2-(2-aminoethoxy)ethanol

Endpoint summary

Additional information

There are some case studies on humans available which are alone not considered sufficient for a final assessment, since all are rated Klimisch 4. However, as there are several positive cases described in the literature, the MAK Commission discussed and assessed the effects as described below:

 

Skin sensitising effects in humans (MAK, 2014)

A 39-year-old metalworker developed workplace-related dermatitis of the hands, which initially healed after a week of work-free time, but recurred after resuming work and finally extended to the arms within three months. After another four-week break from work, the eczema was almost healed, but recurred again within two weeks of continuing the activity. The patient developed an infiltrated vesicular erythema in the epicutaneous test after three days after application of a 1% preparation of the test substance in petrolatum. The cooling lubricant used at his workplace contained 10% of the test substance, but was not available for a epicutaneous test or an application test (Geier et al. 2002).

About twelve months after the introduction of a new cooling lubricant, a 26-year-old metal worker developed vesicular eczema on his hands and forearms. The epicutaneous test showed concentration-dependent pronounced reactions to the 0.6%, 3% and 6% tested cooling lubricant, which also contained 10% 2-(2-aminoethoxy)ethanol. Moreover, a positive result was obtained after three days with a 6% preparation in the "Repeated Open Application Test" (ROAT). An 1% pereparation of 2-(2-aminoethoxy)ethanol in petrolatum led to a clear papular reaction in the patient in the epicutaneous test. No reaction to this preparation was observed in 80 control subjects (Frosch et al. 2002).

A worker reacted strongly positive to the professionally used cooling lubricant, which had been tested both fresh and used. According to the safety data sheet, the cooling lubricant contained a formaldehyde separator, (ethylene dioxy)dimethanol, CAS 3586-55-8, which was not tested separately. When testing the standardized test allergens, the patient showed positive reactions to formaldehyde and the formaldehyde separator methylene bis(methyloxazolidine), as well as to 2-aminoethanol and 2-(2-aminoethoxy)ethanol. Whether the professionally used cooling lubricant contained 2-aminoethanol or 2-(2-aminoethoxy)ethanol remained unclear, as only "alkanolamines" were listed as ingredients in the safety data sheet (Geier et al. 2011).

Between April 2000 and July 2002, 2-(2-aminoethoxy)ethanol was tested as a 1% preparation in petrolatum in a total of 228 employees of the metal industry in the epicutaneous test as part of a study in five centers of the IVDK (Information Network of Dermatological Clinics). Four of the 228 employees tested (1.8%) showed a onefold positive reaction on the third day, and the fourth positively tested person (0.4%) showed a twofold positive reaction (Geier et al. 2002). For three tested individuals (1.3%) a questionable reaction was observed (Geier et al. 2003 a). In 2003, 108 patients were epicutaneously tested with 1% of 2-(2 aminoethoxy)ethanol in petrolatum as a new component of the DKG (German Contact Allergy Group) test series "Cooling lubricants currently" in the clinics of the IVDK. Two of them (1.9%) showed one positive and six tested (5.5%) showed a questionable reaction (Geier et al. 2004).

From June 2004 to June 2005, 144 metalworkers were tested with an extended series of cooling lubricants as part of a study in seven clinics of the IVDK and the occupational dermatology department of Lund University in Malmö. In 137 of them, 2-(2-aminoethoxy)ethanol was also tested, in five cases (3.7%) with a positive result (Geier et al. 2006).

From July 2003 to August 2010, a total of 2972 patients were tested in the IVDK clinics with 2-(2 aminoethoxy)ethanol as part of the DKG test series "Kühlschmierstoffe aktuell". In addition to 35 onefold and ten double positive reactions (a total of 1.5% positive reactions), there were 44 questionable reactions, three follicular reactions and eight classified as irritative. With a positivity ratio (PR)¹⁾ of 78% and a reaction index (RI)²⁾ of -0.1, 2-(2-aminoethoxy)ethanol proves to be a rather problematic test substance. Between September 2010 and June 2012, 2-(2 aminoethoxy)ethanol was tested in 864 patients as part of the DKG test series "Cooling Lubricants". Twelve onefold positive reactions occurred (1.4%), ten reactions rated as questionable and three as irritative. In the two periods, 197 out of 2995 tested (6.6%; 156 single, 36 double and 5 triple positive reactions; 135 questionable, 12 follicular and 37 irritant reactions; PR: 79%; RI: 0.0) and in 41 out of 876 tested (4.7%; 38 simple, 3 double positive reactions; PR: 93%; RI: 0.2) showed a positive reaction (IVDK 2013; original publication not yet available).

Conclusion: There have been reports of positive, clinically relevant epicutaneous test responses to 2-(2-aminoethoxy)ethanol. The negative result of an animal study without the use of adjuvant indicates a low sensitization potential. However, the irritant effect of the substance appears to be an important cofactor which, together with other factors damaging the skin barrier, especially in metal working with often large-scale and regular contact with cooling lubricants, can lead to sensitization, as the positive epicutaneous tests in these occupational groups show. Whether some of the reactions may be due to cross-reactions after sensitization by 2-aminoethanol or other ethanolamines cannot be assessed on the basis of the available data. Although the number of observed cases is relatively small so far, 2-(2-aminoethoxy)ethanol is marked with "Sh" due to the risk of sensitization due to the use of the substance in the metalworking industry, a marking with "Sa" is still not carried out.

 

¹⁾ The positivity ratio is defined as the percentage of simple positive reactions in the totality of positive reactions (Geier et al. 2003 b).

²⁾ The reaction index is defined as the quotient: (a – d – i) / (a + d + i); with: a = number of allergic reactions, d = number of questionable reactions, i = number of irritative reactions (Brasch and Henseler 1992).