O-Cymen-5-olCAS# 39660-61-2 |
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Cas No. | 39660-61-2 | SDF | Download SDF |
PubChem ID | N/A | Appearance | Powder |
Formula | C10H14O | M.Wt | 150.22 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | Soluble in Chloroform,Dichloromethane,Ethyl Acetate,DMSO,Acetone,etc. | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
O-Cymen-5-ol Dilution Calculator
O-Cymen-5-ol Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 6.6569 mL | 33.2845 mL | 66.569 mL | 133.1381 mL | 166.4226 mL |
5 mM | 1.3314 mL | 6.6569 mL | 13.3138 mL | 26.6276 mL | 33.2845 mL |
10 mM | 0.6657 mL | 3.3285 mL | 6.6569 mL | 13.3138 mL | 16.6423 mL |
50 mM | 0.1331 mL | 0.6657 mL | 1.3314 mL | 2.6628 mL | 3.3285 mL |
100 mM | 0.0666 mL | 0.3328 mL | 0.6657 mL | 1.3314 mL | 1.6642 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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A mouthwash formulated with o-cymen-5-ol and zinc chloride specifically targets potential pathogens without impairing the native oral microbiome in healthy individuals.[Pubmed:36891194]
J Oral Microbiol. 2023 Mar 3;15(1):2185962.
BACKGROUND: Many antimicrobial compounds in mouthwashes can have a negative impact on the oral microbiome. O-Cymen-5-ol, a compound derived from a phytochemical, has a targeted mode of action and is being used as an alternative. However, its effect on the native oral microbiome is unknown. AIM: To assess the effect of a mouthwash formulated with O-Cymen-5-ol and zinc chloride on the oral microbiome of healthy individuals. METHODS: A mouthwash formulated with O-Cymen-5-ol and zinc chloride was administered to a cohort of 51 volunteers for 14 days, while another cohort of 49 volunteers received a placebo. The evolution of the oral microbiome in both groups was analysed using a metataxonomic approach. RESULTS: Analysis of the oral microbiome showed that the mouthwash selectively targeted potential oral pathogens while maintaining the integrity of the rest of the microbiome. Specifically, the relative abundance of several potentially pathogenic bacterial taxa, namely Fusobacteriota, Prevotella, Actinomyces, Granulicatella, Abiotrophia, Lautropia, Lachnoanaerobaculum, Eubacterium (nodatum group) and Absconditabacteriales (SR1) decreased, while the growth of Rothia, a nitrate-reducing bacterium beneficial for blood pressure, was stimulated. CONCLUSIONS: The use of O-Cymen-5-ol and zinc chloride as antimicrobial agents in oral mouthwashes is a valuable alternative to classical antimicrobial agents.
Substantivity of mouth-rinse formulations containing cetylpyridinium chloride and O-cymen-5-ol: a randomized-crossover trial.[Pubmed:36575444]
BMC Oral Health. 2022 Dec 27;22(1):646.
BACKGROUND: The efficacy of mouth-rinses strongly depends upon their substantivity. The use of natural and non-toxic products that avoid secondary effects is gaining interest in preventive dentistry. The purpose of this study was to evaluate the substantivity of two formulations of mouth-washing solutions based on cetylpyridinium (CPC) and O-Cymen-5-ol. METHODS: This was a randomized, double-blind, crossover trial conducted at the Faculty of Medicine and Health Sciences of the University of Barcelona. Bacterial re-colonization was followed by live/dead (SYTO(TM)9 + propidium iodide) bacterial staining and measured by confocal laser scanning microscopy and fluorometry. Unstimulated saliva samples were collected from 16 healthy individuals at baseline saliva and then, at 15 min, 30 min and 1, 2, 3, and 4 h after the following mouth-rinses: (i) a single, 1-min mouth-rinse with 15 ml of placebo (negative control); (ii) a single, 1-min mouth-rinse with 15 ml of CPC (0.05%) ; (iii) a single, 1-min mouth-rinse with 15 ml of O-Cymen-5-ol (0.09%); (iv) a single, 1-min mouth-rinse with 15 ml of CPC (0.05%) + O-Cymen-5-ol (0.09%). RESULTS: Proportion of dead bacteria was significantly higher for all mouthrinses during the first 15 min compared to baseline (CPC = 48.0 +/- 13.9; 95% CI 40.98-56.99; p < 0.001, O-Cymen-5-ol = 79.8 +/- 21.0; 95% CI 67.71-91.90; p < 0.05, CPC + O-Cymen-5-ol = 49.4 +/- 14; 95% CI 40.98-56.99; p < 0.001 by fluorometry and 54.8 +/- 23.0; 95% CI 41.50-68.06; p < 0.001, 76.3 +/- 17.1; 95% CI 66.36-86.14; p < 0.001, 47.4 +/- 11.9; 95% CI 40.49-54.30; p < 0.001 by confocal laser scanning microscopy, respectively). Nevertheless, after 4 h, CPC + O-Cymen-5-ol was the only one that obtained significant values as measured by the two quantification methods used (80.3 +/- 22.8; 95% CI 67.15-93.50; p < 0.05 and 81.4 +/- 13.8; 95% CI 73.45-89.43; p < 0.05). The combined use of CPC + O-Cymen-5-ol increased the substantivity of the mouthrinse with respect to mouthrinses prepared with either of the two active products alone. CONCLUSION: The synergistic interaction of CPC and O-Cymen-5-ol prolongs their substantivity. The resulting formulation may be as effective as other antimicrobials, such as triclosan or chlorhexidine, but without their undesirable secondary effects. Thus, mouthrinsing products based on Combinations of CPC and O-Cymen-5-ol may replace in the near future Triclosan and Chlorhexidine-based mouthrinses.
Benefits of a silica-based fluoride toothpaste containing o-cymen-5-ol, zinc chloride and sodium fluoride.[Pubmed:21762159]
Int Dent J. 2011 Aug;61 Suppl 3(Suppl 3):74-80.
Fluoride toothpastes in conjunction with tooth brushing are used to clean teeth, control plaque build-up and for anti-caries benefits. Toothpastes are designed with attractive flavours and appearances to encourage regular prolonged use to maximise these benefits. The incorporation of additional ingredients into toothpaste is a convenient way to provide supplementary protection that fits into people's everyday oral care routine. Such ingredients should not compromise the primary health benefits of toothpaste nor discourage its use. O-Cymen-5-ol and zinc chloride have been incorporated into a sodium fluoride (NaF)/silica toothpaste at 0.1%w/w and 0.6%w/w respectively to provide additional benefits. These include improved gingival health maintenance, in terms of the reduction of plaque, gingival index and bleeding, and an immediate and long lasting reduction in volatile sulfur compounds (VSCs) measured on breath. These benefits can be attributed to the antimicrobial and neutralisation actions of the toothpaste. The use of established fluoride models demonstrated no compromise in NaF bioavailability. The toothpaste was formulated without compromising product aesthetics. The combination of O-Cymen-5-ol and zinc chloride in toothpaste gave superior maintenance of gingival health and reduction in malodour related VSCs without compromising the primary health benefits of the toothpaste or diminishing attributes preferred for the product's use.
In vitro effects of novel toothpaste actives on components of oral malodour.[Pubmed:21762158]
Int Dent J. 2011 Aug;61 Suppl 3(Suppl 3):67-73.
OBJECTIVES: To evaluate the efficacy of a novel toothpaste containing zinc ions and O-Cymen-5-ol to reduce volatile sulfur compounds (VSCs) in in vitro models and to elucidate the mode of action for any activity observed. METHODS: Three models were employed, a chemical neutralisation model to evaluate the chemical reactivity of toothpaste slurries to VSCs, a biofilm perfusion model to measure activity in an orally-relevant biofilm and a planktonic bacterial model to measure antimicrobial effects. RESULTS: The models showed that zinc ions were able to react chemically with hydrogen sulfide to remove this odorous component of halitotic breath. This activity was confirmed within a complex biofilm model, with over 90% of hydrogen sulfide removed from perfusate gas by a slurry of the test toothpaste. CONCLUSIONS: This work provides a mode of action for the clinically observed reduction in VSCs seen for up to 12 hours post brushing with this novel toothpaste.
A randomised clinical trial to assess control of oral malodour by a novel dentifrice containing 0.1%w/w o-cymen-5-ol, 0.6%w/w zinc chloride.[Pubmed:21762157]
Int Dent J. 2011 Aug;61 Suppl 3(Suppl 3):60-6.
OBJECTIVES: To assess the ability of a 0.1% w/w O-Cymen-5-ol/ 0.6% w/w zinc chloride/ sodium fluoride dentifrice to control oral malodour compared to a sodium fluoride control dentifrice. DESIGN: Following baseline measurement of oral volatile sulfur compounds (VSCs), the subjects brushed twice daily for 1 week with either the test or control dentifrice. The VSC concentration in breath samples was monitored up to 12 hours post-treatment, by gas chromatography (GC). RESULTS: 75 subjects were included in the efficacy analysis. Relative to the sodium fluoride control dentifrice group the O-Cymen-5-ol/ zinc chloride/ sodium fluoride dentifrice exhibited statistically significant reductions (P<0.0001) in hydrogen sulfide, methyl mercaptan and total measured VSCs immediately and after 1, 2, 3 and 12 (overnight) hours post-treatment. CONCLUSION: The results of the present clinical study demonstrated that the use of the 0.1% w/w O-Cymen-5-ol/ 0.6% w/w zinc chloride/ sodium fluoride dentifrice over a one week period provided a statistically significant benefit in controlling oral malodour for up to 12 hours post-treatment compared to a sodium fluoride control dentifrice.
Protection against enamel demineralisation using toothpastes containing o-cymen-5-ol, zinc chloride and sodium fluoride.[Pubmed:21762156]
Int Dent J. 2011 Aug;61 Suppl 3(Suppl 3):55-9.
AIM: To evaluate the ability of two experimental toothpastes containing 0.1%w/w O-Cymen-5-ol, 0.6%w/w ZnCl2 and 0.320%w/w NaF to reduce demineralisation of sound human enamel compared with control toothpastes. METHODS: Study 1: Specimens were treated with toothpaste slurries, followed by alternating periods in demineralising and neutral solutions. Demineralisation was assessed using surface microhardness (SMH). Study 2: Specimens were subjected to a 14 day cycling regime of alternating demineralisation/remineralisation with two toothpaste treatments per day, before and after demineralisation. Demineralisation was assessed by cross-sectional microhardness and mineral loss (DeltaZ) was calculated. Test toothpastes were a) 0%w/w or 0.002%w/w NaF placebo, b) 0.055%w/w or 0.149%w/w NaF (dose response), c) 0.320%w/w NaF marketed product, d & e) 0.1%w/w O-Cymen-5-ol, 0.6%w/w ZnCl2 and 0.320%w/w NaF (experimental toothpastes). RESULTS: Study 1: Mean+/-SE % of baseline hardness values were a) 48.0+/-2.1a, b) 66.7+/-1.7b, c) 82.9+/-1.9c, d) 91.7+/-1.4d and e) 94.6+/-2.1d. Study 2: Mean+/-SE DeltaZ values were a) 2114+/-187a, b) 1206+/-132b, c) 303+/-89c, d) 19+/-73c, and e) -10+/-55c. Letters represent different statistical groupings (P<0.05). CONCLUSION: In study 1, both experimental toothpastes were statistically superior to the marketed product and in study 2; they were at least as effective as the marketed product at reducing caries lesion development.
Retention of o-cymen-5-ol and zinc on reconstructed human gingival tissue from a toothpaste formulation.[Pubmed:21762154]
Int Dent J. 2011 Aug;61 Suppl 3(Suppl 3):41-5.
OBJECTIVES: To assess the retention of O-Cymen-5-ol and zinc on reconstructed human gingival tissue delivered by topical applications of toothpaste formulated with 0.1%w/w O-Cymen-5-ol and 0.6%w/w zinc chloride (ZnCl2). METHODS: EpiGingival tissues were treated topically for 2 minutes with either solutions or toothpaste slurries containing O-Cymen-5-ol and ZnCl2. Tissues were rinsed with water between application and the effects of repeat dosing for up to 6 occasions were investigated. Tissues were blot dried, extracted and O-Cymen-5-ol and zinc were measured by HPLC and atomic absorption spectroscopy, respectively. RESULTS: Retention of O-Cymen-5-ol and zinc delivered from solutions to EpiGingival tissues showed a dose response to the concentration and to the number of applications. Significantly higher concentrations of zinc were delivered to EpiGingival tissues by toothpaste compared to equivalent doses delivered from solution. Equivalent doses of O-Cymen-5-ol were delivered from toothpaste and solution. No cytotoxic effects on the EpiGingival tissues, measured by MTT viability, were detected following application of test toothpaste compared to a water control. CONCLUSIONS: Reconstructed human gingival tissue proved to be an effective model for the assessment of active retention from topically applied formulations. The test toothpaste was effective in delivering O-Cymen-5-ol and zinc to oral soft tissue in vitro.
Antimicrobial effects of o-cymen-5-ol and zinc, alone & in combination in simple solutions and toothpaste formulations.[Pubmed:21762153]
Int Dent J. 2011 Aug;61 Suppl 3(Suppl 3):33-40.
OBJECTIVES: This study aimed to evaluate antimicrobial effects of an O-Cymen-5-ol/zinc system. METHODS: O-Cymen-5-ol and zinc gluconate minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined against Streptococcus mutans, Actinomyces viscosus, Porphyromonas gingivalis, Fusobacterium nucleatum and Candida albicans. Synergy was investigated by checkerboard MIC/MBC; inhibition of P. gingivalis protease activity and S. mutans glycolysis were investigated. Slurried toothpastes containing the system were assessed in kill time assays against S. mutans and E. coli. RESULTS: O-Cymen-5-ol MIC was between 1.7 mM to 3.4 mM; MBC was 3.4 mM to 6.7 mM. Zinc gluconate MIC was 2.8 mM to 11 mM; MBC was between 11 mM and >44 mM. The two agents in solution showed synergy (FICI=0.50) against P. gingivalis and F. nucleatum, with MIC of 0.42 mM/0.69 mM for O-Cymen-5-ol/zinc gluconate, respectively. Zinc inhibited glycolysis and protease to a greater degree than O-Cymen-5-ol; glycolysis inhibition by the two agents was additive. O-Cymen-5-ol/zinc chloride in toothpaste showed greater effects than placebo (120s log10 kill=7.35+/-0.40 and 4.02+/-0.40, respectively). CONCLUSIONS: The zinc/O-Cymen-5-ol system has direct antimicrobial effects and inhibits oral disease-related processes. Synergistic effects were seen against anaerobes. A system combining O-Cymen-5-ol and zinc shows properties desirable for incorporation in toothpastes.
Maintenance of gingival health--a measure based on clinical indices.[Pubmed:21762152]
Int Dent J. 2011 Aug;61 Suppl 3(Suppl 3):28-32.
OBJECTIVES: To introduce a variable which directly measures maintenance of gingival health. DESIGN: The maintenance of gingival health index (MGHI) is based on the change in score at each tooth site compared to a reference visit for a clinical index (eg MGI or BI). For a subject the number of sites that (1) improve-NDEC, (2) show no change-NNOCHG or (3) worsen-NINC in score are determined. Then the MGHI for a subject is defined as (NDEC+NNOCHNG)/NINC. RESULTS: This method was applied to two clinical studies and both studies demonstrated significantly better maintenance of gingival health in those subjects who received the experimental 0.1% w/w O-Cymen-5-ol/ 0.6% w/w ZnCl2 dentifrice compared to the 0.204% w/w sodium fluoride control dentifrice based on a gingival and a bleeding clinical index. CONCLUSION: The MGHI is a useful measure to assess the maintenance of gingival health. It is very applicable to the maintenance of gingival health study designs as it directly looks at a measurement of maintaining the health of tooth sites. It also provides a meaningful measure of the relative effectiveness of dentifrice products to the dental practitioner.
A randomised clinical trial to assess maintenance of gingival health by a novel gel to foam dentifrice containing 0.1%w/w o-cymen-5-ol, 0.6%w/w zinc chloride.[Pubmed:21762151]
Int Dent J. 2011 Aug;61 Suppl 3(Suppl 3):21-7.
OBJECTIVES: To assess the ability of 0.1%w/w O-Cymen-5-ol/ 0.6%w/w zinc chloride gel to foam dentifrice to maintain gingival health compared to a sodium fluoride control dentifrice. DESIGN: Following a baseline examination, subjects went through a regimen to bring them to a high level of gingival health. This involved a professional dental prophylaxis supported by oral hygiene instruction prior to commencing study treatment. Subjects brushed twice daily for 12 weeks with either the test or control dentifrice. Examinations for gingival inflammation (MGI), bleeding and plaque were performed after 12 weeks. RESULTS: 205 subjects were included in the efficacy analysis. Relative to the sodium fluoride/ silica control dentifrice group the O-Cymen-5-ol/ zinc chloride gel to foam dentifrice exhibited statistically significant reductions (p<0.0001) in MGI, bleeding and plaque of 32.2%, 26.3% and 20.7% respectively after 12 weeks. CONCLUSION: The results of the present clinical study demonstrate that the use of the 0.1%w/w O-Cymen-5-ol/ 0.6%w/w zinc chloride gel to foam dentifrice over a 12 week period provides a statistically significant benefit in maintaining gingival health compared to a sodium fluoride control dentifrice.
A randomised clinical trial to assess maintenance of gingival health by a novel dentifrice containing 0.1%w/w o-cymen-5-ol and 0.6%w/w zinc chloride.[Pubmed:21762150]
Int Dent J. 2011 Aug;61 Suppl 3(Suppl 3):13-20.
OBJECTIVES: To assess the ability of 0.1%w/w O-Cymen-5-ol/ 0.6%w/w zinc chloride dentifrice to maintain gingival health compared to a sodium fluoride control dentifrice. DESIGN: Following a baseline examination, subjects went through a regimen to bring them to a high level of gingival health. This included a professional prophylaxis supported by oral hygiene instruction prior to commencing study treatment. Subjects brushed twice daily for 12 weeks with either the test or control dentifrice. Examinations for gingival inflammation (MGI), bleeding and plaque were performed after 6 and 12 weeks. RESULTS: 224 subjects were included in the efficacy analysis. Relative to the sodium fluoride/ silica control dentifrice group the O-Cymen-5-ol/ zinc chloride dentifrice exhibited statistically significant reductions (p<0.0001) in MGI, bleeding and plaque of 12.3%, 18.5% and 13.2% respectively after six weeks and 38.1%, 37.8% and 24.2% after 12 weeks. CONCLUSION: The results of the present clinical study demonstrate that the use of the 0.1%w/w O-Cymen-5-ol/ 0.6%w/w zinc chloride dentifrice over a 12 week period provides a statistically significant benefit in maintaining gingival health compared to a sodium fluoride control dentifrice.
Final report on the safety assessment of sodium p-chloro-m-cresol, p-chloro-m-cresol, chlorothymol, mixed cresols, m-cresol, o-cresol, p-cresol, isopropyl cresols, thymol, o-cymen-5-ol, and carvacrol.[Pubmed:16835130]
Int J Toxicol. 2006;25 Suppl 1:29-127.
Sodium p-Chloro-m-Cresol, p-Chloro-m-Cresol (PCMC), Mixed Cresols, m-Cresol, o-Cresol, p-Cresol, Isopropyl Cresols, Thymol, Chlorothymol, O-Cymen-5-ol, and Carvacrol are substituted phenols used as cosmetic biocides/preservatives and/or fragrance ingredients. Only PCMC, Thymol, and O-Cymen-5-ol are reported to be in current use, with the highest concentration of use at 0.5% for O-Cymen-5-ol in perfumes. The use of PCMC in cosmetics is restricted in Europe and Japan. Cresols can be absorbed through skin, the respiratory tract, and the digestive tract; metabolized by the liver; and excreted by the kidney as glucuronide and sulfate metabolites. Several of these cresols increase the dermal penetration of other agents, including azidothymidine. In acute oral toxicity studies, LD50 values were in the 200 to 5000 mg/kg day-1 range across several species. In short-term studies in rats and mice, an o-Cresol, m-Cresol, p-Cresol or m-Cresol/p-Cresol mixture at 30,000 ppm in the diet produced increases in liver and kidney weights, deficits in liver function, bone marrow hypocellularity, irritation to the gastrointestinal tract and nasal epithelia, and atrophy of female reproductive organs. The no observed effect levels (NOEL) of o-Cresol was 240 mg/kg in mink and 778 mg/kg in ferrets in short-term feeding studies, with no significant dose-related toxicity (excluding body weight parameters). In mice, 0.5% p-Cresol, but neither m-Cresol nor o-Cresol, caused loss of pigmentation. Short-term and subchronic oral toxicity tests performed with various cresols using mice, rats, hamsters, and rabbits resulted in no observed adverse effect levels (NOAELs) for mice of 625 ppm and rats of 50 mg/kg day-1, although the NOEL was 2000 ppm in a chronic study using rats. In rabbits, < or =160 mg/kg PCMC was found to produce irritation and erythema, but no systemic effects. Hamsters dosed with 1.5% p-Cresol in diet for 20 weeks had a greater incidence of mild and moderate forestomach hyperplasia as compared to the control. Acute inhalation toxicity studies using rats yielded LC50 values ranging from >20 mg/m(3) for o-Cresol to >583 mg/m(3) for PCMC. No deaths were recorded in mice given o-Cresol at 50 mg/m(3). Cats exposed (short-term) to 9 to 50 mg/m(3) of o-Cresol developed inflammation and irritation of the upper respiratory tract, pulmonary edema, and hemorrhage and perivascular sclerosis in the lungs. Rats exposed (subchronic) to o-Cresol at 9 mg/m(3) had changes in leukocytes, spinal cord smears, nervous activity, liver function, blood effects, clinical signs, and neurological effects. In guinea pigs, exposure to 9 mg/m(3) produced changes in hemoglobin concentrations and electrocardiograms (EKGs). Rats exposed (subchronic) to 0.05 mg/m(3) Mixed Cresols by inhalation exhibited central nervous system (CNS) excitation, denaturation of lung protein, and decreased weight gain. All cresols appear to be ocular irritants. Numerous sensitization studies have been reported and most positive reactions were seen with higher concentrations of Cresol ingredients. Developmental toxicity is seen in studies of m-Cresol, o-Cresol, and p-Cresol, but only at maternally toxic levels. In a reproductive toxicity study of a mixture of m-Cresol and p-Cresol using mice under a continuous breeding protocol, 1.0% caused minimal adult reproductive and significant postnatal toxicity in the presence of systemic maternal toxicity. The o-Cresol NOAEL was 0.2% for both reproductive and general toxicity in both generations. Cresol ingredients were generally nongenotoxic in bacterial, fruit fly, and mammalian cell assays. Thymol did not induce primary lung tumors in mice. No skin tumors were found in mice exposed dermally to m-Cresol, o-Cresol, or p-Cresol for 12 weeks. In the trypthan blue exclusion assay, antitumor effects were observed for Thymol and Carvacrol. Clinical patch testing with 2% PCMC may produce irritant reactions, particularly in people with multiple patch test reactions, that are misinterpreted as allergic responses. o-Cresol, p-Cresol, Thymol, Carvacrol, and O-Cymen-5-ol caused no dermal irritation at or above use concentrations. In two predictive patch tests, PCMC did not produce a sensitization reaction. Overall, these ingredients are not significant sensitizing or photosensitizing agents. The Cosmetic Ingredient Review (CIR) Expert Panel noted some of these ingredients may increase the penetration of other cosmetic ingredients and advised cosmetic formulators to take this into consideration. The CIR Expert Panel concluded that the toxic effects of these ingredients are observed at doses higher than would be available from cosmetics. A concentration limitation of 0.5% was chosen to ensure the absence of a chemical leukoderma effect. For p-Cresol and Mixed Cresols (which contain p-Cresol), the Panel considered that the available data are insufficient to support the safety of these two ingredients in cosmetics. Studies that would demonstrate no chemical leukoderma at concentrations of use of p-Cresol and Mixed Cresols, or would demonstrate a dose response from which a safe concentration could be derived, are needed.