Alkanes, C7-8

Endpoint summary

Description of key information

Skin Irritation

Irritating to the skin

 

Ocular Irritation

Not irritating to eyes

 

Respiratory Irritation

Not irritating to the respiratory tract

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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

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)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Cunicole de Val de Selle, Prouzel, France
- Weight at study initiation: average weight: 2.4 ± 0.05 kg
- Housing: individually housed; polystyrene cages with feeding bottles and troughs
- Diet: Lapins entretien référence 112 C (U.A.R., Villemoisson-sur-Orge, France); ad libitum during the study
- Water: filtered drinking water; ad libitum during the study
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 50 ± 20 %
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin areas of the test animals served as controls

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

15 days after application (at 1, 24, 48, 72 hours and thereafter daily)

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: 6 square centimetre
- Type of wrap if used: gauze bandage and compress


SCORING SYSTEM: OECD Draize Scoring System

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

other: reversible on day 8, but dryness of the skin

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

other: reversible on day 9, but dryness of the skin

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritant / corrosive response data:

At 1 hour after exposure, erythema were observed for all three animals and edema for two of three animals.

Interpretation of results:

other: Irritating

Remarks:

Criteria used for interpretation of results: other: GHS (EU, 2007)

Conclusions:

The test substance was irritating to the skin according to the criteria of the EU and the GHS.

Executive summary:

The test substance was irritating to the skin according to the criteria of the EU and the GHS.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

27 Apr 1987 - 08 May 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

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

GLP compliance:

yes

Remarks:

Sittingbourne Research Centre, Biotechnology and Toxicology Directorate, Sittingbourne, Kent, ME9 8AG, England

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sittingbourne Research Centre Breeding unit
- Age at study initiation: 3-6 months
- Weight at study initiation: 3834-4988 g
- Housing: singly housed in hanging, stainless steel cages with all-mesh floors and tops and half mesh fronts (67x43x45 cm).
- Diet (ad libitum): Standard rabbit diet, S. Q. C.
- Water (ad libitum): filtered but untreated from the public supply
- Acclimation period: at least two weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-19
- Photoperiod: Lighting (fluorescent tube) was automatically switched on for the day (0600 to 1800 hours GMT) and off for the night (1800 to 0600 hours GMT).

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

30 minutes, 24, 48, 72 hours and 7 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: 2 cm x 2 cm
- Type of wrap if used: The patch and surrounding skin were covered by a single layer of gauze and held in place by means of an elastic adhesive bandage.


REMOVAL OF TEST SUBSTANCE
- Washing: After 4 hours the wrapping and patch was removed and the test site washed with water and gently dried.



SCORING SYSTEM: The site was examined and scored for erythema and oedema on a graded scale of 0 to 4.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 30 minutes

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 30 minutes

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal: #1, 2, 3, 4, 5, 6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

SBP 100/140 LNH caused minimal erythema when the application patches were removed. At 72 hours all the rabbits were still affected. All skin effects in all treated animals had cleared by 7 days.

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: OECD GHS

Conclusions:

Hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics caused minimal erythema when the application patches were removed. At 72 hours all the rabbits were still affected. All skin effects in all treated animals had cleared by 7 days.

Executive summary:

Hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics caused minimal erythema when the application patches were removed. At 72 hours all the rabbits were still affected. All skin effects in all treated animals had cleared by 7 days.

Reference 3

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:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

18 September 2000 - 26 July 2004

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:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Covance Research Products Inc. (formerly HRP), Denver, PA, USA
- Age at study initiation: approximately 15 - 16 weeks
- Weight at study initiation: 2.41 - 2.73 kg
- Housing: single housed during study; suspended stainless steel and wire mesh with absorbent paper below cages
- Diet (e.g. ad libitum): PMI Certified Rabbit Diet 5322; feed was analysed and not contaminated; the animals received new feed each day and the old feed, if any, was discarded. Availability of feed was checked at least once daily for all animals.
- Water (e.g. ad libitum): ad libitum, automatic watering system; water was analysed and not contaminated; availability of water was checked at least once daily for all animals
- Acclimation period: 22 days; animals were examined for viability at least once daily
- Other: animal identification by ear tags and corresponding cage identification


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.8 - 22.2°C (64 - 72 degrees Fahrenheit)
- Humidity (%): 30 - 70 % relative humidity
- Photoperiod (hrs dark / hrs light): approx. 12 h light (06.00 - 18.00) and 12 h dark (18.00 - 06.00)

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

see observation period: The test substance was not washed out.

Observation period (in vivo):

1, 24, 48, 72 hours and 7 days

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize Standard Eye Irritation Grading Scale (Draize 1959: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Association of Food and Drug Officials of the US, vol. 49, pp. 2-56.

TOOL USED TO ASSESS SCORE: 2 % sodium fluorescein

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effect

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effect

Irritant / corrosive response data:

Ocular instillation of the test substance elicited conjunctival responses in all animals. Iridic and corneal responses were not evident during the study. Conjunctival responses consisted of redness of Grade 2 in all animals and discharge of Grade 1 and Grade 2 for one animal each at the 1 hour evaluation. Discharge was not evident after the 1 hour evaluation but redness of Grade 1 was noted for 2 animals at the 24 and 48 hour evaluations. Redness of Grade 1 also was noted for all animals at 72 hour evaluation. Irritation was not evident at the Day 7 evaluation and the study was terminated.

Other effects:

All animals survived the study termination and were free of clincial signs during the study.

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: other: GHS (EU, 2007)

Conclusions:

Based on the study design the test substance, hydrocarbons, C7-C9, isoalkanes, is not irritating.

Executive summary:

Based on the study design the test substance, Hydrocarbons, C7-C9, isoalkanes, is not irritating.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

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

Max. score:

4

Reversibility:

not specified

Remarks on result:

other:

Remarks:

average of four animals

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

other:

Remarks:

average of four animals

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

other:

Remarks:

average of four animals

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks on result:

other:

Remarks:

average of four animals

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.

Reference 3

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)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

There is no irritation data for Hydrocarbons, C7-C8, n-alkanes. Skin and eye irritation data are available for structural analogues Hydrocarbons, C7-C9, isoalkanes, and Hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics and respiratory irritation data is available for structural analogues, Octane and 2,2,4-trimethylpentane. This data is read across to 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

 

Hydrocarbons, C7-C9, isoalkanes

The skin irritation potential of the test substance (Hydrocarbons C7-C9, isoalkanes, <2% aromatics) was determined according to OECD 404 (Total Solvants, 2000). The test substance was applied to the intact skin of rabbits for 4 hours under semiocclusive conditions. After removal of the test substance, no oedema, but well-defined to moderate erythema were noted in all three animals. Irritating effects were reversible within 9 days. Under the test conditions, the test substance was irritating to the skin.

 

Hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics

The skin irritation potential of the test substance was determined according to OECD 404 (Shell, 1987). The test substance (read-across) was applied to the intact skin of rabbits for 4 hours under semiocclusive conditions. After removal of the test substance, no edema, but minimal erythema were noted in all animals (score 1). At 72 hours, all rabbits were still affected. All skin effects had cleared by 7 days.

 

In another study, the test substance was placed on intact skin of 4 rabbits, and covered with an occlusive patch (Shell, 1977). After 24 hours of exposure, animals were scored for dermal irritation (24, 48 and 72 h and 7 days after patch removal). Very slight erythema (score 1) were observed in all animals. Very slight edema were only observed at 24 hours after removal of the patches. Based on the experimental data, the test substance was not irritating to the skin.

  

Eye Irritation

 

Hydrocarbons, C7-C9, isoalkanes

The eye irritation potential of hydrocarbons, C7-C9, isoalkanes was determined by instillation of 0.1 mL of the test material into the conjunctival sac of 3 rabbits (ExxonMobil, 2004). Ocular reactions were examined and scored 1, 24, 48, 72 hours after application. At the 1 hour evaluation, conjunctival redness (grade 2) was observed in all animals. Conjunctival redness (grade 0-1) was also noted in all animals at the 72 hour evaluation. All redness was reversible within 7 days. No corneal opacity, iritis or conjunctival chemosis was noted in any of the 3 rabbits.

 

Two further studies, performed according to OECD 404, showed that no ocular irritation in any animal at any time point could be observed for hydrocarbons, C7-C9, isoalkanes (both studies from ExxonMobil, 1997a,b).

 

In another study of ExxonMobil (1962c) conducted similar to OECD 405, at 1 hour after administration, 4 of 6 animals showed slight erythema which completely subsided by the 4 hour observation. The remaining 2 animals showed slight or moderate erythema, slight oedema, and slight discharge. These irritating effects were fully reversible within 72 hours after administration. Under the test conditions, hydrocarbons, C7-C9, isoalkanes was not irritating to the eyes.

 

Hydrocarbons, C7-C9, n-alkanes, isoalkanes, cyclics

The eye irritation potential of 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, 1977). 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 in 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.

 

Respiratory Irritation

 

Octane

In a supporting study (Chevron Phillips Chemicals, 1983), the respiratory tract irritation potential of Octane was examined in male CD-1 mice (4/dose) treated via inhalation. Mice received 2 treatments of 1 minute separated by a 10-minute non-treatment period in a head only exposure chamber of 24.88 or 100 mg/L of Octane. Plethysmographic respiratory patterns (shown to be indicative of irritation) were noted after exposure to room air (control), after the first 1-minute exposure and after the second 1-minute exposure. No graphic patterns indicative of respiratory pauses were evident throughout the exposures, therefore, Octane was not considered to be a respiratory irritant.

2,2,4-trimethylpentane

In a study examining respiratory tract irritancy (Chevron Phillips Chemicals, 1982), exposure to 2,2,4-trimethylpentane at a nominal concentration of 33.52 mg/L of air did elicit an apparent response from the animals upon exposure, however, it did not appear to produce upper airway irritancy in the mice.

Justification for classification or non-classification

Skin Irritation:

Based on available read across data, Hydrocarbons, C7-C8, n-alkanes meets the criteria for classification as a skin irritant (Skin Irrit. 2; H315; causes skin irritation) under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Ocular Irritation:

Based on available read across data, Hydrocarbons, C7-C8, n-alkanes does not meet the criteria for classification as an ocular irritant under the new Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP).

 

Respiratory Irritation:

Based on available read across data, Hydrocarbons, C7-C8, n-alkanes does not meet the criteria for classification as a respiratory irritant under the new Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP).