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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Referred in a recognized source of peer reviewed scientific data on chemicals

Data source

Reference
Reference Type:
publication
Title:
Feeding Studies in Rats with Mineral Hydrocarbon Food Grade White Oils
Author:
Baldwin et al
Year:
1992
Bibliographic source:
Toxicologic Pathology Vol. 20 (3) (Part 1) 426 -435

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Paraffin oils/waxes

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Study observed:

No mortality at all dose groups.

 

At 20000 ppm: treatment-related hematological changes included slight leukocytosis and granulocytosis (both sexes)

 

At³5000 ppm: slight hepatic damage and functional disturbance as indicated by clinical chemistry findings (females)

 

Necropsy revealed treatment-related macroscopic findings or organ weight changes in mesenteric lymph node, spleen, liver, and kidney.

 

At³500 ppm: enlarged mesenteric lymph nodes (females).

At³5000 ppm: dose-related increases in liver weight (both sexes).

At³5000 ppm: increased mean splenic weight (both sexes)

At³10000 ppm: increased kidney weights (females)

 

Microscopic changes: multifocal lipogranulomata in mesenteric lymph node and liver.

At³5000 ppm: histopathological changes in mesenteric lymph node (both sexes)

At³500 ppm: histopathological changes in liver.

At³5000 ppm: chronic capsular splenitis in the spleen (males)/ at 20000 ppm –in females

At³5000 ppm: increased splenic extramedullary hemoppoiesis (females)

 

Tissue analysis showed increased tissue concentration of total hydrocarbon residues in livers and mesenteric lymph nodes of treated animals. Hydrocarbon concentration was higher in organ tissues of females than in males.

 

OTWO:

NOEL (subchronic, oral, males/ females)=10 ppm (0.65 mg/kg bw/day);

LOAEL (subchronic, oral, females) =100 ppm (6.5 -12.2 mg/kg bw/day) –histopathological changes in liver and mesenteric lymph node.

 

HTWO:

NOEL (subchronic, oral, males/ females)=100 ppm (6.4 mg/kg/day);

LOAEL (subchronic, oral, females) =500 ppm (32.5 -57.6 mg/kg bw/day) –histopathological changes in liver.

 

Applicant's summary and conclusion

Conclusions:
Subchronic toxicity feeding studies for mineral paraffin oils conducted with Fischer-344 (F-344) rats reported toxicity effects occured in the liver and mesenteric lymph nodes and characterised by increased organ weights, microscopic inflammatory changes (microgranulomas) and presence of saturated mineral hydrocarbons in affected tissues. In general, the type of toxicity effects seen in F344 rats is associated with strain-specific essentially reactions to a foreign body (i.e. presense of unchanged mineral hydrocarbons in the tissues).