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Description of key information

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:
Between 30-04-1993 and 3-11-1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no deviations from standard test guidelines and no methodological deficiences, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Breeder: IFFA Crédo, 69210 L'ARBRESLE, FRANCE
Number and sex: one group of ten animals (5 males and 5 females)
On the day of the treatment, the animals were approximately 6 weeks old, and had a mean body weight of 176 ± 5 g for the males and 14 ± 6 g for the females.
Acclimatization: at least 5 days before the beginning of the study.
The animals were identified individually by earmarks or ear-notches.
During the acclimatization period and during the main test, the conditions in the animal room were as follow:
temperature: 22 ± 3°C
relative humidity: 50 ± 20 %
light/darkness cycle: 12 h/ 12 h
ventilation: about 13 cycles/hour of filtered, non-recycled air.
The temperature and relative humidity were recorded continuously and records retained.
The housing conditions (temperature, relative humidity, light/dark cycle and ventilation) were checked monthly.
The animals were housed in polycarbonate cages (48 x 27 x 20 cm) covered with a stainless steel lid. Each cage contained 4 to 7 animals of the same sex during the acclimatization period and 5 rats of the same sex during the treatment period. Each cage contained graded, dust-free sawdust.
Bacteriological analysis of the sawdust and detection of possible contaminants (pesticides, heavy metals) are performed periodically.
All the animals had free access to AO4 C pelleted diet.
Each batch of food was analysed (composition and contaminants) by the supplier.
Drinking water filtered by a F.G. Millipore membrane (0.22 micron) was contained in bottles.
Bacteriological and chemical analysis of the water and detection of possible contaminants (pesticides, heavy metals and nitrosamines) ae performed periodically.
There were no contaminants in the diet, water or sawdust at level likely to have influenced the outcome of the study.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The animals were fasted for an overnight period of approximately 18 hours before dosing, but had free access to water.
Food was given approximately 4 hours after administration of the test substance.
Doses:
As the test substance was anticipated to be non toxic at 2000 mg/kg, a limit test was performed by administrating 2000 mg/kg of the test substance to a group of 10 animals (5 males and 5 females). The test substance was adminitrated in its original form taking into consideration that the specific gravity was 1.17.
No. of animals per sex per dose:
2000 mg/kg of the test substance to 5 males and 5 females
Control animals:
yes
Details on study design:
The animals were observed frequently during the hours following administartion of the test substance, for detection of possible treatment-related clinical signs. Observation of the animals wa made at least once a day for a period of 14 days, to determine wether any of the clinical signs were reversible or not.
The animals were checked frequently during the hours followig administartion of the test substance for mortality or signs of morbidity, then at least twice a day thereafter. The time of any deaths was recorded individually, in terms of the number of hours or days after dosing.
The animals were weighted individually just before administration of the test substance, and then on days 5, 8 and 15 for the surviving animals.
The body weight gain of the treated animals was compared to a reference curve of C.I.T. control animals with the same initial weight.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
At 2000 mg/kg the mortality rate was 10 % (one female found dead on day 8)
Clinical signs:
other: At 2000 mg/kg hypoactivity, sedation and piloerection were observed within 4 hours post-treatment. On day 2, sedation and piloerection in 2 animals and hypoactivity in 8 animals were noted. Clinical signs appeared within 15 minutes of treatment and were r
Gross pathology:
Macroscopic examination of the main organs of the animal found dead during the study or those sacrified at the end of the study revealed no apparent abnormalities.
Other findings:
N/A
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions, the LD50 of the test substance n-Hexyl bromide when administrated by oral route in rats was higher than 2000 mg/kg
Executive summary:

At 2000 mg/kg, for 9 of the 10 animals, a marked decreased in spontaneous activity and piloerection within 4 hours following treatment then hypoactivity from day 2 were observed. The surviving animals had fully recovered on day 5 (8 animals) or on day 7 (one animal).

Mortality rate at 2000 mg/kg was 10 % (one female found dead on day 8).

The rate of body weight gain of the surviving animals had slowed down between days 1 and 5. The body weight gain returned to normal thereafter.

A macroscopic examination revealed no abnormalities in the animal found dead during the study or those sacrified et the end of the study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 30-04-1993 to 03-11-1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no deviations from standard test guidelines and no methodological deficiences, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.
Qualifier:
according to guideline
Guideline:
other: OECD Guidelines 404 -
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Species:
rabbit
Strain:
New Zealand White
Sex:
not specified
Details on test animals or test system and environmental conditions:
Breeder: Elevage Cunicole de Val de Selle, 80160 PROUZEL, FRANCE
3 animals were used. The animals were identified individually with a metal tag in the ear.
Weight: on the day of treatment, the animals had a mean body weight of 2.3 ± 0.2 kg.
Acclimatization: at least 5 days before the beginning of the study.
Selection of the animals: the day before treatment, the eyes of each animal were examined in order to use only animals without any signs of cutaneous irritation.
During the acclimatization period and during the main test, the conditions in the animal room were as follow:
temperature: 18 ± 3°C
relative humidity: 50 ± 20 %
light/darkness cycle: 12 h/ 12 h
ventilation: about 13 cycles/hour of filtered, non-recycled air.
The temperature and relative humidity were recorded continuously and records retained.
The housing conditions (temperature, relative humidity, light/dark cycle and ventilation) were checked monthly.
The animals were housed in polystyrene cages (35x 55 x 32 cm). Each cage wa equipped with a food container and a water bottle.
All the animals had free access to 112 C pelleted diet.
Each batch of food was analysed (composition and contaminants) by the supplier.
Drinking water filtered by a F.G. Millipore membrane (0.22 micron) was contained in bottles and provided ad libitum.
Bacteriological and chemical analysis of the water and detection of possible contaminants (pesticides, heavy metals and nitrosamines) ae performed periodically.
There were no contaminants in the diet or water at level likely to have influenced the outcome of the study.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The day before tretment, the flanks of each animal were clipped using electric clippers. Only animal showing no obvious signs of irritancy were used for the study.
As the test substance was anticipated to be irritant, a preliminary assay was conducted on 1 animal with an application of the test substance for 4 hours. The result were then confirmed using 2 additional animals.
A dose of 0.5 ml of the test substance in its original form was applied to a 6 cm2 dry hydrophilic gauze patch and this was then applied to the right flank of the animals.
The left flank did not receive any test substance and served as control. The etst substance and the gauze patch were held in contact with the skin for 4 hours by means of an adhesive hypoallergic aerated semi-oclusive dressing and a restraining bandage.
Subsequently, the dressings were removed and no residual test substance was observed.
The animals were then replaced into their individual cages.
Duration of exposure:
4 days
Doses:
0.5 ml of test substance
No. of animals per sex per dose:
3 animals
Control animals:
other: The left flank of the animals was used as control
Details on study design:
The skin was examined approximately 1, 24, 48 and 78 hours after removal of the dressing.
As there was persistent cutaneous irritation after 72 hours, the observation period was extended to a maximum of 14 days (until day 15) in order to determine the progress of the lesions and theur irreversibility.
Any change in the animals' behaviour was noted.
Preliminary study:
Marked cutaneous reactions were observed for up to 72 hours after removal of the dressing. They consisted of erythema and oedema, scores of 2 to 4 in 3 and 2 animals, respectively.
Erythema was no longer noted on day 8 and oedema by day 6.
Sex:
not specified
Dose descriptor:
LD0
Effect level:
0.5 other: ml per animal
Based on:
test mat.
Mortality:
No mortality was observed
Clinical signs:
other: A dryness of the skin was observed at the treatment site of all the animals between days 6 and 15. No ulceration or necrosis was noted.
Gross pathology:
No autopsy done
Other findings:
N/A
Interpretation of results:
Toxicity Category II
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
As the means scores for erythema, oedema for 2 out of the 3 animals reached the crietria values for irritation, under our the experimental conditions, the test substance, n-Hexyl bromide, was considered as irritant when administred by cutaneous route in rabbits.
It as to be classifed as Skin Irrit. 2 with H315 Causes skin irritation
Executive summary:

Marked cutaneous reactions were observed for up to 72 hours after removal of the dressing. They consusted of erythema and oedema, scores of 2 to 4 in 3 and 2 animals, respectively. The mean score over 24, 48 and 72 hours for individual animals was 2.0, 2.7 and 2.7 for erythema and 0.0, 2.0 and 2.7 for oedema.

Erythema and oedema had reversed by day 8.

Between days 6 and 15, a dryness of the skin was observed at the treatment site. On day 15, a dryness of the skin persisted.

No ulceration or necrosis was noted.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed

Additional information

Key values have been selected from suitable available studies (i.e. use of recognised species for a given endpoint, recognised exposure time)


Justification for selection of acute toxicity – oral endpoint
Only one study available, but done following OECD guideline by a GLP laboratory

Justification for selection of acute toxicity – dermal endpoint
Only one study available, but done following OECD guideline by a GLP laboratory

Justification for classification or non-classification

Based upon the acute dermal irritation results, the test substance as to be classified as Skin Irrit. 2 with H315: Causes skin irritation for acute toxicity according to Directive 67/548/EEC or Regulation (EC) No 1272/2008.