Tin titanium zinc oxide

Endpoint summary

Description of key information

Acute toxicity:
- oral: LD50 >5000 mg/kg bw (OECD 423)
- inhalative: LC50 > 5.7 mg/L air (OECD 403)

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

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Remarks:

Austrian Research Centers GmbH - ARC

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: Crl:(WI)BR

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, D-97633 Sulzfeld.
- Age at study initiation: ca. 8 weeks
- Weight at study initiation: mean 181.7 g
- Fasting period before study: The feed was withdrawn the evening before the administration of the test substance and was offered again about three hours afterwards.
- Housing: Single caging in Makrolon cages type III (39 cm x 23 cm bottom area, 18 cm height). Wire mesh lids. Sanitation of cages once a week.
- Diet (e.g. ad libitum): Ssniff R/M-H maintenance diet for rats and mice (item V1534-3 ) ad libitum, supplied by Ssniff Spezialdiäten GmbH, 59494 Soest, Germany
- Water (e.g. ad libitum): Tap water from an automatic watering system, ad libitum.
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 22.1
- Humidity (%): average of 60.3
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: To:

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50%
- Amount of vehicle (if gavage): 10 ml/kg bw
- Justification for choice of vehicle: The test substance was not soluble in water. Aqueous CMC ist a common vehicle for acute oral toxicity testing.
- Lot/batch no. (if required): 0.5 % aqueous solution of Na-carboxymethylcellulose ("CMC" high viscosity, item No. C-5013, Lot. No. 98H0328, Sigma)

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: by request of the sponsor

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations at least once per day, body weights before administration, 7 and 14 days after the administration
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality

Clinical signs:

other: General findings: No toxic effects were noted during the entire observation period. An orange discolouration of the faeces was observed in all animals 1 d p.a. This finding is not considered to be a toxic effect.

Gross pathology:

All animals were normal at the necropsy 14 d.

Body weights:

	Body weight (g)			Body weight gain (g)
Animal	before admininstration	7 d	14 d	d 0-7	d 7-14
1	174	215	231	41	16
2	183	212	226	29	14
3	188	224	234	36	10

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

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 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Experimental Toxicology and Ecology, BASF SE

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd Laboratory Animal Services, Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: young adult animals (male animals approx. 7 - 8 weeks, female animals approx. 10 – 11 weeks)
- Weight at study initiation: mean 235.3 g (males), 189.9 g (females)
- Housing: single housing, H-Temp (PSU) cages, floor area about 800 cm2 (425x266x185 mm); TECNIPLAST, Germany
- Diet (e.g. ad libitum): Kliba-Labordiät (Maus / Ratte Haltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
- 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

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose/head only

Vehicle:

other: Aerosil

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-nose inhalation system INA 20 (glass-steel construction, BASF SE)
- Exposure chamber volume: volume ca. 55 l
- Method of holding animals in test chamber: animals were restrained in glass tubes and their snouts projected into the inhalation system
- Source and rate of air: compressed air, 1.5 m³/h; the flows were adjusted and continously measured with a flowmeter (rota).
The concentration was adjusted by varying the rotation of dosing wheel.
- System of generating particulates/aerosols: dosing-wheel dust generator (Gericke/BASF) with apertural width of 3 mm
- Treatment of exhaust air: 1.35 m³/h; the flows were adjusted and continously measured with a flowmeter (rota).
- Temperature, humidity, pressure in air chamber: air change of about 27 times/h; 21.9 ± 0.2 °C; 28.2 ± 1.2 %


TEST ATMOSPHERE
- Brief description of analytical method used: the nominal concentration was calculated from the amount of substance dosed and the supply air flow
- Samples taken from breathing zone: yes


VEHICLE
- Composition of vehicle (if applicable): 1% (w/w) of Aerosil

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: the calculation of the particle size distribution was carried out in the inhalation laboratory on the basis of mathematical methods for evaluating particle measurements
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.3-1.4 µm / 2.7


CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: The selection of the concentration for the test group was based on the OECD Guidelines, method 403; EU Directive 92/69/EEC, 93/21/EEC and Environmental Protection Agency (EPA) guidelines because from the available information concerning the test substance no pronounced inhalation toxicity was expected.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

For each sample the dust aerosol concentration in mg/L was calculated from the difference between the weight of the filter prior to and after the sampling, with reference to the sample volume of the inhalation atmospheres.

Duration of exposure:

4 h

Concentrations:

5.7 mg/l

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual body weights shortly before exposure (day 0), weekly thereafter and at the end of the study.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Statistics:

Binomial test was used for statistical evaluation (Steel R.G.D., Torrie J.H. (1984): Principles and procedures of statistics a biometrical approach. McGraw - Hill)

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.7 mg/L air (analytical)

Exp. duration:

4 h

Mortality:

No lethality occurred at the tested concentration of 5.7 mg/L during the study period of 14 days.

Clinical signs:

other: Clinical signs of toxicity comprised visually increased respiration and squatting posture. Findings were observed from hour 1 of exposure through to study day 1. No clinical signs and findings were observed from study day 2 onward.

Body weight:

Mean body weights (g): d0/d7/d14
- Males: 235.3 ± 8.8, 258.3 ± 11.9, 285.9 ± 13.7
- Female: 189.9 ± 7.0, 192.4 ± 6.2, 205.4 ± 10.9

Gross pathology:

All animals underwent gross necropsy after the post-exposure observation period of 14 days.
Diffuse red discoloration of the lung, moderate retraction of the lung tissue and moderate to severe interstitial edema were noted in all male and female animals.
Histopathological examination of the lungs of the one male and one female animals revealed moderate to severe acute diffuse congestion, moderate to severe diffuse intra-alveolar histiocytosis with numerous pigment-loaded macrophages and multifocal interstitial lymphoplasmahistiocytic infiltrates, which is graded as minimal to slight in the male animal and moderate in the female animal. The lung of the examined female animal was more affected. In this female animal, besides the findings described above, emphysema, perivascular cuffing and interstitial fibrosis were noted additionally.

Body weights:

		Body weight (g)
		d 0	d 7	d 14
Male	1	233.9	256.3	284.2
	2	241.8	271.4	303
	3	228.3	247.2	272.7
	4	246.6	269.8	296.6
	5	225.7	246.6	273.1
	Mean	235.3 ± 8.8	258.3 ± 11.9	285.9 ± 13.7
Female	1	182	183.4	189.3
	2	184.3	198.6	208.3
	3	192.4	195.1	201.5
	4	199.6	196	219
	5	191.3	188.7	208.7
	Mean	189.9 ± 7.0	192.4 ± 6.2	205.4 ± 10.9

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 700 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Oral

The acute oral toxicity was evaluated in a study performed under GLP according to OECD guideline 423, where three female Crl:(WI)BR rats were treated with a dose of 5000 mg/kg bw by gavage (BASF, 2007). Since no toxic effects and no mortality were noted during the entire 14 day observation period, the LD50 was found to be >5000 mg/kg bw/day.

Inhalation

For analyzing the acute inhalative toxicity, a study with five male and five female Wistar rats was performed under GLP according to OECD guideline 403 (BASF, 2008). The animals were exposed to a dust-aerosol at a concentration of 5.7 mg/L air with head/nose only for 4 hours. Although clinical signs of toxicity comprised visually increased respiration and squatting posture were observed on the first day, no lethality occurred within the 14 day observation period.

All animals underwent gross necropsy after the post-exposure observation period of 14 days. Subsequent pathology revealed diffuse red discoloration of the lung, moderate retraction of the lung tissue and moderate to severe interstitial edema, whereas the histopathological examination of the lungs of one male and one female animal revealed moderate to severe acute diffuse congestion, moderate to severe diffuse intra-alveolar histiocytosis with numerous pigment-loaded macrophages and minimal to moderate multifocal interstitial lymphoplasmahistiocytic infiltrates. However, based on the survival of all animals, the LC50 was >5.7 mg/L air.

In a further study (Rockwood Pigments UK Ltd, 2014) it was impossible to generate a test atmosphere from the test item. Therefore, it was not possible to proceed to a formal exposure.

Justification for classification or non-classification

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

The available data for acute toxicity 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 acute toxicity) under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.