Short Review
RIFM fragrance ingredient safety assessment, 4-tert-butyltoluene, CAS Registry Number 98-51-1

https://doi.org/10.1016/j.fct.2020.111928Get rights and content

Highlights

  • 4-tert-Butyltoluene; 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: 4-tert-Butyltoluene

  • 2.

    CAS Registry Number: 98-51-1

  • 3.

    Synonyms: Benzene, 1-(1,1-dimethylethyl)-4-methyl-; 4-tert-Butyl-1-methylbenzene; p-tert-Butyltoluene; 1-(1,1-Dimethylethyl)-4-methylbenzene; 1-Methyl-4-tert-butylbenzene; 4-Methyl-tert-butylbenzene; p-Methyl-tert-butylbenzene; Toluene, p-tert-butyl-; 1-tert-Butyl-4-methylbenzene; TBT; 4-tert-Butyltoluene

  • 4.

    Molecular Formula: C11H16

  • 5.

    Molecular Weight: 148.24

  • 6.

    RIFM Number: 5135

  • 7.

    Stereochemistry: Isomer not specified. No stereocenter present

Physical data

  • 1.

    Boiling Point: 190.77 °C (EPI Suite)

  • 2.

    Flash Point: Not Available

  • 3.

    Log KOW: 4.45 (EPI Suite)

  • 4.

    Melting Point: −10.17 °C (EPI Suite)

  • 5.

    Water Solubility: 2.969 mg/L (EPI Suite)

  • 6.

    Specific Gravity: Not Available

  • 7.

    Vapor Pressure: 0.406 mm Hg at 20 °C (EPI Suite v4.0), 0.592 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)

  • 9.

    Appearance/Organoleptic: Not Available

Volume of use (worldwide band)

  • 1.

    <0.1 metric ton per year (IFRA, 2015)

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

  • 1.

    95th Percentile Concentration in Hydroalcoholics: 0.00082% (RIFM, 2016)

  • 2.

    Inhalation Exposure*: 0.0000032 mg/kg/day or 0.00025 mg/day (RIFM, 2016)

  • 3.

    Total Systemic Exposure**: 0.000015 mg/kg/day (RIFM, 2016)

*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 v 2.6OECD QSAR Toolbox v 3.2
III
  • 2.

    Analogs Selected:

    • a.

      Genotoxicity: None

    • b.

      Repeated Dose Toxicity: None

    • c.

      Reproductive Toxicity: None

    • d.

      Skin Sensitization: None

    • e.

      Phototoxicity/Photoallergenicity: None

    • f.

      Local Respiratory Toxicity: Benzene, 1,2,4-trimethyl- (CAS # 95-63-6)

    • g.

      Environmental Toxicity: None

  • 3.

    Read-across Justification: See Appendix below

Metabolism

4-tert-Butyltoluene is readily absorbed through the respiratory and gastrointestinal tracts. Following inhalation exposure in mice, the peak concentrations are achieved within 30 min (Health Council of the Netherlands, 2002). It is widely distributed and found in relatively high amounts in the brain, spinal cord, liver, lungs, kidney, bone marrow, and Harderian gland. 4-tert-Butyltoluene was found in the bile, intestine, adrenals (after 8 h exposure), and blood. The order of distribution

Natural occurrence (discrete chemical) or composition (NCS)

4-tert-Butyltoluene is not reported to occur in foods by the VCF*.

*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 Triskelion, 1963–2014. A continually updated database containing information on published volatile compounds that have been found in natural (processed) food products. Includes FEMA GRAS and EU-Flavis data.

REACH Dossier

Available; accessed 05/03/19 (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, 4-tert-butyltoluene 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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