RIFM fragrance ingredient safety assessment, p-mentha-1,4-diene, CAS Registry Number 99-85-4

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Highlights

  • p-Mentha-1,4-diene; a safety assessment based on RIFM's criteria.

  • A safety assessment based on 7 human health endpoints plus environmental.

  • All endpoints were cleared using target data, read-across, and/or TTC.

Section snippets

Identification

  • 1.

    Chemical Name: p-Mentha-1,4-diene

  • 2.

    CAS Registry Number: 99-85-4

  • 3.

    Synonyms: Crithmene; 1,4-Cyclohexadiene, 1-methyl-4-(1-methylethyl)-; 1-Methyl-4-isopropyl-1,4-cyclohexadiene; Moslene; γ-Terpinene; p-メンター1,3-(-3,7 又は-1,4)-ジエン; 1-Isopropyl-4-methylcyclohexa-1,4-diene; p-Mentha-1,4-diene

  • 4.

    Molecular Formula: C₁₀H₁₆

  • 5.

    Molecular Weight: 136.23

  • 6.

    RIFM Number: 469

  • 7.

    Stereochemistry: Isomer not specified. No stereocenter present and no stereoisomers possible.

Physical data

  • 1.

    Boiling Point: 182 °C (Fragrance Materials Association [FMA]), 169.36 °C (EPI Suite)

  • 2.

    Flash Point: 52 °C (Globally Harmonized System), 125 °F; CC (FMA)

  • 3.

    Log KOW: 4.75 (EPI Suite)

  • 4.

    Melting Point: −31.15 °C (EPI Suite)

  • 5.

    Water Solubility: 3.618 mg/L (EPI Suite)

  • 6.

    Specific Gravity: 0.846 (FMA)

  • 7.

    Vapor Pressure: 0.811 mm Hg at 20 °C (EPI Suite v4.0), 1.15 mm Hg at 25 °C (EPI Suite)

  • 8.

    UV Spectra: No significant absorbance between 290 and 700 nm; molar absorption coefficient is below the benchmark (1000 L mol−1 ∙ cm−1)

Volume of use (worldwide band)

  • 1.

    100–1000 metric tons per year (IFRA, 2015)

Exposure to fragrance ingredient (Creme RIFM Aggregate Exposure Model v2.0)

  • 1.

    95th Percentile Concentration in Fine Fragrance: 0.11% (RIFM, 2019)

  • 2.

    Inhalation Exposure*: 0.00012 mg/kg/day or 0.0090 mg/day (RIFM, 2019)

  • 3.

    Total Systemic Exposure**: 0.0020 mg/kg/day (RIFM, 2019)

*95th percentile calculated exposure derived from concentration survey data in the Creme RIFM Aggregate Exposure Model (Comiskey, 2015, 2017; Safford, 2015, 2017).

**95th percentile calculated exposure; assumes 100% absorption unless modified by dermal absorption data as reported in Section V. It is derived

Derivation of systemic absorption

  • 1.

    Dermal: Assumed 100%

  • 2.

    Oral: Assumed 100%

  • 3.

    Inhalation: Assumed 100%

Metabolism

No relevant data available for inclusion in this safety assessment.

Additional References: None.

Natural occurrence

p-Mentha-1,4-diene is reported to occur in the following foods by the VCF*:

  • Satureja species

  • Cumin Seed (Cuminum cyminum L.)

  • Origanum (Spanish) (Coridothymus cap. (L.) Rchb.)

  • Tarragon (Artemisia dracunculus L.)

  • Mace (Myristica fragrans Houttuyn)

  • Cardamom (Ellettaria cardamomum Maton.)

  • Pistacia atlantica

  • Turpentine Oil (Pistacia terebinthus)

  • Nutmeg (Myristica fragrans Houttuyn)

  • Coriander Leaf (Coriandrum sativum L.)

*VCF (Volatile Compounds in Food): Database/Nijssen, L.M.; Ingen-Visscher, C.A. van;

REACH dossier

Available; accessed 08/28/20 (ECHA, 2018).

Conclusion

The existing information supports the use of this material as described in this safety assessment.

Genotoxicity

Based on the current existing data, p-mentha-1,4-diene does not present a concern for genotoxicity.

Literature Search*

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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References (81)

  • R. Kroes et al.

    Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients

    Food Chem. Toxicol.

    (2007)
  • B. Larsen et al.

    Sampling and analysis of terpenes in air. An interlaboratory comparison

    Atmos. Environ.

    (1997)
  • M.C. Laufersweiler et al.

    Correlation of chemical structure with reproductive and developmental toxicity as it relates to the use of the threshold of toxicological concern

    Regul. Toxicol. Pharmacol.

    (2012)
  • R.E. Rogers et al.

    Characterization of potential human exposure to fragrances during residential consumer product use

    J. Allergy Clin. Immunol.

    (2003)
  • B. Safford et al.

    Use of an aggregate exposure model to estimate consumer exposure to fragrance ingredients in personal care and cosmetic products

    Regul. Toxicol. Pharmacol.

    (2015)
  • B. Safford et al.

    Application of the expanded Creme RIFM consumer exposure model to fragrance ingredients in cosmetic, personal care and air care products

    Regul. Toxicol. Pharmacol.

    (2017)
  • T.W. Schultz et al.

    A strategy for structuring and reporting a read-across prediction of toxicity

    Regul. Toxicol. Pharmacol.

    (2015)
  • J. Shen et al.

    An in silico skin absorption model for fragrance materials

    Food Chem. Toxicol.

    (2014)
  • E.P. Sheppard et al.

    Lemon oil as an expectorant inhalant

    Pharmacol. Res. Commun.

    (1970)
  • V.R. Sunil et al.

    Pulmonary effects of inhaled limonene ozone reaction products in elderly rats

    Toxicol. Appl. Pharmacol.

    (2007)
  • C.K. Wilkins et al.

    Upper airway irritation of terpene/ozone oxidation products (TOPS). Dependence on reaction time, relative humidity and initial ozone concentration

    Toxicol. Lett.

    (2003)
  • P. Wolkoff et al.

    Acute airway effects of ozone initiated d-limonene chemistry: importance of gaseous products

    Toxicol. Lett.

    (2008)
  • P. Wolkoff et al.

    Airway effects of repeated exposures to ozone-initiated limonene oxidation products as model of indoor air mixtures

    Toxicol. Lett.

    (2012)
  • S. Arctander
    (1969)
  • M.A. Bergstrom et al.

    Conjugated dienes as prohaptens in contact allergy: in vivo and in vitro studies of structure--activity relationships, sensitizing capacity, and metabolic activation

    Chem. Res. Toxicol.

    (2006)
  • A. Cassano et al.

    CAESAR models for developmental toxicity

    Chem. Cent. J.

    (2010)
  • J.R. Coats et al.

    Toxicity and neurotoxic effects of monoterpenoids in insects and earthworms

    Am. Canc. Soc. Symp. Ser.

    (1991)
  • A. Duchamp

    Electrophysiological responses of olfactory bulb neurons to odour stimuli in the frog. A comparison with receptor cells

    Chem. Senses

    (1982)
  • ECHA

    Guidance on information requirements and chemical safety assessment

  • ECHA

    Read-across assessment framework (RAAF)

  • ECHA

    p-Mentha-1,4-diene registration dossier

  • ECHA

    p-Cymene registration dossier

  • M.D. Ellis et al.

    Toxicity of seven monoterpenpids to tracheal mites (Acari: tarsonemidae) and their honey bee (Hymenoptera: apidae) hosts when applied as fumigants

    J. Econ. Entomol.

    (1997)
  • A. Falk-Filipsson et al.

    d-Limonene exposure to humans by inhalation: uptake, distribution, elimination, and effects on the pulmonary function

    J. Toxicol. Environ. Health

    (1993)
  • C.D. Forester et al.

    Yields of carbonyl products from gas-phase reactions of fragrance compounds with OH radical and ozone

    Environ. Sci. Technol.

    (2009)
  • M.C. Foti et al.

    Mechanism of inhibition of lipid peroxidation by gamma-terpinene, an unusual and potentially useful hydrocarbon antioxidant.[Supporting Information Attached]

    J. Agric. Food Chem.

    (2003)
  • D.E. Frederick et al.

    A critical test of the overlap hypothesis for odor mixture perception

    Behav. Neurosci.

    (2009)
  • E. Heuberger et al.

    Effects of chiral fragrances on human autonomic nervous system parameters and self-evaluation

    Chem. Senses

    (2001)
  • W.F. Hink et al.

    Toxicity of d-limonene, the major component of citrus peel oil, to all life stages of the cat flea, Ctenocephalides felis (Siphonaptera:Pulicidae)

    J. Med. Entomol.

    (1986)
  • R. Hirota et al.

    Limonene inhalation reduces allergic airway inflammation in Dermatophagoides farinae-treated mice

    Inhal. Toxicol.

    (2012)
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