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Administrative data

Description of key information

All reliable studies on skin and eye irritation for C14-20 Aliphatics (≤2% aromatic) show no or slight irritation effects on rabbit skin and eyes.

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
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:
The justification for read across is provided 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:
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:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

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:
The justification for read across is provided 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

0.0

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:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Fourteen reliable studies were available for skin irritation, dealing with the toxicity of different samples of C14-20 Aliphatics (≤2% aromatic). All studies were conducted similarly or according to OECD guideline 404. All studies show no or slight irritation effects on rabbits' skin. One reliable study was performed with human volunteers exposed to isohexadecane and isoeicosane for 24 h in occlusive conditions. Only slight signs of irritation lead to the conclusion that test substances were not skin irritant.

Nine studies were available for eye irritation, dealing with the toxicity of different samples of C14-20 Aliphatics (≤2% aromatic). All studies were conducted similarly or according to OECD guideline 405. All studies show no or slight irritation effects on rabbits' eyes.

Justification for classification or non-classification

As all reliable studies show no irritation effect or irritation effects slight enough not to classify the test materials, substances of the category do not need to be classified as irritant for skin and eye according to the criteria of Annex VI of Directive 67/548/EEC and CLP Regulation 1272/2008.