Diammonium hydrogenorthophosphate

Endpoint summary

Description of key information

An in vtro eye irritation showed no irritation. No reliable in vivo irritation data on diammonium hydrogenorthophosphate were available. Based on reliable in vivo studies with ammonium dihydrogenorthophosphate showing no or minimal irritation, it is concluded that that diammonium hydrogenorthophosphate is not irritating to skin and eyes. The read-across rationale can be found in the category approach document attached in Section 13 of IUCLID and is fully incorporated in the CSR (see Appendix A).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented, near-guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

24 h exposure under occlusive conditions

GLP compliance:

no

Species:

rabbit

Strain:

Vienna White

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): 80%

Duration of treatment / exposure:

24 h

Observation period:

9 days

Number of animals:

3 male and 3 female

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 72 h

Score:

0.25

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 h, 72 h

Score:

0

Max. score:

0

	time	animal 1	animal 2	animal 3	animal 4	animal 5	animal 6
erythema	24 h	1	1	0	0	0	1
	72 h	0	0	0	0	0	0
	9 d	0	0	0	0	0	0
edema	24 h	0	0	0	0	0	0
	72 h	0	0	0	0	0	0
	9 d	0	0	0	0	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 April 2010 to 08 April 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Qualifier:

according to guideline

Guideline:

other: OECD guideline 437 “Bovine corneal opacity and permeability (BCOP) test method for identifying ocular corrosives and severe irritants”

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Vehicle:

physiological saline

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 µl per cornea
- Concentration (if solution): 20% (w/w)

NEGATIVE CONTROL
- Amount(s) applied (volume or weight with unit): 750 µl of physiological saline per cornea

POSITIVE CONTROL
Amount(s) applied (volume or weight with unit): 750 µl per cornea
Concentration (if solution): 20% (w/w) Imidazole

Duration of treatment / exposure:

240 minuten

Details on study design:

TEST SITE
- Isolated bovine cornea

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 240 minutes

SCORING SYSTEM:
- After exposure the cornea is thoroughly rinsed to remove the test substance followed by immediate opacity measurement and permeability evaluation of the cornea.
- The mean opacity and mean permeability values (OD490) were used for each treatment group to calculate an in vitro score:

In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value).


TOOL USED TO ASSESS SCORE:
- opacitymeter and microplate reader

DATA EVALUATION:
A test substance that induces an IVIS ≥ 55.1 is defined as a corrosive or severe irritant

Irritation parameter:

in vitro irritation score

Run / experiment:

mean after 240 min

Value:

13

Remarks on result:

other: not severe irritant or corrosive

Other effects / acceptance of results:

Score was 13 after 240 minutes, which is below 55.1 and thus substance is not severe irritant or corrosive.

Interpretation of results:

other: not severe irritant or corrosive

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The positive and negative controls were within the historical control data.

The mean in vitro irritancy score was 13 after 240 minutes of treatment with Diammonium hydrogenorthophosphate. Since the mean in vitro irritancy score was below 55.1 after 240 minutes treatment Diammonium hydrogenorthophosphate is considered to be not severe irritant or corrosive.

Finally, it is concluded that this test is valid and that Diammonium hydrogenorthophosphate is not severe irritant or corrosive in the Bovine Corneal Opacity and Permeability test under the experimental conditions described in this report.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

No reliable studies on diammonium hydrogenorthophosphate are present. However, in a reliable skin irriation study performed comparable to OECD 404 guideline, ammonium dihydrogenorthophosphate does show some effects on the erythema, which are minimal and fully reversible within 72 hours.

Eye irritation

An in vitro Bovine Corneal Opacity and Permeability test (OECD 437 guideline) showed that diammonium hydrogenorthophosphate is a not an irritant under the test conditions. In addition, no reliable in vivo studies on diammonium hydrogenorthophosphate are present. However, in a reliable eye irriation study performed comparable to OECD 405 guideline, ammonium dihydrogenorthophosphate does not show any effects on the cornea and iris, but does show some limited effects on the conjunctiva (score 1 out of 3). These were decreasing in time, however not fully reversible within 72 hours (in 2 out of 6 animals). Because reversibility of the findings is expected due to the trend obvious in the individual data, the substance is considered a non-irritant.

Justification for selection of skin irritation / corrosion endpoint:
One in vivo study on the read-across study ammonium dihydrogenorthophosphate is available. Since the study was performed with a substance analogue and the data are read across, the Klimisch score is 2.

Justification for selection of eye irritation endpoint:
One in vitro study on the substance is available.

Justification for classification or non-classification

Based on the available data, diammonium hydrogenorthophosphate does not have to be classified according to Directive 67/548/EC and the CLP Regulation for skin and eye irritation.