Fatty acids, C14-18 and C16-18-unsatd., maleated, reaction products with oleylamine

Endpoint summary

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:

other: Well documented and reported study fully adequate for assessment. The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a recognized contract research organization.

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 204 g, maximum 227 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 acute oral toxicity study in rats treated with a poorly defined formulation probably containing 50% WS400107. In this previous study the LD50 was > 2500 mg/kg extrapolated to neat WS400107. Therefore, in the present acute toxicity study with WS400107 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.

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 attributable to treatment with the test material were not evident. Brown staining on the head in one animal on Days 2 and 3 was considered to be an indication of diet trapped in the fur rather than being a treatment effect.

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 in 5 of the 6 animals. In the other animal a small stomach (atrophy) was recorded.

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 EU regulations (DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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 WS400107 for acute oral toxicity is not required [DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008].

 

Non-classification of WS400107 by the dermal route was reasonable, because of the absence of effects indicative of relevant local irritation or systemic toxicity (apart from the sensitization response) in the available in vitro skin irritation, in vivo eye irritation and local lymph node assay with topical administration of WS400107. In addition, based on the physical-chemical properties of WS400107 systemic exposure after dermal administration is not expected to be higher than after oral administration where all animals survived the highest dose of 2000 mg/kg.

 

Non-classification of WS400107 by the inhalation route was justified, because WS400107 has a very low vapour pressure, decomposes before boiling and is a highly viscous liquid, making the inhalation exposure of humans to vapour or droplet aerosol unlikely.