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Administrative data

Description of key information

Two acute studies performed with bismuth oxy-iodide bromide are available, one with exposure via the oral route, one via the dermal route. In both studies, no mortality were seen at the highest dose tested (2000 mg/kg bw), thus for both routes the LD50 was found to exceed 2000 mg/kg bw. Furthermore, an acute inhalation study is available performed with substance analogue with Sicopal-Gelb L-1110 (a test substance with approximately 57% bismuth vanadate oxide and 43% bismuth molybdenum oxide). The LC50 following four hour inhalation exposure to this test substance was concluded to exceed 5.15 mg/L for male and female Wistar rats. This result is read across to bismuth oxy-iodide bromide.

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:
06- 22 July 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
(2001)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
(2002)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
pH: 7.5 (50g/ L)
Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 11 weeks old).
- Weight at study initiation: 179 - 189 g
- Fasting period before study: yes, overnight prior to dosing and until 3-4 hours after administration of the test substance.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.7 – 21.6
- Humidity (%): 44 - 79
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

In-Life phase: 06- 22 July 2010
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
GAVAGE METHOD: plastic feeding tubes.

Frequency: single dosage, on Day 1.

VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw (10 mL/kg).

DOSAGE PREPARATION: The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle.
Doses:
2000 mg/kg bw

No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
No statistical analysis was performed (the method used is not intended to allow the calculation of a precise LD50 value).
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture was observed for one female on Day 1. Orange faeces was observed for all animals on Days 2 and/or 3.
Body weight:
The changes noted in body weight gain were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study with female rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined.
Executive summary:

An acute oral toxicity study was performed according to OECD/EC test guidelines. Two groups of 3 female rats were dosed with 2000 mg/kg bw. No mortality occurred. Hunched posture was observed for one female on day 1. Orange faeces was observed for all animals on days 2 and/or 3. The changes noted in body weight gain were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals. Based on these data, the oral LD50 value in female Wistar rats was established to exceed 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study was performed according to OECD guideline and GLP principles (Klimisch 1).

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
The rationale to read across the data is attached in Section 13.
Reason / purpose:
read-across source
Duration of exposure:
h
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.15 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred.
Clinical signs:
During exposure rats were observed with increased breathing rate. After expsoure, rats were observed with increased and intermittent breathing and scrubby fur. These symptoms disappeared by day six of exposure.
Body weight:
Body weight increase was comparable to historical control data.
Gross pathology:
Gross pathology revealed slightly yellow lungs in the sacrificed animals.
Interpretation of results:
GHS criteria not met
Conclusions:
Based on an acute inhalation study with Sicopal-Gelb L-1 110, the LC50 following four hour inhalation exposure to the test substance was concluded to exceed 5.15 mg/L for male and female Wistar rats. This result is read across to bismuth oxy-iodide bromide.
Executive summary:

An acute inhalation study was performed with Sicopal-Gelb L-1 110 (a test substance with approximately 57% bismuth vanadate oxide and 43% Bismuth molybdenum oxide) equivalent to OECD guidelines. Male and female Wistar rats (10/sex) were exposed for 4 hours to 5.15 mg/L (MMAD of the particles = 2.6µm). During exposure rats were observed with increased breathing rate. During the 14 days observation period, rats were observed with increased and intermittent breathing and scrubby fur. These symptoms disappeared by day six of exposure. No mortality occurred up to 14 days after exposure. No alterations in body weight increase of the exposed rats was found. At necropsy, slightly yellow lungs in the sacrificed animals was observed. Based on these results, the LC50 was concluded to exceed 5.15 mg/L for male and female Wistar rats. This result is read across to bismuth oxy-iodide bromide.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study was performed with substance analogue with Sicopal-Gelb L-1 110 (a test substance with approximately 57% bismuth vanadate oxide and 43% Bismuth molybdenum oxide) according to OECD guideline (Klimisch 2 study).

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:
06 - 20 July 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and EC guidelines and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
pH: 7.5 (50g/ L)
Species:
rat
Strain:
other: Wistar strain, Crl:WI (Han)
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 11 weeks old)
- Weight at study initiation: 319 - 349 g (males); 192 - 238 g (females)
- Housing: Individually housed in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.7 – 21.6
- Humidity (%): 44 - 79
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

In-Life phase: 06 - 20 July 2010
Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch, successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.
Duration of exposure:
24 hours.
Doses:
2000 mg/kg bw

No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.

Dose volume: 10 mL/kg bw.

DOSAGE PREPARATION: The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle.

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
None.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Chromodacryorrhoea was observed for one female on Day 1.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
On the treated skin area, orange staining, scales and/or scabs were present among all animals during the observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined.
Executive summary:

An acute dermal toxicity study with rats was performed according to OECD/EC test guidelines. In the 5 male and 5 female rats treated, no mortality occurred. On the treated skin area, orange staining, scales and/or scabs were present among all animals during the observation period. Chromodacryorrhoea was observed for one female on Day 1. The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals.

Based on these data, the dermal LD50 value in Wistar rats was established to exceed 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study was performed according to OECD guideline and GLP principles (Klimisch 1).

Additional information

An acute oral toxicity study with Bismuth oxy-iodide bromide (bismuth oxy-iodide bromide) was performed according to OECD/EC test guidelines. Two groups of 3 female rats were dosed with 2000 mg/kg bw. No mortality occurred. Hunched posture was observed for one female on day 1. Orange faeces was observed for all animals on days 2 and/or 3. The changes noted in body weight gain were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals. Based on these data, the oral LD50 value of bismuth oxy-iodide bromide in female Wistar rats was established to exceed 2000 mg/kg.

An acute dermal toxicity study with rats was performed according to OECD/EC test guidelines with Bismuth oxy-iodide bromide (bismuth oxy-iodide bromide). In the 5 male and 5 female rats treated, no mortality occurred. On the treated skin area, orange staining, scales and/or scabs were present among all animals during the observation period. Chromodacryorrhoea was observed for one female on day 1. The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals. Based on these data, the dermal LD50 value of bismuth oxy-iodide bromide in Wistar rats was established to exceed 2000 mg/kg bw.An acute inhalation study was performed with Sicopal-Gelb L-1110 (a test substance with approximately 57% bismuth vanadate oxide and 43% Bismuth molybdenum oxide) equivalent to OECD guidelines. Male and female Wistar rats (10/sex) were exposed for 4 hours to 5.15 mg/L (MMAD of the particles = 2.6µm). During exposure rats were observed with increased breathing rate. During the 14 days observation period, rats were observed with increased and intermittent breathing and scrubby fur. These symptoms disappeared by day six of exposure. No mortality occurred up to 14 days after exposure. No alterations in body weight increase of the exposed rats was found. At necropsy, slightly yellow lungs in the sacrificed animals was observed. Based on these results, the LC50 was concluded to exceed 5.15 mg/L for male and female Wistar rats. This result is read across to bismuth oxy-iodide bromide, although the analogue does not represent all ions present in the target substance. Therefore, in addition it was taken into account that systemic toxicity after oral and dermal uptake of bismuth oxy-iodide bromide was absent, and thus systemic effects after acute inhalation exposure are not expected (only limited uptake, approximately 10% via any route, is expected). This inhalation study with substance analogue bismuth vanadate oxide is considered relevant to read across local effects after inhalation, as the analogue is expected to give similar local effects (both have low water solubility and similar particle sizes).

Justification for classification or non-classification

Based on the available data, bismuth oxy-iodide bromide is not classified for acute oral, dermal or inhalation toxicity according to Regulation (EC) No 1272/2008.