WS-12

General Material Information

Preferred name	WS-12
Trivial Name	(1R,2S,5R)-N-(4-Methoxyphenyl)-5-methyl-2-(1-methylethyl)cyclohexanecarboxamide
Short Description	(1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)cyclohexanecarboxamide
Formula	C18 H27 N O2
CAS Number	68489-09-8
FEMA Number	4681
Flavis Number	16.123
FDA UNII	1L7BVT4Z4Z
Nikkaji Number	J2.926.766I
MDL	MFCD11100191
xLogP3-AA	4.60 (est)
NMR Predictor	External link
JECFA Food Flavoring	2079 (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)cyclohexanecarboxamide
FDA Patent	No longer provide for the use of these seven synthetic flavoring substances
FDA Mainterm	68489-09-8 ; (1R,2S,5R)-N-(4-METHOXYPHENYL)-5-METHYL-2-(1-METHYLETHYL)CYCLOHEXANECARBOXAMIDE
Synonyms	cyclohexanecarboxamide, N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-, (1R,2S,5R)- (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)cyclohexane-carboxamide (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)cyclohexanecarboxamide (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-propan-2-ylcyclohexane-1-carboxamide (1R,2S,5R)-2-iso propyl-N-(4-methoxyphenyl)-5-methylcyclohexanecarboxamide Cyclohexanecarboxamide, N-(4-methoxyphenyl)-5-methyl-2-(1-methylethyl)-, [1R-(1α,2β,5α)]- (1R,2S,5R)-N-(4-Methoxyphenyl)-5-methyl-2-(1-methylethyl)cyclohexanecarboxamide WS 12 [1R,2S,5R]-N-(4-Methoxyphenyl)-p-menthanecarboxamide FEMA 4681 Acoltremon Fema Gras 4681 AR 15512 AR-15512 WS 13

US / EU / FDA / JECFA / FEMA / Scholar / Patents

Google Scholar	Start search
Google Books	Start search
Google Patents	Start search
Perfumer & Flavorists	Start search
EU Patents	Start search
PubMeb	Start search
NCBI	Start search

Literature & References

Leffingwell:	Chirality or Article
	(1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-propan-2-ylcyclohexane-1-carboxamide
NIST Chemistry WebBook:	Search Inchi
Pubchem (cid):	11266244
Pubchem (sid):	74660095

Publications by PubMed
TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain.
Patient experiences at primary care practices using electronic health records.
Practicability and sensitivity to change of the activities-specific balance confidence scale and 12-item Walking Scale for stroke.
Blockade of TRPM8 activity reduces the invasion potential of oral squamous carcinoma cell lines.
Sensitization of capsaicin and icilin responses in oxaliplatin treated adult rat DRG neurons.
Characterization of selective TRPM8 ligands and their structure activity response (S.A.R) relationship.
Menthol derivative WS-12 selectively activates transient receptor potential melastatin-8 (TRPM8) ion channels.
Characterisation of TRPM8 as a pharmacophore receptor.
Prospects for prostate cancer imaging and therapy using high-affinity TRPM8 activators.
Publications by Leffingwell & Associates
Flavor Properties of FEMA GRAS List 25 flavor chemicals

Other Information

(IUPAC):	Atomic Weights of the Elements 2011 (pdf)
Videos:	The Periodic Table of Videos
tgsc:	Atomic Weights use for this web site
(IUPAC):	Periodic Table of the Elements
FDA Substances Added to Food (formerly EAFUS):	View
CHEMBL:	View
HMDB (The Human Metabolome Database):	Search
FDA Listing of Food Additive Status:	View
ChemSpider:	View

Suppliers

BOC Sciences	Gem Aromatics
M&U International	O'Laughlin Industries
Parchem	Santa Cruz Biotechnology
Sigma-Aldrich: Sigma	Tianjin Danjun International
Tocris Bioscience	M&U International LLC
O'Laughlin Industries Inc.	Tianjin Danjun International Trade Co., LTD.

PhysChem Properties

Material listed in food chemical codex	No
Molecular weight	289.41857910156
Boiling Point	447 to 448°C @ 760 mm Hg
Flash Point TCC Value	224.6 °C TCC
logP (o/w)	5.017 est
Solubility
alcohol	Yes
water, 0.5185 mg/L @ 25 °C (est)	Yes
water	No

Organoleptic Properties

Odor Type: Minty
General comment	At 100.00 %. cool minty
Flavor Type: Cooling
cooling
General comment	Cooling

Safety Information

Safety information

Preferred SDS: View

Hazards identification

Classification of the substance or mixture
GHS Classification in accordance with 29 CFR 1910 (OSHA HCS)
None found.
GHS Label elements, including precautionary statements

Pictogram

Hazard statement(s)
None found.
Precautionary statement(s)
None found.
Oral/Parenteral Toxicity:
oral-rat LD50 [sex: F] > 2000 mg/kg (Bradshaw, 2008)
Dermal Toxicity:
Not determined
Inhalation Toxicity:
Not determined

Safety in use information

Category:
flavor enhancers, flavoring agents
Recommendation for WS-12 usage levels up to:
	not for fragrance use.

Maximised Survey-derived Daily Intakes (MSDI-EU):		12.00 (μg/capita/day)
Modified Theoretical Added Maximum Daily Intake (mTAMDI):		150 (μg/person/day)
Threshold of Concern:		90 (μg/person/day)
Structure Class:		III
Use levels for FEMA GRAS flavoring substances on which the FEMA Expert Panel based its judgments that the substances are generally recognized as safe (GRAS).
The Expert Panel also publishes separate extensive reviews of scientific information on all FEMA GRAS flavoring substances and can be found at FEMA Flavor Ingredient Library
publication number: 25
Click here to view publication 25
		average usual ppm	average maximum ppm
baked goods:		1.00000	5.00000
beverages(nonalcoholic):		1.00000	5.00000
beverages(alcoholic):		1.00000	10.00000
breakfast cereal:		1.00000	5.00000
cheese:		-	-
chewing gum:		100.00000	500.00000
condiments / relishes:		-	-
confectionery froastings:		1.00000	10.00000
egg products:		1.00000	10.00000
fats / oils:		1.00000	10.00000
fish products:		-	-
frozen dairy:		5.00000	20.00000
fruit ices:		2.00000	20.00000
gelatins / puddings:		2.00000	20.00000
granulated sugar:		2.00000	20.00000
gravies:		-	-
hard candy:		2.00000	20.00000
imitation dairy:		1.00000	5.00000
instant coffee / tea:		1.00000	5.00000
jams / jellies:		2.00000	20.00000
meat products:		-	-
milk products:		1.00000	5.00000
nut products:		-	-
other grains:		-	-
poultry:		-	-
processed fruits:		1.00000	5.00000
processed vegetables:		-	-
reconstituted vegetables:		-	-
seasonings / flavors:		-	-
snack foods:		-	-
soft candy:		1.00000	20.00000
soups:		1.00000	20.00000
sugar substitutes:		1.00000	20.00000
sweet sauces:		-	-

Food categories according to Commission Regulation EC No. 1565/2000 (EC, 2000) in FGE.06 (EFSA, 2002a). According to the Industry the "normal" use is defined as the average of reported usages and "maximum use" is defined as the 95th percentile of reported usages (EFSA, 2002i).
Note: mg/kg = 0.001/1000 = 0.000001 = 1/1000000 = ppm.
		average usage mg/kg	maximum usage mg/kg
Dairy products, excluding products of category 02.0 (01.0):		0.50000	5.00000
Fats and oils, and fat emulsions (type water-in-oil) (02.0):		0.50000	10.00000
Edible ices, including sherbet and sorbet (03.0):		0.50000	10.00000
Processed fruit (04.1):		0.50000	5.00000
Processed vegetables (incl. mushrooms & fungi, roots & tubers, pulses and legumes), and nuts & seeds (04.2):		-	-
Confectionery (05.0):		1.00000	20.00000
Chewing gum (05.3):		-	-
Cereals and cereal products, incl. flours & starches from roots & tubers, pulses & legumes, excluding bakery (06.0):		0.50000	5.00000
Bakery wares (07.0):		0.50000	5.00000
Meat and meat products, including poultry and game (08.0):		-	-
Fish and fish products, including molluscs, crustaceans and echinoderms (MCE) (09.0):		-	-
Eggs and egg products (10.0):		0.50000	10.00000
Sweeteners, including honey (11.0):		1.00000	20.00000
Salts, spices, soups, sauces, salads, protein products, etc. (12.0):		1.00000	20.00000
Foodstuffs intended for particular nutritional uses (13.0):		-	-
Non-alcoholic ("soft") beverages, excl. dairy products (14.1):		0.10000	1.00000
Alcoholic beverages, incl. alcohol-free and low-alcoholic counterparts (14.2):		0.20000	1.00000
Ready-to-eat savouries (15.0):		-	-
Composite foods (e.g. casseroles, meat pies, mincemeat) - foods that could not be placed in categories 01.0 - 15.0 (16.0):		-	-