Registration Dossier

Administrative data

Description of key information

Skin irritation: Three in vivo studies are available for skin irritation. The study reported by Bullock (1972) as the key study is conducted according to modern guidelines and performed in a GLP accredited facility. The results of this study are sufficient for classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP). The additional studies (Birch, 1972 and Birch, 1973) are provided to support this conclusion. 
Eye irritation: Two in vivo studies are available for eye irritation. The key study (Freeman C, 1987) is conducted to a protocol similar to modern day guidelines and was performed in a GLP accredited facility. Despite only having assessed the eyes of two animals, the results are deemed sufficient for classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP). The supporting study (Birch MD, 1973) supports the use of the key study.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
In vivo study performed prior to the update of REACH in 2016.
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Animals were examined at 24 and 72 hours only. No data reported on reversibility of effects. Study uses intact and abraded skin. No controls were included in the study.
Qualifier:
equivalent or similar to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Animals were examined at 24 and 72 hours only. No data reported on reversibility of effects. Study uses intact and abraded skin. No controls were included in the study.
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
No data
Type of coverage:
not specified
Preparation of test site:
other: Shaved, abraded and intact
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied : 0.5 g


VEHICLE
Used as received.
Duration of treatment / exposure:
24 hours
Observation period:
Up to 72 hours
Number of animals:
6, 3 males and 3 females.
Details on study design:
TEST SITE
- Type of wrap if used: Rubber (occlusive)


REMOVAL OF TEST SUBSTANCE
No data


SCORING SYSTEM:
The Draize dermal method of testing primary irritant substance as described in the Code of Federal Refulations under the Federal Hazardous Substances Labelling Act, Part 191.11, Chapter 1, Title 21.

Compounds producing combined averages (primary irritation indexes) of 2 or less are only mildly irritating; indexes from 2 to 5 are moderate irritants and those with scores above 5 are considered severe or primary irritants.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hrs
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hrs
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hrs
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
The primary dermal irritation index is calculated by the following:

Total ÷ 4 = Primary dermal irritation index
Other effects:
No data

Table 1: Results for Disodium phosphate

Exposure time Hours

Rabbit No.

Mean

 

8M

15M

16M

32F

33F

34F

 

Score

Score

Score

Score

Score

Score

Erythema

24

Intact

1

1

0

0

0

0

0.33

72

Intact

0

0

0

0

0

0

0.00

24

Abraded

3

4

3

3

3

4

3.33

72

Abraded

3

3

3

3

3

2

2.83

Subtotal

6.49

Oedema

24

Intact

0

0

0

0

0

0

0.00

72

Intact

0

0

0

0

0

0

0.00

24

Abraded

1

2

1

1

1

1

1.17

72

Abraded

2

1

2

1

1

1

1.33

Subtotal

2.50

Total score

8.99

(Total/4) Primary Irritation Index

2.25

Result

Moderate Irritant

 

Interpretation of results:
GHS criteria not met
Conclusions:
This study has been selected as the key study because the results are sufficient in order to derive a reliable conclusion on classification and labelling when viewed in conjunction with the supporting data.
Disodium hydrogenorthophosphate is not considered to be classified according to Regulation (EC) No. 1272/2008 (EU CLP).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Remarks:
Study was performed prior to the update of the REACH Regulation and prior to the validation of in vitro test methods.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1986-08-11 to 1986-08-15
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
eyes were irrigated after 20 - 30 sec, rather than after 1 h recommended in the guideline.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Animals, Inc., Denver, Pennsylvania.
- Age at study initiation: 2.43 - 2.71 kg
- Weight at study initiation: young adult
- Housing: individually housed in stainless steel rabbit cages and DACB cageboard bedding was used in the litter pans.
- Diet: ad libitum
- Water:ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68 - 75 ºC
- Humidity (%): 53 - 60 %
- Photoperiod: 12 h dark / 12 h light
Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye of the rabbits were used for treatment, the left eyes served as controls.
Amount / concentration applied:
0.1 g per test eye
Duration of treatment / exposure:
The eyes of two of the rabbits remained unwashed and the eyes of the remaining two rabbits were gently washed approximately 20 - 30 sec after treatment.
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
4 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: gently washed with 100 mL of tap water . The rate of application of the tap water was approximately 100 mL/min.
- Time after start of exposure: 20 - 30 sec


SCORING SYSTEM: Draize


TOOL USED TO ASSESS SCORE: after the 24 h examination with a penlight type light, the eyes were examined with the aid of 2 % sodium fluorescein dye.
Irritation parameter:
cornea opacity score
Basis:
animal: both animals tested
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal: both animals tested
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal: both animals tested
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: both animals tested
Time point:
24/48/72 h
Score:
0.66
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Irritant / corrosive response data:
One h after dosing, mild conjuncitvitis was observed in all eyes. At the 24 h scoring, both of the unwashed eyes had mild conjunctivitis and one of the washed eyes had a slight discharge. Within 48 h of dosing, washed eyes had recovered; both unwashed eyes exhibited slight conjunctivitis which had resolved by the 72 h scoring. Washing the eyes with tap water shortly after exposure decreased both the severity and the duration of the irritation observed.
Other effects:
The mean body weight of the animals was 2.59 ± 0.120 kg on the day prior to dosing. All animals remained healthy throughout the study.

Pretest eye examination

Animal No.

Exam method

Right eye

Left eye

Body weight

(kg)

B5490M

Penlight

N

N

2.57

 

Fluorescein

N

N

B5538M

Penlight

N

N

2.64

 

Fluorescein

N

N

B5492M

Penlight

N

N

2.43

 

Fluorescein

N

N

B5477M

Penlight

N

N

2.71

 

Fluorescein

N

N

Mean

2.59

± SD

± 0.120

B - rabbit

N - normal

M - Male

Individual eye scores:

Animal No.

Cornea

Iris

Conjunctiva

Cornea

Opacity/Area

Iritis

Redness

Chemosis

Discharge

Stain/Area

1 hour

B5490M

0 / 0

0

0

2

3

NA

B5530M

0 / 0

0

0

2

3

NA

B5492M (w)

0 / 0

0

0

1

3

NA

B5477M (w)

0 / 0

0

0

1

3

NA

Primary eye irritation index – unwashed 10.0/110, washed 8.0/110

24 hour

B5490M

0 / 0

0

1

0

3

0 / 0

B5530M

0 / 0

0

1

0

3

0 / 0

B5492M (w)

0 / 0

0

0

0

1

0 / 0

B5477M (w)

0 / 0

0

0

0

0

0 / 0

Primary eye irritation index – unwashed 8.0/110, washed 1.0/110

48 hours

B5490M

0 / 0

0

1

0

2

NA

B5530M

0 / 0

0

1

0

1

NA

B5492M (w)

0 / 0

0

0

0

0

NA

B5477M (w)

0 / 0

0

0

0

0

NA

Primary eye irritation index – unwashed 5.0/110, washed 0.0/110

72 hours

B5490M

0 / 0

0

0

0

0

NA

B5530M

0 / 0

0

0

0

0

NA

B5492M (w)

0 / 0

0

0

0

0

NA

B5477M (w)

0 / 0

0

0

0

0

NA

Primary eye irritation index – unwashed 0.0/110, washed 0.0/110

B - Rabbit

M - Male

(w) - Washed

NA - Not applicable

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study the author concludes that the test material is temporarily approximated to be minimally irritating to unwashed eyes and practically non-irritating to washed eyes.
This study has been selected as the key study because the results are sufficient in order to derive a reliable conclusion on classification and labelling when viewed in conjunction with the supporting data.
Disodium hydrogenorthophosphate is not considered to be classified according to Regulation (EC) No. 1272/2008 (EU CLP).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Three in vivo studies are available for skin irritation. The study reported by Bullock (1972) is selected as the key study as it is conducted according to guidelines similar to current test methods.

Justification for selection of eye irritation endpoint:
Two in vivo studies are available for eye irritation. The key study (Freeman C, 1987) is conducted to a protocol similar to modern day guidelines and was performed in a GLP accredited facility.

Justification for classification or non-classification

The data available for skin and eye irritation of disodium hydrogenorthophosphate conclude that no classification is required according to Regulation (EC) No. 1272/2008 (EU CLP). It is not considered scientifically justified on ethical grounds to repeat in vivo studies for these endpoints as the data provided is sufficient in accordance with REACH Annex XI.