Registration Dossier

Administrative data

Description of key information

Conclusions for irritation/corrosive properties of 2,2-bis[[(2-ethyl-1-oxohexyl)oxy]methyl]propane-1,3-diyl bis(2-ethylhexanoate)(EC# 230-743-8) are based on read across from analogue substances of an existing category (pentaerythritol esters), of which the members were notified under Directive 67/548/EEC (NONS) in 2003/2004. Based on the structural similarity and information available for category members, substance EC# 230-743-8 is not classified as skin / eye irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
08 July 2003 - 18 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to OECD test guidance in compliance with GLP and reported with a valid GLP certificate. The study is read across to an analogous substance; refer to image and further information below.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
Annex V
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Species: Albino Rabbit, New Zealand White, (SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. EC, OECD). Source: Charles River Deutschland, Kisslegg, GermanyNo. of animals: 3 Males.Age and bodyweight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.Identification: Earmark.ConditionsAnimals 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: 16.1 - 23.0°C), a relative humidity of 30-70% (actual range: 43 -79%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relativehumidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.AccommodationIndividually in labelled cages with perforated floors (Scan bur, Denmark, dimensions 56x44x37.5 cm). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.DietStandard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx. 100 g. per day. Certificates of analysis were examined and retained in the NOTOX archives. In addition, pressed hay (BMI, Helmond, the Netherlands) was provided twice a week.WaterFree access to tap-water. Certificates of quarterly analysis were examined and retained in the NOTOX archives.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
3
Details on study design:
All available data relevant to the potential dermal irritation/corrosivity of the substance indicated that no severe effects were to be expected. An in-vitro skin irritation test was considered, but no validated test was found available. Therefore, this in-vivo skin irritation study was started bytreatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 7 days 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 cm2). Whenever considered necessary the treated skin areas were re-clipped at least 3 hours before the observations, tofaciltate scoring..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.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 metallne 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 water.Observations:Mortaliy/ Viabilty Twice daily.Toxicity: At least once daily.Body Weight: Day of treatment (prior to application) and at termination.Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance.The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of the untreated skin of each animal served as controls.
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
erythema score
Max. score:
1
Remarks on result:
other: Max. duration: 1 d; Max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
0.3
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
edema score
Max. score:
1
Remarks on result:
other: Max. duration: 2 d; Max. value at end of observation period: 0 (related to all animals)
Irritant / corrosive response data:
Four hours exposure to 0.5 ml of HATCOL 3331 resulted in very slight erythema and/or very slight oedema in the treated skin-areas of the three rabbits. The skin irritation had resolved within 24 hours in two animals and within 48 hours In the other animal.
Other effects:
CorrosionThere was no evidence of a corrosive effect on the skin.ColourationNo staining of the treated skin by the test substance was observed. Sticky remnants of the test substance were present on the edges of the treated skin area on day 1.Toxicity I MortalityNo symptoms of systemic toxicity were observed in the animals during the test period and no mortaliy occurred.
Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
Read across to structural analogue. Structural details are listed above. Based on the results and according to the EC criteria for classification and labelling requirements, HATCOL 3331 does not have to be classified and has no obligatory labelling requirement for skin irritation.
Executive summary:

Read across to structural analogue. Structural details are listed above. Based on the results and according to the EC criteria for classification and labelling requirements, HATCOL 3331 does not have to be classified and has no obligatory labelling requirement for skin irritation.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
04 August 2003 - 14 August 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to OECD test guidance in compliance with GLP and reported with a valid GLP certificate. The study is read across to an analogous substance; refer to image and further information below.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
Annex V
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Species: Albino Rabbit, New Zealand White, (SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. EC, OECD). Source: Charles River Deutschland, Kisslegg, GermanyNo. of animals: 3 Males.Age and bodyweight: Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.Identification: Earmark.ConditionsAnimals 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: 18.1 - 23.9°C), a relative humidity of 30-70% (actual range: 44 -81%) and 12 hours artificial fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.AccommodationIndividually 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.DietStandard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx. 100 g. per day. Certificates of analysis were examined and retained in the NOTOX archives. In addition, pressed hay (BMI, Helmond, the Netherlands) was provided twice a week.WaterFree access to tap-water. Certificates of quarterly analysis were examined and retained in the NOTOX archives.
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 ML
Duration of treatment / exposure:
4 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
This eye irritation study was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 7 days later, after considering the degree of eye irritation observed in the first animal.A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special atlention was paid to the eyes, which were free from any abnormality.Each animal was treated by instilation of 0.1 ml of the test substance in the conjunctival sac of one of the eyes after gently pullng 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 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.OBSERVATIONSMortality/Viability: Twice daily.Toxicity: At least once daily.Body Weight: Day of treatment (prior to instilation) and at termination.Irritation: The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instilation of the test substance. The irritation scores and a description of all other (local) effects were recorded.
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Max. score:
1
Remarks on result:
other: Max. duration: 24 h; Max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
chemosis score
Max. score:
1
Remarks on result:
other: Max. duration: 24 h; Max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
cornea opacity score
Max. score:
0
Remarks on result:
other: Max. duration: h; Max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
iris score
Max. score:
0
Remarks on result:
other: Max. duration: h; Max. value at end of observation period: 0 (related to all animals)
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 was seen as redness and chemosis. The irritation had completely resolved within 24 hours in all animals.No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instilation revealed no corneal epithelial damage in any of the animals.
Other effects:
CorrosionThere was no evidence of ocular corrosion.Colouration I RemnantsNo staining was observed and no remnants of the test substance were seen on (peri) ocular tissues.Toxicity I MortalityNo symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Interpretation of results:
not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
Read across to structural analogue. Structural details are listed above. Based on the results and according to the EC criteria for classification and labelling requirements, HATCOL 3331 does not have to be classified and has no obligatory labelling requirement for eye irritation.
Executive summary:

Read across to structural analogue. Structural details are listed above. Based on the results and according to the EC criteria for classification and labelling requirements, HATCOL 3331 does not have to be classified and has no obligatory labelling requirement for eye irritation.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Conclusions for irritation/corrosive properties of 2,2-bis[[(2-ethyl-1-oxohexyl)oxy]methyl]propane-1,3-diyl bis(2-ethylhexanoate)(EC# 230-743-8) are based on read across from analogue substances of an existing category (pentaerythritol esters), of which the members were notified under Directive 67/548/EEC (NONS) in 2003/2004. Based on the structural similarity and information available for category members, substance EC# 230-743-8 is not classified as skin / eye irritant.

Results are as follows:

Skin

Read across to structural analogue.

Four hours exposure to 0.5 ml of HATCOL 3331 resulted in very slight erythema and/or very slight oedema in the treated skin-areas of the three rabbits. The skin irritation had resolved within 24 hours in two animals and within 48 hours in the other animal.

Corrosion: There was no evidence of a corrosive effect on the skin.

Colouration: No staining of the treated skin by the test substance was observed. Sticky remnants of the test substance were present on the edges of the treated skin area on day 1.

Toxicity/ Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortaliy occurred.

Eye

Instillation of 0.1 ml of the test substance into one eye of each of three rabbits resulted in irritation of the conjunctivae, which was seen as redness and chemosis. The irritation had completely resolved within 24 hours in all animals.

No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instilation revealed no corneal epithelial damage in any of the animals.

Corrosion: There was no evidence of ocular corrosion.

Colouration / Remnants: No staining was observed and no remnants of the test substance were seen on (peri) ocular tissues.

Toxicity / Mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.


Justification for selection of skin irritation / corrosion endpoint:
OECD GLP Study performed on read across substance. Substances are chemically equivalent.

Justification for selection of eye irritation endpoint:
OECD GLP Study performed on read across substance. Substances are chemically equivalent.

Justification for classification or non-classification

Based on the above mentioned result, classification according to the CLP Regulation (EC) 1272/2008 is not necessary.