Registration Dossier

Diss Factsheets

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across from an early non-GLP, non-guideline experimental investigation on structural analogues.

Data source

Reference
Reference Type:
publication
Title:
Absorption of aliphatic hydrocarbons by rats
Author:
Albro PW and Fishbein L
Year:
1970
Bibliographic source:
Biochimca et Biophysica Acta 219, 437-446

Materials and methods

Objective of study:
other: whole body uptake and excretion study
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The influence of carbon number on the uptake of C14-C30 alkanes from the gut after gavage administration was investigated in male rats.
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
1,13-tetradecadiene
IUPAC Name:
1,13-tetradecadiene
Constituent 2
Reference substance name:
8-hexadecyne
IUPAC Name:
8-hexadecyne
Constituent 3
Reference substance name:
Pristane
IUPAC Name:
Pristane
Constituent 4
Reference substance name:
9-nonadecane
IUPAC Name:
9-nonadecane
Constituent 5
Reference substance name:
pentadecylcolhexane
IUPAC Name:
pentadecylcolhexane
Constituent 6
Reference substance name:
squalene
IUPAC Name:
squalene
Details on test material:
1,13-tetradecadiene (97%, Chemical Samples Co., Columbus, Ohio)
8-hexadecyne (95%, Fareham Research Labs, Willoughby, Ohio)
pristane (Eastman, no address, purity not stated)
Cis+trans 9-nonadecane (99%, Chemical Samples Co., Columbus, Ohio)
pentadecylcolhexane (96%, Chemical Samples Co., Columbus, Ohio)
squalene (General Biochemicals, no address, purity not stated)
Radiolabelling:
no

Test animals

Species:
rat
Strain:
other: CD strain
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Labs (no address)
- Diet (ad libitum): D&G Laboratory Diet, Price-Wilhoite Co., Frederick, Md
- Water (ad libitum): tap water

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on exposure:
Mixtures of hydrocarbons (always including squalane as a marker of recovery) were prepared involving three or four different hydrocarbons in an equal weights ratio (no further details). The mixtures were administered at various dose levels (no further details; 0.8 ml/kg body weight) by stomach tube.

Faeces were collected twice daily and stored in chloroform until excretion of the hydrocarbon ceased (72-96hr).

Each hydrocarbon was tested in three animals and each sample of faeces analyzed at least 3 times.
Duration and frequency of treatment / exposure:
Single treatment with faeces collected for up to 96 hr
Control animals:
yes
Statistics:
The percentage of each hydrocarbon retained by the animals was considered to be 100% minus the percentage excreted, and was calculated using the formula:
R = [(A/S)d-(A/S)f)/(A/S)d] x 100%
where R = percentage retained, A/S = molar ratio of test hydrocarbon to squalane, d = ratio from diet, f = ratio from faeces.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:
The retention / excretion of n-alkanes showed an inverse linear relationship to chain length, with those having more than 29 carbon atoms not absorbed to any significant extent from the gut. Branched, cyclic and unsaturated hydrocarbons included in the study were retained / excreted to a similar extent to n-alkanes with the same total number of carbon atoms. Thus carbon number appeared to be the factor determining retention in this study.

Any other information on results incl. tables

The percentage retention/excretion of n-alkanes showed an inverse linear relationship to chain length as described by the regression line:

Percentage retained = 115.9 - (3.94 x no. carbon atoms)

This line had a correlation -0.995, standard error of estimate Sy.x = 3.30, t = 30.85 and P<0.001.

Paraffins having more than 29 carbon atoms would therefore not be expected to be absorbed to any significant extent from the gut.

The branched, cyclic and unsaturated hydrocarbons included in the study were retained/excreted to a similar extent to corresponding n-saturated hydrocarbons of the same total number of carbon atoms (P>0.9 (2-tailed t-test) or no statistically significant difference in percentage retention). Thus carbon number appeared to be the factor determining retention in this study.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: Carbon number determines the extent of uptake from the gut
The percentage retention of alkanes following gavage administration to the rat was inversely related to carbon chain length, with negligible uptake for C29 and above.
Executive summary:

The influence of carbon number on the uptake of orally administered alkanes was investigated in male C-D rats following gavage administration of mixtures of 1,13-tetradecadiene, 8-hexadecyne, pristine, cis+trans 9-nonadecane and pentadecylcolhexane. Squalene was used as marker of recovery, with excretion of hydrocarbon in faecal samples (collected for up to 96 hr) quantified by GC-FID. The results indicated an inverse linear relationship between chain length and uptake, with minimal uptake from the gut of alkanes containing greater than 29 carbon atoms. The branched, cyclic and unsaturated hydrocarbons included in the study were retained/excreted to a similar extent to the corresponding n-saturated hydrocarbons of the same total number of carbon atoms, with no significant differences in percentage retention. Thus carbon number appeared to be the determining factor influencing uptake from the gut.