Bismuth(3+) neodecanoate

Endpoint summary

Description of key information

Testing was technically not feasible due to the physical form of the pure bismuth(3 +) neodecanoate being intrinsically sticky. However, in vivo data clearly demonstrated that no skin and eye irritating properties could be observed in studies with a mixture of bismuth neodecanoate and neodecanoic acid (liquid). Based on these results bismuth (3 +) neodecanoate is not classified as skin and eye irritant.

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

Remarks:

No details about the animals housing conditions were stated and the age and sex of the animals were not specified. No rationale for in vivo testing was included and sequential testing was not performed. Additionally, the test material was unsufficiently described.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2015-07-28

GLP compliance:

yes

Remarks:

no certificate included

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: New York State Rabbit Development, Hartwick, NY
- Weight at study initiation: 2.36-2.89 kg
- Housing: the animals were individually housed in wire mesh bottom cages in an environment- controlled room
- Diet (e.g. ad libitum): NIH Animal Feed A (certified)
- Water (e.g. ad libitum): yes
- Acclimation period: for a minimum of 5 days

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): undiluted

Duration of treatment / exposure:

4 hours

Observation period:

1.5, 24, 48 and 72 hours post dose

Number of animals:

6 animals

Details on study design:

TEST SITE
- Type of wrap if used: test site was occluded with a one-inch square gauze patch held in place with Blenderm tape


REMOVAL OF TEST SUBSTANCE
- Washing: the exposure sites were gently wiped with clean gauze to remove as much non-absorbed test article as possible
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
1.5, 24, 48 and 72 post-dose

SCORING SYSTEM:
- Method of calculation: Draize skin reaction code

Irritation parameter:

erythema score

Remarks:

left

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Remarks:

right

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Remarks:

left

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

right

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

left

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

right

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

left

Basis:

animal #4

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

right

Basis:

animal #4

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Remarks:

left

Basis:

animal #5

Remarks:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Remarks:

right

Basis:

animal #5

Remarks:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Remarks:

left

Basis:

animal #6

Remarks:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Remarks:

right

Basis:

animal #6

Remarks:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

mean

Remarks:

mean of 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Interpretation of results:

GHS criteria not met

Conclusions:

According to the regulation EC No. 1272/2008 Bismuth neodecanoate (Cos Cat 83) does not need to be classified as irritating to the skin.

Executive summary:

Bismuth neodecanoate was evaluated for its dermal irritation properties in a skin irritation test in rabbits. The back of each of the six rabbits was clipped free of fur on the day prior to dosing. On the day of dosing, a volume of 0.5 mL of bismuth neodecanoate was applied to each test site (left and right of each animal), which was occluded with a one-inch square gauze patch. Four hours post-dose, the patches and remaining material were removed. 4.5, 28, 52 and 76 after dosing the test sites were examined and scored separately for both erythema and edema according to the Draize scale. Very slight erythema and edema were observed in three of six animals. The mean of the grading at 24, 48 and 72 hours after dosing were below the classification criteria given in the regulation EC 1272/2008. Thus, no classification for skin irritation or corrosion is required.

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Details about animal housing conditions were missing and the age and sex of the animals were not stated. Additionally, topical anesthetics and systemic analgesics were not used. No sequential testing was performed and no rationale for in vivo testing was available. The test substance was insufficiently described.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2017-10-09

GLP compliance:

yes

Remarks:

no certificate included

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: New York State Rabbit Development, Hartwick, NY
- Weight at study initiation: 2.42- 3.13 kg
- Housing: The rabbits were individually housed in wire mesh bottom cages in an environment- controlled room
- Diet (e.g. ad libitum): NIH Animal Feed A (certified)
- Water (e.g. ad libitum): yes
- Acclimation period: a minimum of 5 days

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated contralateral eye as negative control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): undiluted

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

The eyes were examined with the aid of sodium fluorescein and the grade of ocular reaction for each animal was recorded at 1, 24, 48 and 72 hours post-dose using the Draize scale for scoring ocular lesions.

Number of animals or in vitro replicates:

6 animals

Details on study design:

PROCEDURE: a volume of 0.1 mL of the test article was instilled into one eye of each rabbit. The test article was instilled into the eye by gently pulling the lower lid away from the eyeball to form a cup into which the test article was deposited. The lid were then held together for one second.
SCORING SYSTEM: Draize scale for scoring ocular lesions
TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

animal #4

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

iris score

Basis:

animal #4

Remarks:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

animal #4

Remarks:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #4

Remarks:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

animal #5

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

iris score

Basis:

animal #5

Remarks:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

animal #5

Remarks:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #5

Remarks:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

animal #6

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

iris score

Basis:

animal #6

Remarks:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

animal #6

Remarks:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #6

Remarks:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Interpretation of results:

GHS criteria not met

Conclusions:

According to the regulation EC No. 1272/2008 bismuth neodecanoate (Cos Cat 83) does not need to be classified as irritating to the eyes.

Executive summary:

To evaluate the ocular irritation potential of the test article an eye irritation study in rabbits was conducted. Bismuth neodecanoate was instilled into one eye of six young adult New Zealand White rabbits. The untreated eye served as negative control. The eyes were examined with the aid of sodium fluorescein and the grade of ocular reaction for each animal was recorded at 1, 24, 48 and 72 hours post-dose using the Draize scale for scoring ocular lesions. Observed eye effects were reversible after 72 hours and the mean of the grading at 24, 48 and 72 hours after dosing were below the classification criteria given in the regulation EC 1272/2008. Thus, no classification for eye irritation is required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion:

Since the physical form of bismuth neodecanoate was identified as being intrinsically sticky, a pre-test was conducted in order to evaluate the feasibility of testing: In a pre-test on one single tissue, the test material was examined for its suitability for the skin irritation testing using EpiDerm. As the test material is highly sticky, application of the test item without application aid was technically not feasible, since the test item adheres strongly with the surface of i.e. a spatula. Consequently, a nylon mesh was used as application aid. However, it was not possible to wash off the complete test material from the surface of the skin tissue, due to the intrinsic properties (sticky) of the test item. Thus, testing was technically not feasible.

Due to these technical limitations, the study cannot be performed according to the guideline OECD439 and therefore the study is cancelled.

A literature research revealed a study report of an in vivo skin irritation test conducted with bismuth neodecanoate. The substance CosCat 83 is synthetically manufactured by the reaction of bismuth trioxide with neodecanoic acid to yield bismuth trisneodecanoate. The final composition of Coscat 83 is 58% bismuth trisneodecanoate and 42% neodecanoic acid. In contrast to the substance subjected to registration, the physical form of Coscat83 was not identified as being intrinsically sticky. Thus, the in vivo skin irritation test could be conducted. The back of each of the six New Zealand White rabbits was clipped free of fur on the day prior to dosing. On the day of dosing, a volume of 0.5 mL of bismuth neodecanoate was applied to each test site (left and right of each animal), which was occluded with a one-inch square gauze patch. Four hours post-dose, the patches and remaining material were removed. 4.5, 28, 52 and 76 after dosing the test sites were examined and scored separately for both erythema and edema according to the Draize scale. Very slight erythema and oedema were observed in three of six animals. The mean of the grading at 24, 48 and 72 hours after dosing were below the classification criteria given in the regulation EC 1272/2008. Thus, no classification for skin irritation or corrosion is required.

 

Eye irritation

Since the physical form of bismuth neodecanoate was identified as being intrinsically sticky, a pre-test was conducted in order to evaluate the feasibility of testing: Bismuth neodecanoate was tested in a pre-test on one single tissue.

Due to the test items characteristics it was not possible to remove the substance from the corneal chamber and to wash it off from the epithelium after incubation. Therefore, remaining test item would have an impact on subsequent opacity and permeability measurements and BCOP-Assay is not feasible for this test substance.

Sticky Substances will adhere to the cornea and it will not be possible to remove it without damaging the cornea. Due to these technical limitations the BCOP assay is not recommended for these substances and therefore the studies were cancelled because the studies cannot be performed according to the guideline OECD437.

 

A literature research revealed a study report of an in vivo skin irritation test conducted with bismuth neodecanoate. The substance CosCat 83 is synthetically manufactured by the reaction of bismuth trioxide with neodecanoic acid to yield bismuth trisneodecanoate. The final composition of Coscat 83 is 58% bismuth trisneodecanoate and 42% neodecanoic acid. In contrast to the substance subjected to registration, the physical form of Coscat83 was not identified as being intrinsically sticky. Thus, the in vivo eye irritation test could be conducted. Bismuth neodecanoate was instilled into one eye of six young adult New Zealand White rabbits. The untreated eye served as negative control. The eyes were examined with the aid of sodium fluorescein and the grade of ocular reaction for each animal was recorded at 1, 24, 48 and 72 hours post-dose using the Draize scale for scoring ocular lesions. Observed eye effects were reversible after 72 hours and the mean of the grading at 24, 48 and 72 hours after dosing were below the classification criteria given in the regulation EC 1272/2008. Thus, no classification for eye irritation is required.

Justification for classification or non-classification

Skin and eye irritation testing with bismuth (3 +) neodecanoate, was technically not feasible due to its physical from being intrinsically sticky.

However, in vivo skin and eye irritation studies conducted with a mixture of bismuth neodecanoate and neodecanoic acid (liquid) demonstrated that no irritating properties could be observed. Based on these results no classification for skin and eye irritation is required.