[ethane-1,2-diylbis[nitrilobis(methylene)]]tetrakisphosphonic acid

Endpoint summary

Description of key information

A skin irritation study found the test material non-irritating when applied as finely ground powder and as a 25% solution-suspension in corn oil to intact skin of male and female rabbits. The result is reported in a study which is similar to guideline but which pre-dated GLP (Younger Laboratories 1968).

The average maximum score of  31.6 out of possible 110 at one hour is reported in a study which is equivalent to guideline but which pre-dated GLP, and in which only total eye irritation scores were included (Younger Laboratories 1968).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1968

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The report was lacking in detail.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

other: albino

Details on test animals or test system and environmental conditions:

No data.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: corn oil. Also applied neat.

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Concentration (if solution): 25% solution-suspension in corn oil. Test substance was also applied neat as a finely ground powder.

Duration of treatment / exposure:

24 hours

Observation period:

'several days'

Number of animals:

3 / dose

Details on study design:

No data.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24/48/72h

Score:

0

Max. score:

0

Remarks on result:

other: as finely ground powder

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24/48/72h

Score:

0

Max. score:

0

Remarks on result:

other: 25% suspension in corn oil

Irritant / corrosive response data:

No skin changes were noted when the compound was applied either in powder form or as a 25% solution-suspension in corn oil. All animals received a score of zero throughout the observation period.

Other effects:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

The compound was classed as non-irritating when applied as finely ground powder and as a 25% solution-suspension in corn oil to intact skin of male and female rabbits. The result is reported in a study which is similar to guideline but not compliant with GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The report was lacking in detail on animal husbandry and test material and individual irritation scores were not included.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Principles of method if other than guideline:

The report was lacking in detail on animal husbandry and test material.

GLP compliance:

no

Species:

rabbit

Strain:

other: 'albino'

Details on test animals or tissues and environmental conditions:

Not provided.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg of finely ground sample were placed in the conjunctival sac of the right eye of each rabbit.

Duration of treatment / exposure:

The eyes were rinsed after 24 hours.

Observation period (in vivo):

168 hours

Number of animals or in vitro replicates:

2M, 1F

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours

SCORING SYSTEM: Draize

Irritation parameter:

other: Average maximum score

Basis:

mean

Time point:

other: 1 hour

Score:

31.6

Max. score:

110

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

The compound was classified as a moderate eye irritant in male and female rabbits. The average maximum score was 31.6 out of possible 110 in one hour.

Other effects:

Discomfort was moderate immediately following application. Moderate discharge and erythema, mild edema, and mild corneal cloudiness developed within one hour. Iris clarity improved slightly overnight due primarily to some disappearance of corneal dullness. Discharge nearly ceased in three days. Iris clarity was normal within seven days. A slight degree of redness and edema remained.

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Time point	Score per animal	Average
60 min	29/33/33	31.6
24 h	24/31/29	28
48 h	19/25/25	23
72 h	13/20/18	17
120h	8/13/10	10.3
168h	4/6/6	5.3

 

 

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The average maximum score of 31.6 out of possible 110 at one hour is reported in a study which is equivalent to guideline but not compliant with GLP. Only total scores were included in the report, however the report states that iris effects had cleared by day 7 indicating that these must have been ≥1 within the 24-72 hour period which serves as the basis for classification. Together with the moderate effects of erythema, oedema and corneal dullness the study is used as weight of evidence to classify EDTMP-H as Category 2 eye irritant.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The key study for skin irritation reports no irritant effects of the test material when applied onto the skin of rabbits as a finely ground powder or as a suspension in corn oil (Younger Laboratories 1968). The study was the most reliable and recent and was selected as key on this basis.

For eye irritation, only total scores were included in the report, however the report states that iris effects had cleared by day 7 indicating that the scores must have been ≥1 within the 24-72 hour period which serves as the standard basis for classification. Based on this and the moderate effects of erythema, oedema and corneal dullness the study is used to classify EDTMP-H as Category 2 Eye Irritant (H319: Causes serious eye irritation).

Justification for classification or non-classification

Based on the available reliable key skin irritation study, EDTMP-H does not meet the criteria for classification as irritant. However, based on the available reliable key eye irritation study, EDTMP-H is classified as Eye Irritant Category 2 (H319: Causes serious eye irritation) according to the criteria of the Regulation (EC) No. 1272/2008.