Registration Dossier

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:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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 levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 5 000 mg/kg bw
Based on:
act. ingr.
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
Body weight:
The body weight changes were within the expected range for this species and age of animals at the end of the study
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