Fatty acids, tall-oil, compds. with oleylamine

Endpoint summary

Description of key information

Oral rat (acute toxic class method):   LD50 > 2000 mg/kg bw  (no mortality at 2000 mg/kg bw).
Acute dermal rat:                                   Waiving, as this study was considered to be scientifically unjustified.      
Acute inhalation rat:                              Exposure based waiving: Exposure of humans to WS400101 by the inhalation route is unlikely, because of its low  vapour pressure, its decomposition at high temperature without boiling and because it is a viscous paste.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

of 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

of 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

of 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries. Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nohsan No. 8147, Agricultural Production Bureau, November 24, 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sprague Dawley rats, strain: Crl:CD(SD) with appropriate range of bodyweight at study start.
- Source: Charles River (UK) Ltd.
- Age at study start (day of dosing): 8 to 12 weeks.
- Weight at start (day of dosing): Females: minimum 212 g, maximum 233 g.
- Fasting period: Overnight immediately prior to dosing until ca. 4 hours post administration.
- Housing: In groups of 3 by sex in solid bottomed polycarbonate cages inside a barriered rodent facility.
- Bedding material: Autoclaved wood flake bedding
- Cage enrichment: Soft white chew block and plastic shelter (chew block removed during fasting).
- Diet: Standard rodent diet (Rat and Mouse No. 1 Maintenance Diet)
containing no added antibiotic, chemotherapeutic or prophylactic agent.
- Drinking water (ad libitum): Pottable drinking water from the public supply
- Acclimation period: At least 5 days before dosing.

Routine analysis of the batch of diet used, water and chew blocks did not provide evidence of contamination that might have prejudiced the study.

ENVIRONMENTAL CONDITIONS

Air conditioned room kept at positve pressure without re-circulation of the filtered fresh air supplied to the room.
Controlled environment, environmental conditions were set at:
- Temperature (°C): 21 ± 2°C
- Relative Humidity (%): 40 to 70%
- Photoperiod (artificial lighting): 12 hrs day / 12 hrs night
- Rate of air exchange: Ca. 15 changes/h

There were no deviations from these ranges, which compromised the quality, integrity or outcome of the study.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

DOSE FORMULATION AND DOSE VOLUME:

- Concentration of test material in vehicle: 200 mg/mL
- Amount (dose volume by gavage): 10 mL/kg bw

Dosing was undertaken within 4 hours of preparation of the test material formulation. Formulations were stirred before and throughout the dosing procedure.

ACUTE TOXIC CLASS METHOD - Rationale for the selection of the starting dose:

The starting dose of 2000 mg/kg was chosen on request of the Sponsor, which, in retrospect, proved to be appropriate, as no animals died at this dose. The Sponsor's request had been based on the absence of mortality in a previous subacute (7-day) oral toxicity study in rats dosed with a test substance chemically similar to WS400101 at up to 1000 mg/kg bw/day. Therefore, in the present acute toxicity study with WS400101 initially a dose of 2000 mg/kg body weight (limit test) was adiministered to 3 female animals. As no mortality occurred, 2000 mg/kg body weight were administered to a further 3 female animals. As none of the 6 animals died, the present study fulfilled the criteria for a limit test.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 (females only)

Control animals:

no

Details on study design:

- Duration of observation period following administration on Day 1: 14 days (Days 1 to 15)
- Frequency of observations and weighing:
Mortality checks: At least twice daily.
Observation of clinical signs: Ca. 3 minutes post dosing and at frequent intervals thereafter on Day 1; subsequently twice daily and on Day 15 in the morning
Weighing of each animal: Day 1 prior to dosing and on Days 8 and 15.
- Necropsy performed: Yes, of all animals.

Statistics:

Not applicable, as there were no deaths and only one dose group. In addition, the acute toxic class method is not intended for the calculation of a precise LD50 value.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths at 2000 mg/kg bw

Mortality:

Dose level Mortality Date of treatment
2000 mg/kg 0/3 (f) 22 March 2011
2000 mg/kg 0/3 (f) 24 March 2011

Clinical signs:

other: Clinical signs were not evident.

Gross pathology:

Necropsy of each animal at the end of the 14-day post treatment observation period (Day 15) did not reveal any macroscopic pathology abnormalities.

Interpretation of results:

not classified

Remarks:

Migrated information No mortality at the limit dose of 2000 mg/kg Criteria used for interpretation of results: EU

Conclusions:

In view of the oral LD50 > 2000 mg/kg bodyweight attained in the present study, its outcome does not necessitate any labelling regarding acute oral toxicity according to REGULATION (EC) 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In the acute oral toxicity study, all animals survived the limit dose of 2000 mg/kg. Therefore, classification of WS400101 for acute oral toxicity is not required [REGULATION (EC) 1272/2008].

 

Non-classification of WS400101 by the dermal route was reasonable, because of:

(1) Systemic exposure to WS400101 or any fraction of it probably being higher by the oral than by the dermal route,

(2) the absence of adverse effects indicative of relevant systemic absorption (apart from the sensitization response) in the available local lymph node assay with WS400101 and the acute or repeat dose oral toxicity studies with WS400101 or its structural analogue WS400151, and

(3) the sensitizing potential of WS400101 necessitates whole body protective precautions, making dermal exposure of humans to it unlikely.

 

Non-classification of WS400101 by the inhalation route was justified, because it has a low vapour pressure, decomposes before boiling and is a viscous paste, making the inhalation exposure of humans to WS400101 vapour or aerosol unlikely.