Registration Dossier

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Description of key information

ANHYDROUS SODIUM PERCHLORATE was evaluated in rabbits for skin and eye irritation according to OECD guidelines 404 and 405 respectively.  The test substance was found to be non-irritant when applied to skin but irritant when applied by the ocular route.
A read-across is provided in section 13 to support the transposition from sodium perchlorate to ammonium perchlorate.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
01 April - 15 July 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 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Grimaud Freres Selection S.A.S., La Corbiere, Roussay, France
- Age at study initiation: 2-4 months
- Weight at study initiation: 2.7 ± 0.3 kg
- Housing: individually in Pajon cages (50x57x75cm)
- Diet: 110C pelleted ad libitum (SAFE, Augy, France)
- Water: Filtered - FG millipore (0.22µm) ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3°C
- Humidity: (30 -70%):
- Air changes: 12 cycles per hr of filtered non-recycled air
- Photoperiod: 12hrs dark /12 hrs light (7:00-19:00)


IN-LIFE DATES: From: 01 April 2008 To: 06 April 2008
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amounts applied: 500mg in its original form placed on a gauze pad moistened with purified water



Duration of treatment / exposure:
up to 4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 square cms
- % coverage: 100%
- Type of wrap if used: Gauze pad held by means of an hypoallergenic aerated semi-occlusive dressing and a restraining bandage


REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: After 4 hours, residual test item was wiped off by means of a dry or moistened cotton pad.


SCORING SYSTEM:
Erythema and eschar formation:
0: no erythema
1: very slight erythema (barely perceptible)
2: well defined erythema
3: moderate to severe erythema
4: severe erythema (beet redness) to slight eschar formation (injuries in depth)

Edema formation:
0: no edema
1: very slight edema (barely perceptible)
2: slight edema (edges of area well-defined by definite raising)
3: moderate edema (raised approx. 1mm)
4: severe edema (raised more than 1mm and extending beyond area of exposure)
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 - 72 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 - 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
After a 3-minute exposure (one animal), no cutaneous reactions were observed. After a 1-hour exposure (one animal) a very slight erythema was
noted from day 1 until day 3. After a 4-hour exposure (three animals) a very slight erythema was noted in all animals on day 1; it persisted on day 2
in one of them. Mean scores over 24, 48 and 72 hours for each animal were 0.3, 0.0 and 0.0 for erythema and 0.0, 0.0 and 0.0 for edema.

After a 3-minute exposure (one animal) no cutaneous reactions were observed (Table1).

After a 1-hour exposure (one animal) a very slight erythema was noted from day 1 until day 3 (Table 2).

After a 4-hour exposure (three animals) a very slight erythema was noted in all animals on day 1; it persisted on day 2 in one of them. Mean scores over 24, 48 and 72 hours for each animal were 0.3, 0.0 and 0.0 for erythema and 0.0, 0.0 and 0.0 for edema (Table 3).

Table 1: Three minute exposure - Cutaneous examinations and mean values of the

scores recorded for the first animal (24, 48 and 72 hours) 

Rabbit No.

Dermal Irritation

Scores

Mean irritation score (1)

1 hour

Day 1

24 hours

Day 2

48 hours

Day 3

72 hours

Day 4

62

Erythema

0

0

0

0

0.0

Edema

0

0

0

0

0.0

Other

*

*

*

*

 

(1): mean of scores on days 2, 3 & 4

*: none

Table 2: One hour exposure - Cutaneous examinations and mean values of the scores recorded

for the first animal (24, 48 and 72 hours)

Rabbit No.

Dermal Irritation

Scores

Mean irritation score (1)

1 hour

Day 1

24 hours

Day 2

48 hours

Day 3

72 hours

Day 4

62

Erythema

1

1

1

0

0.7

Edema

0

0

0

0

0.0

Other

*

*

*

*

 

(1): mean of scores on days 2, 3 & 4

*: none

Table 3: Four hour exposure - Individual cutaneous examinations and mean values of the scores recorded

for each animal (24, 48 and 72 hours)

Rabbit No.

Dermal Irritation

Scores

Mean irritation score (1)

Interpretation

(+)

(-)

1 hour

Day 1

24 hours

Day 2

48 hours

Day 3

72 hours

Day 4

62

Erythema

1

1

0

0

0.3

(-)

Edema

0

0

0

0

0.0

(-)

Other

*

*

*

*

 

 

 

73

Erythema

1

0

0

0

0.0

(-)

Edema

0

0

0

0

0.0

(-)

Other

*

*

*

*

 

 

 

74

Erythema

1

0

0

0

0.0

(-)

Edema

0

0

0

0

0.0

(-)

Other

*

*

*

*

 

 

(1): mean of scores on days 2, 3 and 4

(+): irritant according to EEC criteria

(-): non-irritant according to EEC criteria

*: none

Interpretation of results:
not irritating
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 test item ANHYDROUS SODIUM PERCHLORATE (batch No. lot moyen du 10/01/08 test) was
slightly irritant when applied topically to rabbits. However, according to the classification criteria laid down in Council Directive 67/548/EEC
(and subsequent adaptations), the test item was considered non-irritant.
Executive summary:

The potential of the test item ANHYDROUS SODIUM PERCHLORATE (batch No. lot moyen du 10/01/08 test) to induce skin irritation was evaluated in rabbits according to OECD (No. 404, 24th April 2002) and EC (2004/73/EC, B.4, 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 test item ANHYDROUS SODIUM PERCHLORATE (batch No. lot moyen du 10/01/08 test) was slightly irritant when applied topically to rabbits. However, according to the classification criteria laid down in Council Directive 67/548/EEC and EU regulation (EC) No 1272/2008 (CLP), the test item was considered non-irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
08 April - 04 May 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 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Grimaud Freres Selection S.A.S., La Corbiere, Roussay, France
- Age at study initiation: 2 - 4 months
- Weight at study initiation: 3.0 ± 0.2 kg
- Housing: Individually in Pajon cages (50 x 57 x 75 cm)
- Diet: ad libitum 110C pelleted diet (SAFE, Augy, France).
- Water: ad libitum filtered by a FG Millipore membrane (0.22 micron)
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30 - 70%
- Air changes (per hr): approx. 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 08 April 2008 To: 04 May 2008
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
100 mg of the test item in its original form
Duration of treatment / exposure:
One application to one eye and there was no rinsing after administration. The other eye acted as control.
Observation period (in vivo):
up to 12 days
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
The test material was not removed after exposure


SCORING SYSTEM:

Conjunctival lesions and discharge
Chemosis (lids and/or nictitating membranes)
. no swelling ...............................................................................................................................0
. any swelling above normal (includes nictitating membranes) ...................................... ..1
. obvious swelling with partial eversion of lids......................................................................2
. swelling with lids about half-closed......................................................................................3
. swelling with lids more than half-closed .............................................................................4


Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)
. blood vessels normal ...............................................................................................................0
. a number of blood vessels definitely hyperemic (injected).................................................1
. diffuse, crimson colour, individual vessels not easily discernible ....................................2
. diffuse, beefy red........................................................................................................................3

Discharge
. absence of discharge .............................................................................................................. .0
. slight discharge (does not include small amounts normally found in
inner canthus) ..............................................................................................................................1
. discharge with moistening of lids and hairs adjacent to lids...............................................2
. discharge with moistening of lids and hairs on wide area around the eye........................3

Iris lesions
. normal ..........................................................................................................................................0
. markedly deepened rugae, congestion, swelling, moderate circum-corneal
hyperemia, or injection, any of these or combination of any thereof, iris still
reacting to light (sluggish reaction is positive) .......................................................................1
. no reaction to light, haemorrhage, gross destruction (any or all of these) ......................2

Corneal lesions
Degree of opacity (area most dense taken for reading)
. no ulceration or opacity..............................................................................................................0
. scattered or diffuse areas of opacity (other than slight dulling or normal lustre),
details of iris clearly visible ..........................................................................................................1
. easily discernible translucent area, details of iris slightly obscured ...................................2
. nacreous areas, no details of iris visible, size of pupil barely discernible ..........................3
. opaque cornea, iris not discernible through the opacity.......................................................4

Area of opacity
. one quarter (or less) but not zero..............................................................................................1
. greater than one quarter but less than a half...........................................................................2
. greater than one half but less than three quarters..................................................................3
. greater than three quarters up to whole area. .........................................................................4

Any other lesions observed were noted.

TOOL USED TO ASSESS SCORE: UV lamp/ 0.5% sodium fluorescein
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72h
Score:
2.4
Max. score:
4
Reversibility:
fully reversible within: 7-12 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 7-12 days
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
mean
Remarks:
2 rabbits
Time point:
other: 24-48-72h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
cornea opacity score
Remarks:
Opacity intensity
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72h
Score:
1.4
Max. score:
4
Reversibility:
fully reversible within: 72 hours/ 6 days
Irritation parameter:
cornea opacity score
Remarks:
Opacity area
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72h
Score:
1.6
Max. score:
4
Reversibility:
fully reversible within: 72 hours / 6 days
Irritant / corrosive response data:
Slight to marked chemosis was observed in all animals from day 1 until day 6, 9 or 11.
Slight to severe redness of the conjunctiva was noted in all animals from day 1 until day 6 (one animal) or 11 (two animals).
A clear to whitish purulent discharge was noted in all animals from day 1 until day 3 (two animals) or 4 (one animal).
An iritis was noted in 2/3 animals from day 1 until day 3 or 5 and on day 2 in 1/3 animals.
A slight or moderate corneal opacity was recorded in 2/3 animals on days 2 and 3. In the third animal, a slight to severe corneal opacity, which covered sometimes the whole area of the cornea, was noted from day 1 until day 5.
Brownish area on the third eyelid was observed in 1/3 animals from day 7 until day 11.
Mean scores calculated for each animal over 24, 48 and 72 hours were 2.0, 2.3 and 3.0 for chemosis, 2.3, 2.0 and 2.7 for redness of the conjunctiva, 0.7, 0.3 and 1.0 for iris lesions and 1.0, 1.0 and 2.3 for corneal opacity.

Table 1a: Individual ocular examinations and mean values of the scores recorded for each animal (24, 48 and 72 hours)

Rabbit Number

Region of Eye

Description of ocular reactions

Scores

Mean irritation score (1)

Interpretation

(+)

(-)

1 hour

Day 1

24 hours

Day 2

48 hours

Day 3

72 hours

Day 4

62

Conjunctivae

Chemosis

2

2

2

2

2.0

(+)

Redness

3

3

2

2

2.3

(-)

 

Discharge

1

2

1

0

1.0

 

 

Iris

 

1

1

1

0

0.7

(-)

 

Corneal opacity

Intensity

0

2

1

0

1.0

(-)

Area

0

1

1

0

0.7

 

 

Other

 

*

*

*

*

 

 

Fluorescein

 

/

U

U

U

 

 

 

73

Conjunctivae

Chemosis

2

3

2

2

2.3

(+)

Redness

2

2

2

2

2.0

(-)

 

Discharge

2

2

1

0

1.0

 

 

Iris

 

0

1

0

0

0.3

(-)

 

Corneal opacity

Intensity

0

2

1

0

1.0

(-)

Area

0

1

1

0

0.7

 

 

Other

 

*

*

*

*

 

 

Fluorescein

 

/

U

U

U

 

 

 

816

Conjunctivae

Chemosis

2

3

3

3

3.0

(+)

Redness

2

2

3

3

2.7

(+)

 

Discharge

2

S

S

S

(2)

 

 

Iris

 

1

1

1

1

1.0

(+)

 

Corneal opacity

Intensity

2

2

3

2

2.3

(+)

Area

2

4

4

2

3.3

 

 

Other

 

Su

*

*

*

 

 

Fluorescein

 

/

U

U

U

 

 

 

 

(1): mean of scores on days 2, 3 and 4       (2): not calculable

(+): irritant according to EEC criteria           U: fluorescein (batch No. L653 & P756)

(-): non-irritant according to EEC criteria     /: fluorescein not used

S: whitish purulent discharge Su: residual test item

*: none

Table 1b: Individual ocular examinations of the scores recorded for each animal (from Day 5 to Day 12)

Rabbit Number

Region of Eye

Description of ocular reactions

Scores

Day 5

Day 6

Day7

Day 8

Day 9

Day 10

Day 11

Day 12

62

Conjunctivae

Chemosis

1

1

0

-

-

-

-

-

Redness

1

1

0

-

-

-

-

-

 

Discharge

0

0

0

-

-

-

-

-

 

Iris

 

0

0

0

-

-

-

-

-

 

Corneal opacity

Intensity

0

0

0

-

-

-

-

-

Area

0

0

0

-

-

-

-

-

 

Other

 

*

*

*

-

-

-

-

-

Fluorescein

 

/

/

/

-

-

-

-

-

 

73

Conjunctivae

Chemosis

1

1

1

1

1

1

1

0

Redness

2

2

2

2

1

1

1

0

 

Discharge

0

0

0

0

0

0

0

0

 

Iris

 

0

0

0

0

0

0

0

0

 

Corneal opacity

Intensity

0

0

0

0

0

0

0

0

Area

0

0

0

0

0

0

0

0

 

Other

 

*

*

*

*

*

*

*

*

Fluorescein

 

/

/

/

/

/

/

/

/

 

816

Conjunctivae

Chemosis

2

1

1

1

1

0

0

0

Redness

2

2

1

1

1

1

1

0

 

Discharge

0

0

0

0

S

S

0

0

 

Iris

 

1

0

0

0

0

0

0

0

 

Corneal opacity

Intensity

1

0

0

0

0

0

0

0

Area

1

0

0

0

0

0

0

0

 

Other

 

*

*

ZB

ZB

ZB

ZB

ZB

*

Fluorescein

 

U

U

/

/

/

/

/

/

 

 *: none                                                                       ZB: brownish area on the third eyelid

U: fluorescein (batch No. P756)                                  -:  ocular examination not performed

/: fluorescein not used

Interpretation of results:
other: Category 2
Remarks:
Criteria used for interpretation of results: other: Regulation (EC) No 1272/2008
Conclusions:
Under the experimental conditions of the study, the test item ANHYDROUS SODIUM PERCHLORATE (batch No. lot moyen du 10/01/08 test) was
irritant when administered by the ocular route to rabbits.
Executive summary:
The potential of the test item ANHYDROUS SODIUM PERCHLORATE (batch No. lot moyen du 10/01/08 test) to induce ocular irritation was evaluated in rabbits according to OECD (No. 405, 24th April 2002) and EC (2004/73/EC, B.5, 29th April 2004) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. Under the experimental conditions of the study, the test item ANHYDROUS SODIUM PERCHLORATE (batch No. lot moyen du 10/01/08 test) was irritant when administered by ocular route to rabbits and should be classified as Irritant, Category 2 under CLP (GHS).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

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).

Skin irritation:

In a test on Sodium Perchlorate, three rabbits were exposed by dermal route (semiocclusive) to sodium perchlorate during 4 hours according to the OECD 404 guideline. After a 3-minute exposure (one animal), no cutaneous reactions were observed. After a 1-hour exposure (one animal) a very slight erythema was noted from day 1 until day 3. After a 4-hour exposure (three animals) a very slight erythema was noted in all animals on day 1; it persisted on day 2 in one of them. Mean scores over 24, 48 and 72 hours for each animal were 0.3, 0.0 and 0.0 for erythema and 0.0, 0.0 and 0.0 for edema. This pattern of results does not warrant classification.

Ammonium appears to be less irritating than Sodium based on the respective IUCLID datasets of Ammonium Chloride and Sodium Chloride in rabbits, in spite of the lower pH of the solutions. Therefore the change in cation in Ammonium Perchlorate vs. Sodium Perchlorate should not induce any increase in skin irritation potential.

Therefore it can be concluded that Ammonium Perchlorate does not warrant classification for skin irritation.

Eye irritation:

In a test on Sodium Perchlorate, one eye of three rabbits were exposed to 100 mg of perchlorate sodium according to the OECD 405 guideline.

Slight to marked chemosis was observed in all animals from day 1 until day 6, 9 or 11. Slight to severe redness of the conjunctiva was noted in all animals from day 1 until day 6 (one animal) or 11 (two animals). A clear to whitish purulent discharge was noted in all animals from day 1 until day 3 (two animals) or 4 (one animal). An iritis was noted in 2/3 animals from day 1 until day 3 or 5 and on day 2 in 1/3 animals.

A slight or moderate corneal opacity was recorded in 2/3 animals on days 2 and 3. In the third animal, a slight to severe corneal opacity, which covered sometimes the whole area of the cornea, was noted from day 1 until day 5. Brownish area on the third eyelid was observed in 1/3 animals from day 7 until day 11.

Mean scores calculated for 3 rabbits over 24, 48 and 72 hours were 2.4 for chemosis, 2.3 for redness of the conjunctiva, 1 for discharge of the conjunctivae (2 rabbits), 0.67 for iris lesions, 1.6 for corneal opacity area and 1.4 for corneal opacity intensity.

All observed effects were fully reversible in 12 days. This pattern of results warrants classification as eye irritant.

It is unknown whether the change in cation in Ammonium Perchlorate vs. Sodium Perchlorate increases the eye irritation potential. It seems however unlikely that addition of two components with limited eye irritation potential (perchlorate and ammonium) would result in a global severe/irreversible ocular damage potential as defined by classification rules.

The plant occupational hygienist at HERAKLES Toulouse describes an absence of eye irritation cases among perchlorate workers. However this could be related to use of glasses and to a limited ocular exposure related to the processes. Therefore, in a worst-case approach, the Ammonium Perchlorate classification should be Xi, R36 based on the study on SP. This corresponds to Eye Irrit 2, H319.


Justification for selection of skin irritation / corrosion endpoint:
This study was the only study available to assess the corresponding endpoint

Justification for selection of eye irritation endpoint:
This study was the only study available to assess the corresponding endpoint

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin irritation :

According to experimental data on Sodium Perchlorate, additional bibliography data and a read-across, Ammonium Perchlorate does not need to be classified for skin irritation.

Eye irritation:

Anhydrous sodium perchlorate is classified:

- According to EU regulation (EC) No 1272/2008 (CLP): "irritant to eyes" in Category 2.

Justification : When applied to the eye of an animal, the substance produced at 3 tested animals, a positive response of cornea score opacity (>/= 1), iritis score (>/=1), calculated as the mean scores following grading at 24 and 48 hours after installation of the test material, and which fully reverses in 21 days.

- According to EU Directive 67/584/EEC, anhydrous sodium perchlorate is classified "irritating to eyes - R36".

Justification : The substance, when applied to the eye of the animal, cause significant ocular lesions which occur within 72 hours after exposure and which persist for at least 24 hours. Ocular lesions are significant because the mean score of chemosis is 2.4 (>/= 2).

According to these experimental data on Sodium Perchlorate, additional bibliography data, a read-across and also communication with the occupational hygienist at HERAKLES Toulouse production plant, Ammonium Perchlorate is considered to be classified in the same way as Sodium Perchlorate.