Hydrocarbons, C9, aromatics

Endpoint summary

Description of key information

Skin Irritation

Hydrocarbons, C9 Aromatics:

Hydrocarbons, C9, Aromatics are not corrosives and are mild to moderate dermal irritants for rabbit (OECD TG 404). A series of skin irritation studies were conducted using rabbits and standard test protocols.The mean erythema scores in the four independent key studies ranged from 1.9 to 4.0; mean edema scores in these same studies ranged from 0.0 to 2.2. Therefore, Hydrocarbons, C9 aromatics can be considered to be mildly to moderately irritating to the skin, with any effects generally reversible. In addition, a study was conducted in which 26 human volunteers were dermally exposed to C9 aromatics. Results showed no evidence of aromatics being a dermal irritant to humans. Using qualitative weight of evidence reasoning, the C9 Aromatics may cause mild skin irritation, but results are insufficient to classify.

Hydrocarbons, C10 Aromatics, >1% Naphthalene:

not corrosives or dermal irritants

Ocular Irritation

Hydrocarbons, C9 Aromatics:

C9 Aromatics are not ocular irritating for rabbits (OECD TG 405). All study results indicate that the C9 Aromatics are not ocular irritants to rabbits.

Hydrocarbons, C10 Aromatics, >1% Naphthalene:

not ocular irritants 

Respiratory Irritation

Hydrocarbons, C9 Aromatics:

No studies were located to indicate that C9 Aromatics are respiratory irritants. However, a constituent of the C9 Aromatics, 1,3,5-trimethylbenzene, is classified as STOT Single Exp. 3 (H335: May cause respiratory irritation).

Hydrocarbons, C10 Aromatics, >1% Naphthalene:

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:

29/09/1992-21/10/1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study according to EEC Directive 84/449.

Qualifier:

according to guideline

Guideline:

other: Directive 67/548/EEC (OECD TG 404)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Froxfield Farms U.K. Ltd
- Age at study initiation: 3 to 5 months
- Weight at study initiation: 3.02-3.54 kg
- Housing: singly in hanging stainless steel cages with perforated or wire-mesh flooring, animals identified by cage-labels and ear-tags
- Diet (e.g. ad libitum): Standard Rabbit Diet, S.Q.C., Special Diets Services Ltd.
- Water (e.g. ad libitum): tap water


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-20
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): neat

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, and 72 hrs
7, 14, 21 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: dorsal skin
- Type of wrap if used: 6 cm² lint patch covered with a larger gauze patch


REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water
- Time after start of exposure: 4 hrs


SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.9

Max. score:

2

Reversibility:

fully reversible within: 21 days

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

Desquamation was noted in all animals on day 7. By day 21 all symptoms were fully reversed.

Dermal Scores for Each Animal

	Dermal Response	1 hr	24 hr	48 hr	72 hr	7 days	10 days	14 days
TT017 M	Erythema	1	2	2	2	1	1	0
	Edema	0	0	0	0	0	0	0
TT019 M	Erythema	1	2	2	2	1	0	0
	Edema	0	0	0	0	0c	0	0
TT021 M	Erythema	1	2	2	1	1	0	0
	Edema	0	0	0	0	0d	0	0
TT036 F	Erythema	1	2	2	2	0	0	0
	Edema	0	0	0	0	0	0c	0
TT038 F	Erythema	1	2	2	1	1	0	0
	Edema	0	0	0	0	0	0c	0
TT043 F	Erythema	1	2	2	2	1	0	0
	Edema	0	0	0	0	0c	0b	0

b - slight desquamation

c - desquamation

d - reduced pliability

Summary of other skin irritation studies

End Point

Study Reference

REACH requirement

IUCLID Section

Study Name

Data Waiving

Waiving Justification

Species

Study Result Type

Test Guideline/Qualifier

Test Guideline/Guideline

Test Guideline/Deviations

Reliability

Rational For Reliability

GLP Compliance

Test Materials/Identity

Study Result

Reference Type

Reference Author

Reference Year

Reference Title

Bibliographic Source

Testing Laboratory

Reference Report No.

Owner Company

Company Study No.

Report Date

Data access

8.1 Skin Irritation or Corrosion

7.3.1

Primary Dermal Irritation Study in the Rabbit

Rabbit

experimental result

equivalent or similar to

OECD Guideline 404

Exposure for 24 hrs, rather than 4 hrs.

2

In general agreement with OECD test guideline 404.

No data

MRD-ECH-80-14

not classifiable

study report

ANON

1980

Primary Dermal Irritation Study in the Rabbit

HSPA0139

Bio/dynamics Inc.

6301-80

ExxonMobil Petroleum & Chemical BVBA

80MRL23

31/12/1980

yes

8.1 Skin Irritation or Corrosion

7.3.1

Primary Skin Irritation - Rabbit

Rabbit

experimental result

equivalent or similar to

OECD Guideline 404

Exposure for 24 hrs, rather than 4 hrs, no sex data available, 12 rabbits used, and no data reported for 48 hr time point.

2

Uses Draize Method which is in general agreement with OECD test guideline 404.

No data

MRD-61-14

not classifiable

study report

ANON

1963

Primary Skin Irritation - Rabbit

HSPA0143

Hazleton Laboratories, Inc.

29890

ExxonMobil Petroleum & Chemical BVBA

63MRL2

yes

8.1 Skin Irritation or Corrosion

7.3.1

Primary Dermal Irritation Study in the Rabbit

Rabbit

experimental result

equivalent or similar to

OECD Guideline 404

Study ended on day 7, when there was still unresolved delayed erythema.

2

In general agreement with OECD test guideline 404.

No data

MRD-83-208

not irritating

study report

ANON

1984

Primary Dermal Irritation Study in the Rabbit

HSPA0144

Exxon Biomedical Science, Inc.

320804

ExxonMobil Petroleum & Chemical BVBA

84MRL88

13/04/1984

yes

8.1 Skin Irritation or Corrosion

7.3.1

Primary Dermal Irritation Study in the Rabbit

Rabbit

experimental result

equivalent or similar to

OECD Guideline 404

No

2

In general agreement with OECD test guideline 404 - GLP.

Yes

MRD-85-734

irritating

study report

ANON

1986

Primary Dermal Irritation Study in the Rabbit

HSPA0145

Exxon Biomedical Science, Inc.

273404

ExxonMobil Petroleum & Chemical BVBA

86MRL60

09/04/1986

yes

8.1 Skin Irritation or Corrosion

7.3.1

Primary Dermal Irritation Study in the Rabbit

Rabbit

experimental result

equivalent or similar to

OECD Guideline 404

No

1

In agreement with OECD test guideline 404 - GLP.

Yes

MRD-89-522

not irritating

study report

ANON

1990

Primary Dermal Irritation Study in the Rabbit

HSPA0146

Exxon Biomedical Science, Inc.

252204

ExxonMobil Petroleum & Chemical BVBA

90MRL97

02/02/1990

yes

8.1 Skin Irritation or Corrosion

7.3.1

Primary Dermal Irritation Study in the Rabbit

Rabbit

experimental result

equivalent or similar to

OECD Guideline 404

Exposure for 24 hrs, rather than 4 hrs.

2

In general agreement with OECD test guideline 404.

No data

MRD-ECH-80-14

not classifiable

study report

ANON

1980

Primary Dermal Irritation Study in the Rabbit

HSPA0138

Bio/dynamics Inc.

6301-80

ExxonMobil Petroleum & Chemical BVBA

80MRL20

11/07/1980

yes

8.1 Skin Irritation or Corrosion

7.3.1

Primary Irritation of the Skin

Rabbit

experimental result

equivalent or similar to

OECD Guideline 404

Exposure for 24 hrs, rather than 4 hrs.

2

Uses Draize Method which is in general agreement with OECD test guideline 404. Summary of study only.

No data

Shellsol A

moderate irritant

study report

Coombs, AD, Blair, D, Doak, SM, Carter, BI

1977

The Acute Toxicity of Shellsol A

HSPA0685

Sittingbourne Research Centre

M(T)-1-77

Shell Chemicals Europe BV

June, 1977

yes

Interpretation of results:

other: not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Hydrocarbons, C9, aromatics is a mild skin irritant.

Executive summary:

This study examined the irritation/corrosion of Hydrocarbons, C9, aromatics to rabbit skin. 0.5 ml of test substance was applied to the clipped dorsal skin of 3 male and 3 female rabbits for 4 hrs. Animals were then examined at 1, 24, 48, and 72 hrs, and 7, 14, and 21 days after the end of exposure and scored using the Draize method for signs of erythema, edema, and corrosion. Mean erythema score (24, 48, and 72 hrs) was 1.9, and the mean edema score (24, 48, and 72 hrs) was 0.0. Desquamation was noted in all animals on day 7. By day 21 all symptoms were fully reversed. Hydrocarbons, C9, aromatics, is therefore not corrosive and only mildly irritating to skin. According to EU GHS guidelines, Hydrocarbons, C9, aromatics, would be not be classified as a skin irritant.

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:

1989/12/04 -1989/12/07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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

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: 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 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:

experimental study

Adequacy of study:

key study

Study period:

1990/05/02-1990/05/15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: According to OECD Guideline 405. GLP

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazelton Research Products, Inc.
- Sex: female (6)
- Age at study initiation: 14 weeks
- Weight at study initiation: 2.48-2.75 kg
- Housing: Individually
- Diet (e.g. ad libitum): Agway Certified Diet R.C.A. Rabbit (pellets), restricted with new food each day
- Water (e.g. ad libitum): Automatic watering system, ad libitum
- Acclimation period: 15 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65-70
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: contralateral eye served as control

Amount / concentration applied:

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

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, 4, 24, 48, and 72 hrs post instillation and once per day on days 4 and 7.

Number of animals or in vitro replicates:

Female (6)

Details on study design:

SCORING SYSTEM: Draize scale for ocular irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Time point:

other: 1 hr

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Time point:

24 h

Score:

0.5

Max. score:

1

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Time point:

48 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 72 hrs

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 1 hr

Score:

1.33

Reversibility:

fully reversible within: 48 hrs

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24 h

Score:

0.17

Max. score:

1

Reversibility:

fully reversible within: 48 hrs

Irritation parameter:

chemosis score

Basis:

mean

Time point:

48 h

Score:

0

Irritation parameter:

chemosis score

Basis:

mean

Time point:

72 h

Score:

0

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 1-72 hrs

Score:

0

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 1-72 hrs

Score:

0

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: Mean 24, 48, and 72-hour scores not specified

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: Mean 24, 48, and 72-hour scores not specified

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: Mean 24, 48, and 72-hour scores not specified

Irritant / corrosive response data:

Redness was noted for all animals at the 1 hr observation point, for 3 animals at the 24 hr observation point, and for two animals at the 48 hr observation point. Chemosis was noted for all animals at the 1 hr observation and for 1 animal at the 24 hr observation point. Only one animal was noted in having discharge at the 1 hr time point. All animals were free of any occular irritation after the 48 hr observation. The maximum Draize score was 8 at the 1 hr time point.

Summary of other eye irritation studies:

Chemical Name:

Hydrocarbons, C9, aromatics

Reference Substance:

CAS Number:

64742-95-6

EC Number:

265-199-0

SMILES:

End Point

Study Reference

REACH requirement

IUCLID Section

Study Name

Data Waiving

Waiving Justification

Species

Study Result Type

Test Guideline/Qualifier

Test Guideline/Guideline

Test Guideline/Deviations

Reliability

Rational For Reliability

GLP Compliance

Test Materials/Identity

Study Result

Reference Type

Reference Author

Reference Year

Reference Title

Bibliographic Source

Testing Laboratory

Reference Report No.

Owner Company

Company Study No.

Report Date

Data access

8.2 Eye Irritation

7.3.2

Draize Eye Irritation Studies - Rabbits

Rabbit

Experimental result

Equivalent or similar to

OECD guideline 405

Eyes of some animals were irrigated

2

Acceptable, well-documented study report in general agreement with OECD guideline 405. Not performed according to GLP.

No

MRD-61-14

not irritating

Study report

ANON

1961

Draize Eye Irritation Studies - Rabbits

HSPA0147

Hazleton Laboratories

ExxonMobil Petroleum & Chemical BVBA

61MRL7

yes

8.2 Eye Irritation

7.3.2

Ocular Irritation Study in the Rabbit

Rabbit

Experimental result

Equivalent or similar to

OECD guideline 405

Failed to continue study to 21 days when symptoms were still present at 72 hrs.

2

Similar to OECD guideline 405.

yes

MRD-90-720

not classifiable

Study report

ANON

1990

Ocular Irritation Study in the Rabbit

HSPA0150

Exxon Biomedical Sciences, Inc.

172013

ExxonMobil Petroleum & Chemical BVBA

90MRL166

12/06/1990

yes

8.2 Eye Irritation

7.3.2

Eye Irritation Study in Rabbits

Rabbit

Experimental result

Equivalent or similar to

OECD guideline 405

No

2

Similar to OECD guideline 405.

No data

MRD-ECH-80-14

not irritating

Study report

ANON

1980

Eye Irritation Study in Rabbits

HSPA0148

Bio/dynamics Inc.

29641

ExxonMobil Petroleum & Chemical BVBA

80MRL16

11/07/1980

yes

8.2 Eye Irritation

7.3.2

Eye Irritation

Rabbit

Experimental result

According to

Federal Register, 28, (110), 6.6.1963. para 191.12. Test for eye irritation.

No

2

Summary only of study.

No data

Shellsol A

not irritating

Study report

Coombs, AD, Blair, D, Doak, SM, Carter, BI

1977

The Acute Toxicity of Shellsol A

HSPA0686

Sittingbourne Research Centre

M(T)-1-77

Shell Chemicals Europe BV

June, 1977

yes

Interpretation of results:

other: Not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Based on the individual and mean scores of ocular irritations, test substance would not be considered an ocular irritant under either EU GHS guidelines or under the EU requirements for dangerous substances and preparations guidelines.

Executive summary:

This study was conducted to determine the potential of the substance to cause irritation to the eye in a rabbit model system. Six rabbits were instilled with 0.1 ml of MRD-89 -522, neat. Ocular examinations occurred at 1, 4, 24, 48, and 72 hrs, and days 4 and 7 post instillation. Ocular damage was assessed and scored according to the Draize eye test. All animals survived the exposure. Maximum observed Draize score was 8. Irritation subsided as the study progressed and all animals were clear of ocular irritation after the 48 hr observation. Based on the individual and mean scores, test substance should not be considered an ocular irritant under either EU GHS guidelines or under the EU requirements for dangerous substances and preparations guidelines.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

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

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

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:

exposure-related 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) 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 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 study available

Additional information

Skin Irritation

Hydrocarbons,C9 aromatics are not corrosives and are mild to moderate dermal irritants for rabbits (OECD TG 404). Topical application of Hydrocarbons, C9 Aromatics to the clipped backs of rabbits under semi-occlusive dressing for 4 hours elicited dermal responses in all animals. The mean erythema scores in the four independent key studies ranged from 1.9 to 4.0; mean edema scores in these same studies ranged from 0.0 to 2.2. Therefore, Hydrocarbons, C9 aromatics can be considered to be mildly to moderately irritating to rabbit skin, with any effects generally reversible. In addition, a study was conducted in which 26 human volunteers were dermally exposed to Hydrocarbons, C9 aromatics. Results showed no evidence of aromatics being a dermal irritant to humans. Using qualitative weight of evidence reasoning, the C9 Aromatics may cause mild skin irritation to rabbits, but are not irritating to human skin.

Hydrocarbons, C10 aromatics, >1% Napthalene are not corrosives or dermal irritants for rabbit (OECD TG 404). Topical application of C10 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 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 aromatics under semi-occlusive conditions did not result in signs of primary irritation. In another study at the same concentration, application of C10 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 hydrocarbons, C10 aromatics, >1% napthalene are not irritating to rabbit or human skin.

Ocular Irritation

Hydrocarbons, C9 aromatics are not ocular irritants (OECD TG 405) when evaluated in rabbits following a single 0.1 mL ocular instillation. Testing of Hydrocarbons,C9 Aromatics generally demonstrated reversible conjunctive redness, chemosis, and infrequent discharge in animals. Draize scores were generally low. All study results indicate that the Hydrocarbons,C9 Aromatics are not irritating for rabbits.

Hydrocarbons, C10 aromatics, >1% Napthalene are not ocular irritants (OECD TG 405) when evaluated in rabbits following a single 0.1 mL ocular instillation. Testing of C10 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 hydrocarbons, C10 aromatics, >1% Napthalene are not irritating for rabbits.

Respiratory Irritation

No studies were located to indicate that Hydrocarbons, C9 Aromatics are respiratory irritants. 

Justification for classification or non-classification

Based on available data, Hydrocarbons, C9, aromatics, do not warrant classification as skin, ocular, or respiratory irritants under the Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP). However, a constituent of Hydrocarbons, C9 Aromatics, 1,3,5-trimethylbenzene, is classified as a respiratory irritant (STOT Single Exp. 3: H335) under EU CLP. Therefore, Hydrocarbons, C9, aromatics are also classified as respiratory irritants under EU Regulation (EC) 1272/2008.