Amorphous Mesoporous Magnesium Carbonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1.7.2010-22.7.2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Specific details on test material used for the study:

- Description: white powder
- Batch No.: 078K0138
- Expiration date of the batch: 30 August 2013
- Storage condition of test material: room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd., Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 300 mg/kg dose group: 159 - 189 g; 2000 mg/kg dose group: 173 - 190 g
- Fasting period before study: Animals were fasted overnight prior to dosing
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: 2014 Teklad Global Rodent diet available ad libitum
- Water: mains drinking water available ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: For the purpose of the study the test material was freshly prepared, as required, as a suspension in distilled water.
The test material was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

5 animals/ group

Control animals:

no

Details on study design:

- The study procedure was as follows:
In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose and a single animal was treated.
In the absence of mortality at a dose level of 300 mg/kg, an additional group of 4 animals was treated.
A total of five animals were therefore treated at a dose level of 300 mg/kg in the study.
In the absence of mortality at a dose level of 300 mg/kg, one additional animal was treated at a dose level of 2000 mg/kg.
In the absence of mortality at a dose level of 2000 mg/kg, an additional group of 4 animals was treated.
A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:

At the 300 mg/kg dose level, there were no mortalities and ataxia and/or hunched posture were noted in all animals. However, animals appeared normal two or five days after dosing. All animals showed expected gains in bodyweight over the observation period and no abnormalities were noted at necropsy.
Based on the results at a dose level of 300 mg/kg, a dose level of 2000 mg/kg bodyweight was investigated.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks:

Magnesium Carbonate

Mortality:

At a dose level of 2000 mg/kg, there were no mortalities.

Clinical signs:

Hunched posture was noted in the initial treated animal during the day of dosing. No signs of systemic toxicity were noted in the additional four treated animals.

Body weight:

All animals showed expected gains in bodyweight over the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1: Individual Clinical Observations and Mortality Data - 300 mg/kg

Dose level mg/kg	Animal number & sex	Effects noted after dosing (hours)				Effects noted during period after dosing (days)
		0.5	1	2	4	1	2	3	4	5-14
300	1-0 Female	H	HA	HA	HA	HA	HA	H	H	0
	2-0 Female	H	H	H	H	H	0	0	0	0
	2-1 Female	0	H	HA	HA	H	0	0	0	0
	2-2 Female	H	HA	HA	HA	H	0	0	0	0
	2-3 Female	H	H	H	H	H	0	0	0	0

0 = No signs of systemic toxicity

H = hunched posture

A = ataxia

Table 2: Individual Bodyweights and Bodyweight Changes - 300 mg/kg

Dose level mg/kg	Animal number & sex	Bodyweight (g) at Day			Bodyweight gain (g) during week
		0	7	14	1	2
300	1-0 Female	159	163	181	4	18
	2-0 Female	175	196	214	21	18
	2-1 Female	171	190	199	19	9
	2-2 Female	172	183	196	11	13
	2-3 Female	189	202	217	13	15

Table 3: Individual Clinical Observations and Mortality Data - 2000 mg/kg

Dose level mg/kg	Animal number & sex	Effects noted after dosing (hours)				Effects noted during period after dosing (days)
		0.5	1	2	4	1-14
2000	3-0 Female	0	H	H	H	0
	4-0 Female	0	0	0	0	0
	4-1 Female	0	0	0	0	0
	4-2 Female	0	0	0	0	0
	4-3 Female	0	0	0	0	0

0 = No signs of systemic toxicity

H = hunched posture

  Table 4: Individual Bodyweights and Bodyweight Changes - 2000 mg/kg

Dose level mg/kg	Animal number & sex	Bodyweight (g) at Day			Bodyweight gain (g) during week
		0	7	14	1	2
300	3-0 Female	189	213	228	24	15
	4-0 Female	190	207	214	17	7
	4-1 Female	173	190	217	17	27
	4-2 Female	178	196	216	18	20
	4-3 Female	187	212	217	25	5

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

not classified

Conclusions:

The acute oral median lethal dose (LD50) of magnesium carbonate in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.