Registration Dossier

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
16 Nov 1982 - 19 Jan 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific principles, well documented and sufficient for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report date:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Decyl oleate
EC Number:
222-981-6
EC Name:
Decyl oleate
Cas Number:
3687-46-5
Molecular formula:
C28H54O2
IUPAC Name:
decyl octadec-9-enoate
Details on test material:
- Name of test material (as cited in study report): Oelsaeuredecylester
- Physical state: light yellow, clear, oily liquid
- Analytical purity: no data given

Test animals

Species:
rat
Strain:
other: Wistar Han
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Zentralinstitut fuer Versuchstiere, Hannover, Germany
- Age at study initiation: approx. 4 months
- Weight at study initiation: males: 50-81 g; females: 50-82 g
- Housing: 2-3 animals per cage in macrolon cages type III
- Diet: Altromin 1324 DK pelleted diet (Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21-22 °C
- Humidity: 49-65 %
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
The test material was administered once daily by gavage for five days per week. The control animals were treated in the same way with the respective vehicle only (olive oil; 5 ml/kg bw/d). The dosing solution were prepared daily prior to administration. The application volumes were adopted weekly to the current body weights.
Duration of treatment / exposure:
28 days (21 applications)
Frequency of treatment:
once daily on five days per week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 100 (2%), 500 (10%) and 1000 (20%) mg/kg bw/d (groups 1-4)
Basis:
actual ingested
No. of animals per sex per dose:
10 animals per sex per dose, treated with 21 applications and sacrificed after 28 days
5 animals per sex per sex per dose, treated with 21 applications and remained untreated thereafter for further 28 days (recovery group)
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
All animals were observed daily. The body weight was measured weekly and served as main parameter for the actual health status of the animals. Food and water consumption was determined weekly.
At the end of the study period, urine and feces examinations were conducted.
For haematological examinations, the blood was collected from the orbital plexus during a temporary ether anaesthesia of the animals. The following clinico-chemical parameters were examined:
- Blood: Haematokrit, haemoglobin content, red and white blood cell count, mean cell volume, thrombocyte cell count, differential blood count.
- Enzymes and subtrates in serum: Kidney profile: urea, creatinine, sodium and potassium; adrenal profile: glucose, sodium and potassium; mineral metabolism and parathyroid profile: calcium, inorganic phosphor and alkaline phosphatase; electrolyte profile: sodium, potassium, chloride, albumin, total protein; thyroid profile: cholesterol.


Sacrifice and pathology:
During the section, the absolute and relative weight of the following organs was determined: thyroid, adrenals, thymus, spleen, heart, kidneys, brain, testes and liver.
Gross pathology was conducted with all animals. Additionally, 10 male and 10 female animals of the main test groups (1-4) were also examined histopathologically. The target of the main groups (1-4) was the liver which was examined in 3 male and 3 female animals; in the recovery groups (1-4), the target organs were lungs, pancreas, axillary lymph node, salivary gland and forestomach.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Details on results:
All doses were tolerated in all test animals without test material related mortality or symptoms of intoxication.
Food and water consumption and development of body weight yielded no substance-related deviations during the course of the study in comparison to the control.
A slightly decreased haemoglobin value in the blood of all test groups and slightly decreased phosphorous values in the serum of selected test groups were considered to be not related to treatment.
The examination of urine was without relevant findings, only in one female of test group 4, eggs from parasitic origin were detected. Feces amount was reduced in female animals of group 2 and 4, the appearance of the feces was as expected.
The examination of the eyes revealed no substance related findings.
The absolute and relative organ weights revealed no dose related findings.
The gross section of all animals and the microscopic examination of the high dose and control animals revealed no substance related alterations of inner organs. In some cases, spontaneous findings were noted: Histopathologically, there were some findings in the salivary glands, axillary lymph nodes, pancreas and lungs which were caused by virus infections. The cutaneous mucosa of the forestomach showed either degenerative changes or signs of inflammation. These effects were seen in the test groups, as well as in the controls. Furthermore, changes of the glands in fundus and pylorus were also seen in both treated- and control animals.

For further details on the results obtained, see table 1 in "Remarks on results ...".

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: overall effects: No adverse effect on clinical signs; mortality; body weight; haematology; gross pathology and histopathology.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Table 1: Data of selected parameters determined in the study, which reached statistical significance at least in one value:

food consumption (g/animal/d), group mean values

 

 

 

 

week

group, sex (m/f)

 

 

 

 

 

 

 

1 m

2 m

3 m

4 m

1 f

2 f

3 f

4 f

1

18

16

18

18

14

15

14

15

2

19

18

21**

22**

14

14

15**

16*

3

22

21

21

21*

16

17

15

16

4

17

17

19

19

13

13

13

14

water consumption (ml/animal/d), group mean values

 

 

 

 

week

group, sex (m/f)

 

 

 

 

 

 

 

1 m

2 m

3 m

4 m

1 f

2 f

3 f

4 f

1

29

25*

27

29

27

24

24

24

2

28

25**

30

31*

28

22**

26

27

3

33

29

30

30

32

27

26*

25*

4

30

25

27

29

29

28

24*

24

body weights and weight gain (g)

 

 

 

 

 

 

week

group, sex (m/f)

 

 

 

 

 

 

 

1 m

2 m

3 m

4 m

1 f

2 f

3 f

4 f

0

67

60*

64

67

64

63

60

63

1

107

96**

105

108

96

96

94

95

2

147

137

147

150

123

124

122

124

3

189

178

191

196

146

147

146

147

4

220

208

227

229

161

162

163

173

gain week 0-4

153

148

163

162

97

99

103

110

selected haematology parameters (after week 4)

 

 

 

 

 

 

group, sex (m/f)

 

 

 

 

 

 

 

1 m

2 m

3 m

4 m

1 f

2 f

3 f

4 f

haemoglobin (Hb) mmol/l

10.9

10.1

9.9**

9.8**

10.6

9.9**

9.9**

9.8**

red blood cell count (RBC) T/l

7.2

6.9

6.6

6.8

6.9

6.4

6.0*

6.5

haematokrit (HAT) l/l

0.39

0.38

0.36

0.37

0.36

0.34

0.32**

0.35

alkaline phosphatase (AP) U/l

371

356

390

361

247

211

196*

206

inorganic phosphate

3.1

2.9*

2.7**

2.8*

2.6

2.4*

2.4

2.5

organ weights after 4 weeks

 

 

 

 

 

 

 

group, sex (m/f)

 

 

 

 

 

 

 

1 m

2 m

3 m

4 m

1 f

2 f

3 f

4 f

thyroid absolute (mg)

25

22*

23

23

21

23

19

22

spleen absolute (g)

0.57

0.59

0.63*

0.63

0.46

0.45

0.46

0.46

heart absolute (g)

0.80

0.73*

0.78

0.80

0.61

0.61

0.58

0.64

kidney absolute (g)

1.66

1.58

1.73

1.80

1.19

1.22

1.19

1.28*

thyroid relative (% of body weight)

0.010

0.010

0.009*

0.009

0.013

0.014

0.011

0.013

adrenal relative (% of body weight)

0.025

0.025

0.024

0.025

0.046

0.044

0.039*

0.045

heart relative (% of body weight)

0.33

0.32

0.31**

0.31*

0.36

0.36

0.34

0.37

* = level of significance 95% in comparison with control value

** = level of significance 99% in comparison with control value

Applicant's summary and conclusion

Conclusions:
Under the experimental conditions of this study, the NOAEL obtained was 1000 mg/kg bw/d for male and female rats after repeated oral administration of the test material in a 28 day study.