Amines, C12-18-alkyldimethyl

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 07 DEC 1983 to 12 JAN 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication/study report which meets basic scientific principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

yes

Remarks:

First dose was at the estimated LD50, only 24 h before next animal was treated

GLP compliance:

not specified

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Amines, C12-18-alkyldimethyl

EC Number:

269-923-6

EC Name:

Amines, C12-18-alkyldimethyl

Cas Number:

68391-04-8

Molecular formula:

R-N(Me)2, whereas R= C12-18-alkyl (even numbered, unbranched, saturated)

IUPAC Name:

N,N-dimethyl-C12-18-(even numbered)-alkyl-1-amines

Details on test material:

Based on the qualitative and quantitative information on the composition, the sample used is representative of the boundary composition shared and agreed by each registrant.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hacking and Churchill Limited, Huntingdon, Cambridgeshire, England
- Age at study initiation: 6 weeks
- Weight at study initiation: 83-128 g
- Housing: individually in metal cages with wire mesh floors
- Diet: Spratt´s Rodent Breeding diet, ad libitum, feed was prevented overnight prior to and approximately 4 hours after dosing
- Water: ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-23
- Humidity (%): 45
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

other: oral using a syringe and a plastic catheter

Vehicle:

unchanged (no vehicle)

Doses:

1.0, 1.26, 1.6, 2.0, 2.5 g/kg

No. of animals per sex per dose:

One male and one female rat were treated at the estimated LD50

Control animals:

not specified

Details on study design:

All animals were observed for 7 days after dosing

Statistics:

LD50 values were estimated by probit analysis using a slope estimated from background data.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

1.5 other: g/kg bw

Based on:

test mat.

95% CL:

1.1 - 1.9

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

1.3 other: g/kg bw

Based on:

test mat.

95% CL:

1 - 1.7

Mortality:

Deaths occurred amongst rats treated with1.6 g/kg and higher within two and four days after dosing.
Autopsy revealed congestion or haemorhage of the lungs and pallor of the liver, kidneys and spleen.
Congestion of the blood vessels of the stomach was observed in two animals at a 1.6g/kg

Clinical signs:

other: lethargy and increased salivation amongst rats treated of all dose levels. Decreased respiratory rate and ptosis amongst rats treated at 1.0, 1.6, 2.0 and 2.5 g/kg. Diarrhoea amongst rats treated at 1.6 and 2.0 g/kg.

Any other information on results incl. tables

Sex	Dose (g/kg)	Mortality data on each dosing occasion
		1	2	3	4	5	6	7	8	9
Male	1	0	1	0	1	1	0	1	0	1
	1,26
	1,6
	2
	2,5
Female	1	0	1	1	1	1	0	1	0	1
	1,26
	1,6
	2
	2,5

1: animal died; 0: Animal survived

Sex	Dose (g/kg)	Number of deaths/ N0.desed	Day
			1
			Hours after dosing							2		3		4		5-8
			1/2	1	2	3	4	5	6	a	b	a	b	a	b	a	b
Male	1	0/1
	1,26	0/2
	1,6	3/4								1		2
	2	1/1								1
	2,5	1/1								1
Female	1	0/1
	1,26	0/2
	1,6	4/4								2	1	1
	2	1/1										1
	2,5	1/1										1

The hour/day indicated is the time that the time that the animal was observaed to die or found dead

a First observation

b Second observation

Signs	No. Of the rats showing signs
	Dose (g/kg)
	Number of rats dosed per sex
	1		1,26		1,6		2		2,5
	1 m	1 f	2 m	2f	4m	4f	1m	1f	1m	1f
Pilo-erection	1	1	2	2	4	4	1	1	1	1
Abnormal body carriage (hunched posture)	1	1	2	2	4	4	1	1	1	1
Abnormal gait (waddling)	1	1	2	2	4	4	1	1	1	1
Lethargy	1	1	2	2	3	2	1	1	1	1
Decreased respiratory rate	1	1	0	0	3	2	0	1	1	1
Pallor of the extremites	1	1	2	2	4	4	1	1	1	1
Increased salivation	0	1	1	1	3	3	1	1	1	0
Ptosis	0	1	0	0	2	1	0	1	1	0
Diarrhoea	0	0	0	0	1	1	1	1	0	0

Sex	Dose (g/kg)	Bodyweight (g) at Day
		Day 1	Day 8	Death
Male	1	109	162	-
	1,26	110 119	171 176	- ¡-
	1,6	108 100 101 90	157 '- '- '-	- 80 83 64
	2	126	-	110
	2,5	128	-	112
Female	1	90	139	-
	1,26	102 102	123 124	- '-
	1,6	103 103 83 90	- '- '- '-	86 98 75 85
	2	102	-	84
	2,5	108	-	93

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute median lethal oral doses LD50 to male and female rats of the substance were estimated to be: Males: 1.5 g/kg bw and females: 1.3 g/kg bw. The substance was classified as "toxic cat. IV".

Executive summary:

The study was designed to assess the toxicity following a single oral dose to male and female Sprague-Dawley rats.The animals were oberved for 7 days after dosing. The Doses were: 1.0, 1.26, 1.6, 2.0 and 2.5 g/kg for one male and one female respectively.

The acute median lethal oral doses LD50 and their 95% confidence limits to male and female rats of the substance were estimated to be for males: 1.5 g/kg bw (1.1 to 1.9 g/kg bw) and for females: 1.3 g/kg bw (1.0 to 1.7 g/kg bw).