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Administrative data

Description of key information

Acute oral toxicity: OECD TG 423: LD50 > 2500 mg/kg bw.

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:
03 July 2003 to 22 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 17 December 2001
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Sprague-Dawley CD
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Females, nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 195 - 242 g at day 0. Bodyweights fell within an interval of +/- 20% of the mean initial bodyweight of the first treated group.
- Fasting period before study: overnight fast immediately before dosing and for approximately three to four hours after dosing.
- Housing: Animals were housed in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: free acces was allowed thoughout the study, Certified Rat and Mouse Diet (Code 5LF2) supplied by International Product Supplies Limited, Wellingborough, Northants, UK
- Water: free acces to mains drinking water was allowed thoughout the study
- Acclimation period: at least 5 days
- Enrichment: 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.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): twelve hours continuous light ( 06:00 to 18:00) and twelve hours darkness.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
- Dose volume: 2.06 mL/kg bw, the volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing.

DOSAGE PREPARATION:
- Test material was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level.

CLASS METHOD
- Rationale for the selection of the starting dose: In the absence of data suggesting the test material was toxic, 2000 mg/kg was chosen as the starting dose.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: The animals were observed for deaths or overt signs of toxicity 30 minutes, 1, 2 and 4 hours after dosing and thereafter once daily
- Necropsy of survivors performed: yes, at the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs.
- Body weights: Individual body weights were recorded prior to dosing and seven and fourteen days afer treatment.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: estimated value, based on the schematic diagram presented in annex 2d of OECD 423 (2001).
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.

Individual Body weights and Weekly 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

2000

1-0 Female

195

223

251

28

28

1-1 Female

206

237

255

31

18

1-2 Female

209

245

260

36

15

2-0 Female

206

231

239

25

8

2-1 Female

228

265

280

37

15

2-2 Female

242

291

310

49

19

Interpretation of results:
other: not classified: criteria not met
Remarks:
according to EU CLP Regulation (EC) No. 1272/2008 and its amendments.
Conclusions:
In the acute oral toxicity test the LD50 of the test substance in female rats was estimated by the authors, based on a schematic diagram similar to annex 2d of OECD 423, to be greater than 2500 mg/kg bw. However, based on the results of this study, applying the current schematic diagram presented in Annex 2d of OECD 423 (2001) the LD50 is estimated to be greater than 5000 mg/kg bw and therefore classification is not warranted.
Executive summary:

A study was performed to assess the acute oral toxicity of the substance, in accordance with OECD 423 (Acute Oral Toxicity - Acute Toxic Class Method) and GLP principles. In this study, 6 female rats were administered the substance, orally by gavage, undiluted at a dose level of 2000 mg/kg bw. The rats showed no mortality, there were no signs of systemic toxicity, all animals showed expected gains in body weight over the study period and no abnormalities were noted at necropsy.The acute oral LD50 for the substance in female rats is > 2500 mg/kg bw. According to the schematic diagram presented in annex 2d of OECD 423 (2001) > 2500 can be derived in case 0 or 1 animal died but > 5000 mg/kg bw can be derived when no animals died. In absence of mortality the 5000 mg/kg bw can be selected. This seem somewhat stretched in view of the highest dose being 2000 mg/kg bw and therefore the value of > 2500 mg/kg bw is used.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute oral toxicity:

A study was performed to assess the acute oral toxicity of the substance, in accordance with OECD 423 (Acute Oral Toxicity - Acute Toxic Class Method) and GLP principles. In this study, 6 female rats were administered the substance, orally by gavage, undiluted at a dose level of 2000 mg/kg bw. The rats showed no mortality, there were no signs of systemic toxicity, all animals showed expected gains in body weight over the study period and no abnormalities were noted at necropsy. The acute oral LD50 for the substance in female rats is > 2500 mg/kg bw. According to the schematic diagram presented in annex 2d of OECD 423 (2001) > 2500 can be derived in case 0 or 1 animal died but > 5000 mg/kg bw can be derived when no animals died. In absence of mortality the 5000 mg/kg bw can be selected. This seem somewhat stretched in view of the highest dose being 2000 mg/kg bw and therefore the value of > 2500 mg/kg bw is used.

Justification for classification or non-classification

Based on the results of the acute oral toxicity study the substance does not have to be classified as acute toxic by the oral route in accordance with EU CLP Regulation (EC) No. 1272/2008 and its amendments.