Fatty acids, C18-unsatd., trimers, reaction products with triethylenetetramine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted according to internationally accepted technical guidelines in a contract research organization. The study is scientifically valid and adequate for assessment with acceptable restrictions (e.g. due to limited reporting in times before GLP). Purity and stability of the test material were not reported for the batch of test material used.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

of 1981

Deviations:

yes

Remarks:

Doses of test material were > 5000 mg/kg. Therefore, this was dosed undiluted and dose volumes could not be kept constant but increased with increasing dose up to the double volume of that recommended by OECD 401 for non-aqueous dose formulations

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Division of Pharmacology, FDA, 1959

Deviations:

not specified

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Wistar rats, strain: Winkelmann, Paderborn (SPF-Quality) with appropriate range of bodyweight at study start.
- Weight at study initiation (day of dosing): 181 to 190 g
- Housing: Group housing with up to 5 animals by sex in cages.
- Fasting period: From 16 hours before test start
- Diet (except for fasting period): Commercially available standard laboratory animal diet:
"Standard-Diät tpf(R) Ratte/Maus-Haltung" from Altromin, Lage, Germany
- Water was provided ad libitum

ENVIRONMENTAL CONDITIONS

The animal room was maintained at:
- Temperature (°C): 22 ± 1°C
- Relative Humidity (%): 45 to 55%
- Photoperiod (artificial lighting): 12 h/day

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

- Dose volume: The administered volume of test material, increased with increasing dose thus achieving quite high target doses.
Individual dose volume was calculated based on individual bodyweight
- For different doses and dose volumes, see Table 1 in "Any other information on materials and methods incl. tables"
- Rationale for doses selected: Based on a pre-test, which was not detailed in the study report.

Doses:

see Table 1 in "Any other information on materials and methods incl. tables"

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations:
It has not been clearly specified in the report at what time points clinical signs and mortality were recorded, but the following records have been
reported:
Clinidal signs: At least at 20 to 30 minutes post dosing (Day 0) and 7 and 14 days post dosing.
Mortality: At least at 24 and 48 hours and 7 and 14 days post dosing.
Weighing of each animal: All animals on Day 0 for calculation of individual dose volume and survivors on Day 14 (end of observation period).
- Necropsy performed: Yes, the report seems to suggest that for Groups 1, 4 and 5 all animals were necropsied, whereas for Group 2 possibly
only 9 animals and for Group 3 possibly only 5 animals were necropsied.

Statistics:

LD50 was estimated for 24 hours and 14 days post dosing according to Litchfield and Wilcoxon in connection with the Integral of Gauss.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 4 594 mg/kg bw

Based on:

test mat.

Remarks:

WS400152

Remarks on result:

other: WS400152: at 4594 mg/kg bw , 0% male and 20% female mortality over the 14 day post dosing observation period.

Mortality:

Mortality during the 14-day observation period post dosing:
Dose of Test Material: Equivalent Dose of WS400152: Mortality
8.0 mL/kg bw 3675 mg/kg bw 0/5 (m); 0/5 (f)
10.0 mL/kg bw 4594 mg/kg bw 0/5 (m); 1/5 (f)
12.6 mL/kg bw 5789 mg/kg bw 2/5 (m); 3/5 (f)
15.8 mL/kg bw 7259 mg/kg bw 5/5 (m); 5/5 (f)
20.0 mL/kg bw 9188 mg/kg bw 5/5 (m); 5/5 (f)

m = male, f = female

Clinical signs:

Group 1
Minor clinical signs, i.e. reflexes slightly decreased, at the beginning faeces clearly wet;
20 to 30 minutes post dosing slight apathy, diminished reflexes and slight stomach ache.
Group 2
Reflexes slightly decreased, at the beginning faeces clearly wet;
20 to 30 minutes post dosing apathy, diminished reflexes, stomach ache, increased frequency of respiration.
Groups 3 and 4
Reflexes clearly diminished, intermittently nervous, bristle and untidy fur, mucosae wet at the beginning, faeces wet until premature death or study termination;
20 minutes post dosing severe apathy, pinched eyes, severely diminished reflexes, stomach ache, strongly increased frequency of respiration.
Group 5
20 minutes post dosing severe apathy, pinched eyes, severely diminished reflexes, stomach ache, strongly increased frequency of respiration (followed by the premature death of all animals within 24 hours post administration).

In Groups 1, 2 and 3 differences in appearance and behaviour from "normal" were no longer evident in the survivors at 7 and 14 days post dosing.

Body weight:

There was a dose-related decline in overall group mean body weight gain over the 14 day observation period in the surviving animals of Groups 1, 2 and 3.

Gross pathology:

Gastro-intestinal hyperemia and/or edema were noted at all doses.

Other findings:

For Group 3 diminished food consumption was mentioned.

Any other information on results incl. tables

LD50 oral of test material according to Litchfield and Wilcoxon in connection with the Integral of Gauss:

24 h LD50 = 14.1 (12.5 - 15.9) mL/kg bw, Slope function = 1.36 (1.26 - 1.47)

14 d LD50 = 11.9 (10.4 - 13.6) mL/kg bw, Slope function = 1.30 (1.21 - 1.39)

Equivalent LD50 oral for neat WS400152:

24 h LD50 = 6478 (5743 - 7305) mg/kg bw,

14 d LD50 = 5467 (4778 - 6248) mg/kg bw

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In view of the attained oral LD50 of test material > 10.0 mL/kg bodyweight corresponding to an LD50 > 4594 mg/kg bw for neat WS400152, the outcome of the present study does not necessitate any labelling regarding acute oral toxicity according to EU regulation (REGULATION (EC) 1272/2008). In addition, relevant sex-related differences in toxicity of the test material after single oral administration were not evident.