Registration Dossier

Toxicological information

Acute Toxicity: other routes

Currently viewing:

Administrative data

acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
other information
Study period:
not reported
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: non-physiological exposure route; comparative calculations of the dose relative to environmental exposures are difficult.

Data source

Referenceopen allclose all

Reference Type:
Short-term inflammatory response following intratracheal instillation of fine and ultrafine carbon black in rats
Li XY, Brown D, Smith S et al
Bibliographic source:
Inhalatioin toxicology 11(8), 709-731
Reference Type:
In Vivo and in Vitro Proinflammatory Effects of Particulate Air Pollution (PM10)
Li XY et al.
Bibliographic source:
Environmental Health Perspectives 105, Supplement 5, 1279-1283.
Reference Type:
other: abstract
Comparison of the pro-inflammatory effects of fine and ultrafine carbon black in the lungs.
Li XY, Donaldson K, MacNee W
Bibliographic source:
Annual Congress of the European Respiratory Society, Berlin, Germany, September 20-24, 1997. European Respiratory Journal Supplement. Abstract P2312, p 363s.

Materials and methods

Test guideline
no guideline required
Principles of method if other than guideline:
BAL profile at 6h, 24h and 7d after intratracheal instillation of 125 µg
GLP compliance:
not specified

Test material

Details on test material:
carbon black (Degussa Huber NG90, diameter 200-250 nm and 260 nm), and ultrafine carbon black (Degussa Printex 19, diameter 20 nm; and Printex 90, 14nm)

Test animals

Details on test animals and environmental conditions:
- Age: 12 weeks

Administration / exposure

Route of administration:
other: intratracheally
other: phosphate buffered saline (PBS)
Details on exposure:
The animals were anesthetized with pentobarbitone, and 0.2 mL of PBS- particle suspension (containing 50-125 ug of PM10, or 125 ug of either carbon black or ultrafine carbon black particles) was instilled intratracheally.
The controls for these experiments were animals that did not receive any instillation and animals instilled with 0.2 mL PBS alone.
Six hours after intratracheal instillation of particle suspensions, rats were sacrificed. and 4 mL PBS at 37 deg C was instilled and withdrawn from the lungs. After centrifugation this solution was referred to as bronchoalveolar lavage fluid (BALF). To obtain broncholalveolar lavage (BAL) leukocytes, 4x 8 mL PBS was used to wash the lungs and then collected in a universal tube. The cell suspension was spun and cell pellets were resuspended in Dulbecco´s minimum essential medium (DMEM) plus 0.2% low endotoxin-bovine serum albumin in which the cells from the first lavage were combined. The total number and differential count of BAL leukocytes were obtained. BAL leukocytes from control animals consisted of greater than 99% macrophages.

0, 50 µg (ultrafine carbon black), 125 µg (ultrafine carbon black, carbon black)
No. of animals per sex per dose:
Groups of 3-6 male animals
Control animals:
Statistical analysis: differences between mean values were assessed by analysis of variance.

Results and discussion

Effect levels
Dose descriptor:
other: inflammatory response
Effect level:
125 other: µg
Remarks on result:
other: ultrafine carbon black caused 50% neutrophil alveolitis 6 hours after instillation, still present 7 days later
Other findings:
Compared with animals that had instillations of PBS, carbon black produced a small but significant neutrophil influx. The greatest inflammatory cell influx occurred after instillation of ultrafine carbon black (control 1.5%, carbon black 3.5%, ultrafine carbon black 49.6% neutrophils, p < 0.05). The neutrophil influx was still present 7 days after instillation of ultrafine carbon black, and also occurred following instillation of 50 ug of ultrafine carbon black.
As with the influx of inflammatory leukocytes, the greatest increase in airspace epithelial permeability occurred after instillation of ultrafine carbon black (p< 0.01). Carbon black produced a lesser increase in epithelial permeability (p< 0.05) than PM10 (p< 0.001) or ultrafine carbon black.
Ultrafine carbon black instillation also resulted in a marked increase in LDH levels in BAL fluid. Ultrafine carbon black, compared with carbon black also produced a significant depletion of total lung GSH (control lung GSH 50.4 +/- 9.7, ultrafine carbon black 29.0 +/- 3.7 nmoles/g lung, p < 0.05).
Alveolar leukocytes in both carbon black and ultrafine carbon black instilled animals produced significantly increased amounts of tumour necrosis factor (TNF) compared with control animals, with leukocytes from ultrafine carbon black animals producing most TNF.

Applicant's summary and conclusion

In a rat instillation model ultrafine carbon black at 125 µg produces more lung inflammation and oxidant stress than carbon black at 125 µg. The threshold dose for neutrophil influx occurred at 50 µg.
Executive summary:

6 hours after intratracheal instillation ultrafine carbon black produced an acute neutrophil influx into the airspaces, with accompanying increased epithelial permeabiity. Ultrafine carbon black produced similar qualitative but greater quantitative proinflammatory effects as compared to carbon black and PM10 in the rat lung. The carbon black showed similar activity to the phosphate-bufferd saline vehicle controls. The authors suggest that the effects may be due to a free radical activity of ultrafine particles.