Toxicological profile of diethyl phthalate-avehicle for fragrance and cosmetic ingredients

Food and Chemical Toxicology 39 (2001) 97±108 www.elsevier.com/locate/foodchemtox Review Toxicological pro®le of diethyl phthalate: a vehicle for fragrance and cosmetic ingredients A.M Api * Research Institute for Fragrance Materials Inc., Two University Plaza, Suite 406, Hackensack, NJ 07601, USA Accepted August 2000 Summary Diethyl phthalate (DEP; CAS No 84-66-2) has many industrial uses, as a solvent and vehicle for fragrance and cosmetic ingredients and subsequent skin contact This review focuses on its safety in use as a solvent and vehicle for fragrance and cosmetic ingredients Available data are reviewed for acute toxicity, eye irritation, dermal irritation, dermal sensitization, phototoxicity, photoallergenicity, percutaneous absorption, kinetics, metabolism, subchronic toxicity, teratogenicity, reproductive toxicity, estrogenic potential, genetic toxicity, chronic toxicity, carcinogenicity, in vitro toxicity, ecotoxicity, environmental fate and potential human exposure No toxicological endpoints of concern have been identi®ed Comparison of estimated exposure (0.73 mg/kg/day) from dermal applications of fragrances and cosmetic products with other accepted industrial (5 mg/m3 in air) and consumer exposures (350 mg/l in water; 0.75 mg/kg/day oral exposure) indicates no signi®cant toxic liability for the use of DEP in fragrances and cosmetic products # 2001 Elsevier Science Ltd All rights reserved Keywords: Review; Diethyl phthalate; Phthalate ester; Fragrance; Cosmetic Contents Introduction 98 Acute toxicity 98 Eye irritation in rabbits 98 Dermal irritation in animals 99 Dermal irritation in humans 99 Dermal sensitization in animals 99 Dermal sensitization in humans 100 Potential phototoxicity in humans 100 Percutaneous absorption .101 10 Kinetics and metabolism .101 10.1 Subchronic toxicity in animals Ð dermal exposure 101 10.2 Subchronic toxicity in animals Ð oral exposure .102 11 Teratogenicity and reproductive toxicity 102 12 Estrogenic potential 103 Abbreviations: DEP, diethyl phthalate; FCA, Freund's complete adjuvant; MED, minimum erythema dose * Tel.: +1-201-488-5527; fax: +1-201-488-5594 E-mail address: api@rifm.org 0278-6915/01/$ - see front matter # 2001 Elsevier Science Ltd All rights reserved PII: S0278-6915(00)00124-1 98 A.M Api / Food and Chemical Toxicology 39 (2001) 97±108 13 Genetic toxicology .104 14 Chronic toxicity and carcinogenicity 104 15 In vitro toxicity 105 16 Ecotoxicology and environmental fate 105 17 Potential human exposure 105 18 Discussion and conclusions 106 Acknowledgements 106 References 106 Introduction The diethyl ester of phthalic acid (DEP; CAS No 8466-2) is a clear, colorless, practically odorless liquid (see Fig 1) It has a boiling point of 298 C, a speci®c gravity of 1.12 (20 C) and a vapor pressure of