Boron carbide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 02 - April 12, 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 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal 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

GLP compliance:

yes (incl. QA statement)

Remarks:

GLP according to Chemikaliengesetz and Directive 2004/9/EC

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:

male/female

Details on test animals or test system and environmental conditions:

Test animals:
Species/strain: Healthy rats, WISTAR Crl: WI(Han) (Full-Barrier)
Source: Charles River, 97633 Sulzfeld, Germany
Sex: male and female. The female animals were nulliparous and non-pregnant.
Body weight at the beginning of the study: females: 210 - 218 g, males 237 - 261 g
Age at the beginning of the study: females: 8 - 9 weeks, males: 8 - 9 weeks old
Number of animals: 5 male and 5 female
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 Iight,72 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 individually in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 101109)
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Adequate acclimatisation period (at least five days)

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

Preparation of the Animals:
Approximately 25 hours before the test, the fur was removed from the dorsal area of the trunk by using an electric clipper. Care was taken to avoid abrading the skin, and only animals with healthy intact skin were used. No less than 10% of the body surface was cleared for the application. Prior to the application a detailed clinical observation was made of all animals.

Application:
Water (Aqua ad injectionem (B. Braun Melsungen, lot no. 7494A191, expiry date: 11/2010) was used as vehicle due to its non-irritating
characteristics.
The test item was applied at a single dose (2000 mg/kg bw), uniformly over an area which was approx. 10% of the total body surface. The test item was held in contact with the skin by a dressing throughout a 24-hour period. The dressing consisted of a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner.

Dose Level:
The test item was applied at a single dose of 2000 mg/kg body weight to each animal.

Exposure Period:
The test item was held in contact with the skin throughout a 24-hour period. At the end of the exposure period residual test item was removed by
using lukewarm tap water.

Duration of exposure:

24h

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 male, 5 female

Control animals:

not required

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). Thereafter, the animals were observed for clinical signs once daily until the end of the observation period.
The animals were weighed on day 1 (prior to the application) and on days 8 and 15.

- Necropsy of survivors performed:
All animals were subjected to gross necropsy. All gross pathological changes were recorded

- 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. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Statistics:

Not applicable, no clinical signs of irritation or mortality.

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No intercurrent deaths could be observed for any of the 10 animals tested (5 male, 5 female)

Clinical signs:

other: other: The test item showed no signs of dermal irritation and no acute dermal toxicity characteristics after a single dose application. Slight scratches were observed in 1 of 5 female and 2 of 5 male animals, but these symptoms are not assumed to be relat

Gross pathology:

With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal. (see table 6)

Any other information on results incl. tables

Table 1: Clinical Signs of Systemic Toxicity - Individual Data - Females

AnimalNo./ Sex	Time of Observation (post-dose)	Observations (for signs of dermal irritation, see Table 3)
11/female	during the entire observation period	nf
12/female	during the entire observation period	nf
13/female	during the entire observation period	nf
14/female	during the entire observation period	nf
15/female	during the entire observation period	nf

 

Table 2: Clinical Signs of Systemic Toxicity - Individual Data - males

AnimalNo./ Sex	Time of Observation (post-dose)	Observations (for signs of dermal irritation, see Table 4)
21/female	during the entire observation period	nf
22/female	during the entire observation period	nf
23/female	during the entire observation period	nf
24/female	during the entire observation period	nf
25/female	during the entire observation period	nf

 

Table 3: Skinlrritation-Individual Data –Females

Day after Start  of Application	AnimalNo. 11		AnimalNo. 12		AnimalNo. 13		AnimalNo. 14		AnimalNo. 15
	E/O	comments	E/O	comments	E/O	comments	E/O	comments	E/O	comments
day1	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	s
day2	0/0	*	0/0	*	0/0	*	0/0	*	0/0	*
day3	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	nf
day4	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	nf
day5	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	nf
day6	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	nf
day7	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	nf
day8	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	nf
day9	0/0	nf	0/0	nf	0/0	slight s	0/0	nf	0/0	nf
day10	0/0	nf	0/0	nf	0/0	slight s	0/0	nf	0/0	nf
day11	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	nf
day12	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	nf
day13	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	nf
day14	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	slight s (not on application site)
day15	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	slight s (not on application site)
Comments: E:erythema; O: oedema;1,2,3,4: scoring system laid down in OECD Guideline 404 d: desquamation;es:eschar; s : scratches; N (mm) : necrosis;nf: no findings reversibility: c : completely reversed;nc: not completely reversed; n : not reversed * black discolouration of the application site due to the test item

Table 4: Skinlrritation-Individual Data - Males

Day after Start  of Application	AnimalNo. 21		AnimalNo. 22		AnimalNo. 23		AnimalNo. 24		AnimalNo. 25
	E/O	comments	E/O	comments	E/O	comments	E/O	comments	E/O	comments
day1	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	nf
day2	0/0	*	0/0	*	0/0	*	0/0	*	0/0	*
day3	0/0	nf	0/0	slight s	0/0	nf	0/0	slight es	0/0	nf
day4	0/0	nf	0/0	slight s	0/0	nf	0/0	slight es	0/0	nf
day5	0/0	nf	0/0	slight s	0/0	nf	0/0	slight s	0/0	nf
day6	0/0	nf	0/0	slight s	0/0	nf	0/0	slight s	0/0	nf
day7	0/0	nf	0/0	slight s	0/0	nf	0/0	slight s	0/0	nf
day8	0/0	nf	0/0	nf	0/0	nf	0/0	slight s	0/0	nf
day9	0/0	nf	0/0	nf	0/0	slight s	0/0	nf	0/0	nf
day10	0/0	nf	0/0	nf	0/0	slight s	0/0	nf	0/0	nf
day11	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	nf
day12	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	nf
day13	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	nf
day14	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	nf
day15	0/0	nf	0/0	nf	0/0	nf	0/0	nf	0/0	nf
Comments: E:erythema; O: oedema;1,2,3,4: scoring system laid down in OECD Guideline 404 d: desquamation;es:eschar; s : scratches; N (mm) : necrosis;nf: no findings reversibility: c : completely reversed;nc: not completely reversed; n : not reversed * black discolouration of the application site due to the test item

 

 

Table 5: Absolute Body Weights in g and Body Weight Gain in %

AnimalNo. / Sex	Day 1	Day 1	Day 1	% Day 1-15
11 female	210	209	213	1
12 female	212	215	222	5
13 female	211	209	223	6
14 female	211	214	221	5
15 female	218	219	227	4
21 male	239	259	286	20
22 male	241	263	282	17
23 male	261	286	306	17
24 male	249	273	303	22
25 male	237	244	280	18

 

 

 

Table 6:Macroscopical Findings - Individual Data - Males and Females

AnimalNo./Sex	Organ	Findings at theNecropsy
11 female		nsf
12 female		nsf
13 female		nsf
14 female		nsf
15 female		nsf
21 male		nsf
22 male		nsf
23 male		nsf
24 male		nsf
25 male		nsf

nsf: no specific findings

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the present study, single dermal application of the test item boron carbide to rats at a dose of 2000 mg/kg body weight was associated neither with significant signs of skin irritation nor with signs of toxicity or mortality. In conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC the test item boron carbide has no obligatory labelling requirement for toxicity (for details see Evaluation of Results). The dermal LD50 was determined to be > 2000 mg boron carbide/kg body weight. According to Annex I of Regulation (EC) 1272/2008 the test item boron carbide does not require classification for acute percutaneous toxicity since neither mortalities nor significant clinical signs of toxicity were observed at a dose of 2000 mg/kg body weight. According to OECD-GHS (Globally Harmonized Classification System) the test item boron carbide does not require classification for acute percutaneous toxicity since neither mortalities nor significant clinical signs of toxicity were observed at a dose of 2000 mg/kg body weight.

Executive summary:

On the basis of the test results and in conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC as well as in Annex I of Regulation (EC) 1272/2008, the substance should be not classified.

Limittest: Yes

LD50: > 2000 mg/kg body weight

Species/strain: WISTAR Crl: WI(Han) rats

Vehicle (moistening): Aqua ad injectionem

Number of animals: 5 male and 5 female

Duration of exposure: 24 hours

Method: OECD 402, EC 440/2008, OPPTS 870.1200

Table 1: Results per Step

Sex	Dose (mg/kg bw)	Number of Animals	Number of Intercurrent Deaths
male	2000	5	0
female	2000	5	0

- Signs of toxicity related to dose level used, time of onset and duration:

No treatment-related effects were observed.

- Effect on organs (related to dose level):

No treatment related effects were observed.

- Signs of irritation:

No treatment related effects were observed.