Registration Dossier

Toxicological information

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
other: a case report
Adequacy of study:
other information
Study period:
not reported, published 1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented case report.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1993

Materials and methods

Study type:
poisoning incident
Endpoint addressed:
not applicable
Test guideline
Qualifier:
no guideline required
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
For the development of films a liquid activator containing 2-methylamino ethanol was used. A product which contained boric acid and ethanol was used as stabilizer.

Method

Subjects:
- Number of subjects exposed: 1
- Sex: woman
- Age: 55 years
- Race: european
- Demographic information: From 1954 through 1979 the patient held different jobs which did not involve exposure to specific chemicals. From 1979 through 1989 she was employed as a secretary at a public driver' licence office, and her prime task was to take and develop photographs.
- Known diseases: appendectomy, extrauterine pregnancy, two uterine abrasions after menorrhagia, histerectomy because of myoma uteri, myalgia nuchae and periodically slightly elevated blood pressure.
- Other: The patient is non-smoking and has never used alcoholic beverages.
Ethical approval:
not specified
Route of exposure:
other: inhalation and dermal
Reason of exposure:
unintentional, occupational
Exposure assessment:
estimated
Details on exposure:
The bottle containing liquid activator was generally left open during the entire wirking day. The film negatives which were still covered by a thin layer of the liquid were kept in an open bucket permitting continuous evaporation of the liquid. To enhance the fixation process of the photographs the petient used to hold the negative in one hand, while holding a hair-dryer in the other, blowing each negative film dry for about three minutes. on average she treated about 40 photographs a day in this way, peaking up to 100. She also cleaned the photographic machine with water every day. Sometimes the 2-methylaminoethanol liquid leaked from the photographic machine and she wiped it up from the floor using paper tissues without protecting her hands with gloves. The photographic laboratory was about 2x3 m² and had no artificial ventilation.
Examinations:
- Urine analysis: yes
- Haematology: yes
- Lung function parameters: no
- Other: S gamma-glutamyl transpeptidase and S-Alkaline phosphatase and trombocyte tests, ERCP examination, immunological tests, neurological and EEG examinations, liver biopsy, cysto-retroscopy and urography, cholecystectomy
Medical treatment:
no data

Results and discussion

Clinical signs:
From about 1983 the patient developed irritative symptoms in the mucosa of the eyes, nose, and mouth. From about 1987 she bagan experiencing nausea when eating fat-containing food. She fainted a couple of times and had periodically a senstion of diffuso vertigo. She also developed macroscopic hematuria during the fall of 1987, lasting for several months. From 1989 and onwards she had several episodes with spontaneous hematomas occuring on arms and leggs and several warts developed on the patient' hands and feet, in particular under her right plantar pedis. She had never had warts before. On one ocassion in July 1989 she lost consciousness when driving her car, resulting in a minor accident, but she was not injured.
Results of examinations:
- Urine analysis: macroscopic hematuria during the fall of 1987 and of 1989. Both falls were without pathological findings either by urography or by cystourethroscopy
- Haematology: The results from blood failed to explain the hematuria. Regarding spontaneous hematomas: The thrombocyte-count presented low figures at two examinations: 136 x 10ˆ9/L in 1989, and 142 x 10ˆ9/L in 1990 with the reference level 150-450 x 10ˆ9/L: Other hematological paramaters have been normal at a number of controls.
- Other:
- Liver function: The histological findings of a liver biopsy sampled in May 1989 indicated a slight but unspecific parenchymal affection;
- Cysto-and urography revealed no abnormalities;
- More or less by chance a concrement was found in the gallbladder;
- S-gamma-glutamyl transpeptidase and S-Alkaline phosphatase were both significantly elevated (before and after cholecystectomy). Both these parameters remained elevated despite the operation, yet, as revealed in the following data, the elevated figures do not present a consistent pattern (Table 1).
- The ERCP-examination presented no abnormalities;
- Immunological tests performed to evaluate the possibility of chronic active hepatitis and primary biliary cirrhosis were negative;
- Regarding the accident when driving car: neurological and EEG examinations indicated an obvious focal epileptic activity localized to the fronto-temporal region.
Effectivity of medical treatment:
not applicable
Outcome of incidence:
Cholecystectomy was carried out in January 1988.

Any other information on results incl. tables

Table 1: Enzyme levels

 

S-gamma-glutamyl transpeptidase (U/L)

S-Alkaline phosphatase (U/L)

June 1988

345

344

January 1989

537

377

June 1989

311

349

May 1990

186

269

August 1990

311

-

July 1991

295

352

The S-GGT reference level = 5 -50;

The S-AP reference level = 0 -275.

Applicant's summary and conclusion

Conclusions:
There is no evidence that exposure to 2-methylaminoethanol may result in a pattern of symptomps and signs which involves different organs as well as stimulation of the central nervous system. There is possible relationship between the reported exposure by inhalation and by skin and the irritation of the mucous membranes.
Executive summary:

This report presents a patient who during exposure to 2 -methylaminoethanol developed prolonged hematuria, pathologic liver functions tests, and multiple skin warts. No information could be found in the literature, explaining this unusual combination of illness and symptoms.

Human injuries have been reported after inhalation. In animal testing, repeated exposures might cause liver degeneration and nephritis. 2 -methylaminoethanol could also act as a precursor for choline. In animals, alteration of lipid metabolism and development of fatty liver has been observed after a choline deficiency. There was no information found on whether exposure to 2 methylaminoethanol interferes with regular choline functions. There is some evidence that mammalian tissues can produce PMME (phosphatidylmonomethylethanolamine) and PDME (phosphatidyl-dimethylethanolamine) directly from their corresponding aminoalcohols by a base exchange type reaction. It has been indicated that either these phospholipids or the enzymes may be responsible for their formation and could thus be involved in the process of message transmission across biological membranes (references cited in the original paper). However, there is no apparent explanation for the manifestation of multi-organ disease and its possible relation to the exposure.