Beryllium oxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-02-02 to 2010-05-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study according to OECD 423 guideline and performed under GLP conditions. No deviations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Beryllium oxide

EC Number:

215-133-1

EC Name:

Beryllium oxide

Cas Number:

1304-56-9

Molecular formula:

BeO

IUPAC Name:

oxoberyllium

Details on test material:

- Name of test material (as cited in study report): beryllium oxide powder
- Substance type: Powder
- Physical state: Solid
- Analytical purity: 99.9 %
- Lot/batch No.: UOX Lot-No 1846-B; Batch No. 0000690266
- Expiration date of the lot/batch: Not applicable
- Stability under test conditions: Stable under storage conditions
- Storage condition of test material: At room temperature (range of 20 ± 5 °C, provided by Harlan Laboratories Ltd.), light protected

Test animals

Species:

rat

Strain:

other: Rat, RccHan: WIST(SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V., 5961 NM Horst, The Netherlands
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 181.7 g - 204.4 g (Only animals without any visible signs of illness were used for the study).
- Housing: Room Number: 0105 / Harlan Laboratories Ltd., Füllinsdorf. The animals were accomodated in groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding (‘Lignocel’ J. Rettenmaier&Söhne GmbH&CoKG, 73494 Rosenberg, Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland).
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 60/09 (Provimi Kliba AG, 4303 Kaiseraugst, Switzerland) ad libitum (except for the overnight fasting period prior to oral gavage and approximately 3-4 hours post dosing). Results of analyses for contaminants are archived at Harlan Laboratories Ltd.
- Fasting: approximately 16 to 20 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing.
- Water: Community tap water from Füllinsdorf ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at Harlan Laboratories Ltd.
- Acclimation period:
03-Feb-2010 to 08-Feb-2010 (Group 1, females, 300 mg/kg)
03-Feb-2010 to 10-Feb-2010 (Group 2, females, 2000 mg/kg)
16-Feb-2010 to 22-Feb-2010 (Group 3, females, 2000 mg/kg)

ENVIRONMENTAL CONDITIONS
- Standard laboratory conditions, continuously monitored environment.
- Temperature: 22 ± 3 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period.

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% solution in PEG 300 (w/w). The test item was formulated in PEG 300 at a concentration of 0.03 g/mL or 0.2 g/mL.
- Amount of vehicle (if gavage): Group 1 (300 mg/kg body weight), a 3% solution in PEG 300 (w/v) was prepared.
- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. The test item is insoluble in water according to the Sponsor’s specifications. Therefore, a 20% solution in PEG 300 (w/w) was prepared, which was considered orally applicable. For the oral administration of Group 1 (300 mg/kg body weight), a 3% solution in PEG 300 (w/v) was prepared.
- Lot/batch no. : S60502-099
- Description: Colorless viscous liquid
- Source: Sigma-Aldrich Chemie GmbH, 89555 Steinheim, Germany
- Stability of the Vehicle: Stable under storage conditions
- Expiry Date: 30-Apr-2014
- Storage Conditions: At room temperature (range of 20 ± 5 °C), light protected.

MAXIMUM DOSE VOLUME APPLIED:
The dosing volume was 10 mL/kg body weight.

DOSAGE PREPARATION (if unusual):
The dose formulations were prepared shortly before each dosing occasion using a magnetic stirrer, a spatula and an Ultra-Turrax as homogenizers. The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

CLASS METHOD
- Rationale for the selection of the starting dose:

Doses:

The animals received a single dose of the test item by oral gavage administration at 300 mg/kg or 2000 mg/kg body weight.

No. of animals per sex per dose:

Dose Level Group Animal Number
300 mg/kg 1 1-3
2000 mg/k 2 4-6
2000 mg/kg 3 7-9

Details on study design:

- Study was conducted according to OECD guideline 423.
- Three groups, each consisting of three female RccHan:WIST (SPF) rats were treated with BeO
- Powder by single oral gavage administration at a dosage of 300 mg/kg (Group 1) or 2000 mg/kg body weight (Groups 2-3) and administered at a dosing volume of 10 mL/kg.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were examined daily during the acclimatization period and mortality, viability and
clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15.

Statistics:

No statistical analysis performed.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality was observed

Clinical signs:

No clinical signs were observed

Body weight:

Bodyweight was within the range of what is observed for this strain (please see table below)

Gross pathology:

No macroscopic findings were recorded at necropsy

Other findings:

No clinical signs were observed in three animals treated at 300 mg/kg (Group 1). According to OECD Guideline 423, the next higher dose was 2000 mg/kg. Three animals treated at 2000 mg/kg (Group 2) showed slight sedation and slightly ruffled fur, but all signs were fully reversible. The confirming group of three animals treated at 2000 mg/kg (Group 3) was free of clinical signs throughout the entire observation period.

Any other information on results incl. tables

Table 1 Mortality

Dose level	Group	Animal number	Mortality
300 mg/kg bodyweight	1	1 -3	0
2000 mg/kg bodyweight	2	4 -6	0
2000 mg/kg bodyweight	3	7-9	0

Table 2 Bodyweight

Group	Animal	Day 1	Day 8	Day 15
Group 1	1	193.9	212.8	218.0
	2	203.6	217.5	228.5
	3	184.9	228.5	217.6
Group 2	4	190.5	212.1	224.0
	5	204.4	214.2	220.4
	6	193.7	207.1	210.4
Group 3	7	186.0	197.9	207.4
	8	183.8	194.5	196.6
	9	181.7	193.6	205.2

 

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 (female rat): greater than 2000 mg/kg body weight

Executive summary:

Three groups, each consisting of three female RccHan:WIST (SPF) rats, were treated with BeO powder by single oral gavage administration at a dosage of 300 mg/kg (Group 1) or 2000 mg/kg body weight (Groups 2-3). The test item was formulated in PEG 300 at a concentration of 0.03 g/mL or 0.2 g/mL and administered at a dosing volume of 10 mL/kg.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15.

All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period.

No clinical signs were observed in three animals treated at 300 mg/kg (Group 1). According to OECD Guideline 423, the next higher dose was 2000 mg/kg. Three animals treated at 2000 mg/kg (Group 2) showed slight sedation and slightly ruffled fur, but all signs were fully reversible. The confirming group of three animals treated at 2000 mg/kg (Group 3) was free of clinical signs throughout the entire observation period.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were recorded at necropsy.

The median lethal dose of BeO powder after single oral administration to female rats, observed over a period of 14 days, is:

LD50 (female rat): greater than 2000 mg/kg body weight.