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:
01 - 29 April 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study. Full read-across justification report is attached in section 13.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Anhydrous Sodium Perchlorate
- Physical state: white powder
- Analytical purity: 98.21%
- Purity test date: 10/01/08
- Lot/batch No.: GRL 0005/08
- Expiration date of the lot/batch: February 2010
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: 8 weeks
- Weight at study initiation: 208 ± 9g
- Fasting period before study: 18 hours prior to dosing till 4 hours after dosing
- Housing: polycarbonate cages with stainless steel lid (48x27x20cm); each cage contained autoclaved sawdust (SICSA, Alfortville, France)
- Diet: SSNIFF R/M-H pelleted maintenance diet (ad libitum except for fasting period) SSNIFF Spezialdiaten GmbH, Soest, Germany
- Water : drinking water filtered by a FG Millipore membrane (0.22µm) provided ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 30 - 70%
- Air changes (per hr): 12 cycles of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 hr/12 hr (7:00-19:00)


IN-LIFE DATES: From: 01 April 2008 To: 29 April 2008

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 300 & 2000 mg/kg
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: solubility
- Lot/batch no. (if required): Not reported
- Purity: purified water prepared at CIT by reverse osmosis

MAXIMUM DOSE VOLUME APPLIED: 2.2 mls
DOSAGE PREPARATION (if unusual): N/A

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: animal welfare reasons as no information on the toxic potential of the test item was available
Doses:
300 mg/kg and 2000 mg/kg
No. of animals per sex per dose:
3 females at 300 mg/kg
6 females at 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed frequently during the hours following administration of the test item and at least once per day
thereafter; bodyweights recorded just prior to administration of the test item on day 1 and then on days 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examination of main organs at necropsy
Statistics:
No statistical analysis was performed

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no mortalities
Clinical signs:
No clinical signs were noted at 300mg/kg/day, whereas hypoactivity was noted for all animals given 2000mg/kg/day during the 2 hours following
treatment.
Body weight:
When compared to CIT historical control animals, a slightly lower body weight gain was noted
between day 1 and day 8 in 1/3 females (No. 09) given 2000 mg/kg (33 g versus 34 g in CIT
historical control animals, returning to normal thereafter) and between day 8 and day 15 in
1/3 females (No. 02) given 300 mg/kg and 1/3 females (No. 04) given 2000 mg/kg (7 g and 6 g
versus 8 g in CIT historical control animals respectively). These differences correspond to a lack
less than 1% when considering the final body weight of these animals. As a result, they were not
considered significant. The body weight gain of the other animals was not affected by treatment
with the test item.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.
Other findings:
- Organ weights: N/A
- Histopathology: N/A
- Potential target organs: N/A
- Other observations: None

Any other information on results incl. tables

No deaths and no clinical signs were observed in the three females given 300 mg/kg/day. When compared to CIT historical control animals, a slightly lower body weight gain was noted in 1/3 females between day 8 and day 15 (7 g versus 8 g in CIT historical control animals). As this corresponds to a lack less than 1% when considering the final body weight of this animal, it was not considered significant. The body weight gain of the other animals was not affected by treatment with the test item. Dose-level of 2000 mg/kg (three females then confirmation on three other females) no deaths occurred. Hypoactivity was noted in all animals within 2 hours of treatment; (see Table 1 below). When compared to CIT historical control animals, a slightly lower body weight gain was noted in 1/3 females between day 1 and day 8 (33 g versus 34 g in CIT historical control animals, returning to normal thereafter) and in another female between day 8 and day 15 (6 g versus 8 g in CIT historical control animals). This minor change in body weight was not considered as significant. The body weight gain of the other animals was not affected by treatment with the test item (Tables 2 & 3 below). At necropsy, no apparent abnormalities were observed in any animal.

Table 1: Individual clinical signs and mortality 

Dose level (mg/kg)

 

Time

Females

Mortality

Clinical signs

300

15 min, 1-2hr-4hr - D2 to D15

01-02-03

No

None

2000

(first assay)

15 min

 

1 hr

 

 

2 hr

 

4hr- D2 to D15

04-05-06

 

04

05-06

 

04-05-06

 

04-05-06

No

 

No

No

 

No

 

No

None

 

Hypoactivity

None

 

Hypoactivity

 

None

 

2000

(confirmatory assay)

15 min

 

 

1hr – 2 hr

 

4 hr – D2 to D15

08

07-09

 

07-08-09

 

07-08-09

No

No

 

No

 

No

Hypoactivity

None

 

Hypoactivity

 

None

 

min: minutes

hr: hour

D: day

Table 2: Individual and mean body weight and weekly body weight change of treated rats (g)

Dose level

(mg/kg)

Vol.

mL/kg

Sex

Animals

Days

1

(1)

8

(1)

15

300

10

Female

01

214

43

257

13

270

02

190

44

234

7

241

03

211

52

263

9

272

 

Mean

205

46

251

10

261

SD

13

5

15

3

17

 

2000

(first assay)

10

Female

04

220

46

266

6

272

05

205

37

242

20

262

06

215

35

250

19

269

 

Mean

213

39

253

15

268

SD

8

6

12

8

5

 

2000

(confirmatory assay)

10

Female

07

208

43

251

14

265

08

202

35

237

25

262

09

206

33

239

24

263

 

Mean

205

37

242

21

263

SD

3

5

8

6

2

 

(1): bodyweight gain

SD: standard deviation

Table 3: Body weight - CIT historical data of control animals dosed (water) by oral route

Volume

(mL/kg)

Sex

Days

 

1

(1)

8

(1)

15

10

(water)

Female

Mean

196

39

236

16

252

SD

7

5

9

8

12

n

30

30

30

30

30

(1): bodyweight gain

SD: standard deviation

n:  number of animals 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: Regulation (EC) No 1972/2008 on CLP
Conclusions:
Under the experimental conditions of this study, the oral LD50 of the test item ANHYDROUS SODIUM PERCHLORATE (batch No. lot moyen du 10/01/08 test) was higher than 2000 mg/kg in rats.
Executive summary:
The acute oral toxicity of the test item ANHYDROUS SODIUM PERCHLORATE (batch No. lot moyen du 10/01/08 test) was evaluated in rats according to OECD (No. 423, 17th December 2001) and EC (2004/73/EC, B.1 tris, 29th April 2004) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. Under the experimental conditions of this study, the oral LD0 of the test item ANHYDROUS SODIUM PERCHLORATE (batch No. lot moyen du 10/01/08 test) was higher than 2000 mg/kg in rats.