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Description of key information

Acute toxicity: oral
Acute oral LD50 value for 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one was estimated to be 1185.2141 mg/kg for rats via oral route.

Acute toxicity: inhalation

The study need not be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.


Acute toxicity: dermal

Acute dermal LD50 value of the test substance 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one to rabbit was estimated to be 4095.37 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 185.214 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from QSAR Toolbox 3.4 (2017)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available
Dose descriptor:
LD50
Value:
4 095.37 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from QSAR Toolbox 3.4 (2017)

Additional information

Acute oral toxicity:

To evaluated the acute oral toxicity of target 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (CAS no 509-34-2) and it’s structurally similar read across rhodamine B (CAS no :81-88-9) (70-80% ) and 4-diethylaminophenyl-4'ethoxy carbonylphenyl azomethine-N-oxide (CAS no: 93749-88-3) (50-60%) studies are summarized below

Study 1 is estimated study for target in rats and studies 2, 3 and 4 is experimental study for read across in mice and rats.

Based on the prediction done using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances, the acute oral toxicity in rats was predicted for 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (CAS: 509-34-2).Acute oral LD50 value for 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one was estimated to be 1185.2141 mg/kg for rats via oral route.

Based on this value it can be concluded that the substance is considered to toxic by oral route and classify as Acute tox 4 category as per the criteria mentioned in CLP regulation.

In a supporting study conducted by Smartet al(1984) for read across, acute oral toxicity was evaluated in rats and mice by using rhodamine B in the concentration of 500 mg/kg and 890 mg/kg orally. No mortality observed in treated rats and 560 % mortality observed in mice. Therefore, LD50 was considered to be > 500 mg/kg for rats and 890 mg/kg bw for mice when treated with rhodamine B orally.

In another supporting study conducted by General Electric Silicones (1992) for read across, acute oral toxicity was evaluated Sprague-Dawley maleand female rats by using 4-diethylaminophenyl-4'ethoxy carbonylphenyl azomethine-N-oxide  (CEM-420 E ) in the concentration of 420. 560 and 740 mg/kg body weight orally in propylene glycol by gavage and observed for 14 days. At 420 mg/kg kg, 2 animals died out of 10, at 560 mg/kg bw, 5 animals died out of 10 and at 740 mg/kg bw, 8 animals died out of 10. All deaths occurred within 24 hours of dosing with exception of one animal which was found dead on day 4. Signs of toxicity were coma, tremors. Convulsions, lethargy, laboured, rapid or slow breathing, pale skin or eyes and bloody nose or eye encrustation particularly observed on days 0 and 1. In general, comatous animals which survived, rapidly recovered within 24 hours. Other observations were piloerection. Absent fecal excretion and half closed eyes. As of day 5, no more abnormalities were observed during the 14-day observation period. In addition, No changes in body weight were observed in treated rats. In dead animals, yellowishly discoloured of upper gastrointestinal and respiratory tract, Dark discoloured liver and petechiae of the stomach were observed. Since the test substance suspension turned yellowish in diluted form it was concluded thatthe discolourations were test substance related. In surviving animals at the end of the study revealed fibrosis of the stomach and black discoloured spleen for some animals of the 560 and 740 mg/kg bw were observed. Survivors of 420 mg/kg bw showed no abnormalities at the end of study. Therefore, LD50 was considered to be 600 mg/kg bw (400 – 700 mg/kg ) for male and 500 mg/kg bw (400 – 600 mg/kg ) for female when Sprague-Dawley male and female rats were treated with 4-diethylaminophenyl-4'ethoxy carbonylphenyl azomethine-N-oxide  (CEM-420 E ) orally by gavage.

Thus, based on weight of evidence for target 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (CAS 509-34-2) and its 70-80% structurally similar read across rhodamine B (CAS 81-88-9) and 50-60% structurally similar 4-diethylaminophenyl-4'ethoxy carbonylphenyl azomethine-N-oxide (CAS 93749-88-3) is likely to be hazardous by oral route of exposure and as per criteria of CLP regulation classify under “Category IV”.

Acute toxicity: inhalation
The study need not be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Acute toxicity: dermal
The predicted data for target substance 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (CAS 509-34-2) and the experimental study for its read across substance Spiro[isobenzofuran-13H,9-[9H]xanthen]-3-one, 6-dibutylamino-3-methyl-2-phenylamino- (CAS 89331-94-2)has been investigated for potential of toxicity following via dermal route and is presented below as a weight of evidence approach for classification of the target substance:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one. The Acute dermal LD50 value of the test substance 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one to rabbit was estimated to be 4095.37 mg/kg bw. This value indicates that the substance is not toxic to rabbit and hence is considered to be not classified for Acute dermal toxicity.

Acute dermal toxicity of the substanceSpiro[isobenzofuran-13H,9-[9H]xanthen]-3-one, 6-dibutylamino-3-methyl-2-phenylamino- was determined in Sprague-Dawley rats following 24 hrs of exposure period. Total 10 rats were used for the test i.e. 5 male and 5 female. One day prior to treatment hair was removed from dorso-lumbar region of each rat with electric clippers exposing an area equivalent to 10% of the total body surface. No shaving or chemical depilation was used. The test substance was applied by spreading it evenly over prepared skin. The treated area (50 mm x 50 mm) was then promptly covered with gauze which was held in place with an impermeable dressing encircled firmly around the trunk. At the end of the 24-hr exposure period, the dressings were carefully removed and the treated area of skin decontaminated by washing in warm (30-40 C) water and blotting dry with absorbent paper. Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, the animals were observed once in the morning and again at the end of the experimental day. Clinical signs were recorded at each observation. No deaths occurred at the 2.0 g/kg dose level. Therefore, acute LD50 value of the substanceSpiro[isobenzofuran-13H,9-[9H]xanthen]-3-one, 6-dibutylamino-3-methyl-2-phenylamino-was considered to be >2000 mg/kg bw when applied dermally to male/female Sprague-Dawley rats following 24 hrs of exposure period. This value indicates that the substance is not classified as Acute dermal toxic.

On the basis of evidence from above studies, it can be presumed that there is no potential of target substance to be harmful to rat/rabbit via dermal route of exposure. Hence, based on the above study summarized with dermal routes and by applying weight of evidence approach it can be concluded that 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one is not classified as acute toxic via dermal route.

Justification for classification or non-classification

Based on weight of evidence for target 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (CAS 509-34-2) and its structurally similar read across substances and by applying weight of evidence approach the substance is likely to be hazardous by oral route of exposure and as per criteria of CLP regulation classify under “Category IV” while not classified as toxic via dermal route.

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