Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Regul Toxicol Pharmacol. 2024 May;149:105597. doi:
10.1016/j.yrtph.2024.105597.  Epub 2024 Mar 8.

GARDskin dose-response assay and its application in conducting Quantitative Risk 
Assessment (QRA) for fragrance materials using a Next Generation Risk Assessment 
(NGRA) framework.

Donthamsetty S(1), Forreryd A(2), Sterchele P(3), Huang X(3), Gradin R(2), 
Johansson H(2), Mattson U(2), Lee I(4), Api AM(4), Ladics G(5).

Author information:
(1)International Flavors & Fragrances, Hazlet, NJ, USA. Electronic address: 
shashi.donthamsetty@iff.com.
(2)SenzaGen AB, Lund, Sweden.
(3)International Flavors & Fragrances, Hazlet, NJ, USA.
(4)Research Institute for Fragrance Materials, Mahwah, NJ, USA.
(5)International Flavors & Fragrances, Wilmington, DE, USA. Electronic address: 
gregory.s.ladics@iff.com.

Development of New Approach Methodologies (NAMs) capable of providing a No 
Expected Sensitization Induction Level (NESIL) value remains a high priority for 
the fragrance industry for conducting a Quantitative Risk Assesment (QRA) to 
evaluate dermal sensitization. The in vitro GARDskin assay was recently adopted 
by the OECD (TG 442E) for the hazard identification of skin sensitizers. 
Continuous potency predictions are derived using a modified protocol that 
incorporates dose-response measurements. Linear regression models have been 
developed to predict human NESIL values. The aim of the study was to evaluate 
the precision and reproducibility of the continuous potency predictions from the 
GARDskin Dose-Response (DR) assay and its application in conducting QRA for 
fragrance materials using a Next Generation Risk Assessment (NGRA) framework. 
Results indicated that the GARDskin Dose-Response model predicted human NESIL 
values with a good degree of concordance with published NESIL values, which were 
also reproducible in 3 separate experiments. Using Isocyclocitral as an example, 
a QRA was conducted to determine its safe use levels in different consumer 
product types using a NGRA framework. This study represents a major step towards 
the establishment of the assay to derive NESIL values for conducting QRA 
evaluations for fragrance materials using a NGRA framework.

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.yrtph.2024.105597
PMID: 38460723 [Indexed for MEDLINE]

Conflict of interest statement: 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.


2. Food Chem Toxicol. 2019 Dec;134 Suppl 1:110709. doi:
10.1016/j.fct.2019.110709.  Epub 2019 Jul 29.

RIFM fragrance ingredient safety assessment, isocyclocitral, CAS Registry number 
1335-66-6.

Api AM(1), Belmonte F(1), Belsito D(2), Biserta S(1), Botelho D(1), Bruze M(3), 
Burton GA Jr(4), Buschmann J(5), Cancellieri MA(1), Dagli ML(6), Date M(1), 
Dekant W(7), Deodhar C(1), Fryer AD(8), Gadhia S(1), Jones L(1), Joshi K(1), 
Lapczynski A(1), Lavelle M(1), Liebler DC(9), Na M(1), O'Brien D(1), Patel A(1), 
Penning TM(10), Ritacco G(1), Rodriguez-Ropero F(1), Romine J(1), Sadekar N(1), 
Salvito D(1), Schultz TW(11), Sipes IG(12), Sullivan G(13), Thakkar Y(1), Tokura 
Y(14), Tsang S(1).

Author information:
(1)Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, 
Woodcliff Lake, NJ, 07677, USA.
(2)Member RIFM Expert Panel, Columbia University Medical Center, Department of 
Dermatology, 161 Fort Washington Ave., New York, NY, 10032, USA.
(3)Member RIFM Expert Panel, Malmo University Hospital, Department of 
Occupational & Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, 
Malmo, SE, 20502, Sweden.
(4)Member RIFM Expert Panel, School of Natural Resources & Environment, 
University of Michigan, Dana Building G110, 440 Church St., Ann Arbor, MI, 
58109, USA.
(5)Member RIFM Expert Panel, Fraunhofer Institute for Toxicology and 
Experimental Medicine, Nikolai-Fuchs-Strasse 1, 30625, Hannover, Germany.
(6)Member RIFM Expert Panel, University of Sao Paulo, School of Veterinary 
Medicine and Animal Science, Department of Pathology, Av. Prof. dr. Orlando 
Marques de Paiva, 87, Sao Paulo, CEP, 05508-900, Brazil.
(7)Member RIFM Expert Panel, University of Wuerzburg, Department of Toxicology, 
Versbacher Str. 9, 97078, Würzburg, Germany.
(8)Member RIFM Expert Panel, Oregon Health Science University, 3181 SW Sam 
Jackson Park Rd., Portland, OR, 97239, USA.
(9)Member RIFM Expert Panel, Vanderbilt University School of Medicine, 
Department of Biochemistry, Center in Molecular Toxicology, 638 Robinson 
Research Building, 2200 Pierce Avenue, Nashville, TN, 37232-0146, USA.
(10)Member of RIFM Expert Panel, University of Pennsylvania, Perelman School of 
Medicine, Center of Excellence in Environmental Toxicology, 1316 Biomedical 
Research Building (BRB) II/III, 421 Curie Boulevard, Philadelphia, PA, 
19104-3083, USA.
(11)Member RIFM Expert Panel, The University of Tennessee, College of Veterinary 
Medicine, Department of Comparative Medicine, 2407 River Dr., Knoxville, TN, 
37996- 4500, USA.
(12)Member RIFM Expert Panel, Department of Pharmacology, University of Arizona, 
College of Medicine, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ, 
85724-5050, USA.
(13)Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, 
Woodcliff Lake, NJ, 07677, USA. Electronic address: gsullivan@rifm.org.
(14)Member RIFM Expert Panel, The Journal of Dermatological Science (JDS), 
Editor-in-Chief, Professor and Chairman, Department of Dermatology, Hamamatsu 
University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 
431-3192, Japan.

DOI: 10.1016/j.fct.2019.110709
PMID: 31369852 [Indexed for MEDLINE]


3. Avicenna J Phytomed. 2017 Mar-Apr;7(2):145-156.

Anti-carcinogenic and anti-angiogenic properties of the extracts of Acorus 
calamus on gastric cancer cells.

Rahamooz Haghighi S(1), Asadi MH(2), Akrami H(3), Baghizadeh A(2).

Author information:
(1)Department of Plant Breeding, Faculty of Sciences and Modern Technologies, 
Graduate University of Advanced Technology, Kerman, Iran.
(2)Department of Biotechnology, Institute of Science and High Technology and 
Environmental Sciences, Graduate University of Advanced Technology, Kerman, 
Iran.
(3)Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran.

OBJECTIVE: Acorus calamus (A. calamus) has been used as a medicinal plant in 
Asia for its effects on digestive system for the last 2000 years. To investigate 
the anti-cancer activity of rhizome of A. calamus, the ethanolic and methanolic 
extracts and essential oil of the rhizome were prepared and their effects were 
assessed on human gastric cancer cell line (AGS).
MATERIALS AND METHODS: The viability of cells which were treated with the 
extracts and the essential oil was assessed by MTT assay. To evaluate the 
anti-angiogenic property of the extracts, in vitro tube formation assay was 
done. Cell cycle distribution and the expression of Oct4 and Nucleostemin, after 
treatments, were checked by flowcytometry and quantitative RT-PCR, respectively. 
Furthermore, analysis of essential oil from A.calamus was done by GC-MS.
RESULTS: Our results showed that the growth of AGS cells was inhibited by the 
extracts and essential oil and the extracts inhibited the angiogenesis in HUVEC 
cells. Our data revealed that the extracts and essential oil of A. calamus 
caused G1 arrest in AGS cells and downregulation of Oct4 and NS after treatment. 
By GC-MS analysis, we found new compounds such as epiprezizaene, valencene and 
isocyclocitral in essential oil of A.
CONCLUSION: All together, our results showed that the extracts of A. calamus 
have anti-proliferative and anti-angiogenic effects on cancer cells.

PMCID: PMC5355820
PMID: 28348970

Conflict of interest statement: The authors have no conflicts of interest 
related to this article.