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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted according to internationally accepted testing guidelines and performed according to GLP. Nevertheless the test substance purity is low. Justification for Read Across is reported in the endpoint summary and in the Category Justification Report attached to Section 13 of this dossier.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent, U.K.
- Age at study initiation: approximately five to eight weeks old.
- Weight at study initiation: at the start of the main study the males weighed 122 - 140 g, and the females 120 - 126 g.
- Fasting period before study: not access to drink and food an overnight fast immediately before dosing and for approximately two hours after dosing.
- Housing: animals were housed in groups of up to five by sex in solid-floor polypropylene cages with sawdust bedding.
- Diet: free access to food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, Witham, Essex, U.K.).
- Water: free access to mains drinking water.
- Acclimation period: minimum acclimatisation period of at least five days.

ENVIRONMENTAL CONDITIONS
- Temperature: 19-21°C
- Humidity: 43-55%
- Air changes: 15 changes per hour.
- Photoperiod: lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe.
The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Group 1: 1 male and 1 female (observation period of 5 days)
Group 2: 5 males and 5 females (observation period of 14 days).
Details on study design:
- Duration of observation period following administration: a first group (group 1) was observed for deaths and over signs of toxicity for 5 days; the second group (group 2) was observed for deaths and over signs of toxicity for 14 days.
- Frequency of observations and weighing: individual bodyweights were recorded on the day of dosing in the group 1, prior to dosing on day 0 and on days 7 and 14, or at death in group 2.
- Necropsy of survivors performed: no in the group 1; in the group 2 at the end of the study the surviving animals were killed by cervical dislocation.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: all animals in the group 2 were subjected to gross pathological examination. 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.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Group 1: there were no deaths.
Group 2: one male was killed one hour after dosing having sustained a broken leg. This was done for humane reasons in accordance with current U.K. Home Office guidelines. The death was therefore not attributed to the toxicity of the test material.
Clinical signs:
Group 1: there were no clinical signs of toxicity.
Group 2: no signs of systemic toxicity were noted during the study.
Body weight:
Group 2: surviving animals showed expected gain in bodyweight during the study.
Gross pathology:
Group 2: no abnormalities were noted at necropsy.

Any other information on results incl. tables

Individual clinical observations and mortality data

Dose level (mg/kg bw) Group Animal number & sex Effects noted after dosing (hours) Effects noted after dosing (hours)
1/2 1 2 3 4 1 2 3 4 5 6 7 8 9 10 11 12 13 14
2000 1 1-0 M 0 0 0 0 0 0 0 0 0 0 - - - - - - - - -
2-0 F 0 0 0 0 0 0 0 0 0 0 - - - - - - - - -
2000 2 3-0 M 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
3-1 M 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
3-2 M 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
3-3 M 0 0X - - - - - - - - - - - - - - - - -
3-4 M 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
4-0 F 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
4-1 F 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
4-2 F 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
4-3 F 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
4-4 F 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0: no signs of systemic toxicity

X: animal killed due to broken leg

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information According to the CLP regulation. Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg body-weight.
Executive summary:

Method

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley strain rat. The method used followed that described in the OECD Guidelines No. 401 "Acute Oral Toxicity" referenced as Method B1 in Commission Directive 84/449/EEC.

Following a range-finding study (group 1), a group of ten fasted animals (group 2) was given a single oral dose of undiluted test material, at a dose level of 2000 mg/kg bodyweight. The surviving animals were observed for fourteen days after the day of dosing and were then killed for gross pathological examination.

One male was killed one hour after dosing having sustained a broken leg. This was done for humane reasons in accordance with current U.K. Home Office guidelines. The death was therefore not attributed to the toxicity of the test material.

Results

No signs of systemic toxicity were noted during the study. Surviving animals showed expected gain in bodyweight during the study. No abnormalities were noted at necropsy.

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg body-weight.