Carbon black

Repeated dose toxicity: other routes

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

Test material information

Constituent 1

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

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

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.