Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 246-140-8
CAS number: 24304-00-5
In a subacute inhalation toxicity
study, aluminium nitride (AlN) was administered to 10 Fischer 344
rats/sex/concentration by nose only exposure at concentrations of 0, 2,
10, and 70 mg/m³ for 6 hours/day for 5 days/week for a total of 19
exposures during a 4 week study. The average Mass Median Aerodynamic
Diameter (MMAD) was 1.5 μm; 84% of the aerosol mass consisted of
particles less than 2.4 μm. Five rats/sex/exposure concentration were
evaluated by pathology immediately after the 4 week exposure period, and
five more rats/sex/exposure concentration were held for approximately 10
weeks after the last exposure, and were then evaluated by pathology. In
addition to gross and histopathologic evaluations, there were clinical
observations and determinations of body weights, clinical chemistry,
hematology, urinalysis, and organ weights. Because the only
exposure-related effect were related to the respiratory system in rats
evaluated at 4 weeks, evaluations were focused on rats that were held
for 10 week post-exposure.
After four weeks, there was a mild
inflammatory response in the lungs of rats exposed to 70 mg/m³. In the 2
and 10 mg/m³ groups, there was little or no evidence of a tissue
reaction in the lungs, other than phagocytosis. At the lower exposure
concentrations, virtually all of the visible foreign material in the
lung parenchyma was contained within alveolar macrophages. This foreign
material was presumably AlN or an AlN degradation product. At 70 mg/m³,
approximately 25% of the foreign material was "free” either phagocytized
or freed from dead macrophages.
Following the 10 week post-exposure
period, histologic examination of lungs from rats in the 2 mg/m³ group
indicated that foreign material was present within the alveolar
macrophages, and there were widely scattered small areas of mild
inflammation characterized by slight alveolar type II cell proliferation
and occasional neutrophils. At 10 mg/m³, the changes described above
were increased, and there were reactive changes in the bronchial
associated lymphoid tissue (BALT). At 70 mg/m³, much of the foreign
material was trapped within proteinaceous material filling many of the
Alveolar type II cell proliferation
and the BALT reaction were marked. Lung weights and blood
neutrophil:leukocyte ratios were increased in most groups with pulmonary
inflammation. Overall the reaction was characterized as a proliferative
In rats exposed to 70 mg/m³ and
evaluated immediately after 4 weeks of exposure, there were signs of
upper respiratory tract irritation which included slight goblet cell
hyperplasia of the nasal turbinates. Effects on the upper respiratory
tract were largely resolved at 10 weeks post-exposure, and there were no
upper respiratory tract effects in rats exposed to 2 or 10 mg/m³.
Proliferative pneumonitis was more
severe after the 10 week post-exposure period. Excessive exposure to AIN
exceeded physiologic lung clearance mechanisms, as suggested by the free
foreign material in pulmonary alveoli of rats exposed to this
concentrations of AIN aerosol. This may in part account for the more
pronounced effects at 10 weeks post-exposure.
Overall, AlN predominantly affected
the alveolar macrophages. The NOAEC for male and female rats was 2 mg/m³
based on mild adverse effects in the lungs and observed alveolar
macrophages engulfing foreign material, which is an important step in
the clearing process. The adverse effects at higher concentrations are
considered to justify CLP classification for specific target organ
toxicity (STOT RE2, lung, local).
This sub-acute toxicity study in
the rat is acceptable and satisfies the guideline requirement accordign
to OECD 412 for a sub-acute inhalation study in the rat.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again