Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The reliability is rated Klimish 1

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Ciment Fondu®
- Substance type: mineral
- Physical state: dark grey fine powder
- Composition of test material, percentage of components: Ciment Fondu® is a mixture of more than 99.5% milled clinker of Ciment Fondu® which is the same substance as the registered substance here, and a grinding agent
- Lot/batch No.: 91478
- Expiration date of the lot/batch: 20 oct 2010
- Storage condition of test material: at ambiant temperature
- Other:

Test animals

Species:
rat
Strain:
other: SPF (Specific Pathogen Free) Sprague-Dawley - Crl : OFA (SD)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles RiverLaboratoires France - Domaine des Oncins, 69592 L'Arbresle Cédex, France, or an approved breeding establishment
- Age at study initiation: 8 weeks
- Weight at study initiation: between 189.1 g and 194.6 g
- Fasting period before study : animals were fasted during the night before treatment
- Housing: animals were housed in cages of standard dimensions
- Diet (e.g. ad libitum): RM1 (E)-SQC SDS/DIETEX ad libitum, except during the fasting experimental period
- Water (e.g. ad libitum): ad libitum
- Acclimation period:Minimum of five days before treatment in the laboratory animal house where the experiment took place

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 45-65
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness with light on at 7.30 a.m.

IN-LIFE DATES: From: 25 May 2010 To: 29 June 2010

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10 mL/kg
- Amount of vehicle (if gavage): 5, 50, 300 and 2000 mg/kg body weight
- Justification for choice of vehicle:
- Lot/batch no. (if required): water for irrigation (Baxter, batch 09602B25, expiry date : june 2012)
- Purity:

MAXIMUM DOSE VOLUME APPLIED:

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Doses:
300 and 2000 mg/kg body weight
No. of animals per sex per dose:
three females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were examined clinically once before dosing and twice on the day of treatment (60 min +/- 30 min post-dose and then again between 3 and 4 hours post-dose). Thereafter they were examined clinically at least once a day for 14 days.
On D1 (60 min +/- 30 min post-dose) and on D7 animals were observed according to a standardised observation battery for general clinical signs, neurobehavioural, neurovegetative or psychotropic signs or neurotoxic effects.
Animals were weighted on D1 (day of administration), D7 and D14 during the study, and D15 (day of euthanasia)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, neurobehavioural, neurovegetative or psychotropic signs, neurotoxic effects, body weight

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured during the study
Clinical signs:
No clinical signs were observed during the course of the study
Body weight:
Mean body weight and body weight gains values of treated animals were normal when compared with the range of values usually found in the Centre
Gross pathology:
No gross tissue findings were seen at necroscopy
Other findings:
- Organ : No organ findings were seen at necroscopy

Any other information on results incl. tables

Effects on body weight (mean table) :

Results expressed in g - D: day - No statistical analysis % : variation expressed in percentage in relation to predose values

 
 Treatment   D1  D7  D14
 Ciment fondu® 300 mg/kg  Mean / SEM / % /N  199.8 /4.5 /NA /6 222.6 /5.4 /+11 /6  227.8 /5.9 /+14 /6 
 Ciment fondu® 2000 mg/kg  Mean / SEM / % /N  196.9 /4.5 /NA /6  230.5 /7.7 /+17 /6  236.5 /6.9 /+20 /6

Effects on body weight (individual values) :

Results expressed in g - D : day

 
 Treatment Animal number  D1 D7  D14 
 Ciment fondu® 300 mg/kg  201001298 189.1  212.5  211.7 
   201001299  190.2  208.4 222.7 
   201001300  194.6 218.6  220.1 
   201001301  206.9 222.7  224.7 
   201001302  200.0 227.5  234.4 
   201001303  217.9 245.7  253.0 
Ciment fondu® 2000 mg/kg  20101349  183.5 219.8  220.1 
  201001350  187.9 213.3  220.9 
   201001351  209.3 226.3  240.7 
   201001607  210.0 257.7  258.8 
   201001608  192.3 215.8  225.4 
   201001609  198.5 250.3  252.9 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions adopted, the oral administration of Ciment Fondu® caused no mortality at 300 and 2000 mg/kg and did not
induce clinical signs at these dose levels during a 14-day period, in female Sprague-Dawley rats.

Consequently, the maximal non-lethal dose is higher than 2000 mg/kg body weight.
Executive summary:

At the request of KERNEOS, the toxicity of the test item Ciment Fondu® was evaluated after a single dose administration by the oral (gavage) route in the female rat in accordance with the General Requirements of the OECD Guideline No. 423 (December 17, 2001) and method B1 tris of Commission Directive No. 2004/73/EC (April 29, 2004) adapting to technical progress for the 29th time Council Directive No. 67/548/EEC and subsequent amendments and of Council Regulation No. 440/2008 (30th May 2008) and Regulation No. 1907/2006 (REACH).

In the first step, a group of three females was treated with the starting dose of 300 mg/kg body weight, followed by an additional group of three females at the same dose level.

Then, a group of three females was treated with the dose of 2000 mg/kg body weight, followed by an additional group of three females at the same dose level.

The test item Ciment Fondu® was administered orally to animals, deprived of food since the previous day, in a volume of 10 mL/kg as a brown homogeneous suspension in water.

Mortality was recorded twice a day.

General observations were recorded before the first dosing, twice on D1 (60 minutes±30 minutes and between 3 and 4 hours post-dose) and then at least once a day for 14 days. Functional and neurobehavioural tests were perfomed on D1 and D7.

Animals were weighed on D1, D7 and D14.

All animals were necropsied on D15.

Under the experimental conditions adopted, results obtained were as follows:

• Mortality: no mortality occurred during the study

• Main clinical signs: no clinical signs were observed during the course of the study

• Body weight: mean body weight and body weight gains values of treated animals were normal when compared with the range of values usually found in the Centre

• Main necropsy finding: no organ or gross tissue findings were seen at necropsy

Under the experimental conditions adopted, the oral administration of Ciment Fondu® caused no mortality at 300 and 2000 mg/kg and did not induce clinical signs at these dose levels during a 14-day period, in female Sprague-Dawley rats.

Consequently, the maximal non-lethal dose is higher than 2000 mg/kg body weight.