Ammonium perchlorate

Endpoint summary

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

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:

no

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

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:

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

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

Value:

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

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/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: 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:

other: 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)

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

Value:

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.