Calcium nitrite

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

7 February - 7 March 1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Good quality study, conducted to GLP. The discrepancy in acclimation period is not expected to influence the validity of the results. No details given on vehicle.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: US EPA TSCA Test rules (40 CFR Part 772.112-121 Subpart C)

Version / remarks:

26 July 1979

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Acclimation period of 3 days was used (guideline recommends at least 5 days)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Calcium nitrite

EC Number:

237-424-2

EC Name:

Calcium nitrite

Cas Number:

13780-06-8

Molecular formula:

Ca.2HNO2

IUPAC Name:

calcium nitrite

Test material form:

solid: particulate/powder

Details on test material:

- Density: 2.23 g/ml
- Other: pH: 11.5

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 Breeding Laboratories (Wilmington, MA)
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 200-400 g
- Fasting period before study: Night prior to dosing
- Housing: Individually in suspended, stainless steel wire mesh cages
- Diet (e.g. ad libitum): Commercial rodent ration (Agway Prolab 3000) ad libitum
- Water (e.g. ad libitum): Municipal tap water ad libitum
- Acclimation period: 3 days [current OECD guideline recommends 5 days]

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 72 ± 3°F (20.6-22.9°C)
- Humidity (%): 50 ± 15%
- Air changes (per hr): 10-13
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: not specified, presumably water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): up to 0.86 mL (females) or 1.53 mL (males) (20 mL/kg)
- Justification for choice of vehicle: no data

Doses:

Main test: 100, 200, 300 or 400 mg/kg bw
[Preliminary test: 100, 300, 600, 900 or 1200 mg/kg bw]

No. of animals per sex per dose:

5
[3 males/group in preliminary test]

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily (clinical observations and mortality only)
- Necropsy of survivors performed: yes
- Other examinations performed: no

Statistics:

Calculation of the LD50, probit slope, and 95% confidence limit (CL) for the LD50 were achieved using an Applie II Plus Computer with a programme by Tallarida RJ and Murray RB (1981).

Results and discussion

Preliminary study:

Mortalities were 0, 2, 2, 3 and 3 at respective doses of 100, 300, 600, 900 and 1200 mg/kg bw

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

283 mg/kg bw

Based on:

test mat.

95% CL:

>= 233 - <= 343

Mortality:

In the main test there was no mortality at the lowest tested dose (100 mg/kg bw), while all animals died at the highest tested dose (400 mg/kg bw). A single animal of each sex died at 200 mg/kg bw; 1 male and 4 females died at 300 mg/kg bw.

Clinical signs:

other: At 300 mg/kg bw, bluish cyanotic ears and feet as well as abnormally slow respiration were observed in three males, two of which also showed tremors and convulsions; such effects were also seen in a single female.

Gross pathology:

Necropsy of those animals displaying treatment-related mortality revealed moderate haemorrhaging in the stomach and small intestine. Other observations included a very pale integument, subcutis and liver, along with dusky leaden lungs which contained very little blood when sectioned. Mortailty was attributed to asphyxiation.

No significant lesions were observed in surviving animals.

Other findings:

- Organ weights: no data
- Histopathology: no data
- Potential target organs: no data

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

In a guideline study, to GLP, the acute oral LD50 of calcium nitrite was determined to be 283 mg/kg bw in rats.

Executive summary:

The acute oral toxicity of calcium nitrite (anhydrous powder) was investigated in Sprague-Dawley rats, in a US EPA TSCA guideline study (essentially equivalent to OECD Test Guideline 401), conducted according to GLP. Animals (5/sex/group) were administered the test substance (dissolved in an unspecified vehicle, presumably water) by oral gavage at doses of 100, 200, 300 or 400 mg/kg bw, and observed for up to 14 days. The dose range used in the main test was informed by a preliminary test involving gavage administration at levels of 100, 300, 600, 900 or 1200 mg/kg bw to male rats (3/group).

 

All animals died at the top dose (400 mg/kg bw) in the main test, while there were 2 and 5 deaths at the intermediate doses (200 and 300 mg/kg bw respectively). Deaths occurred within hours of test material administration and were attributed to asphyxiation. No mortality was observed in the low dose group (100 mg/kg bw). In the animals that died, clinical signs of toxicity were limited to discolouration of the ears/feet, tremors and reduced respiration in certain animals in the 300 mg/kg bw dose group. Upon necropsy, toxic effects included moderate haemorrhaging of the stomach and small intestine as well as effects on the skin, liver and lungs. No significant lesions were observed in surviving animals.

 

The acute oral LD50 was determined (using probit analysis) to be 283 mg/kg bw in rats (95% CL 233-343 mg/kg bw). Based on the results of this study, the test material should be classified for acute oral toxicity (category 3) according to EU CLP criteria (EC 1272/2008).