Fatty acids, C18-unsatd., trimers, compds. with oleylamine

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: The study was conducted in compliance with GLP by Byk Gulden Pharmazeutika. The study is scientifically valid and the report is fully adequate for assessment, despite some minor restrictions (due to limited reporting).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Principles of method if other than guideline:

Single oral gavage administration of a formulation containing 31.4% (w/w) WS400151 to 5 to 10 male and/or 5 to 10 female rats/dose group followed by 14 days of observation. The study comprised 3 untreated control and 7 dose groups. Bodyweights were recorded prior to dosing and 7 and 14 days after dosing. In addition, mortality and clinical signs were recorded, but necropsy was not reported.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sprague Dawley rats, IVANOVAS/Kisslegg with appropriate range of bodyweight at study start. Animals were received in 3 batches:
- Weight at study initiation (day of dosing): Males: 148 to 161 g, 183 to 210 g and 145 to 154 g (bw range of males assigned to treated groups)
Females: 146 to 160 g, 155 to 190 g and 138 to 163 g (bw range of females assigned to treated groups)
- Housing: Group housing with up to 5 animals by sex in Makrolon(R) Type 3 cages.
- Bedding material: Dustfree softwood granules.
- Fasting period: Ca. 17 hours prior to dosing
- Diet (ad libitum except during fasting period): Commercially available Altromin(R) R diet.
- Water (ad libitum): Tap-water
- Acclimation period: At least 5 days before start of dosing.

ENVIRONMENTAL CONDITIONS

The animal room was maintained at:
- Temperature (°C): ca. 24°C
- Relative Humidity (%): ca. 50%
- Photoperiod (daylight or artificial lighting): 12 h/day
Night: Dimmed light, 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.
The specific weight of the test material was accounted for when dosing the animals by gavage administration.

Doses:

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

No. of animals per sex per dose:

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

Control animals:

yes

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 shortly after dosing, ca. 1 and 3 hours and 1, 3 and 11 day(s) post dosing.
Mortality: At least several times on the day of dosing (Day 0) and 2, 3, 7 and 14 days post dosing.
Weighing of each animal: All animals on Day 0 (prior to dosing) and 7 and 14 days post dosing.
- Necropsy: Not reported

Statistics:

In view of less than 50% mortality in the top dose group, a specific LD50 value could not be calculated.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 570 mg/kg bw

Based on:

act. ingr.

Remarks:

WS400151

Remarks on result:

other: WS400151: at 1570 mg/kg bw , 20% male and 30% female mortality over the 14 day post dosing observation period.

Mortality:

Mortality during the 14-day observation period post dosing:
Single Dose WS400151 at: Mortality
628 mg/kg bw 0/ 5 (m); 0/ 5 (f)
785 mg/kg bw -/ - (m); 0/ 5 (f)
942 mg/kg bw -/ - (m); 0/ 5 (f)
1099 mg/kg bw 0/ 5 (m); 1/ 5 (f)
1256 mg/kg bw 0/ 5 (m); -/ - (f)
1413 mg/kg bw 0/ 5 (m); -/ - (f)
1570 mg/kg bw 2/10 (m); 3/10 (f)

m = male, f = female

Clinical signs:

other: At 2000 mg/kg test material equivalent to 628 mg/kg WS400151: - immediately after dosing for ca. 10 minutes increased vigilance, increased prying and rearing activity and increased frequency of respiration - then for a brief period single recumbency and

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Conservative classification in view of 25% mortality at the maximum dose tested (equivalent to 1570 mg/kg neat WS400151) Criteria used for interpretation of results: EU

Conclusions:

The maximum dose tested, 5000 mg/kg bw test material equivalent to 1570 mg/kg bw neat WS400151, induced on average 25% mortality. Based on this result it remained unpredictable whether the LD50 (oral, rat) is lower or higher than 2000 mg/kg. Therefore, taking a conservative approach WS400151 was classified as "harmful (Xn)" and "harmful if swallowed (R22)" [DIRECTIVE 67/548/EEC] and as "Category 4 (Warning: Harmful if swallowed) [REGULATION (EC) 1272/2008]. Relevant sex-related differences in toxicity of the test material after single oral administration were not evident.