Anhydro-D-glucitol trioleate

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

other information

Study period:

1968

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1968

Report date:

1968

Materials and methods

Principles of method if other than guideline:

Acute intravenous toxicity in rats.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Anhydro-D-glucitol trioleate

EC Number:

247-569-3

EC Name:

Anhydro-D-glucitol trioleate

Cas Number:

26266-58-0

Molecular formula:

C60H108O8

IUPAC Name:

1,4-anhydro-2,3,6-tri-O-oleoyl-L-iditol

Details on test material:

- Name of test material (as cited in study report): Sorbitantrioleate
- Substance type: organic
- Physical state: amber liquid
- Analytical purity: no data
- Lot/batch No.: 4199c

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Manor Farms Research (internally continued)
- Weight at study initiation: 133-144 g (average 138 g, males), 134-164 g (average 145 g, females)
- Fasting period before study: 16 h
- Diet: ad libitum

Administration / exposure

Route of administration:

intravenous

Vehicle:

propylene glycol

Details on exposure:

The test material was given as a 25% (w/v) dispersion in propylene glycol by hand at a rate of approximately 0.4 mL/min as tail vein infusion.

Doses:

840, 891, 944 and 1000 mg/kg bw (males)
840, 891, 944, 1000, 1060, 1120, 1190 and 1260 mg/kg bw (females)

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations: 15 min, 30 min, 1, 2, 3, 4, 6, 24 and 48 h following injection
- Necropsy of survivors performed: yes, 7 days after test substance administration
- Other examinations performed: clinical signs

Statistics:

LD50 values were calculated using the methods of Weil and Litchfield & Wilcoxon

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

875 mg/kg bw

Based on:

test mat.

Remarks on result:

other: at 7 days, method of Weil

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

960 mg/kg bw

Based on:

test mat.

Remarks on result:

other: at 7 days, method of Litchfield & Wilcoxon

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

1 020 mg/kg bw

Based on:

test mat.

Remarks on result:

other: at 7 days, method of Weil

Effect levels 4

Sex:

female

Dose descriptor:

LD50

Effect level:

1 050 mg/kg bw

Based on:

test mat.

Remarks on result:

other: at 7 days, method of Litchfield & Wilcoxon

Effect levels 5

Sex:

male/female

Dose descriptor:

LD50

Effect level:

943 mg/kg bw

Based on:

test mat.

Remarks on result:

other: at 7 days, method of Weil

Effect levels 6

Sex:

male/female

Dose descriptor:

LD50

Effect level:

975 mg/kg bw

Based on:

test mat.

Remarks on result:

other: at 7 days, method of Litchfield & Wilcoxon

Mortality:

In most cases death occured within ten minutes after injection but some animals died within 24 h to 48 hours after injection (details see table 1.)

Clinical signs:

The signs of intoxication for rats given the test substance included depression, pallor, ataxia, rapid or labored respration, and some convulsions and foam from the nose at death (for details see table 2).

Gross pathology:

The following tissues were examined in all animals that died after injection or were sacrificed at the end of seven days: adrenals, liver, bladder, stomach, spleen, lungs, heart, kidneys, thymus, small and large intestines. Gross pathology on rats which died after injection showed edema, hemorrhage and congestion of the lungs, congestion of the kidneys and hemorrhage in the small intestines. Rats sacrificed seven days after injection revealed no remarkable gross pathology (for details see tables 3 and 4).

Any other information on results incl. tables

Table 1: Mortalities.

Dose [mg/kg bw]	Sex	No. of affected animals / No. of total animals
		24 h	48 h	7 days (total)
1000	male	5/5	-	5/5
944		2/5	-	2/5
891		2/5	-	2/5
840		0/5	-	0/5
1260	female	5/5	-	5/5
1190		2/5	-	2/5
1120		2/5	-	2/5
1060		1/5	1/5	2/5
1000		3/5	-	3/5
944		1/5	-	1/5
891		2/5	-	2/5
840		1/5	-	1/5
1000	male/female	8/10	-	8/10
944		3/10	-	3/10
891		4/10	-	4/10
840		1/10	-	1/10

Table 2: Clinical signs of toxicity.

Dose [mg/kg bw]	Sex	Sign	No. of affected animals / No. of total animals	Time point of observation
1260	female	pallor	5/5	full dose
			1/1	5 – 10 min
		ataxia	5/5	full dose
			1/1	5 – 10 min
		rapid respiration	5/5	full dose
			1/1	5 – 10 min
		convulsions	1/1 (slight)	5 min
			1/1 (rolling)	death
		dead	4/5	5 min
			5/5	15 min
1190	female	pallor	5/5	full dose
			3/5	5 – 15 min
			1/2	1 h
		ataxia	5/5	full dose
			3/5	5 – 15 min
		rapid respiration	5/5	full dose
			3/5	5 – 15 min
		ruffed fur	3/3	30 – 60 min
		convulsions	2/5 (slight)	5 min
		Straub tail	2/5	full dose
		hyperactive	2/5	5 min
		foam from nose	2/5	death
		dead	2/5	10 min
1120	female	pallor	5/5	full dose
			3/4	5 min
			1/3	10 – 30 min
		ataxia	5/5	full dose
			3/4	5 min
			1/3	10 -30 min
		rapid respiration	5/5	full dose
			4/4	5 min
			1/3	10 -30 min
		ruffed fur	2/3	10 min – 1 h
		hyperactive	1/3	10 – 30 min
		dead	1/5	5 min
			2/5	10 min
1060	female	depression	5/5	full dose
			4/4	5 – 30 min
		pallor	5/5	full dose
			4/4	5 – 30 min
			1/3	3 days
		ataxia	5/5	full dose
			4/4	5 – 30 min
		rapid respiration	5/5	full dose
			4/4	5 - 30 min
		ruffed fur	1/3	3 days
		dead	1/5	5 min
			2/5	2 days
1000	male / female	depression	10/10	full dose
			2/2	5 – 10 min
			1/2	15 min
		pallor	10/10	full dose
			2/2	5 min
			1/2	10 min
		rapid respiration	8/10	full dose
			2/2	5 min
			1/2	10 min
		ataxia	10/10	full dose
			2/2	5 min
			1/2	10 min
		convulsions	8/10	death
		foam from nose	8/10	death
		dead	8/10	5 min
944	male / female	depression	10/10	full dose – 5 min
			6/10	10 – 15 min
		pallor	6/10	full dose
			8/10	5 -10 min
			6/10	15 min
		rapid respiration	8/10	full dose – 5 min
			6/10	10 – 15 min
		ataxia	10/10	full dose
			6/10	5 – 15 min
		foam from nose	2/10	death
		dead	2/10	30 min
			3/10	24 h
891	male / female	depression	10/10	full dose
			6/8	5 min
			4/8	10 min
			2/8	15 min
			1/7	30 – 60 min
		pallor	8/10	full dose
			4/8	5 -10 min
			1/8	15 min
		rapid respiration	9/10	full dose
			6/8	5 min
			4/8	10 min
			2/8	15 min
		ataxia	10/10	full dose
			6/8	5 min
			4/8	10 min
			2/8	15 min
		foam from nose	3/10	death
		dead	2/10	5 min
			3/10	30 min
			4/10	24 h
840	male / female	depression	10/10	full dose
			8/10	5 min
			6/10	10 min
			1/10	15 min – 2 h
		pallor	5/10	full dose
			9/10	5 min
			5/10	5 min
			1/10	15 – 30 min
		rapid respiration	3/10	full dose
			6/10	5 – 10min
			1/10	15 – 30 min
		ataxia	10/10	full dose
			5/10	5 min
			3/10	10 min
		dead	1/10	24 h

 

Table 3: Gross pathological findings in male and female rats that died after treatment with the test substance.

Dose [mg/kg bw]	Sex	Organ	No. of affected animals / No. of total animals	Finding
1260	female	lungs	2/5 (1/2 severe)	hemorrhage
			3/5 (2/3 severe)	congestion
			5/5 (1/5 slight, 2/5 severe)	edema
		kidneys	3/5	congested
			2/5 (right)	hydronephrosis
		heart	1/5	enlarged, filled with clotted blood
		small intestine	3/5 (1/3 severe)	hemorrhage
1190	female	lungs	1/2	hemorrhage
			1/2	severe congestion
		kidneys	1/2	congestion
		intestines	2/2	hemorrhage
1120	female	lungs	2/2 (1/2 severe)	hemorrhage
			2/2 (1/2 severe)	edema
		kidneys	1/2	congested medulla
		small intestine	1/2	hemorrhage
1060	female	lungs	1/2	severe hemorrhage
			1/2	severe congestion
			2/2 (1/2 severe)	edema
		kidneys	2/2 (1/2 slight)	congested medulla
		small intestine	2/2 (1/2 slight)	hemorrhage
		liver	1/2	possible focal capsular fibrosis
		spleen	1/2	possible focal capsular fibrosis
		thymus	1/2	slight congestion
		stomach	1/2	erosion, congestion
1000	male / female	lungs	6/8 (3/6 severe, 1/6 focal)	hemorrhage
			1/8	slight congestion
		kidneys	4/8 (2/4 slight)	congestion
			1/8 (right)	hydronephrosis
		small intestines	2/8	hemorrhage
		liver	3/8	dark
			1/8	congenital diaphragmatic hernia
944	male / female	lungs	3/3	hemorrhage
			3/3 (1/3 severe)	edema
		kidneys	2/3	congested
			1/3	congested medulla
		intestines	2/3	hemorrhage
		liver	1/3	motteled
891	male / female	lungs	3/4	hemorrhage
			4/4 (2/4 slight,1/4 severe)	edema
			1/4	focal hemorrhage
		kidneys	1/4	congested
			1/4	slight medullary congestion
		heart	1/4	filled with clotted blood
		small intestines	2/4 (1/2 slight)	hemorrhage
840	male / female	lungs	1/1	hemorrhage
			1/1	edema
		kidneys	1/1	congested

 

Table 4: Gross pathological findings in male and female rats that were sacrificed 7 days after treatment with the test substance.

Dose [mg/kg bw]	Sex	Organ	No. of affected animals / No. of total animals	Finding
1190	female	lungs	1/3	slight congestion
		kidneys	1/3	(right) hydronephrosis
1120	female	lungs	2/3	slight congestion
		kidneys	1/3	(right) hydronephrosis
1060	female	lungs	1/3	slight congestion
944	male / female	kidnyes	3/7	(right) hydronephrosis
891	male / female	lungs	1/6	slight focal hemorrhage
		kidneys	2/6	(right) hydronephrosis
840	male / female	lungs	1/9	slight congestion
		kidneys	1/9	(right) hydronephrosis

 

According to Hodge and Sterner for parenteral administration, the test item would be in the "practically non-toxic" category (0.5 - 1.5 g/kg) of materials.