Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting 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 this publication was well-documented and adheres to basic scientific principles.

Data source

Reference
Reference Type:
publication
Title:
Feeding studies in rats with mineral hydrocarbon food grade white oils
Author:
Baldwin, M.K., Berry, P.H., Esdaile, D.J., Linnett, S.L., Martin, J.G., Peristianis, G.C., Priston, R.J., Simpson, B.J.E., Smith, J.D.
Year:
1992
Bibliographic source:
Toxicologic Pathology, 20(3) part 1:426-435

Materials and methods

Objective of study:
other: Measurement of hydrocarbon residues in tissues
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
This study was conducted as a subchronic study, but tissues were examined for hydrocarbon residues.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: oily liquid
Details on test material:
C16 and C18 hydrocarbons that are constituents of the substance being registered.

- Name of test material (as cited in study report): Oleum-treated white oil and hydrotreated white oil
- Test substance: C16 and C18 hydrocarbons
- Physical state: Liquid
- Analytical purity: Not reported
- Impurities (identity and concentrations): Not reported
- Composition of test material, percentage of components: Not reported
- Lot/batch No.: Not reported
- Other: Both oils were derived from naphthenic crudes of different viscosities. The oleum-treated white oil was refined by oleum treatment following vacuum distillation of atmospheric residue (conventional refining). It has a specific gravity of 0.874 at 15 degrees Celsius and a viscosity of 26 mm2/second at 40 degrees Celsius. The hydrotreated white oil was produced by hydrotreatment of the vacuum distillate of an atmospheric residue. It has a specific gravity of 0.878 at 15 degrees Celsius and a viscosity of 69 mm2/second at 40 degrees Celsius.
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Manston, Kent
- Age at study initiation: 6 to 8 weeks old
- Weight at study initiation: Not reported
- Housing: Individually
- Individual metabolism cages: No
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Not reported
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

IN-LIFE DATES: Not reported

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: "DISTOL"-grade hexane, Fisons
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Each test oil was dissolved in “DISTOL”-grade hexane, Fisons to make a premix, which was used to achieve homogeneous dispersal of the appropriate amount of test oil in each batch of test diet. Controls used solvent mixed in the diet.

DIET PREPARATION
- Rate of preparation of diet (frequency): Within 7 days
- Mixing appropriate amounts with (Type of food): Powdered laboratory rat diet, LAD2 (Special Diet Services, Witham, Essex)
- Storage temperature of food: Not reported


VEHICLE
- Justification for use and choice of vehicle (if other than water): not reported
- Concentration in vehicle: Not reported
- Lot/batch no. (if required): Not reported
- Purity: Not reported


HOMOGENEITY AND STABILITY OF TEST MATERIAL: Stated to be homogeneous, but there was no mention of stability.
Duration and frequency of treatment / exposure:
90 continuous days
Doses / concentrations
Remarks:
Doses / Concentrations:
0 or 20,000 ppm
No. of animals per sex per dose:
Five animals per sex were used per dose for tissue analysis
Control animals:
yes, plain diet
Positive control:
None reported
Details on study design:
- Dose selection rationale: None reported
- Rationale for animal assignment (if not random): Not reported
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: Liver and mesenteric lymph nodes
- Time and frequency of sampling: After 90 days of treatment

METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: Liver and mesenteric lymph nodes
- Time and frequency of sampling: After 90 days of treatment
- From how many animals: Five animals per sex per dose
- Method type(s) for identification: HPLC with refractive index detection
- Limits of detection and quantification: Not reported
- Other: Liver and mesenteric lymph nodes were tested for total hydrocarbon content.


Statistics:
None reported for toxicokinetic portion of the study.

Results and discussion

Preliminary studies:
The C16  and C18 hydrocarbons that are constituents of these oils are metabolized to the corresponding fatty acids of the same carbon chain length as the parent hydrocarbons, suggesting a process of omega  oxidation.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Absorption was not specifically measured. The data indicate absorption occurs, but there is no data on the amount of compound absorbed via oral administration.
Details on distribution in tissues:
Only the liver and mesenteric tissues were examined. The liver had greater levels of total hydrocarbons than the mesenteric lymph nodes, but females had higher levels in both tissues than the males.
Details on excretion:
Not examined

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
Only total hydrocarbons were measured.

Any other information on results incl. tables

No metabolism studies have been reported for unrefined / acid treated oils, but studies have been reported on the metabolism of C16 and C18 hydrocarbons that are constituents of these oils. In this study, it has been shown that the hydrocarbons are metabolised to the corresponding fatty acids of the same carbon chain length as the parent hydrocarbons, suggesting a process of omega oxidation.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no data
No metabolism studies have been reported for unrefined / acid treated oils but studies have been reported on the metabolism of C16 and C18 hydrocarbons that are constituents of these oils. In these studies it has been shown that the hydrocarbons are metabolised to the corresponding fatty acids of the same carbon chain length as the parent hydrocarbons, suggesting a process of omega oxidation.
Executive summary:

Justification for Read Across

C16 and C18 hydrocarbons are constituents of the untreated and acid treated oils being registered.

No metabolism studies have been reported for unrefined / acid treated oils but studies have been reported on the metabolism of C16 and C18 hydrocarbons that are constituents of these oils. In these studies it has been shown that the hydrocarbons are metabolised to the corresponding fatty acids of the same carbon chain length as the parent hydrocarbons, suggesting a process of omega oxidation.

Based on study design and results, this study is classified as reliable with restrictions because this publication was well-documented and adheres to basic scientific principles.