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Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Materials and methods well described; results presented adequately in text, tables and figures.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Biological effects of inhaled magnesium sulphate whiskers in rats
Author:
Hori, H.; et al.
Year:
1994
Bibliographic source:
Occup. Environ. Med. 51: 492-499.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Subchronic effects of inhaled whiskers in rats.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
Magnesium sulphate
EC Number:
231-298-2
EC Name:
Magnesium sulphate
IUPAC Name:
231-298-2
Constituent 2
Reference substance name:
7487-88-9
Cas Number:
7487-88-9
IUPAC Name:
7487-88-9
Constituent 3
Reference substance name:
magnesium sulfate
IUPAC Name:
magnesium sulfate
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): magnesium sulfate whiskers consisting of magnesium sulfate and magnesium hydoxide.
No further details are given.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 4 weeks
No further details are given.

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
other: air
Remarks on MMAD:
MMAD / GSD: Count median length (µm): long whiskers = 12.0 +/- 2.3 and short whiskers = 4.9 +/- 2.1
Count median diameter (µm): long whiskers = 0.44 +/- 1.6 and short whiskers = 0.31 +/- 1.5
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: consisted of a whisker generator and an exposure chamber (volume 0.43m^3) and was made from stainless steel.
- System of generating particulates/aerosols: whiskers were premixed with glass beads (250µm) and put into a hopper. The whiskers mixed with glass beads were supplied from the hopper to a fluidised bed generator. Air from a compressor was passed through a silica gel fixed bed and introduced into the bottom of the fluidised bed. Glass beads with whiskers were moved in the fluidised bed due to airflow and the whiskers were detached from the glass beads.
- Temperature, humidity in air chamber: 25°C, 50%
- Air flow rate: air with whiskers was introduced from the top of the chamber with a flow rate of 150 L/minute.
No further details are given.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The whisker concentration in the chamber was monitored continuously with a digital dust indicator.
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
6 hours per day, 5 days per week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2.3 mg/m3 (short whiskers)
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
4.0 mg/m3 (long whiskers)
Basis:
nominal conc.
No. of animals per sex per dose:
124 rats were divided into 3 groups: 42, 42 and 40 rats per group for short whiskers, long whiskers and controls, respectively
Control animals:
yes
Details on study design:
no data
Positive control:
no data

Examinations

Observations and examinations performed and frequency:
Body weights of the rats were measured every week to obtain the growth curves.
Sacrifice and pathology:
- 5 or 6 rats in each group were killed and dissected at 1, 2, 3 and 4 weeks after the beginning of the exposure, and 2 and 4 weeks, 6 months and 1 year after the end of the exposure.
- In all dissections, the weights of body and organs (lung, liver, kidney and spleen) were measured.
- Lungs were divided and a part was used for the determination of the whiskers; remaining portions were used for histopathological examination.
Statistics:
no data

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not specified
Details on results:
BODY WEIGHT AND WEIGHT GAIN:
Growth curves and survival rates were similar in all groups.

ORGAN WEIGHTS:
Organ weights did not show significant differences.

HISTOPATHOLOGY: NON-NEOPLASTIC.
There was no effect on the Mg contents in the lungs of different groups. Histopathology did not indicate significant differences between control and exposure groups.

No further details are given.

Effect levels

Dose descriptor:
NOAEC
Remarks on result:
not determinable
Remarks:
no NOAEC identified

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Subchronic inhaltion exposure of rats with the test material (short and long magnesium sulphate whiskers) did not affect growth curves, survival rates and organ weights in treated rats compared to control animals. There was no effect on the Mg contents in the lungs of different groups. Histopathology did not indicate significant differences between control and exposure groups.

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