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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See endpoint summary for justification of read-across.
Cross-reference
Reason / purpose:
read-across source
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
13 October 2011 to 08 November 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
(2001)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
(2002)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Rat, RccHan: WIST(SPF)
- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst, The Netherlands
- Age at study initiation: 9-10 weeks
- Weight at study initiation: 171.9 g–197.8 g
- Fasting period before study: overnight fasting period prior to treatment and approximately 3 hours post dose
- Housing: In groups of up to five in Makrolon type-4 cages with wire mesh tops and standard softwood bedding (‘Lignocel’ J. Rettenmaier & Söhne GmbH&CoKG, 73494 Rosenberg, Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst, Switzerland). Paper enrichment, batch no. 75, (Enviro-dri from Lillico Biotechnology, Surrey, UK) was included.
- Diet: Pelleted Harlan Teklad 2914C rodent maintenance diet (batch no. 46/11, Provimi Kliba AG, 4303 Kaiseraugst, Switzerland), ad libitum
- Water: Community tap water from Itingen, ad libitum
- Acclimation period: 5-12 days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From: 18 October 2011 to: 08 November 2011
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.94 ml/kg bw at the 2000 mg/ kg bw dose level
Doses:
sighting study: 300 and 2000 mg/kg bw
main study : 2000 mg/kg bw
No. of animals per sex per dose:
sighting study: 1 female at 300 mg/kg and 1 female at 2000 mg/kg
main study: 4 females at 2000 mg/kg
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2-15
- Frequency of weighing: day 1 (prior to administration) and on test days 8 and 15
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed.
Preliminary study:
The sighting study started with a single female at a dose of 300 mg/kg body weight. As no clinical signs were observed at the initial dose, the next higher dose level of 2000 mg/kg investigated, using a single female. As no mortality occurred at 2000 mg/kg, the sighting study was complete and the main study was conducted at 2000 mg/kg.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal treated at 2000 mg/kg was found dead on test day 2. All other animals survived the scheduled treatment and observation periods.
Clinical signs:
In animal no. 1 treated at 300 mg/kg, decreased activity, hunched posture and ruffled fur were noted on test day 1. Thereafter, the animal was free of clinical signs up to the end of the observation period. In the animals treated at 2000 mg/kg, dragging of limbs, decreased activity, hunched posture, ruffled fur and / or swaying gait were noted on test day 1 and persisted up to test day 3 at the latest. Thereafter, no clinical signs were noted up to test day 15, the end of the observation period.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
In animal no. 6 which died spontaneously, distended stomach was recorded at necropsy. No abnormal macroscopic findings were recorded in the remaining animals at scheduled necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item was tested for acute oral toxicity according to the OECD TG 420, and in compliance with GLP. In the main study one animal treated at 2000 mg/kg was found dead on test day 2. All other animals survived the scheduled treatment and observation periods. The clinical signs recorded at this dose level were dragging of limbs, decreased activity, hunched posture, ruffled fur and/or swaying gait on test day 1 and persisted up to test day 3 at the latest. Based on Annex 3 and 4 of the OECD TG 420, the test item is classified as GHS category 5 corresponding to 2000 mg/kg body weight < LD50 (female rat) < 5000 mg/kgbw. Classificaion for acute oral toxicty according to 67/584/EEC and EC/1272/2008 is not warranted.

Data source

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Purity approx. 99% (GC)

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.

Applicant's summary and conclusion