Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The documentation of the experimental conditions insufficient for an assessment. The test item is a mixture of a large number of different metals, thus a test-item effect correlation cannot be made. Consequently, the references is considered not relevant for the safety assessment of strontium neodecanoate.

Data source

Reference
Reference Type:
publication
Title:
Distribution of metals of inhaled fly ash in various organs of rats at various periods after exposure.
Author:
Srivastava, V.K., et al.
Year:
1984
Bibliographic source:
J. Environ. Sci. Health, A19, 663-677

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
24 male rats were exposed to coal fly ash (0.2-0.4 mg/L) on 6h/d for 15 consecutive days. 24 control rats were kept in a dust-free room. Records of their body weights were maintained. 6 rats of control and 6 rats of the experimental group were sacrificed by decapitation 1, 7, 15 and 30 days after the last inhalation exposure. Before sacrifice, blood was collected from the jugular vein. After sacrifice, lung, liver, heart, kidney, and small intestine was collected, cleaned, wiped, weighed and processed for quantification of metals by atomic absorption spectrophotometry. Serum was also processed likewise. The distribution of metal ions (Na, K, Fe, Ca, Mg, Pb, Zn, Cu, Co, Ni, Cr, Mn, and Sr) in lung, liver, kidney, heart, small intestine and serum on 1, 7, 15 and 30 days after the last inhalation exposure was determined.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
Fly ash (containing different metals such as strontium)
IUPAC Name:
Fly ash (containing different metals such as strontium)
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Fly ash
- Other: low sulfur pulverized coal, containing diffferent metal ions (Na, K, Fe, Ca, Mg, Pb, Zn, Cu, Co, Ni, Cr, Mn, and Sr)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: from the Institute maintained colony (Department of Biochemistry, V.P. Chest Institute, University of Delhi, Delhi-110007, India)
- Weight at study initiation: 150-175 g
- Fasting period before study: no
- Housing: no data
- Diet (ad libitum): Hind lever diet (Hindustan lever Ltd, Bombay)
- Water (ad libitum): free access before and after exposure
- Acclimation period: no data

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
not specified
Vehicle:
not specified
Remarks:
no vehicle
Remarks on MMAD:
MMAD / GSD: no data
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Preparation of the fly ash samples: low sulfur pulverized coal was operated by an electrostatic precipitator (IP Thermal power Plant, New Delhi). Afterwards the bulk was collected and sieved through 400 mesh sieve (37 µm) to remove coarser particles.
- Exposure apparatus: The fly ash aerosol was generated by a Wright dust generator, the dust cloud passed through a large glass vessel, before entering the inhalation chamber
- Inhalation chamber: 624 L capacity
- Dust concentration: 0.2 - 0.4 mg fly ash / L
- Method of particle size determination: light microscope fitted with an eyepiece graticule
- control rats were kept in a dust free room.

TEST ATMOSPHERE
- Samples taken from breathing zone: no data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
The quantification of metals in the tissues and blood serum was estimated by Perkin Elmer Atomic Absorption spectrophotometer (Model 2380)
Duration of treatment / exposure:
15 days
Frequency of treatment:
6 hrs/d on 15 consecutive days
Doses / concentrations
Remarks:
Doses / Concentrations:
0.2-0.4 mg Fly ash/ L
Basis:
no data
No. of animals per sex per dose:
6 male animals in each group (control and test group) and period (1, 7, 15 and 30 days after last inhalation exposure)
Control animals:
yes
Details on study design:
no data
Positive control:
no

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: animals were sacrificed on days 1, 7, 15 and 30 after the last inhalation exposure. Before sacrifice, blood was collected from the jugular vein for serum preparation. After sacrifice, lung, liver, heart, kidney and small intestine (upper 30cm) was collected, cleaned, wiped, weighed and processed for quantification of metals By Perkin Elmer Atomic Absorption spectrophotometer. serum was also processed likewise.

BODY WEIGHT: Yes
- Time schedule for examinations: records of their body weights were maintained

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: No data

CLINICAL CHEMISTRY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
GROSS PATHOLOGY: No data
HISTOPATHOLOGY: No data
Animals were sacrificed by decapitation on 1, 7, 15 and 30 days after the last inhalation exposure.
Other examinations:
no data
Statistics:
no data

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Records of body weights were maintained but not reported
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:
effects observed, treatment-related
Description (incidence and severity):
metal ion concentration was detected in several tissues and blood serum
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
organs were weight after cleaning and wiping. No results were reported
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
- The results showed a profound increase in the concentration of Na, K, Fe, Ca, Mg, Pb, Zn, Cu, Co, Ni, Cr, Mn and Sr in all the tissues and serum of rats after the inhalation exposure to fly ash.
- The increased levels of the metals were highest one day after the last exposure and at later periods their concentration declined which varied from metal to metal and from organ to organ.
- The Sr concentrations were the lowest of all metals in all animals (controls and test animals) at all time points. After one day the Sr concentration was raised in the lung (1.0 µg/g wet tissue), heart (0.5 µg/g wet tissue) and kidney (0.4 µg/g wet tissue) in comparison to the control value (0.3 µg/g wet tissue). The highest concentration was found in the lung (1.1 µg/g wet tissue) and liver (0.6 µg/g wet tissue) after 7 days, which reduced to control value after 30 days in lung and 15 days in liver. The Sr concentration in the kidneys did not change until the end of the test (15 days after last inhalation exposure). The Sr concentration in the small intestine was the same as the control value (0.3 µg/g wet tissue).

Effect levels

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

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Concentration of Sr in tissues after different recovery periods

Days after last inhalation exposure  Control[µg Sr/g wet tissue]  Lung[µg Sr/g wet tissue]  Liver[µg Sr/g wet tissue]  Heart[µg Sr/g wet tissue] Kidney[µg Sr/g wet tissue] Small intestine [µg Sr/g wet tissue]
1 0.3 ± 0.1 1.0 ± 0.1 0.3 ± 0.1 0.5 ± 0.1 0.4 ± 0.1 0.3 ± 0.1
7 0.3 ± 0.1 1.1 ± 0.1 0.6 ± 0.1 0.3 ± 0.1 0.4 ± 0.1 0.3 ± 0.1
15 0.3 ± 0.1 0.6 ± 0.1 0.3 ± 0.1 0.2 ± 0.1 0.4 ± 0.1 0.3 ± 0.1
30 0.3 ± 0.1 0.3 ± 0.1 0.3 ± 0.1 0.2 ± 0.1 - -

Applicant's summary and conclusion

Conclusions:
These results show the translocation of inhaled fly ash metals to extrapulmonary organs. No further conclusions can be drawn from this publication.