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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 20 June 1989 to 12 July 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
In accordance with REACH Annex XI, Section 1.5, of Regulation (EC) No. 1907/2006 (REACH) the standard testing regime may be adapted in cases where a grouping or read-across approach has been applied.

The similarities may be based on:
(1) a common functional group
(2) the common precursors and/or the likelihood of common breakdown products via physical or biological processes, which result in structurally similar chemicals; or
(3) a constant pattern in the changing of the potency of the properties across the category

The proposed source chemical (is a mixture of ammonium orthophosphates and ammonium pyrophosphates and is highly soluble in water (> 10000 mg/L). In aqueous media soluble inorganic orthophosphates and pyrophosphates will dissociate to their ionic constituents; in this case ammonium and orthophosphate or pyrophosphate ions. Diammonium dihydrogenpyrophosphate will dissociate to ammonium cations and pyrophosphate anions. The pyrophosphate anions are unstable in aqueous solutions with the degree of instability varying according to pH. In distilled water they will hydrolyse slowly via abiotic mechanisms to orthophosphate. In natural waters a number of different processes can occur; abiotic hydrolysis, biotic degradation (as a result of the action of phosphatases which cleave pyrophosphates into orthophosphate subunits) and assimilation by organisms in the water. Thus, the target substance (diammonium dihydrogenpyrophosphate) and the source substance (mixture of ammonium orthophosphates and pyrophosphates) will be primarily absorbed as the same inorganic ions: ammonium and orthophosphate and are expected to behave in a similar manner under test conditions.
All (bio) transformation products of the source chemical are common to the target chemical and as such the data is considered to be adequate and reliable for use in the assessment of diammonium dihydrogenpyrophosphate for the toxicity hazard assessment.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
See read-across justification report attached.

3. ANALOGUE APPROACH JUSTIFICATION
See read-across justification report attached.

4. DATA MATRIX
See read-across justification report attached.


Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A dose ranging study was conducted using 2 males and 2 females at each of 5 dose levels: 1000, 2000, 3000, 4000, 5000 mg/kg.
Based on the results of this, a main study was conducted using 5 males and 5 females at 5000 mg/kg.
GLP compliance:
yes
Remarks:
Authentication confirming that the work was performed in accordance with the principles of Good Laboratory Practice signed by study director 18 January 1990.
Test type:
other: not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
Ammonium polyphosphates impurities not otherwise specified
Molecular formula:
not applicable
IUPAC Name:
Ammonium polyphosphates impurities not otherwise specified
Test material form:
liquid
Details on test material:
The identity of the test material is not reported within the study report itself, however the data is referred to in the Toxicological Risks of Selected Flame Retardant Chemicals (2000), Subcommittee on Flame-Retardant Chemicals, Committee on Toxicology, Board on Environmental Studies and Toxicology, National Research Council. ISBN: 0-309-59232-1. The substance LR-2 is an ‘ammonium polyphosphate’ and the author provides the following additional information with regards to the chemical identity of LR2: ‘Based on information provided by the manufacturer (Stewart Miller, Albright and Wilson, pers. commun., Nov. 1, 1999), a typical species distribution of polyphosphates in LR2 is 20% orthophosphate, 40% pyrophosphate,
Specific details on test material used for the study:
The identity of the test material is not reported within the study report itself, however the data is referred to in the Toxicological Risks of Selected Flame Retardant Chemicals (2000), Subcommittee on Flame-Retardant Chemicals, Committee on Toxicology, Board on Environmental Studies and Toxicology, National Research Council. ISBN: 0-309-59232-1. The substance LR-2 is an ‘ammonium polyphosphate’ and the author provides the following additional information with regards to the chemical identity of LR2: ‘Based on information provided by the manufacturer (Stewart Miller, Albright and Wilson, pers. commun., Nov. 1, 1999), a typical species distribution of polyphosphates in LR2 is 20% orthophosphate, 40% pyrophosphate,

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Manston Road, Margate, Kent
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: 136-222 g
- Fasting period before study: 16-18 h before dosing and 3-4 h post-dosing
- Housing: The rats were housed by sex in polypropylene cages with mesh floors suspended over absorbent paper lined trays with a maximum of 6 animals per cage for the dose ranging study and 5 animals per cage for the main study.
- Diet (e.g. ad libitum): Expanded Rat and Mouse Maintenance Diet, supplied by Special Diets Servicest 1 Stepfield , Witham, Essex, EMS lAD
- Water (e.g. ad libitum): Tap water was available ad libitum throughout the study
- Acclimation period: At least 7 days before test commencement

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Mean maximum: 22 °C; Mean minimum: 20 °C
- Humidity (%): 50 %
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light (light hours 0700 - 1900 h)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
Dose volume: 10 mL/kg
Doses:
In dose ranging study: 1000, 2000, 3000, 4000, 5000 mg/kg

In the main study: 5000 mg/kg
No. of animals per sex per dose:
In dose ranging study: 2 animals per sex per dose
In the main study: 5 animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily observatios. Animals were weighed immediately prior to dosing, 7 days after dosing (main study only) nd at sacrifice at the end of the observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Preliminary study:
In the dose ranging study there were no deaths and no clinical signs or gross post mortem observations were noted.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths. Details of test results are given in Table 1.
Clinical signs:
No clinical signs were noted in any of the animals.
Body weight:
Body weight gains, which were acceptable, are detailed in Table 2.
Gross pathology:
No abnormalties were detected in the post mortem observations.

Any other information on results incl. tables

Table 1: Test Results, 5000 mg/kg

Animal/sex

Mortality

Clinical signs

Post Mortem Observations

51-Male

 

 

0/5

NAD

NAD

52-Male

NAD

NAD

53-Male

NAD

NAD

54-Male

NAD

NAD

55-Male

NAD

NAD

56-Female

 

 

0/5

NAD

NAD

57-Female

NAD

NAD

58-Female

NAD

NAD

59-Female

NAD

NAD

60-Female

NAD

NAD

 

NAD = No abnormalities detected

Table 2 – Main study: Body weights, 5000mg/kg

Animal number and sex

Bodyweight (g)

Weight gain (g)

At Dosing

After 7 days

After 14 days

 

51-Male

215

290

290

75

52-Male

164

229

228

64

53-Male

183

225

230

47

54-Male

190

255

265

75

55-Male

222

295

296

74

Mean

195

259

262

67

± S.D.

24

33

32

12

56-Female

148

180

200

52

57-Female

136

170

183

47

58-Female

140

176

190

50

59-Female

169

210

226

57

60-Female

147

187

193

46

Mean

148

185

198

50

± S.D.

13

15

17

4

Applicant's summary and conclusion

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 material in the Sprague Dawley was estimated to be >5000 mg/kg bw .
Executive summary:

The acute oral toxicity potential of a test material, Amgard LR2, was investigated in rats. The vehicle used for the dosing solutions was distilled water. A dose ranging study in pairs of rats indicated that the oral LD50 value is greater than 5000 mg/kg. A main study dose 1eve1 of 5000 mg/kg was selected accordingly. In the main study, no deaths occurred and no clinical signs were noted after oral administration of Amgard LR2 at a dose level of 5000 mg/kg No abnormalities were detected at post mortem. The Median Oral Lethal Dose (LD50) of Amgard LR2 is greater than 5000 mg/kg.