2-propylheptan-1-ol

Endpoint summary

Description of key information

- skin:
   rabbit, 24 h: irritant (TSCAT, OTS 0538594, Doc I.D. 88-920007511, Monsanto Company, 1979; reliable with restrictions)
   GLP In Vitro EPISKIN Skin Irritation Test: irritant (Evonik Oxeno GmbH, 2009; reliable with restrictions)
- eye:
   rabbit, 24 h: mildly irritant (TSCAT, OTS 0538594, Doc I.D. 88-920007511, Monsanto Company, 1979; reliable with restrictions)
   rabbit: mildy irritant (Smyth, H.F. et al., 1962; reliable with restrictions)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

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

Principles of method if other than guideline:

The test was conducted in accordance with the Standard Operating Procedure, In Vitro Skin Irritation Test: Human Epidermis Model (L'Oreal, 2005), supplied by L'Oreal (leading laboratory in the validation of the test for ECVAM) and the OECD Guideline For The Testing of Chemicals (OECD 2008).

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-Propylheptan-1-ol
- Physical state: Clear, colourless liquid
- Analytical purity: 96.2%
- Lot/batch No.: 16.06.2008
- ID Nr.: 0649/82526
- Expiration date of the lot/batch: July 2009
- Storage condition of test material: Room temperature

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Vehicle:

unchanged (no vehicle)

Details on test system:

SKIN DISC PREPARATION
- Procedure used: The maintenance medium was pre-warmed to 37° C. The tissues were removed from the agar and placed into wells of 12 well plates containing 2 ml pre-warmed maintenance medium per well. The tissues were incubated for a minimum of 24 hours at 37 ± 2°C in a humidified atmosphere of 5% C02 in air.
- Quality control for skin discs:histological scoring(HES stained vertical paraffin sections, n = 6): well-dlfferentiated epidermis consisting of a basal layer, several spinousand granular layers and a thick stratum corneum; IC50 determination (after SDS treatment)

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37 ± 2°C
- Temperature of post-treatment incubation (if applicable): 37 ± 2°C

REMOVAL OF TEST MATERIAL AND CONTROLS
- Number of washing steps: 1
- Observable damage in the tissue due to washing: not specified
- Modifications to validated SOP: no

DYE BINDING METHOD
- Dye used in the dye-binding assay: MTT
- Spectrophotometer: not specified
- Wavelength: 540 nm
- Filter: not specified
- Filter bandwidth: not specified

NUMBER OF INDEPENDENT TESTING RUNS / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1

PREDICTION MODEL / DECISION CRITERIA
If the mean tissue viability was equal or less than 50% of the negative control value, the sample was classed as Irritant R38 (EU classification).

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 µL
- Concentration (if solution): undiluted

VEHICLE
- Amount(s) applied (volume or weight with unit): 10 µL
- Concentration (if solution): undiluted

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 10 µL
- Concentration (if solution): 5% in sterile water

Duration of treatment / exposure:

15 ± 0.5 minutes

Duration of post-treatment incubation (if applicable):

42 ± 1 hour

Number of replicates:

3

Irritation / corrosion parameter:

% tissue viability

Value:

10.9

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

positive indication of irritation

Other effects / acceptance of results:

- OTHER EFFECTS:
- Visible damage on test system: not specified
- Direct-MTT reduction: no
- Colour interference with MTT: no

DEMONSTRATION OF TECHNICAL PROFICIENCY: yes

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
- Acceptance criteria met for variability between replicate measurements: yes

- Negative control:

The mean absorbance of the triplicate negative control values was 0.618 which was above the minimum acceptance value of 0.6. The standard deviation of the % viability was 2.8 which was below the maximum acceptance value of 18.

- Positive control: The mean viability of the positive control was 12.5% ± 6.0 of the negative control. These were below the maximum acceptance values of 30% viability and SD of 18.

There was no colour change in the test substance, 2-Propylheptan-l-ol (MTT) solution or the water control (MTT) solution after three hours incubation in the dark at 37 ±2°C in a humidified atmosphere of5% CO2 in air. The test substance had not interacted with the MTT.

Sample	Tissue viability as percentage of mean OD negative control
	Replicate Tissues			Mean +/- SD	Prediction MTT endpoint
Negative Control	102.7	100.2	97.1	100.0 +/- 2.8	not applicable
Positive control	7.7	19.3	10.4	12.5 +/- 6.0	irritant
2-Propylheptan-I-ol	14.7	8.1	9.9	10.9 +/- 3.4	irritant

The Standard Operating Procedure, In Vitro Skin Irritation Test: Human Epidermis Model EPISKIN, EPISKIN Skin Irritation Test-42hours (L'Oreal 2005) recommends analysis of IL-1alpha if the MTT mean tissue viability of the test material is >/= 50%. As the mean tissue viability of test material, 2-Propylheptan-1-ol, was 10.9 % ± 3.4, IL-1 alpha analysis of the medium was not required.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

It was concluded that the test material with a mean tissue viability of 10.9 % ± 3.4, is predicted as a skin irritant.

Executive summary:

The objective of the test was to assess the skin irritancy, in vitro, of the test substance.

The test material was applied to EPISKIN human epidermis skin constructs. The constructs consisted of normal, human-derived epidermal keratinocytes, which had been cultured to form a multilayered, highly differentiated model of the human epidermis with a functional multilayered stratum corneum. The cell viability of the multi layers was determined by mitochondrial dehydrogenase activity. The prediction model uses the percentage viability values (compared to negative control viability) to identify irritant and non-irritant materials.

The test material elicited a mean tissue viability of 10.9 ±3.4 % and was predicted as irritant.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to current guideline requirements and scientifically valid.

Principles of method if other than guideline:

0.5 ml of the undiluted test substance was administered to the skin of 6 New Zealand Albino Rabbits for 24 h to determine the irritant potential of the test substance (according to Federal Hazardous Substance Act).

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-Propylheptanol
- Lot/batch No.: NBP 1282594-A

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

not specified

Preparation of test site:

other: intact and abraded

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml undiluted

Duration of treatment / exposure:

24 h

Observation period:

7 days (168 h)

Number of animals:

6

Details on study design:

SCORING SYSTEM: according to Draize

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(animal 1-6)

Time point:

other: 24-48 - 72 h

Score:

3.78

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: intact skin

Irritation parameter:

edema score

Basis:

mean

Remarks:

(animal 1-6)

Time point:

other: 24 - 48 - 72 h

Score:

3.39

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: intact skin

Other effects:

Severe defatting effect - skin sloughed off in ten to seventeen days.
There was no injury in depth.

Exposition:	24 h (intact skin)
Animal	Reading	Erythema	Edema
1	4 h	1	1
2	4 h	1	1
3	4 h	1	1
4	4 h	1	1
5	4 h	1	1
6	4 h	1	1
1	24 h	4	3
2	24 h	4	4
3	24 h	4	4
4	24 h	4	4
5	24 h	4	3
6	24 h	3	4
1	48 h	4	3
2	48 h	4	3
3	48 h	4	4
4	48 h	4	4
5	48 h	3	3
6	48 h	3	3
1	72 h	4	3
2	72 h	4	3
3	72 h	4	3
4	72 h	4	4
5	72 h	3	3
6	72 h	4	3
1	7 d	0	0
2	7 d	0	0
3	7 d	0	0
4	7 d	0	0
5	7 d	0	0
6	7 d	0	0
1	24 - 72 h	4	3.0
2	24 - 72 h	4	3.3
3	24 - 72 h	4	3.7
4	24 - 72 h	4	4.0
5	24 - 72 h	3.3	3.0
6	24 - 72 h	3.3	3.3
mean (animal 1-6)	24 - 72 h	3.78	3.39

Exposition:	24 h (intact skin)
Animal	Reading	Erythema	Edema
1	4 h	1	1
2	4 h	1	1
3	4 h	1	1
4	4 h	1	1
5	4 h	1	1
6	4 h	1	1
1	24 h	4	3
2	24 h	4	4
3	24 h	4	4
4	24 h	4	4
5	24 h	4	3
6	24 h	3	4
1	48 h	4	3
2	48 h	4	3
3	48 h	4	4
4	48 h	4	4
5	48 h	3	3
6	48 h	3	3
1	72 h	4	3
2	72 h	4	3
3	72 h	4	3
4	72 h	4	4
5	72 h	3	3
6	72 h	4	3
1	7 d	0	0
2	7 d	0	0
3	7 d	0	0
4	7 d	0	0
5	7 d	0	0
6	7 d	0	0
1	24 - 72 h	4	3.0
2	24 - 72 h	4	3.3
3	24 - 72 h	4	3.7
4	24 - 72 h	4	4.0
5	24 - 72 h	3.3	3.0
6	24 - 72 h	3.3	3.3
mean (animal 1-6)	24 - 72 h	3.78	3.39

Primary irritation score: 7.2

The results of the abraded skin were not discussed because they are not relevant for evaluation of the test substance.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Scientifically valid.

Principles of method if other than guideline:

Eye injury in rabbits is recorded in a 10-grade ordinal series and is based upon the degree of corneal necrosis that results from instillation of various volumes and concentrations of chemical.

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-propylheptanol
- Analytical purity: not stated

Species:

rabbit

Strain:

not specified

Vehicle:

other: undiluted sample or solutions in water or propylene glycol

Controls:

not specified

Duration of treatment / exposure:

no data

Observation period (in vivo):

no data

Number of animals or in vitro replicates:

no data

Details on study design:

SCORING SYSTEM: Grade 1 indicates at most a very small area of necrosis resulting from 0.5 ml of undiluted chemical in the eye. Grade 5 indicates a so-called severe burn from 0.005 ml, and Grade 10 indicates a severe burn from 0.5 ml of a 1% solution in water or propylene glycol.

Irritation parameter:

other: degree of corneal necrosis

Time point:

other: no data available

Score:

2

Max. score:

10

The primary eye irritation was graded as 2.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2-Propylheptanol
- Lot/batch No.: NBP 1282594-A

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml undiluted

Duration of treatment / exposure:

24 h

Observation period (in vivo):

7 days (168 h)

Number of animals or in vitro replicates:

6

Details on study design:

SCORING SYSTEM: according to Draize

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 - 72 h

Score:

16.3

Max. score:

110

Reversibility:

fully reversible within: 168 h

Irritant / corrosive response data:

Immediate : Discomfort was moderate with eyes tightly closed;
10 Min.: Slight erythema, copious discharge;
1 h: Slight to moderate erythema, copious discharge;
24 h: Areas of barely perceptible corneal dullness, iris reaction to light was sluggish, moderate to severe erythema, very slight edema, copious discharge;
48 - 120 h: Gradual improvement;
168 h: All scored zero;

Animal	Reading	Cornea	Iris	Conjunctivae
1	1 hr	0	0	10
2	1 hr	0	0	10
3	1 hr	0	0	8
4	1 hr	0	0	8
5	1 hr	0	0	8
6	1 hr	0	0	8
1	24 hrs	5	5	14
2	24 hrs	10	5	14
3	24 hrs	5	5	14
4	24 hrs	10	5	12
5	24 hrs	15	5	14
6	24 hrs	15	5	14
1	48 hrs	0	0	12
2	48 hrs	5	0	8
3	48 hrs	0	0	8
4	48 hrs	5	0	8
5	48 hrs	10	5	14
6	48 hrs	5	0	8
1	72 hrs	0	0	6
2	72 hrs	0	0	4
3	72 hrs	0	0	4
4	72 hrs	0	0	4
5	72 hrs	5	0	8
6	72 hrs	0	0	4
1	5 days	0	0	4
2	5 days	0	0	2
3	5 days	0	0	4
4	5 days	0	0	2
5	5 days	0	0	4
6	5 days	0	0	2
1	7 days	0	0	0
2	7 days	0	0	0
3	7 days	0	0	0
4	7 days	0	0	0
5	7 days	0	0	0
6	7 days	0	0	0
1	24/48/72 hrs	1.7	1.7	10.7
2	24/48/72 hrs	5.0	1.7	8.7
3	24/48/72 hrs	1.7	1.7	8.7
4	24/48/72 hrs	5.0	1.7	8.0
5	24/48/72 hrs	10.0	3.3	12.0
6	24/48/72 hrs	6.7	1.7	8.7
mean animal 1-3	24/48/72 hrs	5.0	1.9	9.4

Animal	Reading	Corneal Opacity	Iris	Conjunctivae Redness
1	1 hr	0	0	10
2	1 hr	0	0	10
3	1 hr	0	0	8
4	1 hr	0	0	8
5	1 hr	0	0	8
6	1 hr	0	0	8
1	24 hrs	5	5	14
2	24 hrs	10	5	14
3	24 hrs	5	5	14
4	24 hrs	10	5	12
5	24 hrs	15	5	14
6	24 hrs	15	5	14
1	48 hrs	0	0	12
2	48 hrs	5	0	8
3	48 hrs	0	0	8
4	48 hrs	5	0	8
5	48 hrs	10	5	14
6	48 hrs	5	0	8
1	72 hrs	0	0	6
2	72 hrs	0	0	4
3	72 hrs	0	0	4
4	72 hrs	0	0	4
5	72 hrs	5	0	8
6	72 hrs	0	0	4
1	5 days	0	0	4
2	5 days	0	0	2
3	5 days	0	0	4
4	5 days	0	0	2
5	5 days	0	0	4
6	5 days	0	0	2
1	7 days	0	0	0
2	7 days	0	0	0
3	7 days	0	0	0
4	7 days	0	0	0
5	7 days	0	0	0
6	7 days	0	0	0
1	24/48/72 hrs	1.7	0.0	10.7
2	24/48/72 hrs	5.0	1.7	8.7
3	24/48/72 hrs	1.7	1.7	8.7
4	24/48/72 hrs	5.0	1.7	8.0
5	24/48/72 hrs	10.0	3.3	12.0
6	24/48/72 hrs	6.7	1.7	8.7
mean animal 1-3	24/48/72 hrs	5.0	1.7	9.4

The average irritation score was 16.3.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

skin:

In a GLP in vitro EPISKIN Skin Irritation Test (Val. 2, Evonik Oxeno GmbH, 2009) the test substance was classified as irritant potential.

The skin irritating potential is confirmed by an in vivo skin irritation/corrosion study (TSCAT, OTS 0538594, Doc I.D. 88-920007511, Monsanto Company, 1979). 0.5 ml of the undiluted test substance was administered to the skin of 6 New Zealand Albino rabbits for 24 h (according to Federal Hazardous Substance Act). The mean scores (24 - 48 -72 h) for erythema and edema were 3.78 and 3.39, respectively. All observed edema and erythema were reversible within 7 days. Additionally, a severe defatting effect was observed. This study was conducted before the implementation of GLP and OECD Guidelines.

eye:

Irritation to eyes was analyzed in a study reliable with restrictions (TSCAT, OTS 0538594, Doc I.D. 88-920007511, Monsanto Company, 1979). Six albino rabbits received a single instillation of 0.1 ml of the undiluted test substance for 24 h. The Mean Overall Irritation Score (24-48-72 h) was 16.3 (max. score: 110) and the test substance was classified as a mild eye irritant (according to Federal Hazardous Substance Act) as all effects were fully reversible within 7 days.

In an additional study, eye injury in New Zealand White rabbits was recorded in a 10-grade ordinal series and was based upon the degree of corneal necrosis that results from installation of 2-Propylheptan-1-ol into the eyes of the rabbits. The administration of the test substance resulted in a grade 2 corneal injury on a scale of 1-10. These results indicate that the test substance caused minimal corneal injury (Smyth, H.F., 1962; Val.2).

Both studies were conducted before the implementation of GLP and OECD Guidelines.

In a GLP-conform BCOP-Test conducted similar to OECD 437 the test substance was negative.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance considered to be classified for skin and eye irritation cat. 2 under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.