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Toxicological information

Repeated dose toxicity: other routes

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Administrative data

Endpoint:
repeated dose toxicity: other route
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
unsuitable test system

Data source

Reference
Reference Type:
publication
Title:
Nano-Sized Carbon Black Exposure Exacerbates Atherosclerosis in LDL-Receptor Knockout Mice
Author:
Niwa Y, Hiura Y, Murayama T, Yokode M, Iwai N
Year:
2007
Bibliographic source:
Circulation Journal 71: 1157 – 1161

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Repeated intratracheal administration of an approximate total dose of 444 mg/kg carbon black within 10 weeks to investigate the effects of CB on the development of atherosclerosis
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Carbon black
EC Number:
215-609-9
EC Name:
Carbon black
Cas Number:
1333-86-4
Molecular formula:
C
IUPAC Name:
Carbon black

Test animals

Species:
mouse
Strain:
other: Low-density lipoprotein receptor knockout mice (LDLR/KO)
Sex:
male

Administration / exposure

Route of administration:
other: intratracheal
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
10 weeks
Frequency of treatment:
One instillation (1mg) per week
Doses / concentrations
Dose / conc.:
1 other: mg/animal per week
Remarks:
in the absence or presence of cholesterol
No. of animals per sex per dose:
5 male / group; 4 groups
Control animals:
yes
Details on study design:
Two groups of mice were subjected to a 10-week endotracheal dispersion of autoclaved CB (1 mg per animal/week) and given isoenergy diets containing 0% or 0.51% Chol. Another 2 groups of mice underwent intratracheal dispersion of air only under isonergy diets with 0% or 0.51% Chol. Intratracheal dispersion of CB and air was performed once a week for 10 weeks under light ether anesthesia

Results and discussion

Applicant's summary and conclusion

Conclusions:
No conclusions can be drawn on the repeated dose toxicity of carbon black. The relevance of the non-validated test system is unclear.
Executive summary:

The experiment was conducted with two groups of low-density lipoprotein receptor knockout mice (LDLR/KO) fed with isoenergetic diets in the absence of cholesterol or presence of 0.51% cholesterol.

Carbon black was not detected by electron microscopy in aortas, livers, kidneys, and spleen of LDLR/KO mice after repeated intratracheal administration.

An accelerated development of atherosclerosis in the mice was studied by examination of Oil red O stained aortic tissue. The stained plaque area was quantifi ed. Mice fed with cholesterol only and those treated with carbon black in addition had a statistically signifi cantly more extensive staining (7 and 13% area stained, respectively). Vehicle or carbon black treated mice showed both about 3% stained area in the absence of cholesterol. The authors interpreted these results that carbon black treatment accelerated development of atherosclerosis.

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