Bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Justification for type of information:

Data is from study report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

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 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:

Bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine

EC Number:

239-816-9

EC Name:

Bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine

Cas Number:

15721-78-5

Molecular formula:

C28-H43-N

IUPAC Name:

4-(2,4,4-trimethylpentan-2-yl)-N-[4-(2,4,4-trimethylpentan-2-yl)phenyl]aniline

Test material form:

other: solid

Details on test material:

Identification : Bis(4-(1,1,3,3-tetramethylbutyl)phenyl amine
Appearance : Off White Solid
Batch number : Lot. 03/31
CAS No. : 15721-78-5
AI Content : 98.72%
Storage conditions : Room temperature (20 - 30 °C)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species:Rattus norvegicus (Rat)
Strain-Wistar
Number and Sex:Six Females
Supplier / Source: In-house animals
Health Status:Healthy young adult animals were used for the study. Females were nulliparous and non pregnant.
Body weight of animals:Minimum: 151 g Maximum: 167 g (Individual body weights were within ± 4% prior to treatment after overnight fasting).
Acclimatisation:Animal nos. 1-3 were acclimatized for 7 days and 4-6 for 9 days, prior to administration of the test item.
Identification :TThe animals were marked temporarily on tail, permanently on toe pad micro tattooing and cage cards. Individual cage cards were labelled with study no., study type, test system, group, dose, sex, animal number experimental start and completion date.
Husbandry Conditions
Diet:All animals were provided conventional laboratory rodent diet (Nutrivet Life Sciences, Pune) ad libitum. Batch No.: 400010.
Bedding:All cages were provided with corn cobs (Sparconn Life Sciences Bangalore) SPAR – 26 /2014 and SPAR – 27 /2014.
Water: Aqua guard filtered tap water was provided ad libitum via drinking bottles.
Husbandry:The animals were housed individually in polycarbonate cages.
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.
Experimental Room Condition
Temperature :Minimum: 19.60 °C Maximum: 21.40 °C
Relative humidity:Minimum: 47.40% Maximum: 58.60%
Light-dark-rhythm: 12:12
Air Changes: More than 12 changes per hour

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

water

Details on oral exposure:

VEHICLE
Distilled water was selected as a vehicle based on solubility testing.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2000 mg/kg bw-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
- Other examinations performed:
clinical signs: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 surviving animals were observed once a day during the 14 day observation period

mortality:All surviving animals were observed twice daily (morning and evening) for morbidity and mortality, throughout the acclimatization and study period

Body weight:All surviving rats were weighed on days 0 (prior to dosing), 7 and 14.

Pathology:At the end of 14 day observation period, all the survived rats were euthanised by overdose of CO2. All the animals were observed for external and internal gross pathology

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Non toxic

Mortality:

No mortality was observed in the animals treated with 2000 mg/kg dose throught out the 14 days observation period

Clinical signs:

other: At 2000 mg/kg, all the animals were normal throughout the experimental period

Gross pathology:

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

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	160	181	193	13.13	20.63
2		157	186	197	18.47	25.48
3		151	175	187	15.89	23.84
4		167	192	208	14.97	24.55
5		162	193	199	19.14	22.84
6		167	203	212	21.56	26.95

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	160.67	188.33	199.33	17.19	24.05
	SD	6.15	9.87	9.31	3.09	2.19
	n	6	6	6	6	6

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

Table 3: Individual Animal Clinical Signs and Symptoms

 

Sex:Female

Animal No.	Group/ Dose (mg/kg)	Hours (Day 0)
		1/2	1	2	3	4
1	G1/ 2000	1	1	1	1	1
2		1	1	1	1	1
3		1	1	1	1	1
4		1	1	1	1	1
5		1	1	1	1	1
6		1	1	1	1	1

 

Animal No.		Group/ Dose (mg/kg)		Days post dosing
			1		2		3		4		5		6		7		8		9		10		11		12		13		14
1		G1/ 2000		1		1		1		1		1		1		1		1		1		1		1		1		1		1
2			1		1		1		1		1		1		1		1		1		1		1		1		1		1
3			1		1		1		1		1		1		1		1		1		1		1		1		1		1
4			1		1		1		1		1		1		1		1		1		1		1		1		1		1
5			1		1		1		1		1		1		1		1		1		1		1		1		1		1
6			1		1		1		1		1		1		1		1		1		1		1		1		1		1

Table 4: Individual Animal Mortality Record

 

Sex:Female

Animal No.	Group/ Dose (mg/kg)	Day of Observation (Day 0 to 14)
		Morning Observations	Evening Observations
1	G1/ 2000	No mortality and morbidity	No mortality and morbidity
2		No mortality and morbidity	No mortality and morbidity
3		No mortality and morbidity	No mortality and morbidity
4		No mortality and morbidity	No mortality and morbidity
5		No mortality and morbidity	No mortality and morbidity
6		No mortality and morbidity	No mortality and morbidity

Table 5: Gross Necropsy Observation

 

Sex:Female                                                                                                                                        

Animal No.	Group/ Dose (mg/kg)	Mode of Death	Gross Observation
			External	Internal
1	G1/ 2000	TS	No abnormality detected	No abnormality detected
2		TS	No abnormality detected	No abnormality detected
3		TS	No abnormality detected	No abnormality detected
4		TS	No abnormality detected	No abnormality detected
5		TS	No abnormality detected	No abnormality detected
6		TS	No abnormality detected	No abnormality detected

Keys:TS =Terminal Sacrifice

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 (Cut-off value) of test chemical was more than 2000 mg/kg body weight.

Executive summary:

Acute Oral Toxicity Study of test chemical in Rats, was conducted. This study was performed as per OECD No. 423.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 providedad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs.Three rats of first group were dosed with starting dose of 2000 mg/kg body weight and the animals did not show any mortality so another three animals of the same group were dosed with 2000 mg/kg body 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 the animals treated with 2000 mg/kg body weight was observed with gain on day 7 and 14, as compared to day 0.At 2000 mg/kg, all the animals were normal throughout theexperimental period

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

Thus considering the CLP Criteria for classification of the substance, it is concluded that test chemical could not exhibit acute toxicity to rat by the oral route.