Calcium bis(dihydrogenorthophosphate)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20/8/1984 to 7/11/1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

details on bodyweight observations during and at the end of the test period were not reported

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

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:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Calcium bis(dihydrogenorthophosphate)

EC Number:

231-837-1

EC Name:

Calcium bis(dihydrogenorthophosphate)

Cas Number:

7758-23-8

Molecular formula:

CaH4O8P2

IUPAC Name:

calcium dihydrogen phosphate

Details on test material:

- Name of test material (as cited in study report): monocalcium phosphate anhydrous
- Physical state: solid; white powder
- Analytical purity: no data
- Lot/batch No.: 525

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Portage, Michigan
- Age at study initiation: no data
- Weight at study initiation: Male: 202-250 g
Female: 153-226 g
- Fasting period before study: 16-18 hours prior to treatment
- Housing: no data


ENVIRONMENTAL CONDITIONS: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED:
dose volume to body weight ratio (mL/kg): 10

Doses:

Male: single dose of 5000 mg/kg bw
Female: 5000, 4467, 3981, 3162 mg/kg bw

No. of animals per sex per dose:

10 males / females per dose group.
40 females in control group.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes (dead animals were also subject to necropsy)
- Other examinations performed: clinical signs

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

3 986 mg/kg bw

Based on:

test mat.

95% CL:

> 3 341 - < 4 757

Mortality:

Male:
At a dose level of 5000 mg/kg bw 3 out of 10 rats died within the first 24 hours (1 rat died before the first observation).
In the vehicle control group no rats died.

Female:
At a dose level of 5000 mg/kg 7 rats died within 24 hours.
At a dose level of 4467 mg/kg 7 rats died within 24 hours.
At a dose level of 3981 mg/kg 3 rats died within 24 hours.
At a dose level of 3162 mg/kg 3 rats died within 24 hours.
No rats died in the control group.

Clinical signs:

other: Male: Dose level: 5000 mg/kg. The following adverse clinical signs were noted; mild to moderate depression (9 rats), diahorrea (1 rat) and piloerection (8 rats). The survivors appeared normal within 24 hours. Dose level: 0 mg/kg. All rats appeared norma

Gross pathology:

See below for details of necropsy.

Any other information on results incl. tables

NECROPSY:

Male; dose level 5000 mg/kg.10 rats were necropsied. Observations for the rats that died during the test included evidence of salivation (1 rat); clear discharge from the nostrils (2 rats); pale lungs (1 rat), reddened lungs (1 rat), a purple-spotted thymus (1 rat), a pale liver (1 rat), darkened spleens (2 rats); test material-like fluid in the gastrointestinal tract (1 rat); a distended stomach filled with clear fluid (1 rat); reddened stomach mucosa (1 rat); pale intestines (1 rat); pale kidneys (1 rat); and gelatinous appearing intestines (1 rat). The survivors were necropsied following termination on day 14. Observations for 1 rat included pale lungs, a pale liver, a darkened spleen, test material-like fluid in the stomach and dark gelatinous-like material lining the stomach.

Male, dose level 0 mg/kg.10 rats were necropsied following termination on day 14 and appeared normal.

Female, dose level 5000 mg/kg.10 rats were necropsied. Observations for the rats that died included evidence of lacrimation (3 rats); reddish stains at the nostrils (1 rat), mottled lungs (4 rats); clear fluid in the thoraic cavity (2 rats); greenish lungs (2 rats); purple-spotted thymus (2 rats); pale livers (6 rats); darkened or dark-tipped spleens (7 rats); test material-like fluid in the gastrointestinal tract (1 rat); distended stomachs filled with clear fluid (4 rats); pale kidneys (5 rats); pale intestines (3 rats); and pale uterine horns (6 rats). The survivors were necropsied following termination on day 14 and appeared normal.

Female, dose level 4467 mg/kg. 9 rats were necropsied (1 rat was cannibalised and therefore not necropsied). Observations for the remaining rats that died during the test included yellowish anogenital stains (2 rats); evidence of lacrimation (1 rat); pale lungs (1 rat); discoloured lungs (1 rat); mottled livers (1 rat); pale kidneys (2 rats); a darkened spleen (1 rat); reddened intestines (1 rat) and gelatinous appearing intestines ( 1rat). The survivors were necropsied following termination on day 14 and appeared normal.

Female, dose level 3981 mg/kg.10 rats were necropsied. Observations for the rats that died included cannabalised facial areas (2 rats); pale lungs (3 rats); pale kidneys (4 rats); reddish-yellow gelatinous fluid in the intestines (4 rats), darkened spleens (2 rats); and a pale spleen (1 rat). The survivors were necropsied following termination on day 14 and appeared normal.

Female, dose level 3162 mg/kg.10 rats were necropsied. Observations for the rats that died included a purple-spotted thymus (1 rat); reddened lungs (3 rats); pale, dark-edged livers (3 rats); darkened spleens (2 rats); and pale kidneys ( 2 rats). The survivors were necropsied following termination on day 14 and appeared normal.

Female, dose level 0 mg/kg. 40 rats were necropsied following termination on day 14 and appeared normal.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of calcium bis(dihydrogenorthophosphate) in the male rat was calculated to be >5,000 mg/kg bw and the LD50 in female rats was calculated to be 3986 mg/kg bw.
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). Calcium bis(dihydrogenorthophosphate) is not considered to be classified according to Regulation (EC) No. 1272/2008 (EU CLP).