Benzo[rst]phenanthro[10,1,2-cde]pentaphene-9,18-dione, reaction products with 1-chlorododecane

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD guideline study performed in accordance with GLP; exact details of test material (certificate of analysis, Characterisation) are not included in the report.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Ten young adult New Zealand White rabbits were obtained from New York State Rabbit Development, Hartwick, New York for use in this study. All housing and care conformed to the standards established in the "Guide for the Care and Use of Laboratory Animals" DHEN Publication No. (NIH) 78-23. The rabbits were individually housed in wire mesh bottom cages in environment-controlled rooms and provided NIH Animal Feed A (certified) and water ad libitum. Animals were identified with ear tags and color coded cage cards. All animals were acclimated a minimum of 5 days. During this acclimation period, the rabbits were examined with respect to their general health to assure their suitability as test animals.

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

2 gm/kg bw

Duration of treatment / exposure:

24h

Observation period:

After an exposure period of 24 hours, the binders were removed. The exposure sites were then gently wiped with clean gauze to remove as much non-absorbed test article as possible. One-half hour after unwrapping, the exposure sites were examined and scored spearately for both erythema and edema on a graded scale of 0 to 4 in accordance with the Skin Reaction code in Appendix 1. The exposure sites were again examined and scored at 48 and 72 hours post-dose. If irritation persisted at the 72 hour post-dose observation period, the sites were furthered examined at 4,7, 10, and 14 days post-dose or until all sites returned to normal, whichever occured first.

Number of animals:

5/sex/dose

Details on study design:

Procedure:
On the day prior to dosing, the back and flanks of each rabbit were clipped free of fur with electric clippers. The test article was administered under an occlusive binder at a level of 2.0 g/kg body weight. The binder consisted of a layer of plastic wrap and stockinette binder, all securely held in place with masking tape. The occlusive binder was applied to maintain contact and minimize evaporation of the test article.

Observations:
After an exposure period of 24 hours, the binders were removed. The exposure sites were then gently wiped with clean gauze to remove as much non-absorbed test article as possible. One-half hour after unwrapping, the exposure sites were examined and scored spearately for both erythema and edema on a graded scale of 0 to 4 in accordance with the Skin Reaction code. The exposure sites were again examined and scored at 48 and 72 hours post-dose. If irritation persisted at the 72 hour post-dose observation period, the sites were furthered examined at 4,7, 10, and 14 days post-dose or until all sites returned to normal, whichever occured first.

All animals were observed frequently on the day of dosing and twice daily for the remainder of the study. All external signs of toxicity or pharmacological effects were noted. Body weights were recorded initially, on days 8 and 15 or at death.

Necropsy:
All animals that died during the study, and all survivors at termination (day 15) were subjected to gross necropsy and abnormalities were noted.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

The individual mean 24.5/48/72 h score for all animals on study was 0.

Time point:

other: 24.5/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other:

Remarks:

The first observation time-point post dose was actually 24.5 hr instead of 24 hr.This has no impact on the evaluation results.

Irritation parameter:

edema score

Basis:

mean

Remarks:

The individual mean 24.5/48/72 h score for all animals on study was 0.

Time point:

other: 24.5/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other:

Remarks:

The first observation time-point post dose was actually 24.5 hr instead of 24 hr.This has no impact on the evaluation results.

Other effects:

One male had soft stool and 2 other males exhibited anorexia temporarily during the study. Animals gained weight throughout the study. There were no noteworthy findings in gross pathology and there was no mortality.

Skin Irritation Scores

	Obs. Post-dose hrs	Rabbit Number
		Males					Females
		3276	3280	3282	3283	3286	3344	3346	3358	3359	3360
Erythema	24.5	0	0	0	0	0	0	0	0	0	0
	48	0	0	0	0	0	0	0	0	0	0
	72	0	0	0	0	0	0	0	0	0	0
Edema	24.5	0	0	0	0	0	0	0	0	0	0
	48	0	0	0	0	0	0	0	0	0	0
	72	0	0	0	0	0	0	0	0	0	0
	Summary of Irritation Potential
Erythema sub-total		0	0	0	0	0	0	0	0	0	0
Edema sub-total		0	0	0	0	0	0	0	0	0	0
Total for Erythema and Edema		0	0	0	0	0	0	0	0	0	0
Individual Animal Score		0	0	0	0	0	0	0	0	0	0

Mean Primary Irritation Score: 0

Interpretation of results:

GHS criteria not met

Conclusions:

Fluorescent Yellow *131, 1577-123, was evaluated for skin irritation potential in male and female New Zealand White rabbits. The test article was applied to each of ten rabbits at a level of 2.0 g/kg body weight. All animals survived the 15 day post-dose observation period. Based on the results, the test article is considered to be non-irritating to the skin of rabbits.

Executive summary:

Fluorescent Yellow *131, 1577-123, was evaluated for skin irritation potential in male and female New Zealand White rabbits. The test article was applied to each of ten rabbits at a level of 2.0 g/kg body weight. All animals survived the 15 day post-dose observation period. Based on the results, the test article is considered to be non-irritating to the skin of rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD guideline study performed in accordance with GLP; exact details of test material (certificate of analysis, Characterisation) are not included in the report.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Animals and Animal Care:
Six young adult New Zealand White rabbits were obtained from New York State Rabbit Development, Hartwick, New York for use in this study.

All housing and care conformed to the standards established in "Guide for the Care and Use of Laboratory Animals" DHEW Publication No. (NIH) 78-23. The rabbits were individually housed in wire mesh bottom cages in an environment-controlled room and provided NIH Animal Feed A (certified) and water ad libitum. Animals were identified with ear tags and color coded cage cards and acclimated for a minimum of 5 days prior to study initiation.

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated eye served as control.

Amount / concentration applied:

0.1 ml of undiluted material was applied to the eye of the rabbit. The other eye served as the untreated control.

Duration of treatment / exposure:

Single exposure. Eyes are not irrigated after test article installation.

Observation period (in vivo):

The treated eyes were examined with the aid of sodium fluorescin and the grade of ocular reaction was recorded for all animals at 1, 24, 48, 72 and 96 hours using the Draize Scale for Scoring Ocular Lesions. Readings were made every 3 days thereafter, if injury persisted, for at least 13 days after treatment or until all signs of reversible toxicity subsided.

Number of animals or in vitro replicates:

6

Details on study design:

The treated eyes were examined with the aid of sodium fluorescin and the grade of ocular reaction was recorded for all animals at 1, 24, 48, 72 and 96 hours using the Draize Scale for Scoring Ocular Lesions.

Irritation parameter:

cornea opacity score

Basis:

other: Mean score for all animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

other: Mean score for all animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

other: Mean score for all animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

other: Mean score for all animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Individual Rabbit Eye Irritation Scores

			Reading
Rabbit Number	Item	Tissue	1 hr	24 hr	48 hr	72 hr
3149	A	Cornea Opacity	0	0	0	0
	B	Cornea Area	0	0	0	0
	(1)	Cornea Total=(AxB)x5	0	0	0	0
	C	Iris	0	0	0	0
	(2)	Iris Total=(C)x5	0	0	0	0
	D	Conjunctiva Redness	1	0	0	0
	E	Conjunctiva Chemosis	0	0	0	0
	F	Conjunctiva Discharge	1	0	0	0
	(3)	Conjunctiva Total (D+E+F)x2	4	0	0	0
		Totals Added= (1+2+3)	4	0	0	0
3150	A	Cornea Opacity	0	0	0	0
	B	Cornea Area	0	0	0	0
	(1)	Cornea Total=(AxB)x5	0	0	0	0
	C	Iris	0	0	0	0
	(2)	Iris Total=(C)x5	0	0	0	0
	D	Conjunctiva Redness	1	0	0	0
	E	Conjunctiva Chemosis	0	0	0	0
	F	Conjunctiva Discharge	0	0	0	0
	(3)	Conjunctiva Total (D+E+F)x2	2	0	0	0
		Totals Added= (1+2+3)	2	0	0	0
3152	A	Cornea Opacity	0	0	0	0
	B	Cornea Area	0	0	0	0
	(1)	Cornea Total=(AxB)x5	0	0	0	0
	C	Iris	0	0	0	0
	(2)	Iris Total=(C)x5	0	0	0	0
	D	Conjunctiva Redness	0	0	0	0
	E	Conjunctiva Chemosis	0	0	0	0
	F	Conjunctiva Discharge	0	0	0	0
	(3)	Conjunctiva Total (D+E+F)x2	0	0	0	0
		Totals Added= (1+2+3)	0	0	0	0
3154	A	Cornea Opacity	0	0	0	0
	B	Cornea Area	0	0	0	0
	(1)	Cornea Total=(AxB)x5	0	0	0	0
	C	Iris	0	0	0	0
	(2)	Iris Total=(C)x5	0	0	0	0
	D	Conjunctiva Redness	1	0	0	0
	E	Conjunctiva Chemosis	0	0	0	0
	F	Conjunctiva Discharge	0	0	0	0
	(3)	Conjunctiva Total (D+E+F)x2	2	0	0	0
		Totals Added= (1+2+3)	2	0	0	0
3155	A	Cornea Opacity	0	0	0	0
	B	Cornea Area	0	0	0	0
	(1)	Cornea Total=(AxB)x5	0	0	0	0
	C	Iris	0	0	0	0
	(2)	Iris Total=(C)x5	0	0	0	0
	D	Conjunctiva Redness	1	0	0	0
	E	Conjunctiva Chemosis	0	0	0	0
	F	Conjunctiva Discharge	0	0	0	0
	(3)	Conjunctiva Total (D+E+F)x2	2	0	0	0
		Totals Added= (1+2+3)	2	0	0	0
3156	A	Cornea Opacity	0	0	0	0
	B	Cornea Area	0	0	0	0
	(1)	Cornea Total=(AxB)x5	0	0	0	0
	C	Iris	0	0	0	0
	(2)	Iris Total=(C)x5	0	0	0	0
	D	Conjunctiva Redness	1	0	0	0
	E	Conjunctiva Chemosis	0	0	0	0
	F	Conjunctiva Discharge	1	0	0	0
	(3)	Conjunctiva Total (D+E+F)x2	4	0	0	0
		Totals Added= (1+2+3)	4	0	0	0

Initial Body Weights:

Animal Number       Initial Body Weight (kg)

83 -3149                     2.18

83 -3150                     2.20

83 -3152                     2.58

83 -3154                     2.48

83 -3155                     2.60

83 -3156                     2.32

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

All animals were clear of effects on corneal opacity, iris, redness or chemosis at the 24 hr time-point and thereafter.

Executive summary:

The primary ocular irritation potential of Fluorescent Yellow #131 was evaluated in this study with New Zealand White rabbits. One group of six albino rabbits received a single, unwashed exposure. Each 0.1- ml dose of the test article was instilled into the lower conjunctival sac of one eye. The other eye served as an untreated control. The eyes were examined for ocular reactions in accordance with the method of Draize at 1, 24, 48 and 72 hours after dosing. All animals were free of effects on corneal opacity, iris, redness and chemosis at the 24 hr timepoint and thereafter.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:

Fluorescent Yellow *131, 1577-123, was evaluated for skin irritation potential in male and female New Zealand White rabbits. The test article was applied to each of ten rabbits at a level of 2.0 g/kg body weight. All animals survived the 15 day post-dose observation period. Based on the results, the test article is considered to be non-irritating to the skin of rabbits.

Eye irritation

The primary ocular irritation potential of Fluorescent Yellow #131 was evaluated in this study with New Zealand White rabbits. One group of six albino rabbits received a single, unwashed exposure. Each 0.1- ml dose of the test article was instilled into the lower conjunctival sac of one eye. The other eye served as an untreated control. The eyes were examined for ocular reactions in accordance with the method of Draize at 1, 24, 48 and 72 hours after dosing. All animals were free of effects on corneal opacity, iris, redness and chemosis at the 24 hr timepoint and thereafter.

Justification for classification or non-classification

Criteria for classification are not met.