Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998-07-01 - 1998-12-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
EEC Methods for the determination of toxicity. Annex to Directive 92/69/EEC (Official Journal No. L383A. 29.12.92). Part B, Method B. 1. Acute toxicity (oral)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
OECD Guideline for Testing of Chemicals No. 401 "Acute Oral Toxicity". Adopted 24 February 1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: granules
Details on test material:
- Substance type: pure substance
- Storage condition of test material: room temperature
- Appearance: Pale yellow granules

Test animals

Species:
rat
Strain:
other: CD rats of Sprague-Dawley origin (Hsd:Sprague-Dawley(CD))
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan U.K. Ltd, Bicester, Oxon, England.
- Age at study initiation: 5-7 weeks
- Weight at study initiation: 99 - 116 g
- Fasting period before study: yes, overnight prior to and for approximately 4 hours after dosing
- Housing: Rats were allocated without conscious bias to cages within the treatment group and housed in groups of five rats of the same sex in metal cages with wire mesh floors in Building R14 Room 6.
- Diet (e.g. ad libitum): standard laboratory rodent diet (Special Diet Services RM1(E) SQC expanded pellet) ad libitum
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 24 °C
- Humidity (%): 38 - 61%
- Photoperiod (hrs dark / hrs light): Lighting was controlled by means of a time switch to provide 12 hours of artificial light (0700 - 1900 hours) in each 24-hour period.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1% w/v aqueous methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% w/v
- Amount of vehicle (if gavage): total volume 10 ml/kg bw

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw (test item) / 10 ml/kg bw (formulated dosing solution)

DOSAGE PREPARATION (if unusual): The test substance was prepared on the day of dosing.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 / sex / dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Cages of rats were checked al least twice daily for any mortalities. Animals were obseived soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals in the main study were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The bodyweight of each rat in the main study was recorded on Days 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortalities observed
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortalities observed
Mortality:
There were no deaths following a single oral dose of the test item to a group of ten rats (five males and five females) at a dosage of 2000 mg/kg bodyweight.
Clinical signs:
Piloerection was observed in all rats soon after dosing. This sign persisted and was accompanied in all animals later during the study by hunched posture, and in one female by abnormal respiration. There were no other clinical signs and recovery of rats was complete by either Day 3 (females), or Day 4 (males).
Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No macroscopic abnormalities were observed for animals killed at study termination on Day 15.

Any other information on results incl. tables

PRELIMINARY STUDY

In the absence of precise toxicological information and to establish a dosing regime for the main study, a group of two rats (one male and one female) was dosed at 1000 mg/kg bodyweight. Clinical signs in these animals included piloerection, hunched posture, waddling/unsteady gait, lethargy and abnormal respiration. Bodyweight gain was considered to be satisfactory for studies of this nature and duration and no abnormalities were observed at study termination on Day 8. On the basis of results from this preliminary study, 2000 mg/kg was selected as a suitable dose level for the main study.

 

Table 1: Signs of reaction to treatment

Signs

No. of rats showing signs

Preliminary study (1000 mg/kg)

Main study (2000 mg/kg)

Male

Female

Male

Female

Piloerection

1

1

5

5

Hunched posture

1

1

5

5

Waddling / unsteady gait

1

1

0

0

Lethargy

1

1

0

0

Abnormal respiration*

1

0

0

1

* Characterized by gasping / noisy respiration

 

Table 2: Individual and group mean bodyweights (g)

Dose (mg/kg)

Sex

Animal number

Bodyweight (g) at Day

1*

8

15

2000

Male

11

99

155

207

12

105

178

234

13

108

173

228

14

108

180

234

15

108

171

225

Mean

106

171

226

Female

16

111

158

187

17

116

179

205

18

111

155

188

19

103

143

173

20

100

151

173

Mean

108

157

185

* Prior to dosing

 

Table 3: Individual body weight changes

Dose (mg(kg)

Sex

Animal number

Bodyweight gains (g) at Day

8

15

2000

Male

11

56

52

12

73

56

13

65

55

14

72

54

15

63

54

Female

16

47

29

17

63

26

18

44

33

19

40

30

20

51

22

Applicant's summary and conclusion

Interpretation of results:
other: EU-GHS criteria not met
Conclusions:
The study was conducted under GLP according to OECD guideline 401 on the registered substance itself. The method is to be considered scientifically reasonable with no deficiencies in documentation. Hence, the results can be considered as reliable to assess the acute oral toxicity in rats.
There were no deaths following a single oral dose of Octadecanoic acid, reaction products with tetraethylenepentamine, to a group of ten rats (five males and five females) at a dosage of 2000 mg/kg bodyweight.
On the grounds of the obtained results, Octadecanoic acid, reaction products with tetraethylenepentamine, can be classified to the following categories:
- category 5 / unclassified – according to the Globally Harmonized System (GHS),
- agents which are beyond categorization – according to the Regulation (EC) No. 1272/2008
Executive summary:

This study was performed to assess the acute oral toxicity of Octadecanoic acid, reaction products with tetraethylenepentamine to the rat. The method followed was that described in:

- EEC Methods for the determination of toxicity. Annex to Directive 92/69/EEC (Official Journal No. L383A. 29.12.92). Part B, Method B. 1. Acute toxicity (oral).

- OECD Guideline for Testing of Chemicals No. 401 "Acute Oral Toxicity". Adopted 24 February 1987.

 

A group of ten fasted rats (five males and five females) received a single oral gavage dose of the test substance, formulated in 1% w/v aqueous methylcellulose and administered at a dose level of 2000 mg/kg bodyweight. This dosage was selected on the basis of results from a preliminary study. All animals were killed and examined macroscopically on Day 15, the end of the observation period.

Clinical signs of reaction to treatment were confined to piloerection and hunched posture, seen in all rats with abnormal respiration also seen in one female. There were no other signs of reaction to treatment and recovery was complete in all animals by Day 4.

All animals were considered to have achieved satisfactory bodyweight gains throughout the study.

No macroscopic abnormalities were observed for animals killed at study termination on Day 15.

The acute lethal oral dose to rats of Octadecanoic acid, reaction products with tetraethylenepentamine was demonstrated to be greater than 2000 mg/kg bodyweight.

 

Octadecanoic acid, reaction products with tetraethylenepentamine will not require labelling with the risk phrase R22 "Harmful if swallowed", in accordance with Commission Directive 93/21/EEC. Similarly, it can be classified to the following categories:

- category 5 / unclassified – according to the Globally Harmonized System (GHS),

- agents which are beyond categorization – according to the Regulation (EC) No. 1272/2008