1,3-diiodopropane

Eye irritation

Administrative data

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

9.10.2017

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1,3-diiodopropane

EC Number:

210-993-4

EC Name:

1,3-diiodopropane

Cas Number:

627-31-6

Molecular formula:

C3H6I2

IUPAC Name:

1,3-diiodopropane

impurity 1

Reference substance name:

1-chloro-3-iodopropane

EC Number:

230-088-8

EC Name:

1-chloro-3-iodopropane

Cas Number:

6940-76-7

Molecular formula:

C3H6ClI

IUPAC Name:

1-chloro-3-iodopropane

impurity 2

Reference substance name:

Unknown Impurity

IUPAC Name:

Unknown Impurity

Test material form:

liquid

Details on test material:

Batch 90423 / CME0032526

Test animals / tissue source

Species:

cattle

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Species from which cornea were derived: Bos primigenius Taurus (fresh bovine corneas)
Fresh bovine eyes were obtained from the slaughterhouse Müller Fleisch GmbH, Industriestraße 42, 75217 Birkenfeld, Germany, on the day of the test. The cattle were between 12 and 60 months old. The eyes were transported to the test facility in Hanks’ Balanced Salt Solution with 1% Penicillin-Streptomycin solution (Penicillin 100 U/mL, Streptomycin 100 µg/mL) in a suitable cooled container within 1 hour.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

750 µL of the liquid test (undiluted)

Duration of treatment / exposure:

10 minutes exposure time for negative control solution, test item or positive control

Duration of post- treatment incubation (in vitro):

2 hours post-incubation

Number of animals or in vitro replicates:

3 replicates each for negative control solution, test item or positive control

Results and discussion

In vitro

Results

Irritation parameter:

in vitro irritation score

Run / experiment:

mean ivis from triplicate measurement

Value:

0.73

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Opacity and Permeability Values: The illuminance (unit: LUX) values which were measured before and after exposure are given in the following table:

Parameter	Negative Control			Test Item			Positive Control
	1. Rep.	2. Rep.	3. Rep.	1. Rep.	2. Rep.	3. Rep.	1. Rep.	2. Rep.	3. Rep.
(I) Measured values before exposure	1030	1040	1037	1043	1048	1049	1055	1063	1063
(I) Measured values after exposure	1014	1015	1014	1000	990	1032	366	352	370

Rep. = Replicate

The values in the following tables present the calculated opacity values, according to evaluation:

Opacity Values Negative Control

Parameter	Negative Control
	1. Rep.	2. Rep.	3. Rep.
Opacity before exposure	3.47	3.06	3.18
Opacity after exposure	4.15	4.10	4.15
Opacity Difference	0.68	1.05	0.97
Mean Opacity Difference	0.90

Rep. = Replicate

 

Opacity Values Test Item and Positive Control

Parameter	Test Item			Positive Control
	1. Rep.	2. Rep.	3. Rep.	1. Rep.	2. Rep.	3. Rep.
Opacity before exposure	2.93	2.73	2.69	2.45	2.14	2.14
Opacity after exposure	4.75	5.20	3.39	81.27	86.07	79.97
Opacity Difference	1.82	2.47	0.69	78.82	83.94	77.83
Opacity Difference corrected	0.92	1.57	-0.20	77.93	83.04	76.94
Mean Opacity Difference corrected	0.77			79.30

Rep. = Replicate

For the permeability measurement, three replicates for each treatment group were measured three times. cMEM without phenol red was measured as blank value as well. The optical density values at 492 nm are given in the following tables:

Optical density at 492 nm of Blank

Parameter	cMEM without phenol red
1. Measurement	0.036
2. Measurement	0.040
3. Measurement	0.037
Mean	0.038

 

Optical density at 492 nm of Negative Control, Test Item and Positive Control

Parameter	Negative Control			Test Item			Positive Control
	1. Rep.	2. Rep.	3. Rep.	1. Rep.	2. Rep.	3. Rep.	1. Rep.	2. Rep.	3. Rep.
1.Measure-ment	0.040	0.040	0.040	0.044	0.036	0.032	0.688	1.177	1.325
2.Measure-ment	0.039	0.040	0.037	0.044	0.035	0.032	0.688	1.180	1.348
3.Measure-ment	0.038	0.041	0.040	0.043	0.036	0.033	0.690	1.162	1.378
1.Measure-ment – blank	0.0023	0.0023	0.0023	0.0063	-0.0017	-0.0057	0.6503	1.1393	1.2873
2.Measure-ment – blank	0.0013	0.0023	-0.0007	0.0063	-0.0027	-0.0057	0.6503	1.1423	1.3103
3.Measure-ment – blank	0.0003	0.0033	0.0023	0.0053	-0.0017	-0.0047	0.6523	1.1243	1.3403
Mean of each replicate	0.0013	0.0027	0.0013	0.0060	-0.0020	-0.0053	0.6510	1.1353	1.3127
Mean of 3 replicates	0.0018			--			--
Corrected	--	--	--	0.0042	-0.0038	-0.0071	0.6492	1.1336	1.3109
Corrected mean of 3 replicates	--			-0.0022			1.0312

Rep. = Replicate

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 HBSS	0.70	0.92	21.91%
	1.09
	0.99
Test Item 1,3-Diiodopropane	0.99	0.73	128.40%
	1.52
	-0.31
Positive Control DMF undiluted	87.66	97.44	6.74%
	100.04
	96.60

Note: the high relative standard deviation of the IVIS of the test item is due to mathematical reasons, as the respective means are very small.

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 mean IVIS of the negative control has to show an IVIS ≤ 3. The validity criteria and findings are given in the following table:

Parameter	Criterion	Found	Assessment
Mean IVIS of negative control HBSS	≤ 3	0.92	ok
Mean IVIS of positive control DMF undiluted	56.53 – 140.26	94.77	ok

 

Values for negative and positive controls were within the range of historical data of the test facility. Therefore, the test system was acceptable.

Assessment: According to OECD Guideline no. 437 (Oct. 2017), a substance with an IVIS ≤ 3 requires no classification for eye irritation or serious eye damage.

Classification Scheme

IVIS	UN GHS
≤ 3	No category
> 3 and ≤ 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 induced serious eye damage, which would be classified as GHS category I. The test item 1,3-Diiodopropane showed no effects on the cornea of the bovine eye. The calculated mean IVIS (In Vitro Irritancy Score) was 0.73.

The experiment is considered as sufficient for the classification of the test item, because all three replicates of the test item lead to the same assessment for the test item.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the test item 1,3-Diiodopropane showed no effects on the cornea of the bovine eye.

Executive summary:

One valid experiment was performed according to the Bovine Corneal Opacity and Permeability (BCOP) Test Method following OECD Guideline 437 and EU Method B.47. Bovine corneas were used. They were collected from slaughtered cattle that were between 12 and 60 months old.

The test item 1,3-Diiodopropane was applied onto the cornea of a bovine eye which had been previously incubated with cMEM without phenol red at 32 ±1 °C for 1 hour and whose opacity had been measured.

The test item was incubated on the cornea for 10 minutes at 32 ±1 °C. After removal of the test item and 2 hours post-incubation, opacity and permeability values were measured. Hank’s Balanced Salt Solution (HBSS) was used as negative control. The negative control showed no irritating effect on the cornea and the calculated mean IVIS (In Vitro Irritancy Score) was 0.92. Dimethylformamide (DMF) undiluted was used as positive control. The positive control induced serious eye damage on the cornea and was within two standard deviations of the current historical mean. The calculated mean IVIS was 94.77.

Under the conditions of this study, the test item 1,3-Diiodopropane showed no effects on the cornea of the bovine eye. The calculated mean IVIS was 0.73. Thus, according to OECD Guideline no. 437 (Oct. 2017), a substance with an IVIS ≤ 3 requires no classification for eye irritation or serious eye damage.