Man-made vitreous (silicate) fibres with random orientation with alkaline and alkali earth oxides (Na2O+K2O+CaO+ MgO+BaO) content greater than 18% by weight and fulfilling one of the CLP Regulation Annex VI Note Q conditions

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Remarks:

other: cross-sectional study of an exposed group with a matched nonexposed reference group

Type of information:

experimental study

Remarks:

Human case study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable well documented publication which meets basic scientific principles.

Data source

Reference

Reference Type:

publication

Title:

Ophtalmologic effects of man-made mineral fibres.

Author:

Stokholm J, Norn M, Schneider T

Year:

1982

Bibliographic source:

Scand J Work Inviron Health; 8:185-190

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

A cross-sectional study of an exposed group with a matched nonexposed reference group. Matching criteria were age, sex and smoking habits.
The exposed group included 15 workers (13 men and 2 women) who had been occupied with the production (control of production line), cutting and packing of Rockwool the test material for at leats six months. Users of contact lenses were excluded. The mean age of each group was 38.
The reference group was selected from the clerical staff of the plant and from employess of the National Institute of Occupational Health.
The investigation program comprised an eye history, based upon a questionnaire and an interview, sampling of conjunctival fluid for quantitative cytology, a general mediacal examination of the external eye, slit lamp examination, measurement of ruptures in the precorneal film, break-up time, and vital staining of cornea and conjunctival to reveal any microepithelial defects and dead or degenerated cells.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

MMVF note Q fibres

IUPAC Name:

MMVF note Q fibres

Details on test material:

- Name of test material (as cited in study report): Man-made mineral fibers (Rockwool®)

Test animals / tissue source

Species:

other: human (case control)

Details on test animals or tissues and environmental conditions:

The exposed group included 15 workers (13 men and 2 women) who had been occupied with the production (control of production line), cutting, and packing of Rockwool for at leats six months. Users of contact lenses were excluded. One woman in the exposed group was sick and absent from work on the second day of investigation. The mean age of each group was 38. The average tobacco consumption was 16 g d.
The reference group was selected from the clerical staff of the plant and from employees of the National Institute of Occupational Health. No member of the reference group had been exposed to dust, fibers, or solvents at work or to any large amount of fibres or dust in their spare time during the week before the investigation started.

Test system

Vehicle:

not specified

Controls:

other: human (case study)

Amount / concentration applied:

Occupational exposure.

Duration of treatment / exposure:

At least six months.

Number of animals or in vitro replicates:

15 workers

Details on study design:

The examination of the external eye was carried out in accordance with ophthalmologic practice. For the counting and classifying of cells in the conjunctival fluid, a quantitative method was used. In the exposed group, the coherent mucus in the inferior conjunctival fornix, the mucous thread, was removed from the right eye on the second examination after staining with 0.25% alcian blue (Microme no 24, Edward Gurr). The mucous thread was then examined for accumulated for accumulated test substance.
Break-up time was measured twice with a stop-watch after a 10 -µl drop of 0.125 % fluorescein (resorcinol phthalein) in isotonic sodium chloride had been instilled in the left eye. This procedure was followed by vital staining of the left eye with a 10 -µl drop of a fluorescein-rose bengal mixture. After 1 min of the installation all the fluorescein-stained microepithelial defects were counted in each of the following areas: lateral bulbar conjunctiva, cornea, medial bulbar conjunctiva, and inferior bulbar conjunctiva. Finally, rose bengal-stained degenerated or dead cells were also counted. In each area, the number of defects was subdivided into four groups: 1, 1-30, 31-200, 101-1000, >1000.

Results and discussion

In vivo

Results

Irritation parameter:

other: see results in field below

Basis:

other: see results in field below

Time point:

other: see results in field below

Reversibility:

not specified

Remarks on result:

not measured/tested

Irritant / corrosive response data:

Questionnaire
Of those in the exposed group, five reported previous eye infections diagnosed by a doctor in comparison with two in the reference group, and four exposed workers reported eye damage needed to be seen by a doctor in comparison with two in the reference group. Whereas none of the reference group used eye medication at the time of the investigation, three people in the exposed group did. Two of these three people used eye medication almost constantly. The third had visited a first aid station because of eye irritation, just before the investigation was conducted. The subject reported that the irritation began shortly after "some dust had blown into my eyes." No foreign body had been found. From the medical interview it appeared that the itching sensation was first and foremost located in the medial bulbar part of the eye. Symptoms were reported to disappear after work, and had usually disappeared by the next morning.

Slit lamp examination
There was no significant difference between break-up times in the two groups, and the mean values were comparable to other findings (11). Nor was there any significant change in break-up time in the exposed group from Monday morning (mean 37.5 s) to Thursday at the end of the workday (mean 40.0 s). The number of epithelial defects, depicted by the fluorescein staining, increased significantly (p = 0.009) for the medial bulbar conjunctiva after 4 d of exposure in comparison with those in the reference group (fig 2). Vital staining did not show any other significant differences between and within the groups. However, a slight increase in the number of rose bengal-stained dead or degenerated cells was observed after 4 d of work.

Conjunctival fluid cytology
In one conjunctival fluid sample an increased number of neutrophils (11,300) and lymphocytes (1,100) was found before exposure to man-made mineral fibers. Moreover one person had a marginally increased number of neutrophils. The other findings were entirely within the normal range (10). After exposure, only samples from 12 workers were suitable for further examination. A pathologically increased neutrophil count was found in six cases (p = 0.06) (range 116 - 1,530). One sample was accompanied by a pathological increase in the number of columnar epithelial cells, nucleated squamous cells, and keratinized nucleated cells. The corresponding mucous thread and mucous clump sample ontained the highest number of fibers
(250) found after a workday. In no case did the lymphocyte count increase after exposure, and no esinophilic granulocytes were found. There was significant correlation between the number of neutrophils and lymphocytes and the number of rose
bengal-stained degenerated and dead cells (r8 = 0.85) but not between the number of neutrophils and lymphocytes and the number of fluorescein-stained epithelial defects (r8 = 0.12). An increased amount of mucus was found in 10 of the 15 conjunctival fluid samples taken on Monday morning and in 8 of the 12 samples taken after exposure. In some of the samples, this increase in mucous content was not accompanied by any subsequent increase in the neutrophilic count.

Dose-effect relationship
We measured the fiber dose by traditional filter methods and by a new method determining the amount of fibers accumulated in the eye (13). Likewise we tested whether a correlation existed between the aforementioned measures of dose and three measures of effect: fluorescein staining, rose bengal staining and con june ti val fluid cytology. There was a significant correlation between the number of fluorescein-stained epithelial defects on the medial bulbar conjunctiva and the number of fibers accumulated in the opposite eye (rs = 0.79, p < 0.01). There was also a significant correlation between the number of fluorescein-stained epithelial defects and the total airborne dust dose determined by filter sampling (r8 = 0.80, p < 0.01) (fig 3). A nonsignificant correlation was found between the number of rose bengal-stained cells and the number of fibers accumulated in the eye (rs = 0.46, p = 0.07).

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The mineral wool is not classified as irritant to the eye in the Council Directive 67/548/EEC according to the results of human case study (adaptation from the Annex X1, 1.1.2).

Executive summary:

Effects of the occupational exposure to MMVF note Q fibres on the outer eye in mineral wool workers was investigated along with a matched non-exposed control group in a cross-sectional study. After 4 working days the workers showed a significantly higher frequency of eye symptoms, microepithelial defects on medial bulbar conjunctiva and neutrophil cell count in conjunctival fluid. The effects were reversible. The mechanism was explained as the same foreign body reaction as is seen for skin irritation. The foreign body reaction can be compared to the mechanical irritant effect from a sand particle. The fibres will align along the surface. In conclusion mineral wool is not classified as irritant to the eye in the Council Directive 67/548/EEC.

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