Registration Dossier

Administrative data

Description of key information

Oral (OECD 420, RL1), rat: LD50 > 2000 mg/kg bw for females

No data for acute dermal and inhalation toxicity are available for tricalcium bis(orthophosphate). Reliable data are available from the structural analogue calcium bis(dihydrogenorthophosphate) CAS 7758 -23 -8:

Dermal (similar to OECD 402, RL2, RA CAS 7758 -23 -8), rabbit: LD50 > 2000 mg/kg bw (limit test)

Inhalation (OECD 403, RL1, RA CAS 7758 -23 -8), rat: LC50 > 2.6 mg/L air (limit test)

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:
The study was performed between 13 April 2010 and 05 May 2010.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
Harlan UK Limited, Bicester, Oxon, UK.

- Age at study initiation:
At the start of the study the animals were eight to twelve weeks of age.

- Weight at study initiation:
The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animal(s).

- Fasting period before study:
overnight fast immediately before dosing

- Housing:
The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes.

- Diet:
(2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed ad libitum throughout the study.

- Water:free access to mains drinking water

- Acclimation period:acclimatisation period of at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.


Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE

- Concentration in vehicle:
For the purpose of the study the test material was freshly prepared, as required, as a suspension in distilled water to give a dose level of 2000mg/kg bodyweight.
- Justification for choice of vehicle: Distilled water was the preferred vehicle of the test method.

MAXIMUM DOSE VOLUME APPLIED:
10ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
1 female at 2000 mg/kg
4 females at 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: Yes
Preliminary study:
A sighting test at a dose level of 2000 mg/kg was performed.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Hunched posture was noted in four animals during the day of dosing and persisted in one animal one day after dosing. No other signs of systemic toxicity were noted.
Body weight:
All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.
Table1              Individual Clinical Observations and Mortality Data

Dose Level mg/kg

Animal Number and Sex

Effects Noted After Dosing
(Hours)

Effects Noted During Period After Dosing
(Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-0

Female

0

0

H

H

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1

Female

0

H

H

H

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2

Female

0

H

H

H

H

0

0

0

0

0

0

0

0

0

0

0

0

0

2-3

Female

0

H

H

H

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0= No signs of systemic toxicity

H = Hunched posture


Table2              Individual Bodyweights and Bodyweight Changes

Dose Level mg/kg

Animal Number and Sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

2000

1-0 Female

163

172

183

9

11

2-0 Female

157

171

190

14

19

2-1 Female

176

183

193

7

10

2-2 Female

160

170

186

10

16

2-3 Female

166

182

184

16

2

 


Table3              Individual Necropsy Findings

Dose Level
mg/kg

Animal Number
and Sex

Time of Death

Macroscopic Observations

2000

1-0 Female

Killed Day 14

No abnormalities detected

2-0 Female

Killed Day 14

No abnormalities detected

2-1 Female

Killed Day 14

No abnormalities detected

2-2 Female

Killed Day 14

No abnormalities detected

2-3 Female

Killed Day 14

No abnormalities detected


Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (EU CLP - Unclassified). Study is sufficient for classification and labelling purposes, in accordance with Regulation (EC) No. 1272/2008 (EU CLP).
This study has been selected as the key study because the results are sufficient in order to derive a reliable conclusion on classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP). Tricalcium (orthophosphate) is not considered to be classified according to Regulation (EC) No. 1272/2008 (EU CLP).
Executive summary:

Introduction. 

The study was performed to assess the acute oral toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

OECD Guidelines for Testing of Chemicals No 420 “Acute Oral Toxicity - Fixed Dose Method” (adopted 17 December 2001)

Method B1 bis Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008

Method. 

Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of test material, as asuspensionindistilled water, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. 

There were no deaths.

Clinical Observations. 

Hunched posture was noted in four animals. There were no other signs of systemic toxicity noted.

Bodyweight. 

All animals showed expected gains in bodyweight.

Necropsy. 

No abnormalities were noted at necropsy.

Conclusion. 

The acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (EU CLP).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No. 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26th July 2010 - 30 August 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Values for relative humidity above the range occasionally occurred, usually following room cleaning, and were considered not to have any influence on the study.
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
yes
Remarks:
Values for relative humidity above the range occasionally occurred, usually following room cleaning, and were considered not to have any influence on the study.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Source:
Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst / Netherlands

- Age at study initiation:
Males: 11 weeks, Females: 11 weeks

- Weight at study initiation:
Males: 300.6 to 318.0 g, Females: 189.6 to 217.6 g

- Fasting period before study:
Not applicable

- Housing:
Animals were housed in groups of 5 of the same sex in Makrolon® type-IV cages with wire mesh tops and standard softwood bedding ("Lignocel" J. Rettenmaier & Söhne GmbH & Co KG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) including paper enrichment (Enviro-dri from Lillico, Biotechnology, Surrey, UK).

- Diet (e.g. ad libitum):
Animals had ad libitum access to a pelleted standard Harlan Teklad 2914C rat maintenance diet (Provimi Kliba AG, 4303 Kaiseraugst, Switzerland) batch no. 20/10 except during the period when the animals were restrained in exposure tubes. Results of the analyses for contaminants and their limits of acceptability are archived at Harlan Laboratories Ltd.

- Water (e.g. ad libitum):
Community tap water from Füllinsdorf ad libitum in water bottles, except during the period when they were restrained in exposure tubes. Results of representative analyses for contaminants are archived at Harlan Laboratories Ltd.

- Acclimation period:
Performed under Harlan Laboratories Study B68308 for eighteen days under laboratory conditions, after a clinical health examination. Only animals without any visible signs of illness were used for the study. A further observation of clinical signs was performed on the day of exposure, before exposure start.


ENVIRONMENTAL CONDITIONS
Optimal Hygienic Conditions (OHC) inside a barrier system. Air-conditioned with 10 - 15 air changes per hour, continuously monitored environment with a temperature range of 22 ± 3 °C, a relative humidity range of 30 - 70% and a 12 hour fluorescent light / 12 hour dark cycle. Values for relative humidity above the range occasionally occurred, usually following room cleaning, and were considered not to have any influence on the study. These data are not reported but retained at Harlan Laboratories Ltd. A radio program was played during most of the light period.

IN-LIFE DATES: From: Day 1 To: Day 14
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Remarks:
flow-past
Vehicle:
clean air
Mass median aerodynamic diameter (MMAD):
>= 2.95 - <= 3.03 µm
Geometric standard deviation (GSD):
>= 2.97 - <= 3.06
Remark on MMAD/GSD:
Mean Mass Median Aerodynamic Diameter (µm) 3.03, 2.95 and 3.03
Geometric Standard Deviation 3.06, 2.97 and 3.04
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
A CR3020 rotating brush aerosol generator connected to a micronizing jet mill. The aerosol generated was then discharged into the exposure chamber through a 63Ni charge neutralizer.

- Exposure chamber volume:
Not applicable (nose-only, flow-past inhalation exposure chamber)

- Method of holding animals in test chamber:
The animals were confined separately in restraint tubes which were positioned radially around the flow-past, nose-only exposure chamber. Only the nose of each animal was exposed to the test atmosphere.

- Source of air:
Compressed air was supplied by means of an oil free compressor and passed respiratory quality filters before it was introduced into the exposure system.

- Method of conditioning air:
Respiratory quality filters

- System of generating particulates/aerosols:
A dust aerosol was generated from the test item using a CR3020 rotating brush aerosol generator connected to a micronizing jet mill. The aerosol generated was then discharged into the exposure chamber through a 63Ni charge neutralizer.

- Method of particle size determination:
Mercer Impactor (Model 02-130, In-Tox. Products Inc., Albuquerque, New Mexico, U.S.A.).

- Treatment of exhaust air:
Filtered

- Temperature, humidity, pressure in air chamber:
The oxygen concentration, temperature and relative humidity of the test atmosphere were measured continuously during the exposure on test aerosol samples taken at a representative exposure port using a calibrated device. The results were recorded manually and are reported at 30 minute intervals from the start of exposure.

TEST ATMOSPHERE
- Brief description of analytical method used:
Gravimetric determinations of aerosol concentration were performed four times during exposure. The samples were collected on a Millipore®durapore filter, Type HVLP loaded in a 47 mm in-line stainless steel filter sampling device. The filters were weighed before and immediately after sampling using a calibrated balance. The test aerosol concentration was calculated from the amount of test item present on the filter and the sample volume.

- Samples taken from breathing zone:
yes

VEHICLE
No vehicle used.

Analytical verification of test atmosphere concentrations:
no
Remarks:
Gravimetric only
Duration of exposure:
4 h
Concentrations:
Mean Achieved (mg/L) 2.6
The nominal aerosol concentration was 7.5 mg/L air.
Mean Mass Median Aerodynamic Diameter (µm) 3.03, 2.95 and 3.03
Inhalable Fraction (% <4 µm) 59.8% , 61.8 and 59.9%
Geometric Standard Deviation 3.06, 2.97 and 3.04
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration:
14 days

- Frequency of observations and weighing:
All animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to treatment on the day of exposure (day 1) and on Days 2, 4, 8 and 15 or at death.

- Necropsy of survivors performed:
yes

- Other examinations performed:
None
Statistics:
No statistical analysis was performed as only one group was allocated to the study.
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.6 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All animals survived the scheduled observation period.
Clinical signs:
other: Slight to moderate ruffled fur was noted in all animals on test day 1, one hour after the end of the exposure and persisted slightly until test day 2 in nine animals. From test day 3 onwards, all animals were free from clinical signs until their scheduled
Body weight:
From test day 1 to test day 2, marginal to slight body weight loss was noted in all animals. Thereafter all animals gained weight until scheduled necropsy.
Gross pathology:
There were no macroscopic findings.
Other findings:
Not applicable.

The nominal aerosol concentration was 7.5 mg/L air.

Interpretation of results:
GHS criteria not met
Conclusions:
The LC50 of Calcium bis(dihydrogenorthophosphate) obtained in this study was estimated to be greater than 2.6 mg/L air (gravimetrically determined mean aerosol concentration). This was the highest technically achievable test concentration. There was no indication of relevant sex-related differences in toxicity of the test item.

In accordance with Regulation (EC) No. 1272/2008 (EU CLP) calcium bis(orthophosphate) is not considered to be classified as acutely toxic via the inhalation route.
Executive summary:

A group of five male and five female albino rats [RccHanTM:WIST(SPF)] was exposed by nose-only, flow-past inhalation for four hours to the test item at agravimetricallydetermined mean concentration of 2.6 mg/L air.All animals were observed for clinical signs and mortality during the inhalation exposure and the subsequent 14-dayobservation period. Body weights were recorded prior to exposure on test day 1, and during the observation period on test days 2, 4, 8 and 15 before necropsy. On test day 15 all animals were sacrificed and necropsied.

The ranges of aerosol concentration, temperature, relative humidity, oxygen content and airflow rate measured during the exposure were considered to be satisfactory for a study of this type. In addition, the test item was considered to be respirable to rats.

 

All animals survived the scheduled observation period.

 

Slight to moderate ruffled fur was noted in all animals after the end of the exposure and was still present in most animals up to test day 2. Thereafter, all animals were free from clinical signs.

 

Transient body weight loss was noted in all animals from test day 1 to test day 2. Normal body weight development was observed thereafter.

 

No macroscopical findings were present at necropsy.

 

In conclusion, the LC50of Calcium bis(dihydrogenorthophosphate) obtained in this study was estimated to be greater than 2.6 mg/L air (gravimetrically determined mean aerosol concentration). There was no indication of relevant sex-related differences in toxicity of the test item.

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:
refer to analogue justification provided in IUCLID section 13
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.6 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All animals survived the scheduled observation period.
Clinical signs:
other: Slight to moderate ruffled fur was noted in all animals on test day 1, one hour after the end of the exposure and persisted slightly until test day 2 in nine animals. From test day 3 onwards, all animals were free from clinical signs until their scheduled
Body weight:
From test day 1 to test day 2, marginal to slight body weight loss was noted in all animals. Thereafter all animals gained weight until scheduled necropsy.
Gross pathology:
There were no macroscopic findings.
Other findings:
Not applicable.

The nominal aerosol concentration was 7.5 mg/L air.

Interpretation of results:
GHS criteria not met
Conclusions:
The inhalative LC50 of tricalcium bis(orthophosphate) obtained from this study was estimated to be greater than 2.6 mg/L air (gravimetrically determined mean aerosol concentration). This was the highest technically achievable test concentration. There was no indication of relevant sex-related differences in toxicity of the test item.
Executive summary:

The inhalative LC50 > 2.6 mg/L was estimated from the LC50 of the source substance calcium bis(dihydrogenorthophosphate). As explained in the justification for type of information, the differences in molecular structure between target and the source are unlikely to lead to differences in the LC50 that are higher than the typical experimental error of the test method.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
2 600 mg/m³
Quality of whole database:
The available information comprises an adequate and reliable study from a reference substance with similar structure and intrinsic properties. Read-across is justified based on structural similarities of the calciumphosphate compounds and their similarities in PC/ECO/TOX properties (refer to read across justification for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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:
20/8/1984 - 7/11/1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
details on bodyweight observations during and at the end of the test period were not reported
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
yes
Remarks:
occlusive dressing was used, skin was abraded, exposure duration 72 hours
Principles of method if other than guideline:
Study states protocols were consitent with or exceeded the requirements of EPA and OECD guidelines at the time of the study.
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
yes
Species:
rabbit
Strain:
other: Stauffland albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Phillips Rabbitry, Soquel, California
- Weight at study initiation: 1.642 - 2.146 kg
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: abdominal skin
- % coverage: no data
- Type of wrap if used: gauze binder

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- For solids, paste formed: no

Duration of exposure:
72 hr
Doses:
0, 2000 mg/kg bw
No. of animals per sex per dose:
5 male and 5 female
Control animals:
other: sham-treated
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: :no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
no data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
A single dermal dose of 2000 mg/kg bw produced no mortalities in a mixed group of albino rabbits (5 male and 5 female).
Clinical signs:
All rabbits in the test group and the sham-exposed control group appeared normal throughout the 14-day test.
Body weight:
No data
Gross pathology:
10 rabbits from the test material exposed group and 4 rabbits from the sham-exposed group were necropsied on day 14 and appeared normal.
Other findings:
- Other observations: local effects: Local dermal effects in the test material group included darkened dose sites, severe erythema, mild edema and the skin at the abrasion marks was separated and filled with reddish fluid and pus-like material. There were no apparent local dermal effects following a 24 hour sham-treatment.
Interpretation of results:
GHS criteria not met
Conclusions:
Calcium bis(dihydrogenorthophosphate) was found to have a dermal LD50 of >2000 mg/kg bw, therefore, calcium bis(dihydrogenorthophosphate) is not considered to be classified according to Regulation (EC) No. 1272/2008 (EU CLP).
This study has been selected as the key study because the results are sufficient in order to derive a reliable conclusion on classification and labelling in accordance with Regulation EC (No.) 1272/2008 (EU CLP).
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:
refer to analogue justification provided in IUCLID section 13
Reason / purpose:
read-across source
Statistics:
no data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
A single dermal dose of 2000 mg/kg bw produced no mortalities in a mixed group of albino rabbits (5 male and 5 female).
Clinical signs:
All rabbits in the test group and the sham-exposed control group appeared normal throughout the 14-day test.
Body weight:
No data
Gross pathology:
10 rabbits from the test material exposed group and 4 rabbits from the sham-exposed group were necropsied on day 14 and appeared normal.
Other findings:
- Other observations: local effects: Local dermal effects in the test material group included darkened dose sites, severe erythema, mild edema and the skin at the abrasion marks was separated and filled with reddish fluid and pus-like material. There were no apparent local dermal effects following a 24 hour sham-treatment.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 of tricalcium bis(orthophosphate) obtained from this study was estimated to be greater than 2000 mg/kg bw. This was the highest dose tested. There was no indication of toxic signs up to this dose.
Executive summary:

The dermal LD50 > 2000 mg/kg bw was estimated from the dermal LD50 of the source substance calcium bis(dihydrogenorthophosphate). As explained in the justification for type of information, the differences in molecular structure between target and the source are unlikely to lead to differences in the LD50 that are higher than the typical experimental error of the test method.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study from a reference substance with similar structure and intrinsic properties. Read-across is justified based on structural similarities of the calciumphosphate compounds and their similarities in PC/ECO/TOX properties (refer to read across justification for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

A acute oral toxicity study according to OECD 420 was performed with tricalcium bis(orthophosphate) in female Wistar rats. Following a sighting test at a dose level of 2000 mg/kg, additional four fasted female animals were given a single oral dose of test material, as a suspension in distilled water, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy at day 14 after treatment. There were no deaths. Hunched posture was noted in four animals up to day 1 after treatment. There were no other signs of systemic toxicity noted. All animals showed expected gains in bodyweight. No abnormalities were noted at necropsy. Therefore, the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.

No data is available regarding inhalation or dermal toxicity with tricalcium bis(orthophosphate). Reliable data for the analogue substance calcium bis(dihydrogenorthophosphate) (CAS 7758 -23 -8) is available and used for assessment. These studies are considered suitable since the calcium phosphate compounds are structural similar. Both substance dissociate into Ca2+ cations and orthophosphate anions and it is assumed that they will undergo the same pathways once entered the body. 

In an inhalation toxicity study (according to OECD 403) with calcium bis(dihydrogenorthophosphate), groups of 11 week old Wistar rats (5/sex) were exposed by inhalation route (nose only) to the test substance as a dust and observed for 14 days. The maximal achievable dose was 2.6 mg/L. The rats were exposed for 4 hours. The ranges of aerosol concentration, temperature, relative humidity, oxygen content and airflow rate measured during the exposure were considered to be satisfactory for a study of this type. In addition, the test item was considered to be respirable to rats. All animals survived the scheduled observation period. Slight to moderate ruffled fur was noted in all animals after the end of the exposure and was still present in most animals up to test day 2. Thereafter, all animals were free from clinical signs. Transient body weight loss was noted in all animals from test day 1 to test day 2. Normal body weight development was observed thereafter. No macroscopical findings were present at necropsy.

In conclusion, the LC50 of calcium bis(dihydrogenorthophosphate) obtained in this study was estimated to be greater than 2.6 mg/L air (gravimetrically determined mean aerosol concentration). There was no indication of relevant sex-related differences in toxicity of the test item.

 

In an acute dermal toxicity study (similar to OECD 402) with calcium bis(dihydrogenorthophosphate), groups of fasted young Stauffland albino rabbits (5/sex) were dermally exposed to the undiluted test substance for 72 hours at 2000 mg/kg bw. and observed for 14 days. The skin was abraded before treatment and test substance was hold in place by an occlusive dressing. This procedure represents a worst case scenario since the exposure duration was 72 hours instead of 24 hours and occlusive dressing and abrasion of the skin was performed. No mortality or unusual clinical signs occurred during this study. At autopsy, no abnormalities were observed. Local dermal effects in the test material group included darkened dose sites, severe erythema, mild edema and the skin at the abrasion marks was separated and filled with reddish fluid and pus-like material. Under the conditions of this study, the LD50 was considered to be >2000 mg/kg bw.

In conclusion, since calcium bis(dihydrogenorthophosphate) is a reliable read across substance and no acute inhalation or dermal toxicity are observed, tricalcium bis(orthophsphate) is considered to be also not acute toxic via dermal and inhalation route.

Justification for classification or non-classification

The available data on acute oral toxicity with tricalcium bis(orthophosphate) (CAS 7758 -87 4) do not meet the criteria for classification according to Regulation (EC) No. 1272/2008, and are therefore conclusive but not sufficient for classification.

Classification regarding acute dermal and inhalation toxicity is not proposed on the basis of read-across from an analogous substance (calcium bis(dihydrogenorthophosphate) (CAS 7758 -23 -8) because the available data on acute dermal and inhalation toxicity with calcium bis(dihydrogenorthophosphate) (CAS 7758 -23 -8) do not meet the criteria for classification according to Regulation (EC) No. 1272/2008, and are therefore conclusive but not sufficient for classification.