9H-Carbazole-9-propanoic acid, 3-[[(4-fluorophenyl)sulfonyl]amino]-1,2,3,4-tetrahydro-, compd. with 1-butanamine (1:1), (3R)-

Endpoint summary

Description of key information

BA-Salz should be considered as harmful after single oral exposure (LD50, rat for Bay u 3405: 1000 - 1250 mg/kg bw).

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 from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-across, GLP study, no guideline mentioned

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann, Borchen, Germany
- Strain: Bor:WISW (SPF Cpb)
- Age at study initiation: adult (187 - 203 g)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

Route of administration:

oral: gavage

Vehicle:

other: 0.5% tylose mucilage

Details on oral exposure:

- Application volume: 20 mL/kg bw

Doses:

Males: 1000, 1250, 1600, 1500, 2500, 4000, and 5000 mg/kg bw
Females: 630, 1000, 1250, 1600, and 2500 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
- Frequency of observations and weighing: at least once daily (clinical signs, mortality) or once weekly (weight gain)
- Necropsy of survivors performed: yes

Statistics:

none

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 000 - 1 250 mg/kg bw

Based on:

test mat.

Mortality:

Doses of 1250 to 4000 mg/kg bw in males and 1000 to 1250 mg/kg bw led to 20 to 80% mortality. All males died in the 5000 mg/kg bw group and all females died in the 1600 and 2500 mg/kg bw groups.

Clinical signs:

other: No clinical signs were seen in males of the 1000 mg/kg bw group. Uncoordinated gait, labored breathing, reduced motility and narrow palpebral fussures were seen in females of the 630 mg/kg bw group and in most of the animals of the higher dose groups. At

Gross pathology:

severe disturbance of microcirculation, especially of liver, spleen and lung may explain the symptoms (liver and spleen nearly black, lung dark red)

Interpretation of results:

harmful

Remarks:

Migrated information

Executive summary:

The acute oral toxicity of Bay u 3405 was moderate with an LD50 value of 1000 - 1250 mg/kg bw in rats. Mortality occurred at doses of 1000 to 1250 mg/kg bw and higher. Clinical signs were observed as uncoordinated gait, labored breathing, reduced motility and narrow palpebral fussures in females of the 630 mg/kg bw group and in most of the animals of the higher dose groups. In animals that died during the observation period a black discoloration of liver and spleen, and a dark-red discoloration of lung was detected as a consequence of severe disturbance of the microcirculation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

The study is GLP compliant and is of high quality

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

BA-Salz is the butyl ammonium salt of Ramatroban (Bay U 3405).

The acute oral toxicity of Bay u 3405 was moderate with an LD50 value of 1000 - 1250 mg/kg bw in rats. Mortality occurred at doses of 1000 to 1250 mg/kg bw and higher. Clinical signs were observed as uncoordinated gait, labored breathing, reduced motility and narrow palpebral fussures in females of the 630 mg/kg bw group and in most of the animals of the higher dose groups. In animals that died during the observation period a black discoloration of liver and spleen, and a dark-red discoloration of lung was detected as a consequence of severe disturbance of the microcirculation.

Justification for selection of acute toxicity – oral endpoint
most relevant study on rats

Justification for classification or non-classification

Based on the study results (oral LD50: 1000 - 1250 mg/kg bw) a classification with R22 (harmful if swallowed) according to Directive 67/548/EEC or with Acute Toxicity Cat. 4 (H302:harmful if swallowed) according to Regulation (EC) No. 1272/2008 (CLP) is required.