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Diss Factsheets

Administrative data

Description of key information

- Oral: discriminating dose >2000 mg/kg, female Wistar rat, OECD 420, Envigo Research Limited, 2018.

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:
14 Aug to 04 Sep 2018
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)
GLP compliance:
yes (incl. QA statement)
Remarks:
Envigo Research Limited, Shardlow Business Park, London Road, Shardlow, Derbyshire, DE72 2GD, UK
Test type:
fixed dose procedure
Limit test:
no
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) Limited, Oxon, UK.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 153 to 188 g
- Fasting period before study: Overnight and for approximately 3 to 4 hours after dosing
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with softwood flake bedding.
- Diet: ad libitum. 2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: Arachis oil BP was used because the test item did not dissolve/suspend in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
Sighting test: 300 and 2000 mg/kg
Main test: 2000 mg/kg
No. of animals per sex per dose:
Sighting test: for each dose 1 animal
Main test: 4 animals
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 minutes, 1, 2, and 4 hours after dosing and then daily for up to 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: yes
- Other examinations 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.

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.
Statistics:
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.

The following computerized system was used in the study: Delta Controls – ORCAview
Preliminary study:
Sighting test: 300 and 2000 mg/kg
- There were no deaths.
- No signs of systemic toxicity were noted during the observation period.
- The animals showed expected gains in body weight over the observation period. See Table 1 in 'Any other information on results incl. tables'.
- No abnormalities were noted at necropsy.
Key result
Sex:
female
Dose descriptor:
discriminating dose
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
There were no deaths.
Clinical signs:
other: No signs of systemic toxicity were noted during the observation period.
Gross pathology:
No abnormalities were noted at necropsy.

Table 1. Individual Body Weights and Body Weight Changes

 

Dose Level (mg/kg)

 

Animal Number and Sex

Body Weight (g) at Day

Body Weight Gain (g) During Week

0

7

14

1

2

300 (sighting test)

1-0 Female

153

174

185

21

11

2000 (sighting test)

2-0 Female

160

170

185

10

15

2000 (main test)

3-0 Female

181

196

211

15

15

3-1 Female

170

192

198

22

6

3-2 Female

188

212

227

24

15

3-3 Female

180

195

217

15

22

Interpretation of results:
GHS criteria not met
Conclusions:
In this GLP compliant oral toxicity test, performed according to OECD 420, 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.
Executive summary:

In this GLP compliant fixed dose oral toxicity test performed according to OECD 420, the acute oral toxicity potential of the test item was assessed in the Wistar strain rat. 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 item via gavage, 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 (14 days). All animals were subjected to gross necropsy.

There were no deaths during the study. All animals showed expected gains in body weight and there were no signs of systemic toxicity. Gross necropsy did not reveal any abnormalities. 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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
GLP compliant OECD 420 study

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity

In this GLP compliant fixed dose oral toxicity test performed according to OECD 420, the acute oral toxicity potential of the test item was assessed in the Wistar strain rat (Envigo Research Limited, 2018). 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 item via gavage, 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 (14 days). All animals were subjected to gross necropsy.

There were no deaths during the study. All animals showed expected gains in body weight and there were no signs of systemic toxicity. Gross necropsy did not reveal any abnormalities.

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.

Justification for classification or non-classification

Based on the available data on acute oral toxicity, classification is not warranted according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.