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Toxicological information

Direct observations: clinical cases, poisoning incidents and other

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Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Visual disturbances in man as a result of experimental and occupational exposure to dimethylethylamine
Author:
Ståhlbom B, Lundh T, Florén I, Akesson B
Year:
1991
Bibliographic source:
Br J Ind Med. 48(1):26-9

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
eye irritation
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The study reports the ocular effects of experimental and occupational exposure on man to various air concentrations of DMEA.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Supplier: Janssen Chemica (Beerse, Belgium)
- Name of test material (as cited in study report): DMEA
- Analytical purity: 99%

Method

Type of population:
general
Subjects:
Four healthy male volunteers (subjects A, B, C, and D) who were non-smokers aged 33 to 53 (mean 43 years), participated in the experimental studies. Their body weights ranged from 75 to 88 (mean 80) kg, and their heights from 1.78 to 1.84 (mean 1.82) m. Subjects A and B wore glasses during all
exposure studies.
Ethical approval:
not specified
Route of exposure:
inhalation
Reason of exposure:
unintentional, occupational
Exposure assessment:
measured
Details on exposure:
The exposure chamber consisted of two polyvinylchloride film (1 mm) cylinders, an inner (height 2.2 m, diameter 1.4 m) and an outer (height 2.4m, diameter 1.8 m). The cylinders were suspended from a 2.0 x 2.0m wood lamellate plate which could he Iifted; during the experiments it was kept 2.7 m above the floor. The chamber contained two chairs and one desk. Desk work was performed in the chamber during the experiments.
Experiments lasting 15 minutes were made without breaks, but during experiments for eight hours, an exposure free period of about five minutes was introduced after each two hours.
The concentration of DMEA in the chamber was monitored continuously by an infrared gas analyser (MIRAN-lA; wavelength 9-3 pm; pathlength 20 25 m). The air concentration of amine in the chamber was also determined during consecutive one hour sampling periods, by the method of Lundh, Stahlbom, and Akesson (unpublished data).
The experiments employed eight hour exposures to 10, 20 (two subjects only), 40, and 50 mg/m3, and 15 minute exposures to 80 and 160 mg/m3 DMEA.
Examinations:
Subjective perception of irritation and visual disturbances (haze, or halo effects, or both) were registered. Ophthalmological examinations were made after eight hours of work without exposure and 15-30 minutes after each exposure to DMEA. The examinations included visual acuity, slit lamp
examination of the anterior segment of the eye, and ultrasonic pachymetry of the cornea (Storz Corneo-Scan; St Louis, MO, USA). Also, during and after exposure, subjective descriptions ofthe visual disturbances were obtained.

Results and discussion

Clinical signs:
Ophthalmological examinations before exposure showed no abnormalities. A visual acuity of 1.0 was obtained for all four subjects after correction.
Results of examinations:
Eight hour exposure experiments:
Three subjects had eye irritation both at the 40 and 50 mg/m3 concentrations of DMEA (see attached table). Visual disturbances (haze) were recorded three to seven hours after the start of exposure by all four subjects at 50 mg/m3, and by one subject after six hours at 40 mg/m3 DMEA. The effects faded within one to three hours after the end of the exposure.
Ocular examinations after the experiments showed oedema of the corneal epithelium in three of the four subjects at the exposure concentration of 50 mg/m3, but only in one subject at 40 mg/m3 DMEA (table). No sign of corneal oedema was found under the eyelids. Slight conjunctival injection was seen in the affected subjects. Visual acuity did not decrease.
Corneal thickness showed a very slight increase with exposure to DMEA in all subjects; it was present already with exposure to 10 mg/m3 DMEA in two of them but no clear dose-response was observed for other 2 subjects.
No subjective effects were recorded in the four volunteers when exposed to 10 and 20 mg/m3 DMEA.

Fifteen minute exposure experiments:
Exposure to concentrations of 80 mg/m3 or 160 mg/m3 of DMEA did not result in any sign of corneal oedema or conjunctival injection, and no visual disturbances were recorded. Visual acuity was not affected. Three of the four subjects, however, recorded eye irritation in both experiments (see attached table).

Applicant's summary and conclusion

Conclusions:
The records for experiments with 15 minute exposure at concentrations of 80 and 160 mg/m3 DMEA, and eight hour exposure at concentrations of 40 and 50 mg/m3 indicate that irritation of the mucous membranes of the eyes seems to be the critical effect ofshort term exposure to DMEA rather than visual disturbances.
Executive summary:

Experimental exposure of four volunteers to 40-50 mg/m3 of N,N-dimethylethylamine for eight hours caused irritation of the mucous membrane of their eyes, subjective visual disturbances (haze), and slight edema of the corneal epithelium. The thickness of the cornea showed a very slight but consistent increase in all four subjects at these exposures and in two subjects exposed to 10 mg/m3 but without dose-response. The effects faded within one to three hours after the end of the exposure. Concentrations of 80 and 160 mg/m3 for 15 minutes caused eye irritation but no visual disturbances or corneal edema. Occupational exposure for eight hours to about 25 mg/m3 of N,N-dimethylethylamine (with peaks above 100 mg/m3) was also associated with eye irritation, haze, and corneal edema. The authors believed that the divergence between their findings and other reports in which visual disturbances occurred at lower concentrations during occupational exposure may be due to peak concentrations.