[[(phosphonomethyl)imino]bis[ethylenenitrilobis(methylene)]]tetrakisphosphonic acid, ammonium salt

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

No data

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1973

Report date:

1973

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

Conducted prior to adoption to OECD test guidelines.

Deviations:

yes

Remarks:

Limited information on test substance, methods, animal/conditions. No information on scoring system used.

Principles of method if other than guideline:

Method: other: Insufficient detail to fully assess comparability with OECD guideline.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

[[(phosphonomethyl)imino]bis[ethane-2,1-diylnitrilobis(methylene)]]tetrakisphosphonic acid

EC Number:

239-931-4

EC Name:

[[(phosphonomethyl)imino]bis[ethane-2,1-diylnitrilobis(methylene)]]tetrakisphosphonic acid

Cas Number:

15827-60-8

Molecular formula:

C9H28N3O15P5

IUPAC Name:

[(bis{2-[bis(phosphonomethyl)amino]ethyl}amino)methyl]phosphonic acid

Constituent 2

Reference substance name:

[[(phosphonomethyl)imino]bis[ethane-2,1-diylnitrilobis(methylene)]]tetrakis phosphonic acid

IUPAC Name:

[[(phosphonomethyl)imino]bis[ethane-2,1-diylnitrilobis(methylene)]]tetrakis phosphonic acid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data


IN-LIFE DATES: No data

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml (equivalent to 85.2 mg active acid including HCl, although the recommended dose of 0.1 ml was achieved for the formulation, this means that the limit dose for the active acid was not attained. The level of irritation of the anhydrous active acid may therefore be underestimated by this study).

Duration of treatment / exposure:

24 hour(s)

Observation period (in vivo):

14 days (10 minutes, 1 hour and 1, 2, 3, 7 and 14 days)

Number of animals or in vitro replicates:

Six

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data
- Time after start of exposure: No data


SCORING SYSTEM: Draize.


TOOL USED TO ASSESS SCORE: No data

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

ca. 47.9

Max. score:

110

Reversibility:

not reversible

Irritant / corrosive response data:

10 minutes: Necrosis in conjunctival sac, slight oedema, copious discharge, slight dullness over cornea.
One hour: No apparent change.
24 hours: Very slight to well defined areas of corneal cloudiness, iris reaction was slow, necrosis in conjunctival sac, slight/moderate oedema, copious discharge containing whitish exudate.
48 to 168 hours: Slight improvement.
14 days: Slight ulceration in lower cornea.

Other effects:

Immediate, severe discomfort with thrashing about and squealing.

Any other information on results incl. tables

CORNEA
24 hours    30, 20, 15, 20, 20, 30  (very slight to well
defined areas of corneal cloudiness)
48 hours    30, 20, 15, 30, 30, 30
72 hours    30, 40, 20, 30, 40, 30
168 hours  45, 40, 10, 40, 40, 30

IRIS
24 hours    5, 5, 5, 5, 5, 5 (iris reaction slow)
48 hours    5, 5, 5, 5, 5, 5
72 hours    5, 5, 5, 5, 10, 5
168 hours  10, 5, 5, 10, 10, 5

CONJUCTIVAE 
24 hours    18, 18, 14, 18, 18, 18 (necrosis in conjunctival
sac) 
48 hours    16, 18, 12, 18, 16, 16
72 hours    16, 16, 12, 18, 14, 12
168 hours  16, 12,   8, 16, 12, 10

14 days after dosing: slight ulceration in lower cornea.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In an eye irritation study (reliability score 4) that was available as a limited summary only, and conducted prior to OECD test guideline and GLP, DTPMP-H was severely irritating to rabbit eyes.

Executive summary:

In an eye irritation study (reliability score 4) that was available as a limited summary only, and conducted prior to OECD test guideline and GLP, 0.1 ml of undiluted Dequest 2060 was instilled into one eye of each of six New Zealand white rabbits. Although the recommended dose of 0.1 ml was achieved for the formulation, this means that the limit dose for the active acid was not attained. The level of irritation of the anhydrous active acid may therefore be underestimated by this study. However, the presence of HCl in the formulation would be predicted to exacerbate the effect seen. After 24 hours the animals were observed for signs of eye irritation and reactions were graded according to the Draize scoring system. Reactions were graded at 10 minutes, 1, 24, 48, 72 and 168 hours, and 14 days. Immediate, severe discomfort with thrashing about and squealing was observed. Ten minutes after instillation, necrosis of the conjunctival sac, slight oedema, copious discharge, and slight dullness over the cornea were observed. There was no apparent further change after one hour. After 24 hours there were very slight to well defined areas of corneal cloudiness, iris reaction was slow, necrosis in conjunctival sac, slight/moderate oedema and copious discharge containing whitish exudate were noted. There was a slight improvement between 48 and 168 hours. After 14 days slight ulceration in lower cornea was recorded.