Diphosphoric acid, compound with 1,3,5-triazine-2,4,6-triamine

Endpoint summary

Description of key information

MPP is non-irritating to the skin but is an irritant to the eyes of rabbits.

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

Study period:

15 June 2004 to 14 April 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Huntingdon Life Sciences, Eye Research Centre, Eye, Suffolk, IP23 7PX, UK

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: reputable laboratory animal supplier
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: suspended cages
- Diet: certified rabbit diet, ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 to 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 light / 12 hours dark

IN-LIFE DATES: From: 1 March 2005 To: 4 March 2005

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5g
- Concentration (if solution): moistened with 0.5ml water

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: on the back of each animal
- % coverage: not reported
- Type of wrap if used: elasticated corset

REMOVAL OF TEST SUBSTANCE
- Washing: residual material was removed by gentle swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Erythema and Eschar formation: scale of 1-4 (1 = no erythema; 4 = severe erythema/eschar formation
Oedema formation: scale of 1-4 (1= no oedema; 4= severe oedema)

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Individual skin reactions

Skin Reaction	Observation Time	Individual Scores-Rabbit Number and Sex			Total
		Male 1	Male 2	Male 3
Erythema/Eschar	1 Hour	0	0	0	(0)
	24 Hours	0	0	0	0
Formation	48 Hours	0	0	0	(0)
	72 Hours	0	0	0	0
Oedema Formation	1 Hour	0	0	0	(0)
	24 Hours	0	0	0	0
	48 Hours	0	0	0	(0)
	72 Hours	0	0	0	0
Sum of 24 and 72-hour Readings (S)                           0
Primary Irritation Index (S/6)                               0/6 = 0.0
Classification                                                   NON-IRRITANT

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No evidence of skin irritation was noted in the study.

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:

18 October 2010 to 7 January 2011

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Eye Irritation (2-1-5), 12 Nohsan No. 8147, Agricultural Production Bureau, November 24, 2000.

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: reputable laboratory animal supplier
- Age at study initiation: 31 or 34 weeks
- Weight at study initiation: 3.69 to 4.30 kg
- Housing: each animal was housed individually in a plastic cage with perforated floors
- Diet: standard laboratory rabbit diet, ad libitum
- Water: drinking water, ad libitum
- Acclimation period: 12 or 20 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 20
- Humidity (%): 40 to 0
- Air changes (per hr): continuous air supply
- Photoperiod (hrs dark / hrs light): 12 hours / 24 hour period

IN-LIFE DATES: From: 3 November 2010 To: 30 November 2010

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated left eye of each animal was used as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL (approximately 92 mg)

Duration of treatment / exposure:

Single exposure

Observation period (in vivo):

15 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none - test substance not removed

SCORING SYSTEM:
Ocular irritation: cornea opacity 0-4; area of cornea 0-4
Corneal ulceration: iris 0-2; conjunctivae redness 0-3; chemosis 0-4
Discharge: 0-4

TOOL USED TO ASSESS SCORE: ophthalmoscope or pencil beam torch

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within:

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 15 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 15 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 8 days

A crimson-red conjunctival appearance was apparent in all animals throughout the first 48 hours after instillation persisting in two at the 72 hour examination; injection of the conjunctival blood vessels was apparent in all cases 24 hours later. Very slight to moderate chemosis was evident in all animals throughout the first 48 hours after instillation persisting in two at the 72 hour examination. Very slight to substantial discharge was also apparent during the first 72 hours after instillation.

Scattered or diffuse areas of opacity covering up to half the corneal surface were apparent in all animals 24 hours after instillation, persisting in one animal at the 48 hour examination and in the remaining animal at the 72 hour observation.

The treated eye of each animal was overtly normal 15 days after instillation.

Interpretation of results:

other: slightly irritating

Remarks:

Criteria used for interpretation of results: other: Kay and Calandra method (1962)

Conclusions:

The highest total mean score was 20.0 occurring at the 24 hour observation; accordingly under the criteria Kay and Calandra (1962) MPP was classified as “mildly irritating” to the eye.

At least 2 out of 3 animals showed a conjunctival redness score ≥2 and an oedema (chemosis) score ≥2 which was reversible within 21 days when. Calculated as the mean scores following grading at 24, 48 and 72 hours after instillation of the test material. MPP is therefore classified under CLP as Irritating to Eyes, Category 2.

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an acute dermal irritation study, the substance a single 4 -hour, semi-occluded application of the test material to the intact skin of three rabbits produced no evidence of skin irritation or corrosive effects.

In an eye irritation study, the substance was administered as a single ocular dose of a volume of 0.1 mL. A crimson-red conjunctival appearance was apparent in all animals throughout the first 48 hours after instillation persisting in two at the 72 hour examination; injection of the conjunctival blood vessels was apparent in all cases 24 hours later. Very slight to moderate chemosis was evident in all animals throughout the first 48 hours after instillation persisting in two at the 72 hour examination. Very slight to substantial discharge was also apparent during the first 72 hours after instillation. Scattered or diffuse areas of opacity covering up to half the corneal surface were apparent in all animals 24 hours after instillation, persisting in one animal at the 48 hour examination and in the remaining animal at the 72 hour observation. The treated eye of each animal was overtly normal 15 days after instillation.

Justification for selection of skin irritation / corrosion endpoint:

A well conducted study performed under GLP in accordance with a recognised guideline.

Justification for selection of eye irritation endpoint:

A well conducted study performed under GLP in accordance with a recognised guideline.

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

Skin irritation

In a dermal irritation study all animals showed zero effects (zero score) throughout the period of the study.

MPP is therefore not classified for skin irritation/corrosion under CLP Regulation No. 1272/2008.

Eye irritation

In an acute eye irritation study conducted on MPP with rabbits, at least 2 out of 3 animals showed a conjunctival redness score ≥2 and an oedema (chemosis) score ≥2 which was reversible within 21 days. Calculated as the mean scores following grading at 24, 48 and 72 hours after instillation of the test material.

MPP is therefore classified under CLP Regulation No. 1272/2008 as Irritating to eyes, Category 2.