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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 based on grouping of substances (category approach)
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 an acceptable well-documented study report that followed sound scientific principles.

Data source

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

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Animals were fed oils in the diet for 13 weeks and hydrocarbon analysis was done on tissues.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: Oily liquid
Details on test material:
- Name of test material (as cited in study report): mineral hydrocarbons; oleum-treated white oil (insufficiently refined, greater than 3% LBO) and hydrotreated white oil (sufficiently refined, less than 3% LBO).
- Substance type: lubricant base oil
-C16 and C18 hydrocarbons
- Physical state: liquid

OTWO
-Specific gravity: 0.874 at 15°C
-Viscosity: 26 mm2/sec at 40°C

HTWO
-Specific gravity: 0.878 at 15°C
-Viscosity: 69 mm2/sec at 40°C
- These oils are constituents of white oils.

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River
- Age at study initiation: six to eight weeks
- Housing: individually caged
- Diet (e.g. ad libitum): laboratory rat diet LAD2 (special diet services, Witham, Essex) was offered ad libitum
- Water (e.g. ad libitum): offered ad libitum


Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: "DISTOL"-grade hexane
Details on exposure:
The test oils were separately incorporated into powdered laboratory rat diet, LAD2 at concentrations ranging from 10 to 20,000 ppm. Each oil was first dissolved in solvent ("DISTOL"-grade hexane) and a premix was used to achieve homogeneous dispersal in each batch of final test diet. An equivalent volume of solvent was also mixed with control diet.
Duration and frequency of treatment / exposure:
Animals were fed diet with test material for 13 weeks. Mean daily intake of food was calculated.
Doses / concentrations
Remarks:
Doses / Concentrations:
Experiment 1, Oleum-treated white oil (OTWO): 5000, 10000, 20000 ppm
Experiment 2, OTWO: 10, 100, 500, 1000, 10000, 20000 ppm
Experiment 1, Hydrotreated white oil (HTWO): 5000, 10000, 20000 ppm
Experiment 2, HTWO: 10, 100, 500, 5000, 10000, 20000 ppm
No. of animals per sex per dose:
Experiment 1 (OTWO and HTWO): three males and three females
Experiment 2 (OTWO and HTWO): six females
Control animals:
no
Details on dosing and sampling:
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled : cardiac blood was collected at terminal necropsy and tail vein blood was taken 7 days prior to necropsy. Haematological variants were monitored and analyzed by autoanalyzer
Statistics:
Statistical analysis of data was accomplished by analysis of variance with a modified Student's t-test procedure for food intake, clinical chemistry, and haematological variants. The Wilcoxon two-sample rank sum test and Fisher's exact test were also used.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
There were no mortalities and no adverse clinical signs associated with feeding either white oil. Treatment-related effects evidenced by haematological, clinical chemical, and pathological changes were generally dose-related and more marked in female than in male rats, and the OTWO caused a greater pathological response than the HTWO. Tissue residues of saturated hydrocarbons were up to 5.2 times higher in female rats than in males. Rats fed 5,000 ppm or more of either white oil showed dose-related alterations in several haematological and clinical chemistry variates associated mainly with hepatic damage or functional alteration. At necropsy, mesenteric lymph nodes were enlarged, and increases in weight of liver, kidney, and spleen were significant. Microscopic changes were characterized by multifocal lipogranulomata in mesenteric lymph node and liver. No changes were observed in rats fed OTWO or HTWO for 90 days at dietary concentrations of 10 or 100 ppm, equivalent to a minimum intake of 0.65 and 6.4 mg/kg/day, respectively. Differences in degree of pathological response associated with each oil may have been due to their differences in specification rather than processing method.

Any other information on results incl. tables

C16 and C18 hydrocarbons that are constituents of lubricant base oils are metabolised to corresponding fatty acids of the same carbon chain length as the parent hydrocarbons, suggesting a process of omega oxidation.

There were no deaths or any clinical signs caused by feeding either OTWO or HTWO at dietary concentrations up to the maximum of 20000 ppm. The only effect noted was a mild increase in food intake of males fed 20000 ppm OTWO during weeks 3 through 6 of the study. The only haematological changes attributes to treatment were slight leukocytosis and granulocytosis in rats of both sexes fed 20000 ppm of either white oil, with slight hypochromic microcytic anaemia in the 20000 ppm OTWO-fed females. Clinical chemistry findings in rats fed 5,000 ppm or more of either white oil indicated slight hepatic damage and functional disturbance. At necropsy, treatment-related organ weight changes occurred in mesenteric lymph node, spleen, liver, and kidney. Analysis of liver and mesenteric lymph node for total hydrocarbon residues showed higher tissue concentrations in females than in males. In both liver and mesenteric lymph node of treated rats, total hydrocarbon concentrations were greater in OTWO-fed rats than in HTWO-fed rats. There were no treatment-related histological changes in mesenteric lymph node or liver of rats fed 500 or 10,000 ppm of either white oil for 25 days. After 90 days lesions were found in mesenteric lymph node, liver, and spleen. Across all analyses (haematology, clinical chemistry, gross necropsy, tissue residue, and histopathology) findings were more marked in in female rats and male or female rats fed OTWO

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: The sufficiently refined hydrocarbons (hydrotreated white oil) are metabolized to the corresponding fatty acids of the same carbon chain length as the parent carbons, suggesting omega oxidation.
In conclusion, the pathological findings in the test animals were quantitatively similar to those previously associated with the ingestion of mineral hydrocarbons by a range of species, but the effects occurred at much lower levels of dietary intake than previously reported. No pathological changes were observed after 25 days of feeding, but after 90 days there were very slight to moderate multifocal granulomatous changes in mesenteric lymph nodes and liver. Although rats fed the oleum-treated highly refined base oil were more affected than those fed the hydrotreated highly refined base oil differences in the specification of each oil rather than processing method were more likely to have accounted for the variation. The insufficiently refined hydrocarbons (oleum-treated highly refined base oil) are suggested to undergo a process of omega oxidation. The sufficiently refined hydrocarbons (hydrotreated highly refined base oil) are metabolized to the corresponding fatty acids of the same carbon chain length as the parent carbons, suggesting omega oxidation.
Executive summary:

In a basic toxicokinetics study, a group of male and female rats were fed oleum-treated highly refined base oil and hydrotreated highly refined base oil in concentrations of 5000, 10000, 20000 ppm and a group of female rats were fed OTWO and HTWO in concentrations of 10, 100, 500, 1000, 10000, 20000 ppm for a period of 13 weeks. Animals were euthanized at the conclusions of the study, after which haematological, clinical chemistry, gross necropsy, tissue residue, and histopathological examination were preformed.

Pathological findings in the test animals were quantitatively similar to those previously associated with the ingestion of mineral hydrocarbons by a range of species, but the effects occurred at much lower levels of dietary intake than previously reported. No pathological changes were observed after 25 days of feeding, but after 90 days there were very slight to moderate multifocal granulomatous changes in mesenteric lymph nodes and liver. Although rats fed the oleum-treated highly refined base oil were more affected than those fed the hydrotreated highly refined base oil differences in the specification of each oil rather than processing method were more likely to have accounted for the variation. The insufficiently refined hydrocarbons oleum-treated highly refined base oils are suggested to undergo a process of omega oxidation. The sufficiently refined hydrocarbons (hydrotreated highly refined bas oils) are metabolized to the corresponding fatty acids of the same carbon chain length as the parent carbons, suggesting omega oxidation.

This study received a Klimisch score of 2 and is classified as reliable with restrictions because it an acceptable well-documented study report that followed sound scientific principles.