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Description of key information

Several acute oral toxicity studies are present. Although one value of 1267 mg/kg bw in rat is below 2000 mg/kg bw, based on weight of evidence evaluation of the other studies available for sodium nitrate the LD50 is >2000 mg/kg bw. In addition,  no acute dermal toxicity study with the substance itself is present. However, a reliable study with potassium nitrate shows an LD50>5000 mg/kg bw. No acute inhalation toxicity study is required as the vapour pressure and the particle size do show that inhalation is a very unlikely route of exposure.

The read-across rationale is attached in the target study 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:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Non GLP
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
full LD50 performed
GLP compliance:
no
Test type:
other: LD50
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: WIGA
- Weight at study initiation: 230-250 (males), 170-190 (females)
- Fasting period before study: 15-20 h
- Diet: Herilan MRH-Haltung, H. Eggersmann KG

IN-LIFE DATES: From: 2 Oct 1980 To: 22 Oct 1980
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 68.1, 46.4, 31.6, 21.5, 14.7 %

DOSE VOLUME APPLIED: 10 mL/kg
Doses:
6810, 4640, 3160, 2150, 1470 mg/kg body weight
No. of animals per sex per dose:
5 males, 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: Before start, Day 2-4, Day 7, Day 13
- Necropsy of survivors performed: yes
- Other examinations performed: histopathology of liver of dead animals
Statistics:
Probit analysis (Finney)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 3 430 mg/kg bw
Mortality:
6810 mg/kg body weight: 5 males, 5 females died
4640 mg/kg body weight: 5 males, 4 females died
3160 mg/kg body weight: 1 males, 3 females died
2150 mg/kg body weight: 0 males, 0 females died
1470 mg/kg body weight: 0 males, 0 females died
Clinical signs:
dyspnoe, apathy, abnormal posture, ataxia, atonia, pain reflex absent, cornea reflex absent, comatose condition, spasms, tremor, piloerection, trismus, cyanosis, dehydration, ptosis, paresis, poor general condition
Body weight:
normal
Gross pathology:
heart: acute congestion,
lungs: multiple acute dilations. discolouration
stomach: red discolouration of glandular stomach, , bloody ulceration or large bleedings
intestine: atonia, diarrhoea,
kidney: pallor
Other findings:
histology liver: vacuolar degeneration
Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Not classified according to Regulation (EC) 1272/2008
Conclusions:
LD50 = 3500 mg/kg (males)
LD50 = 3200 mg/kg (females)
LD50 = 3430 mg/kg (males and females combined)
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The key studies have klimisch code 2.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Endpoint conclusion
Endpoint conclusion:
no study available

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The study was performed with a substance analogue and the data are read across.
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): 17-21C
- Humidity (%):
- Air changes (per hr):
- 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:
all animals appeared active and healthy
Body weight:
all animals gained weight
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 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

Several oral acute toxicity studies with sodium nitrate are available also with many different species. In a study performed comparable to OECD 401 guideline, rats (5/sex/dose) were dosed with 6810, 4640, 3160, 2150, 1470 mg/kg body weight. The LD50 was determined to be 3430 mg/kg bw. Other studies confirmed this finding, although also lower LD50 values were determined, but most often for species not used for classification, e.g. pig, cow. As a weight of evidence approach, the LD50>2000 mg/kg bw is determined.

No acute dermal toxicity study with sodium nitrate was available. However, a reliable OECD 402 guideline study with potassium nitrate showed no effects on mortality, clinical signs, bodyweight, histopathology at the highest dose tested. Therefore the LD50 is determined to be >5000 mg/kg bw.

No acute inhalation toxicity study is available. However, inhalation is a very unlikely route of exposure with a particle size for sodium nitrate prills of 99%>0.85 mm and of crystalline powder of D10=99 micrometer, and a vapour presssur that is assumed to be negligible. In a supporting study in sheep and dog the NOEC was determined to be 1 -5 mg/m3.

Justification for selection of acute toxicity – oral endpoint

Two key studies and several supporting studies on the substance are available.

Justification for selection of acute toxicity – dermal endpoint

One acute dermal study on the read-across substance Potassium nitrate is available.

Justification for classification or non-classification

According to Annex I of Regulation (EC) No. 1272/2008 sodium 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 for the read-across substance potassium nitrate;

- classification for acute inhalation toxicity is not required based on the unlikelihood of exposure due to the particle size and the vapour pressure of the substance.