Tricopper bis(orthophosphate)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 Nov - 06 Dec 2012.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

adopted 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Department of Health of the Government of the United Kingdom, UK

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

1

Reference substance name:

Tricopper bis(orthophosphate)

EC Number:

232-254-5

EC Name:

Tricopper bis(orthophosphate)

Cas Number:

7798-23-4

Molecular formula:

Cu.2/3H3O4P

IUPAC Name:

tricopper bis(orthophosphate)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Supplied by Harlan Laboratories, Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 144-175 g
- Fasting period before study: Overnight
- Housing: In groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK provided ad libitum
- Water (e.g. ad libitum): Mains drinking water provided ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): At least fifteen per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light (06:00 to 18:00)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 mg/mL, 200 mg/mL
- Justification for choice of vehicle: Arachis oil BP was used because the test item did not dissolve/suspend in distilled water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose

Doses:

300 mg/kg, 2000 mg/kg

No. of animals per sex per dose:

1 x 300 mg/kg
5 x 2000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made ½, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily.
- Necropsy of survivors performed: yes
- Other examinations performed: Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.

Results and discussion

Preliminary study:

Individual clinical observations and mortality data are given in Table 1. There was no mortality. No signs of systemic toxicity were noted during the observation period. Individual bodyweights and bodyweight changes are given in Table 2. The animal showed expected gains in bodyweight over the observation period. Necropsy findings are given in Table 3. No abnormalities were noted at necropsy.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One animal was found dead approximately two and a half hours after dosing. There were no other deaths.

Clinical signs:

Hunched posture was noted in three animals. Pilo-erection was also noted in one of these animals. Signs of systemic toxicity also noted in two of these animals were diarrhoea and dehydration and ataxia, lethargy and ptosis were also noted in one animal. There were no signs of systemic toxicity noted in two animals.

Body weight:

The surviving animals showed expected gains in bodyweight over the observation period.

Gross pathology:

Abnormalities noted at necropsy of the animal that died during the study were dark liver, dark kidneys, gaseous stomach, blue coloured liquid present in the stomach and haemorrhagic gastric mucosa. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Any other information on results incl. tables

Table 1 Individual Clinical Observations and Mortality Data – 300 mg/kg

Dose Level mg/kg	Animal number and sex	Effects noted after dosing (hours)				Effects noted during period after dosing (days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
300	1-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

 

Table 2 Individual Bodyweights and Bodyweight Changes – 300 mg/kg

Dose Level mg/kg	Animal number and sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
300	1-0 Female	155	184	204	29	20

Table 3 Necropsy Findings - 300 mg/kg

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
300	1-0 Female	Killed Day 14	No abnormalities detected

Table 4 Individual Clinical Observations and Mortality Data – 2000 mg/kg

Dose Level mg/kg	Animal number and sex	Effects noted after dosing (hours)				Effects noted during period after dosing (days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	2-0 Female	D	D	HD	HDDh	H	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-1 Female	H	HLA	HLAD DhPt	X*
	3-2 Female	0	0	H	HP	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0 = no signs of systemic toxicity

H = hunched posture

D = Diarrhoea

Dh = Dehydration

A = Ataxia

L = Lethargy

Pt = Ptosis

P = Pilo-erection

X* = Animal found dead approximately two and a half hours after dosing

Table 5 Individual Bodyweights and Bodyweight Changes – 2000 mg/kg

Dose Level mg/kg	Animal number and sex	Bodyweight (g) at Day			Bodyweight (g) at Death	Bodyweight Gain (g) During Week
		0	7	14		1	2
2000	2-0 Female	157	171	199		14	28
	3-0 Female	175	202	222		27	20
	3-1 Female	160	-	-	156	-	-
	3-2 Female	152	166	192		14	26
	3-3 Female	144	161	175		17	14

- = Animal dead

Table 6 Necropsy Findings - 2000 mg/kg

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	2-0 Female	Killed Day 14	No abnormalities detected
	3-0 Female	Killed Day 14	No abnormalities detected
	3-1 Female	Found Dead Day 0	Liver: dark Kidneys: dark Stomach: gaseous blue coloured liquid present Gastric mucosa: haemorrhagic
	3-2 Female	Killed Day 14	No abnormalities detected
	3-3 Female	Killed Day 14	No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rats was estimated to be greater than 2000 mg/kg bw.
The test item does not meet the criteria for classification according to CLP Regulation (EC) No 1272/2008 and is therefore conclusive but not sufficient for labelling.