Absorption, Distribution and Excretion
JP-8 aviation kerosene has been reported to cause systemic and dermal toxicity in animal models and humans. Human exposure to JP-8 carries a high risk. This study determined the dermal absorption and dermal toxicity of three components of JP-8 (xylene, heptane, and hexadecane) in weaned piglets. In vivo dermal absorption results showed that, after 30 minutes of exposure, the absorption rate of hexadecane (0.43%) was higher than that of xylene (0.17%) or heptane (0.14%). Hexadecane was detected in two human aortic atherosclerotic cases at concentrations of 40 and 60 ng/g, respectively. …Piglets were exposed to cotton fabrics soaked in JP-8 aviation kerosene for 1 and 4 days, with repeated exposures daily. Skin sections were then taken from both pre- and unexposed skin and placed in a flow-through in vitro diffusion chamber. Five skin-exposed cells and four skin-unexposed cells were injected into 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 skin cells exposed only to JP-8 aviation kerosene were injected with the diluent to determine the retention of hydrocarbons in aviation kerosene on the skin. Absorption parameters such as absorption flux, diffusion coefficient, and permeability coefficient of the studied hydrocarbons were calculated. The data showed that skin pre-exposed to JP-8 aviation kerosene for 1 day and 4 days showed a 2-fold and 4-fold increase in the absorption of specific aromatic hydrocarbons (such as ethylbenzene, o-xylene, and TMB), respectively. Similarly, in the skin pre-exposed to JP-8 for 4 days, the absorption of dodecane and tridecane was higher than in the experiment pre-exposed for 1 day. The absorption of naphthalene and dimethylnitrosamine (DMN) was 1.5 times higher than the control group in both the 1-day and 4-day pre-exposure experiments. Compared to 1-day pre-exposure, the residual levels of chlorobenzene (CHB), naphthalene, and dimethylnitrosamine (DMN) in skin 4 days after pre-exposure were significantly increased, which may indicate that the skin continues to absorb these substances for several days after exposure. A possible mechanism for increased hydrocarbon (HC) absorption in pre-exposed skin may be through extraction of stratum corneum lipids, as confirmed by Fourier transform infrared spectroscopy (FTIR). This study suggests that pre-exposure to aviation kerosene enhances subsequent in vitro transdermal hydrocarbon (HC) absorption; therefore, absorption data from a single exposure of unexposed skin to aviation kerosene for hydrocarbons (HC) may be insufficient to predict the toxicity of repeated exposures. For some compounds, continued absorption may occur several days after the initial exposure. 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 equilibration method. The blood/air PC values for 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 a crucial factor determining the blood/air PC value of n-alkanes. The PC values for muscle/blood, liver/blood, brain/blood, and fat/blood 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), respectively. The tissue/blood PC value was highest in fat and lowest in muscle. The brain/air PC value of undecane was inconsistent with the PC values 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 larger chain n-alkanes (tetane, tetradecane, pentadecane, hexadecane, and heptadecane, n-C13 to n-C17). The measured values of tissue/air and blood/air partition coefficients of n-C8 to n-Cl2 were in good agreement with the predicted values, which enhanced confidence in the prediction of partition coefficients of longer chain n-alkanes. 1-(14)C n-hexadecane is a model compound of non-volatile aliphatic hydrocarbon components in crude oil and was administered to lobsters (Panulirus argus) and American lobsters (Homarus americanus) via intraperitoneal injection. The experiments were conducted in Florida (lobster) and Maine (American lobster), respectively. Animals were sacrificed at different time points from 0.5 hours to 8 weeks after administration. The content of ¹⁴C in tissues and body fluids was analyzed using a combination of digestion or catalytic oxidation and liquid scintillation counting. Selected tissues (hepatopancreas, tail muscle, and hemolymph) were extracted with ethyl acetate to quantify unmetabolized n-hexadecane by thin-layer chromatography. The radioactivity derived from n-hexadecane was highly persistent in both lobster (half-life = 4.6 weeks) and American lobster (half-life = 11.2 weeks). In both lobster species, the hepatopancreas exhibited the highest specific activity, while the tail muscle had the longest radioactive elimination half-life. Although hexadecane was metabolized more rapidly in the lobster hepatopancreas than in the American lobster hepatopancreas, unmetabolized hexadecane persisted in the hepatopancreas of both animals for at least 8 weeks (the longest duration studied).

Toxicity Summary
Identification and Uses: Hexadecane is a colorless liquid. It is used as a solvent, organic intermediate, and ignition standard for diesel fuel. It is also used in the production of detergents. Human Exposure and Toxicity: Acute exposure to hexadecane can cause irritation, central nervous system depression, and gastrointestinal irritation. Animal Studies: In a hexadecane-induced epidermal hyperplasia model in hairless rats, various biochemical indicators, including ornithine decarboxylase activity (ODC) and tissue polyamine levels, were measured. Animals received three applications of 200 μL of pure hexadecane on day 1. ODC activity and polyamine levels (putrescine, spermidine, and spermine) in the epidermis were significantly increased, peaking 12 hours after the start of hexadecane treatment, while DNA synthesis peaked at 24 hours. Histological studies confirmed significant cellular edema 24 hours after treatment, epidermal hyperplasia 48 hours later, and peaking at 72 hours. In vivo experiments in weaned piglets showed that hexadecane induced erythema, which completely subsided 24 hours after patch removal. Hexadecane can cause suffocation when inhaled into the lungs. Ecotoxicity studies: Mussel larvae (Mytilus edulis) exposed to 10 ppm and 50 ppm hexadecane showed a slight decrease in growth rate; however, exposure to 100 ppm hexadecane actually accelerated their growth rate.

---

Interactions
Hexadecane, when combined with 2-butanone or cyclohexane, can enhance the efficacy of local anesthetics. This study aimed to evaluate the dose-related transdermal absorption of various aliphatic and aromatic hydrocarbons. The initial treatment (1X) used a porcine skin flow-through diffusion cell, employing 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) as the hexadecane solvent. Other treatments (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 methods were standardized to ensure good linearity of all tested components in culture medium standards. Absorption parameters, including diffusion coefficient, permeability, steady-state flux, and percentage of absorbed dose, were estimated for all tested hydrocarbons. This method provides a benchmark for assessing interactions between components and between components and diluents (solvents). A quantitative structure-activity relationship (QSPR) model was established using the physicochemical parameters of unknown aviation kerosene hydrocarbons to predict their permeability in this solvent system. The results show that the absorption rates of naphthalene and dimethylnaphthalene (DMN) increase with increasing dosage.

Hexadecane is a colorless liquid. (NTP, 1992)
Hexadecane is a straight-chain alkane containing 16 carbon atoms. It is one of the essential oil components extracted from long pepper. It is both a volatile oil component and a nonpolar solvent and plant metabolite.
Hexadecane has been reported to be present in tea tree (Camellia sinensis), Madagascar vanilla (Vanilla madagascariensis), and several other organisms with relevant data.
Structure

C16H34

226.44

226.266

544-76-3

11006

Colorless to off-white <18°C solid powder,>18°C liquid

0.8±0.1 g/cm3

286.6±3.0 °C at 760 mmHg

64.7 °F (NTP, 1992) ; 18.18 °C ; 18.17 °C ; 18.14 °C

135.0±0.0 °C

0.0±0.3 mmHg at 25°C

1.434

9.26

0

13

16

92.6

0

CCCCCCCCCCCCCCCC

DCAYPVUWAIABOU-UHFFFAOYSA-N

InChI=1S/C16H34/c1-3-5-7-9-11-13-15-16-14-12-10-8-6-4-2/h3-16H2,1-2H3

hexadecane

n-Hexadecane(Standard)

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.)