Registration Dossier

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Description of key information

Key value for chemical safety assessment

Skin sensitisation

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Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July and August 1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study is similar to early test guidelines in compliance with GLP but without range findingn data or concurrent assessment for irritation.
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
other: CBA/Ca/Ola/Hsd strain
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac Limited, Blackthorne, Bicester, Oxon, UK
- Housing: suspended stainless steel cages (18.4cm x 52.3cm x 12.7cm) with one solid sheet side and mesh front, floor, rear and remaining side
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of four days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approximately 21±2°C
- Humidity (%): approximately 55±15%
- Air changes (per hr): approximately 25-30 air-changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
dimethylformamide
Concentration:
0.1, 1, 10 or 30% w/v
No. of animals per dose:
4
Details on study design:
RANGE FINDING TESTS:
none reported


MAIN STUDY

- Test method: Approximately 251 of a 0.1, 1, 10 or 30% w/v concentration of the test sample in DMF was applied, using a variable volume micro pipette, to the dorsal surface of each ear, on three consecutive days .
- Criteria used to consider a positive response: one or more concentrations of the test chemical should elicit a 3-fold or greater increase in isotope incorporation relative to the vehicle control group.

Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Positive control results:
The sensitization potential of hexylcinnamaldehyde was assessed using the method described above. A vehicle control group was similarly treated using acetone.
Key result
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: The application of OS 65271G, at concentrations of 0.1, 1, 10 and 30% w/v in DMF, resulted in an increase in isotope incorporation which was greater than or equal to 3-fold at all four concentrations.

concentration

(% w/v)

 

numberoflymphnodesassayed

 

countsperminute

(cpm)

 

cpmperlymphnode(x102)

 

test:controlratio

 

 

0

(vehicleonly)

 

 

0.1

 

 

1

 

 

10 

 

30

 

 

8

 

 

8

 

 

8

 

 

8

 

 

8

 

 

511

 

 

1904

 

 

1539

 

 

5200

 

 

10463

 

 

0.64

 

 

2.38

 

 

1.92

 

 

6.50

 

 

13.08

 

 

N/A

 

 

3.72

 

 

3.00

 

 

10.16

 

 

20.44

Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance is considered sensitising to skin
Executive summary:

The substance (Total Base Number = 13) was assessed using the LLNA study method in mice tested at 0.1, 1, 10 and 30% w/v in DMF. All concentrations achieved greater or equal to to 3 -fold increase in isotope incorporation conpared to solvent control and the substance is considered sensitising at all concenrtrations.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 February 1993 to 15 April 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Data are from a suitable test methoid in compliance with GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Buehler sensitisation
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Avalialble study data is +12 years.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hilltop Lab Animals, Inc., Scottdale, Pennsylvania
- Age at study initiation:
- Housing: individual, suspended stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 67° to 75° F
- Humidity (%): 40% to 70%
- Air changes (per hr): eleven or more changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: February 23, 1993 To: April 15, 1993
:
Route:
epicutaneous, occlusive
Vehicle:
other: U.S.P. Grade light Mineral Oil
Concentration / amount:
25% (v/w)
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
other: U.S.P. Grade light Mineral Oil
Concentration / amount:
25% (v/w)
Adequacy of challenge:
not specified
No. of animals per dose:
Test sample: 5M/ 5F
+ve control: 3M/ 3F
vehicle control: 3M/ 2F
Details on study design:
RANGE FINDING TESTS:
- No. of exposures: 2
- Exposure period: 24 and 48 h
- Test groups: 10 animals
- Control group: 10 animals
- Site: 4 sites per animal, 2 either side of midline
- Concentrations: 75, 50, 35 and 0% (w/w) of the test material in USP Grade mineral oil

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: once weekly for 3 consecutive weeks
- Test groups: 10 animals
- Control group: 10 animals
- Site: 4 sites per animal, 2 either side of midline
- Concentrations: 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 3
- Exposure period: 14 days after induction or 7 days after previous challenge
- Concentration: 25% (v/v) in USP Grade mineral oil
- Evaluation (hr after challenge): 24 and 48 hr

Challenge controls:
+ve Control (DNCB) at a concentration of 0.07% (v/v) in acetone and solvent control dosed according to above regimen.
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene (DNCB)
Positive control results:
Positve responses were observed in at least 80% of +ve controls. No positive responses were observed in the negative controls for the positve control groups.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25%. No with. + reactions: 10.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25%. No with. + reactions: 8.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: other: Rechallenge 1. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 7.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: other: Rechallenge 1. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 9.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: other: Rechallenge 2. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 7.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: other: Rechallenge 2. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 7.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.07%
No. with + reactions:
6
Total no. in group:
6
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.07%. No with. + reactions: 6.0. Total no. in groups: 6.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.07%
No. with + reactions:
6
Total no. in group:
6
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.07%. No with. + reactions: 6.0. Total no. in groups: 6.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
positive control
Dose level:
0.07%
No. with + reactions:
6
Total no. in group:
6
Remarks on result:
other: Reading: other: Rechallenge 1. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.07%. No with. + reactions: 6.0. Total no. in groups: 6.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
positive control
Dose level:
0.07%
No. with + reactions:
6
Total no. in group:
6
Remarks on result:
other: Reading: other: Rechallenge 1. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.07%. No with. + reactions: 6.0. Total no. in groups: 6.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
positive control
Dose level:
0.07%
No. with + reactions:
6
Total no. in group:
6
Remarks on result:
other: Reading: other: rechallenge 2. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.07%. No with. + reactions: 6.0. Total no. in groups: 6.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
positive control
Dose level:
0.07%
No. with + reactions:
6
Total no. in group:
6
Remarks on result:
other: Reading: other: rechallenge 2. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.07%. No with. + reactions: 6.0. Total no. in groups: 6.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
6
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 25%. No with. + reactions: 6.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 25%. No with. + reactions: 4.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: Reading: other: Rechallenge 1. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 2.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
other: Reading: other: Rechallenge 1. . Hours after challenge: 48.0. Group: negative control. Dose level: 10%. No with. + reactions: 3.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: other: Rechallenge 2. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 1.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
other: Reading: other: Rechallenge 2. . Hours after challenge: 48.0. Group: negative control. Dose level: 10%. No with. + reactions: 3.0. Total no. in groups: 10.0.
Interpretation of results:
sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the Beuhler sensitisation test the substance is considered a sensitiser
Executive summary:

The skin sensitization potential of the test substance was evaluated in guinea pigs using the modified Buehler method. The animals were treated topically with a 100% concentration of the test substance once per week during the three week induction phase. Following a two week rest period, the animals were topically challenged with a 25% concentration of the test substance. After approximately one week the animals were rechallenged with a 10% concentration of the test substance. Following the first rechallenge, the animals then were rechallenged with a 10% concentration of the test substance. The number of animals exhibiting positive sensitization responses for the test substance at 25%, 10% rechallenge, and 10% second rechallenge were 10/10, 9/10, and 7/10, respectively, and the mean 24/48 hour Draize scores were 1.4/1.15, 0.8/0.95, and 0.8/0.85, respectively. The mean 24/48 hour Draize scores for the naïve controls at 25%, 10% rechallenge, and 10% second rechallenge were 0.8/0.06, 0.55/0.6, and 0.3/0.65, respectively. Based on these results the test substance was determined to be a sensitizer.The substance was assessed by means of the Buehler sensitisation test as a challenge concentration of 25% in USP mineral oil following 3 inductions at a concentration of 100%, all with occluded dressings. The test substance (Total Base Number = 13) gave positive sensitising results in 3 separate challenge groups. All positive controls demonstrated positive responses and all vehicle controls gave no response.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 06 May 1992 and 02 July 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP, Guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
not specified
Qualifier:
equivalent or similar to guideline
Guideline:
other: EPA-FIFRA
Deviations:
not specified
Qualifier:
equivalent or similar to guideline
Guideline:
other: EPA-TSCA
Deviations:
not specified
Qualifier:
equivalent or similar to guideline
Guideline:
other: Japanese- MAFF
Deviations:
not specified
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
Available data is +12 years.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
Animal housing and care were based on AAALAC standards and to those published in the Guide for the Care and Use of Laboratory Animals, NIH Publication No. 86-23.
Young adult Hartley Derived Albino guinea pigs were obtained from Harlan Sprague Dawley, Inc., Indianapolis, Indiana, for use in this study. The animals were individually housed in suspended stainless steel cages in an environment controlled room with a 12/12 hour light/dark cycle.
Purina Certified Guinea Pig Chow #5026 and purified water were provided to each animal ad libitum.
The guinea pigs were individually identified using cage cards. All animals were acclimated to the laboratory environment for a minimum of five days prior to dosing. Only those animals judged to be healthy were assigned to the study. All range-finding study animals were weighed on the day prior to
chamber application; main study animals were weighed on the day prior to the first induction and each subsequent chamber application at challenge and rechallenges.
During experimental manipulation, the animals were removed from their cages one at a time to avoid a possible identification errors.
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Remarks:
mineral oil
Concentration / amount:
100%
Adequacy of induction:
not specified
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Remarks:
mineral oil
Concentration / amount:
100%
Adequacy of challenge:
not specified
No. of animals per dose:
53 animals were used as follows

Topical range finding: 2 males, 2 females

Test Group: 5 males, 5 females

Challenge control group: 5 males, 5 females

Rechallenge control group: 5 males, 5 females

Second rechallenge control group: 5 males, 5 females

DNCB Test group: 3 males, 3 females

DNCB Control group: 2 males, 1 female
Details on study design:
Range - finding
Irritation screen : A preliminary irritation screen was performed to determine an appropriate concentration of the test article for the standard sensitization study. Four chambers at four different concentrations (100% as received, and 75%, 50% and 25% w/v OS# 65271 E in USP grade mineral oil) were applied to the clipped area of each animal (one chamber for each level of test article). A dose of 0.3 ml of the freshly prepared test substance or test substance mixture was placed on a 25 mm Hilltop chamber. The chambers then were applied to the clipped surface as quickly as possible.
Approximately 24 and 48 hours following chamber application the test sites were graded using the following scale:
No reaction ........................................................... 0
Slight patchy erythema..........................................+/-
Slight, but confluent or moderate patchy erythema..1
Moderate confluent erythema..............................2
Severe erythema with or without edema.............3

Main Study
Induction phase : On the day prior to dose administration (day -1), the hair was removed from the left side of ten test animals and six DNCB test animals with a small animal clipper. On the following day (day 1) a dose of 0.3 ml of the freshly prepared test solution was placed on a 25 mm Hilltop chamber. The chamber was then applied to the clipped surface of each test animal as quickly as possible. Test animals received 100% OS#65271E. The DNCB test animals received 0.5% w/v DNCB in acetone/ethanol. The trunk of each animal was then wrapped with elastic wrap to prevent removal of the
chamber and the animal returned to its cage. NOTE: The DNCB positive control group was utilized as a common control group for two other Modified Buehler Studies running concurrently for the Sponsor.
Approximately six hours after dosing, the elastic wrap and chamber were removed. The sites for the test animals were wiped with gauze moistened in USP grade mineral oil and the test sites for the DNCB animals were wiped with gauze moistened in distilled water to remove test article residue. The animals were returned to their cages. Test sites were graded for dermal irritation at approximately 24 and 48 hours following chamber application using the scale presented previously. The above induction and grading procedures were repeated for both the test and DNCB test animals on study day 8 and study day 15 so that a total of three consecutive induction exposures were made to the animals. The animals remained untreated after the last induction until the challenge phase of this study.
Challenge phase: On the day prior to challenge dose administration, the hair was clipped from the right side of the test and challenge control animals, and the DNCB test and control animals with a small animal clipper. On day 29, a dose of 0.3 ml of the freshly prepared test substance mixture was placed on a 25 mm Hilltop chamber. The chamber was then applied to the clipped surface of each animal as quickly as possible. Test and challenge control animals received 50% w/v OS# 65271E in USP grade mineral oil. DNCB test and DNCB control animals received two 25 mm Hilltop chambers containing 0.1% w/v or 0.2% w/v DNCB in acetone/ethanol. The trunk of each animal was then wrapped with elastic wrap in order to prevent removal of the chamber and the animal was returned to its cage.
Approximately six hours after dosing, the elastic wrap and chamber were removed. The OS# 65271E test sites were wiped with gauze moistened in USP grade mineral oil and the DNCB test sites were wiped with gauze moistened in distilled water to remove test article residue. The animals were then returned to their cages.
Approximately 20 hours after chamber removal, the exposure sites were depilated using Neet Cream. The depilatory was placed on the test sites and surrounding areas and left on for no more than fifteen minutes. The depilatory was thoroughly removed with a stream of warm, running water. The animals were dried with a towel and returned to their cages.
Approximately 24 and 48 hours after chamber removal, the test sites were graded using the scale presented previously.
Rechallenge phase: The rechallenge was performed on study day 37. On the day prior to rechallenge dose administration, the hair was removed from the right side of the ten test and ten naive rechallenge control animals with a small animal clipper. On the following day, a dose of 0.3 ml of the freshly prepared test solution was placed on a 25 mm Hilltop chamber. The chamber was then applied to the clipped surface of each test and challenge control animal as quickly as possible. Test and rechallenge control animals received 25% w/v OS# 65271E in USP grade mineral oil. The trunk of each animal was then wrapped with elastic wrap in order to prevent removal of the chamber and the animal returned to its cage.
Approximately six hours after dosing, the elastic wrap and chamber were removed. The OS# 65271E test sites were wiped with gauze moistened in USP grade mineral oil and the animals were returned to their individual cages. Procedures for depilation and grading were the same as those described for challenge.
Second rechallenge: The rechallenge was performed on study day 43. On the day prior to rechallenge dose administration, the hair was removed from the right side of the ten test and ten naive rechallenge control animals with a small animal clipper. On the following day, a dose of 0.3 ml of the freshly prepared test substance mixture was placed on a 25 mm Hilltop chamber. The chamber was then applied to the clipped surface as quickly as possible. Test and rechallenge control animals received 10% w/v OS# 65271E in USP grade mineral oil. The trunk of each animal was then wrapped with elastic wrap in order to prevent removal of the chamber and the animal was returned to its cage.
Approximately six hours after dosing, the elastic wrap and chamber were removed. The OS# 65271E test sites were wiped with gauze moistened in USP grade mineral oil and the animals were returned to their individual cages. Procedures for depilation and grading were the same as those described for challenge.
Termination: All animals were removed from study and euthanized using sodium pentobarbital after completion of their final scoring interval or after termination of the study.
Positive control substance(s):
yes
Remarks:
The DNCB positive control group was utilized as a common control group for two other Modified Buehler Studies running concurrently for the Sponsor
Positive control substance(s):
other: 1 -chloro-2,4-dinitrobenzene (DNCB)
Positive control results:
A dinitrochlorobenzene (DNCB) positive control group consisting of six DNCB test and three DNCB control guinea pigs was included in this study. The DNCB test animals received 0.5% w/v DNCB in an acetone/ethanol vehicle for induction and 0.1% w/v and 0.2% w/v DNCB in acetone/ethanol for challenge.
Challenge with DNCB produced substantially stronger dermal responses in animals previously induced with the positive control demonstrating that the test system could detect potential contact sensitizers.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50% OS#65271E in Mineral oil
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% OS#65271E in Mineral oil. No with. + reactions: 9.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50% OS#65271E in Mineral oil
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50% OS#65271E in Mineral oil. No with. + reactions: 9.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
other: Challenge control
Dose level:
50% OS#65271E in Mineral oil
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: Challenge control. Dose level: 50% OS#65271E in Mineral oil. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
other: challenge control
Dose level:
50% OS#65271E in Mineral oil
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: challenge control. Dose level: 50% OS#65271E in Mineral oil. No with. + reactions: 1.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
other: DNCB test
Dose level:
0.1% DNCB in acteone/ethanol
No. with + reactions:
6
Total no. in group:
6
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: DNCB test. Dose level: 0.1% DNCB in acteone/ethanol. No with. + reactions: 6.0. Total no. in groups: 6.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
other: DNCB test
Dose level:
0.1% DNCB in acteone/ethanol
No. with + reactions:
6
Total no. in group:
6
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: DNCB test. Dose level: 0.1% DNCB in acteone/ethanol. No with. + reactions: 6.0. Total no. in groups: 6.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
other: DNCB control
Dose level:
0.1% DNCB in acteone/ethanol
No. with + reactions:
1
Total no. in group:
3
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: DNCB control. Dose level: 0.1% DNCB in acteone/ethanol. No with. + reactions: 1.0. Total no. in groups: 3.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
other: DNCB control
Dose level:
0.1% DNCB in acteone/ethanol
No. with + reactions:
0
Total no. in group:
3
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: DNCB control. Dose level: 0.1% DNCB in acteone/ethanol. No with. + reactions: 0.0. Total no. in groups: 3.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
other: DNCB test
Dose level:
0.2% DNCB in acteone/ethanol
No. with + reactions:
6
Total no. in group:
6
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: DNCB test. Dose level: 0.2% DNCB in acteone/ethanol. No with. + reactions: 6.0. Total no. in groups: 6.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
other: DNCB test
Dose level:
0.2% DNCB in acteone/ethanol
No. with + reactions:
6
Total no. in group:
6
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: DNCB test. Dose level: 0.2% DNCB in acteone/ethanol. No with. + reactions: 6.0. Total no. in groups: 6.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
other: DNCB control
Dose level:
0.2% DNCB in acteone/ethanol
No. with + reactions:
2
Total no. in group:
3
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: DNCB control. Dose level: 0.2% DNCB in acteone/ethanol. No with. + reactions: 2.0. Total no. in groups: 3.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
other: DNCB control
Dose level:
0.2% DNCB in acteone/ethanol
No. with + reactions:
1
Total no. in group:
3
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: DNCB control. Dose level: 0.2% DNCB in acteone/ethanol. No with. + reactions: 1.0. Total no. in groups: 3.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
25% OS#65271E in Mineral oil
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 25% OS#65271E in Mineral oil. No with. + reactions: 10.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
25% OS#65271E in Mineral oil
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 25% OS#65271E in Mineral oil. No with. + reactions: 10.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
other: rechallenge control
Dose level:
25% OS#65271E in Mineral oil
No. with + reactions:
3
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: other: rechallenge control. Dose level: 25% OS#65271E in Mineral oil. No with. + reactions: 3.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
other: rechallenge control
Dose level:
25% OS#65271E in Mineral oil
No. with + reactions:
2
Total no. in group:
10
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: other: rechallenge control. Dose level: 25% OS#65271E in Mineral oil. No with. + reactions: 2.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
10% OS#65271E in Mineral oil
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: other: Second rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 10% OS#65271E in Mineral oil. No with. + reactions: 9.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
10% OS#65271E in Mineral oil
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
other: Reading: other: Second rechallenge. . Hours after challenge: 48.0. Group: test group. Dose level: 10% OS#65271E in Mineral oil. No with. + reactions: 9.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
24
Group:
other: rechallenge control
Dose level:
10% OS#65271E in Mineral oil
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: other: Second rechallenge. . Hours after challenge: 24.0. Group: other: rechallenge control. Dose level: 10% OS#65271E in Mineral oil. No with. + reactions: 1.0. Total no. in groups: 10.0.
Key result
Reading:
rechallenge
Hours after challenge:
48
Group:
other: rechallenge control
Dose level:
10% OS#65271E in Mineral oil
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: Reading: other: Second rechallenge. . Hours after challenge: 48.0. Group: other: rechallenge control. Dose level: 10% OS#65271E in Mineral oil. No with. + reactions: 1.0. Total no. in groups: 10.0.
OS#65271E: Following challenge with 50% w/v OS# 65271E in USP grade mineral oil, dermal scores of 1 to 3 with the majority of the test sites exhibiting slight to severe edema were observed in 9/10 test animals at 24 and 48 hours. Dermal scores in 10/10 challenge control animals were 0 to +/- at 24 hours. Group mean dermal scores were noted to be higher in the test animals as compared to the challenge control animals. Following rechallenge with 25% w/v OS# 65271E in USP grade mineral oil, a stronger dermal response was again noted in the test group as compared to the rechallenge control group. Dermal scores of 1 to 3 with the majority of the test sites exhibiting slight to moderate edema were noted in 10/10 test animals at 24 and 48 hours. Dermal reactions in 10/10 rechallenge control animals were scores of +/- to 1 at 24 and 48 hours. Group mean dermal scores were also higher in the test animals as compared to the rechallenge control animals. Following the second rechallenge with 10% w/v OS# 65271E in USP grade mineral oil, dermal scores of 1 to 2 with the majority of the test sites exhibiting slight to moderate edema were again noted in 9/10 test animals at 24 and 48 hours. Dermal scores of 0 to +/- were noted in the 9/10 control animals at 24 and 48 hours. The number of animals exhibiting positive sensitization responses for the test substance at 50%, 25%, and 10% were 9/10, 10/10, and 9/10, respectively, and the mean 24/48 hour Draize scores were 1.9/2.1, 1.6/2.0, and 1.5/1.5, respectively. The mean 24/48 hour Draize scores for the naïve controls at 50%, 25%, and 10% were 0.2/0.2, 0.7/0.6, and 0.5/0.5, respectively.  Positive Control: Challenge with DNCB produced substantially stronger dermal responses in animals previously induced with the positive control demonstrating that the test system could detect potential contact sensitizers.
Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Under the Conditions of this test, OS#65271E is considered a contact sensitizer in guinea pigs.
Executive summary:
The potential of OS# 65271E (Total Base Number = 13) to elicit a delayed contact hypersensitivity response was evaluated in guinea pigs. Five male and five female guinea pigs were treated topically with 100% OS# 65271E, once per week, for three consecutive weeks. Following a two week rest period, the ten test animals and ten previously untreated (naive) challenge control guinea pigs were topically challenged with 50% w/v OS# 65271E in USP grade mineral oil. Challenge responses in the test animals were compared to those of the challenge controls. Approximately one week after challenge, the ten test animals and ten previously untreated (naive) rechallenge control guinea pigs were topically rechallenged with 25% w/v OS# 65271E in USP grade mineral oil. Rechallenge responses in the test animals were compared to those of the rechallenge controls. Approximately one week after rechallenge, a second rechallenge was then performed with 10% w/v OS# 65271 E in USP grade mineral oil using the ten test animals and ten new naive second rechallenge control animals in order to confirm previous challenge results. Second rechallenge responses in the test animals were compared to those of the second rechallenge controls.A dinitrochlorobenzene (DNCB) positive control group consisting of six DNCB test and three DNCB control guinea pigs was included in this study. The DNCB test animals received 0.5% w/v DNCB in an acetone/ethanol vehicle for induction and 0.1% w/v and 0.2% w/v DNCB in acetone/ethanol for challenge.Delayed contact sensitization was observed following challenge with the OS# 65271 E. Dermal scores of 1 to 3 with the majority of the test sites exhibiting slight to severe edema were observed in 9/10 test animals at 24 and 48 hours. Dermal scores in 10/10 challenge control animals were 0 to+/-at 24 hours. The 24 and 48 hour group mean dermal scores were higher in the test animals than the controls. Following both rechallenges, the test animals exhibited greater dermal responses to the test article than the naive rechallenge and second rechallenge controls. The number of animals exhibiting positive sensitization responses for the test substance at 50%, 25%, and 10% were 9/10, 10/10, and 9/10, respectively, and the mean 24/48 hour Draize scores were 1.9/2.1, 1.6/2.0, and 1.5/1.5, respectively. The mean 24/48 hour Draize scores for the naïve controls at 50%, 25%, and 10% were 0.2/0.2, 0.7/0.6, and 0.5/0.5, respectively.  Challenge with DNCB produced substantially stronger dermal responses in animals previously induced with the positive control demonstrating that the test system could detect potential contact sensitizers.Based on the results of this study, OS# 65271E is considered a contact sensitizer in guinea pigs.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Based on the available animal that all show positive results and the human data that demonstrate positive results at and above 10%w/w concentration it is considered that the low TBN substance is classified as a skin sensitiser. These results also show that the high TBN substance is not a skin sensitizer. 

Classification and Labeling is proposed and explained for Benzenesulfonic acid, mono-C14-24-alkyl derivs., calcium salts using data from skin sensitization studies on natural and synthetic calcium sulfonates. For Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) classification and labeling, EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 applies. 

 

In the lubricant additive industry, calcium sulfonate is a common name for natural and synthetic long-chain alkylbenzenesulfonic acids, calcium salts. Calcium sulfonates, which have surfactant properties, are used as detergents in a broad variety of lubricant applications. In some cases, excess calcium carbonate is added to calcium sulfonates to add acid buffering capacity (commonly known as “overbasing”). Calcium sulfonates with a large excess of calcium carbonate are referred to as high overbased or high total base number (TBN) calcium sulfonates, whereas calcium sulfonates with small amounts of added calcium carbonate are called low overbased or low TBN calcium sulfonates. Animal studies show that calcium sulfonates with a TBN greater than 300 are not skin sensitizers while the results in animals at a TBN of 300 exhibit a mixed skin sensitization response. However, human repeat insult patch tests clearly show that high TBN overbased calcium sulfonates (TBN ≥ 300) are not sensitizers and that low TBN calcium sulfonates do not cause sensitization in a substantial number of persons at concentrations of 10% or lower within the definition of sensitization under EU Regulation (EC) No. 1272/2008.

 

Sensitization:

 

Low TBN Calcium Sulfonates

In a key study the dermal sensitisation of this low TBN substance (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and benzenesulfonic acid, 4-octadecyl, calcium salts; EC 939-141-6; TBN = 13) was evaluated in the local lymph node assay (LLNA) (Lees, 1996). Groups of male mice (4/group) were dose with approximately 25 µL of 0.1, 1, 10 or 30% concentrations of the test material in DMF on the dorsal surface of each ear for three consecutive days. The animals were then injected with 3H-methylthymidine, and the auricular lymph nodes where then collected and prepared for scintillation counting. A three-fold or greater increase in isotope incorporation was observed at all test concentrations. Although investigators have reported that LLNA over predicts the sensitisation potential of surfactants (Basketter & Kimber, 2011; Ball et al., 2011), the positive response in this study is supportive of the sensitisation response for low TBN calcium sulfonates noted in other sensitisation studies.

In another key study the dermal sensitisation of this low TBN substance (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and benzenesulfonic acid, 4-octadecyl, calcium salts; EC 939-141-6; TBN = 13) was evaluated in guinea pigs (Bonnette, 1993b;Table28). The animals were treated topically with a 100% concentration of the test substance once per week during the three week induction phase. Following a two week rest period, the animals were topically challenged with a 50% concentration of the test substance. After approximately one week the animals were rechallenged with a 25% concentration of the test substance. Following the first rechallenge, the animals then were rechallenged with a 10% concentration of the test substance. The number of animals exhibiting positive sensitisation responses for the test substance at 50%, 25%, and 10% were 9/10, 10/10, and 9/10, respectively, and the mean 24/48 hour Draize scores were 1.9/2.1, 1.6/2.0, and 1.5/1.5, respectively. The mean 24/48 hour Draize scores for the naïve controls at 50%, 25%, and 10% were 0.2/0.2, 0.7/0.6, and 0.5/0.5, respectively. Based on these results the test substance was determined to be a sensitiser.

Table28. Dermal Sensitisation Study (Modified Buehler Design) in Guinea Pigs with a 100% Low TBN Calcium Sulfonate (Benzenesulfonic Acid, 4-(Mono-C15-36 Branched Alkyl Derivs., C24 Rich) and Benzenesulfonic Aacid, 4-Octadecyl, Calcium Salts; EC 939-141-6; TBN = 13) Induction: Challenge Results (Bonnette, 1993b)

Group

Concentration

Mean Draize Score

# Positive

Conclusion

24 hours

48 hours

Test

50%

1.9

2.1

9/10

Sensitiser

Control

50%

0.2

0.2

 

 

 

 

 

 

 

 

Test

25%

1.6

2.0

10/10

Sensitiser

Control

25%

0.7

0.6

 

 

 

 

 

 

 

 

Test

10%

1.5

1.5

9/10

Sensitiser

Control

10%

0.5

0.5

 

 

Control = Topical application of test article to naïve animals to account for primary irritation reactions

In another key study the dermal sensitisation of this low TBN substance (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and benzenesulfonic acid, 4-octadecyl, calcium salts; EC 939-141-6; TBN = 13) was evaluated in guinea pigs (Shults, 1993). The animals were treated topically with a 100% concentration of the test substance once per week during the three week induction phase. Following a two week rest period, the animals were topically challenged with a 25% concentration of the test substance. After approximately one week the animals were rechallenged with a 10% concentration of the test substance. Following the first rechallenge, the animals then were rechallenged with a 10% concentration of the test substance. The number of animals exhibiting positive sensitisation responses for the test substance at 25%, 10% rechallenge, and 10% second rechallenge were 10/10, 9/10, and 7/10, respectively, and the mean 24/48 hour Draize scores were 1.4/1.15, 0.8/0.95, and 0.8/0.85, respectively. The mean 24/48 hour Draize scores for the naïve controls at 25%, 10% rechallenge, and 10% second rechallenge were 0.8/0.06, 0.55/0.6, and 0.3/0.65, respectively. Based on these results the test substance was determined to be a sensitiser.

In another key study the dermal sensitisation of this low TBN substance (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and benzenesulfonic acid, 4-octadecyl, calcium salts; EC 939-141-6; TBN = 13) was evaluated in a human repeat insult patch test (Shanahan & Erianne, 1993a;Table 29).A panel of 53 subjects was identified for this test. In the induction phase the undiluted (100% concentration) test substance was administered directly to the skin and covered with a semi-occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 44 subjects that completed the induction phase was topically challenged with the undiluted (100% concentration) test substance. Positive responses (scores ≥ 1) were observed in 9/44 and 6/44 at the 24 and 72 hour readings, respectively. Rechallenge of the six subjects suspective of exhibiting allergic reactions confirmed allergic contact dermatitis in four (4/44 or 9%). Based on these results the test substance was determined to be a sensitiser.

In another key study the dermal sensitisation of this low TBN substance (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and benzenesulfonic acid, 4-octadecyl, calcium salts; EC 939-141-6; TBN = 13) was evaluated in a human repeat insult patch test (Shanahan & Erianne, 1994c;Table 29). A panel of 55 subjects was identified for this test. In the induction phase a 20% concentration of the test substance in mineral oil was administered directly to the skin and covered with a semi-occlusive patch threetimes per week for a total of nine applications. Following a two week rest period, each of the 45 subjects thatcompleted the induction phase was topically challenged with a 20% concentration of the test substance in mineral oil. Positive responses (scores ≥ 1) were observed in 16/45 and 16/45 at the 24 and 72 hour readings (or 48 or 96 hour make up readings), respectively. Approximately 31 % (14/45) of the test population exhibited skin reactivity patterns that were suggestive or indicative of low to moderate grade, induced allergic contact dermatitis. Based on these results the test substance was determined to be a sensitiser.

Table29. Human Repeat Insult Patch Tests (HRIPT) with a Low TBN Calcium Sulfonate (Benzenesulfonic Acid, 4-(Mono-C15-36 Branched Alkyl Derivs., C24 Rich) and Benzenesulfonic Aacid, 4-Octadecyl, Calcium Salts; EC 939-141-6; TBN = 13): Challenge Results

Test Phase

Concentration

# Positive Responses

Conclusion

Study

24 hours

72 hours

Induction

100%

 

 

Sensitiser

Shanahan & Erianne, 1993a

Challenge

100%

9/44

6/44

 

 

 

 

 

 

Induction

20%

 

 

Sensitiser

Shanahan & Erianne, 1994c

Challenge

20%

16/45*

16/45*

*48 or 96 hour make-up readings were required for some subjects

Low TBN Specific Concentration Limit (SCL)

The weight-of-evidence of all the animal and human studies demonstrates that low TBN calcium sulfonates are skin sensitisers. However, well-conducted, reliable, controlled HRIPT studies show that these substances do not cause sensitisation in a substantial number of subjects at 10% and lower.

In another key study the dermal sensitisation of an analogue of this low TBN substance (Sulfonic acids, petroleum, calcium salts; EC 263-093-9; TBN = 30) was evaluated in a human repeat insult patch test (Alworth, Schwartz, & Erianne, 1995c;Table30). Five panels consisting of a total of 166 subjects were identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 142 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 8/142 (5.6%) of the subjects exhibited sensitisation responses. Based on these results the test substance was determined to cause a low incidence of sensitisation characterized by mild to moderate reactions in all but one subject.

In another key study the dermal sensitisation of an analogue of this low TBN substance (Sulfonic acids, petroleum, calcium salts; EC 263-093-9; TBN = 30) was evaluated in a human repeat insult patch test (Eisenberg,1994c;Table30). A panel of 220 subjects was identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of ten applications. Following a two week rest period, each of the 205 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 12/205 (5.8%) of the subjects exhibited sensitisation responses following the 10% challenge. Based on these results the test substance was determined to cause a low incidence of sensitisation characterized by mild to moderate reactions at 10%.

In another key study the dermal sensitisation of an analogue of this Low TBN substance (Benzene, polypropene derivs., sulfonated, calcium salts; EC 616-278-7; TBN = 13) was evaluated in a human repeat insult patch test (Alworth, Schwartz & Erianne, 1995a;Table30). Five panels consisting of a total of 159 subjects were identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 154 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 4/154 (2.6%) of the subjects exhibited sensitisation responses. Based on these results the test substance was determined to cause a low incidence of sensitisation characterized by mild to moderate reactions.

In another key study the dermal sensitisation of an analogue of this low TBN substance (Benzene, polypropene derivs., sulfonated, calcium salts; EC 616-278-7; TBN = 13) was evaluated in a human repeat insult patch test (Eisenberg,1994a;Table30). A panel of 223 subjects was identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of ten applications. Following a two week rest period, each of the 199 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 12/199 (6.0%) of the subjects exhibited sensitisation responses following the 10% challenge. Based on these results the test substance was determined to cause a low incidence of sensitisation characterized by mild to moderate reactions at 10%.

In another key study the dermal sensitisation of this low TBN substance (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and benzenesulfonic acid, 4-octadecyl, calcium salts; EC 939-141-6; TBN = 13) was evaluated in a human repeat insult patch test (Alworth, Schwartz & Erianne, 1995b;Table30). Four panels consisting of a total of 157 subjects were identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 140 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 4/140 (2.9%) of the subjects exhibited sensitisation responses. Based on these results the test substance was determined to cause a low incidence of sensitisation characterized by mild to moderate reactions in all but one subject.

In another key study, the dermal sensitisation of this low TBN substance (Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and benzenesulfonic acid, 4-octadecyl, calcium salts; EC 939-141-6; TBN = 13) was evaluated in a human repeat insult patch test (Eisenberg,1994b;Table30). A panel of 227 subjects was identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of ten applications. Following a two week rest period, each of the 199 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 12/199 (6.0%) of the subjects exhibited sensitisation responses following the 10% challenge. Based on these results the test substance was determined to cause a low incidence of sensitisation characterized by mild to moderate reactions at 10%

In another key study the dermal sensitisation of an analogue of this low TBN substance (Benzene, polypropene derivs., sulfonated, calcium salts; EC 616-278-7; TBN = 85), was evaluated in a human repeat insult patch test (Shanahan & Erianne, 1994a;Table30). A panel of 53 subjects was identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with a semi-occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 48 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 3/48 (6.3%) of the subjects exhibited sensitisation responses. Based on these results the test substance was determined to cause a low incidence of sensitisation characterized by mild to moderate reactions in all but one subject.

In another key study the dermal sensitisation of an analogue of this low TBN substance (Sulfonic acids, petroleum, calcium salts; EC 263-093-9; TBN = 82), was evaluated in a human repeat insult patch test (Shanahan & Erianne, 1994e;Table30). A panel of 60 subjects was identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with a semi-occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 56 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 0/56 (0.0%) of the subjects exhibited sensitisation responses. Based on these results the test substance was determined to not cause a sensitisation response.

In another key study the dermal sensitisation of an analogue of this low TBN substance (Sulfonic acids, petroleum, calcium salts; EC 263-093-9; TBN = 100) was evaluated in a human repeat insult patch test (Shanahan & Erianne, 1994f;Table30). A panel of 52 subjects was identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with a semi-occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 51 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 0/51 (0.0%) of the subjects exhibited sensitisation responses. Based on these results the test substance was determined to not cause a sensitisation response.

In another key study the dermal sensitisation of an analogue of this low TBN substance substance (Benzene, polypropene derivs., sulfonated, calcium salts; EC 616-278-7; TBN = 13) was evaluated in a human repeat insult patch test (DiFiglia, Shanahan & Erianne, 1993d). A panel of 53 subjects was identified for this test. In the induction phase a 1% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 48 subjects that completed the induction phase was topically challenged with a 1% concentration of the test substance in mineral oil. A total of 0/48 (0%) of the subjects exhibited sensitisation responses following the 1% challenge. Based on these results the test substance was determined not to induce irritation or sensitisation at 1%.

Table30. Calcium Sulfonate Human Repeat Insult Patch Tests (HRIPT) with a 10% Induction Phase Concentration

Substance

Challenge

%

Challenge Response

Sensitisation Response (%)

Conclusion

Study

EC 263-093-9 (TBN = 30)

10%

7/142 with mild to moderate erythema/oedema including mild to moderate papular reactions; 1/142 with moderate erythema at 24 hours and severe erythema at 72 hours

8/142 (5.6)

Sensitiser: low incidence with mild to moderate reactions in all but one of 8 subjects

Alworth, Schwartz & Erianne, 1995c

EC 263-093-9 (TBN = 30)

10%

3/205 with mild erythema at original & virgin sites; 1/205 with moderate erythema at both areas; 7/205 with mild erythema original site; 1/205 with mild erythema virgin site

12/205 (5.8)

Sensitiser: low incidence with mild to moderate reactions

Eisenberg., 1994c

 

EC 616-278-7 (TBN = 13)

10%

2/154 with mild to moderate erythema with moderate papular reactions; 2/154 with mild to marked erythema and with moderate oedema and moderate papular reactions in the induction phase that were considered sensitised and, therefore were not challenged

4/154 (2.6)

Sensitiser: low incidence with mild to moderate reactions

Alworth, Schwartz & Erianne, 1995a

EC 616-278-7 (TBN = 13)

10%

6/199 with mild erythema at original sites; 5/199 with moderate erythema original site; 1/199 with moderate erythema virgin site

12/199 (6.0)

Sensitiser: low incidence with mild to moderate reactions

Eisenberg,, 1994a

 

EC 939-141-6 (TBN = 13)

10%

3/140 with mild to moderate erythema with mild to moderate oedema and/or mild to severe papular reactions in some; 1/140 with moderate erythema with mild to severe papular reaction including an adverse reaction report of reaction spreading to back/neck at 96 hrs with erythema deminishing at 192 hours but papular reaction spreading to the eyes

4/140 (2.9)

Sensitiser: low incidence with mild to moderate reactions in all but one of 4 subjects

Alworth, Schwartz & Erianne, 1995b

EC 939-141-6 (TBN = 13)

10%

1/210 with mild erythema original and virgin site; 6/210 with BP to mild erythema original site; 5/210 moderate erythema original site; 1/210 with marked erythema original site; 1/210 with mild erythema virgin site; 1/210 with marked erythema original site

15/210

(7.1)

Sensitiser: low incidence with mild to moderate reactions

Eisenberg, 1994b

 

EC 616-278-7 (TBN = 85)

10%

2/48 with mild to moderate erythema and 1/48 with moderate oedema and papular that spread beyond contact site during induction were not challenged

3/48

(6.3)

Sensitiser: low incidence with mild to moderate reactions

Shanahan, & Erianne, 1994a

EC 263-093-9 (TBN = 82)

10%

56/56 no reaction

0/56

(0)

Not a sensitiser

Shanahan, & Erianne, 1994e

EC 263-093-9 (TBN = 100)

10%

51/51 no reaction

0/51

(0)

Not a sensitiser

Shanahan & Erianne, 1994f

EC 263-093-9 = Sulfonic acids, petroleum, calcium salts

EC 616-278-7 = Benzene, polypropene derivs., sulfonated, calcium salts

EC 939-141-6 = Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and benzenesulfonic acid, 4-octadecyl, calcium salts

In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of low TBN calcium sulfonates is required for sensitisation with a specific concentration limit of 10%.

High TBN Calcium Sulfonates

In another key study the dermal sensitisation ofa high TBN analogue of this substance (Sulfonic acids, petroleum, calcium salts; EC 263-093-9; TBN = 375) was evaluated in guinea pigs (Kiplinger, 1992a;Table 31). The animals were treated topically with a 100% concentration of the test substance once per week during the three week induction phase. Following a two week rest period, the animals were topically challenged with a 25% concentration of the test substance. After approximately one week the animals were rechallenged with a 25% concentration of the test substance. The number of animals exhibiting positive sensitisation responses for the test substance at 25% challenge and 25% rechallenge were 0/12 and 0/12, respectively, and the mean 24/48 hour Draize scores were 0.4/0.4 and 0.4/0.4, respectively. The mean 24/48 hour Draize scores for the naïve controls at 25% challenge and 25% rechallenge were 0.1/0.1 and 0.4/0.3, respectively. Based on these results the test substance was determined not to be a sensitiser.

Table31. Dermal Sensitisation Study (Modified Buehler Design) in Guinea Pigs with a 100% High TBN Calcium Sulfonate (Sulfonic acids, petroleum, calcium salts; EC 263-093-9; TBN = 375) Induction: Challenge Results (Kiplinger, 1992a)

Group

Concentration

Mean Draize Score

# Positive

Conclusion

24 hours

48 hours

Test

25%

0.4

0.4

0/12

Not a sensitiser

Control

25%

0.1

0.1

 

 

 

 

 

 

 

 

Test

25%

0.4

0.4

0/12

Not a sensitiser

Control

25%

0.4

0.3

 

 

In another key study the dermal sensitisation ofa high TBN analogue of this substance (Sulfonic acids, petroleum, calcium salts; EC 263-093-9; TBN = 400) was evaluated in guinea pigs (Reagan, 1988). The animals were treated topically with a 100% concentration of the test substance once per week during the three week induction phase. Following a two week rest period, the animals were topically challenged with a 60% concentration of the test substance. After approximately one week the animals were rechallenged with a 60% concentration of the test substance. The number of animals exhibiting positive sensitisation responses for the test substance at 60% challenge and 60% rechallenge were 4/10 and 0/10, respectively, and the mean 26/48 hour Draize score severity indices were 0.7/0.5 and 0.0/0.2, respectively. The mean 26/48 hour Draize score severity indices for the naïve controls at 60% challenge and 60% rechallenge were 0.5/0.3 and 0.0/0.0, respectively. Based on these results the test substance was determined not to be a sensitiser.

In another key study the dermal sensitisation ofa high TBN analogue of this substance (Sulfonic acids, petroleum, calcium salts; EC 263-093-9; TBN = 375) was evaluated in guinea pigs (Kiplinger, 1992b). The animals were treated topically with a 30% concentration of the test substance once per week during the three week induction phase. Following a two week rest period, the animals were topically challenged with a 25% concentration of the test substance. After approximately one week the animals were rechallenged with a 25% concentration of the test substance. The number of animals exhibiting positive sensitisation responses for the test substance at 25% challenge and 25% rechallenge was 0/12 and 0/11, respectively, and the mean 24/48 hour Draize scores were 0.4/0.3 and 0.4/0.3, respectively. The mean 24/48 hour Draize scores for the naïve controls at 25% challenge and 25% rechallenge were 0.5/0.4 and 0.2/0.2, respectively. Based on these results the test substance was determined not to be a sensitiser.

In another key study the dermal sensitisation ofa high TBN analogue of this substance (Sulfonic acids, petroleum, calcium salts; EC 263-093-9; TBN = 300) was evaluated in guinea pigs (Blaszcak, 1992). The animals were treated topically with a 100% concentration of the test substance once per week during the three week induction phase. Following a two week rest period, the animals were topically challenged with a 25% concentration of the test substance. After approximately one week the animals were rechallenged with a 25% concentration of the test substance. The number of animals exhibiting positive sensitisation responses for the test substance at 25% challenge and 25% rechallenge were 1/20 and 7/20, respectively, and the mean 24/48 hour Draize scores were 0.0/0.2 and 0.4/0.4, respectively. In the naïve controls 0/10 and 4/10 animals, respectively, exhibited positive irritation responses; the mean 24/48 hour Draize scores for the naïve controls at 25% challenge and 25% rechallenge were 0.0/0.0 and 0.5/0.4, respectively. Dermal responses to the corn oil vehicle alone were similar to the treated animals and naïve control. Based on these results the test substance was determined not to be a sensitiser.

In another key study the dermal sensitisation ofa high TBN analogue of this substance (Sulfonic acids, petroleum, calcium salts; EC 263-093-9; TBN = 300) was evaluated in guinea pigs (Kiplinger, 1992c). The animals were treated topically with a 100% concentration of the test substance once per week during the three week induction phase. Following a two week rest period, the animals were topically challenged with a 25% concentration of the test substance. After approximately one week the animals were rechallenged with a 25% concentration of the test substance. The number of animals exhibiting positive sensitisation responses for the test substance at 25% challenge and 25% rechallenge were 4/12 and 5/12, respectively, and the mean 24/48 hour Draize scores were 0.7/0.6 and 0.6/0.5, respectively. The mean 24/48 hour Draize scores for the naïve controls at 25% challenge and 25% rechallenge were 0.3/0.4 and 0.3/0.5, respectively. Based on these results the test substance was determined to be a sensitiser.

In another key study the dermal sensitisation of a high TBN analogue of this substance (Benzene, polypropene derivs., sulfonated, calcium salts; EC 616-278-7; TBN = 300) was evaluated in guinea pigs (Bonnette, 1993a). The animals were treated topically with a 100% concentration of the test substance once per week during the three week induction phase. Following a two week rest period, the animals were topically challenged with a 50% concentration of the test substance. After approximately one week the animals were rechallenged with a 25% concentration of the test substance. Following the first rechallenge, the animals then were rechallenged with a 10% concentration of the test substance. The number of animals exhibiting positive sensitisation responses for the test substance at 50%, 25%, and 10% were 8/10, 10/10, and 7/10, respectively, and the mean 24/48 hour Draize scores were 1.1/2.1, 1.6/1.7, and 1.2/1.2, respectively. The mean 24/48 hour Draize scores for the naïve controls at 50%, 25%, and 10% were 0.5/0.5, 0.7/0.8, and 0.3/0.5, respectively. Based on these results the test substance was determined to be a sensitiser.

In another key study the dermal sensitisation of a high TBN analogue of this substance (Sulfonic acids, petroleum, calcium salts; EC 263-093-9; TBN = 300) was evaluated in a human repeat insult patch test (Shanahan & Erianne, 1994d;Table32). A panel of 213 subjects was identified for this test. In the induction phase a 100% concentration of the test substance was administered directly to the skin and covered with an occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 200 subjects that completed the induction phase was topically challenged with a 100% concentration of the test substance. A total of 0/200 (0%) of the subjects exhibited sensitisation responses following the 100% challenge. Based on these results the test substance was determined not to induce irritation or sensitisation at 100%.

In another key study the dermal sensitisation of a high TBN analogue of this substance (Sulfonic acids, petroleum, calcium salts; EC 263-093-9; TBN = 300) was evaluated in a human repeat insult patch test (DiFiglia, Shanahan & Erianne, 1993c,Table32). A panel of 53 subjects was identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 51 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 0/51 (0%) of the subjects exhibited sensitisation responses following the 10% challenge. Based on these results the test substance was determined not to induce irritation or sensitisation at 10%.

In another key study the dermal sensitisation of an analogue ofa high TBN analogue of this substance (Sulfonic acids, petroleum, calcium salts; EC 263-093-9; TBN = 300) was evaluated in a human repeat insult patch test (DiFiglia, Shanahan & Erianne, 1993d,Table32). A panel of 53 subjects was identified for this test. In the induction phase a 1% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 50 subjects that completed the induction phase was topically challenged with a 1% concentration of the test substance in mineral oil. A total of 0/50 (0%) of the subjects exhibited sensitisation responses following the 1% challenge. Based on these results the test substance was determined not to induce irritation or sensitisation at 1%.

Table32. Human Repeat Insult Patch Tests (HRIPT) with a High TBN Sulfonic acids, petroleum, calcium salts; EC 263-093-9; TBN = 300): Challenge Results

Test Phase

Concentration

#Positive Responses

Conclusion

Study

24 hours

72 hours

Induction

100%

 

 

Not a sensitiser

Shanahan & Erianne, 1994d

Challenge

100%

0/200

0/200

 

 

 

 

 

 

Induction

10%

 

 

Not a sensitiser

DiFiglia, Shanahan & Erianne, 1993c

Challenge

10%

0/51

0/51

 

 

 

 

 

 

Induction

1%

 

 

Not a sensitiser

DiFiglia, Shanahan & Erianne, 1993d

Challenge

1%

0/50

0/50

In another key study the dermal sensitisation of a high TBN analogue of this substance (Benzene, polypropene derivs., sulfonated, calcium salts; EC 616-278-7; TBN = 300) was evaluated in a human repeat insult patch test (Shanahan & Erianne, 1993b;Table33). Five panels consisting of a total of 241 subjects were identified for this test. In the induction phase a 100% concentration of the test substance was administered directly to the skin and covered with an occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 222 subjects that completed the induction phase was topically challenged with a 100% concentration of the test substance in mineral oil. The test substance did not induce any clinically significant irritation contact dermatitis. Only 1/222 (0.0%) of the subjects exhibited a reaction which was of questionable substance-related clinical significance. Based on these results the test substance was determined to not cause sensitisation.

In another key study the dermal sensitisation of a high TBN analogue of this substance (Benzene, polypropene derivs., sulfonated, calcium salts; EC 616-278-7; TBN = 300) was evaluated in a human repeat insult patch test (Wachs, 1993;Table33). A panel of 57 subjects was identified for this test. In the induction phase a 10% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of ten applications. Following a two week rest period, each of the 51 subjects that completed the induction phase was topically challenged with a 10% concentration of the test substance in mineral oil. A total of 0/51 (0.0%) of the subjects exhibited sensitisation responses. Based on these results the test substance was determined to not cause a sensitisation response.

In another key study the dermal sensitisation of a high TBN analogue of this substance (Benzene, polypropene derivs., sulfonated, calcium salts; EC 616-278-7; TBN = 300) was evaluated in a human repeat insult patch test (DiFiglia, Shanahan & Erianne, 1993a;Table33). A panel of 53 subjects was identified for this test. In the induction phase a 1% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 49 subjects that completed the induction phase was topically challenged with a 1% concentration of the test substance in mineral oil. A total of 0/49 (0.0%) of the subjects exhibited sensitisation responses. Based on these results the test substance was determined to not cause a sensitisation response.

In another key study the dermal sensitisation of a high TBN analogue of this substance (Benzene, polypropene derivs., sulfonated, calcium salts; EC 616-278-7; TBN = 300) was evaluated in a human repeat insult patch test (Shanahan & Erianne, 1994b;Table33). A panel of 53 subjects was identified for this test. In the induction phase a 1% concentration of the test substance in mineral oil was administered directly to the skin and covered with an occlusive patch three times per week for a total of nine applications. Following a two week rest period, each of the 49 subjects that completed the induction phase was topically challenged with a 1% concentration of the test substance in mineral oil. A total of 0/49 (0.0%) of the subjects exhibited sensitisation responses. Based on these results the test substance was determined to not cause a sensitisation response.

Table33. Human Repeat Insult Patch Tests (HRIPT) with a High TBN Calcium Sulfonate (Benzene, Polypropene Derivs., Sulfonated, Calcium Salts; EC 616-278-7; TBN = 300): Challenge Results

Test Phase

Concentration

#Positive Responses

Conclusion

Study

24 hours

72 hours

Induction

100%

 

 

Not a sensitiser

Shanahan & Erianne, 1993b

Challenge

100%

1/222

1/222

 

 

 

 

 

 

Induction

10%

 

 

Not a sensitiser

Wachs, 1993

Challenge

10%

0/51

0/511

 

 

 

 

 

 

Induction

1%

 

 

Not a sensitiser

DiFiglia, Shanahan & Erianne, 1993a

Challenge

1%

0/49

0/49

 

 

 

 

 

 

Induction

1%

 

 

Not a sensitiser

Shanahan & Erianne, 1994b

Challenge

1%

0/49

0/49

148 hours

In accordance with EU CLP Regulation (EC) No. 1272/2008, classification is not required for high TBN calcium sulfonates (TBN ≥ 300).

Conclusion

The weight-of-evidence indicates that low TBN calcium sulfonates (TBN < 300) are skin sensitisers with a specific concentration limit (SCL) of 10% and that high TBN calcium sulfonates (TBN ≥ 300) are not skin sensitisers. Studies in guinea pigs and human volunteers show that low TBN Benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and benzenesulfonic acid, 4-octadecyl, calcium salts; (EC 939-141-6; TBN = 13) are skin sensitisers. Numerous well-conducted, reliable, controlled human (HRIPT) studies with benzene, polypropene derivs., sulfonated, calcium salts (EC 616-278-7; TBN values ranging from 13 to 85), sulfonic acids, petroleum, calcium salts (EC 263-093-9; TBN = 30 to 100), and benzenesulfonic acid, 4-(mono-C15-36 branched alkyl derivs., C24 rich) and benzenesulfonic acid, 4-octadecyl, calcium salts (EC 939-141-6; TBN = 13) show that low TBN calcium sulfonates do not cause sensitisation in a substantial number of subjects at 10% and lower. High TBN calcium sulfonates, sulfonic acids, petroleum, calcium salts (EC 263-093-9; TBN = 375 and 400) do not cause skin sensitisation in guinea pigs. Results of guinea pigs studies at TBN = 300 are mixed; two studies of sulfonic acids, petroleum, calcium salts, (EC 263-093-9) report no skin sensitisation while one study of sulfonic acids, petroleum, calcium salts (EC 263-093-9) and one study of benzene, polypropene derivs., sulfonated, calcium salts (EC 616-278-7) report skin sensitisation, However, numerous well-conducted, reliable, controlled human (HRIPT) studies with benzene, polypropene derivs., sulfonated, calcium salts (EC 616-278-7; TBN = 300) and sulfonic acids, petroleum, calcium salts (EC 263-093-9; TBN = 300), also show that high TBN (TBN ≥ 300) do not cause skin sensitisation. In accordance with EU CLP Regulation (EC) No. 1272/2008, classification is required for low TBN calcium sulfonates (TBN < 300) with a specific concentration limit of 10% and classification is not required for high TBN calcium sulfonates (TBN ≥ 300).

 

 

References

 

Alworth KA, Schwartz H & Erianne JA (1995a). Clinical Safety Evaluation OS #18504G @ 10% in Mineral Oil Repeat Insult Patch Test, ETC Entry Nos. 3849.01, 4357.01, 4403.01, Panel Nos. 93081, 95009, 95016, 95032, 95037, 95052, Essex Testing Clinic, Inc., Verona, New Jersey USA.

 

Alworth KA, Schwartz H & Erianne JA (1995b). Clinical Safety Evaluation OS # 87926C (same as OS #87926A) @ 10% in Mineral Oil Repeat Insult Patch Test, ETC Entry Nos. 3848.01, 4357.03, 4403.03, Panel Nos. 93080, 95022, 95045, 95070, 95074, Essex Testing Clinic, Inc., Verona, New Jersey USA.

 

Alworth KA, Schwartz H & Erianne JA (1995c). Clinical Safety Evaluation OS # 65271E @ 10% in Mineral Oil Repeat Insult Patch Test, ETC Entry Nos. 3838.01, 4357.02, 4403.02, Panel Nos. 93072, 95018, 95025, 95062, Essex Testing Clinic, Inc., Verona, New Jersey USA.

 

Ball N, Cagen S, Carrillo J-C, Certa H, Eigler D, Emter D, Emter R, Faulhammer F, Garcia C, Graham C, Haux C, Kolle SN, Kreiling R, Natsch A & Mehling A (2011). Evaluating the Sensitization Potential of Surfactants: Integrating Data from the Local Lymph Node Assay, Guinea Pig Maximization Test, and in vitro Methods in a Weight-of-Evidence Approach. Regulatory Toxicology & Pharmacology 60:389-400.

 

Basketter DA & Kimber I (2011). Skin Irritation, False Positives and the Local Lymph Node Assay: A guideline issue? Regulatory Toxicology & Pharmacology 61(1):137-140.

 

Blaszcak DL (1992). Closed-patch Repeated Insult Dermal Sensitization Study of OS# 18163Q in Guinea Pigs (Buehler Method), Bio/dynamics Project No.: 6153-91, Bio/dynamics Inc., East Millstone,New Jersey USA.

 

Bonnette KL (1993a). Dermal Sensitization Study in Guinea Pigs with OS# 65271E -Modified Buehler Design- (EPA-TSCA, EPA-FIFRA, OECD), SLS Study No. 3263.9, Springborn Laboratories, Inc., Spencerville, Ohio USA.

 

Bonnette KL (1993b). Dermal Sensitization Study in Guinea Pigs with OS# 67708C -Modified Buehler Design- (EPA-TSCA, EPA-FIFRA, OECD), SLS Study No. 3263.10, Springborn Laboratories, Inc., Spencerville, Ohio USA.

 

DiFiglia CJ, Shanahan RW & Erianne JA (1993a). Clinical Safety Evaluation OS #16928AJ (@ 10% in Mineral Oil) Repeated Insult Patch Test, ETC Entry No. 3864.01, Panel No. 93089, Essex Testing Clinic, Inc., Verona, New Jersey USA.

 

DiFiglia CJ, Shanahan RW & Erianne JA (1993b). Clinical Safety Evaluation OS #67708E Repeat Insult Patch Test, ETC Entry No. 3775.01, Panel No. 93027, Essex Testing Clinic, Inc., Verona, New Jersey USA.

 

DiFiglia CJ, Shanahan RW & Erianne JA (1993c). Clinical Safety Evaluation OS #16928AJ (1% in Mineral Oil) Repeat Insult Patch Test, ETC Entry No. 3825.02, Panel No. 93067, Essex Testing Clinic, Inc., Verona, New Jersey USA.

 

DiFiglia CJ, Shanahan RW & Erianne JA (1993d). Clinical Safety Evaluation OS #65271E (1% in Mineral Oil) Repeat Insult Patch Test, ETC Entry No. 3811.01, Panel No. 93059, Essex Testing Clinic, Inc., Verona, New Jersey USA.

 

Eisenberg RR (1994a). Repeat Insult Patch Test 10% w/OS# 18504G In Squibb White Mineral Oil, Experiment Reference No. C94-0115, Consumer Product Testing Co., Fairfield, New Jersey USA.

 

Eisenberg RR (1994b). Repeat Insult Patch Test 10% w/OS# 87926A In Squibb White Mineral Oil, Experiment Reference No. C94-0116, Consumer Product Testing Co., Fairfield, New Jersey USA.

 

Eisenberg RR (1994c). Repeat Insult Patch Test 10% w/OS# 65271E In Squibb White Mineral Oil, Experiment Reference No. C94-0117, Consumer Product Testing Co., Fairfield, New Jersey USA.

Kiplinger GR (1992a). Skin Sensitization Study in Albino Guinea Pigs with OS 47860E, WIL Project Number: WIL-168017, WIL Reasearch Laboratories, Inc., Ashland, Ohio USA.

 

Kiplinger GR (1992b). Skin Sensitization Study in Albino Guinea Pigs with OS 47860E, WIL Project Number: WIL-168018, WIL Reasearch Laboratories, Inc., Ashland, Ohio USA.

 

Kiplinger GR (1992c). Skin Sensitization Study in Albino Guinea Pigs with OS 22969Q, WIL Project Number: WIL-168019, WIL Reasearch Laboratories, Inc., Ashland, Ohio USA.

 

Lees D (1996). OS65271G: Local Lymph Node Assay. Report No. CTL/E/132, Central Toxicology Laboratory, Alderley Park Macclesfield, Cheshire UK.

 

Reagan EL (1988). Dermal Sensitization Study of OS 68022 in Guinea Pigs, FDRL Study No. 9592C, Food & Drug Research Laboratories, Waverly, New York USA.

Shults SK (1993). Dermal Sensitization Study (Closed-Patch Repeated Insult) in Guinea Pigs with OS# 65271E. Document Number: 5577-92-0514-TX-001, Ricerca, Inc., 7528 Auburn Road, Painesville, Ohio USA.

 

Shanahan RW & Erianne JA (1993a). Clinical Safety Evaluation OS #65271E (100%) Repeat Insult Patch Test (Semi-Occulsive) Patch Test, ETC Entry No. 3900.02, Panel No. 93109, Essex Testing Clinic, Inc., Verona, New Jersey USA.

 

Shanahan RW & Erianne JA (1993b). Clinical Safety Evaluation OS #67708E (@ 100%) Repeat Insult Patch Test Patch Test, ETC Entry No. 3870.01, Panel No. 93092, 93123, 93133, 93140, 93147, Essex Testing Clinic, Inc., Verona, New Jersey USA.

 

Shanahan RW & Erianne JA (1994a). Clinical Safety Evaluation OS #65271E @ 20% in Mineral Oil Repeat Insult Patch Test Patch Test, ETC Entry No. 3999.01, Panel No. 93162, Essex Testing Clinic, Inc., Verona, New Jersey USA.

 

Shanahan RW & Erianne JA (1994b). Clinical Safety Evaluation OS #13463M (@ 10% in Mineral Oil) Repeat Insult Patch Test Patch Test, ETC Entry No. 4044.01, Panel No. 94009, Essex Testing Clinic, Inc., Verona, New Jersey USA.  

 

Shanahan RW & Erianne JA (1994c). Clinical Safety Evaluation OS #17759W “Repeat Insult Patch Tests of Varius Sulfonates and Gear Oil Additive Test Articles, ETC Entry No. 4103.02, Panel Nos. 94069, 94071, 94081, 94084, Essex Testing Clinic, Inc., Verona, New Jersey USA.

 

Shanahan RW & Erianne JA (1994d). Clinical Safety Evaluation OS #65841A Repeat Insult Patch Test, ETC Entry No. 4103.01, Panel Nos. 94068, Essex Testing Clinic, Inc., Verona, New Jersey USA.

 

Shanahan RW & Erianne JA (1994e). Clinical Safety Evaluation OS #67708E @ 1% in Mineral Oil Repeat Insult Patch Test, ETC Entry No. 3834.01, Panel No. 93071, Essex Testing Clinic, Inc., Verona, New Jersey USA.

 

Shanahan RW & Erianne JA (1994f). Clinical Safety Evaluation OS #16928AJ Repeat Insult Patch Test, ETC Entry No. 3911.01, Panels Nos. 93117, 93150, 93152, 93157, Essex Testing Clinic, Inc., Verona, New Jersey USA.

 

Wachs GN (1993). Repeat Insult Patch Test OS# 67708E, Experiment Reference No. C-227-93, Consumer Product Testing Co., Fairfield, New Jersey USA.

  

Migrated from Short description of key information:

The sensitisation potential of the substance has been assessed to humans and guinea pigs  On the basis of these data the substance is considered sensitising, but the data available on human vounteers suggests that there is a clear threshold at 10%w/w, above which the substance is sensitising whilst at and below which the substance is not sensitising to humans.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

As determined by ECHA guidance in Appendix R. 8 -11, and considering that no data from use of the substance are available, it is not possible to assess respiratory sensitisation or estimate a threshold or DNEL. It is known, nonetheless, that some, but not all, skin sensitisers can also cause respiratory sensitisation.

Migrated from Short description of key information:

Respiratory sensitisation has not been assessed.  There are currently no validated in vitro or in vivo data and no data available from human exposure (e.g. workers) to demonstrate or deny respiratory senitisation.

Justification for classification or non-classification

Based on the available animal that all show positive results and the human data that demonstrate positive results at and above 10%w/w concentration it is considered that the substance is classified as a skin sensitiser.