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Administrative data

Description of key information

No reliable studies with single superphosphate are present. Based on reliable studies with diammonium hydrogenorthophosphate for acute oral, dermal and inhalation exposure to rats, the oral and dermal LD50 is >2000 mg/kg bw and the LC50 is > 5 mg/L. This is confirmed by acute oral and dermal toxicity studies with calcium (bisdihydrogenorthophosphate). The read-across rationale can be found in the category approach document attached in the target record and is fully incorporated in the CSR.

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:
October 6 – 26, 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Received from Ace Animals, Inc., Boyertown, PA on September 19 and 26, 2000
- Age at study initiation: Young adult (9-11 weeks)
- Weight at study initiation: males 275 – 310 grams and females 195-230 grams
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in
the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least
three times per week.
- Diet (e.g. ad libitum): Purina Rodent Chow #5012
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum by an automatic water dispensing system.
- Acclimation period: 13 or 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature Range: 18-22ºC
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
An initial dose of 2000 mg of the test substance per kilogram of bodyweight was administered to one healthy female rat by oral gavage. Due to the
absence of mortality in this animal a second female received the same dose level. Following the completion of dosing and 100% survival in a total of
three females, a group of three males was tested (simultaneously) at the above dose level. Prior to use, the test substance was ground in a coffee mill and administered by gavage as a 70% w/w suspension in distilled water (preliminary solubility testing indicated that suspension in excess of 70% were too viscous to be administered properly).
Doses:
1 x 2000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: prior to administration and again on Days 7 and 14 (termination) after dosing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
No data
Preliminary study:
no data
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
All animals survived
Clinical signs:
Animals appeared active and healthy throughout the study period
Body weight:
Animals gained weight
Gross pathology:
FEMALES: All tissues/organs No gross abnormalities
MALES: All tissues/organs No gross abnormalities
Other findings:
No data

none

Interpretation of results:
GHS criteria not met
Remarks:
Not classified according to Regulation (EC) No. 1272/2008
Conclusions:
No signs of toxicity were observed. LD50 > 2000 mg/kg.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study has been performed according to OECD and/or EC guidelines and according to GLP principles. However, since the study was performed with a substance analogue and the data are read across, the Klimisch score is 2.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
23 March 2010 - 06 April 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
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:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Crl:WI(Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation:Young adult animals were selected (approximately 10 weeks old).
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: No.
- Housing:
Before exposure:
Group housing of five animals per sex per cage in labeled Macrolon cages (type IV; height 18 cm) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
After exposure:
Group housing as described above, except that a paper sheet was introduced into the cage covering the bedding and cage enrichment to prevent suffocation in case of bad health condition. At the end of the day of exposure the paper sheet was removed.
- Diet (e.g. ad libitum):Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) except during exposure to the test substance.
- Water (e.g. ad libitum):Free access to tap water except during exposure to the test substance.
- Acclimation period: At least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 – 21.7°C
- Humidity (%): 42 – 60%
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 23 March 2010 To: 06 April 2010
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle).
Details on inhalation exposure:
Animals were exposed to the test substance via the inhalatory route. For this purpose the animals were placed in restraining tubes, connected to the exposure chamber.
The design of the exposure chamber was based on the flow past nose-only inhalation chamber (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983). The chamber consisted of 3 animal sections with 8 animal ports each. The number of animal sections and number of open animal ports were adapted to the air flow in such a way that at each animal port the theoretical air flow was on average 1.4 L/min, which ensures an adequate oxygen supply to the test animals. The inlet of the test atmosphere was located at the top section and the outlet was located at the bottom section. The direction of the flow of the test atmosphere guaranteed a freshly generated atmosphere for each individual animal.
The placement of the individual animals in the inhalation chamber is shown in figure 2. All components of the exposure chamber, which could come in contact with the test material, were made of stainless steel, glass, rubber or plastic. To avoid exposure of the personnel and contamination of the laboratory the exposure chamber was placed in a fume hood, which was maintained at a slightly negative pressure.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
5.5 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Diammonium hydrogenorthophosphate was administered as an aerosol by inhalation for a single but interrupted exposure lasting 4 hours and 8 minutes in total to one group of three male and three female Wistar rats. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15).
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air
Exp. duration:
4 h
Mortality:
No mortality occurred and no clinical signs were noted during the study.
Clinical signs:
other: During and after exposure no clinical signs were noted.
Body weight:
Overall body weight gain in males and females were within the range expected for rats of this strain and age used in this type of study.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
GHS criteria not met
Remarks:
Not classified according to Regulation (EC) No. 1272/2008
Conclusions:
The inhalatory LC50, 4h value of Diammonium hydrogenorthophosphate in Wistar rats was considered to exceed 5 mg/L under the conditions in this study.
Executive summary:

Assessment of acute inhalatory toxicity with Diammonium hydrogenorthophosphate in the rat

 

The study was carried out based on the guidelines described in:

- OECD Guidelines, Section 4, Health Effects. No.403, "Acute Inhalation Toxicity", September 2009.

- Commission Regulation (EC) No 440/2008,B.2. Acute Toxicity (inhalation),L142, May 2008.

- EPA OPPTS 870.1300, Acute inhalation Toxicity. EPA 712-C-98-193, August 1998.

- JMAFF, 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.

 

Diammonium hydrogenorthophosphate was administered as an aerosol by inhalation for 4 hours to one group of five male and five female Wistar rats. Animals were subjected to daily observations and determination of body weight on Days 1, 2, 4, 8 and 15. Macroscopic examination was performed after terminal sacrifice (day 15).

 

The mean actual time-weighed concentration was 4.84 ± 0.28 mg/L. The nominal concentration was 442.92 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 1.1%.

 

The Mass Median Aerodynamic Diameter (MMAD) and geometric standard deviation (gsd) were determined twice. The MMAD was 6.0mm and 5.6mm respectively and the gsd was 1.8 in both cases.

 

No mortality occurred and no clinical signs were noted during and after exposure.

 

The body weight gain shown by the animals over the study period was considered to be normal.

 

No abnormalities were found at macroscopic post mortem examination of the animals.

 

Agglomeration of aerosol particles at this high concentration tested resulted in MMAD values to exceed the recommended range of 1 - 4 µm. Additional efforts to reduce the MMAD were unsuccessful and the MMAD remained significantly larger than 4 µm (i.e. use of a micronizing jet-mill and two cyclones, lowering the concentration down to 1 mg/L). Since the gsd of 1.8 determined during the actual exposure indicated that the aerosol was polydisperse and since approximately 20% of the particles were smaller than 4 µm, it can be assumed that test substance deposition in the lower respiratory tract occurred during the exposure.

 

It was therefore considered that the outcome of this study is valid for the limit concentration of 5 mg/L.Since no mortality occurred at the limit concentration, no full study using lower concentrations was conducted.

 

The inhalatory LC50, 4hvalue of Diammonium hydrogenorthophosphate in Wistar rats was considered to exceed 5 mg/L under the conditions in this study.

 

Based on these results Diammonium hydrogenorthophosphate does not have to be classified and has no obligatory labelling requirement for acute inhalation toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2007) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 000 mg/m³
Quality of whole database:
The study has been performed according to OECD and/or EC guidelines and according to GLP principles. However, since the study was performed with a substance analogue and the data are read across, the Klimisch score is 2.

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:
17 October 2000 - 31 October 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Animal Room Temperature Range in study was 17-22°C compared to 22°C± 3° in OECD402. The study integrity was not adversely affected by the deviation.
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Received from Ace Animals, Inc., Boyertown, PA on October 10, 2000
- Age at study initiation: young adult (8-9 weeks)
- Weight at study initiation: males 200-227 grams and females 170-184 grams
- Fasting period before study: not applicable
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): Purina Rodent Chow #5012
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
DAP was applied to the shaved intact skin on the back of each rat and covered with gauze pads. After 24 hours the pads were removed and the test areas gently wiped with water. The animals were observed for a post-dosing period of 14 days. Prior to application, the test substance was ground in a coffee mill and moistened to achieve a dry paste by preparing a 85% w/w mixture.
Duration of exposure:
24 hours
Doses:
No data
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
The animals were observed for a post-dosing period of 14 days.
- Frequency of observations and weighing: The animals were observed for mortality, signs of gross toxicity, and behavioral changes at 1 and 3
hours after application and at least once daily thereafter for 14 days. Individual bodyweights of the animals: prior to test substance application Day 0 and on Days 7 and 14 (termination).
- Necropsy of survivors performed: yes (all animals)
- Other examinations performed: Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma. Tissues and organs of the thoracic and abdominal cavities were examined at necropsy.
Statistics:
No data
Preliminary study:
none
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
All animals survived.
Clinical signs:
All animals appeared active and healthy throughout the test.
Body weight:
All animals gained weight.
Gross pathology:
No gross abnormalities were noted for any of the animals.
Other findings:
No other signs of gross toxicity, adverse pharmacologic effects or abnormal behavior.

none

Interpretation of results:
GHS criteria not met
Remarks:
Not classified according to Regulation (EC) No. 1272/2008
Conclusions:
No signs of toxicity were observed. LD50 > 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 has been performed according to OECD and/or EC guidelines and according to GLP principles. However, since the study was performed with a substance analogue and the data are read across, the Klimisch score is 2.

Additional information

Oral

No reliable studies for single superphosphate are present. However, for acute oral toxicity, diammonium hydrogenorthophosphate showed in an OECD 425 guideline study no mortality and no toxicity to rats up to 2000 mg/kg bw. Therefore the LD50 was determined to be >2000 mg/kg bw. In addition, a reliable study with calcium bis(dihydrogenorthophosphate) is available, performed according to the relevant guidelines (EU and US). The acute oral LD50 in male and female rats was estimated to be > 3986 mg/kg bw. Less reliable studies with single superphosphate itself supported this conclusion, as LD50 was shown to be > 2000 mg/kg bw.

Dermal

No studies for single superphosphate are present. However, for acute dermal toxicity, diammonium hydrogenorthophosphate showed in an OECD 402 guideline study no mortality and no toxicity to rats up to 5000 mg/kg bw. Therefore the LD50 was determined to be >5000 mg/kg bw. In addition, a reliable study with calcium bis(dihydrogenorthophosphate) performed according to the relevant guidelines (EU and US) is available. The LD50 > 2000 mg/kg bw.

Inhalation

No studies for single superphosphate are present. However, for acute inhalation toxicity, diammonium hydrogenorthophosphate particles showed in an OECD 403, EC B.2 and EPA guideline study no mortality and no toxicity to rats up to 5.1 mg/L. Therefore, the LC50 was determined to be >5 mg/L.


Justification for selection of acute toxicity – oral endpoint
One acute oral key study on the read-across substance diammonium hydrogenorthophosphate is available.

Justification for selection of acute toxicity – inhalation endpoint
One acute inhalation study on the read-across substance diammonium hydrogenorthophosphate is available.

Justification for selection of acute toxicity – dermal endpoint
One acute dermal key study on the read-across substance diammonium hydrogenorthophosphate is available.

Justification for classification or non-classification

Based on the data available, single super phosphate does not have to be classified according to the CLP Regulation for acute oral, dermal and inhalation toxicity.