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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: nanoform
Details on test material:
Test materials used in this dossier are all considered to fall under the definition of nano-materials according to the European Commission Recommendation 2011/696/EU as the synthesis and manufacturing of this pigment always yields particulate material with a fine particle size distribution.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent
- Age at study initiation: young adult
- Weight at study initiation: males 274 - 324g, females 244- 260g
- Fasting period before study: /
- Housing: groups of five
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 52-67
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: From: To: /

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical exposure chamber with continuous flow
- Exposure chamber volume: 30 l
- Method of holding animals in test chamber: a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber '0' ring
- Source and rate of air: compressed air was supplied by means of a Gast oil free compressor
- Method of conditioning air: passed through a water trap and respiratory quality filters which removed particulate material above 0.005 pm before
- System of generating particulates/aerosols: produced from the test material using a 'Wright Dust Feed' mechanism located at the top of the exposure chamber and driven by a variable speed motor. The dust feed was connected to a metered compressed air supply.
- Method of particle size determination: determined three times during the exposure period using a Cascade Impactor
- Temperature, humidity, pressure in air chamber: measured by an electronic thermometer/humidity meter (Kane-May Ltd., Welwyn Garden City, Hertfordshire, U.K.) located in a vacant port in the animals' breathing zone of the chamber and recorded every thirty minutes throughout the four-hour exposure period.

TEST ATMOSPHERE
- Brief description of analytical method used: The chamber was maintained under negative pressure. Homogeneity of the test atmosphere within the chamber was not specifically determined during this study, but, chambers of the same design have been fully validated and shown to produce evenly distributed atmospheres in the animals' breathing zone with a wide variety of test materials. (Green J.D. et al. Fundamental and Applied Toxicology 4, 768 - 777, 1984)
- Samples taken from breathing zone: no

VEHICLE
- air

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: particle size of the generated atmosphere of the test material inside the exposure chamber was determined three times during the exposure period using a Cascade Impactor. This device consisted of six impactor stages with stainless steel collection substrates (10, 6, 3.5, 1.6, 0.9 and 0.5 pm cut-off points) and a back up glass fibre filter. collection substrates were weighed before and after sampling and the weight of test material, collected at each stage, calculated by difference. From the results obtained the weight distribution of particles in the size range > 10 pm, 10 - 6 pm, 6 - 3.5 pm, 3.5 -1.6 pm, 1.6 - 0.9 pm and 0.9 - <0.5 pm was calculated.
Analytical verification of test atmosphere concentrations:
no
Remarks:
concentration estimated at regular intervals during the exposure period, gravimetric method used, employed glass fibre filters (Gelman type A/E 25 mm)
Duration of exposure:
ca. 4 h
Concentrations:
5.0 mg/litre
No. of animals per sex per dose:
5 per sex and dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations hourly during exposure, immediately on removal from the restraining tubes at the end of the exposure, one hour after termination of the exposure and subsequently once daily for 14 days, bodyweights were recorded on the day of exposure, days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
Using the mortality data obtained, an estimate of the acute inhalation median lethal concentration (LC50) of the test material was made.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.24 mg/L air
Exp. duration:
4 h
Remarks on result:
other: no mortality occurred
Mortality:
no mortalities
Clinical signs:
other: During exposure wet fur, decreased respiratory rate and test material staining of the fur were noted. On removal from the chamber animals additionally showed hunched posture, lethargy and pilo-erection. Laboured respiration and ptosis were common and ther
Body weight:
Expected bodyweight development was noted throughout the study
Gross pathology:
No abnormalities were detected at necropsy

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
No deaths occurred in a group of ten rats exposed to a mean achieved concentration of 5.24 mg/litre (range 4.25 - 6.33 mg/litre). It was therefore considered that the acute inhalation median lethal concentration (LC50) of the test material in the Sprague-Dawley strain rat was greater than 5.24 mg/litre.