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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:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
GLP compliance:
yes (incl. QA statement)
Remarks:
testing lab.
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Nickel
EC Number:
231-111-4
EC Name:
Nickel
Cas Number:
7440-02-0
Molecular formula:
Ni
IUPAC Name:
nickel
Constituent 2
Chemical structure
Reference substance name:
Cobalt
EC Number:
231-158-0
EC Name:
Cobalt
Cas Number:
7440-48-4
Molecular formula:
Co
IUPAC Name:
cobalt(2+)
Constituent 3
Chemical structure
Reference substance name:
Lithium
EC Number:
231-102-5
EC Name:
Lithium
Cas Number:
7439-93-2
Molecular formula:
Li
IUPAC Name:
lithium
Constituent 4
Chemical structure
Reference substance name:
Aluminium
EC Number:
231-072-3
EC Name:
Aluminium
Cas Number:
7429-90-5
Molecular formula:
Al
IUPAC Name:
aluminum
Test material form:
solid: particulate/powder
Details on test material:
Composition represents the lowest and highest possible concentration of each individual constituent in NCA (estimated by Monte Carlo simulation, taking into account the following ranges of variability:
Sum of of Ni+Co+Al = approx. 1
Li =0.9-1.3
Ni: 0.75-0.99
Co: 0.01-0.2
Al: 0.01-0.2
A more detailed composition can be provided by the data holder, but is not defined in this record as this represents sensitive business information that cannot be shared with co-registrants. The composition, however, fits into the agrees Substance Identity Profile.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Oxon, UK
- Age at study initiation: 8 to 11 weeks
- Weight at study initiation: 199 to 350 g
- Fasting period before study: no
- Housing: groups of 5 of the same sex
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25°C,
- Humidity (%): 30 - 70%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
In order to facilitate aerosolization and reduce particle size, the test itern was ground using a srnall arnount of Diethyl Ether in a Retsch Planetary Ball Mill (Retsch (UK) Ltd, Leeds, UK) the solvent was rernoved via evaporation prior to use. The absorption of the test itern was not
deterrnined.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.05, 0.23, 1.02 and 2.08 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
On the day of exposure (Groups 1 and 3) or prior to the day of exposure (Groups 2 and 4) each rat was acclimatized (for approximately 2 hours) to a tapered polycarbonate restraining tube. During each exposure period, 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. Only the nose of each animal was exposed to the test atmosphere. Following an appropriate equilibration period four groups, each of ten rats (five males and five females), were subjected to a single exposure to the test item for a period of four hours. Based on the expected toxicity of the test item, a target concentration of 2.0 mg/L was used for the first exposure. Further concentrations were selected after consideration of the results of the previous exposure.

Clinical Signs:
All animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for up to fourteen days. Any deaths or evidence of overt toxicity were recorded at each observation.

Body Weight:
Individual body weights were recorded on arrival, prior to treatment on the day of exposure and on Days 1, 3, 7 and 14 or at death.

Necropsy:
At the end of each fourteen day observation period, the surv1vmg animals were killed by intravenous overdose of sodium pentobarbitone. All animals, including those that died during the study were subjected to a füll external and internal examination, and any macroscopic abnormalities were recorded. The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LC0
Effect level:
0.05 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.15 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
see "Any other information on results incl. tables"
Clinical signs:
other: Common abnormalities noted during the study included increased respiratory rate, hunched posture, pilo-erection, generalized black für staining caused by the test item and wet für. There were occasional instances of ataxia and isolated occurrences of tip-
Body weight:
Group 1 - All animals exhibited body weight losses or showed no body weight gain on the first day post-exposure.
Group 2 - All animals exhibited body weight losses on the first day post-exposure.
Group 3 - All animals exhibited body weight losses or showed no body weight gain on the first day post-exposure. The surviving male animal exhibited fürther body weight losses during the first week of the recovery period but then showed body weight gain during the final week of the recovery period.
Group 4 - Two males and two female animals exhibited body weight losses or showed no body weight gains on Day 1 post-exposure. One male showed no body weight gain from Days 1 to 3 post-exposure, whereas four female animals exhibited body weight losses during the same time period. Body weight gains were noted in all animals during the remainder of the recovery period.
Gross pathology:
Dark patches on the lungs were noted in the surviving animal from Group 3. Seven out of 10 surviving animals from Group 4 exhibited abnormally dark lungs or dark patches on the lungs at necropsy.
The following macroscopic abnormalities were detected at necropsy amongst animals that died or were humanely killed during the course ofthe study: Lungs - abnormally dark; Liver- dark, accentuated lobular pattem; Small Intestine - gaseous distension, hemorrhagic.
Due to the observations noted during the study and at necropsy it is considered that deaths noted during the study may have been mainly attributable to systemic toxicity.

Any other information on results incl. tables

Mortility data:

     Deaths      
 Group number  Mean achieved atmosphere concentration (mg/L)  Male Female   Total
 1  2.08  5/5  5/5  10/10
 2  1.02  5/5  5/5  10/10
 3  0.23  4/5  5/5  9/10
 4  0.05  0/5  0/5  0/10

Applicant's summary and conclusion

Interpretation of results:
Category 2 based on GHS criteria
Conclusions:
No mortality was observed at 0.05 mg/L which is the upper threshold value for Cat.1-classification.
A Cat.2 classification is allocated for substances with an LC50 between 0.05 and 0.5 mg/L. 90% mortality was observed at a concentration of 0.23 mg/L,
Based on these observations (no mortality at the lower Cat.2 threshold, ca.100% mortality at the upper Cat.2 threshold), a Cat.2 classification for acute inhalation toxicity is applicable for this substance