511 Evolution and Challenges of Sustainability
Currently, there is a great deal of research directed at studying the skin microbiome,
and some products involved with this technology have been introduced in recent years.
Sullivan et al. patented a skin treatment using Lactobacillus extract (i.e., a postbiotic) for
stimulation of β-defensins in skin cells to increase the skin’s natural defenses against
infection or to make products less irritating by decreasing the microbial density on
sensitive areas of the skin.160 A recent report by Spragge et al. indicated that the intestinal
microbiome protects against pathogens by “nutrient blocking” that is promoted by
diversity of the microflora and by the presence of key species that increase the overlap
between the nutrient use of the GI commensals and pathogens.161 It is believed that a
similar situation may occur on skin.
The intrinsic and extrinsic factors affecting the diverse microflora at the different skin
sites present a very complex system to study. Although single culture studies may be
informative, Boxberger et al. observed that there are clinical implications of the gut-brain-
skin connection in acne so that researchers may need to test with multiple microorganisms
under different conditions to better understand their full range of functions and how they
can be modified to lessen the severity of skin disorders and skin inflammation.162
The CNS may be candidates to be considered as probiotics on skin to lessen the severity of
acne, for wound management, and for down-regulation of the SIS. S. epidermidis, S. hominis,
and S. capitis are prominent members of the skin microbiome. They are able to produce
an array of antimicrobial substances (i.e., short-chain fatty acids from lipase hydrolysis of
sebum triglycerides, AMPs, and PSMs), and their ability to stimulate skin cells to produce
AMPs, including cathelicidins and defensins (to which they are refractory), make them
possible candidates to consider for use as probiotics. We are learning from studies of the
intestinal microbiome and the use of prebiotics. It is likely that selected ingredients will
act similarly and benefit desirable commensal microorganisms in the skin microbiome.
Finding a prebiotic (i.e., substrate) to facilitate growth or colonization resistance by selected
CNS in situ may be a better approach than trying to add living CNS for modulating the
skin microbiome to achieve desirable outcomes.
GAPS IN OUR KNOWLEDGE THAT NEED TO BE ADDRESSED IN FUTURE
PRODUCTS
The evolution of cosmetic preservation has involved transitioning from the use of traditional
preservatives to use of multifunctional ingredients to replace some or all the preservatives
used in some aqueous products. However, there are several gaps in our knowledge that
need to be addressed. These issues are discussed next.
ADEQUATE PRODUCT PRESERVATION
The goal of preservative efficacy testing is to determine the minimum concentration and
types of preservatives or multifunctional ingredients required for the adequate preservation
of aqueous cosmetic products. The acceptance criteria used for preservative efficacy testing
are critical, and more rigorous criteria provide a greater measure of protection than relaxed
criteria.
Unfortunately, there is no consensus on what is necessary or sufficient for preservative
efficacy test acceptance criteria. These criteria range from the rigorous (e.g., linear

512 JOURNAL OF COSMETIC SCIENCE
regression method with target criteria of decimal reduction times [D-values] of ≤4 hours
for pathogens, ≤28 hours for nonpathogenic bacteria, yeast and mold, and bactericidal/
bacteriostatic for Bacillus spores), to the relaxed (e.g., PCPC criteria of at least a 3-log
reduction of bacteria in 7 days), and to the very relaxed (e.g., USP criteria of at least a
2-log reduction of bacteria in 14 days).12,13,163 Sooner or later, companies that have products
that just meet these relaxed acceptance criteria will experience instances of microbial
contamination that result in destruction of batches, recovery of merchandise after
shipment to the trade, or product recalls, even though these companies adhere to GMPs
in every aspect of their manufacturing process. The root cause of the problem often may
be inadequate preservative systems.163
Some companies classify different products as “sensitive” or “low risk,” “medium risk,” or
“high risk,” depending on their experience with microbial contamination.163 This product
classification is inappropriate because manufacturers should not blame products for being
sensitive or high risk when, in fact, the problem is inadequate preservation. The sensitive
products should be reformulated, so they have adequate preservative systems.
A basic requirement for the preservation of aqueous products is that the preservative system
must kill microorganisms fast enough to prevent their adaptation to the preservative
system, because adapted microorganisms are then able to grow in the product. As noted
above, Wolven and Levinstein8 performed challenge tests and concluded that “regardless of
the method employed to demonstrate preservative efficacy, no growth should occur after
seven days.” Orth, Delgadillo and Dumatol determined the maximum allowable rates of
death (i.e., D-values) needed to prevent adaptation of P. aeruginosa, E. coli, and Burkholderia
cepacia were around 30 hours, which is about a 6-log reduction in 7 days.164 These
acceptance criteria may be difficult to achieve in some formulations that do not contain
formaldehyde or formaldehyde donors, especially for spore-formers like Bacillus spp. and
molds. Not meeting target criteria may be acceptable if further testing demonstrates the
formula kills vegetative cells and is bacteriostatic/fungistatic for spores. It was proposed that
additional studies are needed to have enough data to establish the minimum preservative
acceptance criteria requirements for aqueous products.165 It is recommended that cosmetic
manufacturers address this issue.
CROSS-RESISTANCE OF PRESERVATIVES WITH ANTIBIOTICS
In 1998, McMurry, Oethinger and Levy reported that Triclosan interfered with the
biosynthesis of fatty acids by blocking enoyl reductase in E. coli.166 This work showed that
Triclosan—a biocide— may act like an antibiotic that interferes with a single cellular
process (i.e., lipid biosynthesis). Their work suggested that Triclosan resistance could be
part of a larger problem of antimicrobial resistance (AMR) and that overuse of Triclosan in
consumer products may increase this problem.
This was alarming because many people in the cosmetic industry were concerned that there
may be a connection between use of preservatives/biocides and AMR. Many preservatives
and other chemicals used in cosmetics and OTC drugs have been found to induce multiple-
antibiotic resistance. It was reported that salicylate and benzoate may induce multiple-
antibiotic resistance in a number of bacteria including B. cepacia, E. coli, Klebsiella pneumonia,
and S. aureus.167-171 Cohen et al. observed a connection between phenotypic antibiotic
resistance and induction of the multiple-antibiotic resistance (mar) operon, salicylate,