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Administrative data

Description of key information

Studies of acute oral, dermal and inhalation toxicity are available for the submission substance.

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:
15 January - 31 January, 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Conducted prior to GLP, and the availabilty of OECD guidelines. No information on the purity of the test sample, limited information on the animals and the conditions of the testing (such as no information on temperature and humidity) but adequate for the purposes of hazard classification
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Sprague Dawley, Madison, WI
- Age at study initiation: No data
- Weight at study initiation: 221 - 261 g (males) 208 - 215 g (females)
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: 26 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: 19/12/1978 To: 31/1/1979
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
VEHICLE
- Concentration in vehicle: No data
- Amount of vehicle (if gavage): No data
- Justification for choice of vehicle: No data
- Lot/batch no. (if required): No data
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED: No data

DOSAGE PREPARATION (if unusual): No data
Doses:
0.34, 0.50, 0.73, 1.07, 2.31, 5.0 g/kg
No. of animals per sex per dose:
8 rats/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Weight was measured at study initiation, day 7 and study termination
Pharmacotoxic signs were observed at hours 1, 2, 5 and daily thereafter.
- Necropsy of survivors performed: yes
Statistics:
No further data
Sex:
male
Dose descriptor:
LD50
Effect level:
850 mg/kg bw
Based on:
test mat.
95% CL:
700 - 1 130
Sex:
female
Dose descriptor:
LD50
Effect level:
530 mg/kg bw
Based on:
test mat.
95% CL:
380 - 660
Mortality:
No animals died in the 0.34 dosage group
1 male and 6 females died in the 0.5 dosage group
3 males and 6 females died in the 0.73 dosage group
6 males and all females died in the 1.07 dosage group
All animals died in the 2.31 dosage group
All animals died in the 5.0 dosage group
Clinical signs:
0.34 dosage group: all animals appeared normal with no clinical signs
0.5 dosage group - 5.0 dosage group: Animals showed a range of symptoms including diarrhea, hypoactivity, ataxia, decrease limb tone, bradypnea, piloerection, absence of grasping reflex, hypothermic to touch, fasciculations, prostration, bradycardia, loss of pain reflex, loss of placing reflex, flaccidity
Body weight:
0.34 dosage group: average male body weight was 304 day 7 and 334 at termination, while average female body weight was 246 day 7 and 253 at termination
0.5 dosage group: average male body weight was 263 day 7 and 297 at termination, while average female body weight was 255 day 7 and 268 at termination
0.73 dosage group: average male body weight was 321 day 7 and 343 at termination, while average female body weight was 244 day 7 and 245 at termination
1.07 dosage group: average male body weight was 313 day 7 and 348 at termination, while all females died prior to reaching the day 7 weighing point
2.31 dosage group: All animals died prior to reaching the day 7 weighing point
5.0 dosage group: All animals died prior to reaching the day 7 weighing point
Gross pathology:
No significant visible lesions were observed
Other findings:
No further data

No further data

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 was found to be 0.85 g/kg in males and 0.53 g/kg in females. Therefore it is classified as Category 4, signal word warning, hazard statement H302: Harmful if swallowed.
Executive summary:

The test substance Busan 11-M1 was administered to 8 rats/sex/dose male and female Sprague-Dawley rats in dosages administered at 0.34, 0.50, 0.73, 1.07, 2.31, 5.0 g/kg. The test animals were observed for 14 days following administration. Under the conditions of this study, the oral LD50 of the test substance was determined to be 0.85 g/kg in males and 0.53 g/kg in females . Based on this result, Busan 11-M1 is classified as Category 4, signal word warning, hazard statement H302: Harmful if swallowed in accordance with Regulation EC No. 1272/2008.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
530 mg/kg bw
Quality of whole database:
The study is sufficient for the purposes of hazard classification.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 July - 5 August, 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Conducted prior to GLP. No information on the purity of the test sample. No clear information on the conditions of exposure but it seems to be whole body. Thes test was carried out at he maximum achievable concentration.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Kingston, NY
- Age at study initiation: males 45 - 53 days, females 71 - 85 days (upon arrival)
- Weight at study initiation: Males mean group weight range 233.6 - 241.0 g, Females mean group 221.4 - 241.6
- Fasting period before study: No data
- Housing: Individually in stainless steel wire-mesh cages
- Diet (e.g. ad libitum): Purina Rodent Laboratory Chow at libitum during nonexposure periods
- Water (e.g. ad libitum): Tap water ad libitum during nonexposure periods
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.67 - 25.56 °C
- Humidity (%): 61 - 84% during study, 42 - 49% during exposure
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: 01/07/1983 To: 05/08/1983
Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglass chamber (control group), glass and stainless steel chambers (exposed groups)
- Exposure chamber volume: 100L
- Method of holding animals in test chamber: in cages
- Source and rate of air: Generation system and accessory chamber, total chamber airflow 16.7 L/min.
- Method of conditioning air: Wright dust feeds (2) generating into the tangential input duct on the turret top
- System of generating particulates/aerosols: Wright dust feeds (2)
- Method of particle size determination: samples obtained using Andersen Mini Sampler Cascade Impactor placed inside the chamber on top of animal cages
- Treatment of exhaust air: No data
- Temperature, humidity, pressure in air chamber: temperature 23.33 - 23.89, humidity 42 - 49% , no data on pressure

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric concentrations were determined as outlined in "Any other information on materials and methods" below
- Samples taken from breathing zone: yes

VEHICLE
No data

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter): Group 2: Mean = 3.4, S.D. = 0.28; Group 3: Mean 2.8, S.D = 0.14
- GSD (Geometric st. dev.): Group 2: Mean = 1.8, S.D. = 0.13; Group 3: Mean 1.9, S.D = 0.05
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric concentrations
Duration of exposure:
4 h
Concentrations:
Nominal: Group 2 = 14.52 mg/L, Group 3 = 21.70 mg/L
Mean gravimetric concnetrations: Group 2 = 2.98 mg/L (S.D. = 0.15), group 3 = 3.54 mg/L (S.D. = 1.394)
No. of animals per sex per dose:
5/sex/dose
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed prior to exposure, at the start of exposure and at 30 minute intervals during exposure. The animals were observed twice daily for 14 days post exposure. Body weights of all animals were recorded immediately prior to exposure and on Days 2, 3, 4, 7 and 14 post exposure.
- Necropsy of survivors performed: yes
- Other examinations performed: Special attention was paid to lungs and respiratory tract during necropsy. The lungs, lever, kidneys and any other organs exhibiting gross pathologic changes were removed and fixed for histopathology.
Statistics:
No data
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 21.7 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Maximum attainable concentration
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 3.54 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Maximum attainable concentration
Mortality:
One Group 2 male was found dead on Day 2 and one Group 3 female was found dead on Day 1 of exposure.
Clinical signs:
other: During exposure, all Group 2 and 3 animals appeared languid from 30 min through 4 hours. Group 2 animals showed slight dyspnea from hour 2 through 4. Group 2 animals showed rhinorrhea from hour 1 through 4. Dust covered the fur of all Group 2 and 3 animal
Body weight:
Mean body weights of the Group 1 (control) females decrease slightly on days 2 and 4 post exposure. Mean body weights of both sexes of test groups decrease markedly on Day 2 and increased steadily thereafter with the exception of a decrease in the Group 2 female mean body weight on day 14.
Gross pathology:
7 Group 1 (control) animals, 7 of the Group 2 animals and 8 of the group 3 animals had no gross pathology observations.
The lungs of one Group 1 (control) animal showed scattered pinpoint red areas. The lobes of the lung of the Group 2 animal found dead were dark red, and those of the Group 3 animal found dead failed to collapse when thoracic cavity was opened. One or both renal pelves were dilated in one Group 1 (control) female, one Group 2 female and one Group 2 male. The uterine horns of two Group 1 (control) females and one group 3 females were distended with clear fluid.
Other findings:
No further data

No further data

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The inhalation LC50 was found to be >3.54mg/L air (analytical) the maximum attainable concentration. Therefore it does not warrent classification of acute inhalation toxicity according to EU legislation
Executive summary:

In a study conducted by Coate (1983), the test substance, Busan 11-M1, was examined for its ability to cause toxicity when administered via whole-body inhalation to male and female Sprague-Dawley rats. The test animals were exposed to nominal concentrations of the test substance 14.52 mg/L and 21.70 mg/L. The test animals were exposed to the test substance via whole-body inhalation for a period of up to 4 hours. They were then observed for 14 days following treatment to determine the effects. Under the conditions of this study, there were no test substance related mortalities observed and no test substance related adverse effects recorded. The LC50 is greater than >3.54mg/L air (analytical) the maximum attainable concentration.  Based on this result, the test substance does not require classification for acute inhalation toxicity according to Regulation EC No. 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
3 540 mg/m³
Quality of whole database:
The study is sufficient for the purposes of hazard classification.

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:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Conducted prior to GLP, and the availability of OECD guidelines. No information on the purity of the test sample. No information on temperature and humidity) Test was conducted on abraded skin. No information on the size of test site. Animals were immobilised while it is not a recommended method.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
Acute dermal toxicity in the rabbit (abraded skin)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: approximately 14 weeks
- Weight at study initiation: 2-3 kg
- Fasting period before study: No data
- Housing: Individually, in screen bottom cages
- Diet (e.g. ad libitum): continuous access to commercial laboratory feed
- Water (e.g. ad libitum): continuous access to water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): air conditioned
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: No data To: No data
Type of coverage:
occlusive
Vehicle:
other: moistened with physiological saline
Details on dermal exposure:
TEST SITE
- Area of exposure: No data
- % coverage: 100%
- Type of wrap if used: rubber sleeve closely fastened for 24 hours
- Test site abraded

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None
- Time after start of exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): No data
- Constant volume or concentration used: No data
- For solids, paste formed: moistened with physiological saline

VEHICLE
- Amount(s) applied (volume or weight with unit): No data
Duration of exposure:
24 hours
Doses:
2 g/kg
No. of animals per sex per dose:
5/sex/dose
Control animals:
not specified
Details on study design:
- Animals were imobilized during exposure.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were made hourly for 5 hours after treatment initiation and twice daily for the remainder of the observation period.
- Necropsy of survivors performed: yes
Statistics:
No further data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: One female died on day 2
Mortality:
One female died on day 2
Clinical signs:
None observed and no signs of skin irritiation.
Body weight:
All animals gained weight during the study.
Gross pathology:
The liver of one male had white areas, possible tapeworm migration scars. No visible lesions were found in any of the other male test animals.
The liver of one female was slightly pale with a nodule inguinal region (1.5 cm diameter) and another had tapeworm cysts in omentum and white area on liver, probably tapeworm migration scars. No other visible lesions were found in any of the other female animals.
Other findings:
No further data

No further data

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 was found to be >2.0 g/kg body weight. Therefore it does not warrant classification of acute dermal toxicity according to current EU legislation.
Executive summary:

In a study conducted by Thompson (1979) the test substance, Busan 11-M1, was tested for its ability to cause acute dermal toxicity when applied to male and female New Zealand White albino rabbits. The exposure site on each test animal was shaved and abraded prior to application of the test material and the test substance moistened with physiological saline was applied. A rubber sleeve wrap was applied to the test site and remained in place for the 24 hours exposure period. During this exposure period, the test animals were immobilised. Following exposure, the test animals were placed in cages for the 14 day observation period. Under the conditions of this study, the dermal LD50 of Busan 11-M1, was determined to be >2.0 g/kg bw, equivalent to 2000 mg/kg bw. Based on this result, the test substance does not warrant classification for acute dermal toxicity in accordance with Regulation EC No. 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The study is sufficient for the purposes of hazard classification.

Additional information

The acute oral LD5 was found to be 530 mg/kg bw; the acute inhalation LC50 was found to be >3540 mg/m3; the acute dermal LD50 was found to be >2000 mg/kg bw. The substance is therefore shown to be of low acute toxicity by all routes investigated.


Justification for selection of acute toxicity – oral endpoint
Only one study is available for this endpoint

Justification for selection of acute toxicity – inhalation endpoint
Only one study is available for this endpoint

Justification for selection of acute toxicity – dermal endpoint
Only one study is available for this endpoint

Justification for classification or non-classification

The oral LD50 was found to be 850 mg/kg bw in males and 530 mg/kg in females. Therefore it is classified as Category 4, signal word warning, hazard statement H302: Harmful if swallowed.

The results of the acute dermal and inhalation toxicity studies performed with the substance do not trigger classification according to the CLP Regulation.