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Description of key information

The substance was observed to be non corrosive in a corrositex assay.
An analogue of DTBPOK ( potassium dibenzyl phosphate), was considered highly irritant for the eye in a rabbit study.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
between 2012-07-23 to 2012-10-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
In accordance with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 435 (In Vitro Membrane Barrier Test Method for Skin Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
2012-09-07
Test system:
human skin model
Source species:
human
Details on test system:
SOURCE AND COMPOSITION OF MEMBRANE BARRIER USED
- Was the Corrositex® test kit used: Yes
Lot number CT052112
Expiry date May 2014

WAS THE COMPATIBILITY TEST PERFORMED: Yes

WAS THE TIMESCALE CATEGORY TEST PERFORMED: Yes

METHOD OF DETECTION
- Chemical or electrochemical detection system: Chemical detection system

METHOD OF APPLICATION: A membrane disc was placed on top of the vials. An aliquot of test item occupying 0.5 ml was evenly applied onto the top of the membrane disc.

NUMBER OF REPLICATES: 4

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be corrosive to skin if the mean breakthrough time is less than 60 min as the substances was categorized in Category 2.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

VEHICLE
No vehicle

NEGATIVE CONTROL
- Concentration (if solution): 10% w/v
Duration of treatment / exposure:
60 min
Number of replicates:
4
Irritation / corrosion parameter:
penetration time (in minutes)
Run / experiment:
1 to 4
Value:
> 60
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid

Qualification Screen

The test item produced an immediate colour change therefore qualified for use in the CORROSITEX assay.

Categorisation Screen

The test item was assigned into Category 2.

Assay

 

Test item Breakthrough Time

Vial 1

Vial 2

Vial 3

Vial 4

Start time

(hr:min:sec)

00:00:00

00:04:00

00:05:00

00:06:00

Detection time

(hr:min:sec)

Not applicable

Not applicable

Not applicable

Not applicable

Breakthrough time

(hr:min:sec)

Not applicable

Not applicable

Not applicable

Not applicable

 

No breakthrough observed after 60 minutes

  

 

The results of the assay were accepted on condition of adherence to the positive and negative control item ranges given in the following table:

 

Chemical

Concentration

(weight %)

Breakthrough Time

(hr:min:sec)

Positive Control

Sulphuric Acid

95 – 98

00 :01 :00

Negative Control

Citric Acid

10

>60 minutes

hr = hour(s)

min = minute(s)

sec = second(s)

Interpretation of results:
GHS criteria not met
Conclusions:
The test item was considered to be non-corrosive.
Executive summary:

This in vitro study was performed to assess the skin corrosion potential of DTBPOK, in a corrositex assay according to the OECD 435 Guideline and GLP.

The qualification screen qualified the test item for the corrositex assay. The test item was assigned to category 2.

The results for the positive and negative control were acceptable.

In all four replicates, the breakthough time was > 60 minuges. Therefore, DTBPOK is considered to be non-corrosive.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
between 1997-06-02 to 1997-07-21
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
according to GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
1996-21-02
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 16 weeks
- Weight at study initiation: 3.32 kg
- Housing: suspended metal cage
- Diet (e.g. ad libitum): ad libitum (STANRAB SQC Rabbit diet, special diets services, Witham, Essex, UK)
- Water (e.g. ad libitum):ad libitum
- Acclimation period: yes, at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 21 °C
- Humidity (%): 51 to 70%
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From: To: 2 June 1997 to 23 June 1997
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (Approximately 20 mg)
Duration of treatment / exposure:
Only one treatment
Observation period (in vivo):
just after the administration of the test item, 1h, 24h, 48h, 72h (according to the numerical evaluation from Draize J H 1977 "Dermal and Eye Toxicity test")
Additional observation were made on Days 7, 14 and 21 to assess the reversibility of the ocular test.
Number of animals or in vitro replicates:
1 animal
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing

SCORING SYSTEM: according to the numerical evaluation from Draize J H 1977 "Dermal and Eye Toxicity test" in: Principles and Procedures for evaluating the toxicity of Household Substances, National Academy of sciences, Washington DC p 48-49

TOOL USED TO ASSESS SCORE: standard ophtalmoscope
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
55
Reversibility:
fully reversible within: 21d
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
5
Reversibility:
fully reversible within: 14d
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within: 21d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Reversibility:
fully reversible within: 14d
Irritant / corrosive response data:
Individual and total scores for ocular irritation are given in table 1.

Areas of translucent corneal opacity were noted in the treated eye one hour after treatment with area of diffuse corneal opacity at the 24 and 48-hour observations, areas of translucent corneal opacity at 72-hour observation and diffuse corneal opacity at the 7 and 14-day observations. Sloughing of the cornea was noted in the treated eye at the 72-hour observation.

Iridial inflammation was noted in the treated eye one hour after treatment and at the 24, 48, 72-hour and 7-day observations. No other iridial affect were noted

Moderate conjunctival irritation was noted in the treated eye one hour after treatment and at the 24, 48 72-hour and 7-day observation with minimal conjunctival irritation at the 14 and 21-day observations. Pale green discolouration of the nictitating and conjunctival membranes was noted in the treated eye one hour after treatment. An off white appearance of the nictitating membrane and approximately half of the lower conjunctival membrane was noted in the treated eye at the 24, 48 and 72-hour and 7-day observations. An area of haemorrhage approximately 3 mm² in size on the conjunctival membrane of the lower eyelid was noted in the treated eye at 48 and 72-hour and 7-day observations. An abnormally shaped nictitating membrane was noted in the treated eye at the 14 and 21 day observations.

Table 1: Acute irritation test in the rabbit: Individual Scores and total Scores for Ocular Irritation

 

Rabbit Number and Sex

(Bodyweight kg)

IPR = 3

63 Female (3.32)

Time after Treatment

1 hour

24 hours

48 hours

72 hours

7 days

14 days

21 days

CORNEA

 

E = Degree of Opacity

2

1

1

2 SI

1

1

0

F = Area of opacity

4

4

4

3

3

1

 

Score (E x F) x 5

40

20

20

30

15

5

0

IRIS

 

D

1

1

1

1

1

0

0

Score (D x 5)

5

5

5

5

5

0

0

CONJUNCTIVAE

 

A = redness

2G

2W

2WH

2WH

2WH

1AB

1AB

B = Chemosis

2

2

2

2

2

1

0

C = discharge

2

3

3

1

1

0

0

Score (A +B + C) x 2

12

14

14

10

10

4

2

Total Score

57

39

39

45

30

9

2

 

IPR = Initial Pain Reaction

AB = Abnormally shaped nictitating membrane

G = Pale green discolouration of the nictating and conjunctival membrane of lower eyelid

H = Area of haemorrhage approximately 3 mm² located on conjuntival membrane of lower eyelid

W = off white appearance of nictating membrane and approximately half of the lower conjunctival membrane

SI = sloughing of corneal membrane

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The test material produced a maximum total of 57 and was considered to be at least a SEVERE IRRITANT (Class 6 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system (based on the rabbit only).

Under the test conditions, test item is irritating to the eye rabbit and required the classification as Eye Dam. 1 (H318) according to the Regulation (EC) 1272/2008 (CLP).
Executive summary:

In an eye irritation study performed similarly to the OECD No. 405 guideline, 0.1 mL of undiluted test item was instilled into the right eye of 1 female New Zealand White Rabbits. The animal was then observed for 21 days for eye oedema and erythema of the conjunctivae, 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 7, 14 and 21.

The highest score was observed 1 hour after treatment. The effects was not fully reversible during the 21 days of observation, with still effect on conjonctivae ( redness and abnormally shaped nictitating membrane)

 

Under the test conditions, test item is considered as highly irritating to the eye rabbit and is therefore classified as Eye Dam. 1 (H318) according to the Regulation (EC) 1272/2008 (CLP).

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

An in vitro study was performed to assess the skin corrosion potential of DTBPOK, in a corrositex assay according to the OECD 435 Guideline and GLP.

The qualification screen qualified the test item for the corrositex assay. The test item was assigned to category 2.

The results for the positive and negative control were acceptable.

In all four replicates, the breakthough time was > 60 minuges. Therefore, DTBPOK is considered to be non-corrosive.

An in-vivo study (Safepharm 1997) acute eye irritation test in the rabbit was performed to assess the eye irritation potential of potassium dibenzyl phosphate (analogue of DTBPOK) according to the OECD 405 guideline. Results showed that potassium dibenzyl phosphate was considered to be highly irritant for the eye.

Justification for selection of skin irritation / corrosion endpoint:
Only one study available

Justification for selection of eye irritation endpoint:
Only one study available with the potassium dibenzyl phosphate (CAS 78543-37-0), which is an analogue of DTBPOK

Effects on eye irritation: highly irritating

Justification for classification or non-classification

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