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Description of key information

LD50(oral, rat): > 2000 mg/kg body weight (no deaths or adverse effects)
LD50(dermal, rat): > 2000 mg/kg body weight (no deaths or adverse effects)

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
Study period:
Experimental start date: 01 April 2015, Experimental completion date: 22 April 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Female Wistar (RccHan™:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non pregnant. After an acclimatization period of at least 5 days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals were 8 to 12 weeks of age. The body weight variation did not exceed ±20% of the body weight of the initially dosed animal.

The animals were housed in groups of up to four in suspended solid floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival of the previously dosed animals.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 females
Control animals:
no
Details on study design:
Using available information on the toxicity of the test item, 2000 mg/kg was chosen as the starting dose.

A single animal was treated as follows:Dose Level (mg/kg)- 2000, Concentration (mg/mL) -200, Dose Volume (mL/kg)-10, Number of Rats(Female)-1; In the absence of toxicity at a dose level of 2000 mg/kg, an additional group of animals was treated as follows:Dose Level (mg/kg)- 2000, Concentration (mg/mL)-200, Dose Volume (mL/kg)-10, Number of Rats(Female)-4.
A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival of the previously dosed animals.

Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily.

Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.

At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
None recorded
Preliminary study:
A single animal was treated as follows:Dose Level (mg/kg)- 2000, Concentration (mg/mL) -200, Dose Volume (mL/kg)-10, Number of Rats(Female)-1
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.

Red colored staining of the feces was noted in all animals from Day 1 and up to 7 days after dosing.
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
No other findings
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 2000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).
Executive summary:

Introduction The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat. Methods Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of test item, as a suspension in arachis oil BP, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. Results Mortality. There were no deaths. Clinical Observations. There were no signs of systemic toxicity. Red colored staining of the feces was noted in all animals from Day 1 and up to 7 days after dosing. Body Weight. All animals showed expected gains in body weight. Necropsy. No abnormalities were noted at necropsy. Conclusion The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study is GLP compliant and of high quality (Klimish score=1)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Acute oral (OECD 420) toxicity study in the rat were performed in compliance with GLP with FAT 41045.

Acute dermal (OECD 402) toxicity study in the rat were performed in compliance with GLP with FAT 41030 a structural analogue of FAT 41045. Both substances are very similar in their chemical structure and, as demonstrated, in a number of physicochemical properties. Therefore, the use of these studies for read-across is considered to be appropriate, thus avoiding duplicate tests in vertebrate animals.

Premature deaths, adverse clinical signs, adverse effects on bodyweight or macroscopic necropsy findings were not evident in either study. In the dermal toxicity study, discolouration of the skin seen in all animals until observation day 14 or 15 was associated with the observation of residual test material and therefore, may be inherent with the dark red colour of the test material rather than representing an indication of local skin irritation or of an adverse effect.

The acute inhalation toxicity test was waived, as the available acute oral and dermal toxicity studies well cover the requirements of REACH ANNEX VII.


Justification for selection of acute toxicity – oral endpoint
only available test

Justification for classification or non-classification

FAT 41045 is not subject to classification according to the CLP (Reg. 1272/2008) or DSD (Dir. 67/548/EEC) regulations regarding acute toxicity, as no deaths or adverse effects were evident in the acute oral with FAT 41045 and dermal toxicity studies in rats treated with its structural analogue FAT 41030. Non-classification regarding acute toxicity is further supported by the fact that treatment of rats with FAT 41030 for 28 consecutive days produced a no-observed-adverse-effect-level at the highest dose level of 1000 mg/kg/day.

Aspiration toxicity classification is also not applicable, as FAT 41045 is solid and has virtually no vapour pressure.