16,17-dimethoxyviolanthrene-5,10-dione

Endpoint summary

Description of key information

Not irritating to skin or eyes

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:

weight of evidence

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: Consumer Product Safety Commission of the U.S.A. in The Code of Federal Regulations, Title 16, Section 1500.4

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

Code of Federal Regulations, Title 16, Section 1500.41.
Primary irritation to the skin is measured by a patch test technique on the abraded and intact skin of the albino rabbit, clipped Free of heir. A minimum of six subjects are used in abraded and intact skin tests. Introduce under a square patch such as surgical gauze measuring 1 inch x 1 inch, two single layers thick, 0.5 milliliter (in case of Liquids ) or 0.5 gram ( in case of solids and semisolids ) of the test substance. Dissolve solids in an appropriate solvent and apply the solution as for liquids. The animals are immobilized with patches secured in place by adhesive tape. The entire trunk of the animal is then wrapped with an impervious material such as rubberized cloth for the 24-hour period of exposure. This material aids in maintaining the test patches in position and retards the evaporation of volatile substances. After 24 hours exposure, the patches are removed and the resulting reactions are evaluated on the basis of the Draize scores.

GLP compliance:

no

Species:

rabbit

Strain:

other: albino

Type of coverage:

occlusive

Preparation of test site:

other: abraded (3x3 cm) and shaved (3x3 cm) skin

Vehicle:

unchanged (no vehicle)

Remarks:

pasted

Amount / concentration applied:

5 g

Duration of treatment / exposure:

24 hours

Observation period:

up to 72 hours

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure shaved and scarified skin: 2.5x2.5 cm
- Area of exposure shaved skin: 2.5x2.5 cm
- Type of wrap if used: 6 to 8 cm wide PVC sheeting covered by elastic bandage


REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hours


SCORING SYSTEM: Code of Federal Regulations, Title 16, Section 1500.41

Erythema and eschar formation (EEF) : Value*
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

Edema formation (EF):
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well defined by definite raising) 2
Moderate edema (raised approximately 1 mm) 3
Severe edema (raised more than 1 mm and extending beyond area of exp.) 4

*The "value" recorded for each reading is the average value of the six or more animals subject to the test.

Readings are again mode at the end of a total of 72 hours (48 hours after the first reading). An equal number of exposures are mode an areas of skin that have been previously abraded. The abrasions are minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or to produce bleeding. Evaluate the reactions of the abraded skin at 24 hours and at 72 hours, as described in this paragraph. Add the values for erythema and eschar formation at 24 hours and 72 hours for intact skin to the values an abraded skin at 24 hours and 72 hours (four values). Similarly, add the values for oedema formation at 24 hours and at 72 hours for intact and abraded skin (four values). The total of the eight values is divided by four to give the primary irritation score.

Primary Irritation Index (PII) = EEF24h-abraded + EEF72h-abraded + EEF24h-shaved + EEF72h-shaved + EF24h-abraded + EF72h-abraded + EF24h-shaved + EF72h-shaved / 4

ECLASSIFICATION SYSTEM FOR PRIMARY IRRITATION
From “Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics",
published by the Association of Food and Drug Officials of the United States, 1959, page 46.
"Compounds producing combined averages (primary irritation indices) of 2 or less are only mildly irritating; whereas those with indices from 2 to 5 are moderate irritants, and those with scares above 6 are considered severe irritants."

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 + 72 h

Score:

0.01

Max. score:

8

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Remarks:

shaved skin

Basis:

mean

Time point:

other: 24/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Remarks:

shaved skin

Basis:

mean

Time point:

other: 24/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Very slight erythema with very slight oedema was observed in one abraded site at the 24 hours reading.
Five animals did not show any observable response to treatment throughout the 72 hours observation period.
The primary Irritation was calculated to be : 0.1

Interpretation of results:

GHS criteria not met

Conclusions:

not irritating

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: Federal Register 38, No 187

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

FDA Federal Register 38, No 187, Patch-Test, occusive scarified and intact skin

GLP compliance:

no

Species:

rabbit

Strain:

Himalayan

Type of coverage:

occlusive

Preparation of test site:

other: abraded (3x3 cm) and shaved (3x3 cm) skin

Vehicle:

unchanged (no vehicle)

Remarks:

pasted

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

24 hours

Observation period:

up to 72 hours

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure shaved and scarified skin: 2.5x2.5 cm
- Area of exposure shaved skin: 2.5x2.5 cm
- Type of wrap if used: 6 to 8 cm wide PVC sheeting covered by elastic bandage


REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 hours


SCORING SYSTEM: FDA Federal Register 38, No 187

Erythema and eschar formation (EEF) :
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4

Edema formation (EF):
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well defined by definite raising) 2
Moderate edema (raised approximately 1 mm) 3
Severe edema (raised more than 1 mm and extending beyond area of exp.) 4

Mean value of 6 animals

Primary Irritation Index (PII) = EEF24h-abraded + EEF72h-abraded + EEF24h-shaved + EEF72h-shaved + EF24h-abraded + EF72h-abraded + EF24h-shaved + EF72h-shaved / 4

EVALUATION:

0.0 - 0.5 non-irritant
0.6 - 3.0 slightly irritant
3.1 - 5.0 moderately irritant
5.1 - 8.0 severely irritant

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 + 72 h

Score:

0.06

Max. score:

8

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

exact erythema evaluation not possible due to skin staining

Interpretation of results:

other:

Remarks:

not irritating

Conclusions:

not irritating

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

BASF-Testing method

GLP compliance:

no

Species:

rabbit

Strain:

not specified

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

water

Amount / concentration applied:

Concentration: 50% aqueous paste

Duration of treatment / exposure:

Back: 20 hours

Observation period:

24 hours, 8 days

Number of animals:

no data

Details on study design:

TEST SITE
- Area of exposure: back and ear
- % coverage: -
- Type of wrap if used: -


SCORING SYSTEM:
Erythema and Edema
Ø - no effect
(+) - questionable
+ - mild
++ - moderate
+++ - marked

N - necrosis
Sch - scabbing
Na - scar

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 8 days

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

slight reddening after 24 hours, no effects after 8 days

Other effects:

yellow remainder of test item visible

Interpretation of results:

GHS criteria not met

Conclusions:

not irritating

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:

weight of evidence

Study period:

1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1981

GLP compliance:

not specified

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: GAUKLER; OFFENBACH / MAIN, Germany
- Weight at study initiation: 1 male: 2.87 kg; 2 females: 2.85 kg
- Housing: single
- Diet: OVATOR SOLIKANIN 4 MM; MUSKATOR-WERKE DUESSELDORF; Germany; ca 130 g/animal/day
- Water: tap water; ca. 250 mL/animal/day
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25 June 1984 To: 27. June 1984

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL bulk volume (ca. 65 mg test substance)

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

up to 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No
- Time after start of exposure: NA

SCORING SYSTEM: Draize

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.1

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.2

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Interpretation of results:

GHS criteria not met

Conclusions:

Vat Green 1 is not irritating to eyes

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: The Consumer Product Safety Commission of the U. S.A. in The Code of Federal Regulations, Title 16, Section 1500.42

Principles of method if other than guideline:

Code of Federal Regulations, Title 16, Section 1500.42
Six albino rabbits are used for each test substance. Animal facilities for such procedures shall be so designed and maintained as to exclude sawdust, wood chips, or other extraneous materials that might produce eye Irritation. Both eyes of each animal in the test group shall be examined before testing, and only those animals without eye defects or irritation shall be used. The animal is held firmly but gently until quiet. The test material is placed in one eye of each animal by-gently pulling the lower lid away from the eyeball to forma cup into which the test substance is dropped. The lids are then gently held together for one second and the animal is released. The other eye, remaining untreated, serves as a control. For testing liquids, 0.1 millilitre is used. For solids or pastes, 100 milligram of the test substance is used, except that for substances in flake, granule, powder, or other particulate form the amount that has a volume of 0.1 millilitre (after compacting as much as possible without crushing or altering the individual particles, such as by, tapping the measuring container) shall be used whenever this volume weighs less than 100 milligram. In such a case, the weight of the 0.1 millilitre test dose should be recorded. The eyes are not washed following instillation of test material

GLP compliance:

no

Species:

rabbit

Strain:

other: albino

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL bulk volume (47 mg)
- Concentration (if solution): NA

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6

Details on study design:

The eyes are examined and the grade of ocular reaction is recorded at 24, 48 and 72 hours. Reading of reaction is facilitated by use of a binocular loupe, hand slit-lamp, or other expert means. After the recording of observations at 24 hours, any or all eyes may be further examined after applying fluorescein. For this optional test, one drop of fluorescein sodium ophthalmic solution U.S.P. or equivalent is dropped directly on the cornea. After flushing out the excess fluorescein with sodium chloride solution U.S.P. or equivalent, injured areas of the cornea appear yellow; this is best visualized in a darkened room under ultra-violet illumination. Any or all eyes may be washed with sodium chloride solution U.S.P. or equivalent after the 24 hour reading.

Scoring according to "Illustrated Guide for Grading Eye Irritation by Hazardous Substances" (Draize)

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.83

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.06

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

None of the animals gave "positive" reactions
Mild conjunctival reactions only were observed in all six animals

Interpretation of results:

GHS criteria not met

Conclusions:

Caledon Green XBN Grains gave a negative test for eye irritation, according to the definition given in the Code of Federal Regulations

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Various studies for skin or eye irritating properties were conducted wit Vat Green 1. In these studies, Vat Green 1 was not irritating to skin and eyes.