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Description of key information

Oral

Under the conditions of the study, the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

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:
10 January 2017 to 01 February 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)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
2008
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
- Batch No.of test material: CEACK1/16
- Expiration date of the lot/batch: 17 October 2018:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark over silica gel

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: For the purpose of the study the test material was freshly prepared, as required, as a suspension in arachis oil BP. The test material was formulated within 2 hours of being applied to the test system.

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 165 to 187 g
- Fasting period before study: Animals had an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing.
- Housing: In groups of up to 4 in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25 °C
- Humidity: 30 to 70 %
- Air changes: At least 15 changes per hour
- Photoperiod: 12 hours continuous light and 12 hours continuous dark
Route of administration:
oral: gavage
Vehicle:
arachis oil
Remarks:
(BP)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 300 and 2000 mg/kg bw
- Amount of vehicle: 10 mL/kg
- Justification for choice of vehicle: Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
A single animal was treated at 300 mg/kg bw.
Five animals were treated at 2000 mg/kg bw.
Control animals:
no
Details on study design:
OBSERVATIONS
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 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, early and late during normal working days, and once daily at weekends and public holidays. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: 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.

DATA EVALUATION
- Evaluation of data included identification of the number of animals that died during the study (or that were killed for humane reasons), and determination of the nature, severity, onset and duration of the toxic effects. If possible, the signs of evident toxicity were described. Evident toxicity refers to the toxic effects of sufficient severity that administration of the next higher dose level could result in development of severe signs of toxicity and probable mortality. Effects on body weights and abnormalities noted at necropsy were also identified.
- Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.
Statistics:
No statistical analysis was done in conjunction with this study.
Preliminary study:
DOSE LEVEL 300 MG/KG BW
- There was no mortality.
- No signs of systemic toxicity were noted during the observation period.
- The animal showed expected gains in body weight over the observation period.
- No abnormalities were noted at necropsy.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 2000 mg/kg bw was the highest dose tested
Mortality:
There were no deaths.
Clinical signs:
Noisy respiration was noted in two animals during the day of dosing and persisted in one animal 1 day after dosing. No signs of systemic toxicity were noted in three animals during the observation period. Individual clinical observations can be seen in Table 1.
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.

Table 1: Individual Clinical Observations and Mortality Data - 2000mg/kg

Dose Level mg/kg

Animal Number and Sex

Effects Noted After Dosing
(Hours)

Effects Noted During Period After Dosing
(Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

2-0
Female

0

0

Rn

Rn

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-0
Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-1
Female

0

Rn

Rn

Rn

Rn

0

0

0

0

0

0

0

0

0

0

0

0

0

3-2
Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-3
Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0


0=  No signs of systemic toxicity

Rn =Noisy respiration

Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
Under the conditions of the study, the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.
Executive summary:

The acute oral toxicity of the test material was determined in accordance with the standardised guidelines OECD 420 and EU Method B1 bis, under GLP conditions using female Wistar rats.

The test material was formulated in Arachis oil BP, this vehicle was used because the test material did not dissolve/suspend in distilled water.

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, 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.

During the observation period there were no deaths. Noisy respiration was noted in two animals treated at a dose level of 2000 mg/kg. No other signs of systemic toxicity were noted. All animals showed expected gains in body weight and no abnormalities were noted at necropsy.

Under the conditions of the study, the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
One study is available, conducted in accordance with standardised guidelines under GLP conditions. The quality of the database is therefore considered to be high.

Acute toxicity: via inhalation route

Link to relevant study records
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:
JUSTIFICATION FOR DATA WAIVING
In accordance with column 2 of section 8.5.2 of REACH, the acute toxicity by inhalation study has been omitted as scientifically unjustified on the grounds that inhalation exposure to the substance is unlikely under normal conditions of use. The acute toxicity of the substance has been determined adequately by the oral route.
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral

The acute oral toxicity of the test material was determined in accordance with the standardised guidelines OECD 420 and EU Method B1 bis, under GLP conditions using female Wistar rats.

The test material was formulated in Arachis oil BP, this vehicle was used because the test material did not dissolve/suspend in distilled water.

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, 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.

During the observation period there were no deaths. Noisy respiration was noted in two animals treated at a dose level of 2000 mg/kg. No other signs of systemic toxicity were noted. All animals showed expected gains in body weight and no abnormalities were noted at necropsy.

Under the conditions of the study, the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

Inhalation

In accordance with column 2 of section 8.5.2 of REACH, the acute toxicity by inhalation study has been omitted as scientifically unjustified on the grounds that inhalation exposure to the substance is unlikely under normal conditions of use. The acute toxicity of the substance has been determined adequately by the oral route.

Dermal

In accordance with column 2 of section 8.5.3 of REACH, the acute dermal toxicity study has been omitted as scientifically unjustified on the grounds that the acute toxicity of the substance has been determined adequately as not classified by the oral route.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to acute toxicity.