Aluminate(2-),[[N,N'-1,2-ethanediylbis[N-(carboxymethyl)glycinato]](4-)-N,N',O,O',ON] (oxidoborate-µ-oxido)(-1),disodium

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015-2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

first addendum, 2001

Deviations:

yes

Remarks:

3 animals were between 7-8 weeks old because of limited availability of animals but this deviation did not influence the quality or integrity of the results.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

yes

Remarks:

3 animals were between 7-8 weeks old because of limited availability of animals but this deviation did not influence the quality or integrity of the results.

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

3 animals were between 7-8 weeks old because of limited availability of animals but this deviation did not influence the quality or integrity of the results.

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

- Source and lot/batch No.of test material:040802#
- Expiration date of the lot/batch: 06.08.2016
- Purity test date:08/01/2015
- purity: 99.17%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: stable in water, instable after repeated contact to air
- Solubility and stability of the test substance in the solvent/vehicle: 100% - table in water, instable after repeated contact to air
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: no

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: dilution in aqua ad injectabilia
- Preliminary purification step (if any): a correction factor of 1.008 was applied

FORM AS APPLIED IN THE TEST (if different from that of starting material): liquid

OTHER SPECIFICS:

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

- Source:
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: animal n°1 and 2: 8-9 weeks
Animal n° 3-5 : 7-8 weeks
- Weight at study initiation: Animal n°1: 154 g
Animal n°2: 165 g
Animal n°3: 146 g
Animal n°4: 146 g
Animal n°5: 136 g
- Fasting period before study: between 16 and 19 hours prior testing (access to water permitted)
- Housing: The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 02102151120)
- Diet (e.g. ad libitum): Altromin 1324 maintenance diet for rats and mice (lot no. 0922) ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): 12 hr dark / 12 hr light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2000 mg/kg
- Amount of vehicle (if gavage): Animals n° 1/2: 2.5 ml
Animals 3/4/5: 10 ml
- Justification for choice of vehicle: chosen due to its non-toxic characteristics
- Lot/batch no. (if required): 511535 (AlleMan Pharma)

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

DOSAGE PREPARATION (if unusual):
Animal 1/2: 0.504g test item into vehicle (final volume 2.5 ml)
Animal 3/4/5: 2.016g test item into vehicle (final volume 10 ml)

Doses:

2000 mg/kg body weight

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: at least once during the first 30 min and with special attention during the first 4 hours post-dose. Animals were weighed on day 1 prior to the administration, day 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight other:gross pathological changes

Results and discussion

Preliminary study:

1 animal at 2000 mg/kg body weight: no signs

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

> 2 000 mg/kg bw

Based on:

test mat. (total fraction)

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

none

Clinical signs:

2 animals showed slight piloerection the first day, between 120 and 180 min post-administration, but it is not considered to be related to the test item but to the administration procedure and the possible stress induced. No specific findings during the rest of the observation period for these 2 animals nor for the 3 3 others during all the observation duration.

Body weight:

None animals showed weight loss during the observation period.

Gross pathology:

None animals showed specific gross pathological changes during the observation period.

Any other information on results incl. tables

Clinical signs - Individual data :

Animal No./Sex	Time of observation post-dose	Observations
Dose level 2000 mg/kg Body Weight
1/ female 2/ female	0 min - 60 min	no specific findings
1/ female 2/ female	120 min - 180 min	slight piloerection
1/ female 2/ female	240 min - 15 days	no specific findings
3/ female	0 min - 15 days	no specific findings
4/ female	0 min - 15 days	no specific findings
5/ female	0 min - 15 days	no specific findings

Based on these results and according to the acute toxic class method regime no further testing was required.

Absolute body weights in grams and body weight gain in %:

Animal No. / sex	Starting dose (mg/kg bw)	Body Weight (g) - Day 1	Body Weight (g) - Day 8	Body Weight (g) - Day 15	Body Weight Change in comparison to day 1 (%)
1/Female	2000	154	164	183	19
2/Female	2000	165	181	186	13
3/Female	2000	146	167	174	19
4/Female	2000	146	171	185	27
5/Female	2000	136	165	175	29