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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable with restrictions because it is an acceptable well-documented study report that followed sound scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Absorption, of aliphatic hydrocarbons by rats
Author:
Albro, P.W. and Fishbein, L.
Year:
1970
Bibliographic source:
International Journal of Biochemistry, Biophysics and Molecular Biology 219:437.

Materials and methods

Objective of study:
absorption
Principles of method if other than guideline:
The method did not strictly follow the guideline but is deemed appropriate as utilized in this report.
Bile was collected by Kotin et al. and cannulation of the intestinal lymph duct was according to Bollman et al. Everted intestinal sacs were prepared as described by Wilson and Wiseman, and opened-ended sacs were prepared as described by Clarkson and Rothstein.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Read Across to Highly Refined Mineral Oils
Radiolabelling:
no

Test animals

Species:
rat
Strain:
other: C-D strain
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Weight: 250 grams during balance studies, 180 grams during lymph versus portal studies
- Diet: D&G laboratory diet provided ad libitum
- Water : ad libitum during the study




Administration / exposure

Route of administration:
other: intragastric injections
Vehicle:
not specified
Doses / concentrations
Remarks:
Doses / Concentrations:
Balance studies: 0.8 ml/kg body weight of hydrocarbon mixtures
Recirculation in the bile: 5 mg of I-C14 hexadecane in 100 µl of corn oil or intravenous injection of 0.1 ml of rat serum saturated with I-C14 hexadecane
Absorption:
Control animals:
no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The percentage retention of aliphatic hydrocarbons was inversely proportional to the number of carbon atoms and ranged from 60% for C14 to 5% C28 compounds. The major site of absorption was found to be the small intestine.

Any other information on results incl. tables

The retention of hydrocarbons observed in this study was well within the range expected from balance type of experiments in the literature. Radioactivity was detected in the bile within 15 minutes after subcutaneous or intravenous injections were given. The peak concentration of radioactivity was reached within 45 to 60 minutes. All the radioactivity recovered was associated with water-soluble materials, saponifiable lipid, and cholesterol.

Treatment with antibiotics reduced the retention of the hydrocarbons tested to the same extent in both groups of treated rats. Since excretion of hydrocarbon continued for at least 3 days following an intragastric dose, it would appear that the entire small intestine was exposed to significant levels of material. The study was able to detect squalane in feces as early as 5 hours after intragastric administration.

Applicant's summary and conclusion

Conclusions:
The percentage retention of aliphatic hydrocarbons was inversely proportional to the number of carbon atoms and ranged from 60% for C14 to 5% C28 compounds. The major site of absorption was found to be the small intestine.
Executive summary:

Read across justification

In this study highly refined mineral oils (White oils) were tested, but being similar in composition to lubricant base oils, similar toxicokinetic properties would be expected.

In an absorption toxiokinetics study, male C-D rats were dosed with various hydrocarbon mixtures to determine the absorption and retention of various components as evaluated by balance studies, bile assays, the effects of bacteria, studies of absorption in various sections of the GI tract, and lymph and portal absorption.

Based on the results of this study, it was found that the percentage retention of aliphatic hydrocarbons was inversely proportional to the number of carbon atoms and ranged from 60% for C14 to 5% C28 compounds. The major site of absorption was found to be the small intestine. This study received a Klimisch score of 2 and is classified as reliable with restrictions.