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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Skin irritation:

- in vivo (rabbit): slightly/moderately irritating

Eye irritation:

- WoE: not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is performed according to an unspecified guideline unspecified, and provides acceptable basic data.
Qualifier:
according to guideline
Guideline:
other: no data on guideline available
Deviations:
not applicable
Principles of method if other than guideline:
The test substance was applied to the clipped dorsum of 8 rabbits for 4 hours under individual semi-occlusive patches. Reaction grades for erythema, oedema, cracking and scaling were assessed 4, 24, 48, and 72 hours after treatment by using grades ranging from "a"(very slight) to "h"(severe). An overall irritation score was assigned to each tested substance ranging from 0 (normal skin) to 7 (extreme).
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 9-12 weeks
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped 3-4 days before test start, animals in the telogen phase of hair growth were selected
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
0, 24, 48 and 72 hours after treatment, and occasionally up to 7 days after treatment.
Number of animals:
8
Details on study design:
TEST SITE
- Area of exposure: dorsal surface
- Type of wrap if used: 2.5 cm2 of cotton gauze (8 ply folded in two) laid on a piece of thin flexible polythene (3 cm x 3 cm) attached to a piece of zinc oxide plaster (9 cm x 2.5 cm)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): treatment site wiped clean of excess material
- Time after start of exposure: upon patch removal (after 4 hrs)
Irritation parameter:
erythema score
Basis:
mean
Time point:
24 h
Score:
1.6
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
mean
Time point:
48 h
Score:
1.4
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
1.4
Max. score:
4
Reversibility:
no data
Remarks:
after 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
24 h
Score:
1.7
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
48 h
Score:
1.6
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
1.7
Max. score:
4
Reversibility:
no data
Remarks:
after 72 hours
Irritant / corrosive response data:
no other data
Other effects:
no data

Overall Irritation score for each animal

 Animal number 265 272 288  291  311  313  317  322   Total irritation score per group
 Group                  
 Diethyl Phtalate  1 1  1  -  1  1  1  0   6
 Geraniol  3 3  3  -  2  4  4  3  22
 Peppermint Flavour - Arvensis  2 3  3  -  3  3  4  3  21 

Distribution of overall irritation scores (0 -7) within each treatment group

 Overall Irritation Scores 0  1  2  3  4  5  6  7 
 Group                
 Diethyl Phtalate  1 6             
 Geraniol      1 4  2       
 Peppermint Flavour - Arvensis      1 5  1       

In order to classify the test substance, the irritation scoring from "a" to "h" is converted to the grading of skin reactions as defined by OECD Guideline for the testing of chemicals No. 404: Acute Dermal Irritation/Corrosion.

The conversion for erythema:

 Reaction Grades in this study  OECD grading of skin reactions
a (marginal/very slight)  1 (very slight)
 b (slight)  1 (very slight)
 c (fairly distinct)  2 (well defined)  
 d (quite distinct)  2 (well defined)
 e (becoming well developed)  2 (well defined)
 f (well developed)  3 (moderate to severe)
 g (becoming severe)  3 (moderate to severe)
 h (severe)  4 (severe)

The conversion for oedema:

Reaction Grades in this study   OECD grading of skin reactions
 a (marginal/very slight) 1 (very slight) 
 b (slight) 2 (slight) 
 c (fairly distinct) 2 (slight) 
 d (quite distinct) 2 (slight) 
 e (becoming well developed) 3 (moderate) 
 f (well developed) 3 (moderate) 
 g (becoming severe) 4 (severe) 
 h (severe)  4 (severe)
Interpretation of results:
other: not irritating
Remarks:
Based on CLP criteria
Conclusions:
The overall Irritation Score for cornmint oil (Peppermint Flavour - Arvensis) was slightly irritating towards rabbits under the conditions of this test. After conversion of the used irritation scores to the grading of skin reactions as defined by OECD Guideline for the testing of chemicals No. 404: Acute Dermal Irritation/Corrosion, it was concluded that cornmint oil does not have to be classified as irritating in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).
Executive summary:

Cornmint oil (Peppermint Flavour - Arvensis), two control substances (Diethyl Phtalate and Geraniol), and Peppermint Flavour - Brazilian were applied to the clipped dorsum of 8 rabbits for 4 hours under individual semi-occlusive patches. Reaction grades for erythema, oedema, cracking and scaling were assessed 4, 24, 48, and 72 hours after treatment by using grades ranging from "a" (very slight) to "h" (severe). An overall irritation score was assigned to each tested substance ranging from 0 (normal skin) to 7 (extreme). The overall irritation score for Peppermint Flavour - Arvensis was 3 (Slight/moderate erythema and oedema at 24 hours. The reaction generally reduced to slight at 72 hours, but sometimes the slight/moderate reaction was maintained.

In order to classify Peppermint Flavour - Arvensis according to the current guidelines, the reaction grades wee converted to OECD grading of skin reactions. This resulted in an OECD grading for Peppermint Flavour - Arvensis of 1.5 for erythema (very slight - well defined) and 1.7 for oedema (very slight - slight). It is concluded that cornmint oil does not need to be classified as irritating to the skin based on the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
31-Aug-2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test was conducted according to OECD Test Guideline No. 437, 2009, under GLP Standards, and QA.
Qualifier:
according to guideline
Guideline:
other: OECD Guideline for Testing of Chemicals 437: Bovine Corneal Opacity and Permeability (BCOP) Test Method for Identifying Ocular Corrosives and Severe Irritants (September, 2009)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Species:
other: not relevant: in vitro test
Strain:
other: Bovine
Details on test animals or tissues and environmental conditions:
BOVINE EYES:
- Source: Bovine eyes from young cattle were obtained from the slaughterhouse, where the eyes were excised by a slaughterhouse employee as soon as possible after slaughter.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent vehicle
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 ul per cornea

NEGATIVE CONTROL
- Amount(s) applied (volume or weight with unit): 750 ul of physiological saline per cornea

POSITIVE CONTROL
- Amount(s) applied (volume or weight with unit): 750 ul per cornea
- Concentration (if solution): 10% (w/v) Benzalkonium Chloride
Duration of treatment / exposure:
Exposure: 10 minutes
Post incubation period: 120 minutes
Observation period (in vivo):
Not applicable
Details on study design:
TEST SITE: Isolated bovine cornea

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, 3 times
- Time after start of exposure: 10 minutes

SCORING SYSTEM:
- After the 10 minutes exposure and washing step, the corneas were incubated for 120 +/- 10 minutes at 32 °C. After the completion of the incubation period opacity determination was performed by sodium fluorecein treatment. Incubation 90 min. Optical density of the medium determined at 490 nm.
- The mean opacity and mean permeability values (OD490) were used for each treatment group to calculate an in vitro score:
In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value).

TOOL USED TO ASSESS SCORE: opacitymeter and microplate reader.

DATA EVALUATION: A test substance that induces an IVIS ≥ 55.1 is defined as a corrosive or severe irritant.
Irritation parameter:
in vitro irritation score
Run / experiment:
mean at 10 minutes
Value:
4.3
Vehicle controls validity:
not specified
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
No pH effect of the test substance was observed on the rinsing medium.
Interpretation of results:
other: not severe irritant or corrosive
Remarks:
based on CLP criteria
Conclusions:
In the in vitro Bovine Corneal Opacity and Permeability test, cornmint oil (mentha arvensis) did not induce ocular irritation through both endpoints, opacity and permeability, resulting in a mean in vitro irritancy score of 4.3 after 10 minutes of treatment. It is concluded that this test is valid and that Cornmint oil (mentha arvensis) is not severe irritant or corrosive in the BCOP test under the experimental conditions described in the report.
Executive summary:

This in vitro study was performed according to OECD Guideline 437 (2009) to assess the corneal irritation and damage potential of Cornmint oil (mentha arvensis) by means of the Bovine Corneal Opacity and Permeability Assay (BCOP) using fresh isolated bovine corneae. The negative control responses of the opacity and permeability values were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas. The mean in vitro irritancy score of the positive control (10% (w/v) Benzalkonium Chloride) was 119 and was within the historical positive control data range. It was therefore concluded that the test conditions were adequate and that the test system functioned properly. Cornmint oil (mentha arvensis) did not induce ocular irritation through both endpoints, opacity and permeability, resulting in a mean in vitro irritancy score of 4.3 after 10 minutes of treatment. Finally, it is concluded that this test is valid and that Cornmint oil (mentha arvensis) is not severe irritant or corrosive in the BCOP test under the experimental conditions described in the report.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1974
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Read across from peppermint oil. The documentation is a summary of methods and results, individual scores are not included.
Qualifier:
no guideline followed
Principles of method if other than guideline:
In an eye irritation test following the method of Draize, 0.1 ml of 10, 20, 30, 40, 50, or 60% test substance in olive oil was applied to the right eye (conjunctival sac) of rabbits (8 animals/dose group). The upper and lower lids were held closed for one minute. Afterwards, the eyes of 4 animals were rinsed for 1 minute with physiological saline and those of the remaining 4 were not rinsed. The test substance mixture was warmed at the 3 highest concentrations to keep the mixture fluid.
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
No data on test animals and environmental conditions.
Vehicle:
other: Olive oil
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): 10, 20, 30, 40, 50, and 60%
Duration of treatment / exposure:
1 minute and 24 hours
Observation period (in vivo):
24 hours
Number of animals or in vitro replicates:
48 (8/dose group)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): In each dose group the eyes of 4 animals were rinsed for 1 minute with physiological saline, and those of the remaining 4 were not rinsed.
- Time after start of exposure: 1 minute

SCORING SYSTEM: No data

TOOL USED TO ASSESS SCORE: No data
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Remarks:
no effects observed in all concentrations, no individual scores provided
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Remarks:
no effects observed in all concentrations, no individual scores provided
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Remarks:
no effects observed in all concentrations, no individual scores provided
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Remarks:
no effects observed in all concentrations, no individual scores provided
Irritant / corrosive response data:
At 10, 20, 30, 40, 50, or 60% no effects and no reactions were observed.
Other effects:
no other effects reported
Interpretation of results:
study cannot be used for classification
Remarks:
Based on CLP criteria
Conclusions:
At 10, 20, 30, 40, 50, and 60% no effects and no reactions were observed. Under the conditions of this study, 10 to 60% test substance in olive oil was not an eye irritant in rabbits.
Executive summary:

In an eye irritation test following the method of Draize, 0.1 ml of 10, 20, 30, 40, 50, or 60% test substance, Brazilian menthol (peppermint oil), diluted in olive oil, was applied to the right eye (conjunctival sac) of rabbits (8 animals/dose group). The upper and lower lids were held closed for one minute. Afterwards, the eyes of 4 animals were rinsed for 1 minute with physiological saline and those of the remaining 4 were not rinsed. The test substance mixture was warmed at the 3 highest concentrations to keep the mixture fluid. At 10, 20, 30, 40, 50, or 60% no effects and no reactions were observed. Under the conditions of this study, 10 to 60% Brazilian menthol (peppermint oil) in olive oil was not an eye irritant in rabbits. The documentation is a summary of methods and results, individual scores are not included. Therefore, no conclusion on classification in accordance with 67/548/EEC and 1272/2008/EC can be drawn.

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
The read across justification is presented in the document attached to this record.
Reason / purpose for cross-reference:
read-across source
Number of animals or in vitro replicates:
48 (8/dose group)
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Remarks:
no effects observed in all concentrations, no individual scores provided
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Remarks:
no effects observed in all concentrations, no individual scores provided
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Remarks:
no effects observed in all concentrations, no individual scores provided
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Remarks:
no effects observed in all concentrations, no individual scores provided
Irritant / corrosive response data:
At 10, 20, 30, 40, 50, or 60% no effects and no reactions were observed.
Other effects:
no other effects reported
Interpretation of results:
study cannot be used for classification
Remarks:
based on CLP criteria
Conclusions:
The eye irritant properties of cornmint oil were assessed using read across from the source substance peppermint oil. At 10, 20, 30, 40, 50, and 60% no effects and no reactions were observed. Under the conditions of this study, 10 to 60% test substance in olive oil was not an eye irritant in rabbits.
Executive summary:

The eye irritant properties of cornmint oil were assessed using read across from the source substance peppermint oil. In an eye irritation test following the method of Draize, 0.1 ml of 10, 20, 30, 40, 50, or 60% test substance, Brazilian menthol (peppermint oil), diluted in olive oil, was applied to the right eye (conjunctival sac) of rabbits (8 animals/dose group). The upper and lower lids were held closed for one minute. Afterwards, the eyes of 4 animals were rinsed for 1 minute with physiological saline and those of the remaining 4 were not rinsed. The test substance mixture was warmed at the 3 highest concentrations to keep the mixture fluid. At 10, 20, 30, 40, 50, or 60% no effects and no reactions were observed. Under the conditions of this study, 10 to 60% Brazilian menthol (peppermint oil) in olive oil was not an eye irritant in rabbits. The documentation is a summary of methods and results, individual scores are not included. Therefore, no conclusion on classification in accordance with 67/548/EEC and 1272/2008/EC can be drawn.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The key study for skin irritation was performed with cornmint oil (Peppermint Flavour - Arvensis) and resulted in an overall irritation score of 3 indicating slight/moderate erythema and oedema at 24 hours. After conversion of the used irritation scores to the grading of skin reactions as defined by OECD Guideline for the testing of chemicals No. 404: Acute Dermal Irritation/Corrosion, it could be concluded that cornmint oil does not have to be classified as irritating in accordance with 67/548/EEC or 1272/2008/EC.

As the study was not performed according to current guidelines with an irregular scoring system, and the major constituent L-menthol is classified as irritating to the skin and present at levels higher than the thresholds mentioned for classification and labeling (in both 68/548/EEC and 1272/2008/EC), the essential oils belonging to the mint category are considered to be irritating to the skin.

The conclusion on eye irritation was based on a Weight of Evidence approach. An in vitro BCOP test in accordance with OECD437 was performed with Cornmint oil. Results show a mean in vitro irritancy score (IVIS) of 4.3 indicating that the substance is not severe irritant or corrosive (A substance that induces an IVIS ≥ 55.1 is defined as a corrosive or severe irritant).

Additionally, an in vivo eye irritation test with category member peppermint oil was available and used for read across. In this test, peppermint oil was applied to the eyes (conjunctival sac) of eight rabbits per dose group following the method of Draize. Afterwards, the eyes of 4 animals were rinsed for 1 minute with physiological saline and those of the remaining 4 were not rinsed. At 10, 20, 30, 40, 50, or 60% no effects and no reactions were observed. Under the conditions of this study, 10 to 60% Brazilian menthol (peppermint oil) in olive oil was not an eye irritant in rabbits. The documentation is a summary of methods and results, individual scores are not included. Therefore, definite conclusions on classification in accordance with 67/548/EEC and 1272/2008/EC cannot be drawn based on the available study results for cornmint oil.

However, the major constituent L-menthol is classified for Eye Irritation Category 2 according to CLP (Regulation 1272/2008/EC). As this constituent is present at levels higher than the thresholds mentioned for classification and labelling in that Regulation, the essential oils belonging to the mint category can be considered to be irritating to the eye and should also be classified with Eye Irritation Category 2.

According to the Dangerous Substances Directive (67/548/EEC), L-menthol is not classified as an eye irritant and therefore classification of the essential oils belonging to the mint category as eye irritant is also not required.

Justification for selection of skin irritation / corrosion endpoint:

The selected study is the key study for the skin irritation endpoint.

Justification for selection of eye irritation endpoint:

No selection is made as a Weight of Evidence approach was followed which is described below.

Effects on skin irritation/corrosion: slightly irritating

Justification for classification or non-classification

Based on the key information for skin irritation/corrosion, the substance Cornmint oil needs to be classified as irritating to the skin in accordance with the CLP Regulation (1272/2008/EC) and Dangerous Substances Directive (67/548/EEC).

Based on the WoE information for eye irritation, the substance Cornmint oil needs to be classified as irritating to the eye in accordance with the CLP Regulation (1272/2008/EC) but under the Dangerous Substances Directive (67/548/EEC).