Bis(2,4,4-trimethylpentyl)phosphinic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From August 4th to 12th, 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

GLP guideline study with some restrictions: no certificate of analysis and a too short observation period (7 days, whereas occular effects are still observed at the termination of the study by day 7), no data on the animal environmental conditions (Temperature, humidity...)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1982

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

: no certificate of analysis, the observation period is too short (only 7 days, whereas scores are still observed by day 7), no data on the animal environmental conditions (Temperature, humidity...)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2,4,4-trimethylpentyl)phosphinic acid

EC Number:

280-445-7

EC Name:

Bis(2,4,4-trimethylpentyl)phosphinic acid

Cas Number:

83411-71-6

Molecular formula:

C16H35O2P

IUPAC Name:

bis(2,4,4-trimethylpentyl)phosphinic acid

Test material form:

liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Pine Acres Rabbitry, W. Brattleboro, VT
- Age at study initiation: 12 to 14 weeks
- Weight at study initiation: 2.3 to 2.9 kg
- Housing: no data
- Diet (e.g. ad libitum): Charles River Rabbit Formula, Lot #W2162
- 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: From: To:no data

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): not applicable, as the test item is used as supplied (undiluted)ì

Duration of treatment / exposure:

The eye was not rinsed after administration of test item up to the end of the study in 6 animals while the eye of the other 3 animals was rinsed 20 to 30 seconds after the instillation.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

9 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, 6 animals were not rinsed and 3 animals were rinsed. The washing was done with 20 ml of lukewarm distilled water for 1 min
- Time after start of exposure: 20 to 30 seconds after the instillation

SCORING SYSTEM: grading for irritation and injury were made at 24, 48 and 72h and at 4 and 7 days, using the standard scoring system of Draize.

TOOL USED TO ASSESS SCORE: no data

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

animal not rinsed

Basis:

other: 4 out of 6

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Results 2

Irritation parameter:

cornea opacity score

Basis:

other: 1 out of 6

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Results 3

Irritation parameter:

cornea opacity score

Basis:

other: 1 out of 6

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Results 4

Irritation parameter:

iris score

Remarks:

not rinsed

Basis:

other: all animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 5

Irritation parameter:

conjunctivae score

Basis:

other: 1 out of 6

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Results 6

Irritation parameter:

conjunctivae score

Basis:

other: 2 out of 6

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not reversible

Results 7

Irritation parameter:

conjunctivae score

Basis:

other: 2 out of 6

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

not reversible

Results 8

Irritation parameter:

conjunctivae score

Basis:

other: 1 out of 6

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

not reversible

Results 9

Irritation parameter:

chemosis score

Basis:

other: 2 out of 6

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Results 10

Irritation parameter:

chemosis score

Basis:

other: 1 out of 6

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Results 11

Irritation parameter:

chemosis score

Basis:

other: 2 out of 6

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Results 12

Irritation parameter:

chemosis score

Basis:

other: 1 out of 6

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritant / corrosive response data:

Corneal opacity in all 6 unrrigated eyes, which subsided completely in all but 2 eyes by day 7.
No effect on the iris during the course of the study.
Hyperemia was observed in all 6 eyes by day 1, which subsided completely in 3 eyes by day 7.
All 6 eyes also displayed chemosis on day 1, which was not observed in 3 of the eyes by the termination of the study.
The discharge observed in all 6 unirrigated treated eyes on day 1 subsided completely by day 7 in 4 of the eyes.
The 3 eyes treated with the sample and irrigated displayed no corneal opacity or injury of the iris during the treatment and the 7 day observation period. Transient conjunctivae scores (max. 1) for redness and chemosis were observed within the first 3 days of the study for those animals.

Other effects:

no other effects

Any other information on results incl. tables

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test. Only the scores of unirrigated animals are detailed in this table.

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
24 h	0/0/0/0/1/2	No effect	2/2/1/2/1/2	3/3/2/2/2/4
48 h	1/1/1/1/2/2	No effect	1/2/1/1/1/2	1/2/1/2/2/3
72 h	1/1/1/1/2/2	No effect	1/2/3/2/1/2	1/2/2/2/2/3
Average 24h, 48h, 72h	0.7/0.7/0.7/0.7/1.7/2.0	No effect	1.3/2.0/1.7/1.7/1.0/2.0	1.7/2.3/1.7/2.0/2.0/3.3
Reversibility*)	c/c/n/n/c/c	-	c/c/n/n/c/n	c/c/n/n/c/n
Average time (day) for reversion	4/7/-/-/7/7	-	4/7/-/-/4/-	7/7/-/-/7/-

 *) Reversibility: c. = completely reversible;n.c.= not completely reversible; n. = not reversible

Applicant's summary and conclusion

Interpretation of results:

other: classified as an eye irritant according to the CLP Regulation (EC) No.1272/2008

Conclusions:

Eye irritant based on the chemosis scores which are equal or higher than 2 in 4/6 animals.

Executive summary:

In an eye irritation study performed similarly to the OECD No. 405 guideline and in compliance with the GLP, 0.1 ml of undiluted test material was instilled into the conjunctival sac of left eye of 9 Albino New Zealand Rabbits (male). After the instillation the substance was not remained for 6 animals while for the three others the treated eye was washed with water 20 to 30 seconds after the instillation. Animals were then observed for 7 days for eye edema and erythema of the conjunctive, corneal opacity and iris lesion. Eye irritation was assessed and scored according to the Draize scale at 24, 48 and 72 hrs after the instillation of the substance and then at days 4 and 7. The mean individual score were calculated within 3 scoring times (24, 48 and 72 hrs).

For the animals whose eye was not rinsed, the mean individual scores were 1.7/2.3/1.7/2.0/2.0/3.3 for chemosis, 1.3/2.0/1.7/1.7/1.0/2.0 for conjunctival erythema, and 0.7/0.7/0.7/0.7/1.7/2.0 for corneal opacity. All of these effects were not totally reversible within the termination of the study (7 days) in all animals. Indeed, cornea opacity was still observed by day 7 in 2 animals, redness and chemosis of the conjunctiva were still observed in 3 animals. However there is a tendency to reversibility. In addition, there was no effect on the iris of all unirrigated animals. For the animals, whose eye was washed after the instillation, slight and transient effects of the conjunctiva were observed within the first 3 days after the instillation. 

 

Under the test conditions, the test substance is considered as an Eye irritant based on the chemosis scores which are equal or higher than 2 in 4/6 animals.