contract Pharma

    Spark Therapeutics Appoints CTO
    Cryoport Launches ESG Program
    U.S. Govt. Purchases 100k Doses of Lilly's COVID-19 Antibody Cocktail
    Beauty Packaging

    Latest Breaking News From Beauty Packaging

    The Top Beauty Products of 2021, According to HelloGiggles
    Estée Lauder Taps Ana de Armas as Global Brand Ambassador
    Sephora Announces Significant Expansion
    Happi

    Latest Breaking News From Happi

    ACI Urges Senate to Approve Regan as EPA Administrator
    Estée Lauder Signs Actress Ana de Armas
    GUM Recalls Oral Spray
    Ink World

    Latest Breaking News From Ink World

    Etiflex Enters New Markets with Nilpeter FA-22 Installation
    Hydrocarbon Solvents Market to Surpass $8.1 Billion by 2030
    Marshall & Bruce Adds Koenig & Bauer Rapida 106 41-Inch Seven-Color Press
    Label & Narrow Web

    Latest Breaking News From Label & Narrow Web

    FTA converts Forum & INFOFLEX to virtual events
    Xeikon launches two new digital label printing presses
    UFlex adds capacity in packaging films
    Nonwovens Industry

    Latest Breaking News From Nonwovens Industry

    Texas Medical Technology Partners with My Protect Kit
    Mexico City Single-Use Plastics Ban Leads to Tampon Shortage
    Believe Diapers Launch in U.S.
    Orthopedic Design & Technology

    Latest Breaking News From Orthopedic Design & Technology

    Fusion Robotics Receives FDA Clearance for Spinal Navigation and Robotics System
    Kaia Health Unveils Next-Gen Complete MSK Care Solutions
    First Implantation of CTL Amedica's Minimally Invasive Flex Tower
    Printed Electronics Now

    Latest Breaking News From Printed Electronics Now

    Comercial Kywi Improves Customer Service, Front-Store Operations with Zebra Mobile Solution
    Global Printed Circuit Board Market Projected to Reach $69.32 Billion by 2027
    Global Smart Glass Market to Register 6.8% CAGR Between 2021-28: Grand View Research

    Copyright © 2021 Rodman Media. All rights reserved. Use of this constitutes acceptance of our privacy policy The material on this site may not be reproduced, distributed, transmitted, or otherwise used, except with the prior written permission of Rodman Media.

    AD BLOCKER DETECTED

    Our website is made possible by displaying online advertisements to our visitors.
    Please consider supporting us by disabling your ad blocker.


    FREE SUBSCRIPTION Already a subscriber? Login