Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): DIPHENYLSULFON
- Substance type: organic
- Physical state: solid, white crystalline
- Analytical purity: > 99%
- Purity test date: 22/09/2001
- Lot/batch No.: 2111 SA
- Expiration date of the lot/batch: 22/09/2002
- Stability under test conditions: not indicated
- Storage condition of test material: room temperature in the dark
- Other:

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: eight weeks of age
- Weight at study initiation: 179 to 272 g
- Fasting period before study: an overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: they were housed in groups of three by sex in solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): free access to food, certified rat and mouse diet (code 5LF2) supplied by PMI Nutrition International, Nottingham, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would be reasonably be expected to affect the purpose or integrity of the study.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: an acclimatisation period of at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25°c
- Humidity (%): 30 - 70%
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark / 12 hrs light, controlled by a time switch


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 - 20 mg/ml
- Amount of vehicle (if gavage): /
- Justification for choice of vehicle:/
- Lot/batch no. (if required): /
- Purity: /


MAXIMUM DOSE VOLUME APPLIED: 2000 mg/ml


DOSAGE PREPARATION (if unusual):as a suspension


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: based on the results from this dose level further groups of fasted animals were treated at a dose level of 200 mg/kg bodyweight.
Doses:
200 - 2000 mg/kg
No. of animals per sex per dose:
3 females: 2000 mg/kg
3 males and 3 females: 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: the animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for up to 14 days.
- Frequency of observations and weighing: individual bodyweights were recorded prior to dosing and 7 and 14 days after treatment or at death.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, mortality data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
300 - 500 mg/kg bw
Mortality:
All animals treated at a dose level of 2000 mg/kg were killed in extremis one day after dosing.
No deaths were noted at a dose level of 200 mg/kg.
Clinical signs:
Signs of systemic toxicity noted in animals treated at a dose level of 2000 mg/kg were ataxia, hunched posture, lethargy, ptosis, decreased respiratory rate, laboured and gasping respiration, loss of righting reflex, exophthalmos, hypothermia and dehydration. Two animals treated with 2000 mg/kg were found comatose. No signs of systemic toxicity were noted in animals treated at a dose level of 200 mg/kg.
Body weight:
The surviving animals showed expected gains in bodyweight over the study period.
Gross pathology:
Abnormalities noted at necropsy of animals that were killed in extremis during the study were abnormally red lungs, patchy pallor of the liver, pale kidneys and haemorrhagic small intestine.
no abnormallities were noted at necropsy of animals that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD (Crl: CD® (SD) IGS BR) strain rat was estimated to be in the range of 300 - 500 mg/kg bodyweight.
The test material was classified as HARMFUL and the symbol 'Xn' and risk phrase R 22 'HARMFUL IF SWALLOWED' are required according the EU labelling reulations Commision directive 93/21/EEC