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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Dicopper chloride trihydroxide
EC Number:
215-572-9
EC Name:
Dicopper chloride trihydroxide
Cas Number:
1332-65-6
Molecular formula:
ClCu2H3O3
IUPAC Name:
dicopper chloride trihydroxide
Details on test material:
- Name of test material (as cited in study report): Copper oxychloride technical
- Composition of test material, percentage of components: Copper content 57.28% w/w
- Lot/batch No.: 06523

Test animals

Species:
rat
Strain:
other: Crl:CD (SD) IGS BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
Rats 8 to 12 weeks of age, 278 to 332 g (males) and 218 to 255 g (females) were housed by sex and acclimatised for at least 5 days prior to exposure.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
Test atmospheres were generated using a SAG 410 Solid Aerosol Generator connected to a metered air supply. Air samples were taken at approximately 15 minute intervals during exposure and atmosphere concentrations were measured using a glass fibre filter. Exposure chamber temperature, humidity and oxygen levels were measured during the exposure period. The mass median aerodynamic diameter (MMAD) and the particle size were measured on three additional samples taken during exposure with a Marple cascade impactor. Refer to Table 1.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
1.14, 1.79 and 2.77 mg/L
No. of animals per sex per dose:
Groups of five males and five females.
Control animals:
no
Details on study design:
Animals were observed for clinical signs hourly during exposure and one hour after exposure (Day 1), then daily for 14 days following exposure. Body weights were recorded prior to treatment and on Days 7 and 14. Gross pathological examinations were performed on decedents and animals surviving for 14 days. The respiratory tract of all animals was subjected to detailed macroscopic examination.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
2.83 mg/L air
Based on:
test mat.
95% CL:
2.23 - 7.22
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
> 2.77 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
4.74 mg/L air
Based on:
test mat.
95% CL:
3.09 - 384
Exp. duration:
4 h
Mortality:
There were no deaths at 1.14 mg/L. At 1.79 mg/L, one female and two males died overnight following exposure. At 2.77 mg/L, two males died overnight following exposure.
Clinical signs:
other: During exposure, clinical signs included increased respiration rate, laboured and/or noisy respiration. After exposure, all surviving animals showed wet fur, hunched posture, piloerection and fur staining by the test material. These signs are considered
Body weight:
There was a reduction in body weight or a reduction in weight gain in the first week after exposure, but normal body weight gain was recorded in the second week.
Gross pathology:
Lung abnormalities (enlargement, abnormally dark or pale patches were recorded in animals that died during the study. Several of the surviving animals also showed lung abnormalities at terminal kill.
Other findings:
None.

Any other information on results incl. tables

Table 2. Summary of Mortalities

Males

Females

Measured dose
(mg/L)

Mortality

Time of death

Measured dose
(mg/L)

Mortality

Time of death

1.14

0/5

-

1.14

0/5

-

1.79

2/5

Day 2

1.79

1/5

Day 2

2.77

2/5

Day 2

2.77

0/5

-

All fatalities occurred overnight after exposure

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute inhalation LC50 (4 hour) of copper oxychloride technical to the rat was 2.83 mg/L in males (with 95% confidence limits of 2.23 to 7.22 mg/L) and >2.77 mg/L in females. The LC50 for the combined sexes was 4.74 mg/L (with 95% confidence limits of 3.09 to 384 mg/L).
Classification according to Directive 67/548/EEC: Harmful (Xn). R20, Harmful by inhalation.
Classification according to CLP/GHS: Acute Tox. 4, H332: Harmful if inhaled.
Executive summary:

A GLP-compliant study was conducted in accordance with EC Guideline B.2 and OECD 403. Dicopper chloride trihydroxide was used for the study. Test atmospheres were generated using a SAG 410 Solid Aerosol Generator connected to a metered air supply. Male and female Crl:CD (SD) IGS BR rats 8 to 12 weeks of age, 278 to 332 g (males) and 218 to 255 g (females) were housed by sex and acclimatised for at least 5 days prior to exposure. Groups of five males and five females were exposed to an aerosol atmosphere of the test substance at 1.14, 1.79 and 2.77 mg/L for four hours using a nose‑only exposure system. Air samples were taken at approximately 15 minute intervals during exposure and atmosphere concentrations were measured using a glass fibre filter. Exposure chamber temperature, humidity and oxygen levels were measured during the exposure period. The mass median aerodynamic diameter (MMAD) and the particle size were measured on three additional samples taken during exposure with a Marple cascade impactor. Animals were observed for clinical signs hourly during exposure and one hour after exposure (Day 1), then daily for 14 days following exposure. Body weights were recorded prior to treatment and on Days 7 and 14. Gross pathological examinations were performed on decedents and animals surviving for 14 days. The respiratory tract of all animals was subjected to detailed macroscopic examination.

 

There were no deaths at 1.14 mg/L. At 1.79 mg/L, one female and two males died overnight following exposure. At 2.77 mg/L, two males died overnight following exposure. During exposure, clinical signs included increased respiration rate, laboured and/or noisy respiration. After exposure, all surviving animals showed wet fur, hunched posture, piloerection and fur staining by the test material. These signs are considered associated with the restraint procedure, and in isolation are not indicative of toxicity. One hour post exposure, animals at 1.79 and 2.77 mg/L showed increased or decreased respiratory rate, laboured and/or noisy respiration, lethargy, ataxia and tiptoe gait. Ptosis, pallor of extremities and hypothermia were observed in some males at 1.17mm.  On the day following exposure, clinical signs included increased respiratory rate, noisy and/or laboured respiration, hunched posture, pilo-erection and occasional instances of red-brown staining of the snout. One female at 1.79 mg/L showed tiptoe gait on day 2. Some females at 2.77 mg/L also showed ataxia, tiptoe gait, red brown staining around eyes and closed eyes. All survivors showed normal clinical signs by days 7 (at 1.14 mg/L) or days 8 or 9 after exposure. There was a reduction in body weight or a reduction in weight gain in the first week after exposure, but normal body weight gain was recorded in the second week. Lung abnormalities (enlargement, abnormally dark or pale patches were recorded in animals that died during the study. Several of the surviving animals also showed lung abnormalities at terminal kill.

 

The acute inhalation LC50 (4‑hour) of dicopper chloride trihydroxide technical to the rat was 2.83 mg/L in males (with 95% confidence limits of 2.23 to 7.22 mg/L) and >2.77 mg/L in females. The LC50 for the combined sexes was 4.74 mg/L (with 95% confidence limits of 3.09 to 384 mg/L). These confidence limits are wider than would normally be accepted, but it would have been a waste of animals to test further groups, simply in order to establish a more accurate LC50, as this would not have altered the hazard classification of the material. On this basis dicopper chloride trihydroxide is classified as Acute Tox. 4, H332: Harmful if inhaled.


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