Absorption, Distribution and Excretion
Thirty minutes after oral administration of 14C-labeled diallyl phthalate (DAP) to rats and mice, the highest levels of radioactivity were observed in the small intestine, liver, dermis, muscle, blood, and kidneys. After 24 hours, approximately 6-7% radioactivity remained in rats and 1-3% in mice. In rats, 60% of the radioactivity was present in urine, and 30% was exhaled as carbon dioxide. In mice, 91% was present in urine, and only 8% was detected as carbon dioxide. Metabolism/Metabolites Fischer 344 rats and B6C3F1 mice were orally administered 1, 10, or 100 mg/kg of 14(C)-diallyl phthalate, orally or intravenously injected with 10 mg/kg, and placed in metabolic cages for 24 hours. In rats, 25-30% of diallyl phthalates are excreted as carbon dioxide, and 50-70% appear in the urine within 24 hours. In mice, 6-12% of diallyl phthalates are excreted as carbon dioxide, and 80-90% appear in the urine within 24 hours. Monoallyl phthalate (MAP), allyl alcohol, 3-hydroxypropyl mercaptouric acid (HPMA), and an unidentified polar metabolite (PM) were detected in the urine of rats and mice administered diallyl phthalate. The presence of this polar metabolite in the urine of rats administered diallyl phthalate or allyl alcohol suggests that this compound is a metabolite of allyl alcohol. There was no difference in the amount of allyl alcohol excreted by the two animal groups, but mice excreted higher amounts of diallyl phthalate (39% vs 33%), 3-hydroxypropyl mercaptouric acid (28% vs 17%), and polar metabolites (20% vs 8%) than rats. The metabolic pathway of diallyl phthalate (DAP) is as follows: First, the diester is hydrolyzed to produce diallyl phthalate (MAP) and allyl alcohol (AA). AA can be oxidized to acrolein and acrylic acid, and further metabolized to carbon dioxide (CO2). Allyl alcohol and acrolein can also react with reduced glutathione to produce 3-hydroxypropyl mercaptouric acid. Furthermore, allyl alcohol and acrolein can be oxidized to the epoxides glycidyl epoxide and glycidaldehyde. These epoxides can be hydrolyzed to produce glycerol and glyceraldehyde, or they can bind to reduced glutathione. It is currently unclear whether DAP is metabolized in vivo via this pathway. However, some products of the above-mentioned reaction (e.g., diallyl phthalate, 3-hydroxypropyl mercaptouric acid, allyl alcohol) and an unidentified polar metabolite were detected in the urine of rats and mice treated with DAP. ...Dallyl phthalate (DAP) was more hepatotoxic in rats than in mice, and allyl alcohol (AA) also showed the same species-specific toxicity differences. The data suggest that the toxicity of diallyl phthalate may stem from the allyl alcohol produced by its cleavage. To determine whether the differences in hepatotoxicity sensitivity among different species were due to differences in the in vivo distribution and metabolism of diallyl phthalate, we administered 14(C)-labeled diallyl phthalate (1, 10, or 100 mg/kg, orally or 10 mg/kg, intravenously) to Fischer 344 rats and B6C3F1 mice, respectively, and placed them in metabolic cages for 24 hours. In rats, 25-30% of diallyl phthalate is excreted as carbon dioxide, and 50-70% appears in the urine within 24 hours. In mice, 6-12% of diallyl phthalate is excreted as carbon dioxide, and 80-90% appears in the urine within 24 hours. Monoallyl phthalate (MAP), allyl alcohol, 3-hydroxypropyl mercaptouric acid (HPMA), and an unidentified polar metabolite (PM) were detected in the urine of rats and mice administered diallyl phthalate. The presence of this polar metabolite in the urine of rats administered diallyl phthalate or allyl alcohol suggests that this compound is a metabolite of allyl alcohol. There was no difference in the amount of allyl alcohol excreted by the two animal groups, but mice excreted higher levels of monoallyl phthalate (39% vs 33%), 3-hydroxypropyl mercaptouric acid (28% vs 17%), and polar metabolites (20% vs 8%) than rats. Phthalate esters are first hydrolyzed into their monoester derivatives. Once formed, these monoester derivatives can be further hydrolyzed in vivo to phthalic acid or conjugated with glucuronic acid, both of which can be excreted. The terminal or penultimate carbon atom of the monoester can also be oxidized to an alcohol, which can be excreted directly or first oxidized to an aldehyde, ketone, or carboxylic acid. The monoester and its oxidative metabolites are excreted in urine and feces. (A2884)

Toxicity Summary
Phthalate esters are endocrine disruptors. They reduce testosterone production in the fetal testes and decrease the expression of steroid-producing genes by reducing mRNA expression. Some phthalates have also been shown to reduce the expression of insulin-like peptide-3 (insl3), an important hormone secreted by interstitial cells in the testes and crucial for the development of the gubernaculum testis. Animal studies have shown that these effects can disrupt reproductive development and may lead to various malformations in affected offspring. (A2883)

---

Toxicity Data
LC50 (Rat) = 5,200 mg/m3/1h
LD50: 656 mg/kg (oral, rat) (T13)
LD50: 3.8-3.9 g/kg (skin, rabbit) (T29)
LD50: 700 mg/kg (intraperitoneal, mouse) (A724)

---

Non-human Toxicity Values
LD50 Rat Oral 656 mg/kg
LD50 Rabbit Oral 1.7 g/kg /from table/
LD50 Rabbit Skin 3400 mg/kg /from table/
LD50 Mouse Intraperitoneal 700 mg/kg
For more complete non-human toxicity data of diallyl phthalate, please refer to (7 cases in total), please visit the HSDB record page.

Diallyl phthalate is a clear, pale yellow liquid, odorless. (NTP, 1992)
Dallyl phthalate is a phthalate ester. Phthalate esters are esters of phthalic acid, primarily used as plasticizers, mainly for softening polyvinyl chloride (PVC). They are found in a wide variety of products, including adhesives, building materials, personal care products, detergents and surfactants, packaging materials, children's toys, paints, pharmaceuticals, food, and textiles. Phthalate esters have endocrine-disrupting effects and are therefore harmful. Due to these health concerns, the United States and the European Union are phasing out phthalate esters in many products. (L1903)

C14H14O4

246.25856

246.089

131-17-9

8560

Nearly colorless, oily liquid

1.1±0.1 g/cm3

329.1±0.0 °C at 760 mmHg

-70 °C

164.8±20.7 °C

0.0±0.7 mmHg at 25°C

1.524

3.29

0

4

8

18

290

0

C=CCOC(=O)C1=CC=CC=C1C(=O)OCC=C

QUDWYFHPNIMBFC-UHFFFAOYSA-N

InChI=1S/C14H14O4/c1-3-9-17-13(15)11-7-5-6-8-12(11)14(16)18-10-4-2/h3-8H,1-2,9-10H2

bis(prop-2-enyl) benzene-1,2-dicarboxylate

Diallyl phthalate NSC-7667 NSC 7667 NSC7667

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)