Non-graphitic carbon fibre

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-11-20 to 2013-03-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

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:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

carbon

EC Number:

701-026-1

Cas Number:

7440-44-0

Molecular formula:

C up to (C80N5H16O)n

IUPAC Name:

carbon

Test material form:

solid: fibres

Details on test material:

- milled carbonised PAN based fibre (Sigrafil C30 M150 UNS)
- for further details on the test material, see section 1.4, endpoint "Non-graphitic carbon fibre (carbonised PAN based fibre, milled)", attached document "Analytics_milled_carbonised_PAN_based_fibre.pdf"

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, D-97633 Sulzfeld, Germany
- Age at study initiation: not reported
- Weight at study initiation: 146-163 g
- Housing: transparent macrolon cages (type 3-180, floor area 810 cm2), three rats per cage and separated regarding sex if applicable
- Diet (e.g. ad libitum): ad libitum, pelleted diet "Altromin 1324" supplied by Altromin, D-32791 Lage, Germany
- Water (e.g. ad libitum): ad libitum, domestic qualitiy drinking water which is acidified with hydrochloric acid to pH 2.5 to prevent microbial growth
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% (w/v)
- Amount of vehicle (if gavage): 1x 10 mL/kg bw
- Justification for choice of vehicle: non-toxic vehicle, the test item could despite its big volume be suspended in the vehicle and still passed the cannula in a concentration of 20% (w/v)

MAXIMUM DOSE VOLUME APPLIED:
- 1x 10 mL of vehicle with suspended test item at a concentration of 20% (w/v)

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose: because the bioavailability of the milled carbonised PAN based fibre is negligible no toxicity is expected after oral exposure. Hence, the limit dose of 2000 mg/kg bw was chosen as the starting dose.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weight is recorded before administration (day 0) as well as on day 7 and day 14; animals died during the study are weighed as well
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
- Clinical observations are made at 30 min, 2 hrs, 4 hrs and 6 hrs after dosing as well as daily thereafter for a total of 14 consecutive days.
- All signs of illness and behaviour changes are recorded.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No observed mortality

Clinical signs:

other: Piloerection was observed in three animals at 30 minutes, 2 hrs and 4 hrs after application. After 6 hrs as well as from day 1 until the end of the observation period on day 14, no animal showed any abnormalities.

Gross pathology:

Necropsy done, but no signs of pathological signs were found.

Any other information on results incl. tables

Table 1: Results of the daily observation of the animals according to the assessment key (see below)

Group

Animal No.

Dose mg/kg bw

Sex

After administration

Day after administration

30 min

2 hrs

4 hrs

6 hrs

1

2

3

4

5

6

7

8

9

10

11

12

13

14

1

1

2000

female

B

B

B

A

A

A

A

A

A

A

A

A

A

A

A

A

A

A

2

2000

female

B

B

B

A

A

A

A

A

A

A

A

A

A

A

A

A

A

A

3

2000

female

B

B

B

A

A

A

A

A

A

A

A

A

A

A

A

A

A

A

2

1

2000

female

B

B

A

A

A

A

A

A

A

A

A

A

A

A

A

A

A

A

2

2000

female

B

B

A

A

A

A

A

A

A

A

A

A

A

A

A

A

A

A

3

2000

female

B

B

A

A

A

A

A

A

A

A

A

A

A

A

A

A

A

A

A	Normal behaviour
B	Piloerection

Table 2: Individual values of the body weight [in g] of the animals on day 0, 7 and 14

Group	Animal No.	Dose mg/kg bw	Sex	Day 0	Day 7	Day 14
1	1	2000	female	153	172	204
	2	2000	female	163	197	224
	3	2000	female	158	194	221
2	1	2000	female	146	191	219
	2	2000	female	148	216	226
	3	2000	female	154	195	223

Table 3: Average body weight [in g] of the groups on day 0, 7 and 14

Group	Dose mg/kg bw	Sex	Day	Ø	σ	n
1	2000	female	0	158	5	3
			7	188	14	3
			14	216	11	3
2	2000	female	0	149	4	3
			7	201	13	3
			14	223	4	3

Ø: Mean value

σ: Standard deviation

n: Number of animals

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

As there are no deviations from the test protocol and GLP criteria are met the study is regarded as valid. The oral LD50 value of the test substance (milled carbonised PAN based fibre) in rats was found to be above 2000 mg/kg bw under the experimental conditions. The test substance does therefore not meet the classification criteria according to regulation (EC) No. 1272/2008.

Executive summary:

The acute oral toxicity in rats was determined according to the method recommended in the OECD Guideline No. 423 and in the Council Regulation (EC) No. 440/2008 part B.1.tris.

The study was accomplished on two groups, each consisting of three female animals. A starting dose level of 2000 mg/kg bw and a dose volume of 10 mL/kg bw were applied. Animals were observed for a total of 14 days.

All animals survived the administration of the dosing level of 2000 mg/kg bw and only showed slight signs of toxicosis.

The oral LD50 value of the test substance in rats was found to be above 2000 mg/kg bw under the experimental conditions. The test substance does therefore not meet the classification criteria according to regulation (EC) No. 1272/2008.