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Toxicological information

Acute Toxicity: other routes

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Administrative data

Endpoint:
acute toxicity: other routes
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:
Surface area of particle administered versus mass in determining the pulmonary toxicity of ultrafine and fine carbon black: comparison to ultrafine titanium dioxide
Author:
Sager TM and Castranova V
Year:
2009
Bibliographic source:
Part Fibre Toxicol 6(15), 12 pages, doi:10.1186/1743-8977-6-15

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
1, 7, or 42 days postexposure, inflammatory and cytotoxic potential of each particle type was compared on both a mass dosage (mg/rat) as well as an equal surface area dosage (cm2 of particles per cm2 of alveolar epithelium)
GLP compliance:
not specified

Test material

Test material form:
other: (solid: nanoform, no surface treatment; solid: particulate/powder

Test animals

Species:
rat
Strain:
Fischer 344

Administration / exposure

Route of administration:
other: intratracheal
Vehicle:
other: BAL fluid
Doses:
47, 94 and 188 µg/rat
No. of animals per sex per dose:
8 rats/group

Results and discussion

Effect levels
Key result
Dose descriptor:
EC50
Remarks on result:
other: for inflammatory effects, surface area was considered a better dose metric than mass

Applicant's summary and conclusion

Conclusions:
The results indicate that for low toxicity low solubility materials, surface area of particles administered rather than mass burden of particles may be a more appropriate dose metric for pulmonary toxicity studies.
 
Executive summary:

A study was conducted to determine whether mass of particles or surface area of particles is the more appropriate dose metric for pulmonary toxicity studies. In this study, ultrafine CB (ufCB, Printex 90) and fine CB (fCB, Arosperse 15V) suspended in acellular bronchoalveolar lavage fluid (BALF) were administered at various doses to male Fischer 344 rats via intratracheal instillation to assess pulmonary toxicity. The surface areas of the particles were 269.0 m2/g for ufCB and 8.1 m2/g for fCB. At 1, 7, or 42 days postexposure, inflammatory and cytotoxic potential of each particle type was compared on both a mass dosage (mg/rat) as well as an equal surface area dosage (cm2 of particles per cm2 of alveolar epithelium). UfCB particles caused a dose dependent but transient inflammatory and cytotoxic response. On a mass basis, these responses were significantly (65 fold) greater than those for fine sized CB. However, when doses were equalized based on surface area of particles given, the ufCB particles were only slightly (non-significantly) more inflammogenic and cytotoxic compared to the fine sized CB. The pulmonary reaction to ufCB resolved with time. These results indicate that for low toxicity low solubility materials, surface area of particles administered rather than mass burden of particles may be a more appropriate dose metric for pulmonary toxicity studies. In addition, ultrafine titanium dioxide appears to be more bioactive than ufCB on an equivalent surface area of particles delivered basis.