Oxo(propan-2-olato)aluminium

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 03, 2017 to October 18, 2017.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The acute oral toxicity study was undertaken as a bridging study to demonstrate equivalence between the target substance (XP 473) and the source substance (XP 453) for the read-across of other data.
A full discussion of read-across and supporting data is given in the attached justification.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

16 October 2012 and 22 November 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant, guideline study, available as an unpublished report.

Justification for type of information:

This study is the acute oral toxicity for the read-across Source, XP 453. Bridging studies were conducted on the read-across target for acute oral toxicity, Ames, and aquatic toxicity to Daphnia.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

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

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Oxon, UK
- Age at study initiation: At the start of the study the animals were eight to twelve weeks of age
- Weight at study initiation: The bodyweight variation did not exceed ±20% of the bodyweight of the initially dosed animal
- Fasting period before study: Overnight fast immediately before dosing
- Housing: The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes
- Diet: 2014C Teklad Global Rodent diet supplied by Harlan Laboratorius UK Limited, Oxon, UK, was allowed ad libitum throughout the study
- Water: Free access to mains drinking water
- Acclimation period: At least five days


ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25°C
- Humidity: Relative humidity 30 to 70%
- Air changes: The rate of air exchange was at least fifteen changes per hour
- Photoperiod: Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness
- In-life dates: Days 1 to 14

Route of administration:

oral: gavage

Vehicle:

other:

Details on oral exposure:

VEHICLE
- Concentration in vehicle: For the purpose of the study the test item was ground using a mortar and pestle and freshly prepared, as required, as a suspension in arachis oil BP water to give a dose level of 300 or 2000mg/kg bodyweight
- Amount of vehicle: Not stated
- Justification for choice of vehicle: Arachis oil BP was used because the test item did not dissolve/suspend in distilled water
- Lot/batch no. (if required): Not stated
- Purity: Not stated

MAXIMUM DOSE VOLUME APPLIED: 10mL/kg

DOSAGE PREPARATION (if unusual): Not applicable

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.

Doses:

Following a sighting test at dose levels of 300 and 2000 mg/kg, an additional four fasted female animals were given a single oral dose of test
material, as a suspension in Arachis oil BP, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored
during the study. All animals were subjected to gross necropsy.

No. of animals per sex per dose:

1 female at 300 mg/kg
1 female at 2000 mg/kg
4 females at 2000 mg/kg

Control animals:

no

Details on study design:

- 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

Statistics:

No statistical analysis was performed.

Preliminary study:

- Preliminary results: A sighting test at a dose levels of 300 and 2000 mg/kg showed no signs of toxicity or mortality

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

- Lethal results: There were no deaths

Clinical signs:

- Non-lethal results: No signs of systemic toxicity were noted during the observation period.

Body weight:

- Bodyweight results: All animals showed expected gains in bodyweight over the observation period

Gross pathology:

- Gross pathology results: No abnormalities were noted at necropsy

Other findings:

No data reported

Table1              Individual Clinical Observations and Mortality Data -300mg/kg

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
300	1-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0=     No signs of systemic toxicity

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

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
300	1-0 Female	180	202	212	22	10

Table 3              Necropsy Findings -300 mg/kg

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
300	1-0 Female	Killed Day 14	No abnormalities detected

Table4              Individual Clinical Observations and Mortality Data -2000mg/kg

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	2-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0=     No signs of systemic toxicity

Table5              Individual Bodyweights and Bodyweight Changes -2000mg/kg

Dose Level mg/kg	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2000	2-0 Female	155	173	193	18	20
	3-0 Female	171	201	213	30	12
	3-1 Female	172	187	204	15	17
	3-2 Female	168	196	215	28	19
	3-3 Female	158	176	194	16	18

Table 6              Individual Necropsy Findings-2000mg/kg

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	2-0 Female	Killed Day 14	No abnormalities detected
	3-0 Female	Killed Day 14	No abnormalities detected
	3-1 Female	Killed Day 14	No abnormalities detected
	3-2 Female	Killed Day 14	No abnormalities detected
	3-3 Female	Killed Day 14	No abnormalities detected

Interpretation of results:

not classified

Conclusions:

The acute oral median lethal dose (LD50) of aluminum, benzoate C16-18-fatty acids complexes in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.

Executive summary:

Introduction. 

The study was performed to assess the acute oral toxicity of the test material in the Wistar strain rat.The acute oral toxicity of the test item to the Wistar strain rat was assessed in a GLP-compliant study following OECD guideline 420 (adopted 2001) and Method B1 bis Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008 in a proprietary, experimental study (Harlan 2013). The study is considered reliable and relevant for use for this endpoint.

Method. 

Following a sighting test at dose levels of 300 mg/kg bodyweight and 2000 mg/kg bodyweight, a further group of four fasted females was given a single oral dose of test material, as a suspension in Arachis oil BP, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study period of 14 days. All animals were subjected to gross necropsy.

Mortality. 

There were no deaths.

 

Clinical Observations.

There were no signs of systemic toxicity noted in the animal treated at a dose levels of 300 mg/kg bodyweight or 2000 mg/kg bodyweight.

 

Bodyweight. 

All animals showed expected gains in bodyweight.

 

Necropsy. 

No abnormalities were noted at necropsy.

 

Conclusion. 

The acute oral median lethal dose (LD₅₀) of aluminum, benzoate C16-18-fatty acids complexes in the female Wistar strain rat was estimated to be greater than 2000mg/kg bodyweight.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17th December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Oxo(propan-2-olato)aluminium

EC Number:

270-365-0

EC Name:

Oxo(propan-2-olato)aluminium

Cas Number:

68425-65-0

Molecular formula:

C3 H7 Al O2

IUPAC Name:

oxo(propan-2-olato)aluminium

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI rats

Sex:

female

Details on test animals or test system and environmental conditions:

study: 1 (from sighting study) + 4 additional animals
Sex: Female, nulliparous and non pregnant animals
Age of animals: Young adult rat, 8-9 weeks old in sighting and in main study
Body weight in sighting study: 211 g
Body weight range
in main study: 192 - 213 g
Acclimatization time: 5 days in sighting study and 6 days in main study

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Details on oral exposure:

The test item was dosed as a formulation in 1% methyl cellulose solution. A single oral administration - followed by a fourteen-day observation period - was performed by gavage. The day before treatment the animals were fasted. The food but not water was withheld overnight. Animals were weighed before the application and the food was returned 3 hours after the treatment.

Doses:

The sighting study starting dose of 2000 mg/kg was followed by dosing of a further four animals at this level as a limit test for relevant guideline.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

The animals were acclimatized for 5 days in sighting study and 6 days in main study prior to the 14 days post-treatment observation period: necropsy was performed on Day 14.
Animals were observed individually after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h after the treatment and twice each day for 14 days thereafter.
Individual observations were performed on the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
At the end of the observation period all survivor rats were sacrificed under isofluran anaesthesia. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed, and any abnormality was recorded with details of its location, colour, shape and size.

Results and discussion

Preliminary study:

The rat (No.: 7533) dosed at 2000 mg/kg bw XP 473 did not die in sighting study.

Effect levels

Key result

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred at the 2000 mg/kg single oral dose of the test item in the main study. All rats survived until the end of the 14-day observation period.

Clinical signs:

No treatment related symptoms were observed in 2000 mg/kg bw dose throughout the 14-day post-treatment period.

Body weight:

The mean body weight of animals treated with 2000 mg/kg bw dose corresponded to their species and age throughout the study.

Gross pathology:

Slight hydrometra was observed in two females (No.: 7533, 7556). Hydrometra is physiological finding and connected to the oestrus cycle of the animal. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals treated with 2000 mg/kg bw of the test item.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (oral, rat) >2000 mg/kg.