Diphosphoric acid, copper salt

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-10-07 to 2013-10-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Diphosphoric acid, copper salt

EC Number:

233-279-4

EC Name:

Diphosphoric acid, copper salt

Cas Number:

10102-90-6

Molecular formula:

Cu.xH4O7P2

IUPAC Name:

diphosphoric acid, copper salt

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

M 14-30 Copper-II-pyrophosphate
Batch number: 9000022795
Chemical name: diphosphoric acid, copper salt
CAS: 10102-90-6
EC: 233-279-4
Purity: >80% (based on Cu content >34%)
Impurities: <18% water, <2% free orthophosphate, pyrophosphate
Physical state: light blue solid powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Germany GmBH, Sulzfeld, Germany
- Age at study initiation: 8-12 weeks
- Weight at study initiation: between 190 and 250 g
- Fasting period before study: no diet over night prior to application and 3 hours after application
- Housing: signle-caged
- Diet (e.g. ad libitum): conventional laboratory diet (ad libitum with exception regarding fasting prior to and post test material application).
- Water (e.g. ad libitum): ad libitum tap water
- Acclimation period: The animals were kept in their cages for at least 5 days prior to dosing to allow for acclimatisation to the laboratory conditions. The health of animals was controlled by veterinarians or other qualified staff members.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1ml/100 g bodyweight

DOSAGE PREPARATION: Test substance was suspended in distilled water.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A limit test at dose level 2000 mg/kg body weight (b. w.) was carried out since information about toxicity provided by sponsor has indicated that the test material is likely non-toxic at this dose level.

Doses:

The test was performed in a step-wise manner with 2 test series (test and replicate test) at 2000 mg/kg bw.

No. of animals per sex per dose:

Each test group consisted of 3 female animals (6 in total).

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Observation parameters: spontaneous activity, Preyer’s reflex (noise), respiratory rate, convulsions, tremors, body temperature (evaluated by touch), muscle tone, palpebral opening, pupil appearance, salivation, lachrymation, righting reflex and back hair appearance.

- Frequency of observations and weighing: Animals were observed individually after dosing at least once during the first 30 minutes, periodically during the first 24 hours, with special attention given during the first 4 hours and daily thereafter for a total of 14 days.
Individual weights of animals were determined shortly before the test substance was administered, and weekly thereafter. Weight changes were calculated and recorded. At the end of the test surviving animals were weighed and humanely killed.

- Necropsy of survivors performed: yes. All test animals were subjected to gross necropsy. All gross pathological changes were recorded for each animal (included organs: oesophagus, stomach, duodenum, jejunum, ileum, caecum, colon, rectum, spleen, liver, thymus, trachea, lungs, heart, kidneys, urinary bladder, ovaries, uterus, adrenals, pancreas).

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured.

Clinical signs:

No animals showed any adverse clinical signs.

Body weight:

No adverse changes in bodyweight were recorded.

Gross pathology:

There were no abnormal macroscopic findings in any of organs after a 14-day observation period.

Any other information on results incl. tables

 

Table 1: Clinical observations from T0 to 4h; test group 1; dose level 2000 mg/kg

Observation from T0 to 4 h	Test group 1 (2000 mg/kg)
	T1	T2	T3
Spontaneous activity	NAD	NAD	NAD
Preyer’s reflex (noise)	NAD	NAD	NAD
Respiratory rate	NAD	NAD	NAD
Convulsions	NAD	NAD	NAD
Tremors	NAD	NAD	NAD
Body temperature (evaluated by touch)	NAD	NAD	NAD
Muscle tone	NAD	NAD	NAD
Palpebral opening	NAD	NAD	NAD
Pupil appearance	NAD	NAD	NAD
Salivation	NAD	NAD	NAD
Lachrymation	NAD	NAD	NAD
Righting reflex	NAD	NAD	NAD
Back hair appearance	NAD	NAD	NAD
Other	NAD	NAD	NAD
MORTALITY	0	0	0

Key:NAD = no abnormality detected

 

Table 2: Clinical observations from day 1 to day 14; test group 1; dose level 2000 mg/kg

Observation from day 1 – day 14	Test group 1 (2000 mg/kg)
	T1	T2	T3
Spontaneous activity	NAD	NAD	NAD
Preyer’s reflex (noise)	NAD	NAD	NAD
Respiratory rate	NAD	NAD	NAD
Convulsions	NAD	NAD	NAD
Tremors	NAD	NAD	NAD
Body temperature (evaluated by touch)	NAD	NAD	NAD
Muscle tone	NAD	NAD	NAD
Palpebral opening	NAD	NAD	NAD
Pupil appearance	NAD	NAD	NAD
Salivation	NAD	NAD	NAD
Lachrymation	NAD	NAD	NAD
Righting reflex	NAD	NAD	NAD
Back hair appearance	NAD	NAD	NAD
Other	NAD	NAD	NAD
MORTALITY	0	0	0

Key: NAD = no abnormality detected

 

Table 3: Clinical observations from T0 to 4h; test group 2; retest dose level 2000 mg/kg

Observation from T0 to 4 h	Test group 2 (2000 mg/kg)
	T4	T5	T6
Spontaneous activity	NAD	NAD	NAD
Preyer’s reflex (noise)	NAD	NAD	NAD
Respiratory rate	NAD	NAD	NAD
Convulsions	NAD	NAD	NAD
Tremors	NAD	NAD	NAD
Body temperature (evaluated by touch)	NAD	NAD	NAD
Muscle tone	NAD	NAD	NAD
Palpebral opening	NAD	NAD	NAD
Pupil appearance	NAD	NAD	NAD
Salivation	NAD	NAD	NAD
Lachrymation	NAD	NAD	NAD
Righting reflex	NAD	NAD	NAD
Back hair appearance	NAD	NAD	NAD
Other	NAD	NAD	NAD
MORTALITY	0	0	0

Key:NAD = no abnormality detected

 

Table 4: Clinical observations from day 1 to day 14; test group 2; retest dose level 2000 mg/kg

Observation from day 1 to day 14	Test group 2 (2000 mg/kg)
	T4	T5	T6
Spontaneous activity	NAD	NAD	NAD
Preyer’s reflex (noise)	NAD	NAD	NAD
Respiratory rate	NAD	NAD	NAD
Convulsions	NAD	NAD	NAD
Tremors	NAD	NAD	NAD
Body temperature (evaluated by touch)	NAD	NAD	NAD
Muscle tone	NAD	NAD	NAD
Palpebral opening	NAD	NAD	NAD
Pupil appearance	NAD	NAD	NAD
Salivation	NAD	NAD	NAD
Lachrymation	NAD	NAD	NAD
Righting reflex	NAD	NAD	NAD
Back hair appearance	NAD	NAD	NAD
Other	NAD	NAD	NAD
MORTALITY	0	0	0

Key: NAD = no abnormality detected

 

Table 5: Body weight and weight gain in grams

Test group	Animal ID	Day
		D0	D7	D7-D0	D14	D14-D0
1	T1	198.0	230.2	32.2	235.5	37.5
	T2	192.0	227.6	35.6	240.0	48.0
	T3	188.0	225.2	37.0	239.8	51.8
2	T4	212.0	245.3	33.3	248.7	36.7
	T5	213.0	244.8	31.8	242.3	29.3
	T6	220.0	260.1	40.1	272.7	52.7

 

NECROPSY FINDINGS

Table 6. Macroscopic observations, test group 1, dose level 2000 mg/kg

Observed organs	Test group 1 (2000 mg/kg)
	T1	T2	T3
Oesophagus	NAD	NAD	NAD
Stomach	NAD	NAD	NAD
Duodenum	NAD	NAD	NAD
Jejunum	NAD	NAD	NAD
Ileum	NAD	NAD	NAD
Caecum	NAD	NAD	NAD
Colon	NAD	NAD	NAD
Rectum	NAD	NAD	NAD
Spleen	NAD	NAD	NAD
Liver	NAD	NAD	NAD
Thymus	NAD	NAD	NAD
Trachea	NAD	NAD	NAD
Lungs	NAD	NAD	NAD
Heart	NAD	NAD	NAD
Kidneys	NAD	NAD	NAD
Urinary bladder	NAD	NAD	NAD
Ovaries	NAD	NAD	NAD
Uterus	NAD	NAD	NAD
Adrenals	NAD	NAD	NAD
Pancreas	NAD	NAD	NAD

Key: NAD = no abnormality detected

 

Table 7. Macroscopic observations, test group 2, dose level 2000 mg/kg

Observed organs	Test group 1 (2000 mg/kg)
	T4	T5	T6
Oesophagus	NAD	NAD	NAD
Stomach	NAD	NAD	NAD
Duodenum	NAD	NAD	NAD
Jejunum	NAD	NAD	NAD
Ileum	NAD	NAD	NAD
Caecum	NAD	NAD	NAD
Colon	NAD	NAD	NAD
Rectum	NAD	NAD	NAD
Spleen	NAD	NAD	NAD
Liver	NAD	NAD	NAD
Thymus	NAD	NAD	NAD
Trachea	NAD	NAD	NAD
Lungs	NAD	NAD	NAD
Heart	NAD	NAD	NAD
Kidneys	NAD	NAD	NAD
Urinary bladder	NAD	NAD	NAD
Ovaries	NAD	NAD	NAD
Uterus	NAD	NAD	NAD
Adrenals	NAD	NAD	NAD
Pancreas	NAD	NAD	NAD

Key: NAD = no abnormality detected

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test material "M 14-30 Copper-II-pyrophosphate" is higher than 2000 mg/kg body weight by oral route in rat. At this dose level, no mortality occurred and there were no adverse effects on clinical signs and body weight gain or abnormal necropsy finding that could be attributed to treatment with the test material. Therefore, the test material is "not classified" according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures.