Potassium nitrate

Endpoint summary

Description of key information

Based on several studies the oral LD50 is determined to be >2000 mg/kg bw for potassium nitrate. An acute inhalation study performed according to OECD 403 resulted in an LC50 of >0.527 mg/L (highest attainable concentration). An acute dermal toxicity study performed according to OECD 402 resulted in an LD50 of >5000 mg/kg bw. The read-across rationale can be found in the category approach document attached in the appropriate target endpoint record.

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:

2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

Well performed, but limited documented study 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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 60%
DOSAGE PREPARATION:
Prior to use, the test substance was ground in a coffee mill and administered by gavage as a 60% w/w suspension in distilled water (preliminary solubility testing indicated that suspensions in excess of 60% were too viscous to be administered properly).

Doses:

2000 mg/kg b.w.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days after dosing. Bodyweights were recorded prior to administration and again on days 7 and 14 (termination) after dosing. Necropsies were performed on all animals at terminal sacrifice.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

All animals survived

Clinical signs:

other: All animals gained weight

Gross pathology:

No signs of toxicity were observed.

Interpretation of results:

GHS criteria not met

Remarks:

Not classified according to Regulation (EC) 1272/2008

Conclusions:

LD50 > 2000 mg/kg bw

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:

key study

Study period:

June-October 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation.
- Age at study initiation: 8-9 weeks.
- Weight at study initiation: males between 244-279 g and females between 175-197 g.
- Housing: 5 rats/cage according to group and sex in solid polipropylene rat cages (stainless steel grip on top)
- Diet (e.g. ad libitum): rat pellet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Minimum period of 5 days prior to exposure


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 65-68
- Air changes (per hr): Minimum 15 per hour.
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark.

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Inhalation chamber, model head/nose only
- Exposure chamber volume: 63.5 L
- Method of holding animals in test chamber: portholes with transparent perspex rat exposure tubes.
- Source and rate of air: compressed air, 40 liters perminute (inflow)
- Method of conditioning air: air filters and moisture separator.
- System of generating particulates/aerosols: Fluidized bed dust generator system (In-Tox Products, USA)
- Method of particle size determination: Seven stage cascade impactor (Model No 02-150).
- Treatment of exhaust air: 1% sodium hydroxide solution and moisture traps containing silica gel.
- Temperature, humidity, pressure in air chamber: temperature 21.2-23.7 °C, relative humidity 42.1-58.9%, pressure 40 psi

TEST ATMOSPHERE
- Brief description of analytical method used: A open sampler with glass microfibre papers (Whatman International Ltd, Maidstone, England) was used to assess the breathing zone concentration. A suitable measured volume of air (1.77 L per minute) was extracted from the inhalation chamber. At the end of air sampling (1 minute), the glass microfibre papers with the test substance were weighed to determine the concentration of potassium nitrate at the breathing zone of the rats.
- Samples taken from breathing zone: yes, every one hour of exposure.


VEHICLE
- Composition of vehicle: No vehicle

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD 50% 3.13 u, GSD 2.75

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric concentration analysis

Duration of exposure:

4 h

Concentrations:

the maximum achievable concentration (4 hour mean measured value by gravimetric analysis) of potassium nitrate in the air at breathing zone of rats was 0.527 mg/L air.

No. of animals per sex per dose:

5 females and 5 males per group

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Toxic signs and mortality were observed at hourly intervals during the 4 h exposure period and at 1 hour post exposure on the day of exposure. Subsequently, rats were observed daily, twice a day for moribund state and mortality. The detailed clinical signs were recorded once a day.
- Necropsy of survivors performed: yes. Gross pathological examination.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Observations included, but not limited to, evaluation of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic and central nervous system effects, somatomotor activity and behaviours patter and observation of tremor, convulsions, salivation, diarrhea, lethargy, sleep and coma. Body weight was recorded individually, immediately prior to exposure, on day 7 and 14.

Statistics:

As the study conducted was a limit test at the maximum achievable breathing zone concentration, no statistical analysis was required to calculate the LC50.

Preliminary study:

At maximum achievable breathing zone concentration no mortality and lesion of pathological significance were observed in the treatment group as well as in the control group rats.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 0.527 mg/L air

Exp. duration:

4 h

Remarks on result:

other: maximum achievable concentration

Mortality:

No mortality was observed in the control group as well as the treatment group rats.

Clinical signs:

other: No toxic signs were observed in the control group rats as well as in rats treated with 0.527 mg potassium nitrate/L air.

Body weight:

The per cent body weight change of rats from the treatment group were comparable to that of the control group at the end of the experiment.

Gross pathology:

External examination of the terminally sacrificed rats belonginf to both the control and treatment groups did not reveal any lesion of pathological significance.
Visceral examination of control and treatment group rats sacrificed during termination did not reveal any lesion of pathological significance except uuterine distension (rat no 19). Above noticed lesion is physiological/cyclical in nature and coould be considered as spontaneous finding, unrelated with the treatment.

Other findings:

No other findings

Interpretation of results:

GHS criteria not met

Remarks:

Not classified according to Regulation (EC) 1272/2008

Conclusions:

No mortality, no lesion of pathological significance were observed at the maximum achievable breathing zone concentration (0.527 mg/L air). The acute median lethal concentration (LC50) of potassium nitrate was found to be greater than 0.527 mg/L air.

Executive summary:

The study was performed to assess the acute inhalation toxicity (LC50) of potassium nitrate in Wistar rats. The method follow was as per the guidelines of OECD 403 (May 1981).

The study was conducted using inhalation equipment (head/nose only). Two groups of rats comprising of five males and five females each, were used for the study. The rats from Group I were exposed to air passed through inert bed material (iron grid) and served as control group. The rats from Group II were exposed to the maximum achievable breathing zone concentration (0.527 mg/L air) of potassium nitrate. Rats from either group were exposed for 4 hours followed by observation for a period of 14 days. No toxic signs and no mortality were observed in the rats of the control as well as rats treated with potassium nitrate. No effect on body weight was observed during the experiment in the rats from either the control or treated group.

The acute median lethal concentration (LC50) of potassium nitrate was found to be greater than 0.527 mg/L air.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

527 mg/m³ air

Quality of whole database:

The study has klimisch code 1.

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:

October 19 - November 2, 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Principles of method if other than guideline:

limit dose of 5,000 mg/kg tested

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system 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 218-246 grams and females 194-215 grams at experimental start
- Fasting period before study:
- 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: 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Type of coverage:

occlusive

Vehicle:

other: moistened with water

Details on dermal exposure:

TEST SITE
- Area of exposure: dose area of approximately 2 inches x 3 inches
- % coverage: approximately 10% of the body surface

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): (conc. 85%)Five thousand mg/kg of bodyweight of the test substance (6.25 g/kg of test mixture)
- Constant volume or concentration used: yes
- For solids, paste formed: yes

Duration of exposure:

24 hours

Doses:

(conc. 85%) Five thousand mg/kg of bodyweight of the test substance (6.25 g/kg of test mixture)

No. of animals per sex per dose:

5 males and 5 females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days (or other?) 14 days
- Frequency of observations and weighing:
- Necropsy of survivors performed: yes/no Yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
The animals were observed for mortality, signs of gross toxicity, and behavioral changes at 1 and 5 hours after application and at least once daily thereafter for 14 days. 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.

Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

all animals survived

Clinical signs:

other: all animals appeared active and healthy

Gross pathology:

Gross pathology: All animals survived, gained weight and appeared active and healthy. There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behavior. No gross abnormalities were noted for the animals necropsied at the conclusion of the 14-day observation period.

Interpretation of results:

GHS criteria not met

Remarks:

Not classified according to Regulation (EC) 1272/2008

Conclusions:

LD50 > 5,000 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 klimisch code 1.

Additional information

Oral

In an acute oral toxicity study with rabbits, potassium nitrate gave an LD50 of 1900 mg/kg bw. No further information was provided in the publication. The information on methods and results was very limited and the used species (rabbits) is not the preferred one for classification. An also very limited supporting study with rats showed an LD 50 > 2000 mg/kg bw. However, in an OECD 425 guideline study with potassium sodium nitrate showed no signs of toxicity, no mortality, no clinical signs, no effects on bodyweight and no effects on gross pathology at 2000 mg/kg bw.

Dermal

In an OECD 402 acute dermal toxicity study with rats, potassium nitrate did not show any sign of toxicity, no mortality, no clinical signs, no effects on bodyweight and no effects on gross pathology at 5000 mg/kg bw.

Inhalation

In an OECD 403 acute inhalation toxicity study with rats, head/nose exposure was performed. Two groups of rats comprising of five males and five females each, were used for the study. The rats from Group I were exposed to air passed through inert bed material (iron grid) and served as control group. The rats from Group II were exposed to the maximum achievable breathing zone concentration (0.527 mg/L air) of potassium nitrate. Rats from either group were exposed for 4 hours followed by observation for a period of 14 days. No toxic signs and no mortality were observed in the rats of the control as well as rats treated with potassium nitrate. No effect on body weight was observed during the experiment in the rats from either the control or treated group. The acute median lethal concentration (LC50) of potassium nitrate was found to be greater than 0.527 mg/L air, the highest achievable concentration.

Justification for selection of acute toxicity – oral endpoint

One acute oral study on the read-across substance potassium sodium nitrate is available.

Justification for selection of acute toxicity – inhalation endpoint

One study on the substance is available.

Justification for selection of acute toxicity – dermal endpoint

One study on the substance is available.

Justification for classification or non-classification

According to Annex I of Regulation (EC) No. 1272/2008 potassium nitrate is not classified based on the available data:

- classification for acute oral toxicity is not required based on ATE >2000 mg/kg bw;

- classification for acute dermal toxicity is not required based on ATE >2000 mg/kg bw;

- classification for acute inhalation toxicity is not required based on no observed effects at the maximum achievable breathing zone concentration.