Pentacalcium hydroxide tris(orthophosphate)

Endpoint summary

Description of key information

Skin irritation (similar to OECD 404): not irritating 
Eye irritation (similar to OECD 405): not irritating

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The test site area was larger at 2"x2" than the recommened 1"x1".

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

May 12, 1981

Deviations:

yes

Remarks:

minor deviations as test site larger than recommended; for more detail see "Further information on Material and Methods"

Qualifier:

according to guideline

Guideline:

other: U.S. E.P.A. Pesticide Assessment Guidelines; Subdivision F, Hazard Evaluation: Human and Domestic Animals, November 1984; 81-5 Primary Dermal Irritation Study.

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

other: Commission of the European Communities, Council Directive 67/548/EEC, Annex V, Part B.4; May 1, 1987,

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

other: FMC Primary Skin Irritation Protocol (Number 16)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HRP, Inc., Denver, PA on May 12, 1993
- Age at study initiation: The rabbits are referred to as 'young'.
- Weight at study initiation: 2.67 - 2.85 kg
- Housing: The animals were inidividually housed in stainless steel cages. Deosorb indirect 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: The animals were acclimated for a minimum of 5 days prior to study start.

ENVIRONMENTAL CONDITIONS
- Temperature: 65 - 69°F (18.3 - 20.6°C)
- Humidity (%): 45 - 66 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light and 12 hour dark cycle.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: The test material was moistened with physiological saline

Controls:

not required

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:

Six animals were used in this study, three males and three females. Per animal 2 test sites were prepared and dosed.

Details on study design:

TEST SITE
- Other: Per animal there were 2 test sites either side of the spinal column.
- Area of exposure: each site was approximately 26 square cm
- % coverage: no data
- Test material administration: The test material was weighed onto an 8-ply, 2"x2" gauze pad and moistened with physiological saline. The gauze 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: test sites were wiped with gauze moistened with methanol and 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: The FMC 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:

edema score

Basis:

other: all 6 animals tested

Time point:

other: mean 24, 48 and 72 hrs

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

other: all 6 animals tested

Time point:

other: mean 24, 48 and 72 hrs

Score:

0

Max. score:

4

Irritant / corrosive response data:

No irritation was noted on any of the test sites during the study.

Other effects:

All animals remained healthy throughout the study.

Zero scores were recorded at all test sites at all time points, i.e. at 4.5, 24, 48 and 72 hours post exposure.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the test material is judged to be non-irritating to intact skin when applied topically to New Zealand White rabbits.

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:

02/02/1982 to 29-05-1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Study not conducted to current guideline, however study is scientifically sound and acceptable for assessment. 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 in accordance with Regulation (EC) No. 1272/2008 (EU CLP). Pentacalcium hydroxide tris(orthophosphate) is not considered to be classified according to Regulation (EC) No. 1272/2008 (EU CLP).

Qualifier:

according to guideline

Guideline:

other: US EPA Guidelines(24/05/1982) FR22405), OECD Guidelines (1981), and PR Notice 81-3

Deviations:

not specified

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Remarks:

however, study predates the introduction of GLP

Species:

rabbit

Strain:

other: Stauffland albino

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Phillips Rabbitry, Soquel, CA
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: two in a cage in suspended steel cages (24" x 16.5 " x 14").
- Diet: ad libitum; Special Mixture, Gunter Bros., Morgan Hill, CA.
- Water: ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature: 65-70°F (18.3 - 21.1°C)
- no other data pertinent to environmental conditions.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
The solid test material was passed through a #300 mesh screen and the fines were used. 100mg of the test material was used.

VEHICLE
No vehicle used. The test material was not moistened before being placed in the eye.

Duration of treatment / exposure:

Three animals had their eyes washed 20-30 seconds after application and a further six animals did not.

Observation period (in vivo):

1, 24, 48 and 72 hours and then at 4 and 7 days post application.
If after 7 days irritation was present then additional observations would be made every 3-4 days.

Number of animals or in vitro replicates:

9

Details on study design:

REMOVAL OF TEST SUBSTANCE
20-30 seconds after application three animals had their eyes washed with luke warm water for one minute, the remaing six animals did not.

SCORING SYSTEM: The guidelines described by Draize (1965) were used to assign numerical scored to the observed effects.

TOOL USED TO ASSESS SCORE: fluorescein
Fluorescein staining was graded using a modified procedure outlined by the National Research Council (1977)

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.17

Max. score:

3

Reversibility:

fully reversible within: 48 hrs

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Unwashed eyes: Three of the six animals exhibited a redness of the conjuctiva on day 1 after administration. No other effects were observed.
Washed eyes: All zero scores at all timepoints.

Individual eye scores for rabbits whose eyes were unwashed:

Animal No.	Irritation	Pre-dose	Day 1	Day 2	Day 3	Day 4	Day 7
82-M-341	Cornea: opacity	0	0	0	0	0	0
	Cornea: area	0	0	0	0	0	0
	Iris	0	0	0	0	0	0
	Conjuctiva: redness	0	0	0	0	0	0
	Conjuctiva: chemosis	0	0	0	0	0	0
	Conjuctiva: discharge	0	0	0	0	0	0
82-M-342	Cornea: opacity	0	0	0	0	0	0
	Cornea: area	0	0	0	0	0	0
	Iris	0	0	0	0	0	0
	Conjuctiva: redness	0	1	0	0	0	0
	Conjuctiva: chemosis	0	0	0	0	0	0
	Conjuctiva: discharge	0	0	0	0	0	0
82-M-343	Cornea: opacity	0	0	0	0	0	0
	Cornea: area	0	0	0	0	0	0
	Iris	0	0	0	0	0	0
	Conjuctiva: redness	0	0	0	0	0	0
	Conjuctiva: chemosis	0	0	0	0	0	0
	Conjuctiva: discharge	0	0	0	0	0	0
82-M-344	Cornea: opacity	0	0	0	0	0	0
	Cornea: area	0	0	0	0	0	0
	Iris	0	0	0	0	0	0
	Conjuctiva: redness	0	0	0	0	0	0
	Conjuctiva: chemosis	0	0	0	0	0	0
	Conjuctiva: discharge	0	0	0	0	0	0
82-M-345	Cornea: opacity	0	0	0	0	0	0
	Cornea: area	0	0	0	0	0	0
	Iris	0	0	0	0	0	0
	Conjuctiva: redness	0	1	0	0	0	0
	Conjuctiva: chemosis	0	0	0	0	0	0
	Conjuctiva: discharge	0	0	0	0	0	0
82-M-346	Cornea: opacity	0	0	0	0	0	0
	Cornea: area	0	0	0	0	0	0
	Iris	0	0	0	0	0	0
	Conjuctiva: redness	0	1	0	0	0	0
	Conjuctiva: chemosis	0	0	0	0	0	0
	Conjuctiva: discharge	0	0	0	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

The test material was classed as a mild conjuctival irritant to the eyes of stauffland rabbits. Three of the six animals whose eyes were not washed after application exhibited a redness of the conjuctiva. All effects were reversed by day 2. Pentacalcium hydroxide tris(orthophosphate) is has not 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

Skin:

In order to evaluate the skin irritating potential of pentacalcium hydroxide tris(orthophosphate) three in vivo skin irritation studies are availabe. The study performed in 1993 was selected to be the key study since it is the newest study which is similar to OECD 404. This skin iritation test was performed with three male and three female New Zealand White rabbits. A 4-hour semiocclusive exposure to ca. 0.5 g of the unchanged test material produced no effects during the whole observation period on the treated sites of the animals. The mean score for the 24, 48 and 72 hour reading for erythema and edema, respectively was 0. It has to be stressed that the test material was applied to a larger test site as recommended (5 x 5 cm instead of 2.5 x 2.5 cm; deviation to OECD guideline 404). However, this is assumed to be a worst case since the area exposed is larger. This assumption is supported by the supporting studies which were performed similar to older guidelines under occlusive conditions without showing any irritating potential. Even treatment on abraded skin and under occlusive dressing no irritation was observed (studies from 1985 and Bullock&Kamienski, 1971) which reveals a worst case scenario. Under the conditions of these studies, the test substance is considered to be non-irritating to skin.

Eye:

An eye irritation test was performed with nine male Stauffland albino rabbits similar to OECD 405. In 6 animals eyes were left unwashed and in 3 animals eyes were washed out after 20-30 seconds after application of 0.1 g test substance. The animals were observed for 7 days. Evaluating the animals with unwashed eyes, the mean scores for the 24, 48 and 72 hour reading for iritis, cornea opacity and chemosis were 0 at any reading time point. For conjunctivae redness the mean score for the 24, 48 and 72 hour reading was 0.17. The effects were fully reversible after 48 hours. Animals where eyes were washed after treatment showed no irritation at any timepoint. Under the conditions of the study, the test substance was considered to be non-irritating to eyes.

Justification for classification or non-classification

The available data on skin and eye irritation with pentacalcium hydroxide tris(orthophosphate) (CAS 12167 -74 -7) do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.