Absorption, Distribution and Excretion
Despite the global use of over 4.5 billion gallons of JP-8 aviation kerosene annually by governments and industries, little is known about the mechanisms of skin penetration and absorption of aviation kerosene, particularly JP-8. Exposure routes to JP-8 include vapor, liquid, and aerosol. Inhalation and skin contact are the most common routes. Repeated or prolonged exposure to JP-8 may cause irritation, but it remains unclear whether skin penetration of the fuel leads to systemic toxicity. This study aimed to measure the penetration and absorption of JP-8 and its major components in rat skin to assess its potential effects on humans. We used a static diffusion cell to measure the flux of JP-8 and its components across the skin and the skin absorption kinetics. The total flux of hydrocarbon components was 20.3 μg/cm²/h. Thirteen components of JP-8 permeated into the receptor solution. Permeation fluxes ranged from a high of 51.5 μg/cm²/h (additive diethylene glycol monomethyl ether) to a low of 0.334 μg/cm²/h (tetrane). Aromatic components penetrated the skin most rapidly. Six components (all aliphatic) were detected in the skin. After 3.5 hours, the concentrations absorbed through the skin ranged from 0.055 μg/g (tetradecane) to 0.266 μg/g (undecane). These results indicate that (1) JP-8 penetration does not cause systemic toxicity due to the low osmotic flux of all components; and (2) the absorption of aliphatic components through the skin may be the cause of skin irritation. JP-8 has been shown to be toxic in animal models and humans. The possibility of human exposure to JP-8 is high. Quantitative analysis of JP-8 percutaneous absorption is crucial for assessing the health hazards of occupational exposure. This study selected the major components of JP-8, including three aliphatic compounds (dodecane, tridecane, and tetradecane) and two aromatic compounds (naphthalene and 2-methylnaphthalene). We investigated the effects of percutaneous exposure of the above five compounds on the biophysical properties of skin lipids and proteins, as well as macroscopic barrier function. Fourier transform infrared spectroscopy (FTIR) was used to analyze changes in the biophysical properties of lipids and proteins in the stratum corneum (SC). FTIR results showed that all five components of JP-8 significantly (P<0.05) extracted SC lipids and proteins. Macroscopic barrier function was assessed by measuring transepidermal water loss (TEWL). Compared with the control group, all five JP-8 components studied significantly (P<0.05) increased TEWL. Assuming a body surface area of 0.25 m² and an exposure time of 8 hours, the absorption of chemicals was quantified. The results showed that among the aliphatic components of JP-8, tridecane had the highest skin permeability; while among the aromatic components, naphthalene had the highest skin permeability. The absorption of chemicals suggests that the potential systemic toxicity of tridecane, naphthalene, and their methyl derivatives should be monitored. JP-8 is a complex mixture containing more than 200 aliphatic and aromatic hydrocarbons, most of which are toxic. We selected tetradecane and naphthalene as two representative chemical markers for computer simulation. Therefore, we used a human respiratory system model to simulate the transport and deposition of naphthalene and tetradecane vapors. We analyzed inspiratory deposition data and calculated the regional deposition fraction (DF) and deposition enhancement factor (DEF). Vapor deposition is influenced by vapor properties (e.g., diffusion coefficient), airway geometry, breathing pattern, inspiratory flow rate, and airway wall absorption parameters. Specifically, the absorption of vapors by the respiratory tract is largely influenced by the degree of absorption by the airway walls. For example, tetradecane vapor is almost insoluble in the mucus layer, so the amount deposited in the extrathoracic and tracheobronchial (TB) airways is almost zero, i.e., deposition factor (DF) <1%. The remaining vapor may further penetrate and deposit in the alveolar airways. When tetradecane vapor is inhaled, its deposition factor (DF) in the alveolar region ranges from 7% to 24%, depending on the respiratory waveform, inspiratory rate, and mucus layer thickness. In contrast, naphthalene vapor is almost completely deposited in the extrathoracic and tracheobronchial (TB) airways, with very little downstream movement and deposition in the respiratory zone. Under normal respiratory conditions (Q = 15-60 L/min), the distribution factor (DF) of naphthalene vapor in the extrathoracic airways (from the nasal/oral cavity to the trachea) is approximately 12-34%, while it is approximately 66-87% in the airways of patients with tuberculosis (TB). Furthermore, changes in respiratory pathways (e.g., from nasal to oral breathing) may affect vapor deposition in the nasal, oral, nasopharyngeal, and oropharyngeal regions, but have little effect on deposition in the larynx and beyond. The different deposition patterns of naphthalene and tetradecane vapors in the human respiratory system may indicate that these toxic aviation fuel components have different toxicities, thus producing different health effects. 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 were determined using the vial balance method. 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 increases with increasing carbon chain length, indicating that lipophilicity is a crucial determinant of the blood/air ratio for 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 PC value was highest in adipose tissue and lowest in muscle tissue. The brain/air PC value for undecane was inconsistent with the PC values for other n-alkanes. Using the measured partition coefficients of these n-alkanes, linear regression was employed to predict the tissue (excluding brain tissue) and blood/air partition coefficients of larger n-alkanes (tetane, 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 showed good agreement, enhancing our confidence in the prediction of partition coefficients for long-chain n-alkanes. More complete data on the absorption, distribution, and excretion of n-tetradecane (7 types) can be found on the HSDB record page. Metabolism/Metabolites Tetradecane can be metabolized via the cytochrome P450 mixed-function oxidase system. Alternative fuels are being considered in both civilian and military applications. One such alternative is S-8, an alternative jet fuel synthesized using the Fischer-Tropsch synthesis process, which is free of aromatic compounds and primarily composed of straight-chain and branched alkanes. Metabolites of S-8 fuel have not yet been identified in laboratory animals. This study aimed to identify metabolites from male Fischer 344 rats exposed to aerosol S-8 and a designed mixture of straight-chain alkane/polycyclic aromatic hydrocarbons (decane, undecane, dodecane, tridecane, tetradecane, pentadecane, naphthalene, and 2-methylnaphthalene). Blood and tissue samples were collected, and 70 straight-chain and branched alcohols and ketones with 7 to 15 carbon atoms were analyzed. After exposure to S-8, no fuel metabolites were detected in blood, lung, brain, or adipose tissue. Metabolites were detected in liver, urine, and feces. Most metabolites were alcohols and ketones at the 2 and 3 positions of the major hydrocarbons, with only trace amounts at the 1 or 4 positions. After exposure to the alkane mixture, metabolites were detected in blood, liver, and lung tissue. Interestingly, heavy metabolites (3-tetranone, 2-tetranol, and 2-tetradecanol) were observed only in lung tissue, suggesting that metabolism occurred in the lungs. In addition to these heavy 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 parent, primary, and secondary metabolites, and to identify more polar metabolites. Some metabolites may have potential uses as biomarkers of fuel exposure. Jet fuel 8 (JP-8) is a complex mixture of aromatic and aliphatic hydrocarbons. This study aimed to determine the in vitro metabolic rate constants of the semi-volatile n-alkanes nonane (C9), decane (C10), and tetradecane (C14) using a rat liver microsomal oxidation method. Metabolism was assessed by determining the disappearance of parent compounds using gas chromatography. Different concentrations of n-alkanes were incubated with liver microsomes from adult male F-344 rats. The nonlinear kinetic constants for nonane and decane were V_max (nmol/mg protein/min) = 7.26 ± 0.20 and 2.80 ± 0.35, respectively, and K_M (μM) = 294.83 ± 68.67 and 398.70 ± 42.70, respectively. Metabolic capacity, assessed by intrinsic clearance (V_max/K_M), was approximately four times that of decane (0.007 ± 0.001). Even with increased microsomal protein concentration and prolonged incubation time, tetradecane did not undergo significant metabolism. These results indicate a negative correlation between metabolic clearance and the chain length of the n-alkane. These metabolic rate constants will be used to update existing physiological pharmacokinetic (PBPK) models for nonane and decane as part of the development of the JP-8 PBPK model.
Candida lipophila ATCC 8661 was cultured in mineral salt hydrocarbon medium. n-Tetradecane was one of the substrates used. …Analysis of the culture on n-alkane showed that the main components were fatty acids and alcohols with the same chain length as the substrate. In addition, many other fatty acids and alcohols were present. Analysis of the saponified and unsaponified products obtained from the cells showed that the products were essentially identical. The presence of primary alcohols, secondary alcohols, and fatty acids with the same chain length as the n-alkane substrate indicates that both methyl and α-methylene groups were attacked.
For more complete metabolite/metabolite data on n-tetradecane (9 metabolites in total), please visit the HSDB record page.

Toxicity Summary
Identification and Uses: Tetradecane is a colorless liquid. It is used in organic synthesis and also as a solvent for standardizing hydrocarbons and a distillation aid. Human Exposure and Toxicity: In industrial use, tetradecane may cause harm through inhalation, ingestion, or skin absorption. Animal Studies: In rabbit models, topical application of tetradecane resulted in significant hyperplasia of sebaceous glands, epidermis, and hair follicle epithelium. Intravenous injection of 5800 mg/kg was fatal in mice. Animals exhibited altered sleep duration, including changes in the righting reflex. Upon inhalation into the lungs, tetradecane is an asphyxiating agent similar to C6-C10 alkanes. These alkanes are slower to cause death and can cause chemical pneumonia. In a two-phase mouse study on the carcinogenicity of benzo[a]pyrene, tetradecane exhibited carcinogenic and tumor-promoting effects. Tetradecane enhanced the mitogenic response of mouse splenic lymphocytes to phytohemagglutinin. Interactions …This study aimed to evaluate the dose-related transdermal absorption of various aliphatic and aromatic hydrocarbons. The first treatment (1X) used a pigskin 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 the jet fuel), in hexadecane as the solvent. Other treatments (n = 4 cells) used concentrations of 2X and 5X. Headspace solid-phase microextraction (HSP) was employed, and the perfusion samples were analyzed using gas chromatography-flame ionization detection (GC-FID). We normalized the analytical method to ensure good linearity across culture medium standards for all tested components. We estimated the absorption 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. Our results indicate that the absorption of naphthalene and dimethylnaphthalene (DMN) is positively correlated with dosage. Tetradecane enhances the mitotic response of mouse splenic lymphocytes to phytohemagglutinin. The enhancing effects of straight-chain alkanes of specific chain lengths on the mitotic response of mouse splenic lymphocytes to phytohemagglutinin vary. We discovered a biphasic structure-function relationship, in which tetradecane exhibits the strongest mitotic activity.

[1]. He Bo, et al. Tetradecane and hexadecane binary mixtures as phase change materials (PCMs) for cool storage in district cooling systems.Energy.Volume 24, Issue 12, January 1999, Pages 1015-1028.

Tetradecane is a colorless liquid. It must be preheated before ignition. (NTP, 1992)
Tetradecane is a straight-chain alkane consisting of 14 carbon atoms. It is a plant metabolite and a component of volatile oils.
Tetradecane has been reported in Tulafrancsis, tea trees, and other organisms for which relevant data are available.
See also: Alkanes, C14-16 (note moved here); Alkanes, C14-30 (note moved here).

C14H30

198.39

198.235

629-59-4

Tetradecane-d30;204244-81-5

12389

Colorless liquid

0.767

252-254 °C(lit.)

5.8 °C

211 °F

1 mm Hg ( 76.4 °C)

n20/D 1.429(lit.)

5.707

0

0

11

14

74

0

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

BGHCVCJVXZWKCC-UHFFFAOYSA-N

InChI=1S/C14H30/c1-3-5-7-9-11-13-14-12-10-8-6-4-2/h3-14H2,1-2H3

tetradecane

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: 4.55 mg/mL (22.93 mM)

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.)