Copper

Acute Toxicity: inhalation

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: Study conducted in compliance with Good laboratory Practice and internationally accepted guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation 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:

coated copper flakes

IUPAC Name:

coated copper flakes

Test material form:

solid: flakes

Details on test material:

- Name of test material (as cited in study report): Copper powder KU 7600 Standard Material
- Analytical purity: 98%
- Lot/batch No.: 11G0015
- Expiration date of the lot/batch: May 2012
- Storage condition of test material: Cool and dry in a tightly sealed container.
- Particle size distribution: d(0.1) = 4.49 µm, d(0.5) = 10.78 µm (median), d(0.9) = 21.42 µm

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Research Models and Services Germany GmbH. Sandhofer Weg 7, 97633 Sulzfeld, Germany.
- Age at study initiation: Males, approximately 7 weeks. Females, approximately 9 weeks.
- Weight at study initiation: Males, 238 - 262 g. Females, 231 - 245 g.
- Fasting period before study: Feeding was discontinued 16 hours before exposure.
- Housing: Granulated textured wood was used as bedding material for the cages. During the 14-day observation period, the animals were kept by sex in groups of 3 animals in MAKROLON cages (tpe III plus).
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 55% +/- 15%
- Photoperiod (hrs dark / hrs light): 12 hrs dak/12 hrs light.

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Dynamic nose-only inhalation apparatus (RHEMA-LABORTECHNIK, 65719 Hofheim/Taunus, Germany).
- Exposure chamber volume: 40L
- Method of holding animals in test chamber: Animals were held in pyrex tubes at the edge of the chamber in a radial position.
- Source and rate of air: The generator was fed with compressed air (5.0 bar) taken from the surrounding laboratory atmosphere. Air changes 22.5 times per hour.
- Method of conditioning air: Air was filtered using an in-line disposable gas filter.
- System of generating particulates/aerosols: The dust of the test material was generated using a rotating brust dust generator (RBG 1000, PALAS GmbH, Partikel und Lasermesstechnik, 76229 Karlsruhe, Germany).
- Method of particle size determination: Particle size distribution was determined during the exposure period using a cascade impactor.
- Treatment of exhaust air: The exhaust air was drawn through gas wash-bottles.
- Temperature, humidity, pressure in air chamber: The temperature during the exposure period was in the range 21.3 - 21.9°C. Humidity was in the range 60.3 - 64.2%. A positive aire pressure was maintained within the exposure apparatus.. Air flow at the entrance was 900 L/h. Air flow at the exis was 800 L/h.

TEST ATMOSPHERE
- Brief description of analytical method used: The dust inhalation in the inhalation chamber was measured gravimetrically witha n air sample filter and pump controlled by a rotameter. Dust samples were taken once every hour during the exposure. A probe was placed close to the animals' noses and air was drawn through the air sample filter at a constant rate of 5L/minute for 1 minute. The filters were weighed befor and after sampling
- Samples taken from breathing zone: yes.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: See Table 1.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The MMAD was 3.477 µm (1.24 or 5.11 mg/L). The GSD of the MMADs were calculated as 2.61 or 2.77 (1.24 or 5.11 mg/L).

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: A nominal limit concentration of 5 mg/L was chosen.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetrically determined

Duration of exposure:

4 h

Concentrations:

Gravimetrically determined concentrations (with SD) of 1.24 (±0.03) and 5.11 (±0.02) mg Copper powder KU 7600 Standard Material/L air.

No. of animals per sex per dose:

3 males and 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Clinical examinations were made at least once daily until all symptoms subsided, thereafter each working day. Observations on deaths were made at least once daily. Individual weight were determined once during acclimatisation, before exposure on day 1, on days 2, 4, 8 and 15.
- Necropsy of survivors performed: yes.
- Other examinations performed: clinical signs, body weight, lung weight.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.11 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: There was no evidence of respiratory tract irritation

Mortality:

none

Clinical signs:

other: A 4-hour inhalation exposure to Copper powder KU 7600 Standard Material at concentrations of 1.24 or 5.11 mg/L air revealed concentration-related slight to moderate ataxia, slight to moderate tremor and slight to moderate dyspnoea (reduced frequency of re

Body weight:

One of three females treated with the low concentration showed a reduced body weight gain at the end of the study compared to the start value (+2.9%). The two other females showed weight gains of +7.1% and +10.0%.
Two of three females treated with the high concentration showed a reduced body weight gain at the end of the study compared to the start value (+2.5% and +3.3%). The remaining female showed a weight gain of +6.1%.

Gross pathology:

Dark or slight grey-stained discoloured lungs were observed in two males at the dose level of 1.24 mg/L or in one male and 1 female at the dose level of 5.11 mg/L.

Other findings:

There was no evidence of respiratory tract irritation

Any other information on results incl. tables

Results are summarized in table 2 (attached)

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the 4-hour inhalation LC50 of Copper powder KU 7600 Standard Material is >5.11 mg/L air. No evidence of respiratory tract irritation could be observed. The test material is not classified as dangerous. The LOAEC of 1.24 mg/L was used for deriving a short trom inhalation DNEL

Executive summary:

A GLP-compliant acute inhalation test was carried out in the Sprague-Dawley rats in accordance with OECD Guideline 436.  Groups of 3 males and 3 females were exposed for 4 hours to a dry aerosol of Copper powder KU 7600 Standard Material at gravimetrically determined concentrations of 1.24±0.03 and 5.11±0.02 mg /L air using a dynamic nose-only exposure chamber. The aerosol was generated with the aid of a dry, rotating brush dust generator. The MMAD of particles in the animals’ breathing zone was 3.477 µm. GSDs of the MMADs were 2.61 (1.24 mg/L) or 2.77 (5.11 mg/L).

No mortalities were observed at either exposure concentration.  One of three females from the low concentration group and two of three females from the high concentration group showed reduced body weight gain at the end of the study. A 4-hour inhalation exposure to Copper powder KU 7600 Standard Material at concentrations of 1.24 or 5.11 mg/L air revealed concentration-related slight to moderate ataxia, slight to moderate tremor and slight to moderate dyspnoea (reduced frequency of respiration with increased volume) on test day 1 immediately after end of exposure until 3 hours or until test day 4 in all animals, respectively (3 of 3 male and 3 of 3 female animals, each). In addition, reduced motility was observed in all animals at 5.11 mg/L air 2 to 4 days after exposure. Dark or slight grey-stained discoloured lungs were observed in two males from the 1.24 mg/L group and in one male and one female from the 5.11 mg/L exposure group.

The 4-hour inhalation LC50 of Copper powder KU 7600 Standard Material is >5.11 mg/L air.  No evidence of respiratory tract irritation could be observed.  On this basis the test material is unclassified with regard to acute inhalation toxicity.