ChemForward Alternatives

Isopropyl myristate

CASRN#

110-27-0

INCI Name

ISOPROPYL MYRISTATE

Alternate Names

1-Methylethyl tetradecanoate; Tetradecanoic acid, 1-methylethyl ester; 1-Tridecanecarboxylic acid, isopropyl ester; EC 203-751-4; EPA Pesticide Chemical Code 00207; FEMA No. 3556; IPM; Isopropyl tetradecanoate; Tetradecanoic acid, isopropyl;, Tetradecanoic acid, isopropyl ester (ChemIDplus 2020)

Common Trade Names

Crodamol IPM; Deltyl Extra; Emcol-IM; Emerest 2314; Estergel; Isomyst; Kessco IPM; Kesscomir; Plymoutm IPM; Promyr; Sinnoester MIP; Starfol IPM; Stepan D-50; Tegester; Unimate IPM; Wickenol 101 (ChemIDplus 2020)

Molecular Weight

270.5 g/mol

Functional Uses

Isopropyl myristate (isopropyl tetradecanoate) functions as an emollient, binder, perfuming agent, skin conditioning agent and masking agent in cosmetics (EC 2020, CIR 2015). , It is also listed as an inert ingredient for use in pesticide products (U.S. EPA 2010).

Common Impurities

Myristic acid and other free fatty acids up to 1.0%, and unsaponifiable material at up to 0.2%.

Is this a VOC?

Yes

Is this an exempt VOC?

Vapor Pressure

0.00000629 mm Hg

Octanol-water partition coefficient (log Kow)

7.18

Solubility

473376.1207 mg/l

Boiling Point

185 °C

Particle size range as aerodynamic diameter

- - - μm

Hazard Summary

C2C Chemical Rating

x/c-CMR(2)

GHS Health

H336H361

GHS Enviro

None

Assessed by

ToxServices LLC

Assessment Date

Sep 8, 2020

Assessment Expires

Sep 8, 2025

Verification Status

verified

Executive Summary

A ChemFORWARD chemical hazard assessment (CHA) comprises a comprehensive evaluation and hazard classification of 24 human health and environmental toxicity endpoints, based on criteria from the United Nations’ Globally Harmonized System of Classification and Labelling of Substances (GHS) and Cradle to Cradle Certified™ Material Health Assessment Methodology (C2C). As the evaluation includes assessment of oral, dermal, and inhalation routes of exposure, a ChemFORWARD CHA includes 51 written rationales and data summaries to support conclusions and hazard classifications. Isopropyl myristate (IUPAC name: propan-2-yl tetradecanoate) is an alkyl ester that is used as an emollient, binder, skin conditioning agent, perfuming agent and masking agent in cosmetic and personal care products. It is also an inert ingredient in pesticides. Isopropyl myristate is Generally Recognized As Safe (GRAS) for addition to food as determined by the Flavor and Extract Manufacturers Association (FEMA) (U.S. FDA 2020). Isopropyl myristate is a clear, colorless, and odorless liquid, is non-flammable, non-corrosive, non-explosive, and has very low solubility in water. It has a low boiling point and is therefore a volatile organic compound (VOC). Isopropyl myristate is manufactured from isopropyl alcohol and myristic acid. Isopropyl myristate has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel and was determined to be safe for use in cosmetic formulations when formulated to be non-irritating (CIR 2015). It is listed on the Chinese Food and Drug Administration’s Cosmetics Ingredients List. It has not been reviewed by the European Scientific Committee on Consumer Safety (SCCS), and is not listed on Annex II or III of the EC Cosmetics Regulation, California’s Safe Cosmetics Program’s Reportable Ingredients List, or Canada’s Cosmetic Ingredient Hotlist. Isopropyl myristate has been reviewed by the European Food Safety Authority (EFSA) Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), and the Joint Food and Agricultural Organization and World Health Organization (FAO/WHO) Expert Committee on Food Additives (JECFA). Isopropyl myristate has an incomplete toxicological profile. Therefore, ToxServices used alkyl esters of similar fatty acids and alcohols as surrogates, and performed modeling where feasible and when no data were available. Human health concerns include developmental toxicity by the oral route of exposure and transient narcotic effects following acute inhalation exposure at high concentrations. Despite the use of surrogates and modeling, there are a number of data gaps, including reproductive toxicity (dermal and inhalation), developmental toxicity (inhalation), endocrine activity, lactation toxicity, and neurotoxicity following repeated exposure (dermal and inhalation). Additionally, isopropyl myristate enhances the skin penetration potential and hence toxicity potential of other chemicals. Isopropyl myristate has low environmental concerns. It has low acute and chronic aquatic toxicities and terrestrial toxicity, is readily biodegradable, and is non-bioaccumulative. It does not contribute to global warming or deplete the ozone layer. This chemical hazard assessment was performed in accordance with the timeline of animal testing bans in Europe and California. Only studies that comply with in vivo testing timeline bans are used in this ChemFORWARD assessment to classify hazards and assign a point of departure. Endpoint-specific summaries in this assessment specify disclosed dates of animal testing. The testing bans did not affect the evaluation of isopropyl myristate. For purposes of performing a cosmetics ingredient safety assessment, a 5,500 mg/kg/day point of departure is recommended for isopropyl myristate, and is based on the NOAEL of 5,500 mg/kg/day from a GLP-compliant 90-day feeding study with reproductive toxicity assessment in rats exposed to surrogate ethyl oleate (CAS #111-62-6) and a safety factor of 1.

Hazard Tables

How to read the GHS Hazard Summary Table

	Carcinogenicity	Mutagenicity	Reproductive Toxicity	Developmental Toxicity	Acute Toxicity	STOT-Single	STOT-Repeated	STOT- Neurotoxicity-Single	STOT- Neurotoxicity-Repeated	Skin Sensitizer	Respiratory Sensitizer	Skin Corrosion/Irritation	Serious Eye Damage/Eye Irritation	Acute Aquatic Toxicity	Chronic Aquatic Toxicity	Ozone Depletion
Oral Dermal Inhalation	NC Rationale No data were found. Modeling predicts isopropyl myristate will be negative for carcinogenicity via the oral route of exposure based on statistical-based (Danish (Q)SAR database) and expert rule-based (VEGA IRFMN/Antares) models with high reliability. Confidence is low due to lack of measured data. NC Rationale Negative results were reported in two carcinogenicity studies performed in mice. As the studies were non-guideline, and not well detailed in the public literature, the weight of evidence is supplemented with modeling. Modeling predicts isopropyl myristate will be negative for carcinogenicity via the dermal route of exposure based on statistical-based (Danish (Q)SAR database) and expert rule-based (VEGA IRFMN/Antares) models with high reliability. Confidence is high based on the collective weight of evidence from experimental studies and modeling. NC Rationale No data were found. Modeling predicts isopropyl myristate will be negative for carcinogenicity via the inhalation route of exposure based on statistical-based (Danish (Q)SAR database) and expert rule-based (VEGA IRFMN/Antares) models with high reliability. Confidence is low due to lack of data.	NC Rationale Isopropyl myristate tested negative in two bacterial reverse mutation assays, and surrogate compounds tested negative in an in vitro gene cell mutation assay and in vitro chromosome aberration assays. Confidence is high based on reliable data for both gene mutation and chromosomal aberration for the target chemical or strong surrogates.	NC Rationale No adverse effects on reproductive endpoints were found in two studies with surrogate compounds. Confidence is high based on high quality data for strong surrogates. CNP Rationale No data. CNP Rationale No data.	Cat 2 Rationale Reduced pre- and postweaning growth were reported in a one-generation reproductive toxicity study with the surrogate butyl stearate, at a high dose of 6.25% in the diet. Therefore, ToxServices conservatively classified isopropyl myristate to GHS Category 2 for developmental toxicity. Confidence is reduced due to the lack of description of maternal systemic toxicity and hence the inability to determine if the effects are secondary to maternal toxicity. NC Rationale Rationale: No developmental toxicities were observed in two prenatal developmental toxicity studies on isopropyl myristate in rats and rabbits even at maternally toxic doses. In the study in rats, maternal toxicity was found at the highest dose of 1,000 mg/kg/day as clinical signs, dermal irritation and decreased body weight gain, but no developmental parameters were affected up to the highest dose tested. In the study in rabbits, maternal toxicity was observed at the highest dose of 600 mg/kg/day as dermal irritation. While one animal was nongravid, leading to a slightly slower pregnancy rate of the high dose group (94.1% compared to 100% in other groups), the statistical and biological significance is unclear. No developmental toxicity was observed up to the highest dose tested. As no developmental effects were found in these studies, classification is not warranted. Confidence is high based on reliable experimental data. CNP Rationale No data.	NC Rationale Numerous studies demonstrate LD50 values > 5,000 mg/kg, which exceeds the criteria for GHS classification (i.e., 2,000 mg/kg). Confidence is high based on high quality data and weight of evidence from numerous studies. NC Rationale Dermal LD50 values are clearly > 2,000 mg/kg in animal studies, which is the GHS cutoff. ToxServices assigned a “not classified” with low confidence based on limited details reported in the public literature. NC Rationale Two 1-hour inhalation studies resulted in no deaths to exposed animals. The highest exposure resulted in a 1-hour aerosol LC50 value > 41 mg/L, equivalent to >10 mg/L when adjusted to 4-hour exposure duration in accordance with the GHS guidance. This exceeds the GHS guidance value of 5.0 mg/L for dusts/mists, therefore no classification is warranted. Confidence is low based on limited study details reported.	NC Rationale No indications of systemic toxicity are reported in numerous acute oral toxicity studies, accordingly no GHS classification is warranted. Confidence is high based on reliable and consistent results across multiple studies. NC Rationale No indications of systemic toxicity were reported in multiple acute dermal toxicity studies at doses up to 1,834 mg/kg, accordingly GHS classification is not warranted. Confidence is low based on limited details reported in the public literature and that the highest dose tested was below the highest GHS guidance value of 2,000 mg/kg. NC Rationale No indications of respiratory irritation were reported amongst several acute and repeated dose inhalation toxicity studies. One exception includes 2 of 9 monkeys that had wheezing and coughing, however the effects were not dose related, and therefore may be considered not treatment-related. Confidence is high based on numerous studies with both acute and repeated exposures.	NC Rationale No treatment-related observations of systemic toxicity are identified in a 28-day study in rats exposed to isopropyl myristate, or a 90-day study in rats exposed to a surrogate compound. The reported NOAEL for the 28-day study is greater than the duration-adjusted GHS guidance value of 300 mg/kg/day (i.e., 100 mg/kg/day x 3 months/1 month), and the 90-day NOAEL was greater than the GHS guidance value of 100 mg/kg; accordingly, classification is not warranted. Confidence is high based on high quality date for the target compound and a strong surrogate. NC Rationale No indications of systemic toxicity have been reported based on several dermal repeated dose studies with isopropyl myristate at up to 571 mg/kg/day in 28-day studies, which is below the duration-adjusted GHS guidance value of 600 mg/kg/day (i.e., 200 mg/kg/day x 3 months/1 month) for Category 2 for 28-day studies, but above the adjusted GHS guidance value of 60 mg/kg/day for GHS Category 1. Liver toxicity was found in a poorly described 20-day study at a high dose of 3,643 mg/kg/day, which is above the GHS guidance values. As insufficient data are available to demonstrate a lack of adverse systemic effects below the GHS Category 2 cutoff, ToxServices assigned a “not classified” designation with reduced confidence. NC Rationale Several repeated dose inhalation toxicity studies demonstrate lack of adverse systemic effects, therefore GHS classification is not warranted. Confidence is low because the studies were pre-guideline, and not well detailed in the public literature, and testing was not performed up to the GHS guidance value of 0.2 mg/L for mists.	NC Rationale No indications of neurotoxicity were reported in numerous acute oral toxicity studies, therefore GHS classification is not warranted. Confidence is low as the assessment is based on limited reporting of clinical observations and necropsy findings for some studies, and no studies discuss a neurotoxicity assessment. NC Rationale No indications of neurotoxicity were reported in multiple acute dermal toxicity studies, accordingly GHS classification is not warranted. Confidence is low based on limited details reported in the public literature, and the highest tested dose is slightly below the GHS cutoff of 2,000 mg/kg. Cat 3 Rationale Lethargy was reported in an acute inhalation toxicity study where rats were exposed to isopropyl myristate at a very high concentration for 1 hour. This effect was transient as it was only observed during the exposure period. This meets the criteria for GHS category 3 classification. Confidence is low based on lack of control data and the substances tested are mixtures.	NC Rationale No adverse effects were observed based on neurological battery assessments before, during, and after exposure in a 91-day repeated dose toxicity study for rats exposed to a surrogate compound. Confidence is high based on high quality data for a strong surrogate. CNP Rationale No data. CNP Rationale No data.	NC Rationale No sensitization has been observed in numerous animal and human studies. Confidence is high based on high quality data and numerous studies.	NC Rationale Isopropyl myristate is not expected to be a respiratory sensitizer based on extrapolation from negative skin sensitization studies, and lack of structural alerts for respiratory sensitization, therefore GHS classification is not warranted (ECHA 2017). Confidence is low as this evaluation does not include non-immunologic mechanisms of respiratory sensitization, and no specific data are available for respiratory sensitization.	NC Rationale Numerous studies in animals and humans demonstrate minimal irritation at most following exposure durations up to 4 hours and up to 14 days of observation. Mean scores for erythema and edema do not meet the criteria for GHS classification. Confidence is high based on high quality data and numerous studies.	NC Rationale Numerous studies in animals demonstrate minimal irritation at most with effects fully reversible by 48 hours post exposure. Mean scores for do not meet the criteria for GHS classification. Confidence is high based on high quality data and numerous studies.	NC Rationale Water solubility is reported at <0.05 mg/L @ 20ºC, and one reported EC50 value is >0.05 and < 100 mg/L, therefore, it is appropriate to conclude no effects at saturation. Confidence is high based on reliable experimental data.	NC Rationale No chronic values are identified. Based on extrapolation from acute toxicity data, no effect at saturation is expected. As the substance is also readily biodegradable, and the BAF < 500, this exceeds the criteria for GHS category 4 classification. Confidence is low as it is partially based on modeled bioaccumulation data.	NC Rationale Isopropyl myristate is not listed in the Annexes to the Montreal Protocol (and therefore is not classified as GHS Category 1 for ozone layer hazards), as a greenhouse gas in the IPCC report, or as an EPA ozone depleting substance with global warming potential. Confidence is high based on list search.

Other

Explosives: Not classified
Flammable Gases: Not classified
Aerosols: Not classified
Oxidizing Gases: Not classified
Flammable Liquids: Not classified
Flammable Solids: Not classified
Self-reactive substances and mixtures: Not classified
Pyrophoric Liquids: Not classified
Pyrophoric Solids: Not classified
Self-heating Substances and Mixtures: Not classified
Substances and Mixtures which in contact with water, emit flammable gases: Not classified
Oxidizing Liquids: Not classified
Oxidizing Solids: Not classified
Organic Peroxides: Not classified
Corrosive to Metals: Not classified
Desensitized Explosives: Not classified
Lactation Toxicity: Classification not possible (Data gap or insufficient data)
Aspiration: Not classified

How to read the C2CC Hazard Summary Table

Human Health											Environmental							Other
	Carcinogenicity	Mutagenicity	Reproductive & Developmental Toxicity	Endocrine Activity / Disruption	Oral Toxicity	Dermal Toxicity	Inhalation Toxicity	Neurotoxicity	Skin, Eye, and Respiratory Corrosion/Irritation	Sensitization of Skin and Airways	Fish Toxicity	Daphnia Toxicity	Algae Toxicity	Terrestrial Toxicity	Persistence	Bioaccumulation	Climatic Relevance	Other (Human Health)	Organohalogens	Toxic Metals	Other (Environmental Health)
Oral Dermal Inhalation	- G -	G	R G -	- Rationale The weight of evidence indicates that isopropyl myristate is not endocrine active based on TOX21 screening of estrogen, androgen, and thyroid activity screening. There are no indications of endocrine activity or disruption based on gross pathology in reproductive and repeated dose toxicity studies as well as carcinogenicity studies. However, ToxServices identified no in vivo data specifically examine hormone levels. Therefore insufficient data are available to draw a conclusion for this endpoint.	G	G	G	G G Y	G	G	G	G	G	G	G Rationale Isopropyl myristate is readily biodegradable based on >60% degradation in 28 days, and meets the 10-day window. Confidence is high based on high quality data.	G Rationale The estimated BAF is in the range of 100-500. No experimental log Kow values are identified. Therefore, the bioaccumulation potential is low based on the estimated BAF of < 500. Confidence is low as it is based on modeling.	Y	R Rationale Isopropyl myristate is not flammable, explosive, or oxidizing. It is not a VOC. It is however, known to enhance skin penetration, accordingly a red hazard rating is assigned. Additionally, there was no evidence of phototoxicity or photoallergenicity in volunteers exposed to isopropyl myristate.	G	G	G Rationale No other environmental concerns were identified based on data or physicochemical properties. Isopropyl myristate is not expected to be mobile in soil, is not a chelator, and is classified as non-hazardous to water under WGK.

The Cradle to Cradle Material Health Assessment Methodology assigns hazard ratings to 24 individual human and environmental health endpoints. The system is largely based on GHS with the addition of endpoints including but not limited to Persistence, Bioaccumulation Potential and Endocrine Activity/Disruption. The possible C2C Chemical Ratings that can result from ChemForward’s simplified C2C chemical rating logic are:

C2C Chemical Rating	Color	Short Definition	Rules Summary
a	green	preferred in all applications	Chemical has no YELLOW or RED hazards or Cancer data gaps.
b	green	preferred in all applications	Chemical has no YELLOW hazards but lacks long-term cancer studies.
c/b	yellow/ green	acceptable in all applications	Chemical has one or more YELLOW risk flags before considering application. Applications where exposure is possible would result in a ‘c’ rating. Applications where exposure is unlikely or expected to be negligible would result in a ‘b’ rating.
grey/c	grey/ yellow	insufficient information available	Chemical has one or more GREY risk flags before considering application. Applications where exposure is possible would result in a ‘grey’ rating. Applications where exposure is unlikely or expected to be negligible would result in a ‘c’ rating.
x/c	red/ yellow	may be acceptable or problematic depending on application	Chemical has one or more RED risk flags before considering application. Applications where exposure is possible would result in a ‘x’ rating. Applications where exposure is unlikely or expected to be negligible would result in a ‘c’ rating.
N/A	red	problematic in all applications	Chemical is on a regulatory concern list, is climatically active, and/or is an organohalogen.
x-PBT	red	problematic in all applications	Chemical has a RED hazard for Persistence, Bioaccumulation, and another endpoint.
N/A	red	problematic in all applications	Chemical is a toxic metal, all of which have a RED hazard for Cancer, Mutagenicity, or Reproductive toxicity.
N/A	red	problematic in all applications	Chemical is on a regulatory concern list and has a RED hazard for Cancer, Mutagenicity, or Reproductive toxicity.
N/A	purple	banned in all applications	Chemical is on the C2C Certified banned list.

Isopropyl myristate

Hazard Summary

Hazard Tables

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C2C Chemical Ratings

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Verification Status

How to read the GHS Hazard Summary Table

How to read the C2CC Hazard Summary Table