Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
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:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

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:
female
Details on test animals and environmental conditions:
Age and weight range : 6 to 7 weeks old, 150 to 174 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 : 170 to 200 grams
Acclimatisation period : At least 5 days
Veterinary health check : After arrival

Caging
No. of animals/cage : Up to 3 during the study; up to 5 during acclimatisation
Housing : Polysulphone solid bottomed cages measuring 59.5x38x20 cm with nesting material
Cage tray 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 except for dosing procedure indicated in section 4.2.2
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 and recorded and records retained. No relevant deviations occurred.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
As requested by the Sponsor, since similar substances were judged to be non toxic at that dose level, and for regulatory requirements related to the potential registration of the test item in some countries, the animals were treated at a maximum dose level of 5000 mg/kg.
As indicated in OECD guideline no. 423, a first sub-group of one female animal was initially dosed at 5000 mg/kg (Step 1). Since mortality occurred in this animal, a lower dose level of 2000 mg/kg was investigated. Then, a first sub-group of 3 female animals was dosed at a level of 2000 mg/kg (Step 2). Mortality did not occur. A second sub-group, similarly composed, was then dosed at the same dose level (Step 3). No mortality occurred.
No further doses were investigated since the objective of the study had been achieved
Doses:
During the study, the test item was suspended as follows:

Vehicle : Purified water
Concentration : 500 and 200 mg/mL

Concentrations were calculated and expressed in terms of test item corrected for purity (50%).

Frequency of treatment : Once only, on the day of dosing (Day 1).
Fasting procedure : Overnight prior to dosing (Day –1) up to 4 hours after dosing.
Dose calculation : Dose volume of 10 mL/kg of body weight for each animal.


No. of animals per sex per dose:
3 female for 5000 mg/kg
5 female for 2000 mg/Kg
Control animals:
no

Results and discussion

Preliminary study:
Mortality occurred on Day 2 in the first animal initially dosed at 5000 mg/kg (Step 1). Clinical signs observed prior to death (on the day of dosing) were piloerection and reduced activity.
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
No mortality occurred and no clinical signs were noted in the first sub-group of three animals dosed at 2000 mg/kg (Step 2).
No mortality occurred and no clinical signs were seen in the second sub-group of three females (Step 3) treated at the same dose level
Body weight:
Changes in body weight observed during the study were within the expected range for this strain and age of animals
Gross pathology:
The necropsy examination performed in the decedent animal treated at 5000 mg/kg (Step 1) and, at the end of the observation period in the animals dosed at 2000 mg/kg (Steps 2 and 3), did not reveal external or internal alterations

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD0 > 2000 mg/Kg bw
LD50 > 2000 mg/Kg bw
Executive summary:

The acute toxicity ofKH2PO3/K2HPO3was investigated following a single oral administration to the Sprague Dawley rat followed by a 14-day observation period.

A sub-group of 1 female animal was initially dosed at 5000 mg/kg (Step 1). Mortality occurred on Day 2 following dosing. Clinical signs observed prior to death were limited to piloerection and reduced activity.

No mortality occurred and no clinical signs were seen in the 2 sub-groups of animals subsequently dosed at 2000 mg/kg (Steps 2 and 3).

Body weight changes recorded during the study were within the expected range for this strain and age of animals.

No abnormalities were observed at necropsy examination performed in the early decedent animal or in those sacrificed at the end of the observation period.

These results indicate that the test itemKH2PO3/K2HPO3induced mortality in the rat following oral administration of a single dose at a level of 5000 mg/kg. No mortality or other signs of toxicity were observed following dosing at 2000 mg/kg. These results suggest the acute toxicity estimate (ATE) to be greater than 2000 but lower than 5000 mg/kg body weight.