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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Cupric hydroxide
- Composition of test material, percentage of components: 85.9% copper dihydroxide
- Lot/batch No.: 0215913294

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Animals were housed individually and acclimatised prior to dosing.

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Test atmospheres were generated with a NBS dust aerosol generator. The gravimetric test concentrations were determined by dividing the total weight of the test substance collected on a glass fibre filter by the volume of air sampled. The nominal test concentration was calculated by dividing the total weight of the test substance used by the total volume of air passing through the chamber during exposure. The MMAD and the particle size distribution were calculated from two samples taken during exposure with an ITP 7 L/minute cascade impactor. Refer to Table 1. Chamber environmental conditions were monitored during the exposure.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
0.13, 0.30, 0.61 and 2.61 mg/L (time weighted average gravimetric concentrations, 2.61 mg/L was maximum practical).
No. of animals per sex per dose:
Groups of five male and five female rats.
Control animals:
no
Details on study design:
Animals were observed for reaction to treatment during exposure (Day 1) and daily for 14 days following exposure. Mortality was recorded twice daily. Body weights were recorded prior to exposure and after 7 days (Day 8) and 14 days (Day 15). Gross pathological examinations were performed on decedents and animals surviving for 14 days.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
0.5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
0.61 mg/L air
Based on:
test mat.
95% CL:
0.05 - 1.17
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.56 mg/L air
95% CL:
0.2 - 0.92
Exp. duration:
4 h
Mortality:
There were no mortalities at 0.13 and 0.30 mg/L. At 0.61 mg/L, all males and four females died and at 2.61 mg/L, all animals died. All deaths occurred on the day of exposure. Refer to Table 2.
Clinical signs:
Clinical symptoms after exposure were recorded in all surviving animals. The most notable signs were dark material around the face, urine stains, swollen eyelids, lacrimation, salivation, rough haircoat, decreased activity, breathing abnormalities and decreased defecation. All survivors recovered from these signs by the end of the observation period.
Body weight:
Body weight loss was recorded in one female treated at 0.13 mg/L in the second week after treatment and body weight loss or reduced weight gain was recorded in females treated at 0.30 mg/L. Other surviving animals gained weight during the study.
Gross pathology:
At necropsy, the animals which died showed fluid/mucoid contents in the digestive tract, congested meningeal vessels in the brain and mottled lungs.
Other findings:
None.

Any other information on results incl. tables

Table 2. Summary of Mortalities

Gravimetric concentration
(mg/L)

Males

Females

Mortality

Time of death

Mortality

Time of death

0.13

0/5

-

0/5

-

0.30

0/5

-

0/5

-

0.61

5/5

Day 1

4/5

Day 1

2.61

5/5

Day 1

5/5

Day 1

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute inhalation LC50 (4 hour) of copper dihydroxide in the rat was 0.50 mg/L for males (95% confidence interval could not be determined due to lack of partial mortality level), 0.61 mg/L for females (with 95% confidence limits of 0.05 to 1.17 mg/L) and 0.56 mg/L for the sexes combined (with 95% confidence limits of 0.20 to 0.92 mg/L).
Classification according to Directive 67/548/EEC: Toxic (T). R23, Toxic by inhalation.
Classification according to CLP/GHS: Acute Tox. 2, H330: Fatal if inhaled.
Executive summary:

A GLP-compliant acute inhalation toxicity test was conducted in accordance with US EPA 81-3 without significant deviation. Test atmospheres of copper dihydroxide were generated with a NBS dust aerosol generator. Sprague-Dawley rats were housed individually and acclimatised prior to dosing. Groups of five male and five female rats were exposed to an aerosol atmosphere of the test substance at 0.13, 0.30, 0.61 and 2.61 mg/L (time weighted average gravimetric concentrations, 2.61 mg/L was maximum practical) for four hours using a whole body exposure system. The gravimetric test concentrations were determined by dividing the total weight of the test substance collected on a glass fibre filter by the volume of air sampled. The nominal test concentration was calculated by dividing the total weight of the test substance used by the total volume of air passing through the chamber during exposure. The MMAD and the particle size distribution were calculated from two samples taken during exposure with an ITP 7 L/minute cascade impactor. Chamber environmental conditions were monitored during the exposure. Animals were observed for reaction to treatment during exposure (Day 1) and daily for 14 days following exposure. Mortality was recorded twice daily. Body weights were recorded prior to exposure and after 7 days (Day 8) and 14 days (Day 15). Gross pathological examinations were performed on decedents and animals surviving for 14 days.

There were no mortalities at 0.13 and 0.30 mg/L. At 0.61 mg/L, all males and four females died and at 2.61 mg/L, all animals died. All deaths occurred on the day of exposure. Clinical symptoms after exposure were recorded in all surviving animals. The most notable signs were dark material around the face, urine stains, swollen eyelids, lacrimation, salivation, rough haircoat, decreased activity, breathing abnormalities and decreased defecation. All survivors recovered from these signs by the end of the observation period. Body weight loss was recorded in one female treated at 0.13 mg/L in the second week after treatment and body weight loss or reduced weight gain was recorded in females treated at 0.30 mg/L. Other surviving animals gained weight during the study. At necropsy, the animals which died showed fluid/mucoid contents in the digestive tract, congested meningeal vessels in the brain and mottled lungs.

The acute inhalation LC50 (4‑hour) of copper dihydroxide in the rat was 0.50 mg/L for males (95% confidence interval could not be determined due to lack of partial mortality level), 0.61 mg/L for females (with 95% confidence limits of 0.05 to 1.17 mg/L) and 0.56 mg/L for the sexes combined (with 95% confidence limits of 0.20 to 0.92 mg/L). Copper dihydroxide is classified as Acute Tox. 2, H330: Fatal if inhaled.