Registration Dossier

Administrative data

Description of key information

Skin Irritation

Not irritating to the skin

 

Ocular Irritation

Not irritating to eyes

Respiratory Irritation

No studies were located to indicate that Icosane is a respiratory irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1998/09/14 to 1998/09/25
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted according to OECD guideline N°404 in compliance with GLP. Substance analytical certificate not available
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Guideline study
GLP compliance:
yes
Species:
rabbit
Strain:
other: SPF
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Russian from Mollegaard Breeding and Research Centre A/S, Ejby, DK-4623 Lille Skensved.
- Age at study initiation: no data
- Weight at study initiation: 2.1-2.5 kg
- Housing: individually
- Diet (e.g. ad libitum): A pelleted complete rabbit "Altromin 2123" diet ad libitum
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 55 ± 15%
- Air changes (per hr): 10 times/hour
- Photoperiod (hrs dark / hrs light): 12 h/ 12h


IN-LIFE DATES: no data
Type of coverage:
semiocclusive
Preparation of test site:
other: Electric clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL, undiluted
Duration of treatment / exposure:
4 hours
Observation period:
Skin reaction assessed at 1, 24, 48 and 72 hours and 7 days after exposure (after the removal of the patch)
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: ca. 2.5 cm X 2.5 cm (left+ right)
- % coverage: no data
- Type of wrap if used: Nobifix (6 cm width) was loosely wound round the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the test substance was cleaned with lukewarm water and mild soap
- Time after start of exposure: 4 hours


SCORING SYSTEM: in accordance with the OECD guideline 404
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.2
Max. score:
4
Reversibility:
fully reversible
Irritant / corrosive response data:
See Table I, the test substance is slightly irritating:
- The mean individual erythema scores were 0.2, 0.3 and 0.5 respectively
- The mean individual oedema scores were 0.7, 0.0 and 0.0 respectively
Other effects:
none

Table I: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 4

24 h

L: 1/1/1

     R: 0/1/1

L and R: 0/0/0

48 h

L: 0/0/0

     R: 0/0/1

L: 1/0/0

R: 1/0/0

72 h

      L: 0/0/0

      R: 0/0/0

L: 1/0/0

R: 1/0/0

Average 24h, 48h, 72h

L+R: 0.2 -0.3- 0.5

L and R: 0.7-0-0

Reversibility*

C

C

Average time (unit) for reversion

within 72 hours

within 7 days

L: left test flank R: right test flank C: completely reversible

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, DEV 98-25 is not classified as skin irritant according to the criteria of Annex VI of the Directive 67/548/EEC and CLP Regulation 1272/2008.
Executive summary:

In a primary dermal irritation study conducted according to OECD guideline N°404, three rabbits were exposed to 0.5 mL of DEV 98-25 at two skin sites on the back.

Test sites were covered with a semi-occlusive dressing for 4 hours. Animals then were observed for 7 days. The skin reactions were assessed at 1, 24, 48 and 72 hours, as well as 7 days after removal of the dressing. The mean score was calculated across 3 scoring times; 24, 48 and 72 hours after patch removal, for each animal separately.

The mean individual scores were 0.2, 0.3 and 0.5 for erythema and 0.7, 0.0 and 0.0 for edema.

Based upon the directive 67/548/EEC and the CLP Regulation 1272/2008, DEV 98 -25 is not considered as irritating to the rabbit skin.

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:
experimental study
Adequacy of study:
key study
Study period:
28 September 1998 to 02 October 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: OECD guideline N°405, GLP but substance analytical certificate not available (Substance identification: code name with information on test substance).
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
age of animals at study initiation was not reported
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
age of animals at study initiation was not reported
Principles of method if other than guideline:
Guideline study
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
other: SPF albino rabbits of the stock Mol:Russian
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: M & B, Ejby, DK-4623 Lille Skensved, Denmark
- Age at study initiation: no data
- Weight at study initiation: 2.3 - 2.8 kg
- Housing: kept individually in PPO/HIPS cages (Noryl, floor area = 2576 cm²)
- Diet: pelleted complete rabbit diet "Altromin 2123" from Ch. Petersen ad libitum. Analysis for major nutritive components and relevant possible contaminations in the diet are performed regularly.
- Water: domestic quality drinking water acidified with hydrochloric acid to pH 2.5 ad libitum. Analyses for relevant possible contamination in the water are performed regularly.
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C +/- 3°C
- Humidity (%): 55% +/- 15%
- Air changes (per hr): 10
- Photoperiod :12 hrs dark /12 hrs light


IN-LIFE DATES: From: To:
Vehicle:
not specified
Controls:
other: the right eye of the treated animals was used as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL

Duration of treatment / exposure:
24 hours
Observation period (in vivo):
1, 24, 48, 72 hours after application
Number of animals or in vitro replicates:
3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): with 20 mL 0.9% sodium chloride solution
- Time after start of exposure: 24 hrs


SCORING SYSTEM: grading according to OECD 405 recommendation


TOOL USED TO ASSESS SCORE: fluorescein, UV light
Irritation parameter:
cornea opacity score
Basis:
other: mean individual score for all animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: See Table 1 for details
Irritation parameter:
iris score
Basis:
other: mean individual score for all animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: See Table 1 for details
Irritation parameter:
chemosis score
Basis:
other: mean individual score for all animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: See Table 1 for details
Irritation parameter:
conjunctivae score
Basis:
animal: #1 and #3 - Mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
other: See Table 1 for details
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.7
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
other: See Table 1 for details
Irritant / corrosive response data:
Irritant effects on conjunctiva (redness) were minimal at 1 hour in all animals and were fully reversed at 72h in all animals. There were no effects on the cornea and the iris at any time point. Chemosis was not observed at any time point in all animals.
It can be concluded that DV 98-25 would not be classified as eye irritant.
Other effects:
No data

Table 1: DV 98 -25 Acute eye irritation/corrosion study in the rabbit. Scores for ocular lesions.

Rabbit No /

1 h

24 hrs

 

48 hrs

72 hrs

Individual mean score*

weight (kg)

F

3531 / 2.3

Cornea opacity, area

0

0

0

0

0

 

Cornea opacity, degree

0

0

 0

0

0

0.0

Iris

0

0

 

0

0

0.0

Conjunctiva

Chemosis

0

0

 

0

0

0.0

Redness

1

0

 

0

0

0.0

Discharge

3

0

 

0

0

 

3533 / 2.3

Cornea opacity, area

0

0

0

0

0

 

Cornea opacity, degree

0

0

 0

0

0

0.0

Iris

0

0

 

0

0

0.0

Conjunctiva

Chemosis

0

0

 

0

0

0.0

Redness

1

1

 

1

0

0.7

Discharge

3

0

 

0

0

 

3534 / 2.8

Cornea opacity, area

0

0

0

0

0

 

Cornea opacity, degree

0

0

0

0

0.0

Iris

0

0

 

0

0

0.0

Conjunctiva

Chemosis

0

0

 

0

0

0.0

Redness

1

0

 

0

0

0.0

Discharge

3

0

 

0

0

0.0

F: Reading after instillation of oculoguttae fluoresceini.

* Only the scores from the 3 readings (24, 48 and 72 hours) are included in the calculation of the individual mean scores

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
under the test conditions, DV 98-25 is not classified as eye irritant according to the criteria of Annex VI of the Directive 67/548/EEC and the CLP Regulation 1272/2008.
Executive summary:

The eye irritant effect of DV 98-25 was investigated according to the OECD Guideline No. 405 (1987) and EEC B.5 method (1992) and in compliance with Good Laboratory Practice.

Three female albino rabbits were exposed to 0.1 mL of the test article in the left eye. The eyes were examined and the changes were graded according to a numerical scale 1, 24, 48 and 72 hours after dosing.

Minimal conjunctival irritation (redness) was observed in the three rabbits 1 hour after dosing. During the rest of the observation period no abnormalities were observed for two animals while redness (score 1) was still observed up to 48 h in the third animal.

DV 98 -25 is not considered as irritating to the eyes according to Annex VI of the Directive 67/548/EEC and CLP Regulation 1272/2008.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is no skin or eye irritation data available for Icosane. However, data is available for structural analogues, Hydrocarbons, C14-C17, n-alkanes, <2% aromatics; Hydrocarbons, C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C16-C20, n-alkanes, isoalkanes, cyclics, <2% aromatics; and Isohexadecane. This data is read across to Icosane based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

 

Skin irritation

Thirteen reliable read across studies were available for structural analogues Hydrocarbons, C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics; Hydrocarbons, C16-C20, n-alkanes, isoalkanes, cyclics, <2% aromatics and isohexadecane. All studies were conducted similarly or according to OECD guideline 404.All studies show no or slight irritation effects on rabbits' skin.

 

Hydrocarbons, C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics

 

In a key primary dermal irritation study conducted according to OECD guideline N°404, three rabbits were exposed to 0.5 mL of the test material (Hydrocarbons, C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics) at two skin sites on the back TOTAL Solvants, 1998). Test sites were covered with a semi-occlusive dressing for 4 hours. Animals then were observed for 7 days. The skin reactions were assessed at 1, 24, 48 and 72 hours, as well as 7 days after removal of the dressing. The mean score was calculated across 3 scoring times; 24, 48 and 72 hours after patch removal, for each animal separately. The mean individual scores were 0.2, 0.3 and 0.5 for erythema and 0.7, 0.0 and 0.0 for edema. Based upon the CLP Regulation 1272/2008, Hydrocarbons, C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics is not considered as irritating to the rabbit skin.

 

Seven supporting read across studies that tested Hydrocarbons, C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics (Carless, 1997a, b, c; Total Solvants 1996a, b; Anchor Drillin Fluids, 1995a, b) demonstrated that the substance is not considered as irritating to the rabbit skin.

 

Isohexdecane

 

In a supporting clinical test including 15 human volunteers, isohexadecane was applied undiluted on upper arm in occlusive conditions (patch) for 24 h (Hill Top Research, 1994). Skin reactions were scored 30 min and 24 h after removal of the patch. Mild signs of irritation were observed in only 3 volunteers and only slight signs of irritation in 8 volunteers in worse conditions (24-h exposure, occlusive conditions), leading to the conclusion that isohexadecane is not irritant for human skin.

 

The skin irritating properties of the substance BP solvent IH/isohexadecane was assessed in White Vienna rabbits (3 animals of both sexes). The test substance was applied on a wipe put in contact with the shaved skin under semi-occlusive dressing for 24 hours. At the end of exposure, skin reactions were recorded both at 24 hours (patch removal) and 48 hours after the end of exposure (i.e. 72 -hour time observation) according to the Draize scale. Complete observation time was 14 days.

 

Moreover, the behavior, general state and food consumption were also observed. Body weight was measured every day. There was a very slight erythema (score 1) in two rabbits at patch removal (observation time = 24h). At the 72-hour observation, no erythema was observed in all 6 animals. No oedema was noted in any animal at any observation time. No systemic effect was observed following exposure to BP Solvent IH/Isohexadecan. Behavior, general state, fur, food consumption and body weight development were normal (INEOS, 1980). Under these test conditions, the substance BP solvent IH/Isohexadecan is not classified as a skin irritant according to CLP Regulation 1272/2008.

 

Hydrocarbons, C16-C20, n-alkanes, isoalkanes, cyclics, <2% aromatics

 

In a supporting primary dermal irritation study conducted as similar to OECD guideline N°404 in compliance with GLP, six young adult female New Zealand White rabbits were dermally exposed to 0.5 mL of the test material (Hydrocarbons, C16-C20, n-alkanes, isoalkanes, cyclics, <2% aromatics). Test sites were covered with a semi-occlusive dressing for 4 hours. The skin reactions were assessed at 45 minutes, 24, 48 and 72 hours after removal of the dressing. The mean score was calculated across 3 scoring times for all animals at 24, 48 and 72 hours after patch removal. The mean scores over 24, 48 and 72 hours were 0.0 for erythema and for oedema. Based upon the CLP Regulation 1272/2008, Hydrocarbons, C16-C20, n-alkanes, isoalkanes, cyclics, <2% aromatics is not considered as irritating to the rabbit skin (ExxonMobil, 1991a).

 

In another supporting primary dermal irritation study (ExxonMobil, 1991b), according to OECD guideline 404, young adult New Zealand White rabbits (3 males + 3 females) were dermally exposed to 0.5 mL of the test material (Hydrocarbons, C16-C20, n-alkanes, isoalkanes, cyclics, <2% aromatics). Test sites were covered with a semi-occlusive dressing for 4 hours. Dermal responses were evaluated at 45 min, 24, 48, and 72 hours post-dosing according to the Draize method of scoring. Very slight erythema was observed at 45 min in 3 animals, all symptoms reversed by 24 hours. Edema was not noted in any of the animals. The individual mean score for erythema/eschar and oedema for each of the 3 animals was 0. Based upon the CLP Regulation 1272/2008, Hydrocarbons, C16-C20, n-alkanes, isoalkanes, cyclics, <2% aromatics is not considered as irritating to the rabbit skin.

 

Ocular irritation

Seven reliable read across studies were available for eye irritation, dealing with the toxicity of Hydrocarbons, C14-C17, n-alkanes, <2% aromatics; Hydroarbons, C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics; and Isohexadecae. All studies were conducted similarly or according to OECD guideline 405. All studies show no or slight irritation effects on rabbits' eyes.

 

Hydrocarbons, C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics

 

In a key study (TOTAL Solvants, 1998), the eye irritant effect of Hydrocarbons, C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics was investigated according to the OECD Guideline No. 405 (1987) and EEC B.5 method (1992) and in compliance with Good Laboratory Practice. Three female albino rabbits were exposed to 0.1 mL of the test article in the left eye. The eyes were examined and the changes were graded according to a numerical scale 1, 24, 48 and 72 hours after dosing. Minimal conjunctival irritation (redness) was observed in the three rabbits 1 hour after dosing. During the rest of the observation period no abnormalities were observed for two animals while redness (score 1) was still observed up to 48 h in the third animal. Hydrocarbons, C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics is not considered as irritating to the eyes according to the CLP Regulation 1272/2008.

 

Four supporting read across studies that tested Hydrocarbons, C14-C18, n-alkanes, isoalkanes, cyclics, <2% aromatics (Carless, 1997; Total Solvants 1996; Anchor Drilling Fluids, 1995a, b) demonstrated that the substance is not considered to be an ocular irritant.

 

Isohexadecane

 

In a supporting study (INEOS, 1980), the irritant potential of the substance BP Solvent IH/Isohexadecane was assessed by applying 0.1 mL of the test substance in the conjunctival sac of the left eye of 6 male Himalayan rabbits. After application the animals lid were kept closed for 1 second. The right eye was used as control and received 0.1 mL of physiological NaCl solution. The eyes were examined and the changes were graded according to a numerical scale at 15 min, 1, 24, 48 and 72 hours after dosing. No conjunctival chemosis, corneal and iridal lesion were observed throughout the observation period. Slight redness of the conjunctivae was observed in all animals at 1 hour but only in one animal by the 24 hours after instillation. At 48-hour observation period, no redness was observed in any rabbit. Hence, the mean individual score for redness was 0.33-0.0-0.0. BP Solvent IH/Isohexadecane is not classified as eye irritant according to the CLP Regulation 1272/2008.

 

Hydrocarbons, C14 -C17, n-alkanes, <2% aromatics

 

The eye irritant effect of Petrepar-147 was investigated according to the OECD Guideline No. 405 (1981). Three albino rabbits were exposed to 0.1 mL of the test article in one eye. The eyes were examined and the changes were graded according to a numerical scale 1, 24, 48 and 78 hrs and on day 4 and 7 after dosing. The eyes were not rinsed after administration of the test substance. No corneal damage or iridal inflammation was observed. Redness and chemosis were observed in all animals, one hour after instillation. Slight redness was still observed in two animals at 24 hours while slight chemosis was only observed in one rabbit. The eyes of all rabbits were normal 48 hours after instillation. The mean individual scores were 0.33/0.33/0.0 for conjunctival redness and 0.33/0.0/0.0 for chemosis (Petroquimica, 1984). 

Justification for classification or non-classification

Skin Irritation:

Based on the available read across data, Icosane does not meet the criteria for classification as a skin irritant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Eye Irritation:

Based on the available read across data, Icosane does not meet the criteria for classification as an ocular irritant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Respiratory Irritation:

There are no studies that warrant classification as a respiratory irritant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).