Aluminum magnesium oxide

Endpoint summary

Description of key information

Acute oral (OECDTG423): LD50 >2000 mg/kg bw

Acute inhalation (OECDTG403): LC50 >5 mg/L

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:

19 July 2018 - 16 August 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Appendix to Director General Notification, No. 12-Nousan-8147. Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF), November 2000, including the most recent revisions.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 9-12 weeks old
- Weight at study initiation: 166 to 188 g.
- Fasting period before study: Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item. Water was available.
- Housing: Animals were group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: Free access to municipal tap-water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24
- Humidity (%): 40 to 70
- Air changes (per hr): 10 or greater
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 31 July 2018 To: 16 August 2018

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

DOSAGE PREPARATION:
Trial preparations were performed at the Test Facility to select the suitable vehicle and to establish a suitable formulation procedure.
Test item dosing formulations (w/w) were homogenized to visually acceptable levels at appropriate concentrations to meet dose level requirements. The dosing formulations were kept at room temperature until dosing. The dosing formulations were stirred until and during dosing. No adjustment was made for specific gravity of the vehicle. A factor of 1.13 was used to correct for the purity/composition of the test item.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups. The first group was treated at a dose level of 2000 mg/kg bw. Based on the results, one additional group was dosed at 2000 mg/kg bw.

Doses:

2000 mg/kg body weight

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:
Mortality/Moribundity Checks: Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings.
Clinical Observations: Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate).
Body Weights: Animals were weighed individually on Day 1 (predose), 8 and 15. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: Yes. All animals were sacrificed by oxygen/carbon dioxide procedure at the end of the observation period. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.

Statistics:

Not performed.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

Hunched posture and piloerection were noted for the animals on Day 1.

Body weight:

The mean body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. The incidence of slight body weight loss on Day 15 in an individual animal was considered not indicative of toxicity, based on the absence of any corroborative findings in the animal.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

other: Not classified.

Remarks:

According to Regulation (EC) No. 1272/2008.

Conclusions:

In an acute oral toxicity study with female rats, performed according to OECD 423 test guideline and GLP principles, a LD50 >2000 mg/kg bw was determined.

Executive summary:

KW-2200 was administered by oral gavage to two consecutive groups of three female Wistar Han rats at 2000 mg/kg body weight, performed according to OECD 423 test guideline and GLP principles.

No mortality occurred. Hunched posture and piloerection were noted for the animals on Day 1. The mean body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals.

Based on the results, a LD50 >2000 mg/kg bw was determined and KW-2200 does not have to be classified for acute oral toxicity according to Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The study has klimisch code 1.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 August, 1995 - 24 August, 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed according to OECD guidelines and GLP principles.

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(1981)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Crl:[WI]WU BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: appr. 9 weeks
- Weight at study initiation: 305 - 327 g (males); 193 - 201 g (females)
- Fasting period before study: no
- Housing: Group housing of 5 animals/sex in suspended stainless steel cages
- Diet: free access to cereal-based rodent diet (SDS Special Diets Services, Witham, England) (no access to food during exposure)
- Water: free access to tap water (no access to water during exposure)
- Acclimation period: total 17 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 24.0
- Humidity (%): 63 - 89
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose-only inhalation chamber, a modification of the chamber manufactured by ADG Developments Ltd., Codicote, Hitchin, Herts, SG4 8UB, UK.
- Method of holding animals in test chamber: the animals were secured in plastic animal holders
- Exposure chamber volume: 150 L
- Rate of air: mean amount 104 L/min
- System of generating particulates/aerosols: The test atmosphere was generated by passing the test material using a dry material helix feeder to a jet mill. The jet mill was operated with dry pressurized air (less than 1% humidity); the test material was delivered using a slip stream of airconditioned room air and pressurized air. This stream accounted for about 55% of the total amount of air. The generated aerosol was passed to the inlet of the exposure unit and was directed downward through the mixing chambers towards the animal noses. At the bottom of the unit the test atmosphere was exhausted.
- Method of particle size determination: Twice during exposure using a 10-stage Anderson cascade impactor with the largest cut-off size of 32 µm. Due to a technical failure these measurements could not be used to determine the particle size distribution. The particle size distribution measurement, however, had also been carried out the day before exposure during a test run at exactly the same settings as during exposure.
- Treatment of exhaust air: no data
- Temperature, humidity in air chamber: 20. 5 - 21.0°C; 41 - 58%

TEST ATMOSPHERE
- Brief description of analytical method used: The actual concentration in the test atmosphere was determined twice each hour by gravimetric analysis. The nominal concentration was determined by dividing the total amount of test material used by the total volume of air passed through the exposure unit.
- Samples taken from breathing zone: Representative samples were obtained by passing test atmosphere samples at ca. 5 L/min through fiber glass filters. Before sampling the filters were weighed; immediately after sampling the filters were weighed again. The actual concentration was calculated by dividing the amount of test material present on each filter by the volume of the test atmosphere sample taken.

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.9 µm / 2.2 µm

CLASS METHOD
- Rationale for the selection of the starting concentration: Based on the cut off concentration values specified in the UN and EC classification guidelines.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5 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:
Behaviour, clinical signs and mortality: The rats were visually inspected just before exposure, for reactions to treatment during the exposure, shortly after exposure, and at least once daily during the observation period.
Body weights: Body weights were recorded just prior to exposure (day 0), and on days 7 and 14.
- Necropsy of survivors performed: At the end of the 14 day observation period, all rats were killed by exsanguination from the abdominal aorta under ether anaesthesia. All rats were necropsied and examined for gross pathological changes.

Statistics:

No statistical analysis was performed (the method used was not intended to calculate a LC50 value).

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No animals died.

Clinical signs:

other: Slight visually decreased breathing rate was observed in all rats ca. 1.5, 2.5 and 3.5 hours after the start of the exposure. Two males and one female felt cold upon touching shortly after exposure. Dirty fur of the head was seen in 2 females until day 7

Body weight:

Slightly reduced mean body weight gain was generally seen in all rats 7 days after exposure. Normal body weight gain was observed in males at the end of the observation period, whereas body weight gain remained low in 3 females.

Gross pathology:

No abnormalities were observed at necropsy, except for one female that showed sparsely haired abdomen.

Other findings:

None.

The mean actual concentration of the substance during the exposure based on gravimetric analyses was 5.16 ± 0.48 mg/L.

The nominal concentration was calculated to be 14.7 mg/L indicating a generation efficiency of ca. 35%.

The particle size distribution: it was shown that 91.2% of the particles present at the animals' breathing zone were of the respitable size range since they were smaller than or equal to 5.0 µm.

MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.9 µm / 2.2 µm

Interpretation of results:

other: Not classified.

Remarks:

According to Regulation (EC) No. 1272/2008 and its amendments.

Conclusions:

In an acute inhalation toxicity study with male and female rats, performed according to OECD 403 test guideline and GLP principles, an LC50 >5 mg/L was determined for Aluminium-magnesium-carbonate-hydroxide-perchlorate-hydrate

Executive summary:

Aluminium-magnesium-carbonate-hydroxide-perchlorate-hydrate was tested in an acute inhalation toxicity study with nose-only exposure with male and female rats, performed according to OECD 403 test guideline and GLP principles.

No mortality occurred. Slight visually decreased breathing rate was observed in all rats ca. 1.5, 2.5 and 3.5 hours after the start of the exposure. Two males and one female felt cold upon touching shortly after exposure. Dirty fur of the head was seen in 2 females until day 7 of the 14 day observation period. One female additionally showed alopecic areas on the fur on days 7-14. Slightly reduced mean body weight gain was generally seen in all rats 7 days after exposure. Normal body weight gain was observed in males at the end of the observation period, whereas body weight gain remained low in 3 females. No abnormalities were observed at necropsy, except for one female that showed sparsely haired abdomen.

Based on the results, an LC50 >5 mg/L was determined. Aluminium-magnesium-carbonate-hydroxide-perchlorate-hydrate does not have to be classified and has no obligatory labelling requirement for acute inhalation toxicity according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-across information.

Justification for type of information:

See the attached read-across document in section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Interpretation of results:

other: Not classified.

Remarks:

According to Regulation (EC) No. 1272/2008 and its amendments.

Conclusions:

In an acute inhalation toxicity study with male and female rats, performed according to OECD 403 test guideline and GLP principles, an LC50 >5 mg/L was determined for Aluminium-magnesium-carbonate-hydroxide-perchlorate-hydrate. The result is used for read-across to the substance.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 000 mg/m³

Quality of whole database:

The study has klimisch code 1. See the attached read-across rationale in section 13.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral:

KW-2200 was administered by oral gavage to two consecutive groups of three female Wistar Han rats at 2000 mg/kg body weight, performed according to OECD 423 test guideline and GLP principles.

No mortality occurred. Hunched posture and piloerection were noted for the animals on Day 1. The mean body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals.

Based on the results, a LD50 >2000 mg/kg bw was determined.

Acute inhalation:

The read-across substance Aluminium-magnesium-carbonate-hydroxide-perchlorate-hydrate was tested in an acute inhalation toxicity study with nose-only exposure with male and female rats, performed according to OECD 403 test guideline and GLP principles.

No mortality occurred. Slight visually decreased breathing rate was observed in all rats ca. 1.5, 2.5 and 3.5 hours after the start of the exposure. Two males and one female felt cold upon touching shortly after exposure. Dirty fur of the head was seen in 2 females until day 7 of the 14 day observation period. One female additionally showed alopecic areas on the fur on days 7-14. Slightly reduced mean body weight gain was generally seen in all rats 7 days after exposure. Normal body weight gain was observed in males at the end of the observation period, whereas body weight gain remained low in 3 females. No abnormalities were observed at necropsy, except for one female that showed sparsely haired abdomen.

Based on the results, an LC50 >5 mg/L was determined. The results are used for read-across to the substance.

Justification for classification or non-classification

Based on the available study results, KW-2200 does not have to be classified and has no obligatory labelling requirement for acute oral and acute inhalation toxicity according to Regulation (EC) No 1272/2008 and its amendments.