Sodium metaphosphate

Endpoint summary

Description of key information

Skin irritation: Two in vivo studies are available for skin irritation. The key study Freeman C (1990), is comparable to the OECD Guideline No 404 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 study (Bullock 1972) is provided to support this conclusion. 
Eye irritation: A single key study is available for eye irritation. The protocol for this study (Freeman C, 1986) is comparable 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).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin 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:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: FMC Non-Definitive Primary Skin Irritation Protocol (Number 10)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Please see additional information on materials and methods.

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 on June 6, 1990.
- Age at study initiation: Young
- Weight at study initiation: 2.06 - 2.35 kg
- Housing: individually housed in stainless steel cages. DACB cageboard bedding was used in the litter pans.
- Diet (e.g. ad libitum): Purina High Fiber Rabbit Chow 5326 was provided
- Water (e.g. ad libitum): fresh tap water was provided
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-72°F
- Humidity (%): 51-66 %
- Photoperiod (hrs dark / hrs light): 12 hour fluorescent light: 12 hour dark cycle.

IN-LIFE DATES: June 6, 1990 to termination ca. mid June 1990

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: the test material was moistened with physiological saline

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 gram

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3 animals, 1 female and 2 males, were used in this study, per animal two test sites were dosed either side of the spinal column.

Details on study design:

TEST SITE
- Area of exposure: 2" by 2"
- % coverage:
- administration of the test material: The test material was weighed onto an 8-ply, 2"x2" gauze pad and moistened. The pad was secured with hypoallergenic tape. The entire trunk of the animal was wrapped with a semi-occlusive cheesecloth bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, a gauze pad moistened with methanol was used to wipe the test site, the test site was then rinsed with tap water.
- Time after start of exposure: 4 h

SCORING SYSTEM: Approximately 30 minutes after unwrapping, the test sites of each rabbit were scored for irritation using the method of:
Draize J. H., G. Woodard and H. O. Calvery, J. Pharmacol. Exp. Ther., 83, 384 (1944). The 30 minute delay was instituted to allow for regression of pressure and hydration effects.

RATING SYSTEM:
- Non Irritating: No irritation observed in any animal at any scoring interval.
- Slightly irritating: Any animal exhibiting scores of 1 or less at any scoring interval and irritation clearing within 72 hours.
- Mildly irritating: Any animal exhibiting scores of 2 or less at any scoring interval and irritationg clearing within 7 days.
- Moderately irritating: Any animal exhibiting scores of 3 or less at any scoring interval and irritation clearing within 7 days.
- Severely irritating: Any animal exhibiting scores of 4 or less at any scoring interval

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

The only irritation noted was slight erythema in one rabbit 4.5 h after dosing. All irritation resolved within 24h, and the test was terminated following the 72 h scoring.

Other effects:

All animals remained healthy throughout the study.

Table 1 - Individual skin scores at 4.5 hours

Animal # / sex	Left			Right
	ER	ED	O	ER	ED	O
1 / female	1	0	0	1	0	0
2 / male	0	0	0	0	0	0
3 / female	0	0	0	0	0	0
Irritation score = 0.3/ 8.0

ER - erythema and eschar scores

ED - edema

O - Other comments

At all subsequent time points, i.e. at 24 h, 48 h and 72 h, zero scores were recorded for all test sites.

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 to be slightly 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 metaphosphate 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) at 24, 48 and 72 hours after exposure.

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:

From: 01/04/1986 To: 05/04/01986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: FMC Preliminary Eye Irritation Protocol dated March 17, 1986

Deviations:

not specified

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

see deviations in any other information on materials and methods.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Inc., Denver, Pennsylvania on February 26 and March 19, 1986
- Age at study initiation: Young rabbits.
- Weight at study initiation: 2.52kg - 3.26 kg
- Housing: The animals were individually housed in suspended stainless steel cages. DACB cageboard bedding was used in the litter pans.
- Diet (e.g. ad libitum): Purina High Fiber Rabbit Chow 5326, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9°C-25°C (reported as 66°F to 77°F)
- Humidity (%): 32%-55%
- Photoperiod (hrs dark / hrs light): 12 fluorescent light and 12 hour dark cycle.


IN-LIFE DATES: From: 26/02/1986 To: 05/04/1986

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated left eyes of the animal's served as controls

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100mg per eye

Duration of treatment / exposure:

Two of the rabbits were exposed for 20-30 seconds before having their eye's rinsed.
Two of the rabbits did not have their eyes washed during the course of the study - 72 hours.

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

Four animals, two did not have their eyes washed, the other two did.

Details on study design:

REMOVAL OF TEST SUBSTANCE
Two of the four exposed animals had their eyes was 20-30 seconds after exposure.

SCORING SYSTEM:
The eyes were scored for irritation potential using the method of Draize J.H., G. Woodard and H.O. calvery, J. Pharmacol. Exp. ther., 83, 387 (1944).
The Primary Eye Irritation Index was calculated according to Novermber, 1984, U.S. E.P.A. Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals, Series 81-4.

TOOL USED TO ASSESS SCORE: After the 24 hour examination with a penlight type light, the eyes were examined with the aid of fluorescein dye.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

One hour after dosing, both of the unwashed eyes had severe discharge, one of which also had slight chemosis; both of the washed eyes exhibited slight discharge. At the 24-hour and 48-hour scorings, one of the unwashed eyes had a slight discharge. At the 72-hour scoring all irritation had resolved and the test was terminated.

Other effects:

No data.

Table 1 - eye examination, individual scores at one hour

Animal Number	Cornea	Iris	Conjunctiva
	Opacity/Area	Iritis	Redness	Chemosis	Discharge
Male 1	0/0	0	0	1	3
Male 2	0/0	0	0	0	3
Male 3 (w)	0/0	0	0	0	1
Male 4 (w)	0/0	0	0	0	1

(w) - denotes that the eyes of the animal were washed.

Table 1 continued – results at twenty-four hours

Animal Number	Cornea	Iris	Conjunctiva			Cornea
	Opacity/Area	Iritis	Redness	Chemosis	Discharge	Stain/area
Male 1	0/0	0	0	0	1	0/0
Male 2	0/0	0	0	0	0	0/0
Male 3 (w)	0/0	0	0	0	0	0/0
Male 4 (w)	0/0	0	0	0	0	0/0

(w) - denotes that the eyes of the animal were washed.

Table 1 continued – results at forty-eight hours

Animal Number	Cornea	Iris	Conjunctiva			Cornea
	Opacity/Area	Iritis	Redness	Chemosis	Discharge	Stain/area
Male 1	0/0	0	0	0	1	NA
Male 2	0/0	0	0	0	0	NA
Male 3 (w)	0/0	0	0	0	0	NA
Male 4 (w)	0/0	0	0	0	0	NA

(w) - denotes that the eyes of the animal were washed.

Table 1 continued – results at seventy-two hours

Animal Number	Cornea	Iris	Conjunctiva			Cornea
	Opacity/Area	Iritis	Redness	Chemosis	Discharge	Stain/area
Male 1	0/0	0	0	0	0	NA
Male 2	0/0	0	0	0	0	NA
Male 3 (w)	0/0	0	0	0	0	NA
Male 4 (w)	0/0	0	0	0	0	NA

(w) - denotes that the eyes of the animal were 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 non-irritating to washed eyes. Washing the eyes with tap water shortly after exposure decreased both the severity and duration of the irritation observed.
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. This study is therefore submitted as a key study to provide the relevant classification 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 adverse effect observed (not irritating)

Justification for classification or non-classification

The data available for skin and eye irritation of sodium metaphosphate conclude that no classification is required according to regulation (EC) No. 1272/2008 (EU CLP). On ethical grounds it is not considered scientifically justified to repeat in vivo studies for these endpoints as the data provided are sufficient.

There are no data (workplace or study) to suggest that sodium metaphosphate is irritating to the respiratory tract.