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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from a sparingly soluble chromate, not a guideline or GLP study.
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Lung injury, inflammation and Akt signaling following inhalation of particulate hexavalent chromium.
Author:
Beaver, L. M., E. J. Stemmy, et al.
Year:
2009
Bibliographic source:
Toxicol Appl Pharmacol.235(1): 47-56.

Materials and methods

Principles of method if other than guideline:
intranasal exposure of mice to substance, factors associated with lung injury, inflammation and survival signaling were measured in airway lavage fluid and in lung tissue
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): basic zinc chromate suspension, an insoluble particulate form of hexavalent chromium
- Molecular formula (if other than submission substance): ZnCrO4 4Zn(OH)2
- Analytical purity: 99-100%

Test animals

Species:
mouse
Strain:
other: BALB/cJ
Sex:
female

Administration / exposure

Route of administration:
other: intranasal
Duration of treatment / exposure:
up to 48 h after Cr(VI) exposure
Doses / concentrations
Remarks:
Doses / Concentrations:
50 μl dose of particulate basic zinc chromate (concentration 1.2 mg/ml saline, average size of particles 4.73 μm)

Examinations

Other examinations:
bronchoalveolar lavage (BAL) was performed with 3 x 1 mL of PBS;
basic zinc chromate was characterized, histology was examined, as well as flow cytometry, cytospin and cytokin analyses were conducted
Statistics:
Utilising GraphPad Prism version 4.00 for Windows, two tailed, unpaired t tests were completed when comparing two experimental groups, while one-way analysis of variance and a Tukey or Dunnetts post test was completed for multiple sample comparisons. Results are presented as the mean+-standard error of the mean (SEM) and significance was accepted at P<0.05.

Results and discussion

Effect levels

Dose descriptor:
LOAEL
Effect level:
other:
Basis for effect level:
other: zinc chromate concentration 1.2 mg/mL, dose 50 ul

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

A single zinc chromate exposure induced both survival signaling and an inflammatory response in the lung.

Applicant's summary and conclusion

Conclusions:
A single zinc chromate exposure induced both survival signaling and an inflammatory response in the lung.
Executive summary:

In Beaver et al. (2009), the nature of the lung injury, inflammatory response, and survival signalling responses following intranasal exposure of BALB/c mice to particulate basic zinc chromate were determined. Mice were euthanized at indicated time points up to 48 h after Cr(VI) exposure. A single chromate exposure induced an acute immune response in the lung. This was characterized by an increase in IL-6 and GRO-α levels, an influx of neutrophils, and a decline in macrophages in lung airways. Histology of lungs revealed an increase in bronchial cell apoptosis and mucosal injury. Chromate exposure induced injury and inflammation that progressed to alveolar and interstinal pneumonitis, and resulted in a rapid and persistent increase in airways immunoreactive for phosphorylation of the survival signalling protein Akt, on serine 473.