Dipotassium phosphonate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2013, January

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP study, well conducted on the similar substance Reaction mass of dipotassium phosphonate and Phosphonic acid, potassium salt (1:1). Rationale for Read Across is attached at point 13

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Potassium Phosphonate KH2PO3/K2HPO3

IUPAC Name:

Potassium Phosphonate KH2PO3/K2HPO3

Details on test material:

Batch number : 20111216-014
Expiry date : 16 December 2013
Storage at RTC : Room temperature
Certificate of analysis : Supplied by the Sponsor and presented in Addendum I
Test item characterisation : Not undertaken at the testing facility. The determination of the identity, strength, purity, composition,
stability and method of synthesis and/or derivation of the test item was the responsibility of the Sponsor
Sample archiving : Retained within RTC archives for a period of 10 years prior to disposal.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Age and weight range : 6 to 8 weeks old, 176 to 200 grams
(at order)
Supplier : Charles River Italia S.p.A., Calco (Lecco), Italy
Breeder : Charles River Italia S.p.A., Calco (Lecco), Italy
Date of arrival : 17 January 2013
Weight range at arrival : 201 to 206 grams
Acclimatisation period : At least 5 days
Veterinary health check : After arrival

Caging
No. of animals/cage : Individually caged (both during acclimatisation and study)
Housing : Clear polysulphone H-Temp solid bottomed cages measuring 35.5x23.5x19 cm (during acclimatisation) an
d 42.5x26.6x18.5 cm (during the study) with nesting material provided into suitable bedding bags
Cage control : Daily inspected and changed as necessary (at least 3 times/week)

Water and diet
Water : Drinking water supplied to each cage via a water bottle
Water supply : Ad libitum
Diet : 4 RF 18 (Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI) Italy)
Diet supply : Ad libitum throughout the study
Records of analyses of water and diet are kept on file at RTC. Components present in the drinking water or diet are not at a level likely to interfere with the purpose or conduct of the study.

Housing conditions (parameters set)
Room lighting: : Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours
Air changes: : Approximately 15 to 20 air changes per hour
Temperature range: : 22°C ± 2°C
Relative humidity range: : 55% ± 15%
Actual conditions were monitored, recorded and records retained. No relevant deviations occurred

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

Frequency of treatment : Once only, on the day of dosing (Day 1).
Treatment area preparation : On the day before dosing (Day –1).

A single area was clipped free of hair (by an electric clipper equipped with a suitable blade) on the dorsal surfaces of the trunk of each animal, (approximately 10% of body surface).
Care was taken to avoid damage to the skin.

Dose calculation : Aliquots were weighed according to the body weight of each animal measured prior to dosing and corrected for purity (50%).

Duration of exposure:

Exposure time : 24 hours
Washing procedure : After exposure, the adhesive bandage and gauze patch were removed. The treatment area was cleaned by gentle
swabbing of the skin with cotton wool soaked with lukewarm water.

Doses:

5000 mg/Kg bw

No. of animals per sex per dose:

A single group of 5 male and 5 female animals was dosed at a level of 5000 mg/kg

Details on study design:

In life observations
Mortality and morbidity : Twice daily.
Clinical signs : - Day of dosing (on dosing, approximately 1, 2 and 4 hours after dosing).
- Daily thereafter (14 days).
Body weight : Allocation (Day -1), Days 1, 8 and 15.

Terminal studies
Termination : Day 15.
Euthanasia method : Carbon dioxide narcosis.
Necropsy procedure : Necropsy was carried out on all animals (gross necropsy examination for both external and internal
abnormalities, with particular attention to the treatment site).

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 5 000 mg/kg bw

Based on:

act. ingr.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

act. ingr.

Mortality:

No mortality occurred and no clinical signs were observed in male or female animals following treatment

Gross pathology:

No abnormalities were found at necropsy examination performed on all animals at termination of the study

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD0 > 5000 mg/Kg bw
LD50 > 5000 mg/Kg bw

Executive summary:

The acute toxicityof KH₂PO₃/K₂HPO₃wasinvestigated following dermal administration of a single dose to the rat at 5000 mg/kg.

No mortality occurred following dosing and no signs of toxicity were observed.

These results indicate that the test item,KH₂PO₃/K₂HPO₃, has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 5000 mg/kg. The lack of mortality demonstrates the LD50 to be greater than 5000 mg/kg