Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented publication which meets basic scientific principles

Data source

Reference
Reference Type:
review article or handbook
Title:
Skin sensitizing properties of the ethanolamines mono-, di- and triethanolamine. Data analysis of a multicentre surveillance network (IVDK) and review of literature
Author:
Lessmann H, et al.
Year:
2009
Bibliographic source:
Contact Dermatitis, 60, 243-255

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:
Patch test results with DEA on patients collected from 1992 to 2007 were evaluated
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Diethanolamine
- no further data given

Method

Type of population:
general
Ethical approval:
not specified
Route of administration:
dermal

Results and discussion

Results of examinations:
The industrial use of DEA in water-based metalworking fluids, and the regular, even daily exposure to these fluids is regarded as a cause of occupational sensitisation to DEA. Wet work or chemical irritation by solvents or the alkaline cutting fluid itself, and possibly mechanical irritation, seem to be important cofactors contributing to sensitisation in this special occupational group. Therefore, a slightly higher incidence of skin sensitisation in cutting fluid workers is of secondary nature, due to skin conditions not attributable to DEA.

Any other information on results incl. tables

In total 8791 patients were tested with DEA. Of these 157 (1.8%) patients were tested positively to DEA. The reaction index was calculated to -0.17. Most of the reactions were weak positive reactions resulting in a high positive ratio (80.3%).

Frequencies of reactions to DEA in all patients tested from 1992 -2007

DEA (n = 8791)

count

[%]

negative

8413

95.7

irritant

17

0.2

questionable

195

2.2

follicular

9

0.1

+

126

1.4

++

28

0.3

+++

3

0.03

reaction index

-0.17

positivity ratio

80.3%

Regarding the MOAHLFA index, there were only minor differences between patients with positive and those without positive reactions to the diethanolamine. The most obvious difference was the higher proportion of men and patients with occupational dermatitis and hand dermatitis as well as the reduced proportion of patients with atopic dermatitis among patients with positive reactions to DEA.

MOAHLFA-Index Frequency of characteristics (%) in DEA-positive (cases) vs. non positive (controls) patients

DEA

cases

controls

Men

89.8

81.0

Occupational dermatitis

79.6

48.3

Atopic dermatitis

10.8

20.0

Hand dermatitis

81.5

64.8

Leg dermatitis

0.6

1.8

Face dermatitis

2.6

5.0

Age ≥ 40 years

56.7

50.4

Reactions to DEA and occupational exposure (metal workers)

Metal workers represent the main occupational group among DEA-positive patients. If only this subgroup is considered, clearly higher ratios of positive reactions were obtained for DEA. It is striking that the increased ratio of positive reactions to DEA was not due to a relative decrease in the number of irritant or questionable reactions – as would be expected for possibly false positive reactions – since the prevalence of reactions assessed as questionable increased in parallel. The association of sensitization to DEA with (potential) occupational contact becomes even more obvious if only patients employed in cutting (grinding, drilling or shaping) of metal parts are considered since they are expected to be exposed regularly. 60 of the 157 DEA-cases, e.g. 38.2%, were metal workers (currently or formerly) of this subgroup compared with approximately 9% in the control group (not standardized to age). Compared to the control group, other metal workers are not overrepresented in the group of cases. If the prevalence of positive reactions in probably wbMWFs-exposed current male cutting workers is compared with the prevalence in all male patients not working in the metal industry at present, an about 5- to 7-fold higher portion of positive reactions is recorded for DEA, respectively.

Supportive evidence for the association of sensitization to DEA and extensive exposure to cutting fluids is provided by the high proportion of concomitant reactions to some biocides which are mainly used in wbMWFs such as methylenebis(methyloxazolidine), 4,4-dimethyloxazolidine, 1,3,5-tris(2-hydroxyethyl)-triazine, benzylhemiformal or dibromodicyanobutane. The most prominent co-sensitization is observed between the two ethanolamines (MEA and DEA) themselves: 77% of the patients positive to DEA also reacted to MEA; the proportion of patients testing positive to MEA who also tested positive to DEA was 38%. Interestingly, in the period from 1996 to the 2nd quarter of 2003, there were fewer singular reactions to DEA without corresponding reactions to MEA compared to the period from 1992 to 1995. In view of the restricted usage of, and thus exposure to, DEA, this might indicate cross-reactions to DEA after primary sensitization to MEA.

Reactions to DEA associated with other (non-)occupational applications

Data analysis did not reveal other occupational exposure being associated with sensitization to DEA. No pattern of association between non-occupational exposure markers and sensitization to DEA was found in the data.

Applicant's summary and conclusion