Tin titanium zinc oxide

Endpoint summary

Description of key information

Irritation
- skin: not irritating (OECD 404)
- eyes: not irritating (OECD 405)

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No. 8147

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Experimental Toxicology and Ecology, BASF AG

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Centre Lago S. A., 01540 Vonnas, France
- Age at study initiation: ca. 7 months
- Weight at study initiation: 3.86 kg – 3.96 kg
- Housing: single housing in stainless steel wire mesh cages with grating, floor area: 3000 cm²
- Diet (e.g. ad libitum): Kliba-Labordiät (Kaninchen & Meerschweinchenhaltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day)
- Water (e.g. ad libitum): tap water; ad libitum
- Acclimation period:at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Preparation of test site:

other: intact untreated

Vehicle:

water

Controls:

other: Untreated skin sites of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test patch (2.5 cm x 2.5 cm) was covered with an amount of minimally moistened solid preparation (see section 3.5 Test-substance preparation) corresponding to a dose of 0.5 g of undiluted test substance.

Duration of treatment / exposure:

4 h

Observation period:

Immediately after removal of the patch, approx. 1, 24, 48 and 72 h after removal of the patch and then in weekly intervals maximally up to day 14.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Flank
- Type of wrap if used: test patch (Idealbinde, Pfälzische Verbandstoff-Fabrik, Kaiserslautern) and Fixomull® stretch (adhesive fleece), Beiersdorf AG


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with Lutrol and Lutrol / water (1 : 1)
- Time after start of exposure: 4 h


SCORING SYSTEM:
The evaluation of skin reactions was performed according to the quoted guidelines.
- Erythema and eschar formation
0 No erythema
1 = Very slight erythema (barely perceptible)
2 = Well defined erythema
3 = Moderate to severe erythema
4 = Severe erythema (beet redness) to eschar formation preventing grading of erythema

- Edema formation
0 = No edema
1 = Very slight edema (barely perceptible)
2 = Slight edema (edges of area well defined by definite raising)
3 = Moderate edema (raised approx. 1 mm)
4 = Severe edema (raised more than 1 mm and extending beyond area of exposure)

Descriptions of any dermal findings not covered by this scale were recorded

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

Well defined erythema (grade 2) was observed in all animals immediately after removal of the patch and persisted in one animal up to 1 hour. Very slight erythema (grade 1) was noted in two animals after 1 hour and in one animal at the 24-hour reading. The cutaneous reactions were reversible in two animals within 24 hours and in one animal within 48 hours after removal of the patch.

Results:

Readings	Animal	Erythema	Edema	Additional findings
0 h	1	2	0
	2	2	0
	3	2	0
1 h	1	1	0
	2	1	0
	3	2	0
24 h	1	0	0
	2	0	0
	3	1	0
48 h	1	0	0
	2	0	0
	3	0	0
72 h	1	0	0
	2	0	0
	3	0	0
mean 24 - 72 h	1	0.0	0.0
	2	0.0	0.0
	3	0.3	0.0
mean 24 - 72 h		0.1	0.0

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

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:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No. 8147, November 24, 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Experimental Toxicology and Ecology, BASF AG

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Centre Lago S. A., 01540 Vonnas, France
- Age at study initiation: ca. 4 months
- Weight at study initiation: 3.12 kg – 3.25 kg
- Housing: single housing in stainless steel wire mesh cages with grating, floor area: 3000 cm²
- Diet (e.g. ad libitum): Kliba-Labordiät (Kaninchen & Meerschweinchenhaltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day)
- Water (e.g. ad libitum): tap water; ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 – 24
- Humidity (%): 30 – 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

other:

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL bulk volume (about 99 mg of the comminuted test substance)

Duration of treatment / exposure:

24 h

Observation period (in vivo):

Approx. 1, 24, 48 and 72 h after application and then in weekly intervals maximally up to day 28.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with 3 to 6 mL of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe
- Time after start of exposure: about 24 h


SCORING SYSTEM:
The evaluation of eye irritation was performed according to the quoted guidelines:

Cornea
(A) Opacity-degree of density (area most dense taken for reading)
0 = No opacity
1 = Scattered or diffuse area, details of iris clearly visible
2 = Easily discernible translucent areas, details of iris slightly obscured
3 = Opalescent areas, no details of iris visible, size of pupil barely discernible
4 = Opaque, iris invisible

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

Conjunctivae
(A) Redness (refers to palpebral and bulbar conjunctivae 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

(B) Chemosis
0 = No swelling
1 = Any swelling above normal (includes nictitatinq membrane)
2 = Obvious swelling with partial eversion of lids
3 = Swelling with lids about half closed
4 = Swelling with lids about half closed to completely closed

(C) 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, and considerable area around the eye

* not used for assessment


TOOL USED TO ASSESS SCORE: Daylight tubes "Lumilux" (L 58W/860 PLUS ECO 25X1, Osram, Germany)

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

48 h

Score:

1

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Readings:

Readings	Animal	cornea		Iris	conjunctiva			Symptons
		opacity	area		erythema	chemosis	discharge
1 h	1	0	0	0	1	0	0
	2	0	0	0	2	0	1	i
	3	0	0	0	2	0	1	i
24 h	1	0	0	0	0	0	0
	2	0	0	0	1	0	0
	3	0	0	0	2	0	0	i
48 h	1	0	0	0	0	0	0
	2	0	0	0	0	0	0
	3	0	0	0	1	0	0
72 h	1	0	0	0	0	0	0
	2	0	0	0	0	0	0
	3	0	0	0	0	0	0
mean 24 - 72 h	1	0		0	0	0
	2	0		0	0.3	0
	3	0		0	1	0
Mean		0		0	0.4	0

i: scleral vessels injected, circumscribed area

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation

No irritation to skin was found in a study performed under GLP according to OECD guideline 404, where 0.5 g of undiluted test substance was applied to the flank of three New Zealand White rabbits under semiocclusive conditions for 4 hours (BASF, 2008). As a result, the mean scores after 24 – 72 hours for erythema and edema were 0.3 and 0, respectively.

In a supporting study according OECD TG 404 (Rockwood Pigments UK LTD, 2013) the acute dermal irritation potential of the test item in rabbits was investigated. Three healthy, adult male albino rabbits of the New Zealand White strain were selected for the study. Initially one rabbit was tested with a single patch for a period of 4 h. Based on the observation at 24 h post patch removal, the irritation response was confirmed by testing two additional rabbits simultaneously. An amount of 500 mg test item moistened with 0.5 mL distilled water was applied evenly to the intact skin of rabbits. The control skin site of the rabbits was applied with 0.5 mL distilled water and was found normal throughout the experimental period. The treated and the control sites were covered with gauze patch and secured at the margins by non-irritating tape for a period of 4 h. At the end of the exposure period, the residual test item was removed with cotton soaked in distilled water. The skin reactions were observed at 1, 24, 48 and 72 h post patch removal. The mean dermal irritation scores of erythema (0.00 to 0.33) and oedema (0.00) following 24, 48 and 72 h observations were found to be non-significant in all three treated rabbits.

Eye irritation 

Irritation to eyes was evaluated in a study performed under GLP according to OECD guideline 405, where 0.1 mL bulk volume of the test substance was instilled in the eyes of three New Zealand White rabbits (BASF, 2008). After 24 hours the eyes were washed out and analyzed for corneal opacity, iris and conjunctival erythema and chemosis. The resulting mean scores after 24-72 hours were 0, 0, 0.4, 0, respectively. Thus, no irritation was found.

In a supporting study according OECD TG 405 (Rockwood Pigments UK LTD, 2013) the acute eye irritation potential of the test item was investigated. Three healthy, adult, female albino rabbits of New Zealand White strain were selected. Initially one rabbit was tested. Based on the results obtained at 24 h post application observation, the irritation response was confirmed by testing two additional rabbits simultaneously. A volume of 0.1 mL test item (ca. 85 mg) was applied into one eye of each rabbit and the contralateral eye served as the control. Observations were made following the method described in the guidelines at 1 h (on day 0), 24, 48 and 72 h post application. The mean eye irritation scores (following grading at 24, 48 and 72 h post application) of the corneal opacity (0.00), iritis (0.00), conjunctival redness (0.00) and chemosis (0.00) were observed in all three treated rabbits.

In an additional HET-CAM test, no reaction was found when undiluted test substance was applied to three hen eggs for 210 seconds indicating no serious damaging properties to eyes (BASF, 2007).

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available data for skin irritation and eye irritation are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this data, the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.