Ammonium perchlorate

Acute Toxicity: oral

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

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:

no

Test material

Test material information

Constituent 1

Reference substance name:

Anhydrous Sodium Perchlorate

IUPAC Name:

Anhydrous Sodium Perchlorate

Constituent 2

Reference substance name:

Sodium perchlorate

EC Number:

231-511-9

EC Name:

Sodium perchlorate

Cas Number:

7601-89-0

IUPAC Name:

sodium perchlorate

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 or test system 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:

other: 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.

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.