Sodium dihydrogenorthophosphate

Endpoint summary

Description of key information

Skin irritation: Three in vivo studies are available for skin irritation. The study reported by Freeman C (1990) is selected as the key study as it 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 (Bullock, 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 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:

No data

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 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Animals, Inc., Denver, Pennsylvania
- Age at study initiation: Young adult
- Weight at study initiation: 2.25 - 2.67 kg
- Housing: Individually housed in stainless steel cages with DACB cageboard bedding was used in the litter pans.
- Diet: Provided
- Water: Provided

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68 - 72 ºF
- Humidity (%): 51 - 66 %
- Photoperiod (hrs dark / hrs light): 12 h dark / 12 h light

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

physiological saline

Controls:

no

Amount / concentration applied:

0.5 g of test material.

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

Three

Details on study design:

TEST SITE
Area of exposure: From the scapular to the pelvic region. One test site was located on each side of the spinal column.
Type of wrap if used: Test material was weighed onto each 8-ply, 2 x 2 inch gauze pad and moistened with physiological saline. The gauze pad was secured to each test site with hypoallergenic tape. The entire trunk of the animal was wrapped with a semi-occlusive cheesecloth bandage.
The rabbits were dosed approximately 4 h after initiation of the light cycle.

REMOVAL OF TEST SUBSTANCE
Washing: Wrapping and pads were removed and the test sites were wiped with clean gauze moistened with methanol, then rinsed with tap water.
Time after start of exposure: 4 h.

SCORING SYSTEM: Approximately 30 min after unwrapping, the test sites of each rabbit were scored for irritation using the method of Draize. The 30 minute delay was instituted to allow for regression of pressure and hydration effects. The site was evaluated daily thereafter.

Irritation parameter:

erythema score

Basis:

other: all animals tested

Time point:

other: mean 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Irritation parameter:

edema score

Basis:

other: all animals testing

Time point:

other: mean 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

No irritation was noted on any of the test sites during any of the scoring intervals, and the test was terminated following the 72-h scoring.

Other effects:

All animals remained healthy throughout the study.

Table 3. Individual irritation scores

Animal #	Left		Right
	Erythema/eschar	Edema	Erythema/eschar	Edema
	4.5 hours:
B7879F	0	0	0	0
B7847M	0	0	0	0
B7877F	0	0	0	0
	24 hours:
B7879F	0	0	0	0
B7847M	0	0	0	0
B7877F	0	0	0	0
	48 hours:
B7879F	0	0	0	0
B7847M	0	0	0	0
B7877F	0	0	0	0
	72 hours:
B7879F	0	0	0	0
B7847M	0	0	0	0
B7877F	0	0	0	0

Table 4. The group irritation scores for each scoring interval are presented below:

Scoring Interval	Irritation Score
4.5 h	0
24 h	0
48 h	0
72 h	0
Primary Irritation Index
0 / 8.0

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study and based on the FMC rating system, the test material is temporarily approximated by the author to be non-irritating to intact skin when applied topically to New Zealand White rabbits.
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. Sodium dihydrogenorthophosphate is not considered to be classified according to Regulation (EC) No. 1272/2008 (EU CLP) as no effects were noted for the relevant parameters (erythema/eschar or oedema).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Remarks:

In vivo. 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:

1986-07-15 to 1986-07-19

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: No guideline followed

Principles of method if other than guideline:

Monosodium Phosphate (MSP) Technical was instilled into the test eyes of four New Zealand White rabbits at a dose of 0.1 g. The eyes of two rabbits remained unwashed while the eyes of the remaining two rabbits were gently washed with 100 mL of tap water approximately 20 - 30 seconds after treatment. Eyes were assessed for irritation using the method of Draize at 1, 24, 48 and 72 h after instillation.

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, USA.
- Age at study initiation: Young adult
- Weight at study initiation: 2.63 to 2.97 kg
- Housing: Individual housing in stainless steel rabbit cages. DACB cageboard bedding was used in the litter pans.
- Diet: Ad libitum
- Water: Ad libitum
- Sex of animals: Male


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 69 - 74ºF
- Humidity (%): 52 - 58 %
- Photoperiod: 12 h dark / 12 h light


IN-LIFE DATES: From: 15-07-1986 To: 19-7-1986

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye of each rabbit was treated; and the remaining left eye was used as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 g

Duration of treatment / exposure:

2 rabbits were exposed for approximately 30 seconds after treatment.
2 rabbits remined unwashed and therefore exposed for 72 h.

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

4 animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: The eyes of two rabbits remained unwashed. The remaining two rabbits were gently washed with 100 mL of tap water at a rate of 100 mL per minute.
- Time after start of exposure: approximately 20 - 30 seconds after treatment.


SCORING SYSTEM: Draize. The primary irritation index was calculated separately for both washed and unwashed eyes for each scoring interval. Additional assessment of irritation provided by FMC Internal guidelines.


TOOL USED TO ASSESS SCORE: 2 % sodium fluorescein

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

other: all animals tested

Time point:

24/48/72 h

Score:

0.6

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

other: all animals tested

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

other: all animals tested

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

chemosis score

Basis:

other: all animals tested

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

One-hour after instillation, all eyes exhibited mild conjunctivitis. At the 24-h scoring, one of the washed had slight conjunctival redness; both unwashed eyes had slight conjuncitvitis. Washed eyes recovered within 48 h and unwashed eyes recovered within 72 h of dosing. Washing the eyes with tap water shortly after exposure slightly decreased both the severity and the duration of the irritation observed.

Other effects:

None reported

Table 1. Pretest eye examination:

Animal No.	Exam method	Right eye	Left eye	Body weight
B5431M	Penlight	N	N	2.63
	Fluorescein	N	N
B5436M	Penlight	N	N	2.97
	Fluorescein	N	N
B5430M	Penlight	N	N	2.97
	Fluorescein	N	N
B5432M	Penlight	N	N	2.70
	Fluorescein	N	N
Mean				2.82
± S.D.				± 0.178

Table 2. Individual eye scores: 1 hour

Animal Number	Cornea	Iris	Conjunctivae			Other comments
	Opacity/Area	Iritis	Redness	Chemosis	Discharge
B5431M	0 / 0	0	1	1	3	0
B5436M	0 / 0	0	1	1	3	0
B5430M (w)	0 / 0	0	0	1	3	0
B5432M (w)	0 / 0	0	1	0	3	0

Primary Eye Irritation Index = Unwashed 10.0/110, washed 8.0/110

(w) = washed

Table 3. Individual eye scores: 24 hour

Animal Number	Cornea	Iris	Conjunctivae			Cornea
	Opacity/Area	Iritis	Redness	Chemosis	Discharge	Stain / Area
B5431M	0 / 0	0	1	0	1	0 / 0
B5436M	0 / 0	0	1	0	2	0 / 0
B5430M (w)	0 / 0	0	0	0	0	0 / 0
B5432M (w)	0 / 0	0	1	0	0	0 / 0

Primary Eye Irritation Index = Unwashed 5.0/110, washed 1.0/110

(w) = washed

Individual eye scores: 48 hour

Animal Number	Cornea	Iris	Conjunctivae
	Opacity/Area	Iritis	Redness	Chemosis	Discharge
B5431M	0 / 0	0	1	0	0
B5436M	0 / 0	0	1	0	2
B5430M (w)	0 / 0	0	0	0	0
B5432M (w)	0 / 0	0	0	0	0

Primary Eye Irritation Index = Unwashed 4.0/110, washed 0/110

(w) = washed

Table 4. Individual eye scores: 72 hour

Animal Number	Cornea	Iris	Conjunctivae
	Opacity/Area	Iritis	Redness	Chemosis	Discharge
B5431M	0 / 0	0	0	0	0
B5436M	0 / 0	0	0	0	0
B5430M (w)	0 / 0	0	0	0	0
B5432M (w)	0 / 0	0	0	0	0

Primary Eye Irritation Index = Unwashed 0/110, washed 0/110

(w) = washed

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.
Although the study has only been conducted on two animals (unwashed eyes) it is considered to be sufficient for classification and labelling due to the minimal effects noted and is therefore submitted as a key study with supporting data also provided to support the conclusions on classification and labelling.

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 Freeman C (1990) is selected as the key study as it 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).

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. 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).

Justification for classification or non-classification

The data available for skin and eye irritation of sodium dihydrogenorthophosphate 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.