Disodium hydrogenorthophosphate

Endpoint summary

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:

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

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

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

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 or test system 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

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.