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Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

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Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02/08/2017 - 28/08/2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
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 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Chemring/Batch 0727/16
- Expiration date of the lot/batch: 28/04/2019
- Purity test date: 99%


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark
- Stability under test conditions: Due to the short-term nature of the study, no analysis was carried out to determine the stability of the test item formulation.
- Solubility and stability of the test substance in the solvent/vehicle: test item was prepared as a suspension in arachis oil BP
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test item was freshly prepared as a suspension in arachis oil BP
- Preliminary purification step (if any):
- Final dilution of a dissolved solid, stock liquid or gel:
- Final preparation of a solid:

FORM AS APPLIED IN THE TEST (if different from that of starting material)

TYPE OF BIOCIDE/PESTICIDE FORMULATION (if applicable)

OTHER SPECIFICS:
Species:
rat
Strain:
Wistar
Remarks:
RccHan:WIST
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks of age
- Weight at study initiation: The body weight variation did not exceed +/- 20% of the mean body weight at the start of the study
- Fasting period before study: overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing
- Housing: animals were housed in groups of up to 4 in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet and Water :. ad libitum except the period of fasting.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70% Relative humidity
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
- Amount of vehicle (if gavage):
- Justification for choice of vehicle: Arachis oil BP was used because the test item did not dissolve/suspend in distilled water
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED:

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
In the absence of data regarding the toxicity of the test item, 300mg/kg was chosen as the starting dose.
Doses:
300, 2000 mg/kg
No. of animals per sex per dose:
1 female at 300 mg/kg
5 females at 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 30 min, 1, 2 and 4 hours after dosing and then daily for up to 14 days. Individual body weighs were recorded on Day 0 and on Days 7 and 14. morbidity and Mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays.
- Necropsy of survivors performed: yes, animals were killed by cervical dislocation. All animals were subjected to gross necropsy.
- Gross necropsy consisted of an external examination and opening of the abdominal and thoraci cavities. The appareance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
No statistics.
Preliminary study:
A single female animal has been treated with 300 mg/kg of test item.
In the absence of toxicity at a dose level of 300 mg/kg, an additional animal was treated at 2000 mg/kg.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat. (dissolved fraction)
Mortality:
No mortalities at 300 and 2000 mg/kg.
Clinical signs:
No signs of systemic toxicity were noted during the observation period at 300 and 2000 mg/kg.
Body weight:
The animal showed expected gain in body weight over the observation period at 300 and 2000 mg/kg.
Gross pathology:
No abnormalities were noted at necropsy at 300 and 2000 mg/kg.
Other findings:
None
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
LD50 ot the test item in the female Wistar strain rat is estimated to be greater than 2000 mg/kg bw. However no data can confirm that the test item could not be classified at all.
Executive summary:

An acute oral toxicity in the Wistar strain female rat (A. Sanders, 2018, Envigo) has been performed, according the 420 OECD guideline in order to assess the LD50 of the test item.

Following a sighting test at dose levels of 300 and 2000 mg/kg, a further group of 4 fasted female was given a single oral dose of test item, as a suspension in arachis oil BP, at a dose level of 2000 mg/kg. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths, no signs of toxicity, all animals showed expected gains in body weight and no abnormalities were noted at necropsy.

Therefore the LD50 ot the test item in the female Wistar strain rat is estimated to be greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Correct

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Justification for type of information:
The substance has a low vapour of <1 x 10-5 kilopascals and a particle size above 100µm. Therefore, according to the criteria detailed in ECHA guidance R7a an inhalation test is unnecessary.
Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Waived study

Acute toxicity: via dermal route

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Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and, in the absence of an in vivo study by the oral route, no systemic effects after dermal exposure are predicted on the basis of non-testing approaches (e.g. read across, QSAR studies)
Justification for type of information:
Section 8.5.3 of Annex VIII further allows for the waiving of acute dermal toxicity testing because the substance does not meet the criteria for classification for acute toxicity by the oral route (Category 5 according to GHS criteria).
Reviews comparing the classification of oral and dermal hazards indicate that it is rare for the dermal test to yield a more severe classification (Thomas and Dewhurst, 2007; Creton et al., 2010; Seidle et al., 2011, Moore et al., 2013).
Under this premise, dermal toxicity of test chemical meeting this criterion should not result in a more severe classification than the corresponding oral hazard and would be classified as a Category 5 dermal hazard.

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Waived study

Additional information

Justification for classification or non-classification

Test item is not classified under CLP for oral acute toxicity.

Under this premise, dermal toxicity of test chemical meeting this criterion should not result in a more severe classification than the corresponding oral hazard and would be not classified for dermal hazard.

The substance has a low vapour pressurer and a large particle size, is unlikely to present an inhalation hazard and therefore is not classified for this hazard endpoint.