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Administrative data

Description of key information

Irritating to the skin.

Not irritating to the 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:
17 Dec 1991 - 24 Jan 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions
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:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Study was terminated on day 7 despite some animals still showing symptoms.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazelton Research Products, Denver, PA
- Age at study initiation: 13 weeks
- Weight at study initiation: 1.95-2.26 kg
- Housing: suspended stainless steel cages with wire mesh
- Diet: Agway Certified Diet, R.C.A. Rabbit, limited on daily basis
- Water (ad libitum): Elizabethtown Water Company
- Acclimation period: 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: December 17, 1991 To: December 24, 1991
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount applied (volume): 0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
45 minutes, 24, 48, 78 hours and 7 days after end of exposure
Number of animals:
6 males
Details on study design:
TEST SITE
- Area of exposure: dorsal surface
- Type of wrap if used: Test material was introduced under a gauze patch secured with tape. This was covered by a semi-occlusive dressing.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): reverse osmosis water and paper towels
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Score:
0.67
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 45 minutes
Score:
0.2
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 45 minutes
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
edema score
Basis:
animal: #1, 2, 3, 4, 5, 6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritant / corrosive response data:
Erythema was noted in one animal (score of 1) at the 45 min observation. By the 48 hr observation, all animals showed erythema (max. score 2). At study termination on day 7, 5 animals still showed erythema (score of 1). Desquamation was also noted in 5 animals on day 7. No edema was observed during the experiment.

Table: Skin Irritation Results

Animal

Observation

Hours

Day

0.75

24

48

72

7

JEI656M

Erythema

0

0

1

1

0

Edema

0

0

0

0

0

JEI649M

Erythema

1

0

2

1

1

Edema

0

0

0

0

0

JEI653M

Erythema

0

0

1

1

1

Edema

0

0

0

0

0

JEI661M

Erythema

0

1

1

1

1

Edema

0

0

0

0

0

JEI660M

Erythema

0

1

2

1

1

Edema

0

0

0

0

0

JEI657M

Erythema

0

0

1

1

1

Edema

0

0

0

0

0

Interpretation of results:
other: Category 2 irritant
Remarks:
Criteria used for interpretation of results: other: CLP
Conclusions:
The test substance, hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, < 5% n-hexane, is mildly irritating to skin. Although the primary irritation index was only 0.67, the inflammation had not fully resolved by study termination, therefore it is not known if the effects are reversible. The test substance is a Category 2 irritant under OECD GHS guidelines based on persistant irritation.
Executive summary:

This study examined the skin irritation of the test substance hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, < 5% n-hexane. 0.5 ml of test substance was placed on the clipped skin of 6 rabbits, and covered with a semi-occlusive patch. After 4 hrs of exposure, the test substance was removed. Animals were scored for dermal irritation 45 minutes, 24, 48, and 72 hours after patch removal, and also on day 7. The primary irritation index was 0.67. Inflammation had not fully resolved by study termination, therefore it is not known if the effects are reversible. The test substance is a Category 2 irritant under OECD GHS guidelines based on persistant irritation.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 Dec 1989 - 1 Feb 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions
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:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Study terminated on day 7, rather than day 14.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Denver, PA
- Age at study initiation: 12 weeks
- Weight at study initiation: 2.0-3.0 kg
- Housing: suspended stainless steel
- Diet: Agway Certified Diet R.C.A. Rabbit, restricted diet
- Water (ad libitum): Elizabethtown Water Company
- Acclimation period: 22 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-23
- Humidity (%): 30-100
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
45, 24, 48, and 72 hours and 7 days after exposure
Number of animals:
4 male/2 female
Details on study design:
TEST SITE
- Area of exposure: dorsal area
- Type of wrap if used: gauze patch secured with tape, loosely held by a semi-occlusive dressing


REMOVAL OF TEST SUBSTANCE
- Washing (if done): reverse osmosis water with paper towels
- Time after start of exposure: 4 hours


SCORING SYSTEM: Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hr observations
Score:
1.42
Reversibility:
not fully reversible within: some animals still exhibited irritation at study termination on day 7
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 45 minutes
Score:
1.5
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 45 minutes
Score:
0.7
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks:
within 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal: #3, 4, 6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: animal #3, 6: effects occurred after 45 minutes and were fully reversible within 24 hours
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
All animals exhibited erythema (maximum score of 2), and 4 animals exhibited edema (maximum score of 1) at the 45 min observation. These symptoms were mostly gone by the 72 hr. observation. However, three animals still had symptoms at the study termination on day 7. Desquamation was noted in two animals at the day 7 observation.
Other effects:
One animal had poor food consumption on day 4. Another animals had a small amount of stool also on day 4.

Table: Skin Irritation Results

Animal

Observation

Hours

Day

0.75

24

48

72

7

JEH665M

Erythema

2

1

1

2

2

Edema

1

1

1

1

1

JEH666M

Erythema

2

2

2

1

2

Edema

1

1

1

0

0

JEH658M

Erythema

2

1

1

0

0

Edema

1

0

0

0

0

JEH671M

Erythema

1

1

1

1

0

Edema

0

0

0

0

0

JEH708F

Erythema

1

2

1

0

0

Edema

0

1

0

0

0

JEH712F

Erythema

1

1

2

1

1

Edema

1

0

0

0

0

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The test substance, hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, < 5% n-hexane, is mildly irritating to skin. Although the primary irritation index was only 1.42, the inflammation had not fully resolved by study termination, therefore it is not known if the effects are reversible. The test substance is a Category 2 irritant under OECD GHS guidelines based on persistant irritation.
Executive summary:

This study examined the skin irritation of the test substance, hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, < 5% n-hexane. 0.5 mL of test substance was placed on the clipped skin of 6 rabbits, and covered with a semi-occlusive patch. After 4 hrs of exposure, the test substance was removed. Animals were scored for dermal irritation 45 min, 24 h, 48h, and 72 hrs after patch removal, and also on day 7. The primary irritation index was 1.42. Inflammation had not fully resolved by study termination, therefore it is not known if the effects are reversible. The test substance is a Category 2 irritant under OECD GHS guidelines based on persistant irritation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given
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
Principles of method if other than guideline:
according to the Federal Register of the F.D.A. 28 (110), 6.6.1963, para. 191.12. Test for eye irritants
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain: albino
- Source: Ranch Rabbits, Crawley, Sussex
- Weight at study initiation: 3 kg
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as control
Amount / concentration applied:
0.2 mL
Duration of treatment / exposure:
single application
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
2 males, 2 females
Details on study design:
Undiluted solvent was instilled into the conjunctival sac of the right eye of two male and two female albino rabbits; the untreated left eye served as a control. A visual assessment of irritancy was made half an hour after application and again 1, 2, 3 and 7 days later.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 0.5 hrs - 7 days
Score:
0
Max. score:
4
Reversibility:
not specified
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

Conjunctiva redness, chemosis and discharge, Cornea opacity and area, and Iris were scored in 4 animals. In all 4 animals only at timepoint 0.5 hr a very mild irritancy was observed in conjunctiva redness and scored 0 - 1. Thus the overall score can be considered to be 0.

Table: Individual Eye Irritation Scores

Animal

1/2 hr

24 hrs

48 hrs

72 hrs

7 days

1351 Female

Cornea, opacity

0

0

0

0

0

Cornea, area

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctiva, redness

0-1

0

0

0

0

Conjunctiva, chemosis

0

0

0

0

0

Conjunctiva, discharge

0

0

0

0

0

1352 Male

Cornea, opacity

0

0

0

0

0

Cornea, area

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctiva, redness

0-1

0

0

0

0

Conjunctiva, chemosis

0

0

0

0

0

Conjunctiva, discharge

0

0

0

0

0

1422 Female

Cornea, opacity

0

0

0

0

0

Cornea, area

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctiva, redness

0-1

0

0

0

0

Conjunctiva, chemosis

0

0

0

0

0

Conjunctiva, discharge

0

0

0

0

0

1423 Male

Cornea, opacity

0

0

0

0

0

Cornea, area

0

0

0

0

0

Iris

0

0

0

0

0

Conjunctiva, redness

0-1

0

0

0

0

Conjunctiva, chemosis

0

0

0

0

0

Conjunctiva, discharge

0

0

0

0

0

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: other: EU, GHS, 2007
Conclusions:
The purpose of this test was to determine the irritation potential of hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics to rabbit eye. 0.2 mL of test substance was added to the right eye of two male and two female rabbits. The animals were scored for irritation at 0.5 hrs after applications, and also at 1, 2, 3, and 7 days after application. All animals showed conjunctival redness (score of 0-1) at the 0.5 hr observation. No other signs of irritation were noted. The test substance is not irritating to eyes according to OECD GHS guidelines.
Executive summary:

The purpose of this test was to determine the irritation potential of hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics to rabbit eye. 0.2 mL of test substance was added to the right eye of two male and two female rabbits. The animals were scored for irritation at 0.5 hrs after applications, and also at 1, 2, 3, and 7 days after application. All animals showed conjunctival redness (score of 0-1) at the 0.5 hr observation. No other signs of irritation were noted. The test substance is not irritating to eyes according to OECD GHS guidelines.

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

Additional information

There are no skin or eye irritation data available on the Hydrocarbons, C6-C10 (even numbered), n-alkanes, isoalkanes, >5% n-hexane. However, there are reliable data available for a category member. Thus, read-across was conducted based on a category approach.

Two studies of ExxonMobil (1990a and 1992a) showed irritating effects to the skin of rabbits based on persistant irritation at study termination. ExxonMobil (1990a) examined the skin irritation of the hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, < 5% n-hexane, conducted similar to OECD 404. 0.5 mL of test substance was applied on the clipped skin of 6 rabbits, and covered with a semi-occlusive patch. After 4 hours of exposure, the test substance was removed. Animals were scored for dermal irritation 45 min, 24, 48, 72 hours and 7 days after patch removal. All animals exhibited very slight to well-defined erythema. In 3 of 6 rabbits, very slight edema were observed. These symptoms were mostly reversible within 7 days. However, three animals still showed irritating symptoms at the study termination. Desquamation was noted in two animals at day 7 of the observation period.

In a subsequent study of ExxonMobil (1992a), the skin irritation potential of the test substance was determined according to the study design of ExxonMobil (1990a). No edema were noted, but all animals exhibited very slight to well-defined erythema. In 5 of 6 rabbits, these symptoms were not reversible within the observation period of 7 days. Desquamation was also noted in 5 of 6 animals at the study termination.The test substance is skin irritating based on persistant irritation at the end of the observation period of 7 days. An observation period of 14 days was not considered in the study.

In contrast, the skin irritation potential of hydrocarbons, C6-C7, n-alkanes, isoalkanes, cyclics, < 5% n-hexane was determined according to OECD 404 (Shell, 1987a) yielding a negative result. The test substance was applied to the intact skin of rabbits for 4 hours under semiocclusive conditions. After removal of the test substance, no edema, but very slight erythema were noted. At 72 hours 3 of 6 rabbits were still affected. All skin effects in all treated animals had cleared by 7 days.

 

The eye irritation potential of the hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics was determined by instillation of 0.2 mL of the test material into the conjunctival sac of 4 rabbits (Shell, 1977b). A visual assessment of irritancy was made 30 min, 24, 48, 72 hours and 7 days after application. At 30 min after application, a very mild irritancy was observed as mild conjunctival redness (grade 0-1) in all animals. All redness was reversible within 24 hours. No corneal opacity, iritis, conjunctival chemosis, or discharge was noted in any of the 4 rabbits.

Justification for classification or non-classification

Based on read-across from a structurally related substance within a category approach, skin irritating effects are expected from the exposure toHydrocarbons, C6-C10 (even numbered), n-alkanes, isoalkanes, >5% n-hexane. ThereforeHydrocarbons, C6-C10 (even numbered), n-alkanes, isoalkanes, >5% n-hexanewere considered as skin irritant and classified.

CLP: Skin Irritation Category 2

 

Based on read-across from a structurally related substance within a category approach, the available data on the eye irritating potential ofHydrocarbons, C6-C10 (even numbered), n-alkanes, isoalkanes, >5% n-hexaneare conclusive but not sufficient for classification.