[No public or meaningful name is available]

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 Jan - 16 Feb 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

Commission Directive 92/69/EEC

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM, UK GLP Monitoring Authority

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Vapour grown graphitic carbon fibre

Molecular formula:

C

IUPAC Name:

Vapour grown graphitic carbon fibre

Test material form:

solid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Crl:CD® (SO) IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 8 - 12 weeks
- Weight at study initiation: 200 - 350 g
- Fasting period: only during exposure period
- Housing: groups of up to five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes and provided with environmental enrichment items: wooden chew blocks and cardboard "fun tunnels"
- Diet: free access to food (EU Rodent Diet 5LF2, BCM IPS Limited, London, UK)
- Water: free access to mains drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

1.67 µm

Geometric standard deviation (GSD):

9.47

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical exposure chamber, the chamber was maintained under negative pressure.
- Exposure chamber volume: approx. 30 litres (dimensions: 28 cm diameter x 50 cm high)
- Method of holding animals in test chamber: each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber 'O' ring.
- Source and rate of air: oil free compressor, air passed through a water trap and respiratory quality filters before entering the SAG 410
- Flow rate: 60 L/min (120 air changes/h)
- System of generating particulates/aerosols: SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany)
- Method of particle size determination: Marple Personal Cascade Impactor (Westech IS Ltd, Beds., UK) consisting of six calibrated impactor stages (9.6, 6.6, 3.5, 1.8, 0.87 and 0.33 µm cut points) with stainless steel collection substrates and a back up glass fibre filter, housed in an aluminium sampler.
- Treatment of exhaust air: the extract from the exposure chamber passed through a 'scrubber' trap and was connected with a high efficiency filter to a metered exhaust system.
- Temperature in air chamber during exposure [°C]: 24 - 25
- Humidity in air chamber during exposure [%]: 29 - 32
- Oxygen concentration in air chamber during exposure [%]: 20.6 - 20.7

TEST ATMOSPHERE
- Brief description of analytical method used: The actual chamber concentration was measured at regular intervals during the exposure period. The gravimetric method used glass fibre filters (Gelman type A/E 25 mm) placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals' breathing zone and a suitable, known volume of exposure chamber air was drawn through the filter using a vacuum pump. Each filter was weighed before and after sampling in order to calculate the weight of collected test material. The difference in the two weights, divided by the volume of atmosphere sampled, gave the actual chamber concentration. The nominal chamber concentration was calculated by dividing the mass of test material used by the total volume of air passed through the chamber.
- Samples taken from breathing zone: yes
- Mean maximm attainable atmosphere concentration: 1.87 mg/L
- MMAD (Mass median aerodynamic diameter [µm]): 1.67
- Inhalable fraction (% < 4 µm): 65.2
- GSD (Geometric st. dev.): 9.47

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

nominal: 5.1 mg/L
maximum attainable concentration: 1.87 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observation for clinical signs were performed hourly during exposure, immediately at the end of exposure, 1 h after termination of exposure and subsequently daily for 14 days; bodyweights were recorded prior to treatment, on the day of exposure and on Days 7 and 14 or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other: The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity. The lungs, trachea and larynx from each animal were retained in buffered formalin prior to sections being prepared.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1.87 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: mean maximum attainable atmosphere concentration

Mortality:

One male (1/5) and no female (0/5) rat died at the maximum attainable concentration of 1.87 mg/L. The male was found dead at 223 min during the 4 h exposure period.

Clinical signs:

other: Common abnormalities noted during the study included increased respiratory rate, laboured respiration, noisy respiration, hunched posture, pilo-erection, fur staining by the test material and wet fur. There were isolated instances of decreased respiratory

Body weight:

One male animal showed a significant weight loss during Week 1 but recovered to show normal bodyweight development during Week 2. Normal bodyweight development was noted for all other surviving animals during the study.

Gross pathology:

Abnormally dark lungs and pale patches on the lungs were noted in all animals that survived until Day 14. The animal that died during the course of the study showed abnormally dark lungs with dark patches.

Any other information on results incl. tables

 

Table 5: Individual bodyweights

Mean achieved atmosphere concentration [mg/L air]	Animal number and sex	Bodyweight [g] on Day				Increment [g] during week
		0	7	14	At death	1	2
1.87	1 Male	301	324	356		23	32
	2 Male	321	251	331		-70	80
	3 Male	297	312	346		15	34
	4 Male	304	320	369		16	49
	5 Male	325	-	-	316	-	-
	6 Female	263	267	273		4	6
	7 Female	233	253	258		20	5
	8 Female	217	219	232		2	13
	9 Female	242	266	275		24	9
	10 Female	231	254	252		23	-2

 

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Conclusions:

Only one death occurred in a group of ten rats exposed to a mean maximum attainable atmosphere concentration of 1.87 mg/L air for 4 h. The acute inhalation median lethal concentration (LC50, 4 h) of the test item in the Sprague-Dawley Crl:CD® (SD) IGS BR strain rat was, therefore, determined to be > 1.87 mg/L air.