Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Already evaluated by the Competent Authority for Biocides and Existing Substances Regulations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(see 'Principles of method if other than guideline')
Principles of method if other than guideline:
The study design differs from current OECD Test Guideline methods for acute oral toxicity (400, 423, 425). However this study fully meets all data
needs for hazard classification and labelling in the EU.
Review of the study report revealed minor deviations from current scientific and technical standards.

The following minor deviations from current scientific and technical standards were noted:
• Information on the test material including the batch no and the purity were not provided,
• No justification was given for the choice of vehicle,
• The lower limit for the temperature range of the animal room was slightly lower than that recommended in the guideline,
• Age of animals at study initiation is not indicated.

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:
Description: The test material was described as 'Red powder Cuprous Oxide Paint Grade'.
Lot/batch number: Not provided.
Purity: Not provided.
Stability: Not provided.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Source: A Tuck & Sons Limited, Battles-bridge, Essex, UK.
Age/weight at study initiation: On study day 0, males weighed 166 to 216g and the females weighed 135 to 171g. Animals were 4 to 6 weeks of age at the start of the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
Refer to Tables 1 and 2 for information on the dosing regime for the Range Finding study and the Main Study.
Doses:
Range Finding study dose levels: 100, 1000, 5000 mg/kg bw.
Main study dose levels: 200, 431, 928, 2000 mg/kg bw.
No. of animals per sex per dose:
Number of animals per group: 5 males and 5 females.
Control animals:
no
Details on study design:
Postexposure period: 14 days.
Clinical observations: The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 3, 4 and 5 hours after dosing, subsequently once daily for up to 14 days.
Bodyweights: Individual bodyweights were recorded on days 0, 7 and 14.
Necropsy: Surviving animals were killed on day 14. All animals that died during the study and those killed on day 14 were subjected to a macroscopic post mortem examination. The macroscopic appearance of abnormal organs was recorded.
Statistics:
The LD50 and 95% confidence limits were calculated using the method of Litchfield and Wilcoxon.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 340 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
1 625 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 928 - <= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
0/10, 0/10, 4/10 and 8/10 animals died at 200, 431, 928 and 2000 mg/kg bw respectively.
Clinical signs:
See Table 1 for a summary of the findings.
Signs of reaction to treatment observed shortly after dosing in rats at all levels consisted of piloerection, an abnormal body carriage (hunched
posture), lethargy, a decreased respiratory rate and diarrhoea. Other signs of toxicity observed in rats at some dose levels included ptosis, pallor of
the extremities, ataxia and staining around the ano-genital region.
Recovery of the survivors, as judged by external appearance and behaviour, was apparently complete by Day 13.
Body weight:
Depressed bodyweight gains or a bodyweight loss was recorded for female rats at 431 mg/kg bw and above and for male rats at 928 mg/kg bw and
above during the first week of observation, and for most female rats during the second week of observation. Bodyweight gains of the remaining rats
were within normal limits throughout the two week observation period.
Gross pathology:
Autopsy of animals that died revealed pallor of the liver, dark colouration of the kidneys and spleen, gaseous distention of the stomach and ulceration of the glandular region of the stomach and an emptiness and dark staining of the gastro-intestinal tract.
Autopsy of the survivors did not reveal any microscopic abnormalities with the exception of one female at 928 mg/kg bw in which an emptiness of
the gastro-intestinal tract was observed.

Any other information on results incl. tables

Table 1. Summary of findings.

 

Dose

[mg/kg bw]

Sex

Number dead/ number investigated

Time of death (range)

Observations

200

 

Males

0/5

-

Clinical signs observed shortly after dosing in rats at all levels consisted of piloerection, hunched posture, lethargy, a decreased respiratory rate and diarrhoea. Other signs of toxicity observed in rats at some dose levels included ptosis, pallor of the extremities, ataxia and staining around the ano-genital region. 

All surviving animals gained bodyweight during the study.

Autopsy of animals that died revealed pallor of the liver, dark colouration of the kidneys and spleen, gaseous distention of the stomach and ulceration of the glandular region of the stomach and an emptiness and dark staining of the gastro-intestinal tract.

Females

0/5

-

431

Males

0/5

-

Females

0/5

-

928

Males

2/5

Day 5

Females

1/5

Day 6

2000

Male

2/5

Day 5-6

Females

5/5

Day 5-9

LD50 Males and Females: 1340 (918 – 1956) mg/kg bw

LD50 Males only: 1625 (903 – 2925) mg/kg bw

LD50 Females only: between 928 and 2000 mg/kg bw

The results of the Range Finding study are shown in Table 2 below.

Table 2. Range Finding study - Summary of Mortalities.

Dose Level mg/kg

Animals surviving post dosing

Total deaths at 9 days

Day

0

1

2

3

4

5

6

7

8

9

100

 

4

4

4

4

4

4

-

-

-

-

0

1000

 

4

4

4

4

3

3

3

1

1

1

3

5000

 

4

2

2

2

2

1

1

1

0

0

4

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 in the rat (male and females combined) was estimated to be 1340 mg/kg bw.
In this study, cuprous oxide meets the criteria for classification as harmful according to Annex VI of Commission Directive 2001/59/EC. The test
substance should be attributed the symbol Xn: Harmful and the Risk Phrase R:22 Harmful if swallowed.
Executive summary:

Materials and Methods

This study was conducted according to GLP, and to the now obsolete OECD Test Guideline 401 “Acute Oral Toxicity”. The study design differs from current OECD Test Guideline methods for acute oral toxicity (400, 423, 425). However this study meets all data needs for hazard classification and labelling in the EU. Only minor deviations from current scientific and technical standards occurred. These deviations are not considered to have influenced the outcome or the integrity of the study.

Cuprous oxide was administered orally by gavage to groups of 5 male and 5 female fasted Sprague-Dawley rats at a single dose of 200, 431, 928, and 2000 mg/kg bw. The test material was suspended in arachis oil BP.

The animals were observed for deaths or overt signs of toxicity ½, 1, 2 3, 4 and 5 hours after dosing, subsequently once daily for up to 14 days.

Individual bodyweights were recorded on days 0, 7 and 14.

Surviving animals were killed on day 14. All animals that died during the study and those killed on day 14 were subjected to a macroscopic post mortem examination. The macroscopic appearance of abnormal organs was recorded.

On study day 0, males weighed 166 to 216 g and the females weighed 135 to 171 g.

The LD50and 95% confidence limits were calculated using the method of Litchfield and Wilcoxon. Results and Discussion See Table 1 ('Any other information on results') for a summary of findings. 0/10, 0/10, 3/10 and 7/10 animals died at 200, 431, 928 and 2000 mg/kg bw.

Signs of reaction to treatment observed shortly after dosing in rats at all levels consisted of piloerection, an abnormal body carriage (hunched posture), lethargy, a decreased respiratory rate and diarrhoea. Other signs of toxicity observed in rats at some dose levels included ptosis, pallor of the extremities, ataxia and staining around the ano-genital region. Recovery of the survivors, as judged by external appearance and behaviour, was apparently complete by Day 13.

Depressed bodyweight gains or a bodyweight loss was recorded for female rats at 431 mg/kg bw and above and for male rats at 928 mg/kg bw and above during the first week of observation, and for most female rats during the second week of observation. Bodyweight gains of the remaining rats were within normal limits throughout the two week observation period.

Autopsy of animals that died revealed pallor of the liver, dark colouration of the kidneys and spleen, gaseous distention of the stomach and ulceration of the glandular region of the stomach and an emptiness and dark staining of the gastro-intestinal tract.

Autopsy of the survivors did not reveal any microscopic abnormalities with the exception of one female at 928 mg/kg bw in which an emptiness of the gastro-intestinal tract was observed.