Short ReviewRIFM fragrance ingredient safety assessment, 4-tert-butyltoluene, CAS Registry Number 98-51-1
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 Judgment | Toxtree v 2.6 | OECD QSAR Toolbox v 3.2 |
---|---|---|
I | I | I |
- 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
- a.
- 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*
- •
RIFM Database: Target, Fragrance Structure-Activity Group materials, other references, JECFA, CIR, SIDS
- •
ECHA: https://echa.europa.eu/
- •
- •
OECD Toolbox: https://www.oecd.org/chemicalsafety/risk-assessment/oecd-qsar-toolbox.htm
- •
SciFinder: https://scifinder.cas.org/scifinder/view/scifinder/scifinderExplore.jsf
- •
- •
National Library of Medicine's Toxicology Information Services: https://toxnet.nlm.nih.gov/
- •
- •
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.
References (37)
- et al.
Criteria for the Research Institute for fragrance materials, Inc. (RIFM) safety evaluation process for fragrance ingredients
Food Chem. Toxicol. (Formerly Food and Cosmetics Toxicology)
(2015) - et al.
Exposure based waiving: the application of the toxicological threshold of concern (TTC) to inhalation exposure for aerosol ingredients in consumer products
Food Chem. Toxicol. (Formerly Food and Cosmetics Toxicology)
(2009) - et al.
Novel database for exposure to fragrance ingredients in cosmetics and personal care products
Regul. Toxicol. Pharmacol.
(2015) - et al.
Integrating habits and practices data for soaps, cosmetics and air care products into an existing aggregate exposure model
Regul. Toxicol. Pharmacol.
(2017) - et al.
Can light absorption and photostability data be used to assess the photosafety risks in patients for a new drug molecule?
J. Photochem. Photobiol. B Biol.
(2009) - et al.
Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients
Food Chem. Toxicol. (Formerly Food and Cosmetics Toxicology)
(2007) - 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) - 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) - 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) - et al.
A strategy for structuring and reporting a read-across prediction of toxicity
Regul. Toxicol. Pharmacol.
(2015)