Nitric acid, ammonium calcium salt

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 14 - October 3, 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

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

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Calcium nitrate

EC Number:

233-332-1

EC Name:

Calcium nitrate

Cas Number:

10124-37-5

Molecular formula:

Ca(NO3)2

IUPAC Name:

calcium dinitrate

Constituent 2

Reference substance name:

Ammonium nitrate

EC Number:

229-347-8

EC Name:

Ammonium nitrate

Cas Number:

6484-52-2

Molecular formula:

H3N.HNO3

IUPAC Name:

Ammonium nitrate

Constituent 3

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Dihydrogen oxide

Test material form:

solid: granular

Details on test material:

- Name of test material (as cited in study report): CN-nitcal
- Physical appearance: white granules
- Storage conditions:

Test animals

Species:

rat

Strain:

other: Wistar strain Crl:WI

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: 8-9 weeks old
- Weight at study initiation: 176 - 221 g
- Fasting period before study: overnight (for a maximum of 20 hours) prior to dosing until 3-4 hours after administration
- Housing: 3 animals per cage
- Diet (e.g. ad libitum): ad libitum to pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiaten GmbH, Soest, Germany)
- Water (e.g. ad libitum): ad libitum to tap water
- Acclimation period: at least 5 days before start of treatment


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 22.8
- Humidity (%): 46 - 91
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: 14 September 2006 To: 03 October 2006

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: see dosage preparation
- Amount of vehicle (if gavage): see dosage preparation
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.
- Lot/batch no. (if required): not applicable
- Purity: not applicable


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg


DOSAGE PREPARATION (if unusual): The formulation (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. The concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of ml/kg body weight.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The first group was treated at a dose level of 300 mg/kg (according to OECD 423 guideline). The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval beween the dose groups.

Doses:

300 mg/kg (10 ml/kg) body weight
2000 mg/kg (10 ml/kg) body weight

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: mortality: twice daily - body weight: day 1, 8, 15 and at death - clinical signs: once daily from day 1-15
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Mortality:

300 mg/kg (1 dose group) = 0/3
300 mg/kg (2 dose group) = 0/3
2000 mg/kg = 3/3

Clinical signs:

other: 300 mg/kg: Hunched posture 2000 mg/kg: Lethargy, hunged/flat posture, laboured respiration, piloerection, ptosis, hypothermia The surviving animals had recovered from the symptoms by day 2.

Gross pathology:

Abnormalities of the stomach (dark red discolouration of glandular mucosa) were found in the animals that died during the study, at macroscopic post mortem examination. No adnormalities were found in the surviving animals.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 value of CN-Nitcal in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.
According to the OECD 423 test guideline the LD50 cut-off value was considered to be 500 mg/kg body weight.