Aluminum magnesium vanadium oxide

Endpoint summary

Description of key information

Oral (OECD 423, limit test), rat (f): LD50 experimental > 2000 mg/kg bw; LD50 cut-off > 5000 mg/kg bw 
Inhalation (OECD 403, limit test), rat (m/f): LC50 > 5.0 mg/L (nominal); LC50: 4.852 mg/L (analytical)
Dermal (OECD 402, limit test), rat (m/f): LD50 > 2000 mg/kg bw 

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

Study period:

07 - 22 Feb 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Ministère de l'Économie, des Finances et de l'Industrie, Secrétariat général du groupe interministériel des produits chimiques, DGCIS, Service de l'industrie, bureau de la chimie, Paris, France

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER, Le Genest Saint Isle, France
- Age at study initiation: 8 weeks
- Weight at study initiation: 180-196 g
- Fasting period before study: food was removed 1 day before test substance administration (Day -1) and then redistributed 4 h after treatment.
- Housing: animals were housed by groups of 3 in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contained sawdust bedding.
- Diet: pelleted diet M20 (SDS), ad libitum
- Water: tap-water from the public distribution system, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle: 10 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 (for each step)

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: each animal was weighed on Day 0 (before test substance administration), 2, 7 and 14. Systemic examinations were carried out daily during the 14-day observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights, necropsy included macroscopic examination of animals

Statistics:

For body weights, mean values and standard deviations were calculated for all animals.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 experimental

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off according to OECD 423

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Gross pathology:

The macroscopic examination revealed a thinning of the forestomach in 3 of 6 animals.

Interpretation of results:

GHS criteria not met

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII and VIII, 8.5, of Regulation (EC) No 1907/2006.

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

Study period:

30 May - 14 Jun 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

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:

National Institute for Quality- and Organizational Development in Healthcare and Medicines, National Institute of Pharmacy, Budapest, Hungary

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: CRL (WI) BR of Wistar origin

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi-Coop Zrt., Budapest, Hungary
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 229-239 g (males) and 184-188 g (females)
- Housing: animals were individually housed in Type II polycarbonate cages with certified laboratory wood bedding (Lignocel® Hygienic Animal Bedding, J. Rettenmaier & Söhne GmbH+Co. KG, Rosenberg, Germany).
- Diet: ssniff® SM R/M-Z+H complete diet (ssniff Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: drinking water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 8-12
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 30 May 2012 To: 14 June 2012

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

>= 2.3 - <= 2.7 µm

Geometric standard deviation (GSD):

>= 3.05 - <= 3.29

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: anodised aluminium Flow Past Exposure Chamber (CR Equipment SA, Switzerland)
- Exposure chamber volume: 2.8 L
- Method of holding animals in test chamber: animals were held in polycarbonate restraining tubes
- Source and rate of air: filtered air at 15.9 L/min (0.99 L/min to each animal port)
- Method of conditioning air: the air was supplied by an oil-free air compressor and was filtered in a two-stage filter set. The temperature of the air was regulated by a heat exchanger.
- System of generating particulates/aerosols: dust aerosol generator type Wright (TSE Systems GmbH, Bad Homburg, Germany)
- Method of particle size determination: cascade impactor (IN-TOX Products, NM, USA)
- Temperature, humidity: 23.0-26.2 °C, 8.9-24.6%

TEST ATMOSPHERE
- Brief description of analytical method used: the atmosphere generated was measured gravimetrically at regular intervals (approx. 50 min) during exposure by pulling a volume of 5 L of test atmosphere from the exposure chamber through glass fibre filters (Fiberfilm T60A20, Pallflex Product Corp.). The duration of each sampling was 5 minutes. Sampling was performed 5 times: shortly after chamber equilibration and then at regular intervals during the exposure. Samples were collected from a vacant animal exposure port (animals' breathing zone). The actual sampling schedule employed was designed in order to obtain adequate quantities of test item. The achieved average concentration was calculated by combination of the gravimetric results and the recorded real-time data provided by the Aerosol Light Scattering Photometer integrated in the monitoring system of the exposure apparatus. The photometer was calibrated during the technical trials and the recorded data were corrected following the treatment according to the results of gravimetric concentration measurements. The test atmosphere concentration measurements were conducted also during sighting exposure.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: see Table 1 under “Any other information on materials and methods incl. tables")
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.5 µm/3.18 µm (main study); 3.4 μm/2.76 µm (sighting study)

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric and photometric (aerosol light scattering photometer)

Duration of exposure:

4 h

Concentrations:

SIGHTING STUDY:
- 5 mg/L (target concentration)
- 5.8 mg/L (analytical concentration)

MAIN STUDY:
- 5 mg/mL (target concentration)
- 4.852 mg/mL (analytical concentration)
- 16.3 mg/L (nominal concentration)

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: animals were observed for clinical signs at the first, second and third hour during exposure, as soon as practicable following removal from restraint, 1 hour after exposure and subsequently once daily during the 14-day observation period. Individual bodyweights were recorded prior to exposure (Day 0) and on Days 1, 3, 7 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Preliminary study:

A preliminary sighting exposure was performed at a target concentration of 5 mg/L (analytical concentration: 5.8 mg/L) in 1 male and 1 female rat for a period of 4 h. All animals survived the treatment and the following 96 h.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.852 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortalities occurred during the whole study period.

Clinical signs:

other: No clinical signs of toxicity were noted up to the end of the 14-day observation period.

Body weight:

In both genders, body weight loss (-1.6% in males and -2.6% in females) was observed on the day of inhalation exposure. A compensation of body weight loss in males and females was found from Day 3 of the observation period.

Gross pathology:

No macroscopic findings were observed at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

4 852 mg/m³ air

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII and VIII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 - 21 Feb 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Ministère de l'Économie, des Finances et de l'Industrie, Secrétariat général du groupe interministériel des produits chimiques, DGCIS, Service de l'industrie, bureau de la chimie, Paris, France

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER, Le Genest Saint Isle, France
- Age at study initiation: 7 weeks (males) and 8 weeks (females)
- Weight at study initiation: 217-246 g (males) and 198-206 g (females)
- Housing: animals were housed individually during treatment and then in groups of 5 during the observation period. Rats were kept in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid. Each cage contained sawdust bedding.
- Diet: pelleted diet M20 (SDS), ad libitum
- Water: tap-water from the public distribution system, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

other: liquid paraffin

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10
- Type of wrap if used: gauze dressing

REMOVAL OF TEST SUBSTANCE
- Washing: residual test substance was removed by rinsing with liquid paraffin.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 10 mL/kg bw
- Concentration: 0.2 g/mL
- Constant volume or concentration used: yes

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: each animal was weighed on Day 0 (before test substance administration), 2, 7 and 14. Systemic examinations were carried out daily during the 14-day observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights, necropsy included macroscopic examination of animals

Statistics:

For body weights, mean values and standard deviations were calculated for all animals.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Gross pathology:

The macroscopic examination revealed no treatment-related changes.

Other findings:

- Other observations: a slight yellow coloration was noted on the treatment site 24 and 48 h after test substance application in all males (5/5).

Interpretation of results:

GHS criteria not met

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII and VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Oral

An acute oral toxicity study with aluminium magnesium vanadium oxide according to the acute toxic class method (OECD guideline 423) and GLP was performed in female RccHan: WIST rats (2012). Two groups, each consisting of 3 animals, were treated with the test substance diluted in olive oil as vehicle by single oral gavage administration at a limit dose of 2000 mg/kg bw in a stepwise procedure. No mortality and no clinical signs were observed during the study period. All 6 animals showed the expected gain in body weight after treatment. The macroscopic examination revealed a thinning of the forestomach in 3 of 6 animals. Based on the experimental results, the LD50 of aluminium magnesium vanadium oxide was greater than 2000 mg/kg bw. According to the criteria of OECD guideline 423, the LD50 cut-off of aluminium magnesium vanadium oxide may be considered to be greater than 5000 mg/kg bw.

 

Inhalation

The acute inhalation toxicity of aluminium magnesium vanadium oxide was studied in Wistar CRL (WI) BR rats according to OECD guideline 403 and in compliance with GLP (2012). A preliminary sighting study was performed in 1 male and 1 female animal at a target concentration of 5 mg/L of the dust aerosol for a period of 4 h using a nose only exposure system. Since no mortality occurred in this study, 5 male and 5 female animals of the main study were exposed for 4 h to the same target concentration, corresponding to an analytical atmosphere concentration of the dust aerosol of 4.852 mg/L (4852 mg/m³). No mortality and no clinical signs of toxicity were observed in any of the animals during the 14-day observation period. A slight loss in body weights was observed in both genders at the day of inhalation exposure, but was compensated from Day 3 of the observation period. At necropsy, no abnormalities were noted in the animals. Based on these results, the LC50 value for male rats was assumed to be greater than 5 mg/L (5000 mg/m³), corresponding to an analytical concentration of 4.852 mg/L (4852 mg/m³).

 

Dermal

The acute dermal toxicity of aluminium magnesium vanadium oxide was investigated in a study according to OECD guideline 402 and compliant with GLP (2012). In this limit test, 5 male and 5 female Sprague Dawley rats were exposed to the test substance at a dose of 2000 mg/kg bw. The test substance was applied at a concentration of 0.2 g/mL in liquid paraffin onto the clipped dorsal skin of the test animals for 24 h under semiocclusive conditions. After removal of the test substance, animals were observed for a period of 14 days. A slight yellow coloration was noted on the treatment site 24 and 48 h after test substance application in all males. No mortalities and no signs of systemic toxicity were observed. No effect on body weight was noted during the study. At necropsy, no macroscopic findings were recorded. Based on these results, the dermal LD50 value for male and female rats was greater than 2000 mg/kg bw.

Justification for classification or non-classification

The available data on the acute toxicity of aluminium magnesium vanadium oxide do not meet the criteria for classification according to Regulation (EC) 1272/2008 (CLP), and are therefore conclusive but not sufficient for classification.