Dialuminium nickel tetraoxide

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards, well documented and acceptable for publication.

Data source

Reference

Reference Type:

publication

Title:

Changes In Pulmonary Alveolar Macrophages In Rats Exposed To Oxides Of Zinc And Nickel

Author:

Migally N, Murthy RC, Doye A, Zambernard J

Year:

1982

Bibliographic source:

J. Submicrosc Cytol. 14: 621·626

Materials and methods

Principles of method if other than guideline:

Sprague-Dawley rats were exposed to NiO via intratracheal instillation for a single dose. A week later the lungs were prepared for transmission electron microscopy.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Nickel monoxide

EC Number:

215-215-7

EC Name:

Nickel monoxide

Cas Number:

1313-99-1

IUPAC Name:

oxonickel

Details on test material:

- Name of test material (as cited in study report): NiO
- Substance type: color unspecified

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: adult
- Weight at study initiation: 300-500 g
- Housing: cages

Administration / exposure

Route of administration:

other: intratracheal

Vehicle:

physiological saline

Details on exposure:

Injections administered directly into the lungs through the trachea. All animals were held upright on a slanted metal plate· during the intratracheal injections, then returned to their cages.

Doses:

10 mg/mL

No. of animals per sex per dose:

10 males

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 1 wk
- Other examinations performed: histopathology of lung via TEM

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LC0

Effect level:

10 mL/kg bw

Based on:

test mat.

Remarks on result:

other: There was an absence of electron dense structures. The ultrastructure of pulmonary macrophages contained, “invaginated bizarre-shaped nuclei, that lacked prominent nucleoli.

Mortality:

Not reported.

Clinical signs:

Not reported.

Body weight:

Not reported.

Gross pathology:

Not reported.

Other findings:

- Histopathology:
Pulmonary alveolar macrophages (PAM) exhibited “invaginated bizarre-shaped nuclei, that lacked prominent nucleoli… The cytoplasm usually contained numerous primary and secondary lysosomes, pigment aggregation as well as several membranous whorls…Unlike ZnO-exposed lungs, pulmonary interstitial macrophages…were devoid of electron dense structures.

Any other information on results incl. tables

Not applicable.

Applicant's summary and conclusion

Conclusions:

The authors concluded that the absence of electron dense structures in the pulmonary interstitial macrophages of NiO-exposed animals suggests that Ni-associated dense bodies were still contained within the PAM even after a week-long recovery period. This suggests that NiO was not transferred to the interstitial macrophages as was noted in the lungs of ZnO-treated rats.

Executive summary:

In a descriptive study examining the effects of NiO and ZnO on the ultrastructure of pulmonary macrophages (PAM) and pulmonary interstitial macrophages, Migally et al. (1982) exposed male Sprague-Dawley rats (n=10) to a single dose of 10 mg/mL NiO (color unspecified) via intratracheal instillation. One week following exposure, lung tissue was collected and prepared for transmission electron microscopy. The ultrastructure of pulmonary macrophages were described by the authors as, “invaginated bizarre-shaped nuclei, that lacked prominent nucleoli… The cytoplasm usually contained numerous primary and secondary lysosomes, pigment aggregation as well as several membranous whorls…Unlike ZnO-exposed lungs, pulmonary interstitial macrophages…were devoid of electron dense structures.” Based on these findings, the authors concluded that the absence of electron dense structures in the pulmonary interstitial macrophages of NiO-exposed animals suggested that Ni-associated dense bodies were still contained within the PAM even after a week-long recovery period. This suggests that NiO was not transferred to the interstitial macrophages as was noted in the lungs of ZnO-treated rats. The authors further stated that the functional ramifications of these effects remain to be elucidated. STUDY RATED BY AN INDEPENDENT REVIEWER