Potassium nitrate

Endpoint summary

Description of key information

No reliable skin irritation study with potassium nitrate itself is present. However, in a reliable skin irritation study in rabbits (performed comparable to OECD 404) with ammonium nitrate, no signs of skin irritation was observed up to 72 hours.

Potassium nitrate did not show irritation effects in an in vitro and in vivo eye irritation study according to the respective OECD guidelines.

The read-across rationale can be found in the category approach document attached in the appropriate target endoint record.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Sufficient information on the M&M is available to determine the reliability. The study has been performed according to OECD and/or EC guidelines. However, since the study was performed with a substance analogue and the data are read across, the Klimisch score is 2.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Remarks:

study performed before GLP was in place.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bantin and Kingman Ltd., The Field Station, Grimston, Aldbrough, Hull, HU11 4QE
- Weight at study initiation: 2.72-3.23 kg
- Housing: individually in grid floor cages
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum):free access
- Acclimation period: at least 3 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22 C
- Humidity (%): 44-53%
- Air changes (per hr): single air conditioned
- Photoperiod (hrs dark / hrs light):14 hours artificial light (06.00-20.00)

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

other: each animal served as its own control

Amount / concentration applied:

TEST MATERIAL
- Concentration (if solution): 0.5 g moistened with water

Duration of treatment / exposure:

4 hours

Observation period:

up to 72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: covered with gauze patch and plastic collar around the neck


REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with disposable paper towel moistened with water.
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Time point: 1h was taken into account as well

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Time point: 1h was taken into account as well

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Time point: 1h was taken into account as well

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Time point: 1h was taken into account as well

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Time point: 1h was taken into account as well

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Time point: 1h was taken into account as well

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

5

Reversibility:

other: not applicable

Remarks on result:

other: Time point: 1h was taken into account as well

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

5

Reversibility:

other: not applicable

Remarks on result:

other: Time point: 1h was taken into account as well

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

5

Reversibility:

other: not applicable

Remarks on result:

other: Time point: 1h was taken into account as well

Interpretation of results:

GHS criteria not met

Remarks:

Not classified according to Regulation (EC) 1272/2008

Conclusions:

P0018 (ammonium nitrate) was regarded as non-irritant to rabbit skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd., Loughborough, UK.
- Age at study initiation: Animals used within the study were 12-20 weeks old.
- Weight at study initiation: The animals weighed 2.08 or 2.14 kg.
- Housing: Individually housed in suspended cages.
- Diet (e.g. ad libitum): Ad libitum (2030 Teklad Global Rabbit diet supplied by Harlan Laboratories U.K. Ltd, Oxon, UK)
- Water (e.g. ad libitum): Free access to water.
- Acclimatization period: at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 – 23ºC
- Humidity (%): 30 - 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness per day


IN-LIFE DATES:

Vehicle:

unchanged (no vehicle)

Controls:

other: One eye of each animal remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied weight with unit: 0.1 mL (approximately 92 mg)

Duration of treatment / exposure:

Single instillation on Day 1

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48, and 72 hours after instillation of the test substance.

Number of animals or in vitro replicates:

2 Males

Details on study design:

STUDY DESIGN
Animals free of ocular damage were used. Initially, a single rabbit was treated. A volume of 0.1 mL (approximately 92 mg) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The lids were hold together for about one second immediately aftert treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made.

After consideration of the ocular responses produced in the first treated animal, a second animal was treated. In order to minimise pain on application of the test item, one drop of local anaesthetic (Tetracaine hydrochloride 0.5%, Chauvin Pharmaceuticals, Romford, Essex, UK) was instilled into both eyes of the second animal 1 to 2 minutes before treatment.

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation given below.

Any other ocular effects were also noted. Examination of the eyes was facilitated by the use of the light source from a standard opthalmoscope.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

OBSERVATION
The irritation was assessed according to a numerical scoring system (Draize Scale for Scoring Ocular Irritation)

SCORING SYSTEM:

CORNEAL IRRITATION
Degree of opacity (most dense are used)
0: No opacity
1: Scattered or diffuse areas of opacity, details of iris clearly visible
2: Easily discernible translucent area, details of iris slightly obscured
3: Opalescent areas, no details of iris visible, size of pupil barely discernible
4: Opaque, iris not discernible through the opacity

Area of cornea involved:
1: One quarter (or less) but not zero
2: Greater than one quarter, but less than half
3: Greater than half, but less than three quarters
4: Greater than three quarters, up to whole area

IRIS
0: Normal
1: Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination thereof) iris still reacting to light (sluggish reaction is positive)
2: No reaction to light, hemorrhage, gross destruction (any or all of these)

CONJUNCTIVAL IRRITATION
Redness (refers to palpebrae and bulbar conjuntivae, excluding cornea and iris):
0: Vessels normal
1: Vessels definitely injected above normal
2: More diffuse, deeper crimson red, individual vessels not easily discernible
3: Diffuse beefy red

Chemosis:
0: No swelling
1: Any swelling above normal (includes nictitating membranes)
2: Obvious swelling with partial eversion of lids
3: Swelling with lids about half closed
4: Swelling with lids more than half closed

Discharge:
0: No discharge
1: Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2: Discharge with moistening of the lids and hairs just adjacent to lids
3: Discharge with moistening of the lids and hairs a considerable area around the eye

Irritation parameter:

cornea opacity score

Remarks:

mean

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Remarks:

mean

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Remarks:

mean

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

other: not applicable

Irritation parameter:

iris score

Remarks:

mean

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Remarks:

mean (redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

conjunctivae score

Remarks:

mean (redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Remarks:

mean

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

chemosis score

Remarks:

mean

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

mean (discharge)

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

conjunctivae score

Remarks:

mean (discharge)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Irritation
Instillation of approximately 96 mg of Natriumnitrat HQ unbehandelt (non-food grade) (a volume of approximately 0.1 mL) into one eye of each of three rabbits resulted in effects on the cornea, iris and conjunctivae.
The corneal injury consisted of slightly dulling of the luster only. This was seen in two animals and was resolved within 24 hours after instillation in both animals.
Iridial irritation grade 1 was observed in two animals and resolved within 24 hours in both animals.
The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 7 days in all three animals. For redness the mean over 24, 48 and 72 hours was grade 2.0 in all three animals.

Treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.

Corrosion
There was no evidence of ocular corrosion.

See also attached tables

Interpretation of results:

GHS criteria not met

Remarks:

Not classified according to Regulation (EC) 1272/2008

Conclusions:

The material did not meet the criteria for classification as an eye irritant substance according to Regulation (EC) 1272/2008

Executive summary:

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

-OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002)

- Method B5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 440/2008

A single application of the test item to the non-irrigated eye of two rabbits produced moderate conjunctival irritation. One treated eye appeared normal at the 72-Hour observation and the other treated eye appeared normal at the 7-Day observation.

Based on the results, the test material did not meet the criteria for classification as an irritant according to Regulation (EC) 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No reliable skin irritation study with potassium nitrate itself is present.

However, in a reliable skin irritation study in rabbits (performed comparable to OECD 404) with ammonium nitrate, no signs of skin irritation was observed up to 72 hours.

Potassium nitrate did not show irritattion effects on in vitro eye irritation study according to OECD guideline 437 . Following sequential testing strategy, an in vivo eye irritation study in rabbits was performed according to OECD 405. A single application of the test item to the eye of two rabbits produced moderate conjunctival irritation. One treated eye appeared normal at the 72 -hour observation and the other treated eye appeared normal at the 7 -day observation. The test material did not meet the criteria for classification as eye irritant.

Justification for selection of skin irritation / corrosion endpoint:

One in vivo key study on the read-across substance Ammonium nitrate is available. The study has been performed according to OECD and/or EC guidelines. However, since the study was performed with a substance analogue and the data are read across, the Klimisch score is 2.

Justification for selection of eye irritation endpoint:

One in vivo study on the susbstance 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 skin irritation is not required based on no observed effects up to 72 hours of exposure to the read-across substance ammonium nitrate;

- classification for eye irritation is not required based on only very moderate effects observed (corneal opacity < 1, iritis < 1, conjunctival redness < 2 and conjunctival oedema (chemosis) < 2) and full reversibility of the effects.