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EC number: 203-691-9 | CAS number: 109-65-9
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Acute toxicity oral
The acute oral LD50 in male Sprague-Dawley rats was calculated to be 2760.6 mg/kg of body weight; the oral LD50 in females was calculated to be 3160.8 mg/kg of body weight.
Acute toxicity inhalation
LCLO(4 hour) for n-butyl bromide as a vapour is in excess of 25.4 mg/l in air.
Acute dermal toxicity
LD0 of the test substance n-BUTYL BROMIDE was higher than or equal to 2000 mg/kg in rats. No signs of toxicity were observed at this dose.
Key value for chemical safety assessment
Acute toxicity: via oral route
Link to relevant study records
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- October 18, 1979 to November 2, 1979
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- No further information specified.
- GLP compliance:
- no
- Remarks:
- Study pre-dates GLP
- Test type:
- standard acute method
- Limit test:
- no
- Specific details on test material used for the study:
- No further details specified in the study report.
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Fifty (twenty-five/sex) albino rats (Sprague-Dawley) were received for the study from A.R.S. Sprague-Dawley, Madison, Winconsin. The initial body weights of the males ranged from 189 to 230 grams, and the body weights of the females ranged from 195 to 225 grams. The rats were uniquely identified by an ear tag and housed individually in elevated wire-mesh cages. Commercial rodant ration (Purina Rodent Laboratory Chow) and tap water were available ad libitum except where noted otherwise. Rats were used in this study because they have historically been used in safety evaluation studies and are required by appropriate regulatory agencies.
Upon receipt, the twenty-five rats of each sex were assigned to the groups by a table of random numbers. The rats were acclimated to laboratory conditions for approximately one week prior to initiation of treatment. - Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Details on oral exposure:
- Appropriate amounts of the test material were administered by oral gavage following an overnight fast.
- Doses:
- 1000, 1957.9, 3872.6, 7620.8 and 15,000 mg/kg
- No. of animals per sex per dose:
- 10 per dose group (5 male/5 female)
- Control animals:
- no
- Details on study design:
- Observations and Records
All of the rats were observed for mortality and signs and toxic and pharmacologic effects at one, two and four hours post-dose, and twice daily thereafter for fourteen consecutive days. Individual body weights were recorded prior to treatment, on Day 7 and at termination.
Sacrifice and Gross Pathology
At termination (Day 14), all surviving rats were sacrificed by carbon dioxide asphyxiation, necropsied, and observations recorded. Necropsies were also performed on those animals which died during the study. - Statistics:
- The mortality data was analysed by the moving average method (Weil. 1952).
- Key result
- Sex:
- male
- Dose descriptor:
- LD50
- Effect level:
- 2 760.6 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- > 2 234.1 - < 3 411.1
- Key result
- Sex:
- female
- Dose descriptor:
- LD50
- Effect level:
- 3 160.8 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- > 2 411 - < 4 143.8
- Mortality:
- Dose Level (mg/kg) Mortality (%)
Male Female
1000 0 0
1967.9 0 0
3872.6 100 80
7620.8 100 100
15,000 100 100 - Clinical signs:
- other: Clinical observations consisted of depression, rough coat, tremors, slight depression, and red stain on eyes and/or nose, noted at all dose levels: soft feces, ataxia, laboured respiration, and urine stains, noted at the 2967.9, 3872.6, 7620.8 and 15,000
- Gross pathology:
- Gross pathology consisted of bright red discoloration of the lungs, and fluid in the thoratic cavity, urinary bladder (dark black), and stomach and intestine (clear yellow), as well as material in the stomach and intestine (dark red, greenish, oily black, compound-like).
- Other findings:
- No other findings detailed in the study report.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- 08287902 was evaluated for acute oral toxicity in male and female rats. Based upon the findings of this study, the acute oral LD50 in males was calculated to be 2760.6 mg/kg of body weight with 95% confidence limits from 2234.1 to 3411.1 mg/kg of body weight; the oral LD50 in females was calculated to be 3160.8 mg/kg of body weight, with 95% confidence limits from 2411.0 to 4143.8 mg/kg of body weight.
- Executive summary:
08287902 was evaluated for acute oral toxicity in male and female rats. Based upon the findings of this study, the acute oral LD50 in males was calculated to be 2760.6 mg/kg of body weight with 95% confidence limits from 2234.1 to 3411.1 mg/kg of body weight; the oral LD50 in females was calculated to be 3160.8 mg/kg of body weight, with 95% confidence limits from 2411.0 to 4143.8 mg/kg of body weight.
- Endpoint:
- acute toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 08/09/1993 to 22/09/1993
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Version / remarks:
- O.E.C.D. guideline No. 401, 24 February 1987.
- Deviations:
- not specified
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Specific details on test material used for the study:
- No further details specified in the study report.
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Species, strain: rat, Sprague-Dawley ICO: OFA-SD (IOPS Caw).
Reason for choice: rodent species currently required by International Authorities for this type of study.
Breeder: Iffa Credo, 69210 L’Arbresle, France.
Number and sex: one group of 10 animals (5 males and 5 females).
Age/weight: on the day of treatment, the animals were approximately 6 weeks old and had a mean weight of 179 ± 6 g for the males and 152 ± 2 g for the females.
Acclimatisation: at least 5 days before commencement of the study.
Animal identification: the animals were identified individually using perforations or notches in the flap of the ear.
Environment
During the acclimatisation period and during the study, the maintenance conditions of the animal housing facility were as follows:
Temperature: 22 ± 3°C
Humidity: 50 ± 20%
Nyctohemeral period: 12 hrs/12 hrs
Ventilation: around 13 cycles/hour of filtered and non-recycled air.
The temperature and humidity were recorded continuously and the results retained. The accommodation conditions (temperature, humidity, nyctohemeral period and ventilation) were checked each month.
The animals were housed in polycarbonate cages (48 x 27 x 20 cm) fitted with a stainless steel lid. Each cage housed 4 to 7 animals of the same sex for the acclimatisation period and 5 rats of the same sex for the treatment period. Each cage contained sawdust litter made from wood that was screened and had the dust removed (SICSA 94142 Alfortville, France).
Bacteriological analysis of the litter and testing for main contaminants (pesticides, heavy metals) were carried out regularly.
Food and drink
All animals had access to food "Rats and mice maintenance reference A04 C" (U.A.R., 91360 Villemoisson-sur-Orge, France), presented in the form of standardised stoppers.
Each batch of food was analysed (composition and contaminants) by the supplier.
Drinking water, filtered through an F.G. Millipore (0.22 microns), was distributed amongst feeding bottles.
Bacteriological and chemical as well as main contaminants (pesticides, heavy metals and nitrosamines) analyses were carried out regularly.
The non-nutritional substances that may have been present in the food, drinking water or litter were at a level where they were not able to interfere in the good conduct of the study. - Route of administration:
- oral: gavage
- Vehicle:
- unchanged (no vehicle)
- Details on oral exposure:
- The product was administered untouched, taking into account the density of the product d = 1.27.
- Doses:
- 2000 mg/kg
- No. of animals per sex per dose:
- 10 animals (5 males and 5 females).
- Control animals:
- no
- Details on study design:
- Administration was carried out once, orally, using a tube with a stainless steel eccentric tip (diameter: 18 G.2", Perfektum: Poffer & Sons Inc., New Hyde Park, New York 11040, U.S.A.) mounted on a 1 ml glass syringe (graduations of 0.01 ml, Record: Carrieri, 75005 Paris, France).
The volume administered to each animal was adjusted to the body weight determined on the day of treatment.
CLINICAL EXAMINATIONS
Clinical signs
Observation of the animals was carried out frequently during the hours following administration of the product. It was carried out at least once a day for the 14 days afterwards to note reversible or irreversible clinical signs. The appearance or disappearance of clinical signs was recorded for each animal.
Mortality
The mortality check was carried out frequently just after administration of the product and at least twice a day for a minimum of 14 days of observation.
Body weight
The animals were weighed individually just before administration of the product, then on days 5, 8 and 15.
The weight development of the treated animals was compared to a reference curve drawn up at C.I.T from untreated animals of the same initial weight.
PATHOLOGY
Autopsy
On day 15, the animals were sacrificed using inhalation of an excess of CO2 and underwent a macroscopic examination.
Macroscopic examination
After opening the abdominal and chest cavities, a macroscopic examination of the main organs was carried out: digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and other organs with abnormalities.
The macroscopic observations were recorded individually. The organs presenting macroscopic lesions were sampled and preserved in a formaldehyde buffer at 10%.
Microscopic examination
No microscopic examination was carried out. - Statistics:
- Not specified.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD0
- Effect level:
- >= 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortality was found during the observation period.
- Clinical signs:
- other: At 2000 mg/kg, signs of hypoactivity or sedation and piloerection were observed in the 4 hours following the treatment. No clinical sign was observed between days 2 and 15.
- Gross pathology:
- There was no proof of a visible abnormality in the macroscopic examination of the main organs of the animals sacrificed at the end of the study.
- Other findings:
- No further findings reported.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the experimental conditions, the LD 0 of the product n-BUTYL BROMIDE administered orally in rats is greater than or equal to 2000 mg/kg.
- Executive summary:
At the request of the Sponser, the acute toxicity of the product n-BUTYL BROMIDE was assessed orally in rats in accordance with the O.E.C.D guidelines. (No. 401, 24 February 1987). The study was carried out in accordance with the Good Laboratory Practice regulations.
Methods
The product was administered orally to a group of 10 Sprague-Dawley rats (5 males and 5 females) on a liquid diet. Administration was carried out with the product untouched at a dosage of 2000 mg/kg, taking into account the density of the product d = 1.27.
The clinical signs, mortality and weight development of the animals was monitored for a period of 14 days after single-dose administration of the product.
An anatomical pathological examination was carried out on each of the animals that were sacrificed at the end of the study.
Results
At 2000 mg/kg, a significant reduction in the spontaneous activity and piloerection were observed in the four hours following the treatment. No clinical signs were noted at day 2.
Mortality was zero at a dose of 2000 mg/kg.
The weight development in males was slightly slowed between days 1 and 5. The weight development in females was normal.
The autopsy of the animals that were sacrificed at the end of the study did not show any macroscopic abnormality.
Conclusion
Under the experimental conditions, the LD 0 of the product n-BUTYL BROMIDE administered orally in rats is greater than or equal to 2000 mg/kg.
Referenceopen allclose all
Male and Female Cumulative Mortality Dataa
Acute Oral Toxicity Study of 08287902 in Rats
Dosage Level mg/kg |
Time Post-Dose |
Percent Mortality |
||||||||||||||||
Hours |
Days |
|||||||||||||||||
1 |
2 |
4 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
||
Males |
||||||||||||||||||
1000 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1967.9 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
3872.6 |
0 |
0 |
0 |
3 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
100 |
7620.8 |
0 |
0 |
1 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
100 |
15,000 |
0 |
0 |
0 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
100 |
Females |
||||||||||||||||||
1000 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1967.9 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
3872.6 |
0 |
0 |
0 |
0 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
4 |
80 |
7620.8 |
0 |
0 |
1 |
4 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
100 |
15,000 |
0 |
0 |
0 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
100 |
aData based on five animal/sex/group.
KEY to Daily Clinical Observations
N = Normal; D = Depression; R = Rough Coat; B = Red Stain on Nose and/or Eyes; S = Slight Depression; T = Tremors; F = Soft Feces; A = Ataxia; L = Labored Respiration; O = Lacrimation; E = Salivation; U = Urine Stains; H = Hunching; P = Prostrate
Individual Daily Clinical Observations
Acute Oral Toxicity Study of 08287902 in Rats
1000 mg/kg
Animal Number |
Time Post-Dose |
||||||||||||||||
Hours |
Days |
||||||||||||||||
1 |
2 |
4 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
|
Males |
|||||||||||||||||
D66848 |
N |
RD |
DR |
DR DR |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66849 |
N |
DR |
DR |
DR DR |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66850 |
N |
DR |
DR |
DR DR |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66851 |
N |
DR |
DR |
SR SR |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66852 |
N |
DRB |
DRB |
SR SR |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
Females |
|||||||||||||||||
D66853 |
N |
DRT |
DRT |
SRB SRB |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66854 |
N |
DR |
DR |
SRB SRB |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66855 |
SR |
DRBT |
TBDR |
SRB SRB |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66856 |
R |
DRB |
DRB |
DR DR |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66857 |
R |
DR |
DR |
SR SR |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
1967.9 mg/kg
Animal Number |
Time Post-Dose |
||||||||||||||||
Hours |
Days |
||||||||||||||||
1 |
2 |
4 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
|
Males |
|||||||||||||||||
D66868 |
S |
S |
DRA |
DR DR |
R R |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66869 |
SF |
DRFLA |
DRAFL |
DROEL DRSLO |
RB RB |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66870 |
SF |
DRFLA |
DRFLA |
DR DR |
R R |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66871 |
DRA |
DRFLA |
DRFLA |
SR SR |
R R |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66872 |
DA |
DRA |
DRATO |
SR SR |
R R |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
Females |
|||||||||||||||||
D66873 |
S |
DRUA |
DRUAO |
DRBU DRBU |
SR SR |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66874 |
S |
DRUA |
DRUAOL |
DRBU DRBU |
SR SR |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66875 |
S |
DRA |
DRAO |
SU SU |
SR SR |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66876 |
SRF |
DRUT |
DRUFO |
SBU SBU |
SR SR |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66877 |
SR |
DRA |
DROAU |
DBU DBU |
SR SR |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
3872.6 mg/kg
Animal Number |
Time Post-Dose |
||||||||||||||||
Hours |
Days |
||||||||||||||||
1 |
2 |
4 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
|
Males |
|||||||||||||||||
D66878 |
S |
DRA |
DRAOE |
DHPLUB DHPLUB |
Found dead |
||||||||||||
D66879 |
DRAF |
DRAF |
DRAOUF |
Found dead |
|||||||||||||
D66880 |
DRF |
DRAF |
DROUFA |
Found dead |
|||||||||||||
D66881 |
DRF |
DRAFB |
DROU FLE |
DHPLUB DHPLUB |
Found dead |
||||||||||||
D66882 |
S |
DRAT |
DRAT OUF |
Found dead |
|||||||||||||
Females |
|||||||||||||||||
D66883 |
S |
DRAFT |
DRAT OFU |
DRPLU DRPLU |
Found dead |
||||||||||||
D66884 |
SF |
DRAFT |
DRAT OFU |
DRPLU DRPLU |
Found dead |
||||||||||||
D66885 |
S |
DRAT |
DRAT OFU |
DRPLU DRPLU |
Found dead |
||||||||||||
D66886 |
SRF |
DRAF |
DRAT OFU |
DHPUB DPHUB |
DHPUB DHPUB |
SRUPB SRUPB |
SRU SRU |
RU RU |
U U |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
N N |
D66887 |
RF |
DRAFT |
DRAT OFU |
DHPUB DHPUB |
Found dead |
7620.8 mg/kg
Animal Number |
Time Post-Dose |
||||||||||||||||
Hours |
Days |
||||||||||||||||
1 |
2 |
4 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
|
Males |
|||||||||||||||||
D66888 |
R |
DR |
PLEOR |
Found dead |
|||||||||||||
D66889 |
SRAF |
DRFA TB |
Found dead |
||||||||||||||
D66890 |
SR |
SRFA |
DRAFULT |
Found dead |
|||||||||||||
D66891 |
R |
DREA FT |
PLEOR |
Found dead |
|||||||||||||
D66892 |
SR |
DRAT |
PLEOR |
Found dead |
|||||||||||||
Females |
|||||||||||||||||
D66893 |
DRF |
DRFUA |
PROFUL |
Found dead |
|||||||||||||
D66894 |
FDRA |
DRFU AT |
DRFUAT |
DHPLUB DHPLUB |
Found dead |
||||||||||||
D66895 |
DRBA |
DRAB TU |
Found dead |
||||||||||||||
D66896 |
DRBA |
DRAB FT |
PRLTOE UF |
Found dead |
|||||||||||||
D66897 |
SRA |
DRAB FT |
DRUFOTA |
Found dead |
15,000 mg/kg
Animal Number |
Time Post-Dose |
||||||||||||||||
Hours |
Days |
||||||||||||||||
1 |
2 |
4 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
|
Males |
|||||||||||||||||
D66858 |
R |
DR |
ATUDRBL |
Found dead |
|||||||||||||
D66859 |
R |
DRB |
ATUDRB |
Found dead |
|||||||||||||
D66860 |
DR |
PRL |
PRL |
Found dead |
|||||||||||||
D66861 |
RF |
DRF |
BUDRF |
Found dead |
|||||||||||||
D66862 |
R |
DRU |
ADRU |
Found dead |
|||||||||||||
Females |
|||||||||||||||||
D66863 |
R |
TUDRB |
TUADRB |
Found dead |
|||||||||||||
D66864 |
R |
UDRB |
TUADRB |
Found dead |
|||||||||||||
D66865 |
SR |
TUDRB |
TRPLU |
Found dead |
|||||||||||||
D66866 |
R |
TUDRB |
TUADRB |
Found dead |
|||||||||||||
D66867 |
R |
PLR |
PLR |
Found dead |
Gross Pathology Summary
Acute Oral Toxicity Study of 07287902 in Rats
ORGAN DESCRIPTION |
Dosage Level (mg/kg): |
||||
1000 |
1967.9 |
3872.6 |
7620.8 |
15,000 |
|
Number of Animals Examined Number with No Gross Pathology |
10 10 |
10 10 |
10 1 |
10 0 |
10 0 |
LUNGS Bright red |
|
|
|
|
10 |
THORACIC CAVITY Contained Fluid |
|
|
5 |
|
|
STOMACH Contained Dark Red Material Contained Greenish Material Contained Oily Black Material Contained Compound-Like Material Contained Clear Yellow Fluid |
|
|
5 2 |
8 2 |
10 |
INTESTINE Contained Dark Red Material Contained Greenish Material Contained Oily Black Material Contained Compound-Like Material Contained Clear Yellow Fluid |
|
|
5 2 |
8 2 |
10 |
URINARY BLADDER Contained Dark Black Fluid |
|
|
|
2 |
|
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 760.6 mg/kg bw
- Quality of whole database:
- K2
Acute toxicity: via inhalation route
Link to relevant study records
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 19 March to 10 April 1997 and 14 May to 6 June 1997.
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.2 (Acute Toxicity (Inhalation))
- Deviations:
- not specified
- GLP compliance:
- yes
- Test type:
- traditional method
- Limit test:
- no
- Specific details on test material used for the study:
- No further details specified on the study report.
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Fifteen male and 15 female albino rats (Sprague-Dawley) were selected from two consignments of rats obtained from Charles River UK Ltd, Manston Road, Margate, Kent, England on 19 March 1997 (10 male and 10 female) and 14 May (5 male, 5 female). The rats were selected so that males and females would be between 8 weeks and 9 weeks old on the day of exposure. The weight ranges were 182 - 213 g for males and 170 - 187 g for females when placed on the study.
On arrival the rats were allocated to 1 of 3 groups, each of 5 males and 5 females and were identified individually by a number tattooed on the ears. The rats were housed by sex in groups of 5 and acclimatised to laboratory conditions for at least 5 days before the day of exposure.
The holding cages (size 35 cm x 53 cm x 25 cm height) were made of stainless steel sheet and wire mesh and were suspended on a movable rack. While in their cages all rats had free access to a measured excess amount of food (SDS RMI) and tap water. Food and water supplies were analysed routinely to determine the levels of chemical or microbiological contaminants. Room lighting was by artificial light between 8 am and 8 pm daily.
The rats remained in a holding room except for the 4-hour exposure period and an overnight post exposure period when the rats in the test groups were kept in a ventilated cabinet to allow dispersal of any residual test substance.
The temperature and relative humidity of the holding room air was monitored continuously using a Kent Clearspan thermohygrograph. The temperature of the holding area during the study generally remained within the range of 21 °C± 2°C and the relative humidity was normally within the range 55% ± 10%. On one occasion and for a period of less than I hour the temperature and relative humidity of the room air fell to 16.5°C and 37% repectively. The extremes of temperature and relative humidity were considered unlikely to have influenced the results of the study. - Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- nose only
- Vehicle:
- clean air
- Remark on MMAD/GSD:
- Not specified
- Details on inhalation exposure:
- Atmosphere generator
The atmosphere generator, was designed to produce and maintain an atmosphere containing vapour by evaporation of the test substance from a fritted glass disc with a counter current of air. All parts of the generator in contact with the test substance were made of glass. The test substance was delivered to the generator at a constant flow rate from a syringe driven by a syringe pump and the air supplied to the generator was dried, filtered and oil free.
Exposure chambers
The snout-only exposure chambers were of cylindrical form (30 cm id, 45 cm height) and made of aluminium alloy. The chambers had an enclosed volume of approximately 30 litres. The rats were held for exposure in moulded polycarbonate tubes which were attached at evenly spaced ports in the cylindrical section of the chamber. The tubes were tapered at one end to allow the snout only to project into the chamber. The other end was closed by insertion of an expanded plastic bung. A push rod passed through the centre of the bung and was adjusted to maintain the position of a rat during exposure. The tubes were attached to the chamber at parts in the mid-section of the chamber.
The test atmosphere entered the chamber through a port at the top centre of the chamber and was extracted at the base centre below the level of the rats. Each chamber was installed in a large fume cupboard exhausting through an absolute filter.
PROCEDURE
A supply of clean dried air was connected to the vapour generator and the supply pressure was adjusted to give a flow rate of 10 litres per minute measured at the generator outlet tube. An in-line flow meter was used to monitor air flow throughout the exposure.
A syringe filled with the test substance was fitted to the syringe pump and connected to the generator with PTFE tubing. A flow rate of 0.18 ml/minute (Group 2) or 0.22 ml/minute (Group 3) was selected for the exposure. These flow rates were expected to give a vapour concentration of approximately 20 mg/l and in excess of 20 mg/l respectively.
The rats to be exposed were placed into restraining tubes. The tubes were attached to the ports in the mid section of the chamber.
The syringe pump and air supply were switched on and the exposure timed for 4 hours, following a
7-minute equilibration period.
After 4 hours, the supply of test substance was discontinued and the exposure chamber was allowed to clear before the rats were removed for examination.
Following exposure, the rats were returned to the holding cages and food and water supplies were restored. The test rats were kept in a ventilated cabinet overnight and then returned to the holding room for the remainder of the observation period.
The control group was treated similarly but exposed to clean dried air only.
The control rats were returned to the holding room at the end of the exposure procedure.
CHAMBER AIR TEMPERATURE
The air temperature in the exposure chamber was measured with a thermometer and recorded at the start of exposure and then at 30-minute intervals during the 4-hour exposure. - Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- 4 h
- Concentrations:
- 18.0 mg/l or 25.4 mg/l of air.
- No. of animals per sex per dose:
- One control group and 2 test groups each of 5 male and 5 female rats.
- Control animals:
- yes
- Details on study design:
- OBSERVATIONS
Clinical signs
The rats were observed continuously for signs of reaction to the test substance during exposure and at least twice daily throughout the observation period. The clinical signs were recorded at the end of the chamber equilibration period, at 0.25, 0.5 and 1.0 hours and then at hourly intervals during the exposure. During the observation period, the clinical signs were recorded once in the morning and then as necessary following a later check for clinical signs.
Bodyweight
All rats were weighed daily from the day of delivery to the Huntingdon Life Sciences up to and including the day of exposure. During the observation period rats were weighed on Days 7 and 14.
Food and water consumption
The amount of food and water consumed by each cage of rats was measured daily from the day of arrival. The daily mean intakes of food and water for each rat were calculated from the recorded data.
TERMINAL STUDIES
At the end of the 14-day observation period, the rats were killed by intraperitoneal injection of pentobarbitone sodium and exsanguinated when clinically dead.
All rats were subjected to a detailed macroscopic examination. The lungs were infused with, and preserved in, buffered 10% formalin together with samples of the liver and kidneys and retained until the study completion date. - Statistics:
- Not specified
- Key result
- Sex:
- male/female
- Dose descriptor:
- LCLo
- Effect level:
- > 25.4 mg/L air
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Mortality:
- There were no deaths following exposure to the vapour of n-butyl bromide at a concentration of 18.0 mg/l or 25.4 mg/l of air.
- Clinical signs:
- other: During the exposure During exposure, signs seen in rats exposed to n-butyl bromide at 18.0 mg/l or 25.4 mg/l were exaggerated respiratory movements and shallow breathing. In addition, irregular respiration was seen in rats exposed at 25.4 mg/l. During th
- Body weight:
- The rate of bodyweight gain for the test rats was similar to that of the control rats.
- Gross pathology:
- Minimal congestion of all lobes of the lung and a small dark focus on the left lung were seen in 1 male test rat at 18.0 mg/l. There were no other macroscopic abnormalities in any rat.
- Other findings:
- Food consumption
Food consumption for test rats was slightly reduced on the day following exposure ton-butyl bromide. Otherwise food consumption for test rats was similar to that of the controls.
Water consumption
Water consumption in test rats (except for females at 25.4 mg/l) was slightly reduced on the day following exposure to n-butyl bromide. Otherwise water consumption for test rats was similar to that of the control rats. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The LCLO (4 hour) for n-butyl bromide is in excess of 25.4 mg/l in air.
- Executive summary:
Test substance
A colourless liquid identified as n-butyl bromide (Batch No. 5-254-1).
Test animals
Albino rats, (Sprague-Dawley). One control group and 2 test groups each of 5 male and 5 female rats.
Route of administration
By inhalation of a test atmosphere containing a vapour generated from the test substance.
Duration of exposure
4 hours continuous snout only exposure.
Observation period
14 days post exposure.
Results
Exposure levels and mortality
Group Level Mortality
(mg/l) M F Total
1 control 0/5 0/5 0/10
2 18.0 mg/l 0/5 0/5 0/10
3 25.4 mg/l 0/5 0/5 0/10
Clinical signs
Clinical signs seen in rats during exposure to n-butyl bromide were exaggerated respiratory movements and shallow breathing. Irregular respiration was also noted in rats exposed at 25.4 mg/l.
Signs seen in the test rats during a 2 hour post-exposure observation period were staggering, wet fur around the snout and jaws and peripheral vasodilatation. Exaggerated respiratory movements and matted fur were seen in rats exposed at 18.0 mg/1. Lacrimation was observed in 2 female rats. A clear (lacrimation) or red secretion from the eyes was observed in the rats exposed at 25.4 mg/l. On Day 1 of observation, staining around the urogenital region and brown staining on the head were also noted in female rats exposed at 18.0 mg/l.
Additional signs noted in rats exposed at 25.4 mg/l were whole body tremors and lethargy.
Male and female test rats exposed at 18.0 mg/l were normal in appearance and behaviour by Days 2 and 4 of the observation period respectively. Males and females exposed at 25.4 mg/l were normal in appearance and behaviour by Days 1 and 2 of the observation period respectively.
Fur soiled with excreta was evident in all test and control rats during and immediately following exposure. The sign was attributed to the method of restraint.
Bodyweight
The rate of bodyweight gain for the test rats was similar to that of the control rats.
Food and water consumption
Food consumption for test rats was slightly reduced on the day following exposure to n-butyl bromide. Otherwise food consumption for test rats was similar to that of the controls.
Water consumption in test rats (except for females exposed at 25.4 mg/l) was slightly reduced on the day following exposure ton-butyl bromide. Otherwise water consumption for test rats was similar to that of the control rats.
Macroscopic pathology
Minimal congestion of all lobes of the lung and a small dark focus on the left lung were seen in 1 male test rat at 18.0 mg/l. There were no other macroscopic abnormalities in any rat.
CONCLUSION
The LCLO(4 hour) for n-butyl bromide as a vapour is in excess of 25.4 mg/l in air.
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 1977
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- no guideline followed
- GLP compliance:
- no
- Remarks:
- Study pre-dates GLP
- Test type:
- traditional method
- Limit test:
- no
- Specific details on test material used for the study:
- n-Butyl Bromide
Lot No. 11254 - Species:
- rat
- Strain:
- other: Charles River
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Strain: Charles River Rats
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure:
- whole body
- Vehicle:
- clean air
- Remark on MMAD/GSD:
- Not applicable - tet substanfce is a liquid
- Details on inhalation exposure:
- The vapor was generated by bubbling a stream of clean, dry air (-40 °C dewpoint) through the undiluted test material in a gas washing bottle. The resulting air-vapor mixture was then introduced into the exposure chamber.
- Analytical verification of test atmosphere concentrations:
- not specified
- Duration of exposure:
- 4 h
- Concentrations:
- 28.50, 42.88 and 54.97 mg/l air
- No. of animals per sex per dose:
- 10 animals per dose (5 male/5 female)
- Control animals:
- no
- Details on study design:
- Observation period: 14 days
Complete necropsies were done on all rats that lived through the experiment when the study was terminated at the end of the 14-day post-exposure observation period. Similar examinations were done, as quickly after death as possible, on all rats that died during the experiment. - Statistics:
- Not specified
- Key result
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- 37.06 mg/L air
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Mortality:
- Group No. Mortality
Male Female
I 1/5 1/5
II 3/5 3/5
III 5/5 5/5 - Clinical signs:
- other: Ptosis, Dyspnea & Lacrimation reported.
- Body weight:
- The average 2-week bodv weight gains for surviving animals were within the norrnal limits.
- Gross pathology:
- No gross tissue changes attributed to the effects of the test material were observed in any of the rats that lived through the experiment.
Slight to moderate hydrothorax was observed in all rats in test group T-II that died during the experiment (3 male and 3 female rats). Hydrothorax was considered a secondary effect of the test material. Gross tissue changes observed in rats that dies during the experiment (1 male and 1 female from treatment group T-1 and all male and female rats from treatment group T-III) were considered normal post-mortem alterations. - Other findings:
- No further details specified in the study report.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- LC50 37.06 mg/l air
- Executive summary:
Strain: Charles River Rats
Exposure Data: Vapor Whole body exposure – 4 hours in duration, 14 days observation period
No gross tissue changes attributed to the effects of the test material were observed in any of the rats that lived through the experiment.
Slight to moderate hydrothorax was observed in all rats in test group T-II that died during the experiment (3 male and 3 female rats). Hydrothorax was considered a secondary effect of the test material. Gross tissue changes observed in rats that dies during the experiment (1 male and 1 female from treatment group T-1 and all male and female rats from treatment group T-III) were considered normal post-mortem alterations.
LC50 37.06 mg/l air
Referenceopen allclose all
Concentration of n-butyl bromide
Chemical analysis
Group |
Sample |
Time taken (h:min) |
Amount in air (mg/l) |
Nominal concentration1 (mg/l) |
2 |
1 2 3 4 5 |
0:30 1:00 2:00 3:00 3:50 |
15.3 17.2 17.5 19.8 20.3 |
|
Mean sd |
18.0 2.04 |
24.3 |
1Calculated from the weight of test substance dispersed and the total volume of air supplied to the exposure system
sd Standard deviation
Chemical analysis
Group |
Sample |
Time taken (h:min) |
Amount in air (mg/l) |
Nominal concentration1 (mg/l) |
3 |
1 2 3 4 5 |
0:30 1:00 2:00 3:00 3:50 |
25.0 27.3 25.0 25.2 24.7 |
|
Mean sd |
25.4 1.05 |
26.1 |
1Calculated from the weight of test substance dispersed and the total volume of air supplied to the exposure system
sd Standard deviation
Clinical signs during exposure
Group |
Signs |
Number showing signs |
||||||
Time in hours |
||||||||
0* |
0.25 |
0.5 |
1.0 |
2.0 |
3.0 |
4.0 |
||
1M (Control) |
Normal appearance and behaviour Fur soiled with excreta |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
1F (Control) |
Normal appearance and behaviour Fur soiled with excreta |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
2M (18.0 mg/l) |
Normal appearance and behaviour Fur soiled with excreta Shallow respiration Exaggerated respiratory movements |
5 |
5 |
4
1 |
5 4 1 |
5 4 1 |
5 4 1 |
5
5 |
2F (18.0 mg/l) |
Normal appearance and behaviour Fur soiled with excreta Shallow respiration Exaggerated respiratory movements |
5 |
5 |
5 |
5 4 1 |
5 4 1 |
5 4 1 |
5
5 |
3M (25.4 mg/l) |
Normal appearance and behaviour Fur soiled with excreta Irregular respiration Exaggerated respiratory movements Shallow respiration |
5 |
3
2 |
4 1 |
2 3 |
5 |
5
5 |
5
5 |
3F (25.4 mg/l) |
Normal appearance and behaviour Fur soiled with excreta Irregular respiration Exaggerated respiratory movements Shallow respiration |
5 |
5 |
5 |
5 |
5 |
5
5 |
5
5 |
*Clinical signs recorded during the 7-minute equilibration period
Clinical signs during observation period
Group |
Signs |
Number showing sign |
||||||||||||||||
Day of observation period |
||||||||||||||||||
0hr* |
1hr* |
2hr* |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
||
1M (Control) |
Normal appearance and behaviour Fur soiled with excreta |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
1F (Control) |
Normal appearance and behaviour Fur soiled with excreta |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
2M (18.0 mg/l) |
Normal appearance and behaviour Fur soiled with excreta Staggering Wet fur around the snout and/or jaws Peripheral vasodilation Exaggerate respiratory movements Matted fur Brown staining around snout and/or jaws |
5 5 5 5 4 |
5
4 3 5 |
1 1 1 1 1 5 1 |
3
1
2 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
2F (18.0 mg/l) |
Normal appearance and behaviour Fur soiled with excreta Staggering Wet fur around the snout and jaws Peripheral vasodilation Exaggerated respiratory movements Clear secretion from the eyes Matted fur Staining around the uro-genital region Brown staining on the head |
5 5 5 5 5 2 |
5
5 4 5 |
4
1
1 |
1
5 3 |
4
1 |
4
1 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
3M (25.4 mg/l) |
Normal appearance and behaviour Fur soiled with excreta Whole body tremors Staggering Wet fur around the snout and/or jaws Peripheral vasodilation Clear discharge from the eyes |
5 1 5 5 5 2 |
5
1 5 |
5
1 5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
3F (25.4 mg/l) |
Normal appearance and behaviour Fur soiled with excreta Staggering Wet fur around the snout and/or jaws Peripheral vasodilation Clear discharge from the eyes Red discharge from the eyes Lethargy Whole body tremors |
5 5 4 5 4 1 1 2 |
5 1 5
1 1 |
5 1 5
1 1 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
*Clinical signs recorded after exposure on the day of exposure
Individual and group mean bodyweights (g)
Group |
Rat |
Day of observation |
|||||||
-5 |
-4 |
-3 |
-2 |
-1 |
0 |
7 |
14 |
||
1M (Control) |
21 22 23 24 25 |
234 232 228 230 227 |
248 253 242 240 240 |
260 263 251 255 250 |
273 278 258 262 259 |
280 287 264 275 266 |
287 297 269 280 274 |
354 368 310 334 321 |
407 419 337 378 356 |
Mean |
230 |
245 |
356 |
266 |
274 |
281 |
337 |
379 |
|
1F (Control) |
26 27 28 29 30 |
190 197 197 192 203 |
198 191 195 203 198 |
199 210 201 208 203 |
202 211 208 216 208 |
199 208 213 219 212 |
208 201 203 221 209 |
228 225 224 243 230 |
239 244 235 265 244 |
Mean |
196 |
197 |
204 |
209 |
210 |
209 |
230 |
245 |
|
2M (18.0 mg/l) |
31 32 33 34 35 |
242 240 231 221 242 |
261 254 242 234 256 |
273 268 256 248 266 |
278 282 269 259 278 |
290 293 276 271 285 |
298 300 285 272 294 |
335 259 327 314 335 |
379 419 376 343 382 |
Mean |
235 |
249 |
262 |
273 |
283 |
290 |
334 |
380 |
|
2F (18.0 mg/l) |
36 37 38 39 40 |
205 192 205 189 193 |
212 187 196 201 198 |
217 201 209 205 202 |
223 204 209 208 209 |
219 204 217 206 210 |
223 198 209 216 205 |
233 217 230 231 224 |
251 223 243 243 243 |
Mean |
197 |
199 |
207 |
211 |
211 |
210 |
227 |
241 |
|
3M (25.4 mg/l) |
1 2 3 4 5 |
227 252 229 231 250 |
239 262 239 247 262 |
243 268 246 254 268 |
251 274 254 265 276 |
262 283 263 274 283 |
269 288 271 282 292 |
210 322 309 332 320 |
364 364 349 389 359 |
Mean |
238 |
250 |
256 |
264 |
273 |
280 |
319 |
365 |
|
3F (25.4 mg/l) |
6 7 8 9 10 |
211 199 208 196 208 |
217 204 220 203 213 |
218 209 228 203 213 |
220 206 232 200 209 |
225 216 239 211 222 |
223 217 240 214 222 |
244 233 244 223 242 |
257 248 254 234 251 |
Mean |
204 |
211 |
214 |
213 |
223 |
223 |
237 |
249 |
0 = Day of exposure
Group mean daily food consumption (g/rat)
Group |
Days |
||||||||||||||||||
Pre-exposure |
Post-exposure |
||||||||||||||||||
-5 |
-4 |
-3 |
-2 |
-1 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
|
1M (Control) |
35 |
35 |
34 |
34 |
34 |
29 |
35 |
35 |
32 |
36 |
34 |
35 |
37 |
36 |
35 |
35 |
35 |
34 |
32 |
2M (18.0 mg/l) |
35 |
37 |
36 |
35 |
36 |
22 |
32 |
34 |
35 |
35 |
35 |
36 |
37 |
36 |
37 |
36 |
37 |
36 |
37 |
3M (25.4 mg/l) |
33 |
33 |
34 |
34 |
34 |
16 |
31 |
33 |
33 |
33 |
33 |
33 |
33 |
33 |
35 |
33 |
36 |
34 |
33 |
1F (Control) |
21 |
24 |
22 |
22 |
22 |
22 |
28 |
24 |
21 |
25 |
24 |
23 |
25 |
24 |
26 |
24 |
22 |
24 |
22 |
2F (18.0 mg/l) |
23 |
26 |
26 |
23 |
24 |
13 |
23 |
24 |
24 |
27 |
29 |
25 |
23 |
24 |
27 |
26 |
22 |
24 |
25 |
3F (25.4 mg/l) |
25 |
25 |
22 |
26 |
25 |
15 |
23 |
24 |
25 |
23 |
23 |
25 |
24 |
21 |
24 |
26 |
25 |
23 |
22 |
Group mean daily water consumption (g/rat)
Group |
Days |
||||||||||||||||||
Pre-exposure |
Post-exposure |
||||||||||||||||||
-5 |
-4 |
-3 |
-2 |
-1 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
13 |
14 |
|
1M (Control) |
36 |
34 |
35 |
35 |
35 |
34 |
36 |
35 |
33 |
36 |
33 |
34 |
36 |
33 |
36 |
37 |
35 |
34 |
33 |
2M (18.0 mg/l) |
26 |
35 |
36 |
34 |
35 |
23 |
36 |
34 |
28 |
33 |
33 |
33 |
33 |
34 |
32 |
34 |
35 |
36 |
37 |
3M (25.4 mg/l) |
34 |
33 |
34 |
35 |
34 |
21 |
34 |
35 |
33 |
34 |
36 |
34 |
33 |
34 |
35 |
32 |
35 |
33 |
32 |
1F (Control) |
21 |
27 |
24 |
23 |
22 |
25 |
27 |
24 |
21 |
28 |
25 |
24 |
24 |
26 |
28 |
28 |
23 |
28 |
26 |
2F (18.0 mg/l) |
32 |
30 |
28 |
25 |
32 |
17 |
26 |
31 |
23 |
32 |
32 |
33 |
33 |
33 |
34 |
37 |
28 |
34 |
34 |
3F (25.4 mg/l) |
30 |
30 |
26 |
32 |
29 |
26 |
28 |
37 |
35 |
31 |
29 |
33 |
31 |
29 |
31 |
32 |
31 |
27 |
28 |
Macroscopic pathology
Group |
Rat |
Region/organ affected |
Observation |
1M (Control) |
21 22 23 24 25 |
|
No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected |
1F (Control) |
26 27 28 29 30 |
|
No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected |
2M (18.0 mg/l) |
31 32 33 34 35 |
Lungs |
No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Minimal congestion all lobes Small dark subpleural foci left lung |
2F (18.0 mg/l) |
36 37 38 39 40 |
|
No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected |
3M (25.4 mg/l) |
1 2 3 4 5 |
|
No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected |
3F (25.4 mg/l) |
6 7 8 9 10 |
|
No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected |
Group No. |
Total Number of Animals Male/Female |
Nominal Concentration |
Mortality Male – Female |
Weight Gain Male – Female (grams) |
I II III |
5/5 5/5 5/5 |
28.50 mg/l air 42.88 mg/l air 54.97 mg/l air |
1/5 – 1/5 3/5 – 3/5 5/5 – 5/5 |
44 – 46 87 – 35 N.A. – N.A. |
Reactions and Mortality
Group |
Reaction |
Number of Animals Affected |
Time of Onset After Start of Exposure (min) |
Duration |
I |
Ptosis Ptosis Dyspnea Dyspnea Lacrimation Lacrimation Anesthesia Anesthesia Death |
8 2 8 2 8 2 8 2 2 |
10 10 12 12 15 15 220 220 >8<18 hrs. |
>8<18 hrs. Until death >8<18 hrs. Until death >8<18 hrs. Until death 50 min. Until death - |
II |
Ptosis Ptosis Dyspnea Dyspnea Lacrimation Lacrimation Anesthesia Anesthesia Death |
4 6 4 6 4 6 4 6 6 |
5 5 5 5 7 7 180 180 >8<18 hrs. |
>8<18 hrs. Until death >8<18 hrs. Until death >8<18 hrs. Until death 180 min. Until death - |
III |
Ptosis Dyspnea Lacrimation Anesthesia Death Death Death |
10 10 10 10 3 3 4 |
5 5 7 120 150 200 >8<18 hrs. |
Until death Until death Until death Until death - - - |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Value:
- 25 400 mg/m³ air
- Quality of whole database:
- K1
Acute toxicity: via dermal route
Link to relevant study records
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 16.1.96 to 30.1.96
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Version / remarks:
- O.E.C.D. guideline No. 402, 24th February 1987
- Deviations:
- not specified
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- Version / remarks:
- E.C. Directive No. 92/69/E.E.C., B3, 31st July 1992.
- Deviations:
- not specified
- GLP compliance:
- yes
- Test type:
- standard acute method
- Limit test:
- yes
- Specific details on test material used for the study:
- No further details specified in the study report.
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Animals
Species, strain: rat, Sprague-Dawley ICO: OFA-SD (lOPS Caw).
Reason for this choice: rodent species commonly requested by the international regulations for this type of study.
Breeder: Iff a Credo, 69210 L' Arbresle, France.
Number and sex: one group of ten animals (five males and five females).
Age/weight: on the day of treatment, the animals were approximately eight weeks old, and had a mean body weight ± standard deviation of 270 ± 5 g for the males and 221 ± 2 g for the females.
Acclimatization: at least five days before the beginning of the study.
Identification of the animals: the animals were identified individually by earmarks or ear notches.
Environmental conditions
During the acclimatization period and during the main test, the conditions in the animal room were set as follows:
temperature: 21 ± 2°C
relative humidity: 30 to 70%
light/dark cycle: 12 h/12 h
ventilation: about 12 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 regularly.
The animals were housed in polycarbonate cages.
During the acclimatization period each cage (48 cm x 27 cm x 20 cm) contained four to seven animals of the same sex.
During the treatment period, the animals were housed individually (35.5 cm x 23.5 cm x 19.3 cm). Each cage contained dust-free sawdust (SICSA, 94142 Alfortville, France).
Bacteriological analysis of the sawdust and detection of possible contaminants (pesticides, heavy metals) are performed periodically.
Food and water
All the animals had free access to A04 C pelleted diet (U.A.R., 91360 Villemoisson-sur-Orge, France).
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 provided ad libitum.
Bacteriological and chemical analysis of the water and diet and detection of possible contaminants (pesticides, heavy metals and nitrosamines) are performed periodically.
It was verified that no contaminants in the diet or water at levels likely to influence the outcome of the study were present. - Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- As the test substance was anticipated to be non-toxic at 2000 mg/kg, a limit test was performed by application of 2000 mg/kg of the test substance to one group of ten animals (five males and five females).
Preparation of the animals
On the day before treatment, the dorsal area (6 cm x 8 cm) of each animal was clipped using electric clippers. Only animals with healthy intact skin were used for the study.
Administration of the test substance
The test substance was applied in its original form at a dose volume of 2000 mg/kg. It was placed directly on an area of the skin representing approximately 10% (5 cm x 6 cm for the females and 5 cm x 7 cm for the males) of the body surface of the animals. This was calculated according to Meeh's formula. A hydrophilic gauze pad (Semes France, 54183 Heillecourt, France) was then applied to the skin. The test substance and the gauze pad were held in contact with the skin for 24 hours by means of an adhesive hypoallergenic aerated semi-occlusive dressing (Laboratoires de Pansements et d'Hygiene, 21300 Chenove, France) and a restraining bandage (Laboratoires 3M Sante, 92245 Malakoff, France). This dressing prevented ingestion of the test substance by the animals.
No residual test substance was observed at removal of the dressing.
The dose applied to each animal was adjusted according to body weight determined on the day of treatment. - Duration of exposure:
- 24 hours
- Doses:
- single administration
- No. of animals per sex per dose:
- group of ten animals (five males and five females).
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- CLINICAL EXAMINATIONS
The single administration was performed in the morning on day 1; it was followed by a 14-day observation period until day 15.
Clinical signs and mortality
The animals were observed frequently during the hours following administration of the test substance, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day. Type, time of onset and duration of clinical signs and local cutaneous reactions were recorded for each animal individually.
The time of death was recorded individually, in terms of the number of hours or days after dosing.
Body weight
The animals were weighed individually just before administration of the test substance on day 1 and then on days 8 and 15.
The body weight gain of the treated animals was compared to a reference curve of C.I.T. control animals with the same initial body weight.
NECROPSY
On day 15, all animals were killed by CO., inhalation in excess and a macroscopic examination was performed. -
After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed.
In case of macroscopic lesions, organ samples were taken and preserved in 10% buffered formalin.
No microscopic examination was performed. - Statistics:
- Not specified.
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD0
- Effect level:
- >= 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No death occurred during the observation period.
- Clinical signs:
- other: No clinical signs and no cutaneous reactions were observed during the study.
- Gross pathology:
- Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under our experimental conditions, the dermal LD0 of the test substance n-BUTYL BROMIDE was higher than or equal to 2000 mg/kg in rats. No signs of toxicity were observed at this dose.
- Executive summary:
At the request of Elf Atochem S.A., Paris-la-Defense, France, the acute dermal toxicity of the test substance n-BUTYL BROMIDE was evaluated in rats according to O.E.C.D. (No. 402, 24th February 1987) and E.C. (92/69/E.E.C., B3) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.
Methods
The test substance was applied to the skin of one group of ten Sprague-Dawley rats (five males and five females) at a dose of 2000 mg/kg taking into consideration that the density of the test substance was 1.27. The test site was then covered by a semi-occlusive dressing for 24 hours.
Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single administration of the test substance.
All animals were subjected to necropsy.
Results
No cutaneous reactions were observed.
The general behaviour and body weight gain of the animals were not affected by treatment with the test substance.
No death occurred at 2000 mg/kg.
No abnormalities were observed at necropsy.
Conclusion
Under our experimental conditions, the dermal LD0 of the test substance n-BUTYL BROMIDE was higher than or equal to 2000 mg/kg in rats. No signs of toxicity were observed at this dose.
- Endpoint:
- acute toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 16 May 2002- 30 May 2002
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 402 (Acute Dermal Toxicity)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.3 (Acute Toxicity (Dermal))
- Version / remarks:
- Commission Directive
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- standard acute method
- Limit test:
- yes
- Specific details on test material used for the study:
- No further details specified in the study report.
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River UK Ltd.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: their weight were: at least 200 g.
- 5 days of acclimatisation before start of study.
-Free access of water and food (certified rat and mouse diet- code 5LF2)
- Housing: suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hr exposure period and in groups of five, by sex, for the reminder of the study.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 ºC
- Humidity (%): 30-70 %
- Air changes (per hr): at least 15 changes per hr.
- Photoperiod (hrs dark / hrs light): 12 / 12 - Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Details on dermal exposure:
- TEST SITE
Area of exposure:
- % coverage: ca. 10 %
- Type of wrap if used: surgical gauze pad applied to skin with a semi-occluded with a piece of self-adhesive bandage.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material.
- Time after start of exposure: 24-hr
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): N/A
- Constant volume or concentration used: yes
- For solids, paste formed: N/A
VEHICLE
N/A - Duration of exposure:
- 24 hours.
- Doses:
- 2000 mg/kg bw.
- No. of animals per sex per dose:
- 5 per sex per dose
- Control animals:
- no
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Frequent observations of clinical signs were made 1/2, 1, 2, and 4 hours after dosing. Thereafter, observations were made at least once daily for 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross lesions, bodyweight changes, mortality and any other toxicological effects. - Statistics:
- Not specified
- Key result
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- > 2 000 mg/kg bw
- Based on:
- test mat.
- Mortality:
- No mortality during the observation period.
- Clinical signs:
- other: There were no signs of systemic toxicity.
- Gross pathology:
- No abnormalities obderved.
- Other findings:
- N/A
- Interpretation of results:
- practically nontoxic
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- The 24 hours dermal LD50 for 1-bromobutane was found to be > 2000 mg/kg/bw in rats . Therefore, the substance does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with EU labelling regulations Commission Directive 93/21/EEC for classification and
labelling og dangerous substances and preparations. - Executive summary:
In an acute dermal toxicity study, 5 male and 5 female 8-12 weeks Sprague Dawley rats weighing at least 200 g dosed with a limit dose of 2000 mg/kg bw. A gauze pad was applied and then held in place with a semi-occlusive dressing. No dose related changes occurred during the 14 day observation period.
The 24 hours dermal LD50 for 1-bromobutane was found to be > 2000 mg/kg/bw in rats. Therefore, does not meet the critera for classification.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- LD50
- Value:
- 2 000 mg/kg bw
- Quality of whole database:
- K1
Additional information
Acute toxicity oral
08287902 was evaluated for acute oral toxicity in male and female rats. Based upon the findings of this study, the acute oral LD50 in males was calculated to be 2760.6 mg/kg of body weight with 95% confidence limits from 2234.1 to 3411.1 mg/kg of body weight; the oral LD50 in females was calculated to be 3160.8 mg/kg of body weight, with 95% confidence limits from 2411.0 to 4143.8 mg/kg of body weight.
The acute toxicity of the product n-BUTYL BROMIDE was assessed orally in rats in accordance with the O.E.C.D guidelines. (No. 401, 24 February 1987). The study was carried out in accordance with the Good Laboratory Practice regulations.
The product was administered orally to a group of 10 Sprague-Dawley rats (5 males and 5 females) on a liquid diet. Administration was carried out with the product untouched at a dosage of 2000 mg/kg, taking into account the density of the product d = 1.27.
Results
At 2000 mg/kg, a significant reduction in the spontaneous activity and piloerection were observed in the four hours following the treatment. No clinical signs were noted at day 2.
Mortality was zero at a dose of 2000 mg/kg.
The weight development in males was slightly slowed between days 1 and 5. The weight development in females was normal.
The autopsy of the animals that were sacrificed at the end of the study did not show any macroscopic abnormality.
Conclusion
Under the experimental conditions, the LD 0 of the product n-BUTYL BROMIDE administered orally in rats is greater than or equal to 2000 mg/kg.
Acute toxicity inhalation
Albino rats, (Sprague-Dawley). One control group and 2 test groups each of 5 male and 5 female rats.
By inhalation of a test atmosphere containing a vapour generated from the test substance.
4 hours continuous snout only exposure.
14 days post exposure.
Results
Exposure levels and mortality
Group Level (mg/l) Mortality
M F Total
1 Control 0/5 0/5 0/10
2 18.0 mg/l 0/5 0/5 0/10
3 25.4 mg/l 0/5 0/5 0/10
Clinical Signs
Clinical signs seen in rats during exposure to n-butyl bromide were exaggerated respiratory movements and shallow breathing. Irregular respiration was also noted in rats exposed at 25.4 mg/l.
Signs seen in the test rats during a 2 hour post-exposure observation period were staggering, wet fur around the snout and jaws and peripheral vasodilatation. Exaggerated respiratory movements and matted fur were seen in rats exposed at 18.0 mg/l. Lacrimation was observed in 2 female rats. A clear (lacrimation) or red secretion from the eyes was observed in the rats exposed at 25.4 mg/l. On Day 1 of observation, staining around the urogenital region and brown staining on the head were also noted in female rats exposed at 18.0 mg/l.
Additional signs noted in rats exposed at 25.4 mg/l were whole body tremors and lethargy.
Male and female test rats exposed at 18.0 mg/l were normal in appearance and behaviour by Days 2 and 4 of the observation period respectively. Males and females exposed at 25.4 mg/l were normal in appearance and behaviour by Days 1 and 2 of the observation period respectively.
Fur soiled with excreta was evident in all test and control rats during and immediately following exposure. The sign was attributed to the method of restraint.
The rate of bodyweight gain for the test rats was similar to that of the control rats.
Macroscopic pathology
Minimal congestion of all lobes of the lung and a small dark focus on the left lung were seen in 1 male test rat at 18.0 mg/l. There were no other macroscopic abnormalities in any rat.
CONCLUSION
The LCLO(4 hour) for n-butyl bromide as a vapour is in excess of 25.4 mg/l in air.
Acute dermal toxicity
The test substance was applied to the skin of one group of ten Sprague-Dawley rats (five males and five females) at a dose of 2000 mg/kg taking into consideration that the density of the test substance was 1.27. The test site was then covered by a semi-occlusive dressing for 24 hours.
Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single administration of the test substance.
All animals were subjected to necropsy.
Results
No cutaneous reactions were observed.
The general behaviour and body weight gain of the animals were not affected by treatment with the test substance.
No death occurred at 2000 mg/kg.
No abnormalities were observed at necropsy.
Conclusion
Under our experimental conditions, the dermal LD0 of the test substance n-BUTYL BROMIDE was higher than or equal to 2000 mg/kg in rats. No signs of toxicity were observed at this dose.
Justification for classification or non-classification
Acute toxicity oral
The test substance does not meet the criteria under CLP, therefore is Not Classified.
Acute toxicity inhalation
The test substance does not meet the criteria under CLP, therefore is Not Classified.
Acute dermal toxicity
The test substance does not meet the critiera under CLP, therefore is Not Classified.
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