Registration Dossier

Administrative data

Description of key information

Oral, Dermal:
ANHYDROUS SODIUM PERCHLORATE was administered orally and dermally to rats according to OECD Guidelines 423 and 402 respectively.
The LD0 of ANHYDROUS SODIUM PERCHLORATE was found to be higher than 2000 mg/kg when administered via the oral or dermal route.
A read-across is provided in section 13 to support the transposition from sodium perchlorate to ammonium perchlorate.
Inhalation:
Due to the explosivity of finest Ammonium Perchlorate granulometries, it is impossible to carry out the test for safety (testing team and facilities) and ethical (test animals) reasons. The study is not required since reliable acute oral and dermal toxicity data are available (thanks to a read-across). Last, the study is also scientifically useless since there is no reason to suspect that effects upon inhalation could be more important or different than by oral route: oral absorption is itself quick and total, and there is no metabolism for this rather simple ion (both: see 711).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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.
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
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
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
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
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 

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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Recent GLP study conducted according to international guidelines

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
10 - 24 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.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/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: Males 367 ± 12g; Females 237 ± 7g
- Housing:
Acclimation period: 1 - 7 of same sex in polycarbonate cages with stainless steel lid (48x27x20cm).
Treatment period: individually housed in polycarbonate cages with stainless steel lid (35.5x23.5x19.3cm). Each cage contained autoclaved sawdust (SICSA, Alfortville, France).
- Diet: SSNIFF R/M-H pelleted maintenance diet (ad libitum); SSNIFF Spezialdiaten GmbH, Soest, Germany).
- Water: drinking water filtered by a FG Millipore memmbrane (0.22µm) ad libitum.
- Acclimation period: 7 days

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


IN-LIFE DATES: From: 10 April 2008 To: 24 April 2008
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Males approx. 5x7cm; Females approx. 5x6cm
- % coverage: approx. 10%
- Type of wrap if used: adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.


REMOVAL OF TEST SUBSTANCE
- Removed using a dry cotton pad
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): as a single dose at 2000mg/kg adjusted according to the bodyweight determined on the day of
treatment
- Concentration (if solution): Applied as its original formbut purified water was used in order to moisten the test item and ensure a good contact with the skin
- Constant volume or concentration used: yes
- For solids, paste formed: no


VEHICLE
Not applicable
Duration of exposure:
24 hours
Doses:
A single dose
No. of animals per sex per dose:
5 animals/sexe/dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Observed for clinical signs frequently soon after dosing and at least once per day thereafter up until day 15.
Bodyweights recorded just before dose administration on day 1 and then on days 8 and 15
- Necropsy of survivors performed: yes
Statistics:
no
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths during the study
Clinical signs:
No systemic clinical signs were observed during the study. Crusts were noted in 1/5 males (No. 5) from day 10 until day day 15 (end of the
observation period)
Body weight:
When compared to CIT historical control animals, a slightly lower bodyweight gain was noted in 1/5 females (No. 7) between day 1 and day 8;
it returned to normal thereafter
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities
Other findings:
None

No deaths and no systemic clinical signs were observed during the study (Table 1). Crusts were noted in 1/5 males from day 10 until day 15, (Table 2). When compared to CIT historical control animals, a slightly lower body weight gain was noted in 1/5 females between day 1 and day 8; it returned to normal thereafter. The body weight gain of the other animals was not affected by treatment with the test item (Tables 3 & 4). No apparent abnormalities were observed at necropsy in any animal.

Table 1: Individual clinical signs and mortality

Dose-level (mg/kg)

Time

Animals

Mortality

Clinical signs

2000

Males

Females

30 mins

01-02-03-04-05

06-07-08-09-10

No

None

2 hours

Day 2 – Day 15

 

Table 2: Cutaneous reactions

Dose-level (mg/kg)

Time

Animals

Cutaneous reactions

2000

Males

Females

Day 2 to Day 9

01-02-03-04-05

06-07-08-09-10

None

 

Day 2 – Day 15

05

-

Crusts

01-02-03-04

06-07-08-09-10

None

  

 Table 3: Individual and mean body weight and weekly body weight change (g)

Dose level

(mg/kg)

Sex

Animals

Days

1

(1)

8

(1)

15

2000

Male

01

371

37

408

55

463

02

380

43

423

49

472

03

373

45

418

51

469

04

353

36

389

49

438

05

356

37

393

50

443

 

Mean

367

40

406

51

457

SD

12

4

15

2

16

 

2000

Female

06

240

35

275

15

290

07

233

12

245

26

271

08

235

36

271

22

293

09

247

16

263

15

278

10

229

38

267

32

299

 

 

 

 

 

 

Mean

237

27

264

22

286

SD

7

12

12

7

11

(1): bodyweight gain 

SD: standard deviation

Table 4: Body weight - CIT historical data of control animals dosed (purified water) by dermal route

Volume

(mL/kg)

Sex

 

Days

1

(1)

8

(1)

15

5

Male

Mean

328

44

372

46

419

SD

39

13

35

8

37

n

29

29

29

29

29

 

5

Female

Mean

214

25

239

18

257

SD

11

11

16

9

20

n

30

30

30

30

30

(1): bodyweight gain

SD: standard deviation

n: number of animals

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 dermal LD50 of the test item was higher than 2000mg/kg in rats
Executive summary:

The acute dermal 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. 402, 24th February 1987) and EC (92/69/EEC, B.3, 31st July 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. Under the experimental conditions of this study, the dermal 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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Recent GLP study conducted according to international guidelines

Additional information

Justification for read-across: a full read-across report concerning extrapolation from sodium perchlorate to ammonium perchlorate is attached in IUCLID section 13 (Serfass 2010).

Oral acute:

The acute oral toxicity of ANHYDROUS SODIUM PERCHLORATE 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 ANHYDROUS SODIUM PERCHLORATE was higher than 2000 mg/kg in rats.

Although NH4+ is more toxic by oral route than Na+, the change in cation in Ammonium Perchlorate vs. Sodium Perchlorate does not induce any relevant change in single-dose toxicity at the investigated doses, when considering the regulatory cut-offs (testing at up to 2000 mg/kg complete substance).

This is coherent with the low-reliability lethality data which can be found in the literature, which indicate that both perchlorates are of similar acute oral toxicity and that the rat LD50 is between 3500 and 7000 mg/kg for Ammonium Perchlorate.

The lower pH of Ammonium Perchlorate vs. Sodium Perchlorate solutions (4-6 vs. 6-8) is considered not to influence acute oral toxicity.

Due to similar molecular weights for Ammonium Perchlorate/Sodium Perchlorate (117.5/122.4 g/mol), there is no need for conversion of dose-levels.

Therefore, the lethality dose-response data of the Sodium Perchlorate acute oral toxicity study can be directly transposed for the Ammonium Perchlorate dossier: the latter does not warrant classification for acute oral toxicity.

Dermal acute:

The acute dermal toxicity of ANHYDROUS SODIUM PERCHLORATE was evaluated in rats according to OECD (No. 402, 24th February 1987) and EC (92/69/EEC, B.3, 31st July 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. Under the experimental conditions of this study, the dermal LD0 of ANHYDROUS SODIUM PERCHLORATE was higher than 2000 mg/kg in rats.

NH4+ is non-toxic systemically when administered by dermal route at the dose equivalent to the maximal required Ammonium Perchlorate dose.

The lower pH of Ammonium Perchlorate vs. Sodium Perchlorate solutions (4 -6 vs. 6 -8) is not considered to lead to higher systemic toxicity by dermal administration.

Due to similar molecular weights for Ammonium Perchlorate/Sodium Perchlorate (117.5/122.4 g/mol), there is no need for conversion of dose-levels.

Therefore, the lethality dose-response data of the Sodium Perchlorate acute dermal toxicity study can be directly transposed for the Ammonium Perchlorate dossier: the latter does not warrant classification for acute dermal toxicity.


Justification for selection of acute toxicity – oral endpoint
This study was the only study available to assess the corresponding endpoint

Justification for selection of acute toxicity – inhalation endpoint
Fine Ammonium perchlorate granulometries, such as those which could correspond to maximal tendency to become airborne (maximal air concentrations), are classified as explosive. It is impossible to carry out the test for safety and ethical reasons.
The study is also scientifically useless since there is no reason to suspect that effects upon inhalation could be more important or different than by oral route: oral absorption is itself quick and total, and there is no metabolism for this rather simple ion (both: see 7.1.1).

Justification for selection of acute toxicity – dermal endpoint
This study was the only study available to assess the corresponding endpoint

Justification for classification or non-classification

Oral acute:

According to experimental data on Sodium Perchlorate, additional bibliography data and a read-across, Ammonium Perchlorate does not need to be classified for acute oral toxicity (LD0>2000 mg/kg bw).

Dermal acute:

According to experimental data on Sodium Perchlorate, additional bibliography data and a read-across, Ammonium Perchlorate does not need to be classified for acute dermal toxicity (LD0>2000 mg/kg bw).

Inhalation:

No data but based on the almost total oral absorption (see 7.1.1), there is no reason to suspect a higher toxicity by inhalation than by ingestion. No classification is required.