3-(1H-benzimidazol-2-yl)-7-(diethylamino)-2-benzopyrone

Endpoint summary

Description of key information

Estimated LD50 was considered to be 2696.239257813 mg/kg bw  for Sprague-Dawley male and female rats 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from QSAR Toolbox 3.3

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

equivalent or similar to guideline

Guideline:

other: estimated

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

other: Estimation

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: 101 - 133 g
- Fasting period before study: Yes (overnight before dosing, and for approximately 4 hours after dosing).
- Housing: Housed by group in metal cages with wire mesh floors
- Diet (e.g. ad libitum): Ad libitum (except prior to dosing, as described above)
- Acclimation period: 4 or 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.5 ± 1.5°C
- Humidity (%):55 - 67%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light per 24 hours period.

Route of administration:

oral: gavage

Vehicle:

other: 1% Aqueous Methylcellulose

Details on oral exposure:

- Concentration in vehicle: 40% (w/v)
- Amount of vehicle (if gavage): 40 mL/kg bodyweight.

No. of animals per sex per dose:

Preliminary study; two males and two females.
Main study; five males and five females.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days (6 days during the preliminary study).
- Frequency of observations and weighing: Animals were observed shortly after dosing, then at frequent intervals for the remainder of day 1. On subsequent days animals were observed at least twice daily. Individual bodyweights were recorded on days 1, 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight.

Preliminary study:

No deaths were seen during the preliminary study; the main study was subsequently run using the same dose level

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 696.239 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Mortality observed

Mortality:

No data

Clinical signs:

other: No data

Gross pathology:

No data

Other findings:

No data

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(("a" or "b" or "c" or "d" )  and ("e" and "f" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Esters AND Imidazoles by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aliphatic Carbon [-CH2-] AND Aliphatic Carbon [-CH3] AND Aliphatic Nitrogen, one aromatic attach [-N] AND Amino, aliphatic attach [-N<] AND Aromatic Carbon [C] AND Carbonyl, olefinic attach [-C(=O)-] AND Cyclic ester AND Cyclic esters, olefinic type  AND Ester, aromatic attach [-C(=O)O] AND Miscellaneous sulfide (=S) or oxide (=O) AND Nitrogen, two or tree olefinic attach [>N-] AND Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] AND Oxygen, two olefinic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Amine AND Aromatic compound AND Carbonic acid derivative AND Heterocyclic compound AND Lactone AND Tertiary amine AND Tertiary mixed amine by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "d"

Similarity boundary:Target: CCN(CC)c1ccc2C=C(C3Nc4ccccc4N=3)C(=O)Oc2c1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.291

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is <= 9.29

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Estimated LD50 was considered to be 2696.239257813 mg/kg bw when Sprague-Dawley male and female rats were treated with 3-(1H-benzimidazol-2-yl)-7-(diethylamino)-2-benzopyrone.

Executive summary:

Acute oral toxicity was estimated by using QSAR Toolbox 3.3 in Sprague-Dawley male and female rats by using 3-(1H-benzimidazol-2-yl)-7-(diethylamino)-2-benzopyrone. 50 % mortality was obtained at 2696.239257813 mg/kg bw. Therefore, estimated LD50 was considered to be 2696.239257813 mg/kg bw when Sprague-Dawley male and female rats were treated with 3-(1H-benzimidazol-2-yl)-7-(diethylamino)-2-benzopyrone.

The test material does not classify as an acute oral toxicant as per CLP classification.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 696.239 mg/kg bw

Quality of whole database:

Data is Klimish 2 and obtained using SSS QSAR Database, 2016.

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

Acute oral toxicity:

Prediction model based determination and data from read across (RA CAS no 91 -44 -1) have been used to determine the acute oral toxic nature of the test compound 3-(1H-benzimidazol-2-yl)-7-(diethylamino)-2-benzopyrone (CAS no 27425 -55 -4). The summary is as mentioned below:

Based on the prediction done by using QSAR Toolbox 3.3 (2016), acute oral toxicity was estimated in Sprague-Dawley male and female rats by using 3-(1H-benzimidazol-2-yl)-7-(diethylamino)-2-benzopyrone. 50 % mortality was obtained at 2696.239257813 mg/kg bw. Therefore, estimated LD50 was considered to be 2696.239257813 mg/kg bw when Sprague-Dawley male and female rats were treated with 3-(1H-benzimidazol-2-yl)-7-(diethylamino)-2-benzopyrone.

In a study conducted by Gloxhuberet al(1987) and RTECS database (2016) for read across, acute oral toxicity was evaluated in rat by using 7-Diethylamino-4-methylcoumarin orally in the concentrations of 5000 mg/kg bw. 50 % mortality was observed in treated rats. Therefore, LD50 was considered to be 5000 mg/kg bw when rat were treated with 7-Diethylamino-4-methylcoumarin orally.

Thus, based on weight of evidence for target 3-(1H-benzimidazol-2-yl)-7-(diethylamino)-2-benzopyrone (CAS no 27425-55-4) and its read across Coumarin, 7-diethylamino-4-methyl (CAs no 91-44-1) is likely to be non hazardous as per the CLP criteria of classification.

Justification for selection of acute toxicity – oral endpoint
Estimated LD50 was considered to be 2696.239257813 mg/kg bw when Sprague-Dawley male and female rats were treated with 3-(1H-benzimidazol-2-yl)-7-(diethylamino)-2-benzopyrone.

Justification for classification or non-classification

Based on weight of evidence for target 3-(1H-benzimidazol-2-yl)-7-(diethylamino)-2-benzopyrone (CAS no 27425-55-4) and its read across Coumarin, 7-diethylamino-4-methyl (CAs no 91-44-1) is likely to be non hazardous as per the CLP criteria of classification.