Registration Dossier

Toxicological information

Carcinogenicity

Currently viewing:

Administrative data

Description of key information

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study is not required at this level of registration. However, it is included as it provides useful supporting information to the repeated dose studies listed above. This literature paper is classified as K2, reliable with restrictions as it was conducted to a recognised guideline on a known structural analogue, and is a well documented report.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
Deviations:
not specified
Principles of method if other than guideline:
Groups of 50 Fischer 344 rats of each sex were fed diets containing white oil at dietary concentrations of 0, 2.5 or 5%. Body weights and food intakes were recorded throughout the study and after 104 weeks surviving animals were killed.
GLP compliance:
not specified
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
No data reported.
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
Groups of 50 Fischer 344 rats of each sex were fed diets containing white oil at dietary concentrations of 0, 2.5 or 5% for 104 weeks. Dose concentrations are listed below.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data available.
Duration of treatment / exposure:
104 weeks,
Frequency of treatment:
Daily in feed.
Post exposure period:
None; test subjects were terminated at the completion of the study.
Remarks:
Doses / Concentrations:962.2 or 1941.9 mg/kg/day for males, 1135.4 or 2291.5 mg/kg/day for females (2.5 and 5.0%) Basis:nominal in diet
No. of animals per sex per dose:
50
Control animals:
yes
Details on study design:
Groups of 50 Fischer 344 rats of each sex were fed diets containing white oil at dietary concentrations of 0, 2.5 or 5%. Body weights and food intakes were recorded throughout the study and after 104 weeks surviving animals were killed. Blood samples were collected for haematological and clinical chemical determinations and a full necropsy was performed on all animals. Organ weights were recorded and a histopathological examination was undertaken on major organs, all tumours and masses.
Positive control:
No
Observations and examinations performed and frequency:
No specific data.
Sacrifice and pathology:
Blood samples were collected for haematological and clinical chemical determinations and a full necropsy was performed on all animals. Organ weights were recorded and a histopathological examination was undertaken on major organs, all tumours and masses.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
There were slight increases in body weights in both sexes of the 5% group (5% for males and 2.7% for females) at week 104. Food consumption was also increased in the 5% groups (11% for males and 8% for females total increase at week 104). However, no significant treatment-related differences between the control and treated groups were observed for clinical signs, mortality or hematological findings. In the 5% group, absolute liver and kidney weights were increased in males and absolute and relative submaxillary gland weights were reduced in females.
Relevance of carcinogenic effects / potential:
Non-carcinogenic.
Dose descriptor:
NOAEL
Effect level:
>= 1 941.9 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: equivalent to ≥ 5% of daily diet
Remarks on result:
other: Effect type: carcinogenicity
Dose descriptor:
NOAEL
Effect level:
>= 2 291.5 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: equivalent to ≥ 5% of daily diet
Remarks on result:
other: Effect type: carcinogenicity

Absolute and relative weights of heart and spleen were unaffected by treatment. The percentage increases/decreases in the 5% group were:

 

Organ

Absolute

Relative

Female

Submaxillary gland

3% decrease

1.7% decrease

Male

Liver

8.4% increase

not different

Kidney (R)

14.9% increase

not different

Kidney (L)

9.9% increase

not different

 

In the 5% male group, the increased absolute organ weights were attributed to the slight increases in body weights.

 

A variety of tumors developed in all groups, including the control group. However, all the neoplastic lesions were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any tumor type was found for either sex in the treated groups. Granulomatous inflammation in the mesenteric lymph nodes, considered to be a reaction to paraffin absorption, was observed with similar incidence and severity in both sexes of the 2.5 and 5% groups. The authors concluded that under the present experimental conditions, the high dose, about 2000-200,000 times higher than the current temporary acceptable daily intake, did not have any carcinogenic potential in F344 rats. Furthermore, the granulomatous inflammation observed in the mesenteric lymph nodes was not associated with any development of neoplastic lesions.

Conclusions:
A variety of tumors developed in all groups, including the control group. However, all the neoplastic lesions were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any tumor type was found for either sex in the treated groups. Granulomatous inflammation in the mesenteric lymph nodes, considered to be a reaction to paraffin absorption, was observed with similar incidence and severity in both sexes of the 2.5 and 5% groups. The authors concluded that under the present experimental conditions, the high dose, about 2000-200,000 times higher than the current temporary acceptable daily intake, did not have any carcinogenic potential in F344 rats. Furthermore, the granulomatous inflammation observed in the mesenteric lymph nodes was not associated with any development of neoplastic lesions.
Executive summary:

A full justification for the read across applied for this substance is contained within Section 1.4, reference " Explanation of NovaSpec Base Oil - FINAL". This document contains a full explanation of the manufacturing route for the substance and discussion on why this substance should be considered as a UVCB white oil analogous to CAS 8042-47-5. Physical properties of the crude reaction product and the different product grades (or distillate fractions) derive from the general chemical structure characteristics (linear-branched alkanes with characteristic branching length and position). Specific unique chemical structures are not isolated in any process step and due to the tens of thousands of isomers and the high degree and variable nature branching and chain length, the base oil bulk properties are the result of the average structure characteristics. The unique viscosity grades each contain all the same typical chemical structures and predominantly overlapping Molecular Weight distributions. The unique viscosity and volatility characteristics of each viscosity grade derive from the boiling point distribution, a result of the short-path distillation (wiped film evaporation). This is identical to the production of petroleum derived white oils.

Within the test, a variety of tumors developed in all groups, including the control group. However, all the neoplastic lesions were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any tumor type was found for either sex in the treated groups. Granulomatous inflammation in the mesenteric lymph nodes, considered to be a reaction to paraffin absorption, was observed with similar incidence and severity in both sexes of the 2.5 and 5% groups. The authors concluded that under the experimental conditions, the high dose, about 2000-200,000 times higher than the current temporary acceptable daily intake, did not have any carcinogenic potential in F344 rats. Furthermore, the granulomatous inflammation observed in the mesenteric lymph nodes was not associated with any development of neoplastic lesions, and were considered to be a species specific effect. This is discussed above under “repeated dose toxicity”.

No classification is applicable.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 941.9 mg/kg bw/day
Study duration:
chronic
Species:
rat

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A full justification for the read across applied for this substance is contained within Section 1.4, reference " Explanation of NovaSpec Base Oil - FINAL". This document contains a full explanation of the manufacturing route for the substance and discussion on why this substance should be considered as a UVCB white oil analogous to CAS 8042-47-5. Physical properties of the crude reaction product and the different product grades (or distillate fractions) derive from the general chemical structure characteristics (linear-branched alkanes with characteristic branching length and position). Specific unique chemical structures are not isolated in any process step and due to the tens of thousands of isomers and the high degree and variable nature branching and chain length, the base oil bulk properties are the result of the average structure characteristics. The unique viscosity grades each contain all the same typical chemical structures and predominantly overlapping Molecular Weight distributions. The unique viscosity and volatility characteristics of each viscosity grade derive from the boiling point distribution, a result of the short-path distillation (wiped film evaporation). This is identical to the production of petroleum derived white oils.

Within the test, a variety of tumors developed in all groups, including the control group. However, all the neoplastic lesions were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any tumor type was found for either sex in the treated groups. Granulomatous inflammation in the mesenteric lymph nodes, considered to be a reaction to paraffin absorption, was observed with similar incidence and severity in both sexes of the 2.5 and 5% groups. The authors concluded that under the experimental conditions, the high dose, about 2000-200,000 times higher than the current temporary acceptable daily intake, did not have any carcinogenic potential in F344 rats. Furthermore, the granulomatous inflammation observed in the mesenteric lymph nodes was not associated with any development of neoplastic lesions, and were considered to be a species specific effect. This is discussed above under “repeated dose toxicity”.


Justification for selection of carcinogenicity via oral route endpoint:
Available literature study paper

Justification for classification or non-classification

Within the test, a variety of tumors developed in all groups, including the control group. However, all the neoplastic lesions were histologically similar to those known to occur spontaneously in F344 rats, and no statistically significant increase in the incidence of any tumor type was found for either sex in the treated groups. Granulomatous inflammation in the mesenteric lymph nodes, considered to be a reaction to paraffin absorption, was observed with similar incidence and severity in both sexes of the 2.5 and 5% groups. The authors concluded that under the experimental conditions, the high dose, about 2000-200,000 times higher than the current temporary acceptable daily intake, did not have any carcinogenic potential in F344 rats. Furthermore, the granulomatous inflammation observed in the mesenteric lymph nodes was not associated with any development of neoplastic lesions, and were considered to be a species specific effect. This is discussed above under “repeated dose toxicity”.

No classification is applicable.