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

Endpoint summary

Description of key information

MPP has low acute oral (LD50>2000 mg/kg bw) and dermal toxicity (LD50>2000 mg/kg bw) in rats. There are no data available on the acute inhalational toxicity of the notified polymer.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 December 2003 to 5 January 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in accordance with an internationally recognised method

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: reputable supplier of laboratory animals
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 196-206g
- Fasting period: overnight (prior to dosing), 3-4 hours after dosing
- Housing: in groups of three in suspended solid-floor polypropylene cages furnished with wood flakes
- Diet: certified rat and mouse diet, ad libitum.
- Water: mains drinking water, ad libitum:
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70%
- Air changes (per hr): at least 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: From: 8 December 2003 To: 10 December 2003

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 10 ml
- Justification for choice of vehicle: produced suspension suitable for dosing

MAXIMUM DOSE VOLUME APPLIED: 10 ml


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: consideration of all available toxicity information 2000 mg/kg was chosen as the starting dose

Determination by analysis of the concentration, homogeneity and stability of the test material preparations was not appropriate because it was not specified in the Study Plan and is not a requirement of the Test Guideline.

Doses:

2000 mg/kg

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing
and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to dosing and seven and fourteen days after
treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: no

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated as being greater than 2500 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

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

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 September to 9 November 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in accordance with an internationally recognised method

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute dermal toxicity (2-1-2), 12 Nousan No. 8147, Agricultural Production Bureau, November 24, 2000.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: CD (Crl:CD ‘SD’)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: reputable laboratory animal supplier
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 228 to 370 g
- Fasting period before study:
- Housing: solid bottomed polycarbonate cages with stainless steel mesh lid. Housed individually for Day1-10 then returned to groups of five animals of the same sex.
- Diet: standard rodent diet, ad libitum
- Water: potable water taken from public supply, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 40-70
- Air changes (per hr): none, continuous supply
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: From: 16 September 2010 To: 6 October 2010

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 10
- Type of wrap if used: waterproof dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): at end of exposure period the treated area of skin was washed with a mild detergent and water (30-40°C) then acetone (to remove residual test substance), followed by warm water. The treated area was then blotted dry with absorbent paper.
- Time after start of exposure: 24 hours

TEST MATERIAL
The test substance was formulated at a maximum practical concentration of 71.4% w/v in the vehicle and administered at a volume of 2.8 mL/kg bodyweight. The test substance formulation was prepared on the day of dosing

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed:

Mortality: cages of rats were checked at least twice daily for any mortalities.

Clinical observations: animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation. All animals were observed for 14 days after dosing.

Dermal reactions: local dermal irritation at the treatment site was assessed daily

Bodyweight:
The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths to treatment in any animal.

Clinical signs:

other: There was no systemic response to treatment in any animal.

Gross pathology:

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Other findings:

Very slight erythema was seen in one male on Day 2, resolving by Day 3 and in one female from Day 3, resolving by Day 10.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute median lethal dermal dose (LD50) to rats of MPP was demonstrated to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

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

Additional information

In an acute oral toxicity study conducted on rats at a limit dose of 2500 mg/kg, there were no deaths and no signs of systemic toxicity. All animals showed expected bodyweight over the study period and no abnormalities were noted at necrospy. These data indicate that MPP is practically non-toxic at the level tested with an LD50 greater than 2500 mg/kg body weight.

No study for acute toxicity by inhalation is available. Testing is considered to be scientifically unjustified taking into account the physicochemical properties of the substance which make exposure by inhalation unlikely.

In an acute dermal toxicity study conducted on rats at a limit dose of 2000 mg/kg there were no deaths, no systemic response in any animal. No abnormalities were noted at in any animal at macroscopic examination. These data indicate that MPP is practically non-toxic

at the level tested with an LD50 of greater than 2000 mg/kg body weight.

Justification for selection of acute toxicity – oral endpoint

One available study.

Justification for selection of acute toxicity – inhalation endpoint

According to Reach Annex VIII end point 8.5.2, the study does not need to be conducted if inhalation is unlikely taking into account  the substance  particles of an inhalable size. The granulometry study shows that <10% by mass of MPP particles are <10µm, therefore an acute inhalation study is not warranted.  Furthermore, approximately 24%  by mass of particles are > 100 µm, this is accepted as a non-respirable fraction.

Justification for selection of acute toxicity – dermal endpoint

One available study.

Justification for classification or non-classification

Acute toxicity oral

LD50 for single exposure to rats is greater than the category 4 classification band of 300 -2000 mg/kg, as prescribed in table 3.1.1 of CLP Regulation No (EC) 1272/2008. MPP is therefore not classified.

Acute toxicity dermal

LD50 for single exposure to rats is greater than the category 4 classification band of 1000 -2000 mg/kg, as prescribed in table 3.1.1 of CLP Regulation No (EC) 1272/2008. MPP is therefore not classified.

Acute toxicity inhalation

No data available - classification not possible