Bismuth(3+) neodecanoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

No details on test material were included, and details about gavage volume and environmental conditions of the animals were not stated. Study conducted under GLP but no certificate was included. Further, the age of the animals was not stated.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Reference 2

Reference Type:

other company data

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1981-05-12

GLP compliance:

yes

Remarks:

certificate not included

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Bismuth(3+) neodecanoate

EC Number:

251-964-6

EC Name:

Bismuth(3+) neodecanoate

Cas Number:

34364-26-6

Molecular formula:

C10H19O2.xBi

IUPAC Name:

tris[(3,3,5,5-tetramethylhexanoyl)oxy]bismuthine

Details on test material:

- Density: 1.13- 1.14 mg/ml

Specific details on test material used for the study:

Composition statement Cos Cat 83 is attached

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Wilmington, MA
- Housing: animals were individually housed in wire mesh bottom cages in environment-controlled rooms and provided food and water ad libitum
- Acclimation period: at least 5 days
- Weight at study initiation: males: 255.0-317.2 g; females: 213.6- 252.4 g

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Remarks:

undiluted

Details on oral exposure:

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: dose levels based on results of dose range findinge study

Doses:

1000, 1368, 1871, 2559, 3500, 4787 mg/kg bw

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: trial test: 8 days, main study: 15 days
- Frequency of observations and weighing: animals were observed frequently on the day of dosing and twice daily thereafter, body weights were recorded initially, on days 8 and 15 or at death
- Necropsy of survivors performed: yes, all animals that dies during the study and those sacrificed at termination were subjected to a gross necropsy and abnormalities were noted

Statistics:

Miller-Tainter Determination of LD50

Results and discussion

Preliminary study:

A trial test with 10 animals/dose and a dose range finding study with 2 animals/dose were conducted to determine dose levels for the main study. Male and female Sprague Dawley rats (5 animals/dose) were dosed with 5 g/kg bw of bismuth neodecanoate. All animals died during the first four days of observation. A second study was conducted to define the dose levels for the main study. One male and one female rat were dosed with 500, 889, 1581, 2812 and 5000 mg/kg bw and observed for 8 days. Both animals in the high dose groups (2812 and 5000 mg/kg bw) died after 2 days. All animals in the other treatment groups survived. No details about clinical signs and necropsy are stated.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 030 mg/kg bw

Based on:

test mat.

95% CL:

>= 2 437 - <= 3 624

Mortality:

Main study
Males:
3/5 animals died in the 3500 mg/kg bw group
5/5 animals died in the 4787 mg/kg bw group

Females
2/5 animals died in the 1871 mg/kg bw group
2/5 animals died in the 2559 mg/kg bw group
5/5 animals died in the 3500 mg/kg bw group
3/5 animals died in the 4787 mg/kg bw group

Clinical signs:

Trial Test:
5g/kg bw
Decreased activity observed in 4/5 males and all females
Ataxia observed in all males and females
Salivation observed in 1/5 males
Lacrimation observed in 1/5 females
Death observed in all animals

Main study
1000 mg/kg
Ataxia observed in 4/5 males and all females
Decreased activity observed in 1/5 males and 3/5 females

1368 mg/kg
Decreased activity observed in 2/5 males and 4/5 females
Ataxia observed in 4/5 males and all females
Salivation observed in 1/5 males
Lacrimation observed in 1/5 females
Wet-abdomen observed in 2/5 females

1871 mg/kg
Decreased activity observed in 3/5 males and 3/5 females
Ataxia observed in 4/5 males and 4/5 females
Gaspring observed in 1/5 males
Wet-abdomen observed in 1/5 females
Lacrimation observed in 1/5 males and 3/5 females
Diarrhea observed in 1/5 females
Deaths observed in 2/5 females

2559 mg/kg bw
Decreased activity observed in 4/5 males and 5/5 females
Ataxia observed in 3/5 males and 3/5 females
Wet-abdomen observed in 1/5 females
Lacrimation observed in 1/5 males and 3/5 females
Diarrhea observed in 4/5 males
Deaths observed in 2/5 females

3500 mg/kg bw
Decreased activity observed in 5/5 males and 5/5 females
Ataxia observed in 3/5 males and 2/5 females
Salivation observed in 1/5 females and 1/5 males
Wet-abdomen observed in 2/5 females
Lacrimation observed in 1/5 males and 4/5 females
Diarrhea observed in 1/5 males
Deaths observed in 3/5 males and 5/5 females

4787 mg/kg bw
Decreased activity observed in 5/5 males and 5/5 females
Ataxia observed in 5/5 males and 5/5 females
Salivation observed in 1/5 females and 1/5 males
Wet-abdomen observed in 4/5 females
Lacrimation observed in 4/5 females
Diarrhea observed in 1/5 females
Deaths observed in 5/5 males and 3/5 females

Body weight:

Males
Trial Test
5 g/kg bw
339 ± 16.3 g (day1)

Main study
1000 mg/kg bw
Day 1: 266.8 ± 9.1 g; day 8: 330.8 ± 13.4 g; day 15: 376.0 ± 15.7 g

1368 mg/kg bw
Day 1: 262.0 ± 15.7 g; day 8: 328.4 ± 18.9 g; day 15: 376.8 ± 23.3 g

1871 mg/kg bw
Day 1: 261.4 ± 10.0 g; day 8: 313.4 ± 20.4 g; day 15: 358.8 ± 28.7 g

2559 mg/kg bw
Day 1: 255.4 ± 12.1 g; day 8: 307.2 ± 16.0 g; day 15: 354.8 ± 15.8 g

3500 mg/kg bw
Day 1: 255.0 ± 10.9 g; day 8: 307.5 g; day 15: 363.0 g

4787 mg/kg bw
Day 1: 317.2 ± 14.3 g



Females
Trial Test
5 g/kg bw
236.8 ± 3.6 g (day1)

Main study
1000 mg/kg bw
Day 1: 213.6 ± 15.5 g; day 8: 239.0 ± 16.2 g; day 15: 250.2 ± 20.0 g

1368 mg/kg bw
Day 1: 227.8 ± 8.3 g; day 8: 251.4 ± 16.3 g; day 15: 261.2 ± 15.6 g

1871 mg/kg bw
Day 1: 219.4 ± 16.7 g; day 8: 252.7 ± 32.9 g; day 15: 260.0 ± 38.2 g

2559 mg/kg bw
Day 1: 218.4 ± 8.1 g; day 8: 246.7 ± 12.0 g; day 15: 258.0 ± 11.1 g

3500 mg/kg bw
Day 1: 231.8 ± 8.2 g

4787 mg/kg bw
Day 1: 252.4 ± 19.5 g; day 8: 260.0 g; day 15: 264.0 g

Gross pathology:

Trial Test 5 g/kg bw
No noteworthy findings in males and females, except in one female: bladder contains blood-like liquid

Main study
No noteworthy findings in males and females of the dose groups 1000, 1368, 1871, 2559 and 3500 mg/kg bw
No noteworthy findings in males and females of the 4787 mg/kg group, except in one female: intestine contains blood-like liquid

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for male rats was calculated to be 3294 mg/kg bw; the LD50 for female rats was calculated to be 2612 mg/kg bw. The combined LD50 was calculated to be 3030 mg/kg bw.

Executive summary:

Sprague Dawley rats were exposed to Bismuth neodecanoate in an acute oral toxicity study. A trial test with 10 animals/dose and a dose range finding study with 2 animals/dose were conducted to determine dose levels for the main study. Male and female Sprague Dawley rats (5 animals/dose) were dosed with 5 g/kg bw of bismuth neodecanoate. All animals died during the first four days of observation. A second study was conducted to define the dose levels for the main study. One male and one female rat were dosed with 500, 889, 1581, 2812 and 5000 mg/kg bw and observed for 8 days. Both animals in the high dose groups (2812 and 5000 mg/kg bw) died after 2 days. All animals in the other treatment groups survived. No details about clinical signs and necropsy are stated.

Based on these results the main study was conducted with 1000, 1368, 1871, 2559, 3500 and 4787 mg/kg bw bismuth neodecanoate and 5 males and 5 females per dose group. All animals were observed for 14 days and clinical signs were recorded twice daily. Body weight was recorded at day 1, 8 and 15. At the end of the observation period a necropsy of all animals was conducted.

Ataxia, decreased activity, salivation, lacrimation as well as a wet abdomen, diarrhea and death were observed with increasing dose. 3/5 males in the 3500 mg/kg bw group and 5/5 males in the 4787 mg/kg died prematurely, 2/5 females in the 1871 mg/kg bw, 2/5 females in the 2559 mg/kg bw, 5/5 females in the 3500 mg/kg bw and 3/5 females in the 4787 mg/kg bw group died prematurely.

Based on these findings the LD50 for male rats was calculated to be 3294 mg/kg bw; the LD50 for female rats was calculated to be 2612 mg/kg bw. The combined LD50 was calculated to be 3030 mg/kg bw.