Carbon black

Respiratory sensitisation

Administrative data

Endpoint:

respiratory sensitisation: in vivo

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

unsuitable test system

Remarks:

intranasal application

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2006

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Mice were intranasally exposed to ovalbumin (OVA) alone or in combination with ultrafine carbon black particles. The induction of airway inflammation and the immune adjuvant activity were studied in the lungs and lung-draining peribronchial lymph nodes (PBLN) at day 8. OVA-specific antibodies were measured at day 21, and the development of allergic airway inflammation was studied after OVA challenges (day 28)

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:

Balb/c

Sex:

female

Test system

Route of induction exposure:

other:

Route of challenge exposure:

intranasal

No. of animals per dose:

6 / group

Details on study design:

Mice were anaesthetized by an intramuscular injection of ketamine and exposed to 20 µL of OVA (0.5 mg/mL or particle + OVA (3.3 and 0.5 mg/mL, respectively) in PBS by intranasal droplet application on days 0, 1 and 2 (total dose of 200 µg particles and 30 µg OVA). Mice were killed on day 8, or challenged to study asthma-like allergic airway inflammation. For the latter, mice were anaesthetized by an intramuscular ketamine injection and challenged by intranasal droplet application of 20 µL OVA (0.5 mg/mL) in PBS on days 25, 26 and 27. Mice were killed on day 28 by an overdose of pentobarbital.

Results and discussion

Results:

Ultrafine (below 30 nm in diameter) but not fine (over 200 nm in diameter) carbon black particles (200 µg) induced airway inflammation and displayed adjuvant activity. The latter was evidenced by the induction of immune sensitisation to co-administered ovalbumin and demonstrated by increased levels of cytokines associated with a Th2 immune response and by the occurrene of allergic airway inflammation after an intranasal OVA challenge.
Ultrafine carbon black bound 100% of the OVA, whereas fine carbon black only bound around 10% of the OVA.
Allergic airway inflammation as well as a stimulation of local immune responses (changes in cellular composition of BAL and PBLN, and production of a number of type 2 cytokines in PBLN) were found after intranasal challenges with antigen.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

Ultrafine (below 30 nm in diameter) but not fine (over 200 nm in diameter) carbon black particles (200 µg) induced airway inflammation and displayed adjuvant activity. The latter was evidenced by the induction of immune sensitisation to co-administered ovalbumin and demonstrated by increased levels of cytokines associated with a Th2 immune response and by the occurrene of allergic airway inflammation after an intranasal OVA challenge. A systemic antibody response was not detected. The study is not suitable to derive any conclusions about the respiratory sensitisation of carbon black per se.

Executive summary:

In a non-validated mouse allergic airway sensitisation model, mice were intranasally exposed to ovalbumin alone or in combination with carbon black particles. The induction of airway inflammation and the immune response were studied in the lungs and lung-draining peribronchial lymph nodes at day 8. Ovalbumin specific antibodies were measured at day 21, and the development of allergic airway inflammation was studied after ovalbumin challenge at day 28. “Ultrafine” (primary structure below 30 nm in diameter) but not fine (particle size >200 nm in diameter) carbon black particles were shown to induce airway inflammation and displayed adjuvant activity.

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