Dicalcium pyrophosphate

Endpoint summary

Description of key information

One key study is available for acute oral toxicity. This study is performed under the conditions of GLP and to an appropriate OECD guideline. As such, this study is considered to be adequate and reliable for use as a key study for the purpose of REACH Registration and classification and labelling in accordance with EU CLP. 

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:

The study was performed between 19 November 2012 and 20 December 2012.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted to GLP and in compliance with agreed protocols, with no deviations from standard test guidelines (OECD 420, EU Method B1 bis) and no methodological deficiencies. This study has been selected as the key study 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).

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of inspection: 10 July 2012, Date of signature: 31 November 2012

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Oxon, UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: The bodyweight variation did not exceed ± 20% of the initial/mean bodyweight of any previously dosed animal(s).
- Fasting period before study: overnight fast immediately before dosing.
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum (2014C Teklad Global Rodent diet supplied by Harlan Teklad, Oxon, UK)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): at least 15 per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

IN-LIFE DATES: From: Day 0 to Day 14
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

For the purpose of the study the test item was freshly prepared, as required, as a suspension in arachis oil BP. Arachis oil BP was considered to produce a formulation more suitable for dosing than distilled water.
The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.
No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement.

Doses:

300 mg/kg bw, 2000 mg/kg bw

No. of animals per sex per dose:

300 mg/kg bw: 1
5000 mg/kg bw: 5

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 subsequently once daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Preliminary study:

One animal treated at 300 mg/kg bw No mortality observed. See table for clinical observations of the animal treated with 300 mg/kg.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: Dose level: 2000 mg/kg bw: No signs of systemic toxicity were noted during the observation period. Dose Level: 300 mg/kg bw: No signs of systemic toxicity were noted during the observation period.

Gross pathology:

Dose level: 2000 mg/kg bw:
Individual necropsy findings are given in Table 6.
No abnormalities were noted at necropsy.


Dose Level: 300 mg/kg bw:
Necropsy findings are given in Table 3.
No abnormalities were noted at necropsy.

Other findings:

Based on the results at a dose level of 300 mg/kg, a dose level of 2000 mg/kg bodyweight was investigated.
Individual clinical observations and mortality data are given in Table 4.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to > 2000 mg/kg bodyweight (Globally Harmonised Classification System - Not classified).
This study is considered to be reliable and acceptable for use as a key study in accordance with Regulation (EC) No. 1907/2006 (REACH) and for the purposes of classification and labelling in accordance with Regulation (EC) No. 1272/2008 (EU CLP).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

One study exists: study is conducted to GLP and in compliance with agreed protocols, with no deviations from standard test guidelines (OECD 420) and no methodological deficiencies.
The LD50 was found to be > 2000 mg/kg bw.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of acute toxicity – oral endpoint
This study has been selected as the key study 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).

Justification for classification or non-classification

Acute oral toxicity: The oral LD₅₀has been determined to be > 2000 mg/kg bw and therefore in accordance with Regulation (EC) No. 1272/2008 (EU CLP) dicalcium pyrophosphate is not considered to be classified as acutely toxic via the oral route.