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Toxicological information

Repeated dose toxicity: oral

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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

Constituent 1
Chemical structure
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
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 / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2%
Basis:
nominal in diet
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 [x106]

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

Applicant's summary and conclusion