Human Endogenous Metabolite
Dodecane does not have a specific biological target. As an inert hydrocarbon, it functions as a non-polar solvent and disruptor of lipid membranes. In a biological context, its primary effect is to cause skin irritation. It has been shown to significantly upregulate the expression of the pro-inflammatory cytokine TNF-alpha in rat skin, as well as increase transepidermal water loss (TEWL), indicating a disruption of the skin barrier function.

In cell-free assays, Dodecane is primarily used as a non-polar reference standard for GC-MS. It has no specific enzyme inhibition or activation properties. It may be used to determine the efficiency of organic extractions from aqueous solutions. Its inertness makes it a useful medium for studying hydrophobic interactions and membrane partitioning.

In cell-based assays, Dodecane is not typically used to study specific pathways, but its effects on skin can be modeled. In skin cell cultures (e.g., keratinocytes), exposure to Dodecane can be used as a positive control for inducing a mild inflammatory response, characterized by increased TNF-alpha expression and disruption of tight junction proteins.

For a non-cell analytical assay, Dodecane is used as a standard in GC-FID. A stock solution is prepared in hexane. A calibration curve is created by serial dilution to concentrations ranging from 10 to 500 ug/mL. The sample is injected onto a non-polar capillary column and eluted using a temperature ramp (e.g., 50degC to 250degC). The peak area of the sample is compared to the standard curve to determine the concentration.

For in vitro cellular assays, HaCaT human keratinocytes are seeded in a 12-well plate. Upon reaching 80-90% confluency, the cells are treated with Dodecane (e.g., 1-50 uM, diluted in DMSO) for 6-24 hours. The cells are then harvested, and RNA is extracted. The expression of the TNF-alpha gene is quantified by RT-qPCR using TaqMan probes. TNF-alpha protein levels in the cell supernatant are also measured by ELISA.

In vivo, the irritating effect of Dodecane has been studied in a rat model. The dorsal skin of CD HrBi rats is shaved, and Dodecane (230 microL) is applied topically as a single dose. After 1 hour, skin biopsies are taken. The expression levels of TNF-alpha mRNA and protein are significantly higher in the treated skin compared to the control, confirming it as a model of chemical-induced irritation.

Absorption, Distribution and Excretion
Pigs were exposed to cotton fabrics soaked in JP-8 aviation kerosene for 1 and 4 days, with repeated exposures daily. Skin sections were then prepared from both pre- and unexposed skin and placed in flow-through in vitro diffusion cells. Five diffusion cells containing exposed skin and four containing unexposed skin were injected with a mixture of 14 different hydrocarbons (HCs), including nonane, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, ethylbenzene, o-xylene, trimethylbenzene (TMB), cyclohexylbenzene (CHB), naphthalene, and dimethylnaphthalene (DMN), diluted with water and ethanol (50:50). Five additional diffusion cells containing only JP-8 exposed skin were injected with only the diluent to determine the retention of aviation kerosene HCs in the skin. Absorption parameters of the studied HCs, including flux, diffusion coefficient, and permeability coefficient, were calculated. Data showed that skin uptake of certain aromatic hydrocarbons (such as ethylbenzene, o-xylene, and trimethylbromide) increased by 2-fold and 4-fold, respectively, after JP-8 fuel pre-exposure for 1 and 4 days. Similarly, dodecane and tridecane uptake were also higher in skin studies after 4 days of JP-8 pre-exposure than after 1 day. Naphthalene and dimethylnitrosamine (DMN) uptake were both 1.5-fold higher than the control group in both 1-day and 4-day pre-exposure studies. Compared to 1-day pre-exposure, CHB, naphthalene, and DMN remained persistently in the skin after 4-day pre-exposure, which may indicate that the skin continues to absorb these substances for several days after exposure. The possible mechanism for increased hydrocarbon uptake in the skin after fuel pre-exposure may be through extraction of lipids from the stratum corneum, which has been confirmed by Fourier transform infrared spectroscopy (FTIR) analysis. This study indicates that pre-exposure to aviation kerosene enhances subsequent in vitro transdermal uptake of hydrocarbons (HC); therefore, single-dose aviation kerosene HC uptake data without skin contact may be insufficient to predict the toxicity of repeated exposures. For some compounds, continued uptake may occur several days after initial exposure. …This study aimed to evaluate the dose-related transdermal uptake of a variety of aliphatic and aromatic hydrocarbons. The initial treatment (1X) used a porcine skin flow-through diffusion cell with a mixture containing undecane (4.1%), dodecane (4.7%), tridecane (4.4%), tetradecane (3%), pentadecane (1.6%), naphthalene (1.1%), and dimethylnaphthalene (1.3% of aviation kerosene), with hexadecane as the solvent. Other treatments (n=4 cells) were performed at concentrations of 2X and 5X. Headspace solid-phase microextraction fiber technology was used, and gas chromatography-flame ionization detector (GC-FID) was employed to analyze the perfusion samples. We normalized the assay method to ensure good linearity across culture medium standards for all tested components. We estimated the uptake parameters for all tested hydrocarbons, including diffusion coefficient, permeability coefficient, steady-state flux, and percentage of absorbed dose. This method provides a baseline for assessing interactions between components and between components and the diluent (solvent). We established a quantitative structure-activity relationship (QSPR) model to predict the permeability of unknown jet fuel hydrocarbons in this solvent system using their physicochemical parameters. The results showed that the absorption of naphthalene and dimethylnaphthalene (DMN) was positively correlated with dose. We used the vial equilibrium method to determine the partition coefficients (PCs) of octane, nonane, decane, undecane, and dodecane (n-C8 to n-C12 n-alkanes) in rat tissue/air and blood/air. The blood/air ratios for n-alkanes (n-C8 to n-C12) were 3.1, 5.8, 8.1, 20.4, and 24.6, respectively. The lipophilicity of n-alkanes increased with increasing carbon chain length, indicating that lipophilicity is an important determinant of the blood/air ratio of n-alkanes. The muscle/blood, liver/blood, brain/blood, and fat/blood ratios were: octane (1.0, 1.9, 1.4, and 247), nonane (0.8, 1.9, 3.8, and 274), decane (0.9, 2.0, 4.8, and 328), undecane (0.7, 1.5, 1.7, and 529), and dodecane (1.2, 1.9, 19.8, and 671). The tissue/blood partition coefficient (PC value) was highest in adipose tissue and lowest in muscle tissue. The brain/air partition coefficient of undecane was inconsistent with the partition coefficients of other n-alkanes. Using the measured partition coefficients of these n-alkanes, linear regression was used to predict the tissue (excluding brain tissue) and blood/air partition coefficients of longer-chain n-alkanes (tridecane, tetradecane, pentadecane, hexadecane, and heptadecane, i.e., n-C13 to n-C17). The measured and predicted tissue/air and blood/air partition coefficients for n-C8 to n-Cl2 agree well, enhancing confidence in the prediction of partition coefficients for long-chain n-alkanes. Dodecane is primarily absorbed through inhalation and has been detected in breast milk.

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Metabolism / Metabolites
Alternative fuels are being considered in both civilian and military applications. One such alternative is S-8, a jet fuel synthesized via the Fischer-Tropsch synthesis process. It contains no aromatic compounds and is primarily composed of straight-chain and branched alkanes. Currently, no S-8 fuel metabolites have been identified in experimental animals. This study aimed to identify metabolites from exposure of male Fischer 344 rats to aerosolized S-8 and a designed mixture of straight-chain alkanes/polycyclic aromatic hydrocarbons (decane, undecane, dodecane, tridecane, tetradecane, pentadecane, naphthalene, and 2-methylnaphthalene). Blood and tissue samples were collected for analysis of 70 straight-chain and branched alcohols and ketones with 7 to 15 carbon atoms. No fuel metabolites were detected in blood, lungs, brain, or adipose tissue after S-8 exposure. However, metabolites were detected in liver, urine, and feces. Most metabolites were alcohols and ketones at positions 2 and 3 of the main hydrocarbons, with very few metabolites at positions 1 or 4. Following exposure to a mixture of alkanes, metabolites were detected in the blood, liver, and lungs. Notably, the re-metabolites (3-tetranone, 2-tetranol, and 2-tetradecanool) were detected only in lung tissue, potentially indicating that metabolism occurred in the lungs. Apart from these re-metabolites, the metabolic profile observed in this study is consistent with previously reported findings on the metabolism of individual alkanes. Further investigation is needed to determine potential metabolic interactions between the parent, primary, and secondary metabolites, and to identify more polar metabolites. Some metabolites may have potential use as biomarkers for fuel exposure. Dodecane hydroxylation yields the corresponding primary alcohol. It is metabolized by a rat liver microsomal mixed-function oxidase system. Dodecane induces the metabolism of benzo[a]pyrene in the lungs.

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Pharmacokinetic data for Dodecane is not relevant as it is not a drug. As a hydrocarbon, it is highly lipophilic and poorly absorbed from the intestine. If absorbed, it would likely be distributed to adipose tissue. It is metabolized by the cytochrome P450 enzyme system, specifically the CYP4B family, to the corresponding alcohol and then to the acid.

Toxicity Summary
Identification and Uses: Dodecane is a colorless liquid. It is a component of gasoline and is used as a solvent, organic synthesis agent, distillation flux in aviation fuel research, and fuel in the rubber and paper industries. Human Exposure and Toxicity: Dodecane is potentially harmful if inhaled, swallowed, or absorbed through the skin. It can irritate mucous membranes. Animal Studies: Dodecane causes mild to severe skin and respiratory irritation in animals. However, it causes only mild or negligible eye irritation. Rats inhaling 0.2 mL of dodecane died within 24 hours due to progressive edema and hemorrhage. Exposure to saturated vapor concentrations of dodecane in rats showed no effects, including central nervous system depression. Topical application of dodecane to offspring of rats treated on day 1 of gestation with benzo[a]pyrene, chloroquine, or benzo[b]tribenzobenzene resulted in tumors in the offspring. Dodecane has been shown to be a promoter of ultraviolet radiation-induced skin cancer. Dodecane did not increase the mutation rate in the Ames Salmonella Typhimurium mutation assay with or without metabolic activation. However, dodecane can enhance the mutation induced by methylazomethyl acetate at the ouabain resistance site.

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Interactions
This study aimed to evaluate the dose-related transdermal absorption of various aliphatic and aromatic hydrocarbons. The first treatment (1X) employed a porcine skin flow-through diffusion cell using a mixture containing undecane (4.1%), dodecane (4.7%), tridecane (4.4%), tetradecane (3%), pentadecane (1.6%), naphthalene (1.1%), and dimethylnaphthalene (1.3% of the jet fuel), with hexadecane as the solvent. Other treatment groups (n=4 cells) used concentrations of 2X and 5X. Perfusion samples were analyzed using headspace solid-phase microextraction fiber optics and gas chromatography-flame ionization detector (GC-FID). The assay method was normalized to ensure good linearity of all tested components against culture medium standards. Absorption parameters for all tested hydrocarbons, including diffusion coefficient, permeability coefficient, steady-state flux, and percentage of absorbed dose, were estimated. This method provides a baseline for assessing interactions between components and between components and the diluent (solvent). We established a quantitative structure-activity relationship (QSPR) model to predict the permeability of unknown aviation kerosene hydrocarbons in this solvent system using their physicochemical parameters. The results showed that the absorption rates of naphthalene and dimethylnaphthalene (DMN) increased with increasing dose. Aviation kerosene is a complex mixture of aliphatic (ALI) and aromatic (ARO) hydrocarbons, which exhibit significantly different cytotoxic and pro-inflammatory activities in human epidermal keratinocytes (HEK). To elucidate the toxicological interactions among the hydrocarbons in the mixture and their contribution to skin toxicity, we divided nine ALI hydrocarbons and five ARO hydrocarbons into five groups (high/medium/low cytotoxicity and strong/weak IL-8 induction), and performed intra- and inter-group mixing to assess their effects on HEK cell mortality and IL-8 release. This study also evaluated the effect of adding a single hydrocarbon compound to JP-8 fuel on fuel skin toxicity. The results showed that when hydrocarbon compounds are mixed, HEK cell mortality and IL-8 release are not entirely determined by their individual influence on these two parameters. A mixture containing ARO hydrocarbons with high cytotoxicity and weak IL-8 induction induced the lowest HEK cell mortality (7%) and the highest IL-8 production. Antagonistic responses were not always correlated with ALI carbon chain length and ARO structure, and played different roles in the overall toxicity of the mixture. Adding benzene, toluene, xylene, or ethylbenzene alone to JP-8 fuel, even at levels up to tenfold, did not increase HEK cell mortality; however, adding ALI hydrocarbons alone showed dose-related differential IL-8 responses. In an all-ALI environment, no single hydrocarbon was the dominant factor determining HEK cytotoxicity, while the absence of hexadecane led to a 2.5-fold increase in IL-8 production. Overall, decane, undecane, and dodecane were the main hydrocarbons associated with high cytotoxicity, while tetradecane, pentadecane, and hexadecane had the strongest buffering effects, mitigating skin toxicity. The effects of mixtures must be considered when assessing the toxicity of jet fuel to human epidermal keratinocytes (HEK).
Jet fuels are complex mixtures of aliphatic (ALI) and aromatic (ARO) hydrocarbons, exhibiting significant differences in cytotoxicity and pro-inflammatory activity in human epidermal keratinocytes (HEK). To elucidate the skin toxicity of such complex mixtures of jet fuels, this study investigated the effects of structural differences, exposure time, and dose on HEK toxicity, assessed by mortality and IL-8 release. ALI and ARO hydrocarbons were classified into four categories: high cytotoxicity (aliphatic hydrocarbons including octane, nonane, and decane; aromatic hydrocarbons including cyclohexylbenzene, trimethylbenzene, and xylene), low cytotoxicity (aliphatic hydrocarbons including tetradecane, pentadecane, and hexadecane; aromatic hydrocarbons including benzene), high IL-8 release (aliphatic hydrocarbons including decane, undecane, and dodecane; aromatic hydrocarbons including dimethylnaphthalene, cyclohexylbenzene, and ethylbenzene), and low IL-8 release (aliphatic hydrocarbons including tetradecane, pentadecane, and hexadecane; aromatic hydrocarbons including benzene, toluene, and xylene). These four classes of ALI hydrocarbons were mixed together or cross-mixed with the four classes of ARO hydrocarbons. Cytotoxicity and IL-8 production in HEK cells were assessed after 24 hours. Results showed antagonistic cytotoxic effects between ALI and ARO hydrocarbons, with ALI attenuating HEK cell death induced by ARO hydrocarbons. Conversely, ARO hydrocarbons significantly reduced the ALI-induced IL-8 elevation. The study found a synergistic effect between low IL-8 induction and low cytotoxic hydrocarbons, and the highest cytotoxicity and IL-8 induction responses did not entirely correspond to mixtures of high cytotoxicity and high IL-8 induction hydrocarbons. This study supports the view that ARO determines HEK cell death, while ALI is the main factor in inducing pro-inflammatory responses. Mixture effects must be considered when assessing HEK cytotoxicity. In C3H/HEJ mouse skin bioassays, 9-, 2-, and 3-methylbenzo[a]anthracene compounds showed no carcinogenicity in toluene as a solvent. Replacing toluene with n-dodecane resulted in significant tumor formation in all three compounds. The results indicate that…the carcinogenic potential of some non-carcinogenic methylbenzo[a]anthracene can be altered by the solvent used. For more complete data on n-dodecane interactions (11 in total), please visit the HSDB record page.

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Toxicity Data
LC50 (rat) >142 ppm/8 hours

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Dodecane is considered to have low acute toxicity. The oral LD50 is >5000 mg/kg. It is a mild skin and eye irritant but is not a skin sensitizer. Inhalation of high concentrations of vapors can cause respiratory irritation. Chronic exposure may be associated with other health effects, but it is not classified as a carcinogen.

Dodecane is a clear, colorless liquid. (NTP, 1992)
Dodecane is a straight-chain alkane containing 12 carbon atoms. It has been isolated from the essential oils of various plants, including ginger (Zingiber officinale). It is a plant metabolite.
Dodecane has also been reported in tea (Camellia sinensis), aristolochia triangularis, and other organisms with relevant data.

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Dodecane is a research chemical and is not an FDA-approved drug. It has no therapeutic use. It is a standard reference material for gas chromatography and a common solvent in chemical research. It is also used to study skin irritation mechanisms and barrier function.

C12H26

170.33

170.203

112-40-3

93685-81-5

8182

Colorless to light yellow liquid

0.8±0.1 g/cm3

216.1±3.0 °C at 760 mmHg

14.7 °F (NTP, 1992) ; -9.55 °C ; Heat of fusion: 36.8 kJ/mol at melting point ; -9.6 °C ; -9.6 °C

71.1±0.0 °C

0.2±0.2 mmHg at 25°C

1.422

7.13

0

9

12

56.4

0

C([H])([H])(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H]

SNRUBQQJIBEYMU-UHFFFAOYSA-N

InChI=1S/C12H26/c1-3-5-7-9-11-12-10-8-6-4-2/h3-12H2,1-2H3

dodecane

Ba 51-090453

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)

DMSO : ~20 mg/mL (~117.42 mM; with ultrasonication)

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.

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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).

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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)

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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).

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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

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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.

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