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Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
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 3.4
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Qualifier:
according to
Guideline:
other: as mentioed below
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.4
GLP compliance:
not specified
Type of study:
Buehler test
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
Source: Davidson's Mill Farms, South Brunswick, NJ- Age at study initiation: young adult animals were used - Weight at study initiation: males 305-345 g, females 304-361 g- Housing: group housed in suspended stainless steel caging with mesh floors- Diet (e.g. ad libitum): Pelleted purina Guinea Pig Chow, ad libitum- Water (e.g. ad libitum): Filtered tap water, ad libitum- Acclimation period: 7 days ENVIRONMENTAL CONDITIONS- Temperature (°C): 20 - 22 °C- Photoperiod (hrs dark / hrs light): 12 hrs / 12 hrs
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
25 %
Route:
epicutaneous, occlusive
Vehicle:
propylene glycol
Concentration / amount:
25 %
Positive control substance(s):
not specified
Reading:
1st reading
Group:
test group
Dose level:
25%
Clinical observations:
not sensitizing
Remarks on result:
other: Reading: 1st reading. Group: test group. Dose level: 25%. Clinical observations: not sensitizing.

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

(((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and "h" )  and ("i" and "j" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aryl AND Aryl halide AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Heterocyclic spiro rings AND Isobenzofuran AND Lactone AND Phenol AND Xanthene by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl halide AND Fused carbocyclic aromatic AND Fused saturated heterocycles AND Heterocyclic spiro rings AND Isobenzofuran AND Lactone AND Overlapping groups AND Phenol AND Xanthene by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aromatic compound AND Aryl bromide AND Aryl halide AND Carbonic acid derivative AND Carboxylic acid derivative AND Diarylether AND Ether AND Halogen derivative AND Heterocyclic compound AND Hydroxy compound AND Lactone AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic compound AND Aryl bromide AND Aryl halide AND Carbonic acid derivative AND Carboxylic acid derivative AND Diarylether AND Ether AND Halogen derivative AND Heterocyclic compound AND Hydroxy compound AND Lactone AND Phenol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Phenolphthaleins OR Phenols (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as High (Class III) by Toxic hazard classification by Cramer (extension) ONLY

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.7

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.2

Interpretation of results:
not sensitising
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
The substance D & C Orange no. 5 is estimated to be not sensitizing to skin of guinea pigs.
Executive summary:

The skin sensitization potential for D & C Orange no. 5 is estimated using OECD QSAR toolbox version 3.4 The test substance is estimated to be not sensitizing to skin of Hartley guinea pigs.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitization

Skin sensitization effects by (OECD QSAR toolbox v 3.4) were observed for target CAS 596-03-2(D & C Orange no. 5) in guinea pig. The skin sensitization potential for D & C Orange no. 5 is estimated using OECD QSAR toolbox version 3.4.The test substance is estimated to be not sensitizing to skin of Hartley guinea pigs.

In other study by (Yoshiaki Ikarashi, Toshie Tsuchiya and Akitada Nakamura 1996) with similar substance Erythrosine (CAS: 16423-68-0) was observed in mouse. Sensitive mouse lymph node assay skin sensitization assay was performed on female BALB/c strain mice. They were intradermally injected with 50 µl of test chemical –FCA emulsion into two sites of the abdominal skin at both sides of the ventral line. After 5 days 25 µl of test chemical in vehicle was applied to both sides of each ear for three consecutive days. Control mice were treated by intradermal injection of vehicle-FCA emulsion into the abdomen and then after 5 days they were exposed to vehicle alone on the ears for three consecutive days. The increases in LNC number and3HTdR incorporation relative to controls were derived for each experimental group and expressed as SInand SIP, respectively; SI total as obtained from SInX SIP, which indicates the total lymph node activation induced by the test chemical. A chemical was regarded as positive if it showed a SItotalvalue of 3 or more. The SItotalvalue of erythrosine was found to be 1.55 at 5% DMSO concentration. The test material, Erythrosine, is not sensitizing to the skin of BALB/c strain mice in the sensitive mouse lymph node assay.

According to R. Bernardini, E. Novembre, E. Lombardi, N. Pucci, M. E. Rossi and A. Vierucci 2000, the skin sensitizing effects were reported in humans for RA CAS: 16423-68-0. At the age of 8 years, the patient had taken cefaclor suspension (5 ml) (trade name Panacef, Eli Lilly, Florence, Italy, 250 mg/5 ml) for infectious bronchitis. 6 years later, the child was referred to the allergy clinic to determine the cause of this type of adverse reaction. He was now 14 years old, with allergic rhinitis. Panacef suspension contains excipients such as Erythrosine and strawberry which might cause adverse reactions. A skin prick test (SPT) to Erythrosine (10 mg/ml) was carried out on the volar side of the forearm with a plastic lancet (1-mm tip) made by Laboratorio Lofarma (Milan, Italy). A positive control with 10 mg/ml histamine was included. SPT results were assessed as positive (wheal response ≥2+) according to the recommendations of the European Academy of Allergology and Clinical Immunology. The Skin Prick Test result for Erythrosine B was negative (0+).

Based upon the study by (Scientific Committee on Consumer Safety (SCCS) 2010) with read across substance Erythrosine (CAS: 16423-68-0) was observed in guinea pigs. Skin sensitization test was performed on Guinea pig with 0.1% solution of erythrosine for 3 weeks. Animals received 10 intradermal injections of a 0.1% solution of the colour. The last six injections were given using Freund’s adjuvans. After 14 days, a further intradermal injection was given as challenge. A second epidermal, occlusive challenge was given after additional 10 days. After a further intradermal challenge, positive reactions could be observed in 11 of 19 erythrosine-treated animals. After the epidermal challenge, none of the 19 animals exhibited signs of positive reactions. Therefore, a further intradermal challenge was performed later on after which 15 of 19 animals reacted positive. Epidermal challenge did not cause any effect on skin; hence, erythrosine is not regarded as a skin sensitizer.

Another study reported by Guin JD 2003, with another RA substance 518-47-8 observed in humans. The sensitization potential of D&C yellow 8 was determined by performing patch tests on humans. The dye was applied in Finn Chambers and read first at 2 or (more commonly) 3 days and again at 4–7 days. The reactions of the patients were graded as ‘?+ ‘ , ‘+’ and ‘++’ categories 16 patients were tested with the dye. Only 1 positive reactions was reported by a patient. D&C yellow 8 can be considered as a non- sensitizer in humans.

According to E. Nucera, D. Schiavino, E. Merendino, A. Buonomo, C. Roncallo, E. Pollastrini, C. Lombardo, T. De Pasquale, G. Patriarca 2003, the sensitization effects were observed for RA CAS 518-47-8 (sodium fluorescein) in humans. Patch test was conducted on 1 human male patient to evaluate skin sensitising potency of chemical sodium fluorescein. An allergological evaluation (patch tests) with 20% sodium fluorescein was performed. Saline and histamine solutions were used, respectively, as negative and positive controls. The patch test result was negative. Hence, Non-sensitising effects were known in patch test conducted on human male patient applied with 20% sodium fluorescein.

According to Beleña JM, Núñez M, Rodríguez M 2013, the sensitization effects were observed for RA CAS 518-47-8 (sodium fluorescein) in human. An intradermal skin test for predicting an anaphylactoid reaction to i. v. injection of fluorescein solution was performed in 196 patients. Sodium Fluorescein was applied to the skin of 196 male and female pateints with 0.2 ml of intradermal injections. Only 12 patients of 196 tested showed positive reactions. These results are consistent with previous studies. Hence, the chemical sodium fluorescence was considered to be non-sensitising to the skin of humans.

According to Dimitrios C. Kalogeromitros, Michael P. Makris, Xenophon S. Aggelides, Anagnostis I. Mellios, Fani C.Giannoula, Kyriaki A. Sideri,1 Alexander A. Rouvas and Panagiotis G. Theodossiadis 2011, the sensitization effects were observed for RA CAS 518-47-8 (sodium fluorescein) in human. Patients with adequate indication for fluorescein angiography and normal skin responsiveness were subjected to allergy skin-prick and intradermal tests for fluorescein, followed by SFA (sodium fluorescein angiography).One thousand and thirty-seven patients were enrolled in the study. Possible sensitization to fluorescein was evaluated through skin-prick and intradermal tests. For the skin-prick tests, increasing concentrations of sodium fluorescein were used successively (1⁄100, 1⁄10, 1⁄1 dilutions of the full-strength preparation). Intradermal tests were performed using a 1⁄100 dilution of fluorescein 100 mg⁄ml (sodium fluorescein 10%; Institute of Pharmacological Research and Technology, Pallini, Greece). Histamine chloride (10 mg⁄ml; Stallergenes, Paris, France) and 50% glycerin saline solution were used as positive and negative controls, respectively. Intervals of 20 min were kept between each test. Wheal and flare reactions typical of mast-cell activation were evaluated and documented by the allergologist conducting the tests. Prick tests with a wheal diameter at least 3 mm larger than the one produced by the negative control were considered positive. During the intradermal testing, any occurring wheal and flare reaction with a wheal diameter‡5 mm was also considered positive. This study was performed in accordance with the tenets of the Declaration of Helsinki. None of the reactors produced positive skin tests to fluorescein. Sodium fluorescein is non – sensitizing to humans.

 

 

 

On the basis of available information for the target as well as read across substance and applying weight of evidence approach, the test substanceCAS 596-03-2(D & C Orange no. 5) can be considered as not sensitising to the skin.

Migrated from Short description of key information:

Skin sensitization effects by (OECD QSAR toolbox v 3.4) were observed for target CAS 596-03-2(D & C Orange no. 5) in guinea pig. The skin sensitization potential for D & C Orange no. 5 is estimated using OECD QSAR toolbox version 3.4.The test substance is estimated to be not sensitizing to skin of Hartley guinea pigs.

Justification for selection of skin sensitisation endpoint:

Skin sensitization effects by (OECD QSAR toolbox v 3.4) were observed for target CAS 596-03-2(D & C Orange no. 5) in guinea pig. The skin sensitization potential for D & C Orange no. 5 is estimated using OECD QSAR toolbox version 3.4.The test substance is estimated to be not sensitizing to skin of Hartley guinea pigs.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The test substanceD & C Orange no. 5(CAS 596-03-2) was observed in skin sensitizing studies. From these studies it is concluded that the test substanceD & C Orange no. 5(CAS 596-03-2) can be classified as non skin sensitizer.