National Toxicology Program

National Toxicology Program

NTP Report on the Assessment of Contact Hypersensitivity to Iso-E Super in Female BALB/c Mice (CASRN: 54464-57-2)

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program (NTP). The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.

NTP Report Number IMM20702


1-(1,2,3,4,5,6,7,8-Octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)ethanone, commonly referred to as Iso-E Super (IES), is a synthetic terpenoid that is a petroleum-derived aromatic chemical (Scott et al., 2001). Iso-E Super is used as a perfume ingredient as well as in tobacco (Hall and Sanders, 1975a; 1975b; Nogami and Mitsunaka, 1998). Human exposure to Iso-E Super occurs by inhalation, skin contact through the use of IES-containing products, and via ingestion of water or food containing the chemical as a contaminant. Iso-E Super has been reported to cause allergic reactions detectable by patch tests in humans (Frosch et al., 1995)

The objective of this study was to determine the sensitization potential of Iso-E Super following dermal exposure in female BALB/c mice. Measurement of the contact hypersensitivity response was accomplished using the combined local lymph node assay (LLNA) and irritancy assay (IRR). Solubility tests indicated that the highest achievable concentration of Iso-E Super in acetone: olive oil (4:1; AOO) was 50%. Accordingly, the concentrations of Iso-E Super initially used for the combined LLNA and IRR assays were 0.5%, 1%, 2.5%, 5%, 10%, 25%, and 50%.

In the LLNA, Iso-E Super at concentrations of 25% and 50% produced statistically significant increases in the draining lymph node cell proliferation when compared to the vehicle control, and the percent increases in the 25% and 50% Iso-E Super-treatment groups were 172% and 467%, respectively. In the irritancy assay, Iso-E Super at concentrations between 1% and 50% significantly increased the percent ear swelling at 24 hr following the last dermal exposure.

To further confirm the positive LLNA response, the Mouse Ear Swelling Test (MEST) was performed following exposure to Iso-E Super. In the sensitization phase, three concentrations of Iso-E Super (0.5%, 5% and 50%) were used, and a concentration of 50% was applied during the challenge phase. Iso-E Super did not significantly increase mouse ear thickness at either 24 or 48 hr post-challenge at any of the concentrations evaluated.

In summary, under the experimental conditions utilized in this study of female BALB/c mice, Iso-E Super was positive in the LLNA and the irritancy assay, however, it was negative in the MEST.

Report Date: March 2010


Scott M. (2001). 1-(1,2,3,4,5,6,7,8-Octahydro-2,3-8,8-tetramethyl-2-naphthalenyl) ethanone. Review of Toxicological Literature. National Institute of Environmental Health Sciences, Research Triangle Park, NC.

Hall JB, Sanders JM (1975a). Novel tobacco product comprising one or more isomers of an octahydrotetramethyl acetonaphthone. US. Patent 3,907,321. 20 pp. International Flavors and Fragrances, Inc., New York, NY.

Hall JB, Sanders JM (1975b). Perfume composition and perfume articles containing one isomer of an octahydrotetramethyl acetonaphthone. US. Patent 3,929,677. 22 pp. International Flavors and Fragrances, Inc, New York, NY. Abstract from Chem. Abstr. 84:165076.

Nogami M, Mitsunaka K (1998). Malodor reducing composition containing amber and musk materials. Patent no. WO 9,856,337. PCT Int. Appl., 86 pp. The Procter and Gamble Company, USA.

Frosch PJ, Pilz B, Anderson KE, Burrows D, Camarasa JG, Dooms-Goossens A, Ducombs G, Fuchs T, Hannuksela M, Lachapelle JM, Lahti A, Maibach HI, Menne T, Rycroft RJG, Shaw S, Wahlberg JE, White IR, Wilkinson JD (1995). Patch testing with fragrances: Results of a multicenter study of the European Environmental and contact dermatitis research group with 48 frequently used constitutes of perfumes. Contact Dermatitis 33(5):333-342.


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