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Description of key information

LD50 Acute Oral rat > 1683 mg Ca(H2PO3)2 /kg bw

LD50 Acute Dermal rat > 4206 mg Ca(H2PO3)2 /kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

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:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system 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), ItalyBreeder :Charles River Italia S.p.A., Calco (Lecco), ItalyDate of arrival :17 January 2013Weight range at arrival:170 to 200 gramsAcclimatisation period:At least 5 daysVeterinary health check:After arrivalCagingNo. of animals/cage:Up to 3 during the study; up to 5 during acclimatisationHousing :Polysulphone solid bottomed cages measuring 59.5x38x20 cm with nesting materialCage tray control:Daily inspected and changed as necessary (at least 3 times/week)Water and dietWater :Drinking water supplied to each cage via a water bottleWater supply :Ad libitumDiet :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 4.2.2Records 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 waterConcentration:500 and 200 mg/mLConcentrations 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/kg5 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:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
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:
Category 5 based on GHS criteria
Remarks:
No reason for classification according to EU criteria
Conclusions:
LD0 > 2000 mg/kg bwLD50 > 2000 mg/kg bw
Executive summary:

The acute toxicity of KH2PO3/K2HPO3 was 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 item KH2PO3/K2HPO3 induced 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:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
In the assessment of calcium dihydrogenphosphite (Ca(H2PO3)2, CAS 13780-04-6), a read-across approach is followed based on the information available for potassium phosphonate (KH2PO3/K2HPO3 EC 915-179-9). This read-across strategy is based on the hypothesis that the phosphite anion is the driver for the ecotoxicological and toxicological effects of both salts.The read-across hypothesis is justified by the immediate dissociation of calcium dihydrogenphosphate and potassium phosphonate upon dissolution in aqueous media. Both phosphite salts are highly soluble (>200 g/L) and are only present in their dissociated form in solution, i.e. the calcium or potassium cation and the phosphite anion. The transformation of the salts into the ions is rapid and complete in relevant environmental and physiological media and therefore no systemic exposure to the salts as such occurs. Exposure to the non-common cations (Ca2+ and K+) does not influence the prediction of the (eco)-toxicity because both elements are abundantly present in natural environments and emissions from these salts do not significantly increase the exposure concentration for calcium and potassium. Moreover, calcium and potassium are major essential element for living organisms.Further information is included as attachment in section 13 of IUCLID.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across: supporting information
Preliminary study:
Mortality occurred on Day 2 in the first animal initially dosed at 5000 mg KH2PO3 /kg bw, corresponding to 4206 mg Ca(H2PO3)2 /kg bw at equimolar H2PO3- concentrations (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:
> 1 349 - < 3 372 mg/kg bw
Based on:
act. ingr.
Remarks:
dihydrogen phosphite anion
Sex:
female
Dose descriptor:
LD50
Effect level:
> 1 349 mg/kg bw
Based on:
act. ingr.
Remarks:
dihydrogen phosphite anion
Key result
Sex:
female
Dose descriptor:
LD0
Effect level:
> 1 683 - < 4 206 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 1 683 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred and no clinical signs were noted in the first sub-group of three animals dosed at 2000 mg KH2PO3 /kg bw, corresponding to 1683 mg Ca(H2PO3)2 /kg bw at equimolar H2PO3- concentrations (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 KH2PO3 /kg bw, corresponding to 4206 mg Ca(H2PO3)2 /kg bw at equimolar H2PO3- concentrations (Step 1) and, at the end of the observation period in the animals dosed at 2000 mg KH2PO3 /kg bw, corresponding to 1683 mg Ca(H2PO3)2 /kg bw at equimolar H2PO3- concentrations (Steps 2 and 3), did not reveal external or internal alterations
Interpretation of results:
Category 5 based on GHS criteria
Remarks:
No reason for classification according to EU criteria
Conclusions:
LD0 > 1683 and <4206 mg Ca(H2PO3)2 /kg bwLD50 > 1683 mg Ca(H2PO3)2 /kg bw
Executive summary:

The acute toxicity of KH2PO3/K2HPO3 was 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 bw (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 bw (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 KH2PO3/K2HPO3 induced mortality in the rat following oral administration of a single dose at a level of 5000 mg/kg bw. No mortality or other signs of toxicity were observed following dosing at 2000 mg/kg bw. Values were recalculated for Ca(H2PO3)2 based on the assumption that the phosphite anion is the active ingredient reposonsible for the effects. Results for Ca(H2PO3)2 suggests the acute toxicity estimate (ATE) to be greater than 1683 but lower than 4206 mg Ca(H2PO3)2 /kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
1 683 mg/kg bw
Quality of whole database:
The original study is a Klimish 1 guideline study.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

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:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
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), ItalyBreeder :Charles River Italia S.p.A., Calco (Lecco), ItalyDate of arrival :17 January 2013Weight range at arrival:201 to 206 grams Acclimatisation period:At least 5 daysVeterinary health check:After arrivalCagingNo. 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 bagsCage control :Daily inspected and changed as necessary (at least 3 times/week)Water and dietWater :Drinking water supplied to each cage via a water bottleWater supply :Ad libitumDiet :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 hourTemperature 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 hoursWashing 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 observationsMortality 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 studiesTermination :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:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
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:
GHS criteria not met
Conclusions:
LD0 > 5000 mg/kg bw LD50 > 5000 mg/kg bw
Executive summary:

The acute toxicityof 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:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
In the assessment of calcium dihydrogenphosphite (Ca(H2PO3)2, CAS 13780-04-6), a read-across approach is followed based on the information available for potassium phosphonate (KH2PO3/K2HPO3 EC 915-179-9). This read-across strategy is based on the hypothesis that the phosphite anion is the driver for the ecotoxicological and toxicological effects of both salts.The read-across hypothesis is justified by the immediate dissociation of calcium dihydrogenphosphate and potassium phosphonate upon dissolution in aqueous media. Both phosphite salts are highly soluble (>200 g/L) and are only present in their dissociated form in solution, i.e. the calcium or potassium cation and the phosphite anion. The transformation of the salts into the ions is rapid and complete in relevant environmental and physiological media and therefore no systemic exposure to the salts as such occurs. Exposure to the non-common cations (Ca2+ and K+) does not influence the prediction of the (eco)-toxicity because both elements are abundantly present in natural environments and emissions from these salts do not significantly increase the exposure concentration for calcium and potassium. Moreover, calcium and potassium are major essential element for living organisms.Further information is included as attachment in section 13 of IUCLID.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across: supporting information
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 3 372 mg/kg bw
Based on:
act. ingr.
Remarks:
dihydrogen phosphite anion
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 373 mg/kg bw
Based on:
act. ingr.
Remarks:
dihydrogen phosphite anion
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 4 206 mg/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 4 206 mg/kg bw
Based on:
test mat.
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:
GHS criteria not met
Conclusions:
LD0 > 4206 mg Ca(H2PO3)2 /kg bw LD50 > 4206 mg Ca(H2PO3)2 /kg bw
Executive summary:

The acute toxicityof KH2PO3/K2HPO3 was investigated following dermal administration of a single dose to the rat at 5000 mg/kg bw.

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

These results indicate that KH2PO3/K2HPO3 has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 5000 mg/kg bw. The lack of mortality demonstrates the LD50 to be greater than 5000 mg/kg. Values were recalculated for Ca(H2PO3)2 based on the assumption that the phosphite anion is the active ingredient reposonsible for the effects. The corrected LD50 for Ca(H2PO3)2 is greater than 4206 mg Ca(H2PO3)2 /kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 206 mg/kg bw
Quality of whole database:
The original study is a Klimish 1 guideline 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) and the results of those studies are also applicable to the monoconstituent "mono Potassium phosphonate", which is a component and also the favourite species in the gastric environment.

Results for mono Potassium phosphonate were recalculated to calcium dihydrogen phosphite (Ca(H2PO3)2) based on the assumption that the phosphite anion is the active ingredient reposonsible for the effects. No effect has been predicted respectively at 1683 and 4206 mg Ca(H2PO3)2 /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

Results for Ca(H2PO3)2 suggest the acute toxicity estimate (ATE) to be greater than 1683 but lower than 4206 mg/kg body weight.

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

No effect has been predicted for Ca(H2PO3)2 at 4206 mg/kg bw.