Hydrocarbons, C10, aromatics, >1% naphthalene

Endpoint summary

Description of key information

Skin Irritation

not corrosives or dermal irritants

Ocular Irritation

not ocular irritants 

Respiratory Irritation

No studies were located to indicate that Hydrocarbons, C10, aromatics, >1% naphthalene is a respiratory irritant.

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:

experimental study

Adequacy of study:

key study

Study period:

1989/12/04 -1989/12/07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to or similar to guideline study OECD 404: GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Source: l'Abbaye de Bellefontaine
Sex: Male (6)
Age at study initiation: Approximately 12 weeks
Weight at study initiation: 2.5 +/- 0.1 kg
Housing: Individually
Diet (e.g. ad libitum): ad libitum
Water (e.g. ad libitum): Automatic watering system, ad libitum
Acclimation period: 5

ENVIRONMENTAL CONDITIONS
Temperature (°C): 20 +/- 3
Humidity (%): 30-70%
Photoperiod (hrs dark / hrs light): 12/12
Monitored at least once a day

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Amount(s) applied (volume or weight): 0.5 ml
Concentration (if solution): neat

Duration of treatment / exposure:

Test material was administered to the clipped backs as a single dose introduced under a gauze patch and held in contact with the skin by means of a semi-occlusive dressing for 4 hours. Residual test material was then removed.

Observation period:

1, 24, 48, and 72h post application and once per day on Day 7

Number of animals:

Male (6)

Details on study design:

SCORING SYSTEM: Draize scale for dermal irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1 hour

Score:

ca. 1.7

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

ca. 1.8

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

ca. 1.2

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

ca. 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.3

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1 hour

Score:

ca. 2.7

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

ca. 1

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0.33

Irritant / corrosive response data:

Topical application of Coupe Aromatique 180 -230 elicited mild dermal responses. The erythema was noted as slight at the 72 hour time point while the edema that was noted in the animals was completely reversed by the 48 hour observation.

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The average erythema score (24,48, and 72 hours) was 1.3. The average edema score (24,48, and 72 hours) was 0.33. Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

In this study, 6 rabbits were subjected to a 4h dermal (shaved) exposure of 0.5 ml of Coupe Aromatique 180 -230 via a semi-occluded patch. Dermal responses were evaluated at 1, 24, 48, and 72h post-dosing according to the Draize method of scoring. At the 1, 24, and 72 hour observations two animals were noted with a well defined erythema and edema.  The average erythema score (24,48, and 72 hours) was 1.3. The average edema score (24,48, and 72 hours) was 0.33.

Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

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:

1989/12/12 - 1990/1/31

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: In agreement with OECD test guideline 404. GLP

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:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Source: Hazleton Research Products
Sex: Male (3), Female (3)
Age at study initiation: Approximately 12 weeks
Weight at study initiation: 2.00-3.00 kg
Housing: Individually
Diet (e.g. ad libitum): Agway Certified Diet R.C.A. Rabbit (pellets), restricted as per recommendation of supplier
Water (e.g. ad libitum): Automatic watering system, ad libitum
Acclimation period: 22d

ENVIRONMENTAL CONDITIONS
Temperature (°F): 65 to 74
Humidity (%): 30-70%
Photoperiod (hrs dark / hrs light): 12/12
Monitored at least once a day

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Amount(s) applied (volume or weight): 0.5 ml
Concentration (if solution): neat

Duration of treatment / exposure:

Test material was administered to the clipped backs as a single dose introduced under a gauze patch (secured with non-irritating tape) and held in contact with the skin by means of a semi-occlusive dressing for 4 hours. Residual test material was then removed.

Observation period:

45 min, 24, 48, and 72h post application and once per day on Day 7

Number of animals:

Male (3), Female (3)

Details on study design:

SCORING SYSTEM: Draize scale for dermal irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1 hour

Score:

ca. 1

Max. score:

2

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

ca. 1

Max. score:

2

Irritation parameter:

erythema score

Basis:

mean

Time point:

48 h

Score:

ca. 0.83

Max. score:

2

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

ca. 2

Max. score:

2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: Day 7

Score:

ca. 0.67

Max. score:

1

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1 hour

Score:

ca. 0.33

Max. score:

1

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

48 h

Score:

ca. 0

Max. score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

ca. 0.17

Max. score:

1

Irritation parameter:

edema score

Basis:

mean

Time point:

other: Day 7

Score:

ca. 0

Max. score:

0

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 0.94

Irritant / corrosive response data:

Topical application of MRD-89-524 elicited dermal responses in 4 out of 6 animals. At the 1, 24, and 72 hour observations two animals were noted with a well defined erythema and very slight edema. One animal was noted with well defined erythema and three animals were noted with very slight erythema at the 48 hour observation. At day 7, four animals were noted with very slight erythema.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The average erythema score (24,48, and 72 hours) was 0.94. The average edema score (24,48, and 72 hours) was 0.06. Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

In this study, 6 rabbits were subjected to a 4h dermal (shaved) exposure of 0.5 ml of MRD-89-524 via a semi-occluded patch. Dermal responses were evaluated at 1, 24, 48, and 72h post-dosing and on day 7 according to the Draize method of scoring. At the 1, 24, and 72 hour observations two animals were noted with a well defined erythema and very slight edema.  One animal was noted with well defined erythema and three animals were noted with very slight erythema at the 48 hour observation.  At day 7, four animals were noted with very slight erythema. The average erythema score (24,48, and 72 hours) was 0.94. The average edema score (24,48, and 72 hours) was 0.06. Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

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:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From April 23, 1990 to May 24, 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report in agreement with OECD guideline 405-GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

increased number of animals

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research
- Age at study initiation: Approximately 14 weeks
- Weight at study initiation: 2.29-2.75 kg
- Housing: Individual
- Diet (e.g. ad libitum): restricted feeding regimen per manufacturers recommendation
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 15 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): maintained range of 18.3-21.1 °C
- Humidity (%): maintained range of 40-60%
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: 1990-05-08 To: 1990-05-22

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served as control

Amount / concentration applied:

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

Duration of treatment / exposure:

Test material was introduced into the lower conjunctival sac of the right eye of each animal. The upper and lower lids were gently held together for one second prior to releasing to prevent loss of material

Observation period (in vivo):

1, 24, 48, 72 hours post-instillation and once per day on days 4, 7, 10, and 14

Number of animals or in vitro replicates:

Six animals (all females)

Details on study design:

SCORING SYSTEM: Draize Method


TOOL USED TO ASSESS SCORE: 2% sodium fluorescein dye under UV light

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

ca. 1.46

Max. score:

8

Reversibility:

fully reversible within: 14 days

Irritation parameter:

other: redness

Basis:

mean

Time point:

other: 1h

Score:

ca. 1.17

Max. score:

2

Irritation parameter:

other: redness

Basis:

mean

Time point:

24 h

Score:

ca. 0.5

Max. score:

1

Irritation parameter:

other: redness

Basis:

mean

Time point:

48 h

Score:

ca. 0.17

Max. score:

1

Irritation parameter:

other: redness

Basis:

mean

Time point:

72 h

Score:

ca. 0.6

Max. score:

1

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 1h

Score:

ca. 1.67

Max. score:

2

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24 h

Score:

0

Irritation parameter:

chemosis score

Basis:

mean

Time point:

48 h

Score:

0

Irritation parameter:

chemosis score

Basis:

mean

Time point:

72 h

Score:

ca. 0.2

Max. score:

1

Reversibility:

fully reversible within: 14 days

Other effects:

Alopecia around the treated eye was noted for one animal on days 10 and 14.

One animal died prior to study termination (day 3). This animal exhibited poor food consumption, distended abdomen, and small amount of stool on day 2. It was the opinion of the study director that this death was not test material related, but due to a gastro-intestinal problem.

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Classification as an ocular irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

Executive summary:

Application of 0.1ml of MRD-89-523 to the eye of six rabbits elicited slight, transient conjunctival redness, chemosis, and some discharge.  Mean scores for redness at 24, 48, 72 hours were 0.50, 0.17, and 0.60 respectively.  The scores for chemosis were 1.67, 0, and 0.  There were no positive scores for corneal, or iridial irritation.  Ocular irritation was most prominent at the 1 hour, 72 hour and day 4 observations where the total Draize score ranged from 4-12.  Additional observations included alopecia in one animal on days 10 and 14.  All other animals were free of signs of irritation within 14 days of dosing.  

Classification as an ocular irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.

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 study available

Additional information

There is data available for Hydrocarbons, C10, aromatics, >1% naphthalene. This data is supported by information available for structural analogue, Hydrocarbons, C10-C13, aromatics, >1% naphthalene. 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, C10, aromatics, >1% naphthalene

In a key study (TOTAL, 1990a) study, 6 rabbits were subjected to a 4h dermal (shaved) exposure of 0.5 ml of the test material (Hydrocarbons, C10, aromatics, >1% naphthalene) via a semi-occluded patch. Dermal responses were evaluated at 1, 24, 48, and 72h post-dosing according to the Draize method of scoring. At the 1, 24, and 72 hour observations two animals were noted with a well-defined erythema and edema. The average erythema score (24,48, and 72 hours) was 1.3. The average edema score (24,48, and 72 hours) was 0.33. Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

The dermal irritation/corrosion potential of the test material (Hydrocarbons, C10, aromatics, >1% naphthalene) was evaluated in a supporting study in one male and five female white rabbits (ExxonMobil, 1990a). Topical application of a single 0.5 mL dose under semi-occlusive dressing for 4 hours produced well-defined erythema and slight edema immediately after exposure. Irritation persisted 24 hours following the application, at which point the majority of animals showed signs of slight edema and erythema ranging from slight to well-defined. By 48h slight edema was present in one animal, however erythema persisted in all animals ranging from very slight to severe.  The irritation began to subside after 72 hours. By day 7, two animals were free of any dermal irritation while four animals had very slight erythema.  The average scores for erythema at 24, 48, and 72 hours were 1.6, 1.5, and 1.3 respectively. The mean scores for edema were 0.50, 0.33, and 0.17. Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

In another supporting study (ExxonMobil, 1986), the dermal irritation/corrosion potential of the test material (Hydrocarbons, C10, aromatics, >1% naphthalene) on intact skin under semi-occlusive conditions was evaluated in six white rabbits. The test material was administered as a single 0.5 mL dose for 4-hours at two separate dose sites on each animal. Residual test material on the right dose site was removed using a paper towel saturated with water, residual test material on the left dose site was removed using a paper towel saturated with white oil. Dermal exposure to the test material elicited dermal irritation in all animals which was similar for both dose sites. Irritation scores were identical for both sites at the 60 minute and 24-hour observation when erythema ranged from very slight to well-defined and edema ranged from very slight to slight. Erythema scores remained consistent while edema scores decreased at 48- and 72-hours. By study termination very slight erythema was noted for five animals at each dose site and well-defined erythema was noted for one animal at each dose site. Very slight edema was noted for two animals at the right dose site and for three animals at the left dose site. Additional observations included atonia and desquamation for both dose sites. Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Hydrocarbons, C10-C13, aromatics, >1% naphthalene

In a key read across study (ExxonMobil, 1990), 6 rabbits were subjected to a 4h dermal (shaved) exposure of 0.5 ml of the test material (Hydrocarbons, C10-C13, aromatics, >1% naphthalene) via a semi-occluded patch. Dermal responses were evaluated at 1, 24, 48, and 72h post-dosing and on day 7 according to the Draize method of scoring. At the 1, 24, and 72 hour observations two animals were noted with a well-defined erythema and very slight edema. One animal was noted with well-defined erythema and three animals were noted with very slight erythema at the 48 hour observation. At day 7, four animals were noted with very slight erythema. The average erythema score (24,48, and 72 hours) was 0.94. The average edema score (24,48, and 72 hours) was 0.06. Classification as a dermal irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Eye Irritation

Hydrocarbons, C10, aromatics, >1% naphthalene

In a key study (ExxonMobil, 1990c), application of 0.1 mL of the test material (Hydrocarbons, C10, aromatics, >1% naphthalene) to the eye of six rabbits elicited slight, transient conjunctival redness, chemosis, and some discharge. Mean scores for redness at 24, 48, 72 hours were 0.50, 0.17, and 0.60 respectively. The scores for chemosis were 1.67, 0, and 0.  There were no positive scores for corneal, or iridial irritation. Ocular irritation was most prominent at the 1 hour, 72 hour and day 4 observations where the total Draize score ranged from 4-12. Additional observations included alopecia in one animal on days 10 and 14. All other animals were free of signs of irritation within 14 days of dosing. Classification as an ocular irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

In a supporting study (TOTAL, 1990b), application of 0.1ml of the test material (Hydrocarbons, C10, aromatics, >1% naphthalene) to the eye of six rabbits elicited slight, transient conjunctival redness and chemosis. Mean scores for redness at 24, 48, 72 hours were 0.30, 0, and 0 respectively. The scores for chemosis were 0.5, 0, and 0. There were no positive scores for corneal, or iridial irritation. Ocular irritation was most prominent at the 1 hour observation and symptoms were reversed by 48 hours post application. Classification as an ocular irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Hydrocarbons, C10-C13, aromatics, >1% naphthalene

A supporting study (ExxonMobil, 1975), was conducted to determine the potential of the test material (Hydrocarbons, C10-C13, aromatics, >1% naphthalene) to cause irritation to the eye in a rabbit model system. Six rabbits were instilled with 0.1 mL of the test material, neat. Ocular examinations occurred at 1h, 4h, 24h, 48h, 72h, day 4, and day 7 post instillation. Ocular damage was assessed and scored according to the Draize method. All animals survived the exposure. Ocular irritation was most prominent at the 4 hour observation point where the total Draize score ranged from 6 to 13. Irritation subsided as the study progressed and by the 24 hour observation, all animals were clear of ocular irritation. Classification as an ocular irritant is not warranted under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

Respiratory Irritation

No studies were located to indicate that Hydrocarbons, C10, aromatics, >1% naphthalene is a respiratory irritant.

Justification for classification or non-classification

Skin Irritation:

Based on available substance specific and read across data, Hydrocarbons, C10, aromatics, >1% naphthalene does not meet the criteria for classification for skin Irritation under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Ocular Irritation:

Based on available substance specific and read across data, Hydrocarbons, C10, aromatics, >1% naphthalene does not meet the criteria for classification as ocular irritants 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).