α,α-bis[4-(dimethylamino)phenyl]-4-(phenylamino)naphthalene-1-methanol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Data is from experimental report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

The aim of this study was to assess the toxicity potential of the given test chemical after single oral administration in rats and an observation period of 14 days.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

α,α-bis[4-(dimethylamino)phenyl]-4-(phenylamino)naphthalene-1-methanol

EC Number:

229-851-8

EC Name:

α,α-bis[4-(dimethylamino)phenyl]-4-(phenylamino)naphthalene-1-methanol

Cas Number:

6786-83-0

Molecular formula:

C33H33N3O

IUPAC Name:

(4-anilino-1-naphthyl){bis[4-(dimethylamino)phenyl]}methanol

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report):Solvent Blue 4
- Molecular formula: C33H33N3O
- Molecular Weight: 487.644 g/mol
- Substance type:Organic
- Appearance: Blackish powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation:8- 10 weeks at the time of dosing.
- Health Status:Healthy young adult animals were used for the study. Females were nulliparous and non pregnant.
- Weight at study initiation:Minimum: 131 g Maximum: 160 g (Individual body weights were within ± 7% prior to treatment after overnight fasting)
- Fasting period:were fasted for 16 to 18 hours, prior to dosing .
- Housing:The animals were housed individually in polycarbonate cages.
- Bedding:All cages were provided with corn cobs (Sparconn Life Sciences Bangalore) Batch No.: SPAR – 25/2014.
- Room Sanitation:The experimental room floor and work tops were swept and mopped with disinfectant solution every day.
- Cages and water bottle:All the cages and water bottles were changed at least twice every week.
- Diet (e.g. ad libitum):All animals were provided conventional laboratory rodent diet (Nutrivet Life Sciences, Pune) ad libitum. Batch No 400004..
- Water (e.g. ad libitum):Aqua guard filtered tap water was provided ad libitum via drinking bottles
- Acclimation period:Animal nos. 1-3 were acclimatized for 5 days and 4-6 for 11 days prior to administration of the test item..

ENVIRONMENTAL CONDITIONS
-Temperature: Minimum: 19.80°C Maximum: 23.20°C
-Relative humidity:Minimum: 48.70 % Maximum: 69.20 %
-Light-dark-rhythm:12:12
-Air Changes: More than 12 changes per hour

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage):10 ml

Doses:

G1 = 2000 mg/kg bw

No. of animals per sex per dose:

6 female rats

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily
- Necropsy of survivors performed: yes
AAt the end of 14 day observation period, all surviving rats were euthanised by overdose of CO2 for external and internal observations.
- Other examinations performed: Clinical Observation - After test item administration, individual animals were frequently observed at 30 minutes, 1, 2, 3 and 4 hours post dosing on day 0 (day of dosing). Subsequently, all the six animals were observed once a day during the 14 day observation period.
Mortality - All the animals were observed twice daily (morning and evening) for morbidity and mortality, throughout the acclimatization and study period.
Body weight - All the rats were weighed on days 0 (prior to dosing), 7 and 14. Animals were weighed immediately after found dead.
Pathology - At the end of 14 day observation period, all surviving rats were euthanised by overdose of CO2 for external and internal observations

Statistics:

not specified

Results and discussion

Preliminary study:

not specified

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed througout the experimentation period

Clinical signs:

other: At 2000 mg/kg, animal no. 1 and 4 were observed with mild lethargy at 30 minutes, 1, 2, 3, 4 hours and on day 1 post dosing while additionally, animal no. 1 was observed with mild lethargy on day 2 and animal no. 4 was observed with mild diarrhea at 1 and

Gross pathology:

No external and internal gross pathological examination were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice

Other findings:

not specified

Any other information on results incl. tables

Table 1: Individual Animal Body Weight (g) andBody Weight Changes(%)

Sex:Female

Animal No.	Group/ Dose (mg/kg)	Body Weight (gram)			Body Weight Change (%)
		Day 0	Day 7	Day 14	Day 0-7	Day 0-14
1	G1/ 2000	135	160	177	18.52	31.11
2		146	180	199	23.29	36.30
3		137	143	172	4.38	25.55
4		147	166	182	12.93	23.81
5		160	190	206	18.75	28.75
6		131	161	183	22.90	39.69

Key:- = Not Applicable

 

Table 2: Summary of Animal Body Weight (g) and Body Weight Changes (%)

Sex:Female

Group/ Dose (mg/kg)		Rats Body Weight (g)			Body Weight Changes (%)
		Day 0	Day 7	Day 14	0-7	0-14
G1/ 2000	Mean	142.67	166.67	186.50	16.79	30.87
	SD	10.56	16.49	13.19	7.15	6.17
	n	6	6	6	6	6

Keys:SD = Standard Deviation, n = Number of Animals

Keys:- = Not applicable, 1 = Normal, 2 = Found dead, 4 = Abdominal breathing, 145 = Salivation,      155 = Sternal recumbency, 166 = Tremors, + = Mild, ++ = Moderate

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Conclusions:

Under the condition of the study, the acute oral LD50 value of the given test chemical was considered to be >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not exhibits acute oral toxicity in as per CLP criteria of classification

Executive summary:

Acute oral toxicity study was performed as per OECD No. 423 by using the given test chemical in Rats. Six female Wistar rats were selected for acute oral toxicity study. The animals were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, with food withheld but drinking water provided ad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs.

Three rats of group G1 were dosed with starting dose of 2000 mg/kg body weight and the animals showed no mortality post dosing, so another three rats of the same group were dosed with 2000 mg/kg weight and no mortality was observed. Hence, further dosing was stopped.

Body weights were re­corded on day 0 (prior to dosing) 7 and 14. Mean body weight of all six animals was observed with gain on day 7 and 14, as compared to day 0. At 2000 mg/kg, animal no. 1 and 4 were observed with mild lethargy at 30 minutes, 1, 2, 3, 4 hours and on day 1 post dosing while additionally, animal no. 1 was observed with mild lethargy on day 2 and animal no. 4 was observed with mild diarrhea at 1 and 2 hours, followed by normal clinical signs till day 14. Animal no. 2 was observed with normal clinical signs at 30 minutes, mild lethargy at 1, 2, 3 and 4 hours and mild diarrhoea at 1 and 2 hours, followed by normal clinical signs till day 14. Animal no. 3 was observed with mild lethargy at 30 minutes, 1, 2, 3, 4 hours, day 1, 2 and 3 and mild diarrhoea at 2 hours, followed by normal clinical signs till day 14. Animal no. 5 was observed with mild lethargy at 30 minutes, 1, 2, 3 and 4 hours and mild diarrhoea at 1, 2, 3 and 4 hours, followed by normal clinical signs till day 14. Animal no. 6 was observed normal clinical signs at 30 minutes, 1, 2, 3 and 4 hours and mild lethargy on day 1 and 2, followed by normal clinical signs till day 14.

No external and internal gross pathological examination were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifce.

Under the condition of the study, the acute oral LD50 value of the given test chemical was considered to be >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that the given test chemical does not exhibits acute oral toxicity in as per CLP criteria of classification