Phthalates are metabolized and eliminated in urine within hours after exposure. Several reports suggest that concentrations of phthalate metabolites in a spot urine sample can provide a reliable estimation of exposure to phthalates for up to several months. Monoethyl phthalate (MEP) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) urinary concentrations varied considerably during 1 week, but the main contributors to the total variance differed (interday variability, MEHHP; interperson variability, MEP) regardless of the sampling strategy (spot, first morning, 24-hr collection). The nature of the exposure (diet vs. other lifestyle factors) and timing of urine sampling to evaluate exposure to phthalates should be considered. For DEHP and phthalates to which people are mostly exposed through diet, collecting 24-hr voids for only 1 day may not be advantageous compared with multiple spot collections. When collecting multiple spot urine samples, changing the time of collection may provide the most complete approach to assess exposure to diverse phthalates (1).

The probability of nonoccupational exposure to phthalates is high given their use in a vast range of consumables, including personal care products (e.g., perfumes, lotions, cosmetics), paints, industrial plastics, and certain medical devices and pharmaceuticals. Phthalates are of high interest because of their potential for human exposure and because animal toxicity studies suggest that some phthalates affect male reproductive development apparently via inhibition of androgen biosynthesis. In humans, phthalates are rapidly metabolized to their monoesters, which can be further transformed to oxidative products, conjugated, and eliminated. Phthalate metabolites have been used as biomarkers of exposure. Using urinary phthalate metabolite concentrations allows accurate assessments of human exposure because these concentrations represent an integrative measure of exposure to phthalates from multiple sources and routes. However, the health significance of this exposure is unknown. To link biomarker measurements to exposure, internal dose, or health outcome, additional information (e.g., toxicokinetics, inter- and intraindividual differences) is needed. We present a case study using diethyl phthalate and di(2-ethylhexyl) phthalate as examples to illustrate scientific approaches and their limitations, identify data gaps, and outline research needs for using biomonitoring data in the context of human health risk assessment, with an emphasis on exposure and dose. Although the vast and growing literature on phthalates research could not be covered comprehensively in this article, we made every attempt to include the most relevant publications as of the end of 2005 (2).

References______________________________________________________________________

(1) James L. Preau, Jr, Lee-Yang Wong, Manori J. Silva, Larry L. Needham, Antonia M. Calafat Variability over 1 Week in the Urinary Concentrations of Metabolites of Diethyl Phthalate and Di(2-Ethylhexyl) Phthalate among Eight Adults: An Observational Study  Environ Health Perspect. 2010 Dec; 118(12): 1748–1754. Published online 2010 Aug 25. doi: 10.1289/ehp.1002231

(2) Antonia M. Calafat, Richard H. McKee Integrating Biomonitoring Exposure Data into the Risk Assessment Process: Phthalates [Diethyl Phthalate and Di(2-ethylhexyl) Phthalate] as a Case Study  Environ Health Perspect. 2006 Nov; 114(11): 1783–1789. Published online 2006 Jun 12. doi: 10.1289/ehp.9059

Diethyl Phthalate is a chemical compound, diethyl phthalate acid, a member of the esters of benzoic acid.

The name describes the structure of the molecule:

• Diethyl indicates the presence of two ethyl groups (CH₃CH₂-) attached to the molecule.
• Phthalate refers to the derivative of phthalic acid, an aromatic dicarboxylic acid

Description of the raw materials used in its production:

• Phthalic acid - Phthalic acid is the main raw material for the production of diethyl phthalate. It is an aromatic acid obtained from the reaction of o-xylene with phthalic anhydride.
• Ethanol - Ethanol, also known as ethyl alcohol, is an alcohol that serves as a reagent in the synthesis of diethyl phthalate. It can be obtained from various sources, such as carbohydrate fermentation or chemical synthesis from petroleum or natural gas.

Industrial chemical synthesis step-by-step:

• Esterification reaction - Phthalic acid reacts with ethanol in the presence of a catalyst, such as sulfuric acid, to form diethyl phthalate. During this reaction, ethanol loses a water molecule while the ester bond between phthalic acid and ethanol is formed.
• Distillation - The reaction product undergoes distillation to separate diethyl phthalate from unreacted reagents, water, and other by-products. Distillation is carried out at controlled temperatures to separate the components based on their boiling points.
• Purification - The distilled diethyl phthalate undergoes further purification processes to remove any remaining impurities. These processes may include washing, filtration, or chemical treatments.
• Quality control - The purified diethyl phthalate undergoes quality control checks to ensure its purity, composition, and compliance with required standards.

It appears as a colourless liquid with an unpleasant taste that is insoluble in water.

What it is used for and where

Diethyl phthalate has a low molecular weight and is found in personal care products such as cosmetics, shampoos, perfumes, deodorants, lotions and in oral tablets.

Cosmetics

Denaturant. The ionic or polar molecules of this ingredient included in formulations that interact with protein groups, modulate the properties of the solution to suit specific needs.

Film-forming agent. It produces a continuous ultra-thin film with an optimal balance of cohesion, adhesion and stickiness on the skin or hair to counteract or limit damage from external phenomena such as chemicals, UV rays and pollution.

Fragrance. It plays a decisive and important role in the formulation of cosmetic products as it provides the possibility of enhancing, masking or adding fragrance to the final product, increasing its marketability.  The consumer always expects to find a pleasant or distinctive scent in a cosmetic product.

Hair conditioning agent. A significant number of ingredients with specific and targeted purposes may co-exist in hair shampoo formulations: cleansers, conditioners, thickeners, matting agents, sequestering agents, fragrances, preservatives, special additives. However, the indispensable ingredients are the cleansers and conditioners as they are necessary and sufficient for hair cleansing and manageability. The others act as commercial and non-essential auxiliaries such as: appearance, fragrance, colouring, etc. Hair conditioning agents have the task of increasing shine, manageability and volume, and reducing static electricity, especially after treatments such as colouring, ironing, waving, drying and brushing. They are, in practice, dispersants that may contain cationic surfactants, thickeners, emollients, polymers. The typology of hair conditioning agents includes: intensive conditioners, instant conditioners, thickening conditioners, drying conditioners. They can perform their task generally accompanied by other different ingredients.

Plasticiser. Ingredient added to the formulation with the purpose of retaining fragrance and colour, increasing flexibility, flowability, deformability, durability of various ingredients allowing better processing. It softens and makes flexible synthetic polymers that otherwise could not be easily processed, stretched or deformed.

Solvent. It is the substance for dissolving or dispersing surfactants, oils, dyes, flavourings, bactericidal preservatives in solution.In fact, it dissolves other components present in a cosmetic formulation. Solvents are generally liquid (aqueous and non-aqueous).

Pharmaceuticals

Diethylphthalate is used in pharmaceutical formulations as an excipient or solvent and as a vehicle for active pharmaceutical ingredients and as a cofactor in the solubility and stability of drugs. In topical preparations it improves the absorption of active ingredients into the skin and may act as a plasticiser to improve product consistency and spreadability. In oral dosage forms it acts as a plasticiser or film-forming agent. It can also help improve the mechanical properties of tablets, including hardness, flexibility and disintegration.

Other uses

Generally its use is in the plastic sector to soften the plastic.

Safety

It can also be used to denature ethyl alcohol although phthalates are suspected of causing health problems, but the acute toxicity of phthalates is very low (LD 50 1-30g / kg) (1).

However, the experts of the Scientific Committee on Consumer Products SCCP consider that:

"Despite the absence of adequate toxicological data for some of this group of phthalates and in view of the low concentrations found in the perfume samples analysed, there would be no quantifiable risk to the consumer."(2).

The most relevant studies on this chemical compound have been selected with a summary of their contents:

Diethyl Phthalate, studies

• Molecular Formula   C₁₂H₁₄O₄
• Linear Formula  C₆H₄-1,2-(CO₂C₂H₅)₂
• Molecular Weight   222.24 g/mol
• CAS   84-66-2
• EC number    201-550-6 

• Phthalic acid diethyl ester
• Ethyl phthalate
• 1,2-Benzenedicarboxylic acid, diethyl ester
• Phthalic acid, diethyl ester
• o-Bis(ethoxycarbonyl)benzene
• Diethyl 1,2-benzenedicarboxylate
• diethyl benzene-1,2-dicarboxylate
• o-Benzenedicarboxylic acid, diethyl ester
• benzene-1,2-dicarboxylic acid diethyl ester
• ethyl 2-(ethoxycarbonyl)benzoate
• Phthalic acid, bis-iso-nonyl ester
• EINECS 273-520-0
• PubChem Substance ID 329757907
• EC Number: 201-550-6
• MDL number: MFCD00009111

References_____________________________________________________________________

(1) Leitz J, Kuballa T, Rehm J, Lachenmeier DW. Chemical analysis and risk assessment of diethyl phthalate in alcoholic beverages with special regard to unrecorded alcohol. PLoS One. 2009 Dec 2;4(12):e8127. doi: 10.1371/journal.pone.0008127.

(2) Opinion on phthalates 21 mar 07_corr.doc (europa.eu)