Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
From June 23, 1975 to August 15, 1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report Date:
1975

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A repeated insult patch test was performed to study the effect of repeated dermal application of monoethanolamine (concentration: 0.5% aqueous solution) to human volunteers. The study was conducted in two phases induction phase and challenge phase. In the induction phase, test substances (MEA and CnAE6S) patches were applied on the dorsal surface of upper arm in four different orders to eliminate position and order bias. The patches were left in place for 24 hours at each of nine applications over a period of 3 weeks. After 14 days, the treatment sites were challenged on both arms with one set of patches at the original treatment sites and a duplicate set on the other arm. The reactions were scored 48 and 72 hours after patch application in the challenge phase.
GLP compliance:
no
Remarks:
(pre-dates GLP)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Monoethanolamine (MEA)
- TSIN: PZD-75.001a; BTS-1763
- Substance type: Pure active substance
- Analytical purity: 97%
- Composition of test material, percentage of components: 97.0% Monoethanolamine and 3.0% water

No further details on test substance were provided in the study report.

Method

Type of population:
general
Ethical approval:
not specified
Subjects:
- Number of subjects exposed: Total 119 subjects were employed in the study and 90 of them completed the study.
- 29 individuals were dropped due to absence.
- Sex: Males and females
- Age: Adults

Controls:
No
Route of administration:
dermal
Details on study design:
TYPE OF TEST USED: Patch test
ADMINISTRATION
- Type of application: Occlusive
- Description of patch: A patch strip consisting of 7/8 inch diameter circular webril pads located down the centerline a piece of 3M Blenderm adhesive tape was used.
- Vehicle / solvent: Water
- Concentrations: 0.5% aqueous solution of the test substance
- Volume applied: 0.5 mL/patch

Induction patches: The patches were applied for induction on Monday, Wednesday and Friday of each of 3 subsequent weeks at dorsal surface of upper arm, for 24 hours. The test substance was applied on arm in four different orders to eliminate position and order bias.

Challenge patches: After 14 days of final induction patch application, the patches were applied to both arms of subject for challenge (at original site and alternative site).

Testing/scoring schedule: The scoring was performed after removal of each of the 9 induction patches and after 48 and 96 hours of the challenge patch application.

- Removal of test substance: 24 hours after each of the 9 induction patch and 24 hours after the challenge patch.

EXAMINATIONS
- Grading/Scoring system: The scoring system is as follows:
0 = No clearly visible reaction
1 = Faint but distinct reaction, erythema
1E = Mild erythema with few papules
2 = Moderate reaction, erythema
2E = Mild to moderate reaction with edema or papules
3 = Strong reaction, erythema
3E = Strong reaction with marked edema or papules4 = Severe reaction with erythema, papules and/or edema
5 = Vesicular or weeping eczematous reaction
6 = Strong reaction (spreading well outside the test site – bullous reaction

Results and discussion

Results of examinations:
Results of examinations
SYMPTOMS
- Frequency, level, duration of symptoms observed: The total number of score (for both pilot and main test) for no irritation and mild irritation was 998 and 243, respectively. No subject revealed moderate, strong or severe irritation/allergy reaction.
The test substance revealed very mild irritation after patch application to skin.

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 0/90
- Number of subjects with negative reactions: 90/90
- Number of subjects with equivocal reactions: 0/90
- Number of subjects with irritating reactions in induction phase: 56/90 subjects completing the study had faint but distinct erythema (grade 1) and 1/90 subjects had moderate reaction, erythema (grade 2)
- Number of subjects with irritating reactions in challenge phase: 12/90 subjects completing the study had faint but distinct erythema (grade 1).

Any other information on results incl. tables

Scoring interpretation:

- 1, 2, or 3 normally describes the primary irritation of the skin which develops from application of the test substance. However, in the evaluation of a material for its ability to induce an allergic reaction, reactions obtained in the challenge period are the most meaningful.

- A grade of 1, 2, or 3 normally is not suggestive of sensitization, whereas a grade of 4, 5, or 6 usually denotes an allergic response.

- Allergic responses typically do not improve markedly at 96 hours and should be of nearly equal intensity on the original and alternate sites.

- Any grade of 2 or higher necessitates relocation of a patch.

- Grades of 2 or 3 early in the induction period usually are indicative of primary irritation, and a reduction in concentration of the test substance may be warranted.

- A sudden increase in severity of a response in the latter portion of the induction may be suggestive of sensitization.

Applicant's summary and conclusion

Conclusions:
Monoethanolamine (PZD-75.001a; purity: 97%) did not produce skin sensitization in human volunteers when applied topically as 0.5% aqueous solution in human repeated insult patch test (HRIPT).
Executive summary:

The study was designed to evaluate the absence of skin sensitization potential of 0.5% monoethanolamine aqueous solution when applied to human skin in the human repeat insult patch test (HRIPT). The same panel of volunteers were also exposed to 0.1% CnAE6S (ammonium neutralized coconut chain length surfactant with an average ethoxylate value of 6) to evaluate the skin sensitization effect of CnAE6S.

A total of 119 adult male and females were employed in the study and only 90 of them completed the study. In induction phase, subjects were exposed to 0.5 mL of 0.5% aqueous solution of the test substance under occlusive patches on the dorsal surface of upper arm for 24 hours on Monday, Wednesday and Friday for 3 subsequent weeks. The test substances (MEA and CnAE6S) were applied in four different orders to eliminate position and order bias. After 14 days rest period subjects were challenged with two set of patches, one at original site and other at alternative site (to other arm). The application sites were scored after removal of every induction patch and after 48 and 96 hours of removal of challenge patch.

The total score (for both pilot and main test) for no irritation and mild irritation were 998 and 243, respectively. No subjects demonstrated moderate, strong or severe irritation/allergy reaction.

After challenge, 12/90 subjects revealed faint but distinct erythema (grade 1). The overall level of irritation for monoethanolamine was very mild after patch application to skin.

Under the test conditions, 0.5% aqueous solution of monoethanolamine (PZD-75.001a; purity: 97%) did not produce skin sensitization in human volunteers during the human repeated insult patch test.