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

Endpoint summary

Description of key information

Skin Irritation - are not corrosives or dermal irritants
Ocular Irritation - are not ocular irritants 
Respiratory Irritation - are not respiratory irritants

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:

1989/12/12 - 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:

The justification for read across is provided 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:

7 d

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:

7 d

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:

other: Not irritating

Remarks:

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).

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).

Reference 2

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

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: 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).

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).

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

Reason / purpose for cross-reference:

read-across: supporting information

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).

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).

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)

Additional information

Skin Irritation - C10-C15 Aromatics are not corrosives or dermal irritants for rabbit (OECD TG 404). Topical application of C10-C15 Aromatics to the clipped backs of rabbits under semi-occlusive dressing for 4 hours elicited dermal responses in all animals. The dermal responses consisted of erythema ranging from very slight to well defined erythema and very slight edema. A total of 14 animal studies were examined that covered all substance in the category. Five studies used occlusive dressing and did not report sufficient data for classification. Eight studies that were of superior quality and used GLP standards reported data which did not lead to classification. C10-C15 Aromatics are not irritating to human skin when evaluated in a repeated patch test as a 50% w/w preparation. Application of a 50% w/w preparation of C10-C15 Aromatics under semi-occlusive conditions did not result in signs of primary irritation. In another study at the same concentration, application of C10-C15 Aromatics to the skin without or in conjunction with UV irradiation did not elicit an irritation response in any of the study participants. Using qualitative weight of evidence reasoning, the C10-C15 Aromatics are not irritating to rabbit or human skin.

 

Ocular Irritation - C10-C15 Aromatics are not ocular irritants (OECD TG 405) when evaluated in rabbits following a single 0.1 ml ocular instillation. Testing of C10-C15 Aromatics generally demonstrated reversible conjunctive redness, chemosis, and infrequent discharge in animals. Draize scores were generally low. A total of 7 studies were examined that covered all substance in the category. All study results indicate that the C10-C15 Aromatics are not irritating for rabbits.

 

Respiratory Irritation - No studies were located to indicate that C10-C15 Aromatics are respiratory irritants.

 

Justification for classification or non-classification

These findings do not warrant the classification of C10-C15 Aromatics as skin, ocular, or respiratory irritants under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

SKIN IRRITATION: Erythema and edema scores (24, 48, and 72 average) are below the classification threshold requirements: 2.3, the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

OCULAR IRRITATION: Ocular lesion scores (24, 48, and 72 average) are below the classification threshold requirements.

Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP): 0, cornea opacity; 0, iris lesion; >2.0, redness of the conjunctivae; >2.0, oedema of the conjunctivae (chemosis).

RESPIRATORY IRRITATION - There are no studies that warrent classification as a respiratory irritant under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).