Oxazolidine, diheptyl~

Endpoint summary

Description of key information

Skin Irritation

REACH_irritating | rabbit | OECD 404 | #key study#

REACH_not irritating | Human | HRIPT |

Eye Irritation

REACH_not irritating | rabbit | #key study#

REACH_slightly irritating | HET-CAM | #key study#

REACH_slightly irritating | HET-CAM |

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September - October 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

2004

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

ANIMALS
- Species: Albino rabbit, New Zealand White, (SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. EC, OECD). Source: Harlan, Horst, The Netherlands.
- Number of animals: 3 males
- Age and body weight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.
- Identification: Earmark.
- Health inspection: A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.

HUSBANDRY
- Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0 °C (actual range: 21.3 - 23.1 °C), a relative humidity of 30-70% (actual range: 39 - 64%) and 12 hours artificial fluorescent light and 12 hours darkness per day.
- Accommodation: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
- Diet: Pelleted diet for rabbits (K-H from SSNIFF® Spezialdiäten GmbH, Soest, Germany) approximately 100 grams per day. Hay (TecniLab-SMI SV, Someren, The Netherlands) was provided at least three times a week.
- Water: Free access to tap water.
Results of analysis for each batch of diet (nutrients and contaminants), hay and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

7 d

Number of animals:

3

Details on study design:

The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 3 weeks later, after considering the degree of skin irritation observed in the first animal.

Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.
Each animal was treated by dermal application of 0.5 mL of the test substance. The test substance was applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.
After the final observation, the animals were sacrificed by intra-venous injection of pentobarbital Euthesate® (Ceva Sante Animale SV, Naaldwijk, The Netherlands).

Irritation parameter:

erythema score

Basis:

animal: 520

Time point:

24/48/72 h

Score:

2

Reversibility:

fully reversible within: 7 d

Irritation parameter:

erythema score

Basis:

animal: 563

Time point:

24/48/72 h

Score:

2.3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

erythema score

Basis:

animal: 564

Time point:

24/48/72 h

Score:

2.3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

edema score

Basis:

animal: 520

Time point:

24/48/72 h

Score:

1.3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

edema score

Basis:

animal: 563

Time point:

24/48/72 h

Score:

1.7

Reversibility:

fully reversible within: 7 d

Irritation parameter:

edema score

Basis:

animal: 564

Time point:

24/48/72 h

Score:

1.7

Reversibility:

fully reversible within: 7 d

Irritant / corrosive response data:

Four hours exposure to 0.5 mL of the test substance resulted in well defined or moderate to severe erythema and slight oedema in the treated skin-areas of the three rabbits. The skin irritation had
resolved within 7 days after exposure in all animals. There was no evidence of a corrosive effect on the skin.

Other effects:

Sticky and dry remnants of the test substance were present on the skin on Day 1.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2003) the test substance should be classified as: skin irritant (Category 2).

Executive summary:

Primary skin irritation/corrosion study with the test substance in the rabbit (4-hour semi-occlusive application)"

The study was carried out based on the guidelines described in:

OECD No 404, "Acute Dermal lrritation/Corrosion" (2002)

EC, Council Directive 67/548/EEC, An.V, BA (2004), "Acute Toxicity: Dermal Irritation/ Corrosion"

US EPA, OPPTS 870"2500 (1998), Acute Dermal Irritation

JMAFF Guidelines (2000) including the most recent partial revisions"

Three rabbits were exposed to 0.5 mL of the test substance by application onto clipped skin for 4 hours using a semi-occlusive dressing. Skin reactions were assessed 1, 24, 48 and 72 hours and 7 days after exposure.

Exposure to test substance resulted in well defined or moderate to severe erythema and slight oedema in the treated skin-areas of the three rabbits. The skin irritation had resolved within 7 days after exposure in all animals. Sticky and dry remnants of the test substance were present on the skin on Day 1.

Based on these results:

- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2003) the test substance should be classified as: skin irritant (Category 2).

- according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), the test substance should be

labelled as: irritating to skin (R 38).

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

August - October 2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

other: HRIPT (Human Repeated Insult Patch Test)

GLP compliance:

yes

Species:

other: human

Strain:

not specified

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

other: Paraffin

Controls:

yes, concurrent vehicle

yes, concurrent negative control

Amount / concentration applied:

40 µL

Duration of treatment / exposure:

The Induction Phase regimen comprised four (4) consecutive 24-hour application/assessment cycles.
The Challenge Phase regimen comprised four (4) consecutive 24-hour application/assessment cycles conducted on naive skin

Observation period:

6 weeks

Number of animals:

- Induction Phase: 108 subjects
- Challenge Phase: 106 subjects

Details on study design:

See "Any other information on materials and methods"

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: any assessment during the 6 weeks

Score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: any assessment during the 6 weeks

Score:

0

Irritant / corrosive response data:

In regard to the test item, no effects like edema, papules, vesicles, spreading, soap effect, fissuring, desquamation, dryness, pigmentation, folliculitis, tape reaction or crusting, were observed during the complete study.

Other effects:

None

RESULTS

Erythema grade

Grade	Visible effect	Induction Phase (number of subjects: 108)	Challenge Phase (number of subjects: 106)
0	None	108	106
1	Faint redness, entire site might not be involved	0	0
2	Moderate redness, entire site involved	0	0
3	Intense redness	0	0
-	Number of subjects manifesting effects	0	0

Incidence of miscellaneous effects

In regard to the test item, no other effects (edema, papules, vesicles, spreading, soap effect, fissuring, desquamation, dryness, pigmentation, folliculitis, tape reaction, crusting) were observed during the complete study.

In regard to Paraffin viscous (vehicle control), faint, spotty redness was detected on one subject on Thursday of Week#1.

In regard to Saline 0.9% (negative control), faint, spotty redness was detected on one subject on Thursday and Friday of Week #1.

SUMMARY

Induction Phase:

No adverse effects were detected on any of the one-hundred-and-eight (108) subjects concerning whom data were acquired.

1292 post-application assessments were conducted during this phase.

Challenge Phase:

No adverse effects were detected on any of the one-hundred-and-six (106) subjects concerning whom data were acquired.

424 post-application assessments were conducted during this phase.

Significance of the effects:

The data indicate that the test article may be considered innocuous in so far as it's capabilities to elicit the signs or symptoms of inflammation under the conditions of this patch test regimen.

FINDlNGS

The investigator met Sponsor's requirement to provide data on one hundred compliant subjects.

The data strongly support a finding that the test item, as tested, is not a skin irritant.

Interpretation of results:

GHS criteria not met

Conclusions:

On the basis of the study's observations and the lack of any data obtained during the follow-up period to the contrary, the test item, as tested, was found to possess neither skin sensitizing nor skin irritating propensities.

Executive summary:

ABSTRACT

The test item, a pale yellow liquid, was received by Product Investigations on 24 August 2007. The sample was subrnitted by Henkel KGaA for a patch test to determine whether it possesses any skin-irritating and/or sensitizing propensities. Also submitted was a sample of Paraffin viscous to serve as a vehicle control. At the request of Sponsor, the investigator provided sterile physiological saline solution to serve as a negative control.

To accomplish this, Product Investigations initiated a repeated insult patch test of the study and control articles. The regimen for each article was identical and conducted concurrently on the same study population consisting of one-hundred-and-nine (109) adult volunteers at the outset. The study was conducted in three phases, an Induction Phase of three weeks, an Intermediate/Rest Phase of two weeks, and a Challenge Phase of one week.

The regimen comprised four (4) consecutive 24-hour application/assessment cycles conducted during Weeks #1, #2, and #3. Such cycles were initiated on Monday, Tuesday, Wednesday, and Thursday of Weeks #1 and #3; and on Tuesday, Wednesday, Thursday, and Friday of Week #2, the clinic being closed on Monday of that week because of the Labor Day Holiday.

The procedure for preparing and applying a patching device was as follows: a technician delivered 40 µL of the study article evenly over the surface of the 2cm x 2cm non-woven fabric pad of an occlusive, stand-alone patching device; the technician applied the prepared device on the upper portion of the left side of a presenting subject's back. For all applications, save #8, the technician rernoved the device in the clinic after it had been in situ for approximately twenty-four hours. Five to ten minutes after she had removed the device, the technician assigned a grade in accordance with her assessment of the magnitude of the effect being manifested by the skin. The device constituting Application #8 was applied on Friday of Week #2 and removed on Saturday by the subject or helper at home. When the subject returned to the clinic on Monday of Week #3, the effect being manifested by the skin at that time was assessed and graded by a technician. The assessment and grading of effects on Friday of Week #3 marked the end of the Induction Phase for the one-hundred-and-two (102) subjects who had undergone all twelve application/assessment cycles and for whom further surveillance was not indicated.

Starting on Monday ofWeek #4, applications were continued on six subjects to make up for applications missed because of absences during the scheduled regimen.

After the effects of Application #12 were assessed and graded, a subject was given a recess until Monday, 1 October 2007.

The Challenge Phase regimen comprised four (4) consecutive 24-hour application/assessment cycles conducted on the naive skin of the study article's designated challenge site on the upper portion of the left side of each presenting subject's back.

Data were acquired on one-hundred-and-eight (108) subjects during the Initial/Induction Phase.

No data were acquired concerning the one subject who failed to return after receiving the initial application.

In regard to the test item, no adverse effects were detected on any of the one-hundred-and-eight (108) subjects during the Initial/lnduction Phase.

In regard to Paraffin viscous (vehicle control), faint, spotty redness was detected on one subject on Thursday of Week#1.

In regard to Saline 0.9% (negative control), faint, spotty redness was detected on one subject on Thursday and Friday of Week #1.

Data were acquired on one-hundred-and-six (106) subjects during the Challenge Phase. No data were acquired concerning three subjects who failed to return after the hiatus.

No adverse effects attributable to any of the articles under study were detected on any of the one-hundred-and-six (106) subjects conceming whorn data were acquired during the Challenge Phase.

On the basis of the above-cited observations and the lack of any data obtained during the follow-up period to the contrary, the test item, as tested, was found to possess neither skin sensitizing nor skin irritating propensities.

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:

key study

Study period:

September - October 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

2004

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

1998

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

ANIMALS
- Species: Albino rabbit, New Zealand White, (SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. EC, OECD). Source: Harlan, Horst, The Netherlands.
- Number of animals: 3 males
- Age and body weight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.
- Identification: Earmark.
- Health inspection: A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.

HUSBANDRY
- Conditions: Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 ± 3.0°C (actual range: 21.4 - 24.0°C), a relative humidity bf 30-70% (actual range: 44 - 66%) and 12 hours artificial fluorescent light and 12 hours darkness per day.
- Accommodation: Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
- Diet: Pelleted diet for rabbits (K-H from SSNIFF® Spezialdiäten GmbH, Soest, Germany) approximately 100 grams per day. Hay (TecniLab-SMI SV, Someren, The Netherlands) was provided at least three times a week.
- Water: Free access to tap water.
Results of analysis for each batch of diet (nutrients and contaminants), hay and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

n.a. (not rinsed)

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3

Details on study design:

The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner one week later, after
considering the degree of eye irritation observed in the first animal.
Each animal was treated by instillation of 0.1 mL of the test substance, in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.
Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any bright green stained area, indicating epithelial damage, was estimated as a percentage of the total corneal area. Since no residual test substance was seen, the treated eyes were not rinsed with tepid tap water.
After the final observation, the animals were sacrificed by intra-venous injection of pentobarbital Euthesate® (Ceva Sante Animale BV, Naaldwijk, The Netherlands).

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

Instillation of 0.1 mL of the test substance into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness (grade 1) and discharge (grade 1). The irritation had completely resolved within 24 hours. No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage. There was no evidence of ocular corrosion.

Other effects:

No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2004) and EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC).

Executive summary:

Acute eye irritation/corrosion study with Sa 34 in the rabbit

The study was carried out based on the guidelines described in:

OECD No 405 (2002) "Acute Eye Irritation / Corrosion"

EC, Council Directive 67/548/EEC, An. V, B.5, (2004) "Acute Toxicity: Eye Irritation / Corrosion"

EPA, OPPTS 870.2400 (1998): "Acute Eye Irritation"

JMAFF guidelines (2000); including the most recent partial revisions.

Single samples of 0.1 mL of the test substance were instilled into one eye of each of three rabbits.

Observations were made 1, 24, 48 and 72 hours after instillation.

Instillation of the test substance resulted in irritation of the conjunctivae, which consisted of redness and discharge. The irritation had completely resolved within 24 hours.

Based on these results the test substance does not have to be classified and has no obligatory labelling requirement for eye irritation according to the Globally Harmonized System of

Classification and Labelling of Chemicals (GHS) of the United Nations (2004) and EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC).

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

according to guideline

Guideline:

other: HET-CAM, Reaction Time Method

Principles of method if other than guideline:

Reaction-Time Method
Transparent test substances were tested by the reaction-time method. The reaction-time period and reaction intensity of effects on the CAM like haemorrhage, lysis of the vessels and protein coagulation (intravascular and/or extravascular) were visually evaluated. In order to compare the results of in vitro with in vivo experiments and to minimize effects due to biological variation of the charges of the eggs, an irritation index of the reference substance “Texapon ASV” was calculated [5% active substance, pH approx. 7]. This concentration was classified as being moderately irritating to rabbit‘s eyes.

GLP compliance:

yes

Species:

chicken

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Chorionallantoic membrane (CAM) of fertilized chicken eggs

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent positive control

Amount / concentration applied:

300 µL

Duration of treatment / exposure:

5 min.

Number of animals or in vitro replicates:

6

Details on study design:

see "Any other information on materials and methods"

Irritation parameter:

in vitro irritation score

Remarks:

Q

Run / experiment:

Mean

Value:

0.07

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

valid

Remarks:

1.00

Results test substance

Haemorrhage: 106 seconds

Lysis: 152 seconds

Coagulation: -

Irritation Indices (RI): 50.8 (SD = 4.7)

Q-value: 0.07 +/- 0.01

Results reference substance

Haemorrhage: 20 seconds

Lysis: 26 seconds

Coagulation: -

Irritation Indices (RI): 698.6 (SD = 33.3)

Q-value: 1.00 +/- 0.05

Interpretation of results:

GHS criteria not met

Conclusions:

According to the test conditions and the HET-CAM classification scheme, the undiluted test substance is classified as "slightly irritating" after contact with mucous membranes or eyes.

Executive summary:

The irritation potential of the test substance was evaluated with the in vitro method HET-CAM by analysing the time-dependent occurrence of specific effects to the membrane and/or vessels of the CAM. The individual test results were interpreted in comparison to the effects of the reference substance "Texapon ASV" [5% active substance (AS)]. This internal benchmark is defined to be a moderately irritating compound to the rabbit eye in vivo.

The test substance [90% AS] was tested undiluted by the reaction-time method.

Haemorrhage and lysis were detected following application of the test substance to the CAM.

According to the test conditions and the HET-CAM classification scheme, the undiluted test substance is classified as "slightly irritating" after contact with mucous membranes or eyes. As indicated by the study monitor, the result is in agreement with historical animal data.

Reference 3

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

March 2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

other: HET-CAM, Reaction Time Method

Principles of method if other than guideline:

Reaction-Time Method
Transparent test substances were tested by the reaction-time method. The reaction-time period and reaction intensity of effects on the CAM like haemorrhage, lysis of the vessels and protein coagulation (intravascular and/or extravascular) were visually evaluated. In order to compare the results of in vitro with in vivo experiments and to minimize effects due to biological variation of the charges of the eggs, an irritation index of the reference substance “Texapon ASV” was calculated [5% active substance, pH approx. 7]. This concentration was classified as being moderately irritating to rabbit‘s eyes.

GLP compliance:

no

Species:

chicken

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Chorionallantoic membrane (CAM) of fertilized chicken eggs

Vehicle:

other: undiluted and 50% in olive oil

Controls:

yes, concurrent positive control

Amount / concentration applied:

300 µL

Duration of treatment / exposure:

5 min.

Number of animals or in vitro replicates:

6

Details on study design:

In this study the test substance was tested undiluted and as a 50% dilution in olive oil by the reaction-time method.
The test substance was added in approx. 300 μL to six eggs with at least well developed blood vessels. The amount of the added test substance covered approx. 25 % of the CAM.

Irritation parameter:

in vitro irritation score

Remarks:

Q

Run / experiment:

Mean

Value:

0

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

valid

Remarks:

1.00 +/- 0.05

Other effects / acceptance of results:

The undiluted test substance induced no reaction in the reaction-time method till five minutes. In a pre-experiment the test substance was tested 50% diluted in olive oil, also no reaction were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test substance was predicted to be slightly irritating.

Executive summary:

The irritation potential of the test substance was evaluated with the in vitro method HET-CAM by analysing the time-dependent occurrence of specific effects to the membrane and/or vessels of the CAM. The individual test results were interpreted in comparison to the effects of the reference substance "Texapon ASV" [5% active substance (AS)]. This internal benchmark is defined to be a moderately irritating compound to the rabbit eye in vivo.

The undiluted test substance induced no reaction in the reaction-time method till five minutes.

In a pre-experiment the test substance was tested 50% diluted in olive oil, also no reaction were observed.

According to the test conditions and the HET-CAM classification scheme, the undiluted test substance is classified as "slightly irritating" after contact with mucous membranes or eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The test substance did not produce skin irritation and eye irritation, when tested in rabbit according to OECD TG 404 and 405. The HRIPT test in humans was performed with a concentration of 0.1 % of the test item, which is too low to do the assumption that the substance could be not irritating.  

The substance does not need to be classified for irritation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.