Aluminum magnesium oxide

Acute Toxicity: oral

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

Test guideline 4

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

Test material

Test material information

Constituent 1

Reference substance name:

Aluminum magnesium oxide

EC Number:

234-386-9

EC Name:

Aluminum magnesium oxide

Cas Number:

11137-98-7

Molecular formula:

Al2MgxO(3+x) where x = 4.3-4.6

IUPAC Name:

Aluminum magnesium oxide

Test material form:

solid: particulate/powder

Details on test material:

- Appearance: White powder
- Storage condition: At room temperature desiccated

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels

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.

Applicant's summary and conclusion

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.