Registration Dossier

Administrative data

Description of key information

Studies on acute toxicity of the test item were not performed. Since both substances are Ba-salts with comparable structur and similar solubility, information on acute toxicity were derived from experimental data of a structural analogue. Four studies were performed to evaluate acute oral and inhalative  toxicity of the test substance to the rat (according OECD 401 and 403). The test substance did not induce mortalities, abnormalities or clinical signs when applied oral. Also single administration via the respiratory system did not cause health effects or mortalities. The LD50 for oral toxicity is considered to be > 10.000 mg/kg bw, LC50 is > 5.24 mg/l air.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: read across substance, well documented, OECD guideline and GLP conform
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, Kastengrund, SPF breeding colony
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 181-182 g
- Housing: groups of 5
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: not necessary (breeding at identical conditions)
- fasting period: from about 16 hours before to 3 - 4 hours after treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 + /- 3
- Humidity (%): 55 +/- 20
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 %
- Amount of vehicle (if gavage): 10 ml/kg body weight

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days 4
- Frequency of observations and weighing: Symptoms were recorded twice every day, weighed weekly
- Necropsy of survivors performed: yes
Statistics:
not necessary
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occurred during the whole study.
Clinical signs:
animals showed sunken flanks, stilted gait and squatting posture, all clinical signs of intoxication were reversible one day after application
Body weight:
Development of body weight was not impaired.
Gross pathology:
The animals killed at the end of the observation period showed no macroscopically visible changes.
Other findings:
Additionally red colored feces was observed one day after application.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP and guideline conform study, in life data are not given, read across substance
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes
Limit test:
yes
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., Manston, Kent
- Age at study initiation: young adult
- Weight at study initiation: males 274 - 324g, females 244- 260g
- Fasting period before study: /
- Housing: groups of five
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Humidity (%): 52-67
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: From: To: /
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical exposure chamber with continuous flow
- Exposure chamber volume: 30 l
- Method of holding animals in test chamber: a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber '0' ring
- Source and rate of air: compressed air was supplied by means of a Gast oil free compressor
- Method of conditioning air: passed through a water trap and respiratory quality filters which removed particulate material above 0.005 pm before
- System of generating particulates/aerosols: produced from the test material using a 'Wright Dust Feed' mechanism located at the top of the exposure chamber and driven by a variable speed motor. The dust feed was connected to a metered compressed air supply.
- Method of particle size determination: determined three times during the exposure period using a Cascade Impactor
- Temperature, humidity, pressure in air chamber: measured by an electronic thermometer/humidity meter (Kane-May Ltd., Welwyn Garden City, Hertfordshire, U.K.) located in a vacant port in the animals' breathing zone of the chamber and recorded every thirty minutes throughout the four-hour exposure period.

TEST ATMOSPHERE
- Brief description of analytical method used: The chamber was maintained under negative pressure. Homogeneity of the test atmosphere within the chamber was not specifically determined during this study, but, chambers of the same design have been fully validated and shown to produce evenly distributed atmospheres in the animals' breathing zone with a wide variety of test materials. (Green J.D. et al. Fundamental and Applied Toxicology 4, 768 - 777, 1984)
- Samples taken from breathing zone: no

VEHICLE
- air

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: particle size of the generated atmosphere of the test material inside the exposure chamber was determined three times during the exposure period using a Cascade Impactor. This device consisted of six impactor stages with stainless steel collection substrates (10, 6, 3.5, 1.6, 0.9 and 0.5 pm cut-off points) and a back up glass fibre filter. collection substrates were weighed before and after sampling and the weight of test material, collected at each stage, calculated by difference. From the results obtained the weight distribution of particles in the size range > 10 pm, 10 - 6 pm, 6 - 3.5 pm, 3.5 -1.6 pm, 1.6 - 0.9 pm and 0.9 - <0.5 pm was calculated.
Analytical verification of test atmosphere concentrations:
no
Remarks:
concentration estimated at regular intervals during the exposure period, gravimetric method used, employed glass fibre filters (Gelman type A/E 25 mm)
Duration of exposure:
ca. 4 h
Concentrations:
5.0 mg/litre
No. of animals per sex per dose:
5 per sex and dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations hourly during exposure, immediately on removal from the restraining tubes at the end of the exposure, one hour after termination of the exposure and subsequently once daily for 14 days, bodyweights were recorded on the day of exposure, days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
Using the mortality data obtained, an estimate of the acute inhalation median lethal concentration (LC50) of the test material was made.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.24 mg/L air
Mortality:
no mortalities
Clinical signs:
other: During exposure wet fur, decreased respiratory rate and test material staining of the fur were noted. On removal from the chamber animals additionally showed hunched posture, lethargy and pilo-erection. Laboured respiration and ptosis were common and ther
Body weight:
Expected bodyweight development was noted throughout the study
Gross pathology:
No abnormalities were detected at necropsy
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No deaths occurred in a group of ten rats exposed to a mean achieved concentration of 5.24 mg/litre (range 4.25 - 6.33 mg/litre). It was therefore considered that the acute inhalation median lethal concentration (LC50) of the test material in the Sprague-Dawley strain rat was greater than 5.24 mg/litre.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5.24 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Read across justification

Acute toxicity of the test substance was not examined. The test item shares high structural similarity to an analogue substance, since both are Ba-salts which differ in one additional ethyl-group only. Both substances are poor soluble in water and octanol and dissolve most likely in an acidic environment (e.g. stomach). Therefore, it is acceptable to derive information on acute toxicity from experimental data of the analogue substance.

Procedure and observations

 To evaluate the acute oral toxicity, single doses (6000 and 10.000 mg/kg bw) of the test article were administrated to groups of 10 male and 10 female rats by oral gavage (Ciba 1973). Following dosing, the animals were observed for 7d. There were no deaths as a result of treatment with the test article. Within 2 hours after treatment rats in both dosage groups showed dyspnoea, exophthalmus, curved position and ruffled fur. These symptoms became more accentuated as the dose was increased. The animals had recovered within 3 to 6 days.

Antoher acute oral toxicity study was conducted in 1993 (Hoechst). A single dose of 2000 mg/kg bw was administrated to groups of 5 rats/sex by gavage. The animals were observed for 14 days and twice daily checked for clinical symptoms or mortalities. All animals survided until scheduled necropsy; gross necropsy did not reveal any findings. Symptoms like hunched posture or stilted gait resolved within 1 day. In addition, red stained feces was observed.

To evaluate the acute inhalative toxicity, male and female rats (5/sex/dose) were exposed for 4h to a dust aerosol (range 4.25 - 6.33 mg/l air, nose only) of the test item (BASF 2010). Following dosing, the animals were observed for 14d. Examination of clinical signs and viability were performed daily, weighing on day 1, 7 and 13 after treatment. There were no deaths as a result of treatment with the test article. Clinical signs of toxicity or changes in body weight gain were not observed during the observation period. Gross necropsy was without any findings.

Similar results were determined in another inhalation study (Hoechst 1993). Animals (rats, 5/sex/dose) were exposed to dust (4.13 mg/l air, nose only) for 4h and observed for further 7 days. One male animal died accidentially during exposure; this death is not considered as treatment related. All other animals survided until scheduled necropsy; gross necropsy did not reveal any findings. Symptoms like irregular respiration, uncoordinated gait or trembling resolved within post observation period.

Discussion

Application of the test substance via oral or inhalative route did not induce any signs of toxicity. None of the animals died due to treatment, viability and bodyweight gain were unaffected by the test article. The test item was not tested for acute dermal toxicity. With regard to the physico-chemical properties of the substance (pH, structure, solubility), the very limited skin penetration and the absence of systemic and local effects in acute oral and acute inhalation studies dermal toxicity is not likely.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute toxicity under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

 

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No. 1272/2008, as amended for the second time in Directive (EC 286/2011).