Diphosphoric acid, copper salt

Endpoint summary

Description of key information

Oral: LD50(rat, f) > 2000 mg/kg bw (OECD 423, GLP)
Inhalation: LC50(4 h, rat, m/f) >1-5 mg/L (OECD 436, GLP)
Dermal: No study available

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

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

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

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).

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.

 

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The study is conducted under the conditions of GLP and in accordance with an appropriate guideline (OECD 423). This study has been assigned a Klimisch reliability of 1. The database is considered to be of high quality.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013-04-04 to 2013-05-13

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Deviations:

no

Principles of method if other than guideline:

Deviations from study plan:

Deviation No. 1 (02 May 2013)
Animals from Group 2 were acclimatised to the restraint tubes on the day of exposure.

Deviation No. 2 (02 May 2013)
Two male animals from Group 2 were slightly larger than 20% of the mean group weight of Group 1 males at the start of the test.

These deviations are considered not to affect the purpose or validity of the study.

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection: 10 July 2012, Date of signature 30 November 2012

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): IP37: Copper (II)-pyrophosphate
- CAS Number: 10102-90-6
- EC Number: 233-279-4
- Description: Pale blue powder
- Batch: 9000022795
- Analytical purity: >80% (based on Cu content > 34% )
- Impurities (identity and concentrations): <18% water, < 2% free orthophosphate, pyrophosphate
- Expiration date of the lot/batch: 29 September 2014
- Storage condition of test material: Room temperature, in the dark
- Other: No correction for purity was made.

Species:

rat

Strain:

other: RCC Han : WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd
- Age at study initiation: 8 - 12 weeks old
- Weight at study initiation: 200g - 300g*
- Fasting period before study:
- Housing: animals were housed in groups of 3 by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes and provided with environmental enrichment items.
- Diet (e.g. ad libitum): ad libitum with the exception of the exposure period.
- Water (e.g. ad libitum): ad libitum with the exception of the exposure period.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

*2 Group 2 males were slightly lighter than 20% of the mean group weight of group 1 males, this was considered to be a slight deviations the 2 group 2 males were found to be out of the desired range by 16g and 13g respectively.

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: A dust atmosphere was produced from the test item using a SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany) located adjacent to the exposure chamber. The SAG 410 was connected to a metered compressed air supply. A particle separator was introduced before the aerosol entered the exposure chamber (Group 2 only) in order to help achieve the lower target atmosphere concentration (1mg/L) within the exposure chamber.
- Exposure chamber volume: The cylindrical exposure chamber had a volume of approximately 30 L (dimensions 28 cm diameter by 50 cm high)
- Method of holding animals in test chamber: Prior to the day of exposure (Group 1) and on the day of exposure (Group 2) each rat was acclimatised (for approximately 2 hours) to a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber ‘O’ ring. Only the nose of each animal was exposed to the test atmosphere.
Following an appropriate equilibrium period two groups, each of six rats (3 males and 3 females), were subjected to a single exposure to the test item for a period of 4 hours.
- Source and rate of air: Compressed air was supplied by means of an oil free compressor.
- Method of conditioning air: Air passed through a water trap and respiratory quality filters before it was introduced to the SAG 410.
- System of generating particulates/aerosols: see attached figures
- Method of particle size determination: see below
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: The temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/humidity meter (Hanna Instruments Ltd, Beds., UK) located in a vacant port in the animals’ breathing zone of the chamber and recorded every thirty minutes throughout the four-hour exposure period. Individual values are recorded in the tables included as Annexes.
The concentration within the chamber was controlled by adjusting the test item feed rate from the SAG 410. The extract from the exposure chamber passed through a ‘scrubber’ trap and was connected with a high efficiency filter to a metered exhaust system. The chamber was maintained under negative pressure. See attached diagram of system (Figures 1 and 2)

TEST ATMOSPHERE
- Brief description of analytical method used: Homogenecity of the test atmosphere within the chamber was not specifically determined during this study. Chambers of the same design (ADG Developments Ltd, Hitchin, Herts, UK) have been fully validated and shown to produce evenly distributed atmospheres in the animals’ breathing zone with a wide variety of test materials (Green JD et al, 1948)
Oxygen levels within the exposure chamber were measured by an electronic oxygen analyser (Servomex (UK) Ltd, Crowbrough, East Sussex). The test atmosphere was generated to contain 19% oxygen. Individual values are given in the table Annexes attached.
The actual chamber concentration was measured at regular intervals during the exposure period. The gravimetric method used glass fiber filters placed in a filter holder. The holder was temporarily sealed in a vacant port in the exposure chamber in the animals’ breathing zone and a suitable, known volume of exposure chamber air was drawn through the filter using a vacuum pump.
Each filter was weighed before and after sampling in order to calculate the weight of collected test item. The difference in the two weights, divided by the volume of atmosphere sampled, gave the actual chamber concentration.
The nominal chamber concentration was calculated by dividing the mass of test item. The difference in the two weights, divided by the volume of atmosphere sampled, gave the actual chamber concentration.
The nominal chamber concentration was calculated by dividing the mass of the test item used by the total volume of air passed through the chamber.
The nominal chamber concentrations were calculated by dividing the mass of the test item used by the total volume of air passed through the chamber during each exposure. The nominal concentrations were 170% and 335% of the actual mean achieved atmosphere concentration for Groups 1 and 2 respectively and shows that keeping the aerosol airborne was relatively straightforward for each exposure group.

- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: the particle size of the generated atmosphere inside the exposure chamber was determined three times during the exposure using a Marple Personal Cascade Impactor (Westech IS Ltd, Beds, UK). The devices consisted of six impactor stages (8.6, 5.5, 3.8, 1.7, 0.86 and 0.41 µm cut points) with stainless steel collection substrates and a back up glass fiber filter, housed in an aluminium sampler. The sampler was temporarily sealed in a sampling port in the animals’ breathing zone and a suitable, known volume of exposure chamber air was drawn through it using a vacuum pump.
The collection substrates and back up filter were weighed before and after sampling and the weight of the test item, collected at each stage, calculated by difference.
The mean amount for each stage was used to determine the cumulative amount below each cut-off point size. In this way, the proportion (%) of aerosol less than 8.6, 5.5, 3.8, 1.7, 0.86 and 0.41 µm cut points was calculated.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The resulting values were converted to probits and plotted against Log10 cut-point size. From this plot, the Mass Median Aerodynamic Diameter (MMAD) was determined (as the 50% point) and the geometric standard deviation was calculated. In addition the proportion (%) of aerosol less than 4 µm (considered to be the inhalable fraction) was determined.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: Based on the expected toxicity of the test item, a target concentration of 5.0 mg/L was used for the first exposure. The second concentration was selected after consideration of the results of the first exposure.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric method

Duration of exposure:

4 h

Concentrations:

Dose group 1: 5.16 mg/L
Dose group 2: 1.08 mg/L

No. of animals per sex per dose:

3 males and 3 females per dose group.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for up to 14 days. Any evidence of overt toxicity was recorded at each observation.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other:

Body Weight: Individual body weights were recorded on arrival, prior to treatment on the day of exposure and on Days 1, 2, 3, 7 and 14.
Necropsy: At the end of the 14 day observation period the animals were killed by intravenous overdose of sodium pentobarbitone. All animals were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded. The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1.08 - < 5.16 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Group 1 (5.16 mg/L): 2/3 males died, 1/3 females died (total 3/6 deaths)
Group 2 (1.08 mg/L) No deaths

Clinical signs:

other: Clinical observations are given in tables 6-9 (attached). Signs of hunched posture and pilo-erection are commonly seen in animals for short periods on removal from the chamber following 4-hour inhalation studies. Wet fur is commonly recorded both during a

Body weight:

Individual body weights, together with body weight changes are given in Table 10 and 11.

GROUP 1 – All surviving animals exhibited body weight losses on Day 1 post-exposure and from Days 1 to 3 post-exposure. Reasonable body weight development was noted in all animals during the remainder of the recovery period.
GROUP 2 – All animals exhibited body weight losses on Day 1 post-exposure. Two male animals exhibited further body weight losses from Days 1 to 3 post-exposure. Reasonable body weight development was noted in all animals during the remainder of the recovery period.

Gross pathology:

Individual necropsy findings are given in Tables 12 and 13.

Two instances of dark patches on the lungs and one instance of pale patches on the lungs were noted in the surviving group 1 animals. With the exception of one instance of dark patches on the lungs no macroscopic abnormalities were detected at necropsy amongst Group 2 animals.

The following macroscopic abnormalities were detected in the animals that died during the course of the study (Group 1 only) at necropsy:

Lungs – abnormally dark
Liver – accentuated lobular pattern
Kidneys – dark
Stomach – gaseous distension
Small intestine – gaseous distension
Large intestine – gaseous distension
Due to the observations noted it is considered that the deaths noted during the study may have been mainly attributed to local toxicity.

Other findings:

DOSE GROUP 2 - 1.08 mg/L (clinical findings).
During exposure occasional instances of increased respiratory rate were noted. On removal from the chamber all animals exhibited increased respiratory rate and there were occasional instances of laboured respiration. One hour post-exposure, little or no change in the condition of animals in Group 2 were noted. One day after exposure all animals exhibited increased respiratory rate, laboured respiration and hunched posture, pilo-erection was also noted in male animals. Animals recovered to appear normal from Days 9 to 10 post-exposure.

Exposure Chamber Concentration

The test atmosphere was sampled seventeen times during each exposure period and the actual concentration of the test item calculated. The mean values obtained were:

 

Group Number	Atmosphere Concentration
	Mean achieved (mg/L)	Standard Deviation	Nominal (mg/L)
1	5.16	0.20	8.77
2	1.08	0.08	3.62

 

The exposure chamber concentrations are given in Tables 1 and 2 and are presented graphically in Figures 3 and 4 (attached).

The chamber flow rate was maintained at 60 L/min providing 120 air changes per hour.

The theoretical chamber equilibration time (T99) was 3 minutes*

*The test atmosphere was generated for 17 minutes and 21 minutes prior to animal insertion (for Groups 1 and 2 respectively) to ensure the test item concentration was being achieved.

 

Particle Size Distribution

Group Number	Mean achieved atmosphere concentration (mg/L)	Mean mass median aerodynamic diameter (µm)	Inhalable fraction (% < 4µm)	Geometric standard deviation
1	5.16	3.06	60.9	267
2	1.08	1.99	82.3	2.14

 

The particle size distribution data are presented in Tables 3 and 4 and graphs showing the distribution are presented in Figures 5 to 8 (attached).

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute inhalation LC50 was determined to be in the range from >1 mg/L to 5 mg/L for the test substance.

Executive summary:

Three out of six animals died at a mean achieved atmosphere concentration of 5.16 mg/L, whereas, no deaths occurred in a group of six rats exposed to a mean achieved atmosphere concentration of 1.08 mg/L. It was therefore considered that the acute inhalation median lethal concentration (4hr LC50) of IP37: Copper (II)-pyrophosphate, in RccHanTM: IST strain rat, was in the range >1 mg/L to 5 mg/L (Category 4).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

The study was conduced according to guideline and GLP.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

The acute oral toxicity of copper pyrophosphate was tested in rats in a study following OECD Guideline 423 and under GLP conditions (Entzian, 2013). Two groups of 3 female Wistar rats each were sequentially given the test substance (suspended in water) at a single dose of 2000 mg/kg bw by oral gavage.No mortality occurred and no clinical signs of systemic toxicity or effects on body weight gain were observed during the 14-day observation period.Gross necropsy revealed no treatment-related findings.

The oral LD50 of copper pyrophosphate in female rats was thus estimated to be > 2000 mg/kg bw.

In an earlier study conducted similarly to OECD Guideline 423, the oral LD50 was estimated to be > 2000 mg/kg bw in a group of 3 female Sprague Dawley rats (Richeux, 2004).In this study, no mortality, clinical signs, body weight effects or abnormal macroscopic findings were observed.

The available data indicates that copper pyrophosphate is not acutely toxic by the oral route. Due to the lack of mortality and any adverse toxic effects, the classification criteria for acute toxicity Category 5 according to GHS are not fulfilled.

Acute inhalation toxicity

An acute inhalation toxicity study was conducted with copper pyrophosphate in rats according to OECD 436 and in compliance with GLP (Griffiths, 2014). Two groups of RccHanTM:WIST rats (3 per sex and concentration level) were nose only exposed to the test material for 4 h at analytical concentrations of 1.08 and 5.16 mg/L air.The test atmosphere consisted of particles with a mean mass median aerodynamic diameter of 1.99 and 3.06 µm with a fraction of inhalable particles of 82.3 and 60.9% at the low and high concentrations, respectively.

Mortalities occurred on Day 1 (one male) and 2 (one male and one female) following exposure to 5.16 mg/L. There were no deaths in the 1.08 mg/L group. Clinical signs commonly observed included increased respiratory rate, laboured respiration, hunched posture, pilo-erection and wet fur. Occasionally, decreased respiratory rate, noisy respiration and tip-toe gait were also noted. Animals exposed to 1.08 and 5.16 mg/L recovered to appear normal from Days 9-10 and 11 post-exposure, respectively. All animals in the 1.08 mg/L group showed body weight loss on Day 1 post-exposure, and two males of this group showed a slight further body weight loss from Days 1 to 3. Similarly, all surviving animals in the 5.16 mg/L group exhibited body weight loss on Day 1 and from Days 1 to 3 post-exposure. Reasonable body weight development was noted in all animals of both groups during the remainder of the recovery period.

Two instances of dark patches on the lungs and one instance of pale patches in the lungs were noted in the surviving animals exposed to 5.16 mg/L. One instance of dark patches on the lungs was observed in one female of the 1.08 mg/L group; all other animals of this group showed no gross abnormalities.

Among the animals that died during the study, macroscopic abnormalities included abnormally dark lungs, accentuated lobular pattern in the liver, dark kidneys and gaseous distension of the stomach, small and large intestine. Due to these observations, it was considered that deaths may have been mainly attributable to local toxicity.

The 4 h LC50 in male and female rats was considered to be > 1-5 mg/L (LC50 cut-off value: 5 mg/L). Copper pyrophosphate thus fulfils the classification criteria for acute toxicity by inhalation Category 4 according to Regulation (EC) No 1272/2008 (CLP) and GHS.

Acute dermal toxicity

This information is not available.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

Based on available data on acute oral toxicity the test item is not classified according to Regulation (EC) No 1272/2008 (CLP).

Based on available data on acute inhalation toxicity the test item is classified into Category 4 for acute inhalation according to Regulation (EC) No 1272/2008 (CLP).