Diammonium dihydrogenpyrophosphate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

16/06/1988 to 30/06/1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline 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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: FMC Non-Definitive Dermal Toxicity Protocol (Number 7)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

see any additional information on methods.

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tetrapotassium pyrophosphate

EC Number:

230-785-7

EC Name:

Tetrapotassium pyrophosphate

Cas Number:

7320-34-5

Molecular formula:

H4O7P2.4K

IUPAC Name:

tetrapotassium diphosphate

Details on test material:

- Name of test material (as cited in study report): Tetrapotassium pyrophosphate
- Substance type: White solid
- Physical state: solid
- Analytical purity: data on file with sponsor
- Reference No.: 600A-5072X
- Stability under test conditions: data on file with sponsor
- Storage condition of test material: Room temperature
- Other:
FMC-T#: 636
Date received: 03/05/1988
Formulation: Technical

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Animals, Inc., Denver, Pennsylvania on May 18, 1988
- Age at study initiation: Young
- Weight at study initiation: 2.21 - 2.74 kg
- Housing: individually housed in stainless steel cages. DAGB cageboard bedding was used in the litter pans.
- Diet (e.g. ad libitum): ad libitum; Purina High Fiber Rabbit Chow 5326
- Water (e.g. ad libitum): ad libitum; fresh tap water
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 67 - 74°F
- Humidity (%): 52 - 69 %
- Photoperiod (hrs dark / hrs light): 12 hour fluorescent light: 12 hour dark cycle.


IN-LIFE DATES: May 18, 1988 - 13/06/1988

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
The test material was weighed out onto a 4" by 4" 8-ply gauze pad. The gauze was held in place with hypoallergenic tape. The test site was occluded with impervious plastic sheeting. Immediately after dosing each animal was fitted with an everted plastic Elizabethan collar. The collars remained in place until termination of the study.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hour after exposure the wrapping was removed. The test site was wiped cleaned with a gauze moistened with methanol and then rinsed with tap water.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Please see additional information on materials and methods.
- Constant volume or concentration used: yes
- For solids, paste formed: no

VEHICLE
- The test material was moistened with physiological saline.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6: 3 female, 3 males each at 2000 mg/kg bw.

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14
- Frequency of observations and weighing: The animals were observed for mortality and clinical signs ( local irritation excluded) at approximately 3 hours after dosing and daily thereafter for 14 days. Bodyweights were taken on the day of dosing and again on days 7 and 14. A description of the local irritation was recorded on days 1, 3, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

no data

Results and discussion

Preliminary study:

no data

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

None of the animals died during the study

Clinical signs:

other: All animals remained healthy durng the observation period.

Gross pathology:

No gross lesions were found.

Other findings:

Results for local irritation are reported in Table 2.

Any other information on results incl. tables

Table 1 - Individual bodyweights

Animal # / sex	Day 0 (kg)	Dose (g)	Amount applied (mg/cm^2)	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

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the test material is approximated to be relatively non-toxic.

In accordance with Regulation (EC) No. 1272/2008 (EU CLP) tetrapotassium pyrophosphate is not considered to be acutely toxic via the dermal route.