3',6'-bis(diethylamino)spiro[isobenzofuran-1(3H),9'-[9H]xanthene]-3-one

Endpoint summary

Description of key information

Skin Irritation:

The dermal irritation potential of 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) was predicted using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances.

3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) was estimated to be not irritating to the skin of rabbits. On the basis of the estimated result,3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) can be considered to be not irritating to skin and can be classified under the category "Not Classified" as per CLP regulation.

Eye Irritation:

The irritation potential of 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) was evaluated according to the Draize test.

3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) was instilled into the rabbits eyes and effects were observed (duration and number of animals not specified). 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) was observed to be irritating to rabbit eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

For evaluation of dermal irritation potential of3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) , 5 studies for the target chemical along with relevant read across substances are summarized as follows:

Studies 1,2 are estimated data for 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49)

Study 1:

The dermal irritation potential of 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) was predicted using theOECD QSAR toolbox version 3.4 with log kow as the primary descriptor and considering the five closest read across substances.

3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) was estimated to be not irritating to the skin of rabbits. On the basis of the estimated result,3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) can be considered to be not irritating to skin and can be classified under the category "Not Classified" as per CLP regulation.

Study 2:

Skin irritation effects were estimated by four different model i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49).

Based on estimation, No severe skin irritation effects were known when 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) was exposed to rabbit skin.

Both estimated studies (1,2) are in agreement with each other, suggesting that 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) is not irritating to skin.

Studies 3, 4, 5 are the experimental data for the relevant read across substances.

Study 3:

Acute Dermal Irritation/Corrosion of Solvent Blue 4 (6786-83-0) in rabbits, was performed in a OECD GLP laboratory (Sustainability Support Services (Europe) has letter of access). This study was performed as per OECD guideline 404.

 

Three healthy young adult male rabbits were used for conducting acute dermal irritation study. Body weights were recorded on day 0 (prior to application) and at termination.

Rabbits with good intact skin were selected for the study. The hairs of all the rabbits were clipped at contralateral sites, approximately 24 hours prior to treatment. A dose of 0.5 ml of test item (as such) was applied to the skin, over an area of approximately 6 x 6 cm clipped of hair on one side of rabbits. The other untreated side was kept as control area and 0.5 ml of distilled water was applied at this site. At the end of 4 hours, the gauze patch was removed and test item application site was wiped with water without altering the integrity of the epidermis. Initially, the test item was applied to the clipped area of skin of one rabbit. The test site was covered with gauze patch. After 4 hours of exposure in animal no. 1, there was very slight erythema (barely perceptible) and very slight oedema (barely perceptible) observed at 1 hour of observation. At 24 hour very slight erythema (barely perceptible) and no oedema was observed. Hence the confirmatory test was conducted on additional two animal (No. 2 and 3)to confirm the non irritant nature of the test item. At 48 and 72 hours observation no erythema and no oedema was observed in animal no 1. The patch was removed after 4 hours and rabbits were observed for erythema and oedema at 1, 24, 48 and 72 hours after patch removal, evaluated and graded as per Draize Method. In animals no. 2 and 3 at 1 hour observation post patch removal, revealed very slight erythema (barely perceptible) and very slight oedema (barely perceptible). At 24 hour observation post patch removal, revealed very slight erythema (barely perceptible) and no oedema in animal no. 2 whereas very slight erythema (barely perceptible) and very slight oedema (barely perceptible), in animal no. 3. At 48 hour post patch removal very slight erythema (barely perceptible) and no oedema was observed in animal no. 2 and 3. At 72 hour post patch removal, both the animals recovered to normal.The individual mean score at24, 48 and 72 hoursfor animal nos. 1, 2 and 3 were 0.33, 0.67, 0.67 and 0.00, 0.00, 0.33, for erythema and oedema formation, respectively.  

Hence, it was concluded that Solvent Blue 4 (CAS No. - 6786-83-0) was Non-Irritating to the skin of female New Zealand White rabbits under the experimental conditions tested and Classified as "Not Classified" as per CLP Regulation.

Study 4:

The skin irritation study of the similar substance 3520-42-1 (C.I. Acid Red 52) was carried out (THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS (SCCNFP) /0803/ 23 April 2004) in 6 Albino-Himalaya rabbits to determine its irritation potency. The test sample was applied topically at concentration of 500mg to one intact and one additionally scarified flank of each of six rabbits under occlusion for 24 hours exposure period. The scoring of skin reactions was performed immediately, 48 hours and 73 hours after removal of the occlusive patch.

Since the test chemical did not elicit any skin reactions at the application site of any rabbit all scores were 0, therefore C.I. Acid Red 52 (CAS No: -3520-42-1) was considered to be not irritating on rabbits’ skin.

Study 5:

A skin irritation study of the similar substance 302776-68-7 (Diethylamino hydroxybenzoyl hexyl benzoate) was conducted (Opinion on Benzoic acid, 2-[4-(diethylamino)-2-hydroxybenzoyl]-, hexylester-COLIPA n° S83- SCIENTIFIC COMMITTEE ON CONSUMER PRODUCTS (SCCP)- 20 June 2006) in 3 young adult White New Zealand rabbits. The test was performed according to OECD 404 Guidelines.The test material was applied topically to intact skin of rabbits at concentration of 500mg for exposure period of 4 hours under semi-occlusive dressing and the skin reactions were scored after 72 hours. Slight erythema was observed in 2 animals on the day of application. No oedema was observed. The third animal did not show any skin reactions. The cutaneous reactions were reversible in the animals within 48 hours after removal of the patch at latest. The average score (24 to 72 hours) for irritation was calculated to be 0.1 for erythema and 0.0 for oedema. Considering the observed cutaneous reactions as well as the average score for irritation, the test substance Diethylamino hydroxybenzoyl hexyl benzoate (CAS No: -302776-68-7) was not irritating to the skin of New Zealand White rabbits.

The read across studies also supports to the possibility of 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) being not irritating to skin.

Therefore, by applying the weight of evidence approach, 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) can be considered to be not irritating to skin. It can be classified under the category “Not Classified” as per CLP regulation.

Eye Irritation:

For evaluation of ocular irritation potential of3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) , 3 studies for the target chemical along with relevant read across substance are summarized as follows:

Study 1:

The irritation potential of 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) was evaluated according to the Draize test.

3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) was instilled into the rabbits eyes and effects were observed (duration and number of animals not specified).

3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) was observed to be irritating to rabbit eyes.

Studies 2,3 are the experimental data for the relevant read across substance.

Study 2:

The study reports the evaluation of 17 patients who were exposed (Journal of Toxicology: Clinical Toxicology, 25:7, 603-607; 1987) to aerosolized similar substance 81-88-9 (Rhodamine B).

Approximately 10 lbs =(4.53kg) 4530000mg of Rhodamine B powder was spilled onto the floor of a vehicle maintenance shop. A cleanup crew began to sweep up the powder from the floor . This resulted in an aerosol of Rhodamine B dust that dispersed throughout the building contaminating the hair , skin, eyes, and clothing of most of the shop employees.

Sixteen o f the patients (94%) complained of symptoms such as redness, burning sensation..etc. One patient (6%) denied any symptoms despite being exposed to the dust for 15 minutes without a surgical mask. The most frequently reported symptom was burning o f the eyes which occurred in 82% of the patients . Four of the patients (24%) were placed on humidified oxygen because of respiratory symptoms. Five of the patients (29%) underwent irrigation of their eyes secondary to eye burning.

After being discharged from the hospital, follow up was maintained. Ten of the patients (59%) reported that their symptoms had resolved within 4 hours of their exposure to the dust. One patient (6%) reported that his symptoms lasted 12 hours and 2 patients (12%) reported their symptoms lasted 24 hours. Three of the patients (18%) could not remember the duration of their symptoms.

Burning of eyes was observed in 82% of the patients. Based on these effects Rhodamine B may be considered as irritating to eyes.

Study 3:

The irritation potential of the similar substance 81-88-9 (Rhodamine B) was evaluated (OTS0571300, CIBA-GEIGY CORP, last updated 1992) according to the "Appraisal of the Safety of Chemicals in Foods, Drug and Cosmetics" (959) of the US Association of Food and Drug Officials (AFDO).

The test chemical was tested on 6 rabbits (3 males, 3 females) of the Russian breed (obtained from the breeder, weighing 1.5-1.8 kg).Rabbits were housed separately in metal cages and fed with standard diet of Nafag and drinking water ad libitum. Only the rabbits which showed normal ophthtalmic findings were used for the study.

0.1 g of Rhodamine B was instilled into the conjunctival sac of the left eye of the rabbits. After application, the eyelids were held open for few seconds. The right eye served as control. The eyes of 3 animals were rinsed 1 minute after exposure with physiological saline. The reactions were assessed by hand slit lamp after 1,6 hours and 1,2,3,6,8 days according to the scoring pattern mentioned in "Appraisal of the Safety of Chemicals in Foods, Drug and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO). The maximum possible score was 110.

The overall irritation index

0 – 10 – minimal

10 – 25 – slight

26 – 55 – moderate

56 -65 – marked

86 – 110 - extreme

Under the conditions of the study, Rhodamine B caused marked irritation when applied to the rabbit eyes. The mean irritation index for unrinsed eyes was 74.2/110; and 72/110 for rinsed eyes. Rinsing the eyes following instillation was of no effect.

Hence, Rhodamine B can be considered as an eye irritant.

The read across studies also supports to the possibility of 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) being irritating to eyes.

Therefore, by applying the weight of evidence approach, 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) can be considered to be irritating to eyes. It can be classified under the category “Category 2 (irritating to eyes)” as per CLP regulation.

Justification for classification or non-classification

Available information for the target substance indicates that 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) was not likely to cause any irritation to skin , but it causes eye irritation. 3',6'-bis(diethylamino)-3H-spiro[2-benzofuran-1,9'-xanthen]-3-one (Solvent Red 49) can be classified under the category "Not Classified" for Skin Irritation, and “Category 2 (irritating to eyes)" for Eye Irritation as per CLP regulation.