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Administrative data

Description of key information

LD50 Acute Oral rat > 2000 mg/Kg bw
LD50 Acute Dermal rat > 5000 mg/Kg bw

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:
2013, January
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well described GLP study
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
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.
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
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.
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
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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study is a Klimish 1 study

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
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:
2013, January
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well described GLP study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
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
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).
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
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 toxicity of KH2PO3/K2HPO3was investigated 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
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The study is a Klimish 1 study

Additional information

Acute toxicity studies per oral and dermal exposure have been performed on the multiconstituent substance "Reaction mass of dipotassium phosphonate and Phosphonic acid, potassium salt (1:1)" (Salvador, 2013). The monoconstituent "mono Potassium phosphonate"is the favourite species in the gastric environment.

No effect has been reported respectively at 2000 and 5000 mg/Kg bw for oral and dermal exposure

Justification for classification or non-classification

Oral acute toxicity

The substance is not classified for oral toxicity because it doesn't meet the classification criteria of the CLP regulation n. 1272/2008:

Oral (mg/kg bodyweight)

Category 1: ATE ≤ 5

Category 2: 5 < ATE≤ 50

Category 3: 50 < ATE≤ 300

Category 4: 300 < ATE≤ 2 000

The substance had no effect at 2000 mg/Kg bw

Inhalation acute toxicity

According to the Annex VIII of the REACH Regulation n. 1907/2006, inhalation route is not considered appropriate, based also on vapour pressure and the test can be waived.

Dermal acute toxicity

The substance is not classified for dermal toxicity because it doesn't meet the classification criteria of the CLP regulation n. 1272/2008:

Dermal (mg/kg bodyweight)

Category 1: ATE ≤ 50

Category 2: 50 < ATE≤ 2000