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Sensitisation data (human)

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Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From 1988-08-26 to 1988-11-11
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Procedure perdormed in compliance with Good Clinical Practice. Study conducted according to acceptable scientific conditions; number of volunteers, applied dose, observation time and observed parameters are acceptable. Substance identification: commercial name available from industrial for code name Substance analytical certificate not available in the report
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
read-across: supporting information
Reference
Endpoint:
sensitisation data (humans)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
From 1988-08-26 to 1988-11-11
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Procedure perdormed in compliance with Good Clinical Practice. Study conducted according to acceptable scientific conditions; number of volunteers, applied dose, observation time and observed parameters are acceptable. Substance identification: commercial name available from industrial for code name Substance analytical certificate not available in the report
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
reference to same study
Results of examinations:
SYMPTOMS
- Frequency, level, duration of symptoms observed: No symptoms observed.

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 0
- Number of subjects with negative reactions: 29
- Number of subjects with equivocal reactions: 0
- Number of subjects with irritating reactions: 0

OTHER RESULTS:
Responses of greater intensity than the degree of erythema usually anticipated with 2 MED's were not observed in any of the 29 panelists on the irradiated sites occupied by the test material during the induction phase.

Table 7.10.4/2: Preliminary Phase I Study results: Intensity of responses observed on irradiated sites:

Duration of Exposure

Subject number

10 seconds

20 seconds

30 seconds

40 seconds

50 seconds

1

0

0

1

2

3

2

0

0

1

2

2

3

0

0

1

2

3

4

0

0

0

1

3

5

0

0

1

2

3

6

0

1

1

2

3

7

0

0

1

1

2

8

0

1

1

2

3

9

0

0

1

2

2

10

0

0

1

1

2

11

0

0

1

2

2

12

0

0

1

2

3

13

0

0

1

2

3

14

0

0

0

1

3

15

0

0

1

2

3

16

0

0

0

1

3

17

0

0

0

1

2

18

0

0

1

2

3

19

0

0

1

1

2

20

0

1

2

2

3

21

0

0

0

1

3

22

0

0

1

2

3

23

0

0

1

1

2

24

0

0

1

1

2

25

0

0

1

2

3

26

0

0

1

1

3

27

0

0

0

1

3

28

0

0

1

2

2

29

0

0

1

1

3

30

0

1

1

2

3

Irritating reactions were observed for the 30 panelists. The least duration of UV-B exposure which produced erythema of Grade 1 (considered as the qualifying erythematous reaction) or greater was selected as the MED value for each panelist.

In four individuals, an exposure of 20 seconds of UV-B sufficed to produce the qualifying erythematous reactions. Exposure of 30 seconds in twenty individuals and 40 seconds in six individuals were required to achieve the same intensity of response.

Conclusions:
Under the test conditions, MRD-88-295 is not considered as a photocontact allergen, a primary irritant or a contact allergen.
Executive summary:

This data is being read across from the source study that tested Hydrocarbons, C14 -C19, isoalkanes, cyclics, <2% aromatics based on analogue read across.

This study included three phases which evaluated different propensities of the MRD-88-295 test substance as the first phase was only a preliminary test condition study.

The phase III of the study was performed to determine the potential of MRD-88-295 to cause dermal irritation and sentization in humans with or without UV irradiation.

A preliminary Phase I study was conducted to determine the Minimum Erythemogenic Dose (MED) for each member of a group of thirty panelists when the skin is irradiated by UV-B light. The least duration of UV-B exposure which produced erythema of Grade 1 or greater was selected as the MED value for each panelist. One volunteer was dropped out at the end of the phase II of the study.

Twenty-nine humans were exposed to MRD-88-295 for 24 hours followed by UV-B and UV-A irradiation (during three weeks). Then, exposure to MRD-88-295 was repeated for 24 hours. Dermal examinations occured at 24, 48 and 72 h test substance post-exposure. Dermal irritation and damage was scored according to a modified Draize scale. The most severe reaction noted in all experimental paradigms was noted as a "1" for slight erythema. MRD-88-295 did not elicit any effects which could be construed as a characteristic of a phototoxic propensity or of a primary irritant. MRD-88-295 showed no evidence being a photocontact allergen and no evidence of being either a primary irritant or a contact allergen.

Under these test conditions, MRD-88-295 was not classified as a irritant to skin and a skin sensitiser.

Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
A preliminary Phase I study was conducted to determine the Minimum Erythemogenic Dose (MED) for each member of a group of thirty panelists when the skin of each is irradiated by UV-B light.
The aim of this Phase III study was the determination of the photocontact and contact allergenic capabilities of MRD-88-295 in Human skin.
This study was performed with the same 30 panelists of the phase I.
On each side of the back, 9 test sites were used for experimental purposes with 10th site serving as a control (no test substance applied). The left side of the back was used to evaluate the irritant and contact allergenic propensities. The evaluation of photocontact irritation and allergenic propensities were performed on the right side. MRD-88-295 solution at 50% in petrolatum was used at each experimental site for the evaluation of the propensities.
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics
EC Number:
920-114-2
IUPAC Name:
Hydrocarbons, C14-C19, isoalkanes, cyclics, <2% aromatics
Constituent 2
Reference substance name:
Isopar V
IUPAC Name:
Isopar V
Constituent 3
Reference substance name:
MRD-88-295
IUPAC Name:
MRD-88-295
Details on test material:
- Name of test material (as cited in study report): MRD-88-295
- Substance type: petroleum product, UVCB
- Analytical purity: 100% Commercial product
- Physical type: Clear Colorless Liquid
- Lot/batch No.: 1
- Storage condition of test material: at room temperature

Method

Type of population:
general
Ethical approval:
confirmed, but no further information available
Subjects:
- Number of subjects exposed: 29
- Sex: male and female, no additional data
- Age: no data
- Race: no data
- Demographic information: no data
- other : panel 88-70
Clinical history:
A past/present medical history and a brief physical was performed and obtained for each individual. Candidates were excluded for any one of the following reasons: systemic illness which might have contra-indicated participation in another sensitization study within the past 10 weeks.
Controls:
Controls were performed
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: patch test and UV exposure

ADMINISTRATION
- Type of application: semi-occlusive
- Description of patch: adhesive strips
- Vehicle / solvent: petrolatum
- Concentrations: 50% w/w
- Volume applied: 0.3g
- Testing/scoring schedule: according to a modified Draize scale
- Removal of test substance: no data

CONTROL:
Negative control was conducted in the same way as described above (semi-occlusive patch) but without test substance administration.

Results and discussion

Results of examinations:
SYMPTOMS
- Frequency, level, duration of symptoms observed: No symptoms observed.

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 0
- Number of subjects with negative reactions: 29
- Number of subjects with equivocal reactions: 0
- Number of subjects with irritating reactions: 0

OTHER RESULTS:
Responses of greater intensity than the degree of erythema usually anticipated with 2 MED's were not observed in any of the 29 panelists on the irradiated sites occupied by the test material during the induction phase.

Any other information on results incl. tables

Table 7.10.4/2: Preliminary Phase I Study results: Intensity of responses observed on irradiated sites:

Duration of Exposure

Subject number

10 seconds

20 seconds

30 seconds

40 seconds

50 seconds

1

0

0

1

2

3

2

0

0

1

2

2

3

0

0

1

2

3

4

0

0

0

1

3

5

0

0

1

2

3

6

0

1

1

2

3

7

0

0

1

1

2

8

0

1

1

2

3

9

0

0

1

2

2

10

0

0

1

1

2

11

0

0

1

2

2

12

0

0

1

2

3

13

0

0

1

2

3

14

0

0

0

1

3

15

0

0

1

2

3

16

0

0

0

1

3

17

0

0

0

1

2

18

0

0

1

2

3

19

0

0

1

1

2

20

0

1

2

2

3

21

0

0

0

1

3

22

0

0

1

2

3

23

0

0

1

1

2

24

0

0

1

1

2

25

0

0

1

2

3

26

0

0

1

1

3

27

0

0

0

1

3

28

0

0

1

2

2

29

0

0

1

1

3

30

0

1

1

2

3

Irritating reactions were observed for the 30 panelists. The least duration of UV-B exposure which produced erythema of Grade 1 (considered as the qualifying erythematous reaction) or greater was selected as the MED value for each panelist.

In four individuals, an exposure of 20 seconds of UV-B sufficed to produce the qualifying erythematous reactions. Exposure of 30 seconds in twenty individuals and 40 seconds in six individuals were required to achieve the same intensity of response.

Applicant's summary and conclusion

Conclusions:
Under the test conditions, MRD-88-295 is not considered as a photocontact allergen, a primary irritant or a contact allergen.
Executive summary:

This study included three phases which evaluated different propensities of the MRD-88-295 test substance as the first phase was only a preliminary test condition study.

The phase III of the study was performed to determine the potential of MRD-88-295 to cause dermal irritation and sentization in humans with or without UV irradiation.

A preliminary Phase I study was conducted to determine the Minimum Erythemogenic Dose (MED) for each member of a group of thirty panelists when the skin is irradiated by UV-B light. The least duration of UV-B exposure which produced erythema of Grade 1 or greater was selected as the MED value for each panelist. One volunteer was dropped out at the end of the phase II of the study.

Twenty-nine humans were exposed to MRD-88-295 for 24 hours followed by UV-B and UV-A irradiation (during three weeks). Then, exposure to MRD-88-295 was repeated for 24 hours. Dermal examinations occured at 24, 48 and 72 h test substance post-exposure. Dermal irritation and damage was scored according to a modified Draize scale. The most severe reaction noted in all experimental paradigms was noted as a "1" for slight erythema. MRD-88-295 did not elicit any effects which could be construed as a characteristic of a phototoxic propensity or of a primary irritant. MRD-88-295 showed no evidence being a photocontact allergen and no evidence of being either a primary irritant or a contact allergen.

Under these test conditions, MRD-88-295 was not classified as a irritant to skin and a skin sensitiser.