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REACH

Tripotassium orthophosphate

EC number: 231-907-1 | CAS number: 7778-53-2

Life Cycle description
Uses advised against

Toxicological information

Endpoint summary

Administrative data

Description of key information

Three studies are available to assess the acute oral toxicity of tripotassium orthophosphate. All studies indicate that tripotassium orthophosphate has a low potential for systemic toxicity following acute administration via the oral route. A weight of evidence approach has been implemented to reduce unnecessary animal testing. The LD50 of tripotassium orthophosphate is known to be > 2,000 mg/kg bw and is therefore not classified according to Regulation (EC) No 1272/2008 (EU CLP).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference 1

Endpoint:: acute toxicity: oral
Type of information:: experimental study
Adequacy of study:: weight of evidence
Study period:: No data
Reliability:: 2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:: study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:: according to guideline
Guideline:: other: No data
Deviations:: not applicable
Principles of method if other than guideline:: Twenty Wister-derived rats were fasted for 24 h prior to administration of the test substance by oral gavage of a g/kg bw basis. Each animal received the desired dosage in a single administration. The animals were observed for signs of toxicity and survival at 1, 3, 6, 24, 48 and 72 h and daily thereafter for a total of 14 days. Body weights were taken at 7 and 14 days. All animals were autopsied and observed for gross pathological organ changes.
GLP compliance:: not specified
Test type:: standard acute method
Limit test:: no
Species:: rat
Strain:: Wistar
Sex:: male/female
Details on test animals or test system and environmental conditions:: TEST ANIMALS
- Source: Zartman Farms, Douglassvillle, Pa.
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: approximately 24 prior to testing.
- Housing: individually
- Diet: adlibitum
- Water: no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Route of administration:: oral: gavage
Vehicle:: not specified
Details on oral exposure:: VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle: no data
- Justification for choice of vehicle:no data
- Lot/batch no.: no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: no data

DOSAGE PREPARATION: no data

CLASS METHOD
- Rationale for the selection of the starting dose: no data
Doses:: 2.44, 3.26, 4.07, 4.48 and 4.89 g/kg bw.
No. of animals per sex per dose:: 4 animals per dose, sex ratio not specified.
Control animals:: not specified
Details on study design:: - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for signs of toxicity were taken at 1, 3, 6, 24, 48, 72 and daily thereafter for a total of 14 days. Body weights were taken initially at 7 and 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight
Statistics:: The 24-h and 14-day LD50 determination was calculated in accordance with the method of Miller and Tainter (1944).
Sex:: male/female
Dose descriptor:: LD50
Effect level:: 4 260 mg/kg bw
Based on:: test mat.
Mortality:: Dose-related mortality was observed.
Clinical signs:: other: Male and female rats exhibited respiratory depression, ataxia, loss of righting, ptosis, piloerection, decreased locomotor activity.
Gross pathology:: Autopsies revealved no outstanding gross pathological organ changes.
Other findings:: No data
Interpretation of results:: GHS criteria not met
Conclusions:: The acute oral LD50 for 20 rats at 24 h and 14 days was 4.26 ± 0.15 g/kg bw.

This study is considered to fulfil the data requirements as defined under Annex XI, section 1.2. of Regulation (EC) N. 1907/2006 (REACH) as part of a weight of evidence approach and no further testing is considered necessary.

Reference 2

Endpoint:: acute toxicity: oral
Type of information:: experimental study
Adequacy of study:: weight of evidence
Study period:: No data
Reliability:: 4 (not assignable)
Rationale for reliability incl. deficiencies:: documentation insufficient for assessment
Qualifier:: according to guideline
Guideline:: other: no data
Deviations:: not applicable
Principles of method if other than guideline:: Single oral dose - 20 % aqueous solution applied to 5 rabbits (male and female).
GLP compliance:: no
Remarks:: Study pre-dates GLP
Test type:: other: No data
Limit test:: no
Species:: rat
Strain:: Sprague-Dawley
Sex:: male/female
Details on test animals or test system and environmental conditions:: No data
Route of administration:: oral: unspecified
Vehicle:: water
Details on oral exposure:: VEHICLE
- Concentration in vehicle: Single dose was administered as a 20 % aqueous solution
Doses:: 3160, 3980, 5010 and 6310 mg/kg.
No. of animals per sex per dose:: Either 2 males and 3 females , or 3 males and 2 females per group.
Control animals:: not specified
Details on study design:: - Duration of observation period following administration: 14 days
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs
Statistics:: No data
Sex:: male/female
Dose descriptor:: LD50
Effect level:: 4 500 mg/kg bw
95% CL:: >= 4 000 - <= 5 060
Remarks on result:: other: 20 % aqueous solution
Mortality:: See table.
Clinical signs:: other: Reduced appetite and activity (1 to 2 days in survivors), increasing weakness, collapse and death.
Gross pathology:: Lung and liver hyperaemia and acute gastrointestinal inflammation was observed in decedents.
In survivors, the viscera appeared normal.
Other findings:: No data
Interpretation of results:: GHS criteria not met
Conclusions:: The single oral dose LD50 of tripotassium phosphate was 4500 mg/kg with 95 % confidence limits of 4000 - 5060 mg/kg.

This study is considered to fulfil the data requirements as defined under Annex XI, section 1.2. of Regulation (EC) N. 1907/2006 (REACH) as part of a weight of evidence approach and no further testing is considered necessary.

Reference 3

Endpoint:: acute toxicity: oral
Type of information:: experimental study
Adequacy of study:: weight of evidence
Study period:: No data
Reliability:: 4 (not assignable)
Rationale for reliability incl. deficiencies:: documentation insufficient for assessment
Qualifier:: according to guideline
Guideline:: other: No data
Deviations:: not specified
Principles of method if other than guideline:: Acute oral screening test in male rats.
GLP compliance:: no
Remarks:: Study pre-dates GLP
Test type:: other: 'standard acute oral screen'
Limit test:: no
Species:: rat
Strain:: not specified
Sex:: male
Details on test animals or test system and environmental conditions:: No data
Route of administration:: oral: unspecified
Vehicle:: water
Details on oral exposure:: No data
Doses:: 1000 and 4640 mg/kg
No. of animals per sex per dose:: Males only.
Control animals:: not specified
Details on study design:: - Duration of observation period following administration: 14 days
Statistics:: No data
Preliminary study:: No data
Sex:: male
Dose descriptor:: LD50
Effect level:: > 1 000 mg/kg bw
Mortality:: At 4640 mg/kg all 4 animals died by 18 h.
Clinical signs:: other: Acute depression and pain reaction at 4640 mg/kg dose level.
Gross pathology:: Corrosion of gastrointestinal tract.
Other findings:: No data.
Interpretation of results:: study cannot be used for classification
Conclusions:: The acute oral LD50 of tripotassium orthophosphate, under the conditions of the test, was reported to be > 1000 mg/kg.

This study is considered to fulfil the data requirements as defined under Annex XI, section 1.2. of Regulation (EC) N. 1907/2006 (REACH) as part of a weight of evidence approach and no further testing is considered necessary.

Endpoint conclusion

Endpoint conclusion:: no adverse effect observed
Dose descriptor:: LD50
Value:: 4 260 mg/kg bw
Quality of whole database:: LD50 > 2,000 mg/kg bw
Three studies are available to assess the acute oral toxicity of tripotassium orthophosphate in addition a number of supporting data on analogous substances are available to support the conclusion. All studies indicate that tripotassium orthophosphate has a low potential for systemic toxicity following acute administration via the oral route.

Acute toxicity: via inhalation route

Link to relevant study records

Reference 1

Endpoint:: acute toxicity: inhalation
Type of information:: experimental study
Adequacy of study:: key study
Study period:: No data
Reliability:: 1 (reliable without restriction)
Rationale for reliability incl. deficiencies:: guideline study
Justification for type of information:: REPORTING FORMAT FOR THE ANALOGUE APPROACH
See read-across justification report under Section 13 ‘Assessment Reports’.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.

The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category

Both the Na+ and the K+ cation have a similar biological function and therefore orthophosphate salts of these types are not considered to differ in their systemic toxicity profile; differences arise in their local effects profile due to the increasing or decreasing acidity/alkalinity and buffering capacities of the substances. This has been shown not to have an effect on systemic toxicity. In addition, both salts have been shown to be of similar low toxicity in acute oral studies. These studies are supported by a number of acute oral studies on similar compounds which all show potassium and sodium orthophosphates to possess low systemic toxicity via the oral route (See section 7.2.1.) and therefore comparisons can be drawn to allow read-across for the acute inhalation endpoint.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across justification report under Section 13 ‘Assessment Reports’.

3. ANALOGUE APPROACH JUSTIFICATION
See read-across justification report under Section 13 ‘Assessment Reports’.

4. DATA MATRIX
See read-across justification report under Section 13 ‘Assessment Reports’.
Reason / purpose for cross-reference:: read-across: supporting information
Qualifier:: according to guideline
Guideline:: EPA OPP 81-3 (Acute inhalation toxicity)
Deviations:: no
Qualifier:: according to guideline
Guideline:: other: U.S. Environmental Protection Agency Toxic Substances Health Effects Test Guidelines, October 1984 (PB82-232984) Acute Inhalation Toxicity Study
Deviations:: no
Qualifier:: according to guideline
Guideline:: OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:: no
Qualifier:: according to guideline
Guideline:: EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:: no
Qualifier:: according to guideline
Guideline:: other: FMC Acute Inhalation Toxicity Protocol Number 27
Deviations:: no
GLP compliance:: yes
Test type:: standard acute method
Limit test:: yes
Species:: rat
Strain:: Sprague-Dawley
Sex:: male/female
Details on test animals or test system and environmental conditions:: TEST ANIMALS
- Source: Charles River Laboratories, Kingston, NY.
- Age at study initiation: young adult
- Weight at study initiation: males: 274 ± 9.1; females 217 ± 7.3
- Fasting period before study: not reported
- Housing: Individually housed in stainless steel suspended rat cages. Desorb bedding was used in the litter pans.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: a minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 69 - 73ºF
- Humidity (%): 41 - 70 %
- Photoperiod (hrs dark / hrs light): 12 h dark/ 12 h light
Route of administration:: inhalation: dust
Type of inhalation exposure:: whole body
Vehicle:: other: unchanged (no vehicle)
Details on inhalation exposure:: GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Rochester type exposure chamber
- Exposure chamber volume: 150 L
- Method of holding animals in test chamber: test animals were assigned to and housed in individual compartments of a wire mesh cage bank (all on the same horizontal level) during the exposure. The cage position assignment ensured equal distribution of both sexes throughout the cage bank.
- Source and rate of air: breathing grade compressed air
- System of generating particulates/aerosols: a BGI Wright dust feeder II was used to generate the test atmosphere. The test material was desiccated and packed into large dust cups. Breathing grade compressed air was metered to the Wright dust feeder through 1/4 inch teflon tubing by a Matheson® 605 rotameter with metal float. Rotameter back pressure was controlled using a Matheson®3104-C regulator. The dust feeder back pressure was controlled using a Marshalltown® back pressure gauge. The test material was made airborne by compressed air dispersing the material into the exposure chamber. The concentration of the test atmostphere was controlled by the delivery rate setting of the wright dust feeder.
- Method of particle size determination: the aerodynamic particle size distribution was determined by gravimetric analysis of the test material collected on the impactor stages and subsequent determination of the MMAD, geometric SD and other particule size parameters by logarithmic-probability plotting.
- Temperature, humidity, pressure in air chamber: Chamber and room air temperature and relative humidity were monitored continuously during the exposure with FMC wet/dry bulb hygrometers. Measurements were recorded at 30 min intervals.
At the end of the exposure, the chamber was cleared for 30 min by drawing room air through it at the same flow rate (31.9 L/min) prior to removing the animals.

TEST ATMOSPHERE
- Brief description of analytical method used: chamber air samples were taken on Gelman® Type A/E 47 mm glass fibre filters held in cassettes at approximately 1 h intervals during exposure to determine the airborne concentration of test material. The airborne concentration of the test material was determined gravimetrically by drawing a known amount of chamber air through the filter. The concentration was calculated by dividing filter weight gain by the sample volume. The samples were taken from the centre of the chamber directly over the animal exposure caging.
Atmospheric monitoring:
The chamber homogeneity determination showed that the test atmosphere was homogeneously distributed throughout the test chamber (cv = 7.10 %).
The dust feeder was operated at what was considered a maximum setting which would allow reliable operation. At this setting the delivery rate required the dust feeder to be manually assisted during the exposure. The chamber airflow was operated at as low flow rate which would allow timely chamber equilibrium and maintain a slight negative pressure in the chamber. The difference between gravimetric and nominal concentration was attributed to sedimentation of larger particles and / or adhesion of the test material to surfaces in the exposure chamber.

- Samples taken from breathing zone: yes
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The MMADs ranged from 5.87 to 6.82 μm with geometric standard deviations ranging from 2.55 to 2.92. The fraction of particles less than or equal to 1 μm in mass aerodynamic diameter, based on the log probability graphs, ranged from 0 to 3.6 %. The fraction of particles less than or equal to 10 μm in mass aerodynamic diameter, based on the log probability graphs, ranged from 65.9 to 69.1 %. These results indicated the test material was respirable in size to the rat. The MMAD represents the smallest size that could be acheived in this study. The material had a static electric charge when generated causing the particles to agglomerate and / or adhere to surfaces inside the chamber.
Analytical verification of test atmosphere concentrations:: yes
Remarks:: chamber air samples were taken on Gelman® Type A/E 47 mm glass fibre filters held in cassettes at approximately 1 h intervals during exposure to determine the airborne concentration of test material
Duration of exposure:: 4 h
Concentrations:: Nominal concentration: 37.35 mg/L
Mean analytical data ±SD (Gravimetric concentration): 0.83 ± 0.065 mg/L
No. of animals per sex per dose:: 5/sex/dose
Control animals:: not specified
Details on study design:: - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed for signs of toxicity and mortality at 15 min intervals during the first h of exposure , hourly for the remainder of the exposure, upon removal from the chamber, at 1 h post-exposure, twice daily thereafter for 13 days and once on day 14.
- Necropsy of survivors performed: yes, all animals were sacrificed and submitetd to gross necroscopy.
- Other examinations performed: body weights were recorded on days 0, 1, 2, 4, 7 and 14.
Statistics:: None reported
Preliminary study:: No data
Sex:: male/female
Dose descriptor:: LC50
Effect level:: > 0.83 mg/L air (analytical)
Exp. duration:: 4 h
Mortality:: There were no deaths during the study.
Clinical signs:: other: The incidence of clinical signs were highest at the removal from chamber observations. Clinical signs noted during the exposure included lacrimation and squinting eyes. Clinical signs noted following the exposure incuded chromodacryorrhea, lacrimation, n
Body weight:: Most animals lost weight through day 1 of the study and then began to gain weight in a normal pattern. At termination all animals had exhibited increases in body weight over their day 0 values.
Gross pathology:: There were no gross internal lesions observed in any animal necropsy.
Other findings:: no data
Interpretation of results:: GHS criteria not met
Conclusions:: Under the conditions of this study, the test material caused no mortality when administered for 4 h to Sprague Dawley rats at a mean, maximum attainable concentration of 0.83 mg/L. Based on this, the LC50 for monosodium phosphate is considered to be greater than 0.83 mg/L. This study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement for this endpoint.

Reference 2

Endpoint:: acute toxicity: inhalation
Type of information:: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:: key study
Justification for type of information:: REPORTING FORMAT FOR THE ANALOGUE APPROACH
See read-across justification report under Section 13 ‘Assessment Reports’.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.

The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category

Both the Na+ and the K+ cation have a similar biological function and therefore orthophosphate salts of these types are not considered to differ in their systemic toxicity profile; differences arise in their local effects profile due to the increasing or decreasing acidity/alkalinity and buffering capacities of the substances. This has been shown not to have an effect on systemic toxicity. In addition, both salts have been shown to be of similar low toxicity in acute oral studies. These studies are supported by a number of acute oral studies on similar compounds which all show potassium and sodium orthophosphates to possess low systemic toxicity via the oral route (See section 7.2.1.) and therefore comparisons can be drawn to allow read-across for the acute inhalation endpoint.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across justification report under Section 13 ‘Assessment Reports’.

3. ANALOGUE APPROACH JUSTIFICATION
See read-across justification report under Section 13 ‘Assessment Reports’.

4. DATA MATRIX
See read-across justification report under Section 13 ‘Assessment Reports’.
Reason / purpose for cross-reference:: read-across: supporting information
Reason / purpose for cross-reference:: read-across source
Duration of exposure:: h
Preliminary study:: No data
Sex:: male/female
Dose descriptor:: LC50
Effect level:: > 0.83 mg/L air (analytical)
Exp. duration:: 4 h
Mortality:: There were no deaths during the study.
Clinical signs:: other: The incidence of clinical signs were highest at the removal from chamber observations. Clinical signs noted during the exposure included lacrimation and squinting eyes. Clinical signs noted following the exposure incuded chromodacryorrhea, lacrimation, n
Body weight:: Most animals lost weight through day 1 of the study and then began to gain weight in a normal pattern. At termination all animals had exhibited increases in body weight over their day 0 values.
Gross pathology:: There were no gross internal lesions observed in any animal necropsy.
Other findings:: no data
Interpretation of results:: GHS criteria not met
Conclusions:: Tripotassium orthophosphate was considered to have an LC50 of greater than 0.83 mg/L as found in the source study performed with monosodium phosphate.
Executive summary:: Tripotassium orthophosphate was considered to have an LC50 of greater than 0.83 mg/L as found in the source study performed with monosodium phosphate. As explained in the justification for type of information, the differences in molecular structure between tripotassium orthophosphate and monosodium phosphate are unlikely to lead to differences in the acute toxicty that are higher than the typical experimental error of the test method.

Endpoint conclusion

Endpoint conclusion:: no adverse effect observed
Quality of whole database:: LC50 >830 mg/m3
One key study is available to assess the acute inhalation toxicity of the analogous substance sodium dihydrogenorthophosphate.

Acute toxicity: via dermal route

Link to relevant study records

Reference 1

Endpoint:: acute toxicity: dermal
Type of information:: experimental study
Adequacy of study:: weight of evidence
Study period:: No data
Reliability:: 4 (not assignable)
Rationale for reliability incl. deficiencies:: documentation insufficient for assessment
Remarks:: .
Qualifier:: according to guideline
Guideline:: other: no data
Deviations:: not applicable
Principles of method if other than guideline:: Applied as a 40 % aqueous solution.
GLP compliance:: no
Remarks:: Study pre-dates GLP
Test type:: other: no data
Species:: rabbit
Strain:: New Zealand White
Sex:: male/female
Details on test animals or test system and environmental conditions:: No data
Type of coverage:: not specified
Vehicle:: water
Details on dermal exposure:: TEST MATERIAL
- Concentration: 40 % aqueous solution
Duration of exposure:: 24 h
Doses:: 5010 and 7940 mg/kg
No. of animals per sex per dose:: 1 male only at 5010 mg/kg dose; 1 male and 1 female at 7940 mg/kg dose.
Control animals:: not specified
Details on study design:: - Duration of observation period following administration: 14 days
- Other examinations performed: Clinical signs
Statistics:: No data
Sex:: male/female
Dose descriptor:: LD50
Effect level:: > 7 940 mg/kg bw
Remarks on result:: other: 40 % aqueous solution
Mortality:: There were no mortalities.
Clinical signs:: other: Reduced appetite and activity (2 to 3 days).
Gross pathology:: Viscera appeared normal in survivors.
Other findings:: No data
Interpretation of results:: GHS criteria not met
Conclusions:: The LD50 of tripotassium phosphate when applied dermally as a 40 % aqueous solution was > 7940 mg/kg.

This study is considered to fulfil the data requirements as defined under Annex XI, section 1.2. of Regulation (EC) N. 1907/2006 (REACH) as part of a weight of evidence approach and no further testing is considered necessary.

Reference 2

Endpoint:: acute toxicity: dermal
Type of information:: experimental study
Adequacy of study:: weight of evidence
Study period:: 11-03-1987 to 25-03-1987
Reliability:: 2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:: study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:: according to guideline
Guideline:: other: no data
Deviations:: not applicable
Principles of method if other than guideline:: Ten New Zealand white rabbits (5 per dose) were treated with tripotassium phosphate at dosage levels of 20 and 300 mg/kg. The test material was in contact with the intact skin for 24 h under an occlusive wrap. Observations were conducted at approximately 3 h on the day of dosing and daily thereafter for 14 days. Skins were scored for irritation (Draize method) at approximately 24, 48, 72h after application as well as days 4, 7 and 14 of the study. Body weights were recorded on Day 0, 7 and 14 of the study. A gross necropsy was performed on all animals.
GLP compliance:: yes
Test type:: standard acute method
Limit test:: no
Species:: rabbit
Strain:: New Zealand White
Sex:: male
Details on test animals or test system and environmental conditions:: TEST ANIMALS
- Source: Hazleton Research Animals Inc., Denver, Pennsylvania.
- Age at study initiation: Young adult
- Weight at study initiation: 2.20 - 2.96 kg
- Housing: Individually in stainless steel rabbit cages with DACB cageboard bedding was used in the litter pans
- Diet: Ad libitum
- Water: Ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 68 - 77 ºF
- Humidity (%): 28 - 44 %
- Photoperiod (hrs dark / hrs light): 12 h fluorescent light and 12 h dark.

IN-LIFE DATES: 11-03-1987 to 25-03-1987
Type of coverage:: occlusive
Vehicle:: physiological saline
Details on dermal exposure:: TEST SITE
- Area of exposure: The trunk from the scapular to the pelvic region
- % coverage: Not stated but covered by a 4 x 4 inch gauze
- Type of wrap if used: 8 ply 4 x 4 inch gauze pad held in place with hypoallergenic tape. The test site was occluded with impervious plastic sheeting

REMOVAL OF TEST SUBSTANCE
- Washing: The test sites were wiped with clean gauze moistened with tap water.
- Time after start of exposure: approximately 24 h after application.

TEST MATERIAL
- Amount applied: 300 mg/kg and 20 mg/kg
- Constant volume or conc: Moistened with physiological saline
Duration of exposure:: 24 h
Doses:: 20 and 300 mg/kg
No. of animals per sex per dose:: 5 males/dose
Control animals:: not specified
Details on study design:: - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for toxicity were conducted at approximately 3 h on the day of dosing and daily thereafter for 14 days. Skins were scored for irritation (draize method) at approximately 24 ,48 and 72 h after application, as well as 4, 7 and 14 of the study. Body weights were recorded on Day 0, 7 and 14 of the study.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight, mortality and skin irritation
Statistics:: No data
Preliminary study:: Not applicable
Sex:: male
Dose descriptor:: approximate LD50
Effect level:: > 300 mg/kg bw
Mortality:: There were no deaths attributed to the administration of the test material.
Clinical signs:: other: There were no clinical signs attributed to the administration of the test material.
Gross pathology:: There were no treatment related gross internal lesions observed in any animal at necropsy.
Other findings:: Skin irritation: Several test sites had slight erythema, slight oedema and desquamation. One rabbit in the 300 mg/kg group had moderate erythema, focal necrosis, eschar and desquamation. At termination on Day 14, one rabbit in the 300 mg/kg group had eschar and desquamation and one rabbit in the20 mg/kg group had desquamation.
Interpretation of results:: study cannot be used for classification
Conclusions:: Under the conditions of the study the test material was temporarily approximated to be slightly irritating and practically non-toxic. This study is not considered to be suitable for classification and labelling according to Regulation (EC) No 1272/2008 (EU CLP), as the highest dose level was 300 mg/kg bw. This study is provided to support the conclusion that sodium and potassium orthophosphates are of low systemic toxicity.

This study is considered to fulfil the data requirements as defined under Annex XI, section 1.2. of Regulation (EC) No. 1907/2006 (REACH) as part of a weight of evidence approach and no further testing is considered necessary.

Reference 3

Endpoint:: acute toxicity: dermal
Type of information:: experimental study
Adequacy of study:: weight of evidence
Study period:: No data
Reliability:: 4 (not assignable)
Rationale for reliability incl. deficiencies:: documentation insufficient for assessment
Qualifier:: according to guideline
Guideline:: other: no data
Deviations:: not specified
Principles of method if other than guideline:: An acute screening test in rabbits.
GLP compliance:: not specified
Test type:: standard acute method
Species:: rabbit
Strain:: not specified
Sex:: not specified
Details on test animals or test system and environmental conditions:: No data
Type of coverage:: not specified
Vehicle:: unchanged (no vehicle)
Details on dermal exposure:: No data
Duration of exposure:: No data
Doses:: 4640 mg/kg
No. of animals per sex per dose:: 2 animals, sex not specified
Control animals:: not specified
Details on study design:: - Duration of observation period following administration: 14 days
Statistics:: No data
Sex:: not specified
Dose descriptor:: LD50
Effect level:: > 4 640 mg/kg bw
Mortality:: There was no mortality
Clinical signs:: other: Skin irritation and corrosion were observed. No apparent signs of toxicity were observed.
Gross pathology:: No data
Other findings:: No data
Interpretation of results:: GHS criteria not met
Conclusions:: No apparent signs of toxicity were observed under the test conditions. The LD50 was determined to be >4640 mg/kg bw. Local effects of skin irritation and corrosion were observed.

This study is considered to fulfil the data requirements as defined under Annex XI, section 1.2. of Regulation (EC) N. 1907/2006 (REACH) as part of a weight of evidence approach and no further testing is considered necessary.

Endpoint conclusion

Endpoint conclusion:: no adverse effect observed
Dose descriptor:: LD50
Value:: 4 640 mg/kg bw
Quality of whole database:: LD50 > 2000 mg/kg bw
One key study and a number of supporting studies are provided. All studies support no classification.

Additional information

Justification for classification or non-classification

Acute toxicity: oral:The acute oral median dose (LD50) of tripotassium orthophosphate in the rats was reported to be 4260 mg/kg bw and is therefore not classified according to Regulation (EC) No 1272/2008 (EU CLP).

Acute toxicity: inhalation: The acute inhalation median concentration (LC50) of the analogous substance sodium dihydrogenorthophosphate in male and female rats was estimated to be greater than 0.83 mg/L. The result was achieved at the maximum attainable concentration and is considered to be equivalent to a limit test conducted at 5 mg/L and therefore sodium dihydrogenorthophosphate is not considered to be classified according to Regulation (EC) No 1272/2008 (EU CLP). In addition the authors state that the particles of sodium dihydrogenorthophosphate were prone to agglomeration and / or adherence to the surfaces of the chamber and therefore it stands to reason that this study is acceptable for assessment and no further animal testing is justified.

This result is deemed to be adequate for read-across to tripotassium orthophosphate and therefore tripotassium orthophosphate is considered to be of a similar low risk for systemic toxicity via the inhalation route.

Therefore, it can be reliably concluded that tripotassium orthophosphate does not exhibit systemic toxicity via the inhalation route and should not be classified according to Regulation (EC) No 1272/2008 (EU CLP) and it is deemed scientifically unjustified to repeat this study with tripotassium orthophosphate in vivo.

Acute toxicity: dermal: The acute dermal median dose (LD50) of dipotassium hydrogenorthophosphate in the female Wistar strain rat was estimated to be greater than 4640 mg/kg bw and is therefore not classified according to Regulation (EC) No 1272/2008 (EU CLP). No further studies are considered to be necessary.

Dose g/kg bw	Animal no. & sex	Test day			Dose (g/kg bw)	Animal no. & sex	Test day
Dose g/kg bw	Animal no. & sex	0	7	14	Dose (g/kg bw)	Animal no. & sex	0	7	14
2.44	1 M	240	275	305	4.48	1 M	210	-	-
	2 M	220	255	295		2 M	230	-	-
	3 F	200	225	235		3 F	200	-	-
	4 F	210	220	230		4 F	205	215	235
3.26	1 M	220	240	375	4.89	1 M	230	-	-
	2 M	240	255	295		2 M	220	-	-
	3 F	210	220	230		3 F	225	-	-
	4 F	210	220	235		4 F	210	-	-
4.07	1 M	235	265	290
	2 M	235	-	-
	3 F	220	275	235
	4 F	225	230	240

Dosage (mg/kg)	Average initial weight		Mortalities/dosed			Time of mortality
Dosage (mg/kg)	Male	Female	Male	Female	Combined	Time of mortality
3160	235	225	0 / 3	0 / 2	0 / 5	One to two days
3980	215	245	0 / 2	2 / 3	2 / 5
5010	225	235	2 / 3	1 / 2	3 / 5
6310	220	230	2 / 2	3 / 3	5 / 5

Dose (mg/kg)	Conc. (%)	Mortality ratio	Mortality interval	Animal wt. range	Weight change
1000	20	0 / 4	-	190 g
4640	20	4 / 4	18 h	170 g	-

Exposure Date	Mean Analytical Data ± SD (mg/L)	Nominal Concentration (mg/L)	Mortality
	Gravimetric Concentration		# Dead / # Exposed
			Male	Female
1993-08-06	0.83 ± 0.065	37.35	0 / 5	0 / 5

	Study day
	0	1	2	4	7	14
Males	274 ± 9.1	270 ± 10.4	277 ± 11.1	293 ± 10.3	313 ± 10.6	348 ± 13.4
Females	217 ±7.3	218 ± 5.9	215 ± 6.1	222 ± 6.8	228 ± 9.9	238 ± 10.2

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Tripotassium orthophosphate

Endpoint summary

Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

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Reference 1

Reference 2

Reference 3

Endpoint conclusion

Acute toxicity: via inhalation route

Link to relevant study records

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Reference 1

Reference 2

Endpoint conclusion

Acute toxicity: via dermal route

Link to relevant study records

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Reference 1

Reference 2

Reference 3

Endpoint conclusion

Additional information

Justification for classification or non-classification

Dose	No. per group	Hour						Day											Total
Dose	No. per group	1	3	6	24	48	72	4	5	6	7	8	9	10	11	12	13	14	Total
2.44	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4
3.26	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4	4
4.07	4	4	4	4	3	3	3	3	3	3	3	3	3	3	3	3	3	3	3
4.48	4	4	4	4	2	1	1	1	1	1	1	1	1	1	1	1	1	1	1
4.89	4	4	3	3	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Observation	Time after treatment
	Day 0										Day 1		Day 2		Day 3
	Hour										Day 1		Day 2		Day 3
	PT	0.25	0.50	0.75	1	2	3	4	R	1PE	AM	PM	AM	PM	AM	PM
Chromodacryorrhea	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Lacrimation	0	3	3	3	3	3	3	3	5	2	0	0	0	0	0	0
Material on fur	0	0	0	5	5	5	5	5	5	5	5	5	5	5	0	0
Nasal discharge	0	0	0	0	0	0	0	0	2	1	0	0	0	0	0	0
Squinting eyes	0	5	5	5	5	5	5	5	1	0	0	0	0	0	0	0
Death (cumulative)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Animal #	Day 0 (g)	Day 1 (g)	Day 2 (g)	Day 4 (g)	Day 7 (g)	Day 14 (g)
Male
AC8941M	262	260	266	280	299	330
AC8942M	277	268	277	292	311	351
AC8943M	281	683	293	307	327	365
AC8944M	282	279	283	298	319	354
AC8945M	266	261	268	287	309	340
Mean	274	270	277	293	313	348
SD	± 9.1	± 10.4	± 11.1	± 10.3	± 10.6	± 13.4

Female
AC8951F	209	212	212	216	223	228
AC8952F	227	223	222	231	242	251
AC8953F	221	223	216	223	225	238
AC8954F	217	220	220	224	232	245
AC8955F	211	211	207	214	216	228
Mean	217	218	215	222	228	238
SD	± 7.3	± 5.9	± 6.1	± 6.8	± 9.9	± 10.2

Animal	Type, Time of Death	Term Body Weight (g)	Body Weight Change (g)	Internal Findings
Male
AC8941M	S (14)	330	+ 68	No gross lesions
AC8942M	S (14)	351	+ 74	No gross lesions
AC8943M	S (14)	365	+ 84	No gross lesions
AC8944M	S (14)	354	+ 72	No gross lesions
AC8945M	S (14)	340	+ 74	No gross lesions
Female
AC8951F	S (14)	228	+ 19	No gross lesions
AC8952F	S (14)	251	+ 24	No gross lesions
AC8953F	S (14)	238	+ 17	No gross lesions
AC8954F	S (14)	245	+ 28	No gross lesions
AC8955F	S (14)	228	+ 17	No gross lesions

Dosage (mg/kg)	Initial weight		Mortalities/dosed
Dosage (mg/kg)	Male	Female	Male	Female	Combined
5010	2.1	-	0 / 1	-	0 / 1
7940	2.3	1.9	0 / 1	0 / 1	0 / 2

Dosage level (mg/kg)	Mean body weights ± SD (kg)
	Day
	0	7	14
300	2.52 ± 0.220	2.33 ± 0.172	2.45 ± 0.167
20	2.39 ± 0.322	2.19 ± 0.139	2.53 ± 0.216

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Tripotassium orthophosphate

Endpoint summary

Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint conclusion

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint conclusion

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint conclusion

Additional information

Justification for classification or non-classification

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