Sodium methanolate

Endpoint summary

Description of key information

Skin Irritation: corrosive 
Eye irritation: corrosive 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Well documented report, details missing

Principles of method if other than guideline:

The test substance (ca. 0.5 g of the 80% suspension in water) was applied to a 2.5 x 2.5 cm application site of white Vienna rabbits for 3 min under occlusive conditions. The skin was left intact. Animals were observed for 8 days and skin changes were observed on working days. Findings were recorded after 24, 48 hours and at the end of the observation period. Findings were graded as described in OECD test guideline 404.

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler
- Weight at study initiation: 2.91 and 3.0 kg

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

other: untreated skin of the same animals

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ca. 0.5 g
- Concentration (if solution): 80%

Duration of treatment / exposure:

3 minutes

Observation period:

8 days

Number of animals:

2

Details on study design:

no information given

Irritation parameter:

erythema score

Basis:

other: 1 animal of 2

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

extended patchy necrosis (not specified if animal 1 or 2), which led to full thickness necrosis of the skin (day 8)

Irritation parameter:

erythema score

Basis:

other: 1 animal of 2

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other:

Remarks:

patchy necrosis (not specified if animal 1 or 2), which led to full thickness necrosis of the skin (day 8)

Irritation parameter:

edema score

Basis:

other: 1 animal of 2

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other:

Remarks:

extended in 1 animal (not specified if animal 1 or 2)

Irritation parameter:

edema score

Basis:

other: 1 animal of 2

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 day

Remarks on result:

other:

Remarks:

extended in 1 animal (not specified if animal 1 or 2)

Irritation parameter:

erythema score

Basis:

other: 1 animal of 2

Time point:

48 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: extended patchy necrosis (not specified if animal 1 or 2), which led to full thickness necrosis of the skin (day 8)

Irritation parameter:

erythema score

Basis:

other: 1 animal of 2

Time point:

48 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: very severe necrosis (parchement-like; not specified if animal 1 or 2), which led to full thickness necrosis of the skin (day 8).

Irritation parameter:

edema score

Basis:

animal: 1 animal of 2

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: extended in 1 animal (not specified if animal 1 or 2)

Irritation parameter:

edema score

Basis:

other: 1 animal of 2

Time point:

48 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: extended in 1 animal (not specified if animal 1 or 2)

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Remarks on result:

not determinable

Remarks:

score not provided due to sever necrosis

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Remarks on result:

not determinable

Remarks:

score not provided due to severe necrosis

Irritant / corrosive response data:

- 3 min: Erythema: 2 (2/2 animals), Edema 0 (2/2 animals)
- 8 days: Erythema: 4 (Necrosis, leather-like, 2/2 animals), Edema: 1 (2/2 animals)

Interpretation of results:

Category 1A (corrosive) based on GHS criteria

Conclusions:

The test material was found to be corrosive to rabbit skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

study design not suitable for categorization of corrosion

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd.
- Age at study initiation: twelve to sixteen weeks
- Weight at study initiation: 2.4 - 2.9 kg
- Housing: individually in suspended metal cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-18
- Humidity (%): 60-75
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

A quantity of 0.5 g of the test material, moistened with 0.5 mL of distilled water, was introduced under a 2.5 cm X 2.5 cm gauze patch and placed in position on the shorn skin.

Duration of treatment / exposure:

4 hours

Observation period:

Due to severe adverse dermal reactions and for animal welfare reasons the study was terminated after the one-hour observation.

Number of animals:

6

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 1 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Due to severe adverse dermal reactions and for animal welfare reasons the study was terminated after the one-hour observation.

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 1 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 1 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

other: 1 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

other: 1 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

other: 1 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 1 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 1 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 1 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #4

Time point:

other: 1 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #5

Time point:

other: 1 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal #6

Time point:

other: 1 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Due to severe adverse dermal reactions and for animal welfare reasons the study was terminated after the one-hour observation.

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Due to severe adverse dermal reactions and for animal welfare reasons the study was terminated after the one-hour observation.

Interpretation of results:

Category 1A (corrosive) based on GHS criteria

Conclusions:

The test material was found to be corrosive to rabbit skin.

The observation schedule was not suitable to determine the corrosivity category, however the early study termination for ethical reasons indicates a high corrosivity of the substance. For precautionary reasons, the study result is assessed with Cat 1A.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Well documented report, details missing

Principles of method if other than guideline:

according to BASF-internal standards

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

Amount applied: 50 µL

Duration of treatment / exposure:

24 h

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

2

Irritation parameter:

other: Signs of necrosis

Basis:

animal #1

Time point:

other: 1 h

Reversibility:

not reversible

Remarks on result:

other: Grey discoloration of the nictating membrane. Severe corneal opacity. Severe pain reaction after application of the test substance.

Irritation parameter:

other: Signs of necrosis

Basis:

animal #2

Time point:

other: 1 h

Reversibility:

not reversible

Remarks on result:

other: Grey discoloration of the nictating membrane. Severe corneal opacity. Severe pain reaction after application of the test substance.

Irritation parameter:

other: Signs of necrosis

Basis:

animal #1

Time point:

24 h

Reversibility:

not reversible

Remarks on result:

other: Grey discoloration of the nictating membrane and the conjunctiva (partly). Moderate conjuctival redness, slight oedema, severe corneal opacity. Necrosis of the edges of the eye lids.

Irritation parameter:

other: Signs of necrosis

Basis:

animal #2

Time point:

24 h

Reversibility:

not reversible

Remarks on result:

other: Grey discoloration of the nictating membrane and the conjunctiva (partly). Moderate conjuctival redness, slight oedema, severe corneal opacity. Necrosis of the edges of the eye lids.

Irritation parameter:

other: Signs of necrosis

Basis:

animal #1

Time point:

other: 8 days

Reversibility:

not reversible

Remarks on result:

other: Severe necrosis, severe suppuration, eyelids shrunken.

Irritation parameter:

other: Signs of necrosis

Basis:

animal #2

Time point:

other: 8 days

Reversibility:

not reversible

Remarks on result:

other: Severe necrosis, severe suppuration, eyelids shrunken.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

due to signs of necrosis

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

due to signs of necrosis

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

due to signs of necrosis

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

due to signs of necrosis

After 1 h: Grey discoloration of the nictating membrane. Severe corneal opacity. Severe pain reaction after application of the test substance.

After 24 h: Grey discoloration of the nictating membrane and the conjunctiva (partly). Moderate conjuctival redness, slight oedema, severe corneal opacity. Necrosis of the edges of the eye lids.

After 8 days: Severe necrosis, severe suppuration, eyelids shrunken.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The test material was found to be corrosive to rabbit eye.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

In a standard skin irritation/corrosion test according to EPA OPP 81-5 and GLP, solid sodium methanolate moistened with water was applied to the skin of 6 rabbits for 4 hours under semiocclusive conditions. Due to severe necrosis at all application sites, the study was terminated one hour after removal of the patches for human reasons. The observation schedule was not suitable to determine the corrosivity category, however the early study termination indicates a high corrosivity of the substance. (Evonik, 1988).

In another study on 2 rabbits, an 80% solution of sodium methanolate in water was highly corrosive after 3 minutes of exposure to the skin and resulted in necrosis that was irreversible after the 8-day post exposure observation period (BASF SE, 1979).

In addition, a 30% sodium methanolate solution in methanol was highly corrosive to the skin of rabbits when exposed for 1 to 15 minutes. Necrosis was already observed after an exposure time of 1 minute. A severe pain reaction was observed shortly after the application of the test substance (BASF SE, 1978). As a 30% sodium methanolate solution in methanol was used for testing, the results are not reliable as this kind of exposure does neither reflect a possible exposure situation nor is in line with current guidelines. Therefore, the study was disregarded for hazard assessment.

 

Eye irritation

In a preliminary non-GLP study with two rabbits, 50 mL [note: presumably 50 µL] of a sodium methanolate solution (30% in methanol) were administered to the eyes. Already after 1 h, grey discolouration of the nictating membrane and severe corneal opacity were observed. After 24 h, observations included grey discolouration of the nictating membrane and the conjunctiva (partly), moderate conjunctival redness, slight edema, severe corneal opacity and necrosis of the edges of the eye lids. The effects were irreversible within the 8-day observation period. At this time point, severe necrosis, severe suppuration and shrunken eyelids were observed. The substance was corrosive to rabbit eye (BASF SE, 1978).

 

Conclusion

Sodium methanolate was highly corrosive to rabbit skin and eyes. Based on the skin and eye irritation data, it can be assumed that sodium methanolate will also cause irritation/corrosion to the mucous membranes of the upper respiratory tract in case of an exposure via the inhalation route. As the corrosivity is mediated by the exothermic liberation of sodium hydroxide, the data for the hydroxide may be important for the evaluation of this endpoint as well. For sodium hydroxide (CAS No. 1310-73-2), OECD (2002) concluded that based on the animal data a NaOH solution of 8% can be considered corrosive. Based on human data, concentrations of 0.5 to 4% were irritating to the skin and concentrations slightly lower than 0.5% were considered non-irritating. 

 

References not included in IUCLID:

OECD SIDS Initial Assessment Report for SIAM 14 (2002): Sodium Hydroxide (CAS No: 1310-73-2).

Justification for classification or non-classification

According to Annex VI of the CLP regulation (EC 1272/2008), potassium methanolate is classified as corrosive (Skin Corr. 1B - H314). This classification was also confirmed in an in vitro skin corrosion test according to OECD guideline 435 with potassium methanolate. However, taken also into account the harmonised classification for the hydrolysis product potassiumhydroxide (Skin Corr. 1Aat≥2%)according to CLP Regulation No 1272/2008, Annex VI Table 3.1 a worst-case approach was undertaken for potassium hydroxide and therefore, potassium methanolate fulfils the criteria for classification as corrosive causing severe burns:

 

CLP / UN-GHS: Skin Corr. 1A - H314