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Sensitisation data (human)

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Endpoint:
sensitisation data (humans)
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
Between 28 Ju;y 1993 and 8 September 1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Good clinical practices (GCP) statement; uses one of a number acceptable methods but criteria for subject selection were not described
Justification for type of information:
REPORTING FORMAT FOR THE CATEGORY APPROACH
1. HYPOTHESIS FOR THE CATEGORY APPROACH
The read across follows Scenario 5 - Qualitatively and quantitatively similar effects are caused by a common compound, which is formed from all category members (as described in the 2017 Read-Across Assessment Framework document).
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
TARGET: Benzenesulfonic acid, di-C10-14-alkyl derivs., sodium salts
SOURCE: Benzene, polypropene derivs., sulfonated, calcium salts
3. CATEGORY APPROACH JUSTIFICATION
Linear and non-linear or branched alkylbenzene sulfonates are anionic surfactants with molecules characterized by a hydrophobic (apolar) and a hydrophilic (polar) group. As a group of chemicals, they are generally mixtures of closely related isomers and homologues. Each molecule contains an aromatic ring sulfonated at the para position and attached to either a linear or a branched alkyl chain at any position except the terminal carbons. The sulfonate group is a common functional group present in each of the category members, and is expected to exhibit similar biological activities with little influence from the length of carbon chain. The cation components of the chemicals (e.g. calcium, magnesium, sodium, or barium) are not expected to contribute significantly to the toxicity.
4. DATA MATRIX
See Read Across document attached to CSR

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guideline
Guideline:
other: no guideline stated
Principles of method if other than guideline:
To determine the irritation and/or sensitization potential of the test article after repeated application under semi-occlusive patch test conditions to the skin of human subjects (non-exclusive panel).
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
Description: Brown viscous liquid

Method

Type of population:
general
Ethical approval:
confirmed and informed consent free of coercion received
Subjects:
Fifty-three (53) subjects, 11 males and 42 females, ranging in age from 20 to 65 years were empaneled for this test.
The subjects were informed of the nature of the test, including possible adverse reactions. Written informed consent was obtained.
Additionally, the subjects were considered dependable and able to read and understand instructions. The subjects did not exhibit any physical or dermatological condition that would have precluded application of the test article.
Clinical history:
The subjects did not exhibit any physical or dermatological condition that would have precluded application of the test article.
Route of administration:
dermal
Details on study design:
Induction Phase
The Induction Phase was initiated on: July 28, 1993.
A sufficient quantity of the test article was applied directly to the skin with a cotton-tip applicator. In addition, a thin layer was also placed onto a 2 cm x 2 cm square of Webril cotton fabric affixed to Scanpor (Allerderm) semi-occlusive surgical tape which was applied to the back of each subject, between the scapulae and waist, adjacent to the spinal mid-line.
The subjects were instructed to remove the patch 24-hours after application. Twenty-four hour rest periods followed the Tuesday and Thursday removals and 48-hour rest periods followed each Saturday removal. The site was scored by a trained examiner just prior to the next patch application. This procedure was repeated every Monday, Wednesday and Friday until nine (9) applications of the test article had been made.
Procedurally, if a subject developed a positive reaction of a 2-level erythema or greater during the Induction phase or, at the discretion of the Study Director, if the skin response warranted a change in site, the patch would be applied to a previously unpatched, adjacent site for the next application. If a 2-level reaction (or greater) occurred at the new site, no further applications would be made. However, any reactive subjects would be subsequently Challenge patch tested.

Challenge Phase
After a rest period of approximately two weeks (no applications of the test article), the Challenge patch was applied to a previously unpatched (virgin) test site. The site was scored 24 and 72-hours after application. All subjects were instructed to report any delayed skin reactivity which might have occurred after the final Challenge patch reading. When warranted, selected test subjects were called back to the Clinic for additional examinations and scoring to determine possible increases or decreases in Challenge patch reactivity.
The final Challenge patch reading was made on: September 8, 1993.

Results and discussion

Results of examinations:
Forty-four (44) subjects satisfactorily completed the test procedure. Nine (9/53) subjects discontinued for either personal reasons unrelated to the conduct of the study, or for their protection, at the discretion of the Principal Investigator. Discontinued panellist data are shown up to the point of discontinuation.
Scattered, transient, barely perceptible (+) to mild (1-level) non-specific or low-grade patch test irritant responses were observed on twelve (12) test panelists (Subject nos. 1, 3 [disc.], 4, 11, 14, 23, 28, 38, 40, 42, 52) during the Induction and/or Challenge phases of the study.
None of these responses was considered to be irritant or allergic in nature.

Moderate (2-level) to marked (3-level) dermal reactivity was observed on twenty-three (23) test panelists (Subject nos. 7, 8, 10, 12, 13, [disc.], 15, 16, 18, 19,21,22,24,26,29, [disc.], 32 [disc.], 34 [disc.], 35, 37 [disc.] 43, 45, 46, 47, 48 [disc.]) during the Induction and/or Challenge phases of the study. The observed reactions appear to exhibit both irritant and, in certain instances, allergic properties. Following discussion with and approval by the Study Sponsor, six panelists were selected for follow-up (rechallenge) patch testing (Subject nos. 8, 10, 18,21,24 and 45) to better define the nature of their reactivity. At the request of the Sponsor, the above subjects will be requested to rechallenge with a related test article (Calcium sulfonate) which had been found to be nonsensitising in pre-clinical studies.

Rechallenge of the six subjects suspected of exhibiting allergic reactions confirmed allergic contact dermatitis in four (4/44 or 9%).

Any other information on results incl. tables

TABLE 1 - individual Scores
Panel No: 93109
Repeated Insult Patch Test - Semi-Occlusive
Test Article: Calcium sulfonate (100 %)
Subj. No. Induction Challenge
Virgin Site
Exposure Number
1 2 3 4 5 6 7 8 9 24 hr 72 hr
1 0 0 0 0 0 0 0 0 0 1 0
2 0 0 0 0 0 0 0 0 0 0 0
3 0 1 0 0 0 0 Discontinued
4 0 0 + 0 0 0 0 0 0 0 0
5 0 0 0 0 0 0 0 0 0 0 0
6 0 0 0 0 0 0 0 0 0 0 0
7 0 0 0 0 0 0 0 0 0 2 0
8 0 0 0 0 0 0 0 0 0 2 2 (96 hrs = 2) N
9 0 0 0 0 0 0 0 0 0 0 0
10 0 0 0 0 0 0 0 0 + + 2( 96 hr = 2) #
11 0 0 0 0 0 + - 0 0 + 0
12 0 2c 2 - - - - - - 1  + ( 96 hr = +)
13 + 0 0 1 2ec 3e - - Discontinued*
14 0 0 0 0 0 0 0 0 0 + 0
15 2c 0 2 - - - - - - 2  + N
16 0 0 0 0 0 2c 2 - - 0 0
17 0 0 0 0 0 0 0 0 0 0 0
18 0 0 0 0 0 0 0 0 0 2 2 (96 hrs = 2)^
19 0 0 0 0 0 2c 1 1 2 0 0
20 0 0 0 0 0 0 0 0 0 0 0
21 0 0 0 1 + 1 2c 2 - 2 2 (96 hrs = 1)
22 0 2c 0 0 0 0 0 0 0 + 0
23 0 0 0 + 0 0 0 0 0 0 0
24 0 0 0 0 0 0 0 0 0 1 2 (96 hrs = 2) N
25 0 0 0 0 0 0 0 0 0 0 0
26 0 0 0 0 0 0 1 2c 1 0 0
27 0 0 0 0 0 0 0 Discontinuet
28 0 0 0 0 0 0 0 0 0 + 0
29 0 0 0 0 0 2c 2 - - + 0
30 0 0 0 0 0 0 0 2sp +sp Discontinued*
31 0 0 0 0 0 0 0 0 0 Discontinued
32 1 2ec 3spv Discontinued*
33 0 0 0 0 0 0 0 0 0 0 0
34 0 0 0 0 0 2c 0 2  - (N) Discontinued*
35 0 0 2c 0 2 - - - - 0 0
36 0 0 0 0 0 0 0 0 0 0 0
37 2ec 0 0 0 2 - - - -  - **  - **
38 0 0 0 0 0 0 0 0 0 + 0
39 0 0 0 0 0 0 0 0 0 0 0
40 0 0 0 0 0 0 0 0 0 + 0
41 0 0 0 0 0 0 0 0 0 0 0
42 0 0 0 0 0 1 + + 0 0 0
43 0 2ec 0 0 2 - - - - + 0
44 0 0 0 0 0 0 0 0 0 0 0
45 0 0 0 0 2c + 2 - - 2 2 (216 hr = 2p)
46 0 0 2c 0 0 - - - - +  + N
47 0 0 0 2c 0 2 - - - 1 0
48 0 0 0 0 0 1 2c 2eps -  - **  - **
49 0 0 0 0 0 0 0 0 0 0 0
50 0 0 0 0 0 0 0 0 0 0 0
51 0 0 0 0 0 0 0 0 0 0 0
52 0 0 0 0 0 0 0 + 0 0 0
53 0 0 0 0 0 0 0 0 0 0 0
Scale: 0 = No evidence of any effect
+ = barely Perceptible {Minimal faint, uniform or spotty erythema)
1 = Mild (Pink, uniform erythema covering most of the contact site)
2 = Moderate (Pink-red erythema uniform in the entire contact site)
3 = Marked (Bright-red erythema with/without petechiae or papules)
4 = Severe (Deep-red erythema with/without vesiculadon or weeping) 
# = (192 hr = 1)
^ = (192 hr = 0)
 - = no patch application
c = change in patch site
e = mild to moderate oedema
p = mild to marked level of papules
s =  reaction spread beyond contact site
v = vesiculation
N = Subject unable to return for follow-up reading
(N) = Marked (3-level) erythema with spreading and papules present on upper back, wrist, chest, abdomen and jaw.
* = Subject discontinued from the panel at the discretion of the Principal Investigator due to the severity of Induction reactivity to the test article
** = Suject not Challenge patched with test article (only) due to severity of Induction reactivity (i.e., also considered discontinued)

Addendum to Final Report:

Purpose:

To better define the clinical relevance and/or reproducibility of Induction and/or Challenge patch reactivity observed on six (6) test subjects (nos. 8, 10, 18, 21, 24 and 45) to Test Article (undiluted) during a Repeated Insult Patch Test (RIPT), ETC Panel No, 93109. At the Sponsor's request, the test article Calcium sulfonate (a mixture of Calcium sulfonate and a dispersant) was used as the rechallenge test material.

Procedure:

Subject nos. 8, 10, 18 and 21 returned to the Clinic on October 4, 1993 and were patched on the back with Calcium sulfonate on previously unpatched (virgin) test sites under semi-occlusive conditions. Additionally, the subjects were requested to openly apply the test article using a cotton-tipped applicator, to the left antecubital fossa three (3) times daily for four (4) consecutive days. The subjects returned to the Clinic 24-hours later, patches were removed and the test sites were scored by a trained examiner using the scoring scale used for the original 9 Repeated Insult Patch Test. Additional readings of the test sites were taken 48, 72 and 96 hours after patch application and the repetitive open test sites were examined and scored daily. Subject nos. 24 and 45 did not return for rechallenge because they were either unable to or they did not wish to participate.

Table 2
Results and Discussion:
Subject No. ETC I.D. Tart Dermal Reactivity
24 hr 48 hr 72 hr 96 hr
8 3948.01 Calcium sulfonate semi-occlusive 0 1ps 1ps 1ps
open 0 0  +ps +ps
10 3948.01 Calcium sulfonate semi-occlusive 0 0 0 0
open 0 0 0 0
IK 3948.01 Calcium sulfonate semi-occlusive 0 1ps 1ps 1ps
open 0 1ps 2ps* 2ps
21 394S.01 Calcium sulfonate semi-occlusive 0 0 0 0
open 0 0 0 0
 * Discontinued applying to arm after nine (9) open applications
p = scattered papules
s = reaction spread beyond contact site

Original RIFT patch test reactivity was not duplicated on either Subject no. 10 or 21 under serni-occlusive or repetitive open patch test condition (i.e., no confirmed induced allergic contact dermatitis).

Subject nos, 8 and 18 both exhibited identical semi-occlusive patch test reactions — mild (1-level) erythema, with scattered papules and spreading of the reaction beyond the actual patch test contact site. In addition, both subjects exhibited erythematous dermal reactivity to the repetitive open exposure test conditions, also accompanied, by scattered and spreading beyond the application sites.

The rechallenge reactivity exhibited by both Subject nos. 8 and 18 is considered indicative of allergic contact dermatitis. Since both of these test subjects exhibited negative Induction patch reactivity during the original RIPT study, the reactions observed at Challenge and confirmed at rechallenge (with Calcium sulfonate) indicated that the first Calcium sulfonate test article induced the original allergic responses and the other Calcium sulfonate was capable of "cross-reacting" or triggering allergic reactivity in at least 2 of the original RIPT reactors.

Applicant's summary and conclusion

Conclusions:
Under the conditions of a repeated insult (semi-occlusive) patch test procedure, Test Article: Calcium sulfonate (Total Base Number = 13) induced both irritant and probable allergic contact dermatitis in human subjects.
Executive summary:

To determine the irritation and/or sensitization potential of the test article after repeated application under semi-occlusive patch test conditions to the skin of human subjects (nonexclusive panel).

Fifty-three (53) subjects, 11 males and 42 females, ranging in age from 20 to 65 years were empaneled for this test.

The 9 Repeated Insult (semi-occlusive) Patch Test (9 RIPT) was conducted.

Under the conditions of a repeated insult (semi-occlusive) patch test procedure, the test article: Calcium sulfonate (Total Base Number = 13) induced both irritant and probable allergic contact dermatitis in human subjects.