N-hexane

Endpoint summary

Description of key information

Skin Irritation

Not 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

Study period:

1970

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable with restrictions because it is an acceptable, well-documented publication, but it deviates from OECD Guideline 404 in that test substance was applied for 24 hours.

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:

Test substance was applied for 24 hrs.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2-3 kg

Type of coverage:

semiocclusive

Preparation of test site:

other: both intact and abraded shaved skin was tested

Duration of treatment / exposure:

24 hrs

Observation period:

24 and 72 hrs

Number of animals:

6 males

Details on study design:

TEST SITE
- Type of wrap if used: gauze

SCORING SYSTEM: Draize

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hrs

Score:

1.92

Max. score:

3

Reversibility:

no data

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: 24/48/72h's score not specified

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: 24/48/72h's score not specified

Irritant / corrosive response data:

All six rabbits showed irritation ranging from a score of 1 to 3 on both intact and abraded skin.

Conclusions:

The primary dermal irritation index (PDII) was 1.92 which is calculated from the average erythema score and the average oedema score. Additionally, the exposure period was 24 hours.

Executive summary:

This study examined the potential of the test substance hexane to cause irritation to skin. Test substance was applied to both intact and abraded skin of 6 male rabbits. The test area was covered with gauze for 24 hrs. After the exposure period, the animals were scored for irritation at 24 and 72 hrs after start of exposure. The primary dermal irritation index (PDII) was 1.92 which is calculated from the average erythema score and the average oedema score. Additionally, the exposure period was 24 hours.

Reference 2

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

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:

1970

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable with restrictions because it is an acceptable, well-documented study report that follows a protocol similar to OECD Guideline 405.

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 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2-3 kg

Vehicle:

unchanged (no vehicle)

Controls:

other: contralateral eye used as control

Amount / concentration applied:

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

Duration of treatment / exposure:

72 hrs

Observation period (in vivo):

72 hrs

Number of animals or in vitro replicates:

6 males

Details on study design:

SCORING SYSTEM: Draize

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hrs

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritant / corrosive response data:

1 animal had a redness score of 1 at 24 hrs. No other signs of irritation were noted.

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The mean conjunctivae, chemosis, iris, and cornea scores were 0.33, 0.0, 0.0 and 0.0 respectively.

Executive summary:

This study examined the potential of hexane to cause irritation to eyes. Approximately 0.1 ml of test substance was placed in the eyes of six male rabbits. The rabbits were examined for signs of irritation at 24, 48, and 72 hrs after start of exposure. Only 1 animal showed signs of irritation (score of 1) at 24 hrs. The mean conjunctivae, chemosis, iris, and cornea scores were 0.33, 0.0, 0.0, and 0.0 respectively. 

Reference 2

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

Skin, eye and respiratory irritation data is available for n-hexane. Additionally, skin and eye irritation data is available for structural analogue, 5-80% n-hexane. This data is read across to n-hexane 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

 

5-80% n-hexane

In a key skin irritation study of C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane  (Hine, 1970), test material was applied to both intact and abraded skin of 6 male rabbits. The test area was covered with gauze for 24 hrs. After the exposure period, the animals were scored for irritation at 24 and 72 hrs after start of exposure. The primary dermal irritation index (PDII) was 1.92 which is calculated from the average erythema score and the average oedema score. 

 

n-hexane

In a primary dermal irritation study (Phillips Petroleum Company, 1982), 6 male and 6 female rabbits were dermally exposed to n-Hexane. Animals then were observed for 72 hours. Irritation was scored by the method of Draize. In this study n-Hexane is not a dermal irrtant. No erythema, edema, or other dermal effects were noted at twenty-four or seventy-two hours after administration of the test material. Therefore, the primary irritation score was calculated to be zero.

 

Eye Irritation

 

5-80% n-hexane

In a key eye irritation study of C-6 normal and iso paraffins (hexanes) and naphthenes (methyl-cyclohexane, dimethylcyclohexane), 25-35% n-hexane (Hine, 1970), the potential of hexane to cause irritation to eyes was examined. Approximately 0.1 ml of test substance was placed in the eyes of six male rabbits. The rabbits were examined for signs of irritation at 24, 48, and 72 hrs after start of exposure. Only 1 animal showed signs of irritation (score of 1) at 24 hrs. The mean conjunctivae, chemosis, iris, and cornea scores were 0.33, 0.0, 0.0, and 0.0 respectively. 

 

n-hexane

In an eye irritation study (Phillips Petroleum Company, 1982) an amount of n-Hexane was instilled into the conjunctival sac of 3 male and 3 female rabbits and observed for 7 days. The animal eyes were washed. Irritation was scored by the method of Draize. Conjunctival redness was noted in two rabbits at one hour postinstillation and had cleared by twenty-four hours. No corneal opacity, iritis, conjunctival chemosis, or discharge was noted in any of the six rabbits. In this study n-hexane is not considered an eye irritant based on the irritation scores.

 

In an eye irritation study (Phillips Petroleum Company, 1982) an amount of n-Hexane was instilled into the conjunctival sac of 3 male and 3 female rabbits and observed for 7 days. The animal eyes remained unwashed. Irritation was scored by the method of Draize. No corneal opacity, iritis, conjunctival redness, chemosis, or discharge was noted in any of the six rabbits during the observation period. In this study n-hexane is not considered an eye irritant based on the irritation scores.

 

Respiratory Irritation

 

n-hexane

In an acute inhalation toxicity study (Phillips Petroleum Company, 1982), groups of 4 mice were exposed by inhalation route at nominal concentration 31.86 mg/L. Increased respiration rates and excessive animal movement were noted in all 4 of the test animals primarily during the exposure periods. No alteration in breathing patterns was noted in any of the animals that would be indicative of upper airway irritation. Based on these results, exposure to N-Hexane at a nominal concentration of 31.86 mg/L of air did elicit an apparent response from the test animals upon exposure, however, it did not appear to produce upper airway irritancy in the mice.

Justification for classification or non-classification

Skin Irritation:

n-hexane is classified as a skin irritant (Skin Irrit. 2; H315; causes skin irritation) under Annex VI of the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Ocular Irritation:

Based on available data, n-hexane 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 data, n-hexane 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).