Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Already evaluated by the Competent Authorities for Biocides and Existing Substance Regulations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
These deviations are not considered to have influenced the outcome or the integrity of the study.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Cuprous oxide
Lot/batch number: Batch No 8558
Specification: No information was provided on the specification of the sample used in this study.
Description: Dark red/brown powder.
Purity: Not reported
Stability: Not reported.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Source: Charles River (U.K.) Limited, Manston, Kent, UK.
Age/weight at study initiation: At pre-dose, males weighed 188 to 237 g and females weighed 160 to 183 g. No information was provided on the age of the animals.

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
nose only
Vehicle:
other: None
Details on inhalation exposure:
Test material was used as supplied.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
ca. 4 h
Concentrations:
Group Nominal (mg/ml) Analytical (mg/l) % respirable particles (<4.7 µm)
1 20.10 5.09 65.1
2 11.53 3.45 52.4
3 12.54 4.43 57.9
No. of animals per sex per dose:
5 males and 5 females per group.
Control animals:
no
Details on study design:
Duration of observation period following administration: 14 days
Observations: All rats were observed for clinical signs at frequent intervals throughout the exposure period and for the first 1 h post dosing. All
surviving animals were observed at least once daily during the subsequent 14 day post exposure period.
Body weights: All the rats were weighed immediately before dosing and on Days 2, 3, 4, 7, 10 and 14 post-exposure.
Terminal Studies: All mortalities were subjected to a macroscopic post mortem examination as soon as possible after death.

At the end of the 14 day observation period the animals were sacrificed and subjected to a macroscopic post mortem examination as follows:
-Each rat was examined prior to opening the abdominal and thoracic cavities.
-The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.
-All organs were examined in situ.
-The lungs of each animal were removed and weighed to allow calculation of lung-to-body weight ratios.
Statistics:
Method of determination of LD50: Finney

Results and discussion

Preliminary study:
See below.
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 5.63 mg/L air (analytical)
Based on:
test mat.
95% CL:
> 4.39 - < 6.54
Exp. duration:
4 h
Mortality:
The mortality pattern observed was as follows:

Dose Group/Dose Level Animal No/ sex Time of Death

1 - 5.09 mg/l 4 M, 7 F Found dead at 11:00 h on Day 1 post exposure
10 F Found dead at 13:30 h on Day 1 post exposure
3 M, 8 F Found dead at 10:00 h on Day 2 post exposure

2 - 3.45 mg/l 13 M Found dead at ca. 11:00 h on Day 2 post exposure

3 - 4.43 mg/l 23 M Found dead at ca 11:00 h on Day 1 post exposure
22 M Found dead at ca 11:00 h on Day 2 post exposure

Clinical signs:
other: Animals from all groups showed struggling behaviour and increased urination and defecation during loading into the restraint tubes. Respiratory depression (ca 40%) was noted for all groups during exposure to cuprous oxide. Following exposure all animals
Body weight:
All animals which survived exposure to cuprous oxide exhibited a body weight loss. The weight loss had been regained by Day 7 of the observation
period, however, the overall weight gain recorded at the end of the 14 day observation period was considered to be reduced.
Gross pathology:
Gross pathological examination of those animals which died following exposure to cuprous oxide revealed the lungs to have a haemorrhagic
appearance. Brown areas were observed in the lungs of several animals, from all dose levels, sacrificed at the end of the 14 day observation period.
These brown areas may possibly be due to the accumulation of pigment-laden (haemosiderin) macrophages. However, without histopathological
evidence this cannot be confirmed.
Lung to Body Weight Ratios: For all animals that died following exposure to cuprous oxide were markedly elevated. This was attributed to the
presence of pulmonary haemorrhage and oedema. Values observed for the animals, especially the females, sacrificed at the end of the 14 day
observation period were considered to be slightly elevated. This finding may be attributable to residual pulmonary damage and/or to the lower body weight profile observed.
Other findings:
Not reported.

Any other information on results incl. tables

Table 1: Acute inhalation toxicity study - Summary of findings

Dose [mg/l]

Number of dead /
number of investigated

Time of death (range)

Observations

5.09

2/5 males

3/5 females

Day 1 or 2 post exposure

Respiratory depression was noted for all groups during exposure. Following exposure all animals exhibited a generally depressed condition.

Premature decedents showed extensive lung haemorrhaging and elevated lung to body weight ratios. Lungs of animals sacrificed after 14 days showed areas of brown discolouration.

4.43

2/5 males

0/5 females

Day 1 or 2 post exposure

3.45

1/5 males

0/5 females

Day 2 post exposure

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LC50 (4h) in the male and female Sprague Dawley rat was found to be 5.36 mg/l. In this study, cuprous oxide does not meet the criteria for
classification for acute inhalation toxicity according to Annex VI of Commission Directive 2001/59/EC.
Executive summary:

Materials and methods

This study was conducted according to GLP. Deviations from OECD Test Guideline 403 (adopted 12 May 1981) are discussed under point 2.3. Three groups of 5 female and 5 male Sprague-Dawley rats were exposed by the nose-only to cuprous oxide for 4 hours. The mean chamber concentrations of cuprous oxide measured in breathing zone samples using a gravimetric method were at 3.45, 4.45 or 5.09 mg/l. All the rats were observed for clinical signs at frequent intervals throughout the exposure period and for the first 1 h post dosing. All surviving animals were observed at least once daily during the subsequent 14 day post exposure period.

Body weights were recorded immediately before dosing and on Days 2, 3, 4, 7, 10 and 14 post-exposure. All animals were subjected to a macroscopic post mortem examination. The lungs of each animal were removed and weighed to allow calculation of lung to body weight ratios. At pre-dose, males weighed 188 to 237 g and females weighed 160 to 183 g.

Results and discussion

Respiratory depression was noted during exposure. Following exposure all animals exhibited a generally depressed condition, respiratory abnormalities and a body weight loss.

The delayed death pattern observed was possibly due to pulmonary haemorrhage resulting in respiratory failure/insufficiency and probable oedema. Macroscopic examination of the lungs of the animals sacrificed following the 14 day observation period revealed areas of brown discolouration. The accumulation of pigment-laden macrophages at the site of possible haemorrhagic foci may account for these discoloured areas.The LC50 (4 h) with 95% confidence limits of cuprous oxide was calculated to be 5.36 mg/l (4.39-6.54 mg/l). See Table 1 for a summary of the results of this study.