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Description of key information

The data available is performed on analogous substances. This data is considered adequate and reliable to fulfil the information requirements as part of a weight of evidence. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
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.
Reason / purpose for cross-reference:
read-across source
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,
Preliminary study:
In the dose ranging study there were no deaths and no clinical signs or gross post mortem observations were noted.
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.

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

Interpretation of results:
GHS criteria not met
Conclusions:
Diammonium dihydrogenpyrophosphate is estimated to have an estimated LD50 of >2000 mg/kg bw/day.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The source data, performed on an analogous substance, is GLP compliant and has a Klimisch reliability of 1.

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
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
Diammonium dihydrogenpyrophosphate is a soluble inorganic salt consisting of pyrophosphate anions and ammonium cations. Similarities between the source chemical (sodium acid pyrophosphate) and the target chemical (diammonium dihydrogenpyrophosphate) are based on the following:
(1) The source chemical (sodium acid pyrophosphate) and the target substance (diammonium dihydrogenpyrophosphate) are structurally similar substances. Both are soluble inorganic phosphate salts. In vivo both substances will be (bio)transformed into their respective ionic forms; phosphate anions (either diphosphate or orthophosphate depending on degree of metabolism) and cations; either ammonium or sodium. Exposure to the non-common compound, the sodium ion, will not result in toxicological effects at the dose levels tested. Similarly, the effects of different phosphate moieties are not considered to be toxicologically significant due to in vivo (bio) transformation.
(2) Both substances contain the bio transformation product: orthophosphate. Pyrophosphate will ultimately be converted to orthophosphate in vivo. The key moiety for the assessment of diammonium dihydrogenpyrophosphate is the ammonium cation and as such the effects of the target compound (diammonium dihydrogenpyrophosphate) are expected to be equal to or worse than the effects of the source substance (sodium acid pyrophosphate) for the property under consideration.
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.
Reason / purpose for cross-reference:
read-across source
Duration of exposure:
h
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.58 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
See Table 1.
One female died on day 1 and one male died on day 14 post-exposure.
Clinical signs:
other: See Table 1. Clinical signs noted during the exposure included lacrimation, material on fur, oral discharge and squinting eyes. Incidence of clinical signs was highest at the removal from chamber observation. Signs gradually resolved during the study, how
Body weight:
See Table 2.
Most animals lost weight through day 4 of the study, then began to gain weight in a normal pattern. At termination all surviving animals exhibited increases in body weight over their day 0 values.
Gross pathology:
See table 3.
There were no gross internal lesions observed in any animal which survived to study termination. One male which died on day 14 had discoloured lungs with many light red nodules. This animal was also observed to have a corneal opacity in one eye.
Other findings:
No data

See attached file for Tables 1, 2 and 3.

Interpretation of results:
GHS criteria not met
Conclusions:
Diammonium dihydrogenpyrophosphate is estimated not to be classifed for acute toxicity via the inhalation route.
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
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
Diammonium dihydrogenpyrophosphate is a soluble inorganic salt consisting of pyrophosphate anions and ammonium cations. Similarities between the source chemical (tetrapotassium pyrophosphate) and the target chemical (diammonium dihydrogenpyrophosphate) are based on the following:
(1) The source chemical (tetrapotassium pyrophosphate) and the target substance (diammonium dihydrogenpyrophosphate) are structurally similar substances. Both are soluble inorganic phosphate salts. In vivo both substances will be (bio)transformed into their respective ionic forms; phosphate anions (either diphosphate or orthophosphate depending on degree of metabolism) and cations; either ammonium or potassium. Exposure to the non-common compound, the potassium ion, will not result in toxicological effects at the dose levels tested. Similarly, the effects of different phosphate moieties are not considered to be toxicologically significant due to in vivo (bio) transformation.
(2) Both substances contain the bio transformation product: orthophosphate. Pyrophosphate will ultimately be converted to orthophosphate in vivo. The key moiety for the assessment of diammonium dihydrogenpyrophosphate is the ammonium cation and as such the effects of the target compound (diammonium dihydrogenpyrophosphate) are expected to be equal to or worse than the effects of the source substance (tetrapotassium pyrophosphate) for the property under consideration.
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.

Reason / purpose for cross-reference:
read-across source
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.1 mg/L air
Exp. duration:
4 h
Mortality:
One female died on day 6 post-exposure
Clinical signs:
other: See Table 1. Incidence of clinical signs was highest at the removal from chamber observation. Clinical signs generally persisted up to day 13 post-exposure and then gradually subsided. The observation period was extended to allow for abatement of clinica
Body weight:
See Table 2 and 3.
Most animals lost weight through day 4 of the study then began to gain weight in a normal pattern. At termination all surviving animals exhibited increases in body weight over their day 0 values.
Gross pathology:
See Table 4.
There was no gross internal lesions noted in any animal which survived to study termination. The animal that died on day 6 post-exposure had all lobes and surfaces of the lungs mottled dark red and red.

Table 1 - Incidence of clinical signs – male

 

Observation

Day 0

Day 1

Day 2

Day 3

Hour

PT

0.25

0.50

0.75

1

2

3

4

R

1PE

AM

PM

AM

PM

AM

PM

Abdominogenital staining

0

0

0

0

0

0

0

0

0

0

5

5

5

5

5

5

Chromodacryorrhea

0

0

0

0

0

0

0

0

5

2

2

2

2

2

2

2

Decreased feces

0

0

0

0

0

0

0

0

0

0

0

0

1

1

1

1

Dehydration

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1

1

Decreased locomotion

0

0

0

0

0

0

0

0

1

0

0

0

0

0

0

0

Emaciated

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Lacrimation

0

5

5

5

5

5

5

5

3

2

1

1

0

0

0

0

Material on Fur

0

0

5

5

5

5

5

5

5

5

5

5

5

5

5

5

Opacity

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Oral discharge

0

0

0

3

3

3

3

3

5

1

0

0

0

0

0

0

Rales

0

0

0

0

0

0

0

0

1

1

0

0

0

0

0

0

Scab on Snout

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Squinting Eyes

0

5

5

5

5

5

5

5

3

3

2

2

2

2

2

2

Unthriftiness

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Death (cumulative)

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Table 1 continued - Incidence of clinical signs - male

Observation

Day

4

5

6

7

8

9

10

11

AM

PM

AM

PM

AM

PM

AM

PM

AM

PM

AM

PM

AM

PM

AM

PM

Abdominogenital staining

3

3

3

2

1

1

0

0

0

0

0

0

0

0

0

0

Chromodacryorrhea

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Decreased feces

3

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Dehydration

1

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Decreased locomotion

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Emaciated

0

3

3

3

0

0

0

0

0

0

0

0

0

0

0

0

Lacrimation

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Material on Fur

5

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Opacity

0

1

1

1

1

1

2

2

2

2

2

2

2

2

2

2

Oral discharge

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Rales

0

1

1

1

0

0

0

0

3

3

3

3

2

1

0

0

Scab on Snout

1

1

1

1

1

1

1

1

1

1

1

1

0

0

0

0

Squinting Eyes

2

1

1

0

0

0

0

0

0

0

0

0

0

0

0

0

Unthriftiness

0

5

4

4

3

1

1

1

1

1

1

1

0

0

0

0

Death (cumulative)

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
Diammonium dihydrogenpyrophosphate is estimated not to be classifed for acute toxicity via the inhalation route.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The source data, performed on analogous substances, is GLP compliant and has a Klimisch reliability of 1.

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
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.

Reason / purpose for cross-reference:
read-across source
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,
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Mortality data is given in Table 1.
There were no deaths.
Clinical signs:
Individual clinical observations are given in Table 1.
No signs of systemic toxicity were noted during the study.
Body weight:
Individual bodyweights, together with weekly bodyweight gains are given in Table 3.
All animals showed expected gain in bodyweight during the study.
Gross pathology:
Individual necropsy findings are given in Table 4.
No abnormalities were noted at necropsy.

Table 1: Individual clinical observations and mortality data

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

1-0 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-1 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-2 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-3 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-4 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-0 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-3 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-4 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

Table 2: Individual Dermal Reactions

Dose Level mg/kg

Animal number and sex

Effects noted during period after dosing

(days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

 

 

 

 

 

 

 

2000

1-0 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-1 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-2 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-3 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-4 Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-0 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-3 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-4 Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0 = no signs of dermal irritation

Table 3: Individual bodyweights and weekly bodyweight gain

Dose Level

mg/kg

Animal number and sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

 

 

 

 

2000

1-0 Male

226

276

321

50

45

1-1 Male

242

289

354

47

65

1-2 Male

224

255

306

36

51

1-3 Male

225

256

298

31

42

1-4 Male

225

256

298

31

42

2-0 Female

227

242

269

15

27

2-1 Female

228

243

271

15

28

2-2 Female

219

234

253

15

19

2-3 Female

206

220

244

14

24

2-4 Female

229

245

278

16

33

 

Table 4: Individual Necropsy Findings

Dose Level

mg/kg

Animal Number and Sex

Time of Death

Macroscopic Observations

 

 

 

 

 

 

2000

1-0 Male

Killed Day 14

No abnormalities detected

1-1 Male

Killed Day 14

No abnormalities detected

1-2 Male

Killed Day 14

No abnormalities detected

1-3 Male

Killed Day 14

No abnormalities detected

1-4 Male

Killed Day 14

No abnormalities detected

2-0 Female

Killed Day 14

No abnormalities detected

2-1 Female

Killed Day 14

No abnormalities detected

2-2 Female

Killed Day 14

No abnormalities detected

2-3 Female

Killed Day 14

No abnormalities detected

2-4 Female

Killed Day 14

No abnormalities detected

Interpretation of results:
GHS criteria not met
Conclusions:
Diammonium dihydrogenpyrophosphate is estimated to have an estimated LD50 of >2000 mg/kg bw/day.
Executive summary:

A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Method B3 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directi ve 91/325/EEC).

A group of ten animals (five males and five females) was given a single 24-hour, semi-occluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination.

There were no deaths . No signs of systemic toxicity or skin irritation were noted during the study.

All animals showed expected gain in bodyweight during the study.

No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight . No symbol or risk phrase is required according to EC labelling regulations.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
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
Diammonium dihydrogenpyrophosphate is a soluble inorganic salt consisting of pyrophosphate anions and ammonium cations. Similarities between the source chemical (tetrapotassium pyrophosphate) and the target chemical (diammonium dihydrogenpyrophosphate) are based on the following:
(1) The source chemical (tetrapotassium pyrophosphate) and the target substance (diammonium dihydrogenpyrophosphate) are structurally similar substances. Both are soluble inorganic phosphate salts. In vivo both substances will be (bio)transformed into their respective ionic forms; phosphate anions (either diphosphate or orthophosphate depending on degree of metabolism) and cations; either ammonium or potassium. Exposure to the non-common compound, the potassium ion, will not result in toxicological effects at the dose levels tested. Similarly, the effects of different phosphate moieties are not considered to be toxicologically significant due to in vivo (bio) transformation.
(2) Both substances contain the bio transformation product: orthophosphate. Pyrophosphate will ultimately be converted to orthophosphate in vivo. The key moiety for the assessment of diammonium dihydrogenpyrophosphate is the ammonium cation and as such the effects of the target compound (diammonium dihydrogenpyrophosphate) are expected to be equal to or worse than the effects of the source substance (tetrapotassium pyrophosphate) for the property under consideration.
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.
Reason / purpose for cross-reference:
read-across source
Preliminary study:
no data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None of the animals died during the study
Clinical signs:
All animals remained healthy durng the observation period.
Body weight:
See Table 1. All but one rabbit gained weight during the study.
Gross pathology:
No gross lesions were found.
Other findings:
Results for local irritation are reported in Table 2.

Table 1 - Individual bodyweights

Animal # / sex

Day 0

(kg)

Dose

(g)

Amount applied

(mg/cm2)

Day 7

(kg)

Day 14

(kg)

1 / male

2.21

4.4

42.7

2.27

2.42

2 / male

2.66

5.3

51.5

2.65

2.78

3 / male

2.25

4.5

43.7

2.27

2.36

Mean ± SD

2.37 ± 0.249

 

46.0 ± 4.82

2.40 ± 0.219

2.52 ± 0.227

 

 

 

 

 

 

4 / female

2.55

5.1

49.5

2.69

2.85

5 / female

2.74

5.5

53.4

2.40

2.64

6 / female

2.54

5.1

49.5

2.56

2.60

Mean ± SD

2.61 ± 0.113

 

50.8 ± 2.25

2.55 ± 0.145

2.70 ± 0.134

Table 2 - Local irritation

Animal # / sex

Day 1

Day 3

Day 7

Day 14

(kg)

1 / male

N

N

De

De

2 / male

Er

Er

Es

Es, De

3 / male

Ed, Ne, Cb

Ed, Ne, Cb

Ts, Ne,Cb

Ne, Es, Ex, Tb, Ts

 

 

 

 

 

4 / female

Er

Er

Es, Tb

Es

5 / female

Er

N

N

N

6 / female

N

N

Es, Ts, Tb

Es, Ex

N - normal

De - desquamation

Er - Erythema

Ed - Edema

Ne - Necrosis

Cb - Chemcially burned

Ts - Skin thickening

Ex - Exfoliation

Tb - Tissue bleeding

Interpretation of results:
GHS criteria not met
Conclusions:
Diammonium dihydrogenpyrophosphate is estimated to have an estimated LD50 of >2000 mg/kg bw/day.
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
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
Diammonium dihydrogenpyrophosphate is a soluble inorganic salt consisting of pyrophosphate anions and ammonium cations. Similarities between the source chemical (sodium acid pyrophosphate) and the target chemical (diammonium dihydrogenpyrophosphate) are based on the following:
(1) The source chemical (sodium acid pyrophosphate) and the target substance (diammonium dihydrogenpyrophosphate) are structurally similar substances. Both are soluble inorganic phosphate salts. In vivo both substances will be (bio)transformed into their respective ionic forms; phosphate anions (either diphosphate or orthophosphate depending on degree of metabolism) and cations; either ammonium or sodium. Exposure to the non-common compound, the sodium ion, will not result in toxicological effects at the dose levels tested. Similarly, the effects of different phosphate moieties are not considered to be toxicologically significant due to in vivo (bio) transformation.
(2) Both substances contain the bio transformation product: orthophosphate. Pyrophosphate will ultimately be converted to orthophosphate in vivo. The key moiety for the assessment of diammonium dihydrogenpyrophosphate is the ammonium cation and as such the effects of the target compound (diammonium dihydrogenpyrophosphate) are expected to be equal to or worse than the effects of the source substance (sodium acid pyrophosphate) for the property under consideration.
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.
Reason / purpose for cross-reference:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 95% confidence limits not reported.
Mortality:
No deaths occurred during the study.
Clinical signs:
No clinical signs were observed during the course of the study.

There were no signs of dermal irritation.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Other findings:
None.

Table1              Individual Clinical Observations and Mortality Data

Dose Level

mg/kg

Animal Number and Sex

Effects Noted After Initiation of Exposure (Hours)

Effects Noted After Initiation of Exposure (Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0

Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-1

Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-2

Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-3

Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-4

Male

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-3

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-4

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

See attachment for Tables 2 - 4

Interpretation of results:
GHS criteria not met
Conclusions:
Diammonium dihydrogenpyrophosphate is estimated to have an estimated LD50 of >2000 mg/kg bw/day.
Executive summary:

Introduction. The study was performed to assess the acute dermal toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following

OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted24 February 1987)

Method B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No. 440/2008

Method. A group of ten animals (five males and five females) was given a single, 24-hour, semi‑occluded dermal application of the test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Dermal Irritation. There were no signs of dermal irritation.

Bodyweight. All animals showed expected gains in bodyweight over the study period.

Necropsy. No abnormalities were noted at necropsy.

Conclusion. The acute dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
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
Diammonium dihydrogenpyrophosphate is a soluble inorganic salt consisting of pyrophosphate anions and ammonium cations. Similarities between the source chemical (tetrapotassium pyrophosphate) and the target chemical (diammonium dihydrogenpyrophosphate) are based on the following:
(1) The source chemical (tetrasodium pyrophosphate) and the target substance (diammonium dihydrogenpyrophosphate) are structurally similar substances. Both are soluble inorganic phosphate salts. In vivo both substances will be (bio)transformed into their respective ionic forms; phosphate anions (either diphosphate or orthophosphate depending on degree of metabolism) and cations; either ammonium or sodium. Exposure to the non-common compound, the sodium ion, will not result in toxicological effects at the dose levels tested. Similarly, the effects of different phosphate moieties are not considered to be toxicologically significant due to in vivo (bio) transformation.
(2) Both substances contain the bio transformation product: orthophosphate. Pyrophosphate will ultimately be converted to orthophosphate in vivo. The key moiety for the assessment of diammonium dihydrogenpyrophosphate is the ammonium cation and as such the effects of the target compound (diammonium dihydrogenpyrophosphate) are expected to be equal to or worse than the effects of the source substance (tetrasodium pyrophosphate) for the property under consideration.
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.
Reason / purpose for cross-reference:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died during treatment or observation periods.
Clinical signs:
Local effects: mild erythema and dedema.
Sins of toxcity: all animals appeared normal throughout.
Body weight:
no data
Gross pathology:
No gross abnormalities were noted.
Interpretation of results:
GHS criteria not met
Conclusions:
Diammonium dihydrogenpyrophosphate is estimated to have an estimated LD50 of >2000 mg/kg bw/day.
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
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
Diammonium dihydrogenpyrophosphate is a soluble inorganic salt consisting of pyrophosphate anions and ammonium cations. Similarities between the source chemical (tetrapotassium pyrophosphate) and the target chemical (diammonium dihydrogenpyrophosphate) are based on the following:
(1) The source chemical (tetrasodium pyrophosphate) and the target substance (diammonium dihydrogenpyrophosphate) are structurally similar substances. Both are soluble inorganic phosphate salts. In vivo both substances will be (bio)transformed into their respective ionic forms; phosphate anions (either diphosphate or orthophosphate depending on degree of metabolism) and cations; either ammonium or sodium. Exposure to the non-common compound, the sodium ion, will not result in toxicological effects at the dose levels tested. Similarly, the effects of different phosphate moieties are not considered to be toxicologically significant due to in vivo (bio) transformation.
(2) Both substances contain the bio transformation product: orthophosphate. Pyrophosphate will ultimately be converted to orthophosphate in vivo. The key moiety for the assessment of diammonium dihydrogenpyrophosphate is the ammonium cation and as such the effects of the target compound (diammonium dihydrogenpyrophosphate) are expected to be equal to or worse than the effects of the source substance (tetrasodium pyrophosphate) for the property under consideration.
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.
Reason / purpose for cross-reference:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 mg/kg bw
Based on:
test mat.
Mortality:
No mortality.
Clinical signs:
No clinical signs.
Body weight:
No effects on bodyweight were recorded.
Gross pathology:
No effects.
Interpretation of results:
GHS criteria not met
Conclusions:
Diammonium dihydrogenpyrophosphate is estimated to have an estimated LD50 of >2000 mg/kg bw/day.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
A weight of evidence approach is applied. The source data, performed on analogous substances, are GLP compliant and have Klimisch reliabilities of 1 or 2.

Additional information

Justification for classification or non-classification

All the available data supports the evidence that diammonium dihydrogenpyrophosphate is not considered to be acutely toxic in accordance with Regulation (EC) No. 1272/2008 (EU CLP).