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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Study performed between 11 August 2011 and 15 September 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 2000
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Esterification products of Fatty acids C18 unsaturated and triethanolamine
EC Number:
939-649-8
Cas Number:
1474044-69-3
Molecular formula:
Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance)
IUPAC Name:
Esterification products of Fatty acids C18 unsaturated and triethanolamine
Test material form:
liquid: viscous

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Female Wistar (RccHan:WIST) strain rats were supplied by Harlan Laboratories UK Ltd.
- Age at study initiation: Eight to twelve weeks of age
- Weight at study initiation: 171 - 187g. The bodyweights fell within an interval of ±20% of the mean initial bodyweight of the first treated group.
- Fasting period before study: Overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: The animals were housed in groups of three in suspended solid floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Food (2014C Teklad Global Rodent diet) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Set to achieve limits of 19 to 25°C
- Humidity (%): Set to achieve limits of 30 to 70%
- Air changes (per hr): At least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Remarks:
Used for the 300 mg/kg dose level only.
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/ml for 300 mg/kg dose level

MAXIMUM DOSE VOLUME APPLIED:
10 ml/kg for 300 mg/kg dose level. 2.11 ml/kg for 2000 mg/kg dose level.

DOSAGE PREPARATION:
For the purpose of the 2000 mg/kg dose level, the test item was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. For the purpose of the 300 mg/kg dose level, the test item was freshly prepared, as required, as a solution at the appropriate concentration in arachis oil BP.

The test item was formulated within approximately two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
Doses:
300 mg/kg and 2000 mg/kg
No. of animals per sex per dose:
3 females at 300 mg/kg
9 females at 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for up to fourteen days. Due to a technician error, the second group of animals treated at a dose level of 2000 mg/kg were killed on Day 7. A third group of animals was therefore treated at a dose level of 2000 mg/kg.

Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death.

- Necropsy of survivors performed: yes; At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
None recorded.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Mortality:
Individual mortality data are given in Table 1 (attached background material).
There were no deaths.
Clinical signs:
Individual clinical observations are given in Table 2 and Table 3 (attached background material).
There were no signs of systemic toxicity.
Body weight:
Individual bodyweights and weekly bodyweight changes are given in Table 4 and Table 5 (attached background material).
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
Individual necropsy findings are given in Table 6 and Table 7 (attached background material).
A cavity in the right kidney was noted at necropsy of one animal treated at a dose level of 2000 mg/kg. This was considered to be a genetic defect and not test item related. No abnormalities were noted at necropsy of the remaining animals.
Other findings:
None

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2500 mg/kg bodyweight (Globally Harmonised Classification System – Unclassified).
Executive summary:

Introduction.

The study was performed to assess the acute oral toxicity of the test item following a single oral administration in the Wistar strain rat. The method was designed to be compatible with the following

- OECD Guidelines for the Testing of Chemicals No. 423 “Acute Oral Toxicity – Acute Toxic Class Method” (adopted 17 December 2001)

- Method B1 tris Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008

- United States Environmental Protection Agency Health Effects Test Guidelines OPPTS 870.1100 Acute Oral Toxicity, 2002

- Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 2000

Method.

A group of three fasted females was treated with the test item at a dose level of 300 mg/kg bodyweight. Based on the results from this dose level further groups of fasted females were treated at a dose level of 2000 mg/kg bodyweight. Dosing was performed sequentially.

The test item was administered orally undiluted or as a solution in arachis oil BP. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. 

There were no deaths.

Clinical Observations. 

There were no signs of systemic toxicity.

Bodyweight. 

All animals showed expected gains in bodyweight over the study period.

Necropsy. 

A cavity in the right kidney was noted at necropsy of one animal treated at a dose level of 2000 mg/kg. This was considered to be a genetic defect and not test item related  No abnormalities were noted at necropsy of the remaining animals.

Conclusion.

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2500 mg/kg bodyweight (Globally Harmonised Classification System – Unclassified).

The test item does not meet the criteria for classification according to the Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Dangerous Substances.