Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 11 May 2010 and 15 June 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to GLP and internationally accepted guideline

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure

Test material

Constituent 1
Chemical structure
Reference substance name:
Kieselguhr, soda ash flux-calcined
EC Number:
272-489-0
EC Name:
Kieselguhr, soda ash flux-calcined
Cas Number:
68855-54-9
Molecular formula:
SiO2
IUPAC Name:
dioxosilane
Details on test material:
Sponsor's identification: soda-ash flux calcined kieselguhr
Description : white powder
Lot number : 211184
Date received : 10 February 2010
Expiry date : 31 December 2013
Storage conditions: room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd., Oxon, UK
- Age at study initiation: Eight to twelve weeks of age
- Weight at study initiation:
- Fasting period before study: Overnight fast immediately before dosing
- Housing: Housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes
- Diet: 2014 Teklad Global Rodent diet supplied by Harlan Laboratories U.K. Ltd., Oxon, UK ad libitum
- Water: ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25°C
- Humidity: 30 to 70%
- Air changes: At least fifteen changes per hour
- Photoperiod: Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential
Doses:
300 mg/kg (preliminary study)
2000 mg/kg (main study)
No. of animals per sex per dose:
One animal treated at a dose level of 300 mg/kg and a total of five animals were treated at a dose level of 2000 mg/kg in the study
Details on study design:
Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on day 0 (the day of dosing) and on days 7 and 14.


Results and discussion

Preliminary study:
Individual clinical observations and mortality data are given in Table 1. There was no mortality. No signs of systemic toxicity were noted during the observation period. Individual bodyweights and bodyweight changes are given in Table 2. The animal showed expected gains in bodyweight over the observation period. Necropsy findings are given in Table 3. No abnormalities were noted at necropsy. Based on the results at a dose level of 300 mg/kg, a dose level of 2000 mg/kg bodyweight was investigated.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths
Clinical signs:
Hunched posture was noted in all animals. Ataxia was also noted in one animal. All animals appeared normal three days after dosing. Individual clinical observations and mortality data are given in Table 4

Body weight:
All animals showed expected gains in bodyweight over the observation period. Individual bodyweights and bodyweight changes are given in Table 5.
Gross pathology:
No abnormalities were noted at necropsy. Individual necropsy findings are given in Table 6

Any other information on results incl. tables

Table 1: Individual Clinical Observations and Mortality Data -300mg/kg

Dose Level mg/kg

Animal Number and Sex

Effects Noted After Dosing
(Hours)

Effects Noted During Period After Dosing
(Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

300

1-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0=     No signs of systemic toxicity

Table 2: Individual Bodyweights and Bodyweight Changes -300mg/kg

Dose Level

mg/kg

Animal Number
and Sex

Bodyweight (g) at Day

Bodyweight Gain (g)
During Week

0

7

14

1

2

300

1-0 Female

166

186

198

20

12

Table 3: Necropsy Findings -300 mg/kg

Dose Level
mg/kg

Animal Number
and Sex

Time of Death

Macroscopic Observations

300

1-0 Female

Killed Day 14

No abnormalities detected

Table 4: Individual Clinical Observations and Mortality Data -2000mg/kg

Dose Level mg/kg

Animal Number and Sex

Effects Noted After Dosing
(Hours)

Effects Noted During Period After Dosing
(Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

2-0

Female

0

HA

H

H

H

H

0

0

0

0

0

0

0

0

0

0

0

0

3-0

Female

0

H

H

H

H

H

0

0

0

0

0

0

0

0

0

0

0

0

3-1

Female

0

H

H

H

H

H

0

0

0

0

0

0

0

0

0

0

0

0

3-2

Female

0

H

H

H

H

H

0

0

0

0

0

0

0

0

0

0

0

0

3-3

Female

0

H

H

H

H

H

0

0

0

0

0

0

0

0

0

0

0

0

0=      No signs of systemic toxicity

A =      Ataxia

H =      Hunched posture

Table 5: Individual Bodyweights and Bodyweight Changes -2000mg/kg

Dose Level

mg/kg

Animal Number
and Sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

2000

2-0 Female

178

199

204

21

5

3-0 Female

187

192

212

5

20

3-1 Female

196

203

216

7

13

3-2 Female

186

195

213

9

18

3-3 Female

189

195

203

6

8

Table 6: Individual Necropsy Findings -2000mg/kg

Dose Level
mg/kg

Animal Number
and Sex

Time of Death

Macroscopic Observations

2000

2-0 Female

Killed Day 14

No abnormalities detected

3-0 Female

Killed Day 14

No abnormalities detected

3-1 Female

Killed Day 14

No abnormalities detected

3-2 Female

Killed Day 14

No abnormalities detected

3-3 Female

Killed Day 14

No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of kieselguhr soda ash flux calcined was >2000mg/kg and is therefore not classified in accordance with CLP Regulation (EC) no. 1272/2008