9,10-Anthracenedione, 1,4-diamino-, N,N'-bis(4-C7-17-branched alkylphenyl) derivs.

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from study report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Acute Inhalation Toxicity Study of 9,10-Anthracenedione, 1, 4-Diamino-N-N’-Bis (4-C7-17-Branched Alkyl phenyl) Derives in albino rat

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

9,10-Anthracenedione, 1, 4-Diamino-N-N’-Bis(4-C7-17-Branched Alkyl phenyl) Derives

Cas Number:

97862-23-2

IUPAC Name:

9,10-Anthracenedione, 1, 4-Diamino-N-N’-Bis(4-C7-17-Branched Alkyl phenyl) Derives

Constituent 2

Reference substance name:

9,10-Anthracenedione, 1,4-diamino-, N,N'-bis(4-C7-17-branched alkylphenyl) derivs

IUPAC Name:

9,10-Anthracenedione, 1,4-diamino-, N,N'-bis(4-C7-17-branched alkylphenyl) derivs

Constituent 3

Reference substance name:

9,10-Anthracenedione, 1,4-diamino-, N,N'-bis(4-C7-17-branched alkylphenyl) derivs.

EC Number:

308-067-0

EC Name:

9,10-Anthracenedione, 1,4-diamino-, N,N'-bis(4-C7-17-branched alkylphenyl) derivs.

Cas Number:

97862-23-2

Molecular formula:

C48H62N2O2

IUPAC Name:

9,10-Anthracenedione, 1,4-diamino-, N,N'-bis(4-C7-17-branched alkylphenyl) derivs.

Details on test material:

-Substance Name: 9,10-Anthracenedione, 1,4-diamino-, N,N'-bis(4-C7-17-branched alkylphenyl) derivs
-Substance type: Organic
-Physical state: Liquid

Specific details on test material used for the study:

Name: 9, 10-Anthracenedione, 1, 4-Diamino-N-N’-Bis (4-C7-17-Branched Alkylphenyl) Derives
- Physical state: Dark blue liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source : Institute for Industrial Research & Toxicology
Age : 7 to 9 weeks
Sex : Male and Female
Body weight range :200 ±20g
Identification : By cage tag and corresponding colour body marking
No. of animals per dose group :10 (5 males and 5 females)
No. of dose group : Two :Group I – Limit test (5 mg/L) and Group II – Confirmatory test (5 mg/L)
Acclimatization :Twenty healthy albino rats were selected and acclimatized for standard laboratory condition for period of one week in experimental room under veterinary examination.
Randomization : After acclimatization and veterinary examination all the selected rats randomly divided into two groups of five females and five males.
Nutritional conditions :For feeding conventional Laboratory diets may be used with an unlimited supply of drinking water.
HUSBANDRY
Environmental conditions :Air conditioned rooms with 10-15 air changes per hour, temperature between 19-25 0C, relative humidity 30-60% and illumination cycle set to 12 hours artificial fluorescent light and 12 hours dark.
Accommodation :Groups of five animals of similar sex in polypropylene cages with stainless steel grill top, facilities for food and water bottle, and bedding of clean paddy husk.
Diet : Pelleted feed supplied by Pranav agro Industries Ltd., B7/6 Ramesh Nagar, Delhi, India
Water : Community tap water passed through ‘Aqua Guard on line water filter’, was kept in glass bottles, ad-libitum

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: 0.1% tween 80 in Distilled water

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:Nanotek aerosol generator
- Exposure chamber volume: 8 liters
- Method of holding animals in test chamber:For the inhalation purpose the rats were placed in polycarbonate holder tubes positioned radically around exposure chamber, so that only the snouts and nostrils of the animals were exposed to the aerosol.
- Source and rate of air: No data available
- Method of conditioning air:The chamber was maintained at a slightly negative pressure to prevent leakage of the test atmosphere from system, as well as its dilution with outside air.
- System of generating particulates/aerosols:Nanotek aerosol generator
- Method of particle size determination:
- Treatment of exhaust air: The exhaust air was decontaminated by subsequent passage through 1% NaOH solution, silica gel and activated charcoal filters.
- Temperature, humidity, pressure in air chamber: Temperature- 23.29±1.08 - 23.47±1.74, Relative humidity (%): 46.31±3.24 - 47.34±3.56

TEST ATMOSPHERE
- Brief description of analytical method used: No data available
- Samples taken from breathing zone: no

VEHICLE
- Composition of vehicle (if applicable):0.1% tween 80 in Distilled water
- Concentration of test material in vehicle (if applicable): 5 mg/L
- Justification of choice of vehicle: No data available
- Lot/batch no. (if required): No data available
- Purity: No data available

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: less than 1 micron
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): No data available

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration:No data available

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Concentrations:

5 mg/L

No. of animals per sex per dose:

Total: 20
Group I – Limit test (5 mg/L) : 5 males and 5 females
Group II – Confirmatory test (5 mg/L): 5 males and 5 females

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:closely observed for any clinical signs of toxicity at various intervals such as 1 hr, 2 hrs, 4 hrs, and 6 hrs on the day of test compound aerosol exposure and later on twice a day throughout the experimentation period of 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: Mortality, clinical signs, body weight and gross pathology were examined.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No mortality observed

Mortality:

No mortality was recorded in any of the Wistar albino rats in both limit test and confirmatory test after 4 hours of exposure.

Clinical signs:

other: No clinical signs of intoxication at the tested aerosol concentration of 5 mg/L observed for the period of 14 days.

Body weight:

No significant increase or decrease in body weight on day 7th and 14th were observed when compared with day 0.

Gross pathology:

No gross pathological changes were observed in treated rats.

Any other information on results incl. tables

EXPOSURE ATMOSPHERE DATA 

Parameters	Group-I (5 mg/L) (limit test)	Group-II (5 mg/L) (confirmatory test)
Chamber temperature °C (Mean ± S.E.)	23.29±1.08	23.47±1.74
Relative humidity (%)  (Mean ± S.E.)	46.31±3.24	47.34±3.56
Oxygen content (%) (Mean ± S.E.)	20.21±1.16	21.34±1.52

 

Mean Body Weight (gm)

S.No.	Groups	BODY WEIGHT (gm)
		DAY 0	DAY 7^th	% gain or loss	DAY14^th	% gain or loss
1.	Group-I (5.0 mg/L)	200.37	205.69	2.65	211.71	5.65
2.	Group-II (5.0 mg/L)	203.11	209.82	3.30	214.24	5.47

CLINICAL SIGNS AND MORTALITY

Group: I Limit test                                                                         Dose: 5.0 mg/L

Parameters	Incidence of Clinical Signs Observed after Dosing on																			Mortality
	Day 0					DAY
	Min	Hour
	30	1	2	4	6	1	2	3	4	5	6	7	8	9	10	11	12	13	14	Total	%
Mortality (total)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0/10	0
Clinical Signs	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

 

0         =   No clinical sign (Normal)

+         =   Mild

++        =   Moderate

+++      =   High

++++  =         Severe

CLINICAL SIGNS AND MORTALITY

Group: II Confirmatory test                                                                    Dose: 5.0 mg/L

Parameters	Incidence of Clinical Signs Observed after Dosing on																			Mortality
	Day 0					DAY
	Min	Hour
	30	1	2	4	6	1	2	3	4	5	6	7	8	9	10	11	12	13	14	Total	%
Mortality (total)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0/10	0
Clinical Signs	0	0	0	0	6	0	0	0	0	0	0	0	0	0	0	0	0	0	0

 0         =   No clinical sign (Normal)

+         =   Mild

++        =   Moderate

+++      =   High

++++    =   Severe

SUMMARY OF NECROPSY FINDING

 

S. No.	Fate	Wistar albino rats
		Dose (mg/l)
		5.0 (limit test)	5.0 (confirmatory test)
1	Terminal sacrifice	10/10	10/10
2	Found Dead	0/10	0/10
3	Abnormalities detected	0/10	0/10

INDIVIDUAL ANIMAL FATE & NECROPSY FINDINGS

Group: I Limit test                                                                          Dose: 5.0 mg/L       

Animal ID	Fate	Time	Gross Findings
20172-1	TS	Day 14	NAD
20172-2	TS	Day 14	NAD
20172-3	TS	Day 14	NAD
20172-4	TS	Day 14	NAD
20172-5	TS	Day 14	NAD
20172-6	TS	Day 14	NAD
20172-7	TS	Day 14	NAD
20172-8	TS	Day 14	NAD
20172-9	TS	Day 14	NAD
20172-10	TS	Day 14	NAD

Day 0 is the day of exposure

TS=Terminal Sacrifice

NAD=No Abnormality Detected

FD=Found Dead

INDIVIDUAL ANIMAL FATE & NECROPSY FINDINGS

Group: II Confirmatory test                                                                    Dose:5.0 mg/L       

Animal ID	Fate	Time	Gross Findings
20172-11	TS	Day 14	NAD
20172-12	TS	Day 14	NAD
20172-13	TS	Day 14	NAD
20172-14	TS	Day 14	NAD
20172-15	TS	Day 14	NAD
20172-16	TS	Day 14	NAD
20172-17	TS	Day 14	NAD
20172-18	TS	Day 14	NAD
20172-19	TS	Day 14	NAD
20172-20	TS	Day 14	NAD

Day 0 is the day of exposure

TS=Terminal Sacrifice

NAD=No Abnormality Detected

FD=Found Dead

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Conclusions:

Acute lethal Concentration (LC50) of test compound was found be more than 5 mg/L. when Wistar Albino Male and Female rats were inhaled for 4 hours.

Executive summary:

In a acute inhalation toxicity study,Wistar Albino Male and Female rats were exposed with test chemical in the concentration of 5 mg/L in a dynamic nose-only cylindrical chamber built from stainless steel and glass. The chamber had a volume of 8 liters with inner and outer chamber to minimize the fluctuation in concentration and temperature for 4 hours. No mortality was recorded in any of the Wistar albino rats in both limit test and confirmatory test after 4 hours of exposure. No clinical signs of intoxication at the tested aerosol concentration of 5 mg/L observed for the period of 14 days. No significant increase or decrease in body weight on day 7^thand 14^thwere observed when compared with day 0. No gross pathological changes were observed in treated rats. After 72 hrs, the result obtained from limit test was confirmed in another 10 animal of both sex at similar concentration. No effects were observed in exposed rats at 5 mg/L. Therefore, Acute lethal Concentration (LC50) of test compound was found be more than 5 mg/L. when Wistar Albino Male and Female rats were inhaled for 4 hours.