Boron carbide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 03 - April 23, 2010

Reliability:

1 (reliable without restriction)

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Commission Regulation (EC) No. 440/2008,L 142, Annex Part B, 30 May 2008

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: EPA OPPTS 870.1000 (Acute toxicity testing background)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

GLP according to German Chemikaliengesetz and Directive 2004/9/EC

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Boron carbide

EC Number:

235-111-5

EC Name:

Boron carbide

Cas Number:

12069-32-8

Molecular formula:

CB4

IUPAC Name:

2,3,4,5-tetraboratetracyclo[2.1.0.0¹,³.0²,⁵]pentane

Details on test material:

Boron carbide, powder, technical grade, purity 97%, trade name: TETRABOR , batch no. 908M1300, supplied by ESK Ceramics GmbH & Co. KG

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species/strain: Healthy rats, WISTAR rats Crl: WI(Han) (Full-Barrier)
Source: Charles River, 97633 Sulzfeld, Germany
Sex: female, non-pregnant, nulliparous

Age at the beginning of the study: 9 - 10 weeks old
Body weight at the beginning of the study:
Animals no. 1 - 3, step 1: 157 - 164 g;
Animals no. 4 - 6, step 2: 166 - 178 g;
The animals were derived from a controlled full barrier maintained breeding system (SPF).

Housing and Feeding Conditions
- Full-barrier in an air-conditioned room
- Temperature: 22 ± 3°C
- Relative humidity: 55 ± 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 1310)
- Free access to tap water, sulphur acidified to a pH value of approx. 2.8 (drinking water, municipal residue control, microbiological control at regular
intervals)
- The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 040509)
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Adequate acclimatisation period (at least five days).

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

cotton seed oil

Remarks:

(Sigma, lot no. 038K0009, expiry date: 1110412010

Details on oral exposure:

Prior to the administration a detailed clinical observation was made of all animals.

Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.

For all animals of the first and second step, 2 g of the test item were suspended in the vehicle to gain a final volume of 10 ml and to achieve a dose of 2000 mg/kg body weight at a dose volume of 10 ml/kg body weight. The dose formulations were made shortly before each dosing occasion.

The test item was administered at a single dose by gavage using a feeding tube.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 females per dose per step

Control animals:

no

Details on study design:

Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.

- Necropsy of survivors performed: yes

- Other examinations performed:
- Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic
and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to
observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- body weight
- gross necropsy: All gross pathological changes were recorded.

Statistics:

Not relevant due to no toxic effects observed in Limit test

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortalities, Limit Test

Mortality:

No intercurrent deaths (see table 1)

Clinical signs:

other: other: No signs of toxicity observed (see table 2)

Gross pathology:

No abnormalities detected (see table 4)

Any other information on results incl. tables

Table 1: Results per Step

Step	Sex/no.	Dose (mg/kg)	Number of animals	Number of intercurrent deaths
1	female/ 1-3	2000	3	0
2	female/ 4-6	2000	3	0

 

Table 1: LD50 cut off

 

Dose (unit)	Number of animals investigated	Number of intercurrent deaths	LD50 cut off
2000 mg/kg bodyweight	6	0	unclassified

 

 

Table 2: Clinical Signs - Individual Data

 

Animal no. /sex	Time of observation post-dose	Observations
1/female	during the whole observation period	no signs of toxicity
2/female	during the whole observation period	no signs of toxicity
3/female	during the whole observation period	no signs of toxicity
4/female	during the whole observation period	no signs of toxicity
5/female	during the whole observation period	no signs of toxicity
6/female	during the whole observation period	no signs of toxicity

 

Table 3: Absolute Body Weights in g and Body Weight Gain in %

 

Animal no. /sex	g Day 1	g Day 8	g Day 15	% Day 1-15
1 /female	157	188	197	26
2 /female	164	194	200	22
3/female	162	179	189	17
4 /female	166	182	184	11
5 /female	178	207	205	15
6/female	169	191	195	15

 

Table 4:Macroscopical Findings - Individual Data

 

Animal no./sex	Organ	Findings at the necropsy
1 /female	-	NAD
2 /female	-	NAD
3/female	-	NAD
4 /female	-	NAD
5 /female	-	NAD
6/female	-	NAD

NAD: No Abnormalities Detected

Applicant's summary and conclusion

Interpretation of results:

not classified

Conclusions:

Under the conditions of the present study, single oral application of the test item Boron Carbide B4C to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality.
The median lethal dose of Boron Carbide B4C after single oral administration to female rats, observed over a period of 14 days is: LD50 cut off (rat): unclassified
In conformity with the criteria given in Annex VI to Commission Directive 2001/591 EC the test item Boron Carbide B4C has no obligatory labelling requirement for toxicity.
According to Annex I of Regulation (EC) 1272/2008 the test item Boron Carbide B4C was unclassified.
According to OECD-GHS (Globally Harmonized Classification System) the test item Boron Carbide B4C has no obligatory labelling requirement for toxicity.

Executive summary:

Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was suspended in a vehicle (cottonseed oil) at a concentration of 0.2 g/ml- and administered at a dose volume of 10 ml/kg. All animals after their entrance at BSL were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. All animals survived until the end of the study without showing any signs of toxicity. Throughout the 14-day observation period, the weight gain of the animals was within the expected range. At necropsy, no macroscopical findings were observed in any animal of any step. On the basis of the test results given below and in conformity with the criteria given in Annex VI to Commission Directive 2001/591EC as well as in Annex I of Regulation (EC) 1272/2008, the substance should be not classified.