Absorption, Distribution and Excretion
/After/ oral admin of (14)C dimethyl phthalate to rats or mice, radioactivity was found in the blood and various tissues. Maximum values for radioactivity were observed within 1 hr. Tissue radioactivity was highest in the kidneys, followed in decreasing order by the liver, fat, and spleen. After 24 hr, 91% of the admin dose had been excreted in the urine and 4.1% in the feces.
The percutaneous absorption of a series of phthalate esters, dimethylphthalate, diethylphthalate, dibutyl phthalate, and di-(2-ethylhexyl) phthalate, was measured through human and rat epidermal membranes mounted in glass diffusion cells. The esters were applied directly to the epidermal membranes. Following application to the membranes, a lag phase followed by a linear phase of absorption was detected for each phthalate diester. Human skin was less permeable than rat skin for all four diesters. There appeared to be a trend to an increasing lag time with increasing molecular weight, but this relationship did not always hold true. The phthalate diesters were determined to have a 300 fold range of aqueous solubility and a wide range of lipophilicity. Once the diesters had contacted the human epidermal membrane, a slight increase in the permeability of the skin was detected. Relatively large changes in permeability were detected in the membrane following exposure.
This study examined the extent of dermal absorption of a series of phthalate diesters in the rat. Those tested were dimethyl, diethyl, dibutyl, diisobutyl, dihexyl, di(2-ethylhexyl), diisodecyl, and benzyl butyl phthalate. Hair from a skin area (1.3 cm in diameter) on the back of male F344 rats was clipped, the 14(C)phthalate diester was applied in a dose of 157 mumol/kg, and the area of application was covered with a perforated cap. The rat was restrained and housed for 7 days in a metabolic cage that allowed separate collection of urine and feces. Urine and feces were collected every 24 hr, and the amount of (14)C excreted was taken as an index of the percutaneous absorption. At 24 hr, diethyl phthalate showed the greatest excretion (26%). As the length of the alkyl side chain increased, the amount of (14)C excreted in the first 24 hr decreased signficantly. The cumulative percentage dose excreted in 7 days was greatest for diethyl, dibutyl, and diisobutyl phthalate, about 50-60% of the applied (14)C; and intermediate (20-40%) for dimethyl, benzyl butyl, and dihexyl phthalate. Urine was the major route of excretion of all phthalate diesters except for diisodecyl phthalate. This compound was poorly absorbed and showed almost no urinary excretion. After 7 days, the percentage dose for each phthalate that remained in the body was minimal showed no specific tissue distribution. Most of the unexcreted dose remained in the area of application. These data show that the structure of the phthalate diester determines the degree of dermal absorption. Absorption maximized with diethyl phthalate and then decreased significantly as the alkyl side chain length increased.
DMP is readily absorbed from the skin, intestinal tract, the peritoneal cavity, and lung.
For more Absorption, Distribution and Excretion (Complete) data for DIMETHYL PHTHALATE (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
Intestinal extracts from man, ferrets and the baboon, as well as liver extracts from the latter 2 species, break down dimethyl phthalate to the monoester.
In vitro studies on metabolism of dimethylphthalate, dibutyl phathalate, di-n-octyl phthalate ... and diethylhexyl phthalate by rat liver and kidney liver homogenates have demonstrated that the lower the molecular weight of phthalate ester the faster the rate of metabolism. Rate of degradation of esters by rat kidney homogenates was relatively slow when compared with that by liver homogenates.
Of a single dose of 120 mg dimethyl phthalate admin to rats by stomach tube, 44.6% was detected in the urine, consisting of 77.5% as the monomethyl ester with 14.4% as 0-phthalate acid and 8.1% as intact dimethyl phthalate.
... In a host-mediated mutagenesis assay, rats were injected ip with dimethyl phthalate (DMP) (2 g/kg body weight); urine was collected for 24 hr, extracted, and analyzed for ... phthalic acid-containing derivatives. The extracted urine ... contained an equivalent of 1.96 mg phthalate/mL urine. More than 97% of the phthalic acid-containing derivatives present in the extracted urine consisted of the nonmutagenic metabolite of DMP, monomethyl phthalate (MMP). In vitro experiments showed that rat liver homogenates hydrolyzed 93% of carbonyl-labeled (14)C-DMP (7.7 mM) to MMP in 2 hr and bound 0.07 nmol of ((14)C)phthalate/mg liver macromolecules. By contrast, rat epidermal homogenates metabolized only 5% and bound 38-fold higher levels of carbonyl-labeled (14)C-DMP (2.66 nmol/mg of macromolecules), with no detectable binding to nucleic acids. Compared to epidermis and plasma, liver had a fivefold higher rate of DMP monoesterase activity (1240 nmol/hr/mg protein), which, when inhibited by 67%, resulted in a 4.4-fold increase in phthalate-bound hepatic macromolecules (0.31 vs. 0.07 nmol of carbonyl-labeled (14)C-DMP/mg macromolecules). In addition to MMP, formaldehyde was produced during the metabolism of DMP by liver. When ethanol was used to inhibit the oxidation of DMP-derived methanol by hepatic homogenates, there resulted a 74% reduction in the accumulation of formaldehyde and similar reductions of 71 and 73% in the binding of methyl-labeled (14)C-DMP to nucleic acids and macromolecules. (Methyl-labeled, unlike carbonyl-labeled, (14)C-DMP yields a (14)C-labeled methanol when hydrolyzed.) These results indicate that the DMP diester ... binds to epidermal and hepatic macromolecules other than nucleic acids, and that although the rapid hepatic metabolism of DMP to its monoester (MMP) and methanol affords protection against higher levels of phthalate binding as well as against DMP-induced bacterial mutagenesis, it also oxidizes DMP-derived methanol to formaldehyde, a metabolite that binds macromolecules, including nucleic acids.
For more Metabolism/Metabolites (Complete) data for DIMETHYL PHTHALATE (12 total), please visit the HSDB record page.
Phthalate esters are first hydrolyzed to their monoester derivative. Once formed, the monoester derivative can be further hydrolyzed in vivo to phthalic acid or conjugated to glucuronide, both of which can then be excreted. The terminal or next-to-last carbon atom in the monoester can also be oxidized to an alcohol, which can be excreted as is or first oxidized to an aldehyde, ketone, or carboxylic acid. The monoester and oxidative metabolites are excreted in the urine and faeces. (A2884)

Toxicity Summary
IDENTIFICATION AND USE: Dimethyl phthalate (DMP) is a pale yellow, or colorless, oily liquid (solid below 42 °F) with slight aromatic odor. It is used as plasticizer for nitrocellulose and cellulose acetate, resins, and in solid rocket propellants; lacquers; plastics; rubber; coating agents; safety glass; and molding powders. Formerly it was used as a repellant for flies on horses and cows, and as a leech repellant. DMP is not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. HUMAN EXPOSURE AND TOXICITY: In man, dimethyl phthalate has caused skin irritation reactions and skin sensitization was induced in one individual. Repeated inhalation of the vapor irritated the nose and upper respiratory tract. If swallowed, DMP may cause irritation of the stomach, dizziness, and unconsciousness. In one fatal case of suicidal ingestion of a mixture containing dimethyl phthalate and ketone peroxides, the principal toxic symptoms were marked esophagitis, gastritis, and hemorrhage. Mortality of human sperm in vitro was reduced by 25% in cultures containing 0.4 mM DMP for 18 hr. Chromosomal damage was not induced in human white blood cells. DMP is not a known human carcinogen. ANIMAL STUDIES: DMP caused irritation and ulceration when repeatedly applied to mouse skin, but in rabbits it produced only weak skin and eye effects. Acute oral and dermal toxicity in a number of animal species was low. Oral studies in rats indicated repeated exposure may produce kidney damage and mild effects on the liver. Kidney and liver injury was seen in rabbits on repeated skin contact with DMP. By inhalation, severe mucous membrane irritation was observed in cats exposed at 250 ppm, and at 1250 ppm, animals appeared depressed. In mice inhaling 0.7-1.8 mg/cu m DMP (4 hr/day) for 4 mo, changes in the frequency of respiration, function of the nervous system, liver, and kidneys, and blood morphology were observed. Testosterone in testis and in serum and dihydrotestosterone in serum were significantly decreased in rats fed diets containing 2% dimethylphthalate for 1 week. The offspring of mice and rats treated orally or dermally were normal, whereas fetal deaths and malformations were seen when pregnant rats were given intraperitoneal injections. DMP did not enhance the tumor yield of an established skin carcinogen when applied repeatedly to the skin of mice. Mutagenic activity was observed in Salmonella typhimurium (Ames test). There was apparently some evidence of chromosome damage in the liver cells of rats given repeated skin application of DMP but not in the bone marrow cells of mice treated by single injection. In cultured Chinese hamster ovary cells, DMP induced sister-chromatid exchanges in only the presence of metabolic activation. DMP did not induce chromosomal aberrations, with or without metabolic activation, in cultured Chinese hamster ovary cells. Therefore, DMP is mutagenic only in certain in vitro studies after metabolism. This is probably due to the formation of a reactive species such as formaldehyde. Since DMP is not mutagenic in vivo, any reactive metabolites appear to be quickly detoxified. ECOTOXICITY STUDIES: 100 ppm DMP were acutely toxic to Palaemonetes pugio (grass shrimp) larvae. DMP at a concn of 100 ppm significantly increased the duration of larval development to the first postlarval stage. Bioavailability of phthalate congeners, including/ dimethyl phthalate to earthworms (Eisenia fetida) was studied when earthworms were exposed to two artificially contaminated agricultural and forest soils. DMP was not detected in earthworms.
Phthalate esters are endocrine disruptors. They decrease foetal testis testosterone production and reduce the expression of steroidogenic genes by decreasing mRNA expression. Some phthalates have also been shown to reduce the expression of insulin-like peptide 3 (insl3), an important hormone secreted by the Leydig cell necessary for development of the gubernacular ligament. Animal studies have shown that these effects disrupt reproductive development and can cause a number of malformations in affected young. (A2883)

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Toxicity Data
LCLo (cats) = 9,630 mg/m3/6H
LD50: 6800 mg/kg (Oral, Rat) (T13)
LD50: 3375 mg/kg (Intraperitoneal, Rat) (T13)
LD50: 38000 mg/kg (Dermal, Rat) (L1332)
LD50: 324 mg/kg (Intravenous, Rat) (L1332)

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Interactions
... Mice were epicutaneously sensitized with fluorescein isothiocyanate (FITC) dissolved in acetone containing a phthalate ester. Sensitization was evaluated as ear swelling after a challenge with FITC. Draining lymph node cells obtained 24 hr after skin sensitization were examined for FITC fluorescence by means of flow cytometry. FITC-positive cells were characterized with anti-CD11c and anti-CD11b by three-color flow cytometry. ... When mice were sensitized with FITC in acetone containing di-butyl phthalate (DBP) or di-n-propyl phthalate (DPP), strong enhancement of the ear-swelling response was observed. Di-methyl phthalate (DMP) and di-ethyl phthalate (DEP) were less effective but produced some enhancement. ...

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Non-Human Toxicity Values
LD50 Rat oral 6800 mg/kg
LD50 Rat oral 2860 mg/kg
LD50 Rat intraperitoneal 3375 mg/kg.
LD50 Rat dermal 38000 mg/kg
For more Non-Human Toxicity Values (Complete) data for DIMETHYL PHTHALATE (13 total), please visit the HSDB record page.

[1]. Impacts of dimethyl phthalate on the bacterial community and functions in black soils. Front Microbiol. 2015 May 5;6:405.

Dimethyl phthalate appears as a water-white liquid without significant odor. Denser than water and insoluble in water. Hence sinks in water. Flash point 300 °F. Eye contact may produce severe irritation and direct skin contact may produce mild irritation. Used in the manufacture of a variety of products including plastics, insect repellents, safety glass, and lacquer coatings.
Dimethyl phthalate is a phthalate ester, a diester and a methyl ester.
Dimethyl phthalate has many uses, including in solid rocket propellants, plastics, and insect repellants. Acute (short-term) exposure to dimethyl phthalate, via inhalation in humans and animals, results in irritation of the eyes, nose, and throat. No information is available on the chronic (long-term), reproductive, developmental, or carcinogenic effects of dimethyl phthalate in humans. Animal studies have reported slight effects on growth and on the kidney from chronic oral exposure to the chemical. EPA has classified dimethyl phthalate as a Group D, not classifiable as to human carcinogencity.
Dimethyl phthalate has been reported in Allium ampeloprasum, Cryptotaenia canadensis, and other organisms with data available.
Dimethyl phthalate is a phthalate ester. Phthalate esters are esters of phthalic acid and are mainly used as plasticizers, primarily used to soften polyvinyl chloride. They are found in a number of products, including glues, building materials, personal care products, detergents and surfactants, packaging, children's toys, paints, pharmaceuticals, food products, and textiles. Phthalates are hazardous due to their ability to act as endocrine disruptors. They are being phased out of many products in the United States and European Union due to these health concerns. (L1903)

C10H10O4

194.19

194.057

131-11-3

Dimethyl phthalate (Ring-d4);93951-89-4;Dimethyl phthalate-d6;85448-30-2

8554

Colorless to light yellow liquid

1.2±0.1 g/cm3

282.7±8.0 °C at 760 mmHg

2 °C(lit.)

146.1±0.0 °C

0.0±0.6 mmHg at 25°C

1.515

1.64

52.6

0

4

4

14

200

0

O=C(OC)C1=CC=CC=C1C(OC)=O

NIQCNGHVCWTJSM-UHFFFAOYSA-N

InChI=1S/C10H10O4/c1-13-9(11)7-5-3-4-6-8(7)10(12)14-2/h3-6H,1-2H3

dimethyl benzene-1,2-dicarboxylate

NSC-15398; NSC 15398; Dimethyl phthalate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 本产品在运输和储存过程中需避光。

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

DMSO : ~100 mg/mL (~514.99 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (12.87 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (12.87 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (12.87 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。