Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From January to April 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
Directive CEE 84/449/CEE annex V
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): DIBROMO- 1,6-HEXANE
- Substance type: colorless liquid
- Physical state: Liquid
- Analytical purity: 98,4%
- Purity test date: 98,4%
- Lot/batch No.: TVV 01-07
- Storage condition of test material: Packaged in a glass bottle and stored in aluminium foils

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Albino - ICO: OFA-SD (IOPS Caw) provided by Iffa Crédo (69210 L'Arbresle, France).
- Age at study initiation: +/- 5 weeks
- Weight at study initiation:
* Males: 161 +/- 13 g
* Females: 140 +/- 9 g
- Fasting period before study: The day before the treatment, the animals deprived from food but had access to water ad libitum 18 hours before administration. They are feeding 4 hours after treatment.
- Housing: Animals are housed for 4-7 animals of the same sex during the period of acclimatization and 5 of the same sex during the study.
The animals wer held in polycarbonate cages (dimensions 48 x 27 x 20 cm) equipped with a stainless steel lid forming a feeding trough, and a polycarbonate bottle (500 ml). Animals were lying on a litter of sawdust and dust sifted (Societe Parisienne of Sawdust 93500 Pantin, France). The analysis of residues and potential contaminant is performed regularly (Laboratoire Municipal, 76000 Rouen, France).
- Diet (e.g. ad libitum): Ad libitum - called "Rat and Mouse Maintenance" reference A04 C (U.A.R. 91360 Villemoisson-sur-Orge, France) provided throughout the duration of the study with the exception of a period of fasting during the treatment.
- Water (e.g. ad libitum): Ad libitum - drinking water filtrated on a 0.22 micron membrane (Millipore, 78140 Vélizy, France).
- Acclimation period: for a minimum period of 5 days where rats are daily observed.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 50 +/- 20%
- Air changes (per hr): air-conditioned room/ the air is not recycled but filtred.
- Photoperiod (hrs dark / hrs light): 12 H light - 12 H dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle and amount of vehicle:
* First essay: 2000 mg/kg - Volume : 1.25 ml/kg of undiluted test item - Density of the testing substance: 1.6
* Second essay: 200 mg/kg - Volume : 10 ml/kg as a solution in PEG 300
- Justification for choice of vehicle: No justification given in the report
Doses:
* First essai: 2000 mg/kg
* Second essai: 200 mg/kg
No. of animals per sex per dose:
* First essay: 5 males - 5 females
* Second essay: 5 males - 5 females
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
* clinical signs: frequently after the adminstration (hours), then at least once per day
* Mortality: frequently after the adminstration (hours), then 2 times per day
* Weight: weighted before the administration, then at day 5, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed:
Pathology: organs observation

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 60% mortality : 2 males and 4 females at the end of expsoure
Mortality:
No mortality was noted during the observation period at a dose of 200 mg/kg and was 60% between day 2 and day 5 at a dose of 2000 mg/kg.
Clinical signs:
Clinical signs in the hours following administration of the test substance are:
- At dose of 200 mg/kg: hypokinesia, piloerection and sedation up to 4 hours p.a. in all animals
- At dose of 2000 mg/kg: sedation, hypokinesia, piloerection to Day 4, ptosis after 1 and 2 hours.
No symptoms persisted after 6 hours at a dose of 200 mg/kg and after Day 5 at 2000 mg/kg.
Body weight:
The weight change of surviving animals was normal at 200 mg/kg.
At a dose of 2000 mg/kg, the weight gain was reduced until Day 5 but was normal at the end of the observation period.
Gross pathology:
No anomaly was observed after gross examination of the principal organs of the animals found dead during the study or sacrificed at the end of study.
Due to the absence of lesions in the macroscopic examination, no histological examination was performed.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under our experimental conditions, the LD50 of the test substance DIBROMO- 1,6-HEXANE, given to the Rat by oral route was about 2000 mg/kg, with a mortality rate of 60% at this dose level .
Executive summary:

Materials and Methods

In a first assay, the test substance was administered by oral route to a group of 10 fasted Sprague-Dawley rats (5 males and 5 females) . The test item was administered undiluted at a dose level of 2000 mg/kg taking i nto consideration the density of the test substance (d =1.6). In a second assay the test substance was administered to a group of 10 rats at a dose level of

200 mg/kg in solution in Polyethylene Glycol 300 and at a volume of 10 ml/kg. The mortality, general behaviour and bodyweight gain of the animals were observed for a period of 14 days after the single administration of the test substance. A necropsy was performed on each animal found dead during the study or sacrificed at the end of the study.

Results

There was no mortality at the dose level of 200 mg/kg and the mortalfty rate was 60% after 5 days at the dose level of 2000 mg/kg. The clinical signs observed consisted in a reduction of the spontaneous activity and piloerection in the 4 hours following the administration of the test substance at 200 mg/kg or during 4 days at 2000 mg/kg. The bodyweight gain of the animals was not influenced by the treatment at 200 mg/kg and was reduced until D 5 at 2000 mg/kg and remained normal thereafter. The macroscopic examination of all the animals found dead during the study or sacrificed at the end of the study revealed no abnormality .