RIFM fragrance ingredient safety assessment, cis-3-hexenyl isovalerate, CAS Registry Number 35154-45-1

https://doi.org/10.1016/j.fct.2021.112533Get rights and content

Highlights

  • •

    cis-3-Hexenyl isovalerate; 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: cis-3-Hexenyl isovalerate

  • 2.

    CAS Registry Number: 35154-45-1

  • 3.

    Synonyms: (Z)-Hex-3-enyl isovalerate; Isovaleric acid, 3-hexenyl ester, (z)-; ｱﾙｶﾝ酸(C = 1–16)ｱﾙｹﾆﾙ(C = 4–8); Hex-3-en-1-yl 3-methylbutanoate; cis-3-Hexenyl isovalerate

  • 4.

    Molecular Formula: C₁₁H₂₀O₂

  • 5.

    Molecular Weight: 184.27

  • 6.

    RIFM Number: 974

  • 7.

    Stereochemistry: Cis isomer specified.

Physical data

  • 1.

    Boiling Point: 105 °C at 20 mm Hg (Fragrance Materials Association [FMA]), 224.17 °C (EPI Suite)

  • 2.

    Flash Point: 185 °F; CC (FMA)

  • 3.

    Log KOW: 4.01 (EPI Suite)

  • 4.

    Melting Point: −9.97 °C (EPI Suite)

  • 5.

    Water Solubility: 19.61 mg/L (EPI Suite)

  • 6.

    Specific Gravity: 0.88 (FMA)

  • 7.

    Vapor Pressure: 0.0693 mm Hg at 20 °C (EPI Suite v4.0), 0.07 mm Hg at 20 °C (FMA), 0.106 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

Volume of use (worldwide band)

  • 1.

    0.1–1 metric ton per year (IFRA, 2015)

Exposure to fragrance ingredient (Creme RIFM Aggregate Exposure Model v1.0)

  • 1.

    95th Percentile Concentration in Fine Fragrance: 0.0015% (RIFM, 2017b)

  • 2.

    Inhalation Exposure*: 0.00014 mg/kg/day or 0.0095 mg/day (RIFM, 2017b)

  • 3.

    Total Systemic Exposure**: 0.00087 mg/kg/day (RIFM, 2017b)

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

**95th percentile calculated exposure; assumes 100% absorption unless modified by

Derivation of systemic absorption

  • 1.

    Dermal: Assumed 100%

  • 2.

    Oral: Assumed 100%

  • 3.

    Inhalation: Assumed 100%

Computational toxicology evaluation

  • 1.

    Cramer Classification: Class I, Low

Expert JudgmentToxtree v3.1OECD QSAR Toolbox v4.2
III

  • 2.Analogs Selected:

    • a.

      Genotoxicity: cis-3-Hexen-1-yl acetate (CAS # 3681-71-8)

    • b.

      Repeated Dose Toxicity: cis-3-Hexen-1-yl acetate (CAS # 3681-71-8)

    • c.

      Reproductive Toxicity: cis-3-Hexen-1-yl acetate (CAS # 3681-71-8)

    • d.

      Skin Sensitization: Hex-3-enyl acetate (CAS # 1708-82-3) and cis-3-hexen-1-yl acetate (CAS # 3681-71-8)

    • e.

      Phototoxicity/Photoallergenicity: None

    • f.

      Local Respiratory Toxicity: None

    • g.

      Environmental Toxicity: None

  • 3.

Metabolism

No relevant data available for inclusion in this safety assessment.

Additional References:

None.

Natural occurrence

cis-3-Hexenyl isovalerate is reported to occur in the following foods by the VCF*:

Capsicum speciesNectarine
Cherimoya (Annona cherimolia Mill.)Salvia species
Elderberry (Sambucus nigra L.)Sea buckthorn (Hippophae rhamnoides L.)
Lamb's lettuce (Valerianella locusta)Tea
Mastic (Pistacia lentiscus)Turpentine oil (Pistacia terebinthus)
Mentha oils

*VCF (Volatile Compounds in Food): Database/Nijssen, L.M.; Ingen-Visscher, C.A. van; Donders, J.J.H. (eds). – Version 15.1 – Zeist (The Netherlands): TNO

Reach dossier

cis-3-Hexenyl isovalerate has been pre-registered for 2010; no dossier available as of 10/01/20.

Conclusion

The maximum acceptable concentrationsa in finished products for cis-3-hexenyl isovalerate are detailed below.

IFRA
Categoryb		Description of Product TypeMaximum Acceptable Concentrationsa in Finished Products (%)c
1Products applied to the lips (lipstick)0.077
2Products applied to the axillae0.023
3Products applied to the face/body using fingertips0.46
4Products related to fine fragrances0.43
5ABody lotion products applied to the face and body using the hands (palms), primarily leave-on0.11
5BFace

Genotoxicity

Based on the current existing data, cis-3-hexenyl isovalerate 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. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. RIFM staff are employees of the Research Institute for Fragrance Materials, Inc. (RIFM). The Expert Panel receives a small

First page preview

First page preview
Click to open first page preview
View PDF

References (39)

  • J. Shen et al.

    An in silico skin absorption model for fragrance materials

    Food Chem. Toxicol.

    (2014)
  • S. Arctander
    (1969)
  • A. Cassano et al.

    CAESAR models for developmental toxicity

    Chem. Cent. J.

    (2010)

  • Guidance on information requirements and chemical safety assessment

  • (Z)-Hex-3-enyl acetate registration dossier

  • Read-across assessment framework (RAAF)

  • Volume of Use Survey

    (2015)
  • M. Na et al.

    Fragrance Skin Sensitization Evaluation and Human Testing, Dermatitis

    (2020)

  • Guidance Document on the Reporting of integrated Approaches to Testing and assessment (IATA). ENV/JM/HA(2015)7

    • Cited by (0)

    View full text
    © 2021 Elsevier Ltd. All rights reserved.