Dicopper hydroxide phosphate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Study was performed between 23/11/2010 and 07/12/2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

The test species used in this study was mice. The test guideline states that the preferred rodent species is rat; however the guideline also states that other rodent species may also be used and as such this is not considered to be a deficiency.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dicopper hydroxide phosphate

EC Number:

235-285-2

EC Name:

Dicopper hydroxide phosphate

Cas Number:

12158-74-6

Molecular formula:

Cu2HO5P

IUPAC Name:

dicopper hydroxide phosphate

Specific details on test material used for the study:

- Name of test material (as cited in study report): dicopper hydroxide phosphate
-CAS Number: 12158-74-6
- EC Number: 235-285-2
- Purity test date: 15/01/2009
- Lot/batch No.: 08004
- solid: particulate/powder

Test animals

Species:

mouse

Strain:

Balb/c

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BIOSERV
- Age at study initiation: no data
- Weight at study initiation: 17.8 g - 21.2 g
- Fasting period before study: 3 hours
- Housing: no data
- Diet (e.g. ad libitum): ad libitum, no diet 3 hours before and 1 hour after application
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23°C
- Humidity (%): 40 - 60%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Test solution and vehicle (distilled water were administered by force-feeding under a volume of 2 ml/100 g bodyweight, using a suitable graduated syringe fitted with an oesophageal metal cannula.

Doses:

300 mg/kg bw
2000 mg/kg bw

No. of animals per sex per dose:

3 females per dose.
6 females in control groups.

Control animals:

yes

Remarks:

All control animal recieved the vehicle (distilled water).

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighed on Day 0, Day 7 and Day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2 animals treated with 2000 mg/kg bodyweight died between day 1 and day 14.
None of the animals treated with 300 mg/kg bodyweight died during the 14 day observation period.

Clinical signs:

other: See tables below.

Gross pathology:

See tables below.

Any other information on results incl. tables

Test series 1 – Animals treated with 2000 mg/kg bw

 Table 1: Clinical observations from T0 to 4 hours

Observation	Test group 1 (2000 mg/kg bw)			Control group 1 (vehicle
	Animal 1	Animal 2	Animal 3	Animal 1	Animal 2	Animal 3
Spontaneous activity	NAD	NAD	NAD	NAD	NAD	NAD
Preyer’s reflex (noise)	NAD	NAD	NAD	NAD	NAD	NAD
Respiratory rate	NAD	NAD	NAD	NAD	NAD	NAD
Convulsions	NAD	NAD	NAD	NAD	NAD	NAD
Tremors	NAD	NAD	NAD	NAD	NAD	NAD
Body temperature (evaluated by touch)	NAD	NAD	NAD	NAD	NAD	NAD
Muscle tone	NAD	NAD	NAD	NAD	NAD	NAD
Palpebral opening	NAD	NAD	NAD	NAD	NAD	NAD
Pupil appearance	NAD	NAD	NAD	NAD	NAD	NAD
Salivation	NAD	NAD	NAD	NAD	NAD	NAD
Lachrymation	NAD	NAD	NAD	NAD	NAD	NAD
Righting reflex	NAD	NAD	NAD	NAD	NAD	NAD
Back hair appearance	NAD	NAD	NAD	NAD	NAD	NAD
MORTALITY	0	0	0	0	0	0

 NAD = No abnormalities noted

  

Table 2: Clinical observations from day 1 to day 14

Observation	Test group 1 (2000 mg/kg bw)			Control group 1 (vehicle)
	Animal 1	Animal 2	Animal 3	Animal 1	Animal 2	Animal 3
Spontaneous activity	Decreased	Decreased	NAD	NAD	NAD	NAD
Preyer’s reflex (noise)	NAD	NAD	NAD	NAD	NAD	NAD
Respiratory rate	NAD	NAD	NAD	NAD	NAD	NAD
Convulsions	NAD	NAD	NAD	NAD	NAD	NAD
Tremors	NAD	NAD	NAD	NAD	NAD	NAD
Body temperature (evaluated by touch)	Decreased	Decreased	NAD	NAD	NAD	NAD
Muscle tone	Decreased	Decreased	NAD	NAD	NAD	NAD
Palpebral opening	NAD	NAD	NAD	NAD	NAD	NAD
Pupil appearance	NAD	NAD	NAD	NAD	NAD	NAD
Salivation	NAD	NAD	NAD	NAD	NAD	NAD
Lachrymation	NAD	NAD	NAD	NAD	NAD	NAD
Righting reflex	Limited	Limited	NAD	NAD	NAD	NAD
Back hair appearance	NAD	NAD	NAD	NAD	NAD	NAD
MORTALITY	1	1	0	0	0	0

 NAD = No abnormalities noted

 

Table 3: body weight and weight gain in grams

Day	Test group 1 (2000 mg/kg bw)			Control group 1 (vehicle)
	Animal 1	Animal 2	Animal 3	Animal 1	Animal 2	Animal 3
Day 0	21.2	20.6	20.5	18.6	19.4	17.8
Day 7	n/a	n/a	17.4	20.3	20.2	21.0
Day 7 – Day 0	n/a	n/a	-3.1	1.7	0.8	3.2
Day 14	n/a	n/a	17.1	20.8	21.0	20.9
Day 14 – Day 0	n/a	n/a	-3.4	2.2	1.6	3.1

 n/a = not applicable due to early mortality.

 

Table 4: macroscopic observation at necropsy

Observed Organs	Test group 1 (2000 mg/kg bw)			Control group 1 (vehicle)
	Animal 1	Animal 2	Animal 3	Animal 1	Animal 2	Animal 3
Oesophagus	NAD	NAD	NAD	NAD	NAD	NAD
Stomach	1, 2	1, 3	NAD	NAD	NAD	NAD
Duodenum	NAD	NAD	NAD	NAD	NAD	NAD
Jejunum	NAD	NAD	NAD	NAD	NAD	NAD
Ileum	NAD	NAD	NAD	NAD	NAD	NAD
Caecum	NAD	NAD	NAD	NAD	NAD	NAD
Colon	NAD	NAD	NAD	NAD	NAD	NAD
Rectum	NAD	NAD	NAD	NAD	NAD	NAD
Spleen	NAD	NAD	NAD	NAD	NAD	NAD
Liver	NAD	NAD	NAD	NAD	NAD	NAD
Thymus	NAD	NAD	NAD	NAD	NAD	NAD
Trachea	NAD	NAD	NAD	NAD	NAD	NAD
Lungs	NAD	NAD	NAD	NAD	NAD	NAD
Heart	NAD	NAD	NAD	NAD	NAD	NAD
Kidneys	NAD	NAD	4	NAD	NAD	NAD
Urinary bladder	NAD	NAD	NAD	NAD	NAD	NAD
Ovaries	NAD	NAD	NAD	NAD	NAD	NAD
Uterus	NAD	NAD	NAD	NAD	NAD	NAD
Adrenals	NAD	NAD	NAD	NAD	NAD	NAD
Pancreas	NAD	NAD	NAD	NAD	NAD	NAD

 

NAD = No abnormality detected

1.    Strong gas development

2.    Test material still visible in stomach 2 days after application

3.    Test material still visible in stomach 3 days after application

4.    Atypical appearance of kidneys (yellow) due to restricted blood flow

[SEE 'OVERALL REMARKS, ATTACHMENTS' FOR DATA RELATING TO ANIMALS TESTED WITH 300 MG/KG BW]

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The LD50 of dicopper hydroxide phosphate has been determined to be in the range of > 300 to < 2000 mg/kg bw.

Executive summary:

The LD50 of dicopper hydroxide phosphate has been determined to be in the range of > 300 to < 2000 mg/kg bw and as such is classified as acutely toxic via the oral route, category 4 (EU CLP).  This study has been selected as the key study in accordance with Regulation (EC) No. 1907/2006 (REACH) because the results are sufficient in order to derive a reliable conclusion on classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP).