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

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6-9-2014 to 7-18-2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study performed in accordance with GLP. The only exception is that GLP characterization of the test material was not carried out.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Age at study initiation: 9 to 10 weeks
- Weight at study initiation: Minimum: 166.4, Maximum: 187.4
- Fasting period before study: overnight fasting and three hours post-dosing
- Housing: Rats were housed three rats/cage in standard polypropylene solid bottom cages which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). These cages have stainless steel top grills with steam sterilized corn cob bedding material and facilities for pelleted feed and drinking water (polypropylene bottle fitted with sipper tube). Rack units were rotated once in a week.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 to 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 23 °C
- Humidity (%): 65 to 67% relative humidity
- Air changes (per hr): 18 air changes/hour
- Photoperiod (hrs dark / hrs light): The photoperiod was 12 hours artificial light and 12 hours darkness, light hours being 06:00 h – 18:00 h which was maintained through an automatic timer.

IN-LIFE DATES: From: June 12, 2014 To: July 4, 2014

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: When the information suggests that mortality is unlikely at the highest dose level (2000 mg/kg body weight), then a limit test should be conducted. An initial dose of 2,000 mg/kg may be administered to three animals, in a step-wise method if necessary.

Dose Administration:
Individual dose volume was adjusted according to body weight, dose level and specific gravity of the test item. All rats were dosed by oral gavage (day 1) using a metal cannula attached to a BD 1 mL disposable syringe which was graduated up to 1 mL. Rats were fasted overnight prior to dosing until three hours post-dosing.

Limit Study:
Three female rats from set 1 were given a single dose of 2000 mg C.I. Solvent Red 175/kg body weight. As no mortality was observed up to approximately 48 hours at this dose level, another three female rats from set 2 were administered with the same dose of 2000 mg C.I. Solvent Red 175/kg body weight. As no mortality was observed at this dose level, further testing was not required.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed for signs of toxicity and mortality at ½, 1, 2, 3, 4 and 6 hours postadministration on the day of dosing. Subsequently, they were observed twice a day for morbidity and mortality for a period of 14 days following oral dosing. The clinical signs were recorded once a day. Individual body weights were recorded prior to dosing on day 1, and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: A gross pathological examination at necropsy consisting of an external examination and opening of abdominal and thoracic cavities was performed. The stomach of each rat was opened, the contents rinsed/removed, and the mucosal surface was examined for signs of irritation, erosions, ulcers or any other findings. Gross macroscopic changes, if any, were recorded.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed in any of the rats treated at the dose level of 2000 mg C.I. Solvent Red 175/kg body weight.

Clinical signs:

other: No sign of toxicity was observed in rats treated at the dose level of 2000 mg C.I. Solvent Red 175/kg body weight.

Gross pathology:

External examination of the terminally sacrificed rats did not reveal any pathological lesions in any of the treated animals. Visceral examination of rats sacrificed at termination did not reveal any pathological lesions in any of the treated animals.

TABLE 1: Test Sequence, Doses, Specific Gravity and Mortalities

Sex: Female

Rat No.	Dose (mg/kg body weight)	Dose Volume (mL)	Mortality after Dosing at
			½ - 6 h	24 h	48 h	72 h	5 – 8 Day	9 – 15 Day
1	2000	0.41	O	O	O	O	O	O
2	2000	0.40	O	O	O	O	O	O
3	2000	0.42	O	O	O	O	O	O
4	2000	0.45	O	O	O	O	O	O
5	2000	0.42	O	O	O	O	O	O
6	2000	0.43	O	O	O	O	O	O

Key: O = Survived

Note: The test substance was administered as received.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No mortality was observed in the treated rats. Rats treated with the C.I. Solvent Red 175 at 2000 mg/kg body weight showed no signs of toxicity. The acute oral LD50 of the C.I. Solvent Red 175 was estimated to be greater than 2000 mg/kg body weight in female Wistar rats.

Executive summary:

An acute oral toxicity study (Acute Toxic Class Method) was conducted using female Wistar rats given a single oral dose of C.I. Solvent Red 175 (undiluted, as received). A Limit Test was conducted with 2000 mg/kg body weight. The first set of three rats survived; hence an additional set of three female Wistar rats each received a single dose of 2000 mg/kg body weight according to the Acute Toxic Class Method. No mortality was observed in the treated rats. Rats treated with the C.I. Solvent Red 175 at 2000 mg/kg body weight showed no signs of toxicity. All animals were active and healthy and gained body weight during the course of the study.

External and visceral examination of terminally sacrificed rats did not reveal any pathological lesions in any of the treated animals. The acute oral LD50 of the C.I. Solvent Red 175 was estimated to be greater than 2000 mg/kg body weight in female Wistar rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

good

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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 402 (Acute Dermal Toxicity)

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

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

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

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. 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.

Duration of exposure:

24h

Doses:

2 gm/kg bw

No. of animals per sex per dose:

5

Control animals:

no

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 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.

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.

Statistics:

Data Evaluation:
In evaluating the average irritation, scores for individual intact exposure sites were recorded spearately for each of the scoring time intervals. Based on the 24, 48 and 72 hours post-dose observation periods, a total for erythema and eschar formation was added to a total for edema, then divided by 3 to yield the individual animal score. The mean of the ten scores was calculated and this represents the mean primary score.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None observed

Clinical signs:

other: 1 male had soft stool and 2 other males exhibited anorexia temporarily during the study.

Gross pathology:

There were no noteworthy findings

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:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Application of the test material to the skin of rabibits at a dose level of 2 g/kg did not produce lethality. The LD50 for this compounds is consequently >2 g/kg.

Executive summary:

Fluorescent Yellow *131, 1577-123, was evaluated for acute dermal toxicity 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 this result, the acute dermal LD50 of the test article is considered to be greater than 2.0 g/kg. In addition, the above referenced test article is considered to be non-irritating to the skin of rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

good

Additional information

Acute Oral toxicity:

An acute oral toxicity study (Acute Toxic Class Method) was conducted using female Wistar rats given a single oral dose of C.I. Solvent Red 175 (undiluted, as received). A Limit Test was conducted with 2000 mg/kg body weight. The first set of three rats survived; hence an additional set of three female Wistar rats each received a single dose of 2000 mg/kg body weight according to the Acute Toxic Class Method. No mortality was observed in the treated rats. Rats treated with the C.I. Solvent Red 175 at 2000 mg/kg body weight showed no signs of toxicity. All animals were active and healthy and gained body weight during the course of the study.

External and visceral examination of terminally sacrificed rats did not reveal any pathological lesions in any of the treated animals. The acute oral LD50 of the C.I. Solvent Red 175 was estimated to be greater than 2000 mg/kg body weight in female Wistar rats.

Acute Dermal toxicity

Fluorescent Yellow *131, 1577-123, was evaluated for acute dermal toxicity 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 this result, the acute dermal LD50 of the test article is considered to be greater than 2.0 g/kg. In addition, the above referenced test article is considered to be non-irritating to the skin of rabbits.

Justification for classification or non-classification

Criteria for classification not met.