6H-Dibenz[c,e][1,2]oxaphosphorin-6-propanoic acid, butyl ester, 6-oxide

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March - April 2014

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of coverage:

other: Commercially available Epi-200-Kit

Irritation / corrosion parameter:

other: erythema score

Value:

>= 1

Remarks on result:

other:

Remarks:

Time point: 2014. (migrated information)

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Executive summary:

Three tissues of the human skin model EpiDerm^TMwere treated with KCCS DOB11 for 60 minutes.

30 µL of the liquid test item (using a nylon mesh) were applied to each tissue and spread to match the tissue size (0.63 cm²; as indicated by supplier).

DPBS-buffer was used as negative control, 5% SDS-solution was used as positive control.

After treatment with the negative control, the absorbance values were within the required acceptability criterion of 0.8≤mean OD≤2.8. The positive control showed clear irritating effects. Variation within tissues was acceptable (< 18%).

After the treatment with the test item, the relative absorbance values were reduced to 3.3 %. This value is well below the threshold for irritation potential (50%).

 

Therefore, KCCS DOB11 is considered as “irritant in the Human Skin Model Test”.

In the UN GHS System for skin irritating substances, KCCS DOB11should be classified in UN GHS category 2.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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:

May - June 2014

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Opacity and Permeability Values

The absorption (570 nm) and opacity values which were measured before and after exposition are given in the following table:

Parameter	Negative Control
Absorption before exposition	0.1532	0.1552	0.1546
Absorption after exposition	0.3141	0.1982	0.2154
Opacity before exposition	1.4230	1.4296	1.4276
Opacity after exposition	2.0611	1.5783	1.6421
Opacity Difference	0.6381	0.1488	0.2145

 

Mean opacity difference of the negative control is 0.3338.

 

Absorption and Opacity Values Test Item and Positive Control

Parameter	Test Item KCCS DOB11			Positive Control
Absorption before exposition	0.1691	0.1434	0.2106	0.1500	0.1336	0.1624
Absorption after exposition	0.5621	0.6625	0.8231	1.8089	2.0742	2.1406
Opacity before exposition	1.4760	1.3912	1.6241	1.4125	1.3602	1.4534
Opacity after exposition	3.6484	4.5973	6.6543	64.4021	118.6315	138.2293
Opacity Difference	2.1723	3.2060	5.0302	62.9896	117.2713	136.7758

 

For the permeability measurement, three replicates for each treatment group were measured. The optical density values at 490 nm are given in the following table:

Repl.	Negative Control			Test Item KCCS DOB11			Positive Control
Meas.	0.0043	0.0041	0.0060	0.0089	0.0072	0.0087	0.1856	0.1992	0.1594
Corr.	0.0215	0.0205	0.0300	0.0445	0.0360	0.0435	0.9280	0.9960	0.7970
Mean	0.0240			--

 

IVIS Values

The calculated IVIS for each replicate and the corresponding means are presented in the following table:

Test Group	IVIS	Mean IVIS	Relative Standard Deviation IVIS
Negative Control 0.9 % NaCl	0.961	0.694	36.5 %
	0.456
	0.665
Test Item	2.146	3.396	42.8 %
	3.052
	4.989
Positive Control 20 % imidazole	76.216	118.590	31.7 %
	131.518
	148.037

Classification

According to OECD Guideline no. 437 (Jul. 2013), a substance with an IVIS >3 and≤ 55 induces effects on the cornea, that cannot be classified in a UN GHS Category.

IVIS	UN GHS Category Eye Damage
≤ 3	No Category
> 3;≤ 55	No prediction can be made
> 55	Eye damage Category I

 

In the negative control, no signs of eye irritation were observed. The positive control showed seriouseye damage.

The test item KCCS DOB11 showed effects on the cornea of the bovine eye. The calculated IVIS (in vitro irritancy score) is 3.396.

Validity

According to the guideline, the test is considered as valid if the positive control causes an IVIS that falls within two standard deviations of the current historical mean. The negative or solvent control has to show an IVIS between 0 and 3.

The validity criteria and findings are given in the following table:

Parameter	Criterion	Found	Assessment
IVIS of negative control 0.9% NaCl	0 - 3	0.694	ok
IVIS of positive control 20 % imidazole	35.6 - 130.4	118.590	ok

 

Two values of the positive control were not within the range of historical data of the test facility.This can be seen as uncritical because difference was marginal and the mean value was within the demanded range as well as within historical data. The study is considered as valid, because only one replicate of the test item gave a discordant prediction from the mean whereas the other two led to same assessment for the test item. The discordant replicate showed a value far below 65.

Interpretation of results:

other: KCCS DOB11 induces effects on the cornea. It cannot be classified in a UN GHS Category for eye damage. Because of the negative test result a sequential testing strategy is necessary.

Remarks:

Criteria used for interpretation of results: expert judgment

Conclusions:

A mean IVIS of 3.396 was calculated. Under the conditions of this test, the test item KCCS DOB11 showed effects on the cornea of the bovine eye. According to OECD Guideline no. 437 (Jul. 2013), a substance with an IVIS > 3 and ≤ 55 induces effects on the cornea, that cannot be classified in a UN GHS Category for eye damage.

Executive summary:

One valid experiment was performed. Bovine corneas were used. They were collected from slaughtered cattle which were between 12 and 60 months old.

The test item KCCS DOB11 was brought onto the cornea of a bovine eye which had been incubated with cMEM without phenol red at 32±1 °C for one hour and whose opacity had been measured. The test item was incubated on the cornea for 4 hours at 32±1 °C. After removal of the test item, opacity and permeability values were measured.

Physiological sodium chloride solution was used as negative control. The negative control showed no irritating effect on the cornea.

20% Imidazole solution was used as positive control. The positive control induced serious eye damage on the cornea.

Under the conditions of this test, the test item KCCS DOB11 showed effects on the cornea of the bovine eye. The calculated IVIS (in vitro irritancy score) is 3.396. According to OECD Guideline no. 437 (Jul. 2013), a substance with an IVIS > 3 and≤ 55 cannot be classified in a UN GHS Eye Damage Category.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Skin irritation

KCCS DOB11 is considered as “irritant in the Human Skin Model Test” following EU-Method B.46 resp. OECD 439.

Eye irritation

The test item KCCS DOB11 was brought onto the cornea of a bovine eye. A mean IVIS of 3.396 was calculated. Under the conditions of this test, the test item KCCS DOB11 showed effects on the cornea of the bovine eye. According to OECD Guideline no. 437 (Jul. 2013), a substance with an IVIS > 3 and≤ 55 cannot be classified in a UN GHS Eye Damage Category.

Because of the negative BCOP test result another in vitro test has been performed (the Human Cornea Model test).

Although the Human Cornea Model test has not been validated by ECVAM so far the test item KCCS DOB11 is considered as not/minimal eye irritant based on both test results (BCOP and the Human Cornea Model).