Methyl 3-pyridyl ketone

Endpoint summary

Description of key information

Skin corrosion: OECD 431, GLP, human skin model EpiDerm, 3 min or 1h incubation: non-corrosive to skin
Skin irritation: OECD 439, GLP, human skin model EpiDerm, 1h incubation: irritant to skin
Eye irritation / corrosion: OECD 437, GLP, Bovine Corneal Opacity and Permeability Test: IVIS > 3 and ≤ 55 induces effects on the cornea, that cannot be classified in an UN GHS Category for eye damage

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:

2015-08-05 - 2015-10-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP OECD 439 guideline study without deviations on the registered substance itself.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

B.46 BIS. “IN VITRO SKIN IRRITATION: RECONSTRUCTED HUMAN EPIDERMIS MODEL TEST”, dated 24. Aug. 2009

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

OECD Guideline for the Testing of Chemicals, Version 439, 26. July 2013, “In Vitro Skin Irritation: Reconstructed Human Epidermis (RhE) Test Method”

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Landesamt für Umwelt, Wasserwirtschaft und Gewerbeaufsicht, Kaiser-Friedrich-Straße 7, 55116 Mainz, Germany

Species:

other: EpiDermTM tissue consisting of human-derived epidermal keratinocytes

Strain:

other: not applicable

Details on test animals or test system and environmental conditions:

not applicable

Type of coverage:

other: not applicable

Preparation of test site:

other: not applicable

Vehicle:

unchanged (no vehicle)

Controls:

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

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30µL

Duration of treatment / exposure:

60 min

Observation period:

42 h postincubation + 3 h incubation with MTT

Number of animals:

in total, 3 6-well plates were used

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Rinsing with DPBS buffer
- Time after start of exposure: 60 min

SCORING SYSTEM: Formazan production as described in OECD Guideline 439

Irritation / corrosion parameter:

other: other: Formazan production

Value:

46.6

Remarks on result:

other:

Remarks:

Basis: mean. Time point: 1 h incubation, 42h postincubation. Reversibility: other: not applicable. Remarks: Test item; below the threshold for skin irritation (50%).. (migrated information)

Irritation / corrosion parameter:

other: other: Formazan production

Value:

3.3

Remarks on result:

other:

Remarks:

Basis: mean. Time point: 1 h incubation, 42h postincubation. Reversibility: other: not applicable. Remarks: Positive control; below the threshold for skin irritation (50%).. (migrated information)

Irritant / corrosive response data:

The relative absorbance values were reduced to 46.6 % after the treatment. This value is below the threshold for skin irritation (50%). Therefore, the test item is considered as irritant to skin. For details see "Any other information on results incl. tables"

Findings and Results

Measured Values

As blank, the optical density of isopropanol was measured in eight wells of the 96-well-plate. The measured values and their mean are given in the following table:

Table Absorbance values blank isopropanol (OD at 570 nm)

Replicate	1	2	3	4	5	6	7	8	Mean
Absorbance	0.036	0.036	0.036	0.037	0.034	0.035	0.036	0.035	0.036

 

The absorbance values of negative control, test item and positive control are given in the following table:

Table Absorbance Values negative control, test item and positive control (OD at 570 nm)

Designation	Measurement	Negative Control	3-Acetylpyridine	Positive Control
Tissue 1	1	1.925	0.926	0.101
	2	1.922	0.935	0.102
Tissue 2	1	1.830	0.895	0.098
	2	1.857	0.900	0.097
Tissue 3	1	1.804	0.826	0.087
	2	1.800	0.826	0.088

 

From the measured absorbances, the mean of each tissue was calculated, subtracting the mean absorbance of isopropanol. Mean and relative standard deviation (comparison of the three tissues) were also calculated.

Table Mean Absorbance Values

Designation	Negative Control	3-Acetylpyridine	Positive Control
Mean – blank (tissue 1)	1.888	0.895	0.066
Mean – blank (tissue 2)	1.808	0.862	0.062
Mean – blank (tissue 3)	1.766	0.790	0.052
Mean of the three tissues	1.821	0.849	0.060
Relative standard deviation of the three tissues	3.4%	6.3%	12.0%

 

Comparison of Formazan Production

For the test item and the positive control, the following percentage values of formazan production were calculated in comparison to the negative control:

Table % Formazan Production

Designation	3-Acetylpyridine	Positive Control
% Formazan production (tissue 1)	49.1%	3.6%
% Formazan production (tissue 2)	47.3%	3.4%
% Formazan production (tissue 3)	43.4%	2.9%
% Formazan production (mean)	46.6%	3.3%

 

Assessment and Validity

Skin Irritation Potential of the Test Item

The relative absorbance values were reduced to 46.6 % after the treatment. This value is below the threshold for skin irritation (50%). Therefore, the test item is considered as irritant to skin.

 

Validity and Acceptability

Validity criteria and results are stated in the following table:

Table Validity

Criterion	Demanded	Found
OD of negative control	≥ 0.8 and ≤ 2.8	1.8
% Formazan production of positive control SDS	<=20% of negative control	3.3%
Variation within replicates (RSD)	< 18%	3.4% (negative control) 12.0% (positive control) 6.3 % (test item)

 

All validity criteria were met.

Values for negative control and for positive control were within the range of historical data of the test facility.

Therefore, the experiment is considered valid.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Testing was performed via a GLP OECD 439 guideline study on the registered substance itself. The present in vitro method is recommended in a tiered testing approach, it was used as follow-up study to an OECD 431 study in which 3-Acetylpyridine was found to be non-corrosive to skin.
The validity criteria are met, making the results sufficiently reliable to assess the irritating potential of 3-Acetylpyridine to the skin. The present in vitro method allows the identification of irritating chemical substances and mixtures.
The relative absorbance values were reduced to 46.6 % after the treatment. This value is below the threshold for skin irritation (50%). Therefore, the test item is considered as irritant to skin according to the guideline.

Executive summary:

In an OECD 439 (in vitro skin irritation) study under GLP, 1 valid experiment was performed.

 

3 tissues of the human skin model EpiDerm^TM were treated with 3-Acetylpyridine for 60 minutes.

30 µL of the 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, OD was 1.8. The positive control showed clear irritating effects. Relative absorbance was reduced to 3.3 %.

Variation within tissues was acceptable (< 18%).

 

After the treatment with the test item, the relative absorbance values were reduced to 46.6 %. This value is below the threshold for irritation potential (50%).

 

Therefore, 3-Acetylpyridine is considered as skin irritant in the Human Skin Model Test.

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:

2015-09-02 - 2015-11-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP OECD 437 guideline study without deviations on the registered substance itself.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

OECD Guideline No. 437, edition adopted 26. Jul. 2013: “Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage"

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)

Version / remarks:

EU Method B. 47: “Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants” adopted 09. Dec. 2010

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Landesamt für Umwelt, Wasserwirtschaft und Gewerbeaufsicht, Kaiser-Friedrich-Straße 7, 55116 Mainz, Germany

Species:

other: Bos primigenius Taurus (fresh bovine corneas)

Strain:

not specified

Details on test animals or tissues and environmental conditions:

not applicable

Vehicle:

unchanged (no vehicle)

Controls:

other: 0.9% NaCl in demin. water (negative control), Dimethylformamide undiluted (positive control)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 µL

Duration of treatment / exposure:

10 min

Observation period (in vivo):

2 h + 90 min post-incubation

Number of animals or in vitro replicates:

3 replicate corneas for each treatment group (negative control solution, test item and positive control)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, rinsing with cMEM with phenol red and final rinsing with cMEM without phenol red
- Time after start of exposure: 10 min

SCORING SYSTEM: Opacity value, calculated from the measured absorbance at 570 nm

TOOL USED TO ASSESS SCORE: fluorescein absorbance measurement

Irritation parameter:

other: IVIS (in vitro irritancy score)

Basis:

other: cornea #1

Time point:

other: 10 min incubation, 210 min postincubation

Score:

58.02

Reversibility:

other: not applicable

Remarks on result:

other: Test item; 1st experiment; IVIS>55, Eye damage Category I

Irritation parameter:

other: IVIS (in vitro irritancy score)

Basis:

other: cornea #2

Time point:

other: 10 min incubation, 210 min postincubation

Score:

56.98

Reversibility:

other: not applicable

Remarks on result:

other: Test item; 1st experiment; IVIS>55, Eye damage Category I

Irritation parameter:

other: IVIS (in vitro irritancy score)

Basis:

other: cornea #3

Time point:

other: 10 min incubation, 210 min postincubation

Score:

40.21

Reversibility:

other: not applicable

Remarks on result:

other: Test item; 1st experiment; IVIS > 3 and ≤ 55, No prediction can be made

Irritation parameter:

other: IVIS (in vitro irritancy score)

Basis:

mean

Remarks:

all corneas

Time point:

other: 10 min incubation, 210 min postincubation

Score:

51.74

Reversibility:

other: not applicable

Remarks on result:

other: Test item; 1st experiment; IVIS > 3 and ≤ 55, No prediction can be made

Irritation parameter:

other: IVIS (in vitro irritancy score)

Basis:

mean

Remarks:

all corneas

Time point:

other: 10 min incubation, 210 min postincubation

Score:

86.24

Reversibility:

other: not applicable

Remarks on result:

other: Positive control; 1st experiment; IVIS>55, Eye damage Category I

Irritation parameter:

other: IVIS (in vitro irritancy score)

Basis:

mean

Remarks:

all corneas

Time point:

other: 10 min incubation, 210 min postincubation

Score:

1.64

Reversibility:

other: not applicable

Remarks on result:

other: Negative control; 1st experiment; IVIS ≤ 3, No category

Irritation parameter:

other: IVIS (in vitro irritancy score)

Basis:

other: cornea #1

Time point:

other: 10 min incubation, 210 min postincubation

Score:

51.85

Reversibility:

other: not applicable

Remarks on result:

other: Test item; 2nd experiment; IVIS > 3 and ≤ 55, No prediction can be made

Irritation parameter:

other: IVIS (in vitro irritancy score)

Basis:

other: cornea #2

Time point:

other: 10 min incubation, 210 min postincubation

Score:

34.5

Reversibility:

other: not applicable

Remarks on result:

other: Test item; 2nd experiment; IVIS > 3 and ≤ 55, No prediction can be made

Irritation parameter:

other: IVIS (in vitro irritancy score)

Basis:

other: cornea #3

Time point:

other: 10 min incubation, 210 min postincubation

Score:

40.14

Reversibility:

other: not applicable

Remarks on result:

other: Test item; 2nd experiment; IVIS > 3 and ≤ 55, No prediction can be made

Irritation parameter:

other: IVIS (in vitro irritancy score)

Basis:

mean

Remarks:

all corneas

Time point:

other: 10 min incubation, 210 min postincubation

Score:

42.16

Reversibility:

other: not applicable

Remarks on result:

other: Test item; 2nd experiment; IVIS > 3 and ≤ 55, No prediction can be made

Irritation parameter:

other: IVIS (in vitro irritancy score)

Basis:

mean

Remarks:

all corneas

Time point:

other: 10 min incubation, 210 min postincubation

Score:

28.53

Reversibility:

other: not applicable

Remarks on result:

other: Positive control; 2nd experiment; IVIS > 3 and ≤ 55, No prediction can be made

Irritation parameter:

other: IVIS (in vitro irritancy score)

Basis:

mean

Remarks:

all corneas

Time point:

other: 10 min incubation, 210 min postincubation

Score:

0.27

Reversibility:

other: not applicable

Remarks on result:

other: Negative control; 2nd experiment; IVIS ≤ 3, No category

Irritant / corrosive response data:

In the negative control, no signs of eye irritation were observed in both experiments.
In the first experiment, the positive control induced serious eye damage, which would be classified as GHS category 1. In the second experiment, the positive control showed effects on the cornea of the bovine eye.
The test item 3-Acetylpyridine showed effects on the cornea of the bovine eye. The calculated IVIS (in vitro irritancy score) is 51.74 in the first experiment and 42.16 in the second experiment.

Findings and Results

Two experiments were performed. The first experiment was insufficient for classification because 2 of the 3 replicates gave discordant predictions from the mean. The second experiment was valid and sufficient for classification.

 

Opacity and Permeability Values of the First Experiment

For each treatment group (negative control solution, test item and positive control), three replicates were measured.

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

 

Table Absorbance and Opacity Values Negative Control

Parameter	Negative Control
Absorbance before exposition	0.1470	0.1538	0.1572
Absorbance after exposition	0.1946	0.1689	0.2103
Opacity before exposition	1.4028	1.4250	1.4362
Opacity after exposition	1.5653	1.4754	1.6229
Opacity Difference	0.1625	0.0504	0.1868

Mean opacity difference of the negative control is 0.1332.

 

Table Absorbance and Opacity Values Test Item and Positive Control

Parameter	Test Item3-Acetylpyridine			Positive Control
Absorbance before exposition	0.1266	0.1427	0.1681	0.1947	0.1535	0.1125
Absorbance after exposition	1.4215	1.4031	1.4020	1.9553	1.4636	2.0453
Opacity before exposition	1.3384	1.3890	1.4727	1.5657	1.4240	1.2957
Opacity after exposition	26.3937	25.2988	25.2348	90.2194	29.0804	110.9941
Opacity Difference	25.0552	23.9098	23.7622	88.6537	27.6564	109.6984

 

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:

 

Table Optical density at 490 nm

Replicate	Negative Control			Test Item 3-Acetylpyridine			Positive Control
Measured values	0.0181	0.0290	0.0133	0.4614	0.4629	0.2412	0.0873	0.2001	0.2144
*Corrected values	0.0905	0.1450	0.0665	2.3070	2.3145	1.2060	0.4365	1.0005	1.0720
Mean	0.1007			--

*Note: In order to correct the path length, a factor of 5 was taken into account when calculating the IVIS.

 

IVIS Values of the First Experiment

IVIS was calculated using the values in tables and the equation stated above.

Example:

IVIS (Test Item 3-Acetylpyridine, Repl. 1) = (25.0552– 0.1332) + [15 * (2.3070– 0.1007)] = 58.02

 

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

 

Table IVIS

Test Group	IVIS	Mean IVIS	Relative Standard Deviation IVIS
Negative Control 0.9% NaCl	1.52	1.64	32.3%
	2.23
	1.18
Test Item 3-Acetylpyridine	58.02	51.74	19.3%
	56.98
	40.21
Positive Control DMF undiluted	93.56	86.24	48.7%
	41.02
	124.14

 

 

Opacity and Permeability Values of the Second Experiment

For each treatment group (negative control solution, test item and positive control), three replicates were measured.

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

 

Table Absorbance and Opacity Values Negative Control

Parameter	Negative Control
Absorbance before exposition	0.1510	0.1524	0.1513
Absorbance after exposition	0.2742	0.2410	0.2125
Opacity before exposition	1.4158	1.4204	1.4168
Opacity after exposition	1.8802	1.7418	1.6312
Opacity Difference	0.4644	0.3214	0.2144

Mean opacity difference of the negative control is 0.3334.

 

Table Absorbance and Opacity Values Test Item and Positive Control

Parameter	Test Item3-Acetylpyridine			Positive Control
Absorbance before exposition	0.1718	0.1233	0.1739	0.1920	0.1791	0.2384
Absorbance after exposition	1.3855	1.2214	1.3230	1.4546	1.2253	1.4819
Opacity before exposition	1.4853	1.3283	1.4925	1.5560	1.5104	1.7314
Opacity after exposition	24.2941	16.6495	21.0378	28.4839	16.7996	30.3319
Opacity Difference	22.8088	15.3211	19.5453	26.9280	15.2892	28.6005

 

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:

 

Table Optical density at 490 nm

Replicate	Negative Control			Test Item3-Acetylpyridine			Positive Control
Measured values	-0.0009	-0.0013	-0.0005	0.3908	0.2593	0.2781	0.0695	0.0689	0.0693
*Corrected values	-0.0045	-0.0065	-0.0025	1.9540	1.2965	1.3905	0.3475	0.3445	0.3465
Mean	-0.0045			--

*Note: In order to correct the path length, a factor of 5 was taken into account when calculating the IVIS.

 

IVIS Values of the Second Experiment

IVIS was calculated using the values in tables and the equation stated above.

Example:

IVIS (Test Item3-Acetylpyridine, Repl. 1) = (22.8088–0.3334) + [15 * (1.9540 – (-0.0045))] = 51.85

 

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

 

Table IVIS

Test Group	IVIS	Mean IVIS	Relative Standard Deviation IVIS
Negative Control 0.9% NaCl	0.40	0.27	43.6%
	0.22
	0.18
Test Item 3-Acetylpyridine	51.85	42.16	21.0%
	34.50
	40.14
Positive Control DMF undiluted	31.88	28.53	25.5%
	20.19
	33.53

 

 

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 control has to show an IVIS ≤ 3.

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

 

Table Validity

Parameter	Criterion	Found	Assessment
IVIS of negative control 0.9% NaCl	≤ 3	1.64 (first experiment) 0.27 (second experiment)	ok
IVIS of positive control DMF undiluted	22.80 – 123.60	86.24 (first experiment) 28.53 (second experiment)	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 (Jul. 2013), a substance with an IVIS > 3 and ≤ 55 induces effects on the cornea, that cannot be classified in an UN GHS Category.

 

Table Classification Scheme

IVIS	UN GHS Category Eye Damage
≤ 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 in both experiments.

In the first experiment, the positive control induced serious eye damage, which would be classified as GHS category 1. In the second experiment, the positive control showed effects on the cornea of the bovine eye.

The test item 3-Acetylpyridine showed effects on the cornea of the bovine eye. The calculated IVIS (in vitro irritancy score) is 51.74 in the first experiment and 42.16 in the second experiment.

Interpretation of results:

other: inconclusive, no prediction can be made

Conclusions:

Testing was performed via a GLP OECD 437 guideline study on the registered substance itself. The present in vitro method is recommended in a tiered testing approach and the validity criteria are met, making the results sufficiently reliable to assess the corrosivity of 3-Acetylpyridine to the eye. The present in vitro method allows the identification of corrosive chemical substances and mixtures or of substances which do not require classification.
Two experiments were performed. The first experiment was insufficient for classification because 2 of the 3 replicates gave discordant predictions from the mean. The second experiment was valid and sufficient for classification. Under the conditions of this study, the test item 3-Acetylpyridine showed effects on the cornea of the bovine eye. The calculated IVIS (in vitro irritancy score) is 51.74 in the first experiment and 42.16 in the second experiment.
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 an UN GHS Category for eye damage.
Hence, no conclusion can be drawn whether the substance needs to be classified as eye irritant, for a clear distinction an in vivo study would be required based on the current state of the art. However, based on the tonnage band o the substance, in vivo testing is not required, and with regard to animal welfare no further testing will be performed and the result of the present study will be considered inconclusive.

Executive summary:

In an OECD 437 (in vitro eye corrosion) study under GLP, two experiments were performed. The first experiment was insufficient for classification because 2 of the 3 replicates gave discordant predictions from the mean. The second experiment was valid and sufficient for classification.

Bovine corneas were used. They were collected from slaughtered cattle which were between 12 and 60 months old.

The test item 3-Acetylpyridine was brought onto the cornea of a bovine eye which had been incubated with cMEM without phenol red at 32 ± 1 °C for 1 h and whose opacity had been measured. The test item was incubated on the cornea for 10 min. at 32 ± 1 °C. After removal of the test item and 2 h post-incubation, 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 in both experiments. The calculated IVIS (in vitro irritancy score) is 1.64 in the first experiment and 0.27 in the second experiment.

Dimethylformamide (DMF) undiluted was used as positive control. In the first experiment, the positive control induced serious eye damage on the cornea and falls within two standard deviations of the current historical mean. The calculated IVIS (in vitro irritancy score) is 86.24. In the second experiment, the positive control induced effects on the cornea and falls within two standard deviations of the current historical mean. The calculated IVIS (in vitro irritancy score) is 28.53.

 

Under the conditions of this study, the test item 3-Acetylpyridine showed effects on the cornea of the bovine eye. The calculated IVIS (in vitro irritancy score) is 51.74 in the first experiment and 42.16 in the second experiment.

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 an UN GHS Category for eye damage.

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There is one study available according to OECD guideline 439, which allows the distinction between irritating and non-irritating substances and mixtures. The other available study was previously performed within a tiered testing strategy according to OECD guideline 431, which allows the distinction between corrosive and non-corrosive substances and mixture. As the OECD 431 study revealed that 3-Acetylpyridin needs to be classified as not corrosive to skin, but an irritating effect could not be excluded, the OECD 439 study was performed. Here, the test item is considered as irritant to skin according to the guideline. Both studies are classified as Klimisch 1, the guidelines are validated and no indication is given that the results are not relevant for human risk assessment.

Similar quality considerations apply for an OECD 437 eye irritation / corrosion study.The calculated IVIS (in vitro irritancy score) is 51.74 in the first experiment and 42.16 in the second experiment. Hence, the study is inconclusive for a definite classification, as a substance with an IVIS > 3 and ≤ 55 induces effects on the cornea, that cannot be classified in an UN GHS Category for eye damage. Nevertheless the tonnage-driven data requirements under REACH are fully met, as according to Annex VII only in vitro data is required, and no additional testing in vivo must be performed.

Justification for selection of skin irritation / corrosion endpoint:
One of two equally reliable high quality in vitro studies. The chosen study was performed according to OECD guideline 439, which allows the distinction between irritating and non-irritating substances and mixtures. The other available study was previously performed within a tiered testing strategy according to OECD guideline 431, which allows the distinction between corrosive and non-corrosive substances and mixture. As the OECD 431 study revealed that 3-Acetylpyridin needs to be classified as not corrosive to skin, but an irritating effect could not be excluded, the OECD 439 study was performed and chosen here as it allows a refined classification.

Justification for selection of eye irritation endpoint:
Only study available. The given, tonnage driven data do not allow a distinct conclusion whether the substance needs to be classified as eye irritant or not.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

The available OECD 431 study revealed that 3-Acetylpyridin needs to be classified as not corrosive to skin. In the OECD 439 study,after the treatment with the test item, the relative absorbance values were reduced to 46.6 %. This value is below the threshold for irritation potential (50%). Leading to the conclusion that the test item is irritating to the skin.

In the OECD 437 eye irritation / corrosion study, the calculated IVIS (in vitro irritancy score) is 51.74 in the first experiment and 42.16 in the second experiment. Hence, the study is inconclusive for a definite classification, as a substance with an IVIS > 3 and ≤ 55 induces effects on the cornea, that cannot be classified in an UN GHS Category for eye damage.