Manganese dioxide

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well conducted study although relevance is questionable due to method of application of the test material.

Data source

Reference

Reference Type:

publication

Title:

Significance of serum calcium, inorganic phosphates and alkaline phosphatase in experimental manganese toxicity

Author:

Chandra SV, Imam Z and Nagar N

Year:

1973

Bibliographic source:

Industrial Health, 11(43): 43-47

Materials and methods

Principles of method if other than guideline:

Rabbits were injected intratracheally manganese dioxide (400 mg/kg) and the serum calcium, inorganic phosphates and alkaline phosphatase levels were determined. Histological examinations were also carried out on the parathyroids, bones and kidneys.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Manganese dioxide

EC Number:

215-202-6

EC Name:

Manganese dioxide

Cas Number:

1313-13-9

Molecular formula:

MnO2

IUPAC Name:

dioxomanganese

Details on test material:

- Name of test material (as cited in study report): Manganese dioxide
- Patricle size of test material: < 5 µm

Results and discussion

Any other information on results incl. tables

In treated animals the level of serum calcium remained within normal limits up to 120 days, at 180 days the mean serum calcium level was significantly greater than control, this was also noted at 240 days. There was a significant decrease in the level of inorganic phosphates in manganese treated animals at 120 days and there was gradual lowering in the level at 180 and 240 days. Alkaline phosphatase activity showed significant decrease as early as 60 days and showed further decline as the experiment progressed. At 60 days kidneys of experimental animals were swollen and congested. At 240 days very fine granularity was observed with a thickened capsule which was adhered to the surface of the organ. Macroscopic examination showed further abnormalities such as haemorrhages and necrosis. No gross or microscopic abormaility was observed in parathyroids and bones in both groups.

Applicant's summary and conclusion

Conclusions:

A significant decrease in the levels of serum alkaline phosphatase, inorganic phosphates and an increase in calcium was noted at 180 days. These biochemical alterations occurred at a much earlier stage than the development of symptoms of manganese encephalopathy which are of great significance to detect early toxicity. The significance of intracheal instillation to hazard assessment for the inhalation route needs to be treated with care as other mechanisms come into effect that would not be seen in the normal inhalation of dust. The use of the rabbit for this study is also not considered a standard animal model for inhalation testing.

Executive summary:

Rabbits were injected intratracheally manganese dioxide (400 mg/kg) and the serum calcium, inorganic phosphates and alkaline phosphatase levels were determined. Histological examinations were also carried out on the parathyroids, bones and kidneys.

Under the conditions of the study, a significant decrease in the levels of serum alkaline phosphatase, inorganic phosphates and an increase in calcium was noted at 180 days. These biochemical alterations occurred at a much earlier stage than the development of symptoms of manganese encephalopathy which are of great significance to detect early toxicity. The significance of intracheal instillation to hazard assessment for the inhalation route needs to be treated with care as other mechanisms come into effect that would not be seen in the normal inhalation of dust. The use of the rabbit for this study is also not considered a standard animal model for inhalation testing.