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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
The study was not performed according to a test guideline and GLP, and only one dose was tested. Furthermore, deviations from the experimental study plan due to power failure resulted in a repeat of the study. Overall, the study report extensively described study procedure and results and is sufficient to be used as supporting data for this endpoint.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report date:
1983

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
48 Rats per test group were exposed via inhalation to three different insulation materials containing calcium silicates for 12 months. One dose was tested, animals were exposed for 7 hrs/day for 224 days. From each test group, 12 animals were sacrificed after termination of the exposure, the other animals were allowed to live out their normal lifespan and were killed 19 months after termination of the exposure. Observations include body weight,survival time, histopathology, and hematology.
Due to a power failure after nine months, the study was repeated with four new groups of rats. Reported results are from this second study.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Reference substance name:
Calcium silicate
EC Number:
233-250-6
EC Name:
Calcium silicate
Cas Number:
10101-39-0
IUPAC Name:
calcium oxosilanediolate
Constituent 2
Reference substance name:
Caposil 16
IUPAC Name:
Caposil 16
Constituent 3
Reference substance name:
Newtherm 800
IUPAC Name:
Newtherm 800
Constituent 4
Reference substance name:
Paratemp AF
IUPAC Name:
Paratemp AF
Details on test material:
- Name of test material (as cited in study report): Three separate insulation materials containing calcium silicate composites: Caposil 16, Newtherm 600, Paratemp AF
- Composition of test material, percentage of components:
Caposil 16: 70% tobermorite, 2% quartz, 3-15% CaCO3, 19% MMF, 2% other
Newtherm 800: 75% tobermorite, 5% quartz, 4-12% CaCO3, 9% MMF, 5% other
Paratemp AF: 80% tobermorite, 2% quartz, 3-12% CaCO3, 3% MMF, 10% other

Test animals

Species:
rat
Strain:
other: HAN SPF
Sex:
not specified
Details on test animals or test system and environmental conditions:
No detailed information available

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
not specified
Remarks:
animals were exposed in dust chamber, whole body exposure is assumed
Vehicle:
not specified
Remarks on MMAD:
MMAD / GSD: All particles ≥ 2 um, details provided below (Any other information on materials and methods incl. tables)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The used dust generation system consisted of a guide to hold a 50*25*200 mm block of calcium silicate material, a variable speed electric motor driving a piston which pushes the block into a rotating wire brush, and a jet of compressed air to carry the dust into the chamber ventilation air flow.
- Further details can be found in Becket (1975) and Timbrell (1970).

TEST ATMOSPHERE
- Brief description of analytical method used: Respirable dust concentration was assessed using both the Casella MRE 113A horizontal elutriator system (Dunmore et al., 1964), and the IOM vertical elutriator (Becket, 1975).

VEHICLE: Not applicable
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Total dust samples and respirable samples were taken for analysis each month from each inhalation chamber.
Duration of treatment / exposure:
7 hrs/day
Frequency of treatment:
224 days/year
Doses / concentrations
Dose / conc.:
10 mg/m³ air (nominal)
No. of animals per sex per dose:
48 animals/dose
Control animals:
yes, sham-exposed
Details on study design:
No details available
Positive control:
Not applicable

Examinations

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

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Monthly

FOOD CONSUMPTION: No data

FOOD EFFICIENCY: No data

WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: At start and at end of the study
- Parameters: Total red cell count, haemoglobin content, packed cell volume (haematocrit), mean corpuscular volume, mean corpuscular haemoglobijn content, and total white cell count

CLINICAL CHEMISTRY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Other examinations:
Not applicable
Statistics:
Survival: Cox's Proportional Hazard Model (Cox, 1972), BMD programme using product limit method of calculation
Body weight:Graphical comparison

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:
no effects observed
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
Mean survival was not significantly different from control survival, mean survival time was 773.7 days for Caposil 16, 774.1 days for Newtherm 800, 800.2 days for Paratemp, and 791.6 days for the control animals. Furthermore, no differences in body weight and no clinical symptoms were observed. In exposed animals, dust-containing macrophages accumulated in the lung tissue during exposure, but after recovery these declined substantially in number until few remained in old animals. Animals treated with Newtherm 800 showed small silicotic lesions in the lungs and lymph nodes which could be related to exposure. Furthermore, exposure to Paraterm AF and Caposil 16 resulted in the formation of a number of small benign lesions, however, this was not statistically significant.
All haematological parameters were within normal values except white blood cell levels. Absolute white blood cell count was statistically increased, where no significant increase was observed in the percentages of the white cell types between exposed and control animals. Histopathology revealed the formation of a few small silicotic lesions in the lungs and lymph nodes in animals exposed to Newtherm 600. In Caposil 16 and Paratemp AF exposed animals, no statistically significant histopathological effects were observed.

Effect levels

Key result
Dose descriptor:
NOAEC
Effect level:
10 mg/m³ air (nominal)
Based on:
other: respirable dust
Sex:
not specified
Basis for effect level:
other: No effects were observed

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In rats exposed to three different calcium silicate insulation products (Caposil 16, Newtherm 600 and Paratemp AF) by inhalation at 10 mg/m3 for one year (7 hrs/day during 224 days, respirable concentration), no relevant effects were observed on bodyweight, survival, clinical signs, haematology and histopathology, although some small lesions were observed in rats exposed to Newtherm 600.
Executive summary:

48 Rats per test group were exposed via inhalation to three different insulation materials containing calcium silicates for 12 months. One dose was tested, animals were exposed for 7 hrs/day for 224 days. From each test group, 12 animals were sacrificed after terimation of the exposure, the other animals were allowed to live out their normal lifespan and were killed 19 months after termination of the exposure. Observations include body weight,survival time, histopathology, and hematology.

It was concluded that the exposure to three different calcium silicate insulation products (Caposil 16, Newtherm 600 and Paratemp AF) by inhalation at 10 mg/m3 for one year (7 hrs/day during 224 days) did not result in relevant effects on bodyweight, survival, clinical signs, haematology and histopathology, although some small lesions were observed in rats exposed to Newtherm 600. It should be noted that this product contains 5% Quartz, whereas the other two tested products contain around 2% Quartz. In contrast, the substance that is registered with the current dossier (xonotlite/tobermorite) contains less than 1% Quartz.