Magnesium hydroxide sulfate (Mg6(OH)10(SO4)), hydrate (1:3)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not reported.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Biological effects of inhaled magnesium sulphate whiskers in rats.

Author:

Hori, H., Kasai, T., Haratake, J., Ishimatsu, S., Oyabu, T., Yamato, H., Higashi, T. & Tanaka, I.

Year:

1994

Bibliographic source:

Occupational and Environmental Medicine, Vol. 51, pp. 492-499.

Materials and methods

Objective of study:

absorption

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The test material was suspended in distilled water, and was intratracheally injected into the lungs of each of 30 golden hamsters. The same amounts of distilled water were injected into five hamsters as a control group. Hamsters were killed and dissected at 10, 20, 40, 60, and 80 minutes after the injection, and the amounts of magnesium in the lungs were determined by a wet washing method. The residual amounts of the whiskers were calculated from the amounts of magnesium.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

MOS-HIGE, short whiskers

IUPAC Name:

MOS-HIGE, short whiskers

Details on test material:

Count median length: 4.9 µm (2.1)
Count median diameter: 0.31 µm (1.5)
Aspect ratio: 15.8
Surface area: 9.5 m3/g
True density: 2.3 g/cm3
Bulk density: 0.084 g/cm3

Radiolabelling:

no

Test animals

Species:

hamster, Syrian

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
not reported.

- Age at study initiation:
not reported.

- Weight at study initiation:
not reported.

- Fasting period before study:
not reported.

- Housing:
not reported.

- Individual metabolism cages: yes/no
not reported.

- Diet (e.g. ad libitum):
not reported.

- Water (e.g. ad libitum):
not reported.

- Acclimation period:
not reported.

ENVIRONMENTAL CONDITIONS
not reported.

IN-LIFE DATES: All animals were sacrificed within 80 minutes of test initiation.

Administration / exposure

Route of administration:

intratracheal

Vehicle:

water

Details on exposure:

TYPE OF INHALATION EXPOSURE: other: Intratracheal injection

DETAILS ON INTRATRACHEAL DOSING
- Exposure apparatus:
Not reported.

- Composition of vehicle (if applicable):
distilled water

- Concentration of test material in vehicle (if applicable):
4mg/ml

- Dose volume:
0.275 ml per hamster

Duration and frequency of treatment / exposure:

Single exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
Concentration: 4mg/ml
Corresponding dose: ca. 1.1mg/ml

No. of animals per sex per dose / concentration:

6

Control animals:

yes, concurrent vehicle

Positive control reference chemical:

not applicable to test methodology

Details on study design:

- Dose selection rationale:
not reported.

Details on dosing and sampling:

PHARMACOKINETIC STUDY
- Tissues and body fluids sampled:
Lungs

- Time and frequency of sampling:
Animals were sacrificed 10, 20, 40, 60 and 80 minutes

Results and discussion

Preliminary studies:

Not applicable to test methodology.

Main ADME results

Type:

absorption

Results:

The test material (characterised by the Magnesium content) was rapidly removed from the lungs.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Table 1 shows the magnesium content in hamster lungs after intratracheal instillation.
Magnesium was removed rapidly from the lungs. The table also shows the residual amount of short whiskers per lung calculated from the measured amount of magnesium. Because magnesium content in the control rats was high, the deposited amounts of magnesium in the exposed rats were estimated by subtracting the amounts of magnesium in the controls from that in the exposures. The column (1) of the residual amount of the short whiskers in table 1 shows
the estimated residual amounts of the short whiskers in the lungs obtained by subtracting the average amounts of magnesium per lung weight of the controls (equation 1):
As shown in table 1, however, the average lung weights of the exposed groups were significantly greater than those of the control group except for the 10 minutes clearance period. The reason for this may be that the lung weights were changed by the injected fluid because the dissection times after the instillation were so short. As the periods until the dissection of the controls were longer than the exposure groups, a part of the injected liquid in the control rats could already have been absorbed and transferred into the body fluids.
If this is the case, the correction for body weight may be more suitable because the body weights were not significantly different between the control and the exposure groups.
The column (2) in the table shows the calculated amount of the short whiskers estimated by the amount of magnesium in the lungs with correction for average body weight of the control hamsters (equation 2):
The injected amount of short whiskers was 1100µg (1.1 mg). Therefore, the results in table 4 indicate that the residual amounts of short whiskers decreased to less than one tenth at 80 minutes after the instillation.

Details on distribution in tissues:

not applicable to study methodology.

Details on excretion:

not applicable to study methodology.

Metabolite characterisation studies

Metabolites identified:

not measured

Any other information on results incl. tables

Table 1. Magnesium content and residual amound of short whiskers in hamster lungs: intratracheal installation study.

Period (min)	Body weight (g)	Lung weight (g)	Magnesium content in the lung (µg)	Residual amount of short whiskers
				(1) (µg/g lung)	(2) (µg/g lung)
0 (control)	121 (7)	0.54 (0.05)	81.7 (8.6)	-	-
10	119 (8)	0.61 (0.05)	321.1 (17.0)	729.9 (44.1)	755.1 (45.5)
20	122 (12)	0.70 (0.09)**	277.5 (19.8)	548.0 (80.6)	608.5 (37.5)
40	122 (5)	0.67 (0.03)**	173.9 (10.5)	228.9 (20.0)	275.4 (34.2)
60	119 (12)	0.67 (0.09)**	135.3 (12.6)	110.8 (12.9)	160.1 (25.3)
80	126 (5)	0.67 (0.03)**	119.9 (8.3)	61.4 (13.1)	95.3 (23.2)

Applicant's summary and conclusion

Conclusions:

The test material was rapidly removed from the lungs, decreasing to less than 1/10 of the test dose at 80 minutes after dosing.

Executive summary:

To measure the clearance rate of the whiskers from the lungs, an intratracheal installation was performed in golden (syrian) hamsters. The half-life of the whiskers in the lung was determined as 17.6 minutes by temporally measuring the magnesium concentration up to 80 minutes after the installation.