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,
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,
