Sorbitan monolaurate, ethoxylated

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

20 Nov 1947 - 15 Nov 1949

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given (analytical purity of test substance not given, only one dose level, limited evalutation and documentation of parameters).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1949

Report date:

1949

Materials and methods

Principles of method if other than guideline:

Life-span (2 years) feeding study with the test substance at 2% in diet in male rats.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sorbitan monolaurate, ethoxylated

EC Number:

500-018-3

EC Name:

Sorbitan monolaurate, ethoxylated

Cas Number:

9005-64-5

Molecular formula:

Molecular formula cannot be given as substance is a mixture.

IUPAC Name:

Sorbitan monolaurate, ethoxylated (1-6.5 moles ethoxylated)

Details on test material:

- Name of test material (as cited in study report): polyoxyethylene sorbitan monolaurate 21
- Analytical purity: no data

Test animals

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 54 - 63 g
- Housing: Rats were placed in cages with 10 animals in a group.
- Diet: All animals received a banal diet of ground Purina Fox Chow and greens once or twice weekly.
- Water: ad libitum

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Mixing appropriate amounts with (Type of food): The test material was intimately mixed with the diet (Fox Chow), content 2%

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

104 weeks

Frequency of treatment:

daily, 7 days/week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
2%
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
2000 mg/kg bw/d
Basis:
other: calculation based on the assumption of an average body weight of 200 g and an average food consumption of 20 g/animal

No. of animals per sex per dose:

50 (control), 30 (dose group)

Control animals:

yes, plain diet

Examinations

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: at end of study

BODY WEIGHT: Yes
- Time schedule for examinations: The animals were weighed in groups twice weekly for 6 weeks and weekly thereafter.

HAEMATOLOGY: Yes
- Time schedule for collection of blood: 6, 12, 17 and 24 months
- Parameters checked in table 2 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 6, 12, 17 and 24 months
- Parameters checked in table 2 were examined.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes , the following organs were examined: heart, lungs, spleen, stomach, liver, intestines, adrenals, kidneys, bladder, prostate, brain and thyroid.

HISTOPATHOLOGY: Yes, the following organs were examined: heart, lungs, spleen, stomach, liver, intestines, adrenals, kidneys, pancreas, bladder, prostate, testicles, salivary gland, brain, bone marrow, muscle and thyroid

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Details on results:

CLINICAL SIGNS AND MORTALITY
All animals were well-developed and well-nourished with a weight within the normal range. For details on mortalities see table 1.

BODY WEIGHT AND WEIGHT GAIN
Body weight and body weight gain was within the normal range and similar in the dose and control group. Average body weight of survivors at the end of the study: 412.2 g in dose group and 378.0 g in control group.

HAEMATOLOGY
Variations were within the normal range (for details see table 2).

CLINICAL CHEMISTRY
Variations were within the normal range (for details see table 2).

GROSS PATHOLOGY
The following organs were examined and didn't show any treatment related alterations: heart, lungs, spleen, stomach, liver, intestines, adrenals, kidneys, bladder, prostate, brain and thyroid.

HISTOPATHOLOGY: NON-NEOPLASTIC
The following organs were examined and didn't show any treatment related alterations: heart, lungs, spleen, stomach, liver, intestines, adrenals, kidneys, pancreas, bladder, prostate, testicles, salivary gland, brain, bone marrow, muscle and thyroid.

Effect levels

Dose descriptor:

NOAEL

Effect level:

> 2 other: % in diet

Based on:

test mat.

Sex:

male

Basis for effect level:

other: corresponding to 2000 mg/kg bw/d, calculation based on the assumption of an average body weight of 200 g and an average food consumption of 20 g/animal

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1: Survival / mortalities.

	No. of affected animals
	Dose group	Control
Initial animals	30	50
Survivors after 6 months	25	30
Survivors after 12 months	18	16
Survivors after 17 months	13	9
Survivors after 24 months	8	1
Cause of deaths:
Sacrificed for study (prior to end of experiment)	3	4
Accidental deaths	1	1
Unknown	9	14
Infection	8	18
Neoplasm	0	1
Sick animals sacrificed	1	11
Sacrificed at end of study	7	1

Table 2: Blood picture and blood chemistry of experimental and control animals.

Time-point	Treatment	Hb [%]	RBC [x10^6]	WBC	Blood sugar [mg %]	Urea N2 [mg %]	Cholesterol [mg %]
6 months	control	17.6	8.2	12500	95	18	-
		15.9	8.0	7500	89	20	-
	dosed	14.8	7.5	9400	99	20	-
12 months	control	9.9	5.9	13600	84	20	-
	dosed	14.1	6.92	5150	81	18	-
17 months	control	12.4	9.5	6300	20	66	77
	dosed	8.2	6.3	17650	24	134	87
24 months	control	13.2	9.3	5150	87	18	130
	dosed	13.3	7.8	5100	67	9	280
		15.0	8.3	6500	61	17	-
		14.3	8.9	5550	90	18	-
		13.1	7.5	9450	56	14	270
		12.9	9.2	9550	70	13	110
		12.6	8.8	7800	103	16	-
		13.2	10.4	9400	73	13	-

HB = hematokrit, RBC = red blood cell count, WBC = white blood cell count