title: Criteria for the Research Institute for Fragrance Materials, Inc. (RIFM) safety evaluation process for fragrance ingredients.
abstract: The Research Institute for Fragrance Materials, Inc. (RIFM) has been engaged in the generation and evaluation of safety data for fragrance materials since its inception over 45 years ago. Over time, RIFM's approach to gathering data, estimating exposure and assessing safety has evolved as the tools for risk assessment evolved. This publication is designed to update the RIFM safety assessment process, which follows a series of decision trees, reflecting advances in approaches in risk assessment and new and classical toxicological methodologies employed by RIFM over the past ten years. These changes include incorporating 1) new scientific information including a framework for choosing structural analogs, 2) consideration of the Threshold of Toxicological Concern (TTC), 3) the Quantitative Risk Assessment (QRA) for dermal sensitization, 4) the respiratory route of exposure, 5) aggregate exposure assessment methodology, 6) the latest methodology and approaches to risk assessments, 7) the latest alternatives to animal testing methodology and 8) environmental risk assessment. The assessment begins with a thorough analysis of existing data followed by in silico analysis, identification of 'read across' analogs, generation of additional data through in vitro testing as well as consideration of the TTC approach. If necessary, risk management may be considered.
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA. Electronic address: amapi@rifm.org.
authors.forename: A M
authors.initials: AM
authors.lastname: Api
authors.affiliation: Member RIFM Expert Panel, Columbia University Medical Center, Department of Dermatology, 161 Fort Washington Ave., New York, NY 10032, USA.
authors.forename: D
authors.initials: D
authors.lastname: Belsito
authors.affiliation: Member RIFM Expert Panel, Malmo University Hospital, Department of Occupational & Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, Malmo SE-20502, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Bruze
authors.affiliation: Firmenich SA, Case Postale 239, 1211 Geneva 8, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Cadby
authors.affiliation: Member RIFM Expert Panel, University of Nebraska Lincoln, 230 Whittier Research Center, Lincoln, NE 68583-0857, USA.
authors.forename: P
authors.initials: P
authors.lastname: Calow
authors.affiliation: 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.
authors.forename: M L
authors.initials: ML
authors.lastname: Dagli
authors.affiliation: Member RIFM Expert Panel, University of Wuerzburg, Department of Toxicology, Versbacher Str. 9, 97078 Würzburg, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Dekant
authors.affiliation: Givaudan International SA, 5 chemin de la parfumerie, CH1214 Vernier, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Ellis
authors.affiliation: Member RIFM Expert Panel, Oregon Health Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Fryer
authors.affiliation: International Flavors & Fragrances Inc., 800 Rose Lane, Union Beach, NJ 07735, USA.
authors.forename: M
authors.initials: M
authors.lastname: Fukayama
authors.affiliation: Symrise AG, Muehlenfeldstrasse 1, D-37603 Holzminden, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Griem
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA.
authors.forename: C
authors.initials: C
authors.lastname: Hickey
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA.
authors.forename: L
authors.initials: L
authors.lastname: Kromidas
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Lalko
authors.affiliation: 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.
authors.forename: D C
authors.initials: DC
authors.lastname: Liebler
authors.affiliation: Member RIFM Expert Panel, Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Miyachi
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA.
authors.forename: V T
authors.initials: VT
authors.lastname: Politano
authors.affiliation: Takasago International Corporation, 4 Volvo Drive, Rockleigh, NJ 07647, USA.
authors.forename: K
authors.initials: K
authors.lastname: Renskers
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA.
authors.forename: G
authors.initials: G
authors.lastname: Ritacco
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA.
authors.forename: D
authors.initials: D
authors.lastname: Salvito
authors.affiliation: Member RIFM Expert Panel, The University of Tennessee, College of Veterinary Medicine, Department of Comparative Medicine, 2407 River Dr., Knoxville, TN 37996-4500, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: Schultz
authors.affiliation: Member RIFM Expert Panel, Department of Pharmacology, College of Medicine, University of Arizona, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ 85724-5050, USA.
authors.forename: I G
authors.initials: IG
authors.lastname: Sipes
authors.affiliation: Firmenich SA, Case Postale 239, 1211 Geneva 8, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Smith
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA.
authors.forename: D
authors.initials: D
authors.lastname: Vitale
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Boulevard, Woodcliff Lake, NJ 07677, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Wilcox
mesh_terms: D000047:Academies and Institutes / Q000331:legislation & jurisprudence*; D000818:Animals; D003257:Consumer Product Safety / Q000331:legislation & jurisprudence* / Q000592:standards*; D004249:DNA Damage / Q000187:drug effects; D003663:Decision Trees; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination / Q000592:standards; D004781:Environmental Exposure / Q000009:adverse effects*; D017408:Guidelines as Topic; D006801:Humans; D023421:Models, Animal; D019055:No-Observed-Adverse-Effect Level; D010476:Perfume / Q000737:chemistry / Q000592:standards / Q000633:toxicity*; D018570:Risk Assessment; D012958:Societies, Scientific / Q000331:legislation & jurisprudence / Q000592:standards
chemical_list: D010476:Perfume
keywords: Environmental toxicology; Fragrance material; Human health toxicology; Safety assessment