Registration Dossier

Administrative data

Description of key information

Based on an in vitro skin irritation test, conducted according to OECD 439 and GLP principles, and based on an in vivo skin irritation test, conducted according to OECD 404 and GLP principles, it was concluded that the substance is not irritating to the skin. Based on an in vivo eye irritation study, conducted in accordance with OECD 405 and according to GLP principles, it was concluded that the substance is also not irritating to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 22, 2010 - November 26, 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study has been performed in accordance with OECD 404 (2002), EU Method B.4 (2008), EPA OPPTS 870.2500 (1998) and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(2002)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
(1998)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 13 - 14 weeks
- Weight at study initiation: 3.4 - 3.5 kg
- Housing: individually in ABS - plastic rabbit cages
- Diet: ad libitum (autoclaved hay and Altromin 2123 maintenance diet)
- Water: ad libitum (tap water)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: the substance was moistened with aqua ad injectionem
Controls:
other: the untreated right side of the dorsal area served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g

VEHICLE
- Vehicle: aqua ad injectionem (Delta Select, lot no. 05007A, expiry date: June 2013)
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 females (1 female subsequently followed by 2 females)
Details on study design:
TEST SITE
Approximately 25 hours before treatment, the dorsal fur was clipped with electric clippers.
The test item was applied to a gauze patch and was moistened with aqua ad injectionem.
The patch was then applied to the skin on a small area (approx. 6 cm^2) on the left side of the dorsal area.
The gauze was held in place with non-irritating tape. The patch was fixed with a semi-occlusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing: yes, using aqua ad injectionem
- Time after start of exposure: 4 hours

OBSERVATIONS
- Clinical signs: approximately 1, 24, 48 and 72 hours after patch removal
- Body Weight: at the start of the study and 72 hours after patch removal
- Irritation: the skin reactions were assessed at approximately 1, 24, 48 and 72 hours after patch removal. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM
The irritation was assessed according to the numerical scoring system according to OECD 404.
Irritation parameter:
erythema score
Basis:
animal: #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72h after patch removal
Score:
0
Max. score:
4
Remarks on result:
other: No irritant or corrosive effects were observed
Irritation parameter:
edema score
Basis:
animal: #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72h after patch removal
Score:
0
Max. score:
4
Remarks on result:
other: No irritant or corrosive effects were observed
Irritant / corrosive response data:
No irritant or corrosive effects were observed
Other effects:
- No significant clinical signs of toxicity were observed
- No mortalities were observed
- No significant body weight changes were observed
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a skin irritation study with rabbits, performed in accordance with OECD 404 (2002), EU Method B.4 (2008), EPA OPPTS 870.2500 (1998) and according to GLP principles, no irritation was observed.
Executive summary:

In an in vivo skin irritation study in rabbits, conducted in accordance with OECD 404 (2002), EU Method B.4 (2008), EPA OPPTS 870.2500 (1998) and according to GLP principles, 3 female rabbits were semi-occlusively exposed for 4 hours to 0.5 g of the (moistened) substance. No irritant or corrosive effects were observed. No significant clinical signs of toxicity nor mortalities were observed. Based on the result of this study, the substance does not need to be classified for skin irritation/corrosion in accordance with the CLP Regulation.

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:
experimental study
Adequacy of study:
key study
Study period:
November 17, 2010 - January 19, 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study has been performed in accordance with OECD 405 (2002), EU Method B.5 (2008), EPA OPPTS 870.2400 (1998) and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(2002)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
(1998)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: approximately 19 weeks old
- Weight at study initiation: >2 kg
- Housing: individually housed in ABS - plastic rabbit cages, floor 4200 cm^2
- Diet: autoclaved hay and Altromin 2123 maintenance diet (lot no. 0955), ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): at least 10 per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

IN-LIFE DATES: From: November 28, 2010 To: December 3, 2010
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
Not applicable (the treated eyes were not rinsed)
Observation period (in vivo):
Not applicable (after 72 hours no ocular lesions were found in any animal)
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE: Not applicable
SCORING SYSTEM: in accordance with OECD 405
TOOL USED TO ASSESS SCORE: fluorescein (only 72 hours after installation)
Irritation parameter:
cornea opacity score
Basis:
other: Mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0
Max. score:
4
Remarks on result:
other: Individual mean scores: 0-0-0
Irritation parameter:
iris score
Basis:
other: Mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0
Max. score:
2
Remarks on result:
other: Individual mean scores: 0-0-0
Irritation parameter:
conjunctivae score
Basis:
other: Mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0
Max. score:
3
Remarks on result:
other: Individual mean scores: 0-0-0
Irritation parameter:
chemosis score
Basis:
other: Mean for animals #1, #2 and #3
Time point:
other: Mean value of score at 24, 48 and 72 h after installation
Score:
0
Max. score:
4
Remarks on result:
other: Individual mean scores: 0-0-0
Irritant / corrosive response data:
- In none of the animals, any effects on the cornea were observed
- In none of the animals, any effects on the iris were observed
- In all animals, conjunctival redness (score: 1) was observed after 1 hour
- In animal #2 and #3 chemosis (score: 1) was observed after 1 hour
Other effects:
- Animal #1 and #3 had a slight discharge after 1 hour

- No mortalities nor significant clinical signs of toxicity were observed

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute eye irritation study in 3 rabbits, conducted in accordance with OECD 405 (2002), EU Method B.5 (2008), EPA OPPTS 870.2400 (1998) and according to GLP principles, irritant effects were observed which were fully reversible within 24 hours. Based on the results of this study, the substance does not need to be classified for eye irritation.
Executive summary:

An acute eye irritation study was conducted in 3 rabbits in accordance with OECD 405 (2002), EU Method B.5 (2008), EPA OPPTS 870.2400 (1998) and according to GLP principles. In none of the animals, any effects on the cornea and iris were observed. Conjunctival redness (score: 1) was observed in all animals after 1 hour. In two animals chemosis (score: 1) was observed after 1 hour. All ocular effects fully reversed within 24 hours. Based on the results of this study, the substance does not need to be classified for eye irritation.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In an in vitro skin irritation test according to OECD 439 using a human skin model ( EPISKIN Standard Model), the influence of Halophosphate on the viability of human skin was tested. After 15 minutes, the substance was removed and cells were cultured for 42 hours. Survival of unexposed skin was set at 100%, the positive control had a mean cell viability of 6% whereas Halophosphate showed cell viability of 101%. Since the mean relative tissue viability after exposure to halophosphate was above 50%, it can be concluded that Halophosphate is not irritating in the in vitro skin irritation test.

In an in vivo skin irritation study in rabbits, conducted in accordance with OECD 404 (2002), EU Method B.4 (2008), EPA OPPTS 870.2500 (1998) and according to GLP principles, 3 female rabbits were semi-occlusively exposed for 4 hours to 0.5 g of the substance. No irritant or corrosive effects were observed. No significant clinical signs of toxicity were observed.

Eye irritation

An eye irritation study was conducted in 3 rabbits in accordance with OECD 405 (2002), EU Method B.5 (2008), EPA OPPTS 870.2400 (1998) and according to GLP principles. In none of the animals, any effect on the cornea and iris was observed. Conjunctival redness (score: 1) was observed in all animals after 1 hour. In two animals chemosis (score: 1) was observed after 1 hour. All ocular effects fully reversed within 24 hours, therefore it can be concluded that Halophosphate is not irritating in the in vivo eye irritation test.


Justification for selection of skin irritation / corrosion endpoint:
There are 2 studies available, an in vitro and an in vivo study. Both studies are suitable for the endpoint conclusion, the in vivo study is selected.

Justification for selection of eye irritation endpoint:
Only one study available

Justification for classification or non-classification

Based on the results of an in vitro skin irritation study, an in vivo skin irritation study and an in vivo eye irritation study, the substance does not need to be classified for skin or eye irritation according to CLP Regulation (EC) No 1272/2008.