Hydroquinone

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Study meets basic scientific principles as a report of health surveillance data of HQ-exposed workers with specific evaluation of early eye effects; study sufficiently documented, acceptable as key study

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Corneal and conjunctival pigmentation among workers engaged in manufacture of hydroquinone.

Author:

Anderson B

Year:

1947

Bibliographic source:

Arch Ophthalmol 38, 812 - 826

Reference 2

Reference Type:

publication

Title:

Quinone vapors and their harmful effects. I. Corneal and conjunctival injury.

Author:

Sterner JH, Oglesby FL, Anderson B

Year:

1947

Bibliographic source:

J Ind Hyg Toxicol 26, 60 - 73

Reference 3

Reference Type:

publication

Title:

Quinone vapors and their harmful effects. II. Plant exposures associated with eye injuries.

Author:

Oglesby FL, Sterner JH & Anderson B

Year:

1947

Bibliographic source:

J Ind Hyg Toxicol 29, 74 - 84

Reference 4

Reference Type:

review article or handbook

Title:

Hydroquinone.

Author:

Grant WM, Schuman JS (Eds.)

Year:

1993

Bibliographic source:

Toxicology of the Eye, 4th ed., Charles C. Thomas Publisher, Springfield, IL, pp. 801 - 804

Materials and methods

Study type:

health record from industry

Endpoint addressed:

eye irritation

repeated dose toxicity: inhalation

Principles of method if other than guideline:

Health survey for occular changes by ophthalmoscopic examination; systemic effects by thorough physical and hematological examination

Test material

Test material information

Constituent 1

Reference substance name:

exposure to hydroquinone dust and benzoquinone vapours during hydroquinone production

IUPAC Name:

exposure to hydroquinone dust and benzoquinone vapours during hydroquinone production

Method

Type of population:

occupational

Ethical approval:

not specified

Details on study design:

Survey of the personnel of the hydroquinone production plant of the Tennessee Eastman Corporation, Kingsport, Tennessee:
- Assessment of number and types of ocular lesion in about 50 workmen
- Annual physical examinations of systemic diseases including investigation of hematological parameters as hemoglobin concentration, counts of erythrocytes and leukocytes, hematocrit, sedimentation rate, icterus index, and differential leukocyte counts

Exposure:
During the manufacture of hydroquinone by oxidation of aniline to benzoquinone and subsequent reduction to hydroquinone, workers were both exposed to hydroquinone dust, especially at operations of packaging the final product, and to benzoquinone vapor, predominantly at primary steps (see also Overall remarks). As the oxidation-reduction system BQ-HQ is relatively labile, hydroquinone is converted into the more volatile quinone in the presence of moisture so that exposure to hydroquinone also includes exposure to benzoquinone. As the workers circulated between different working operations, all workers principally were exposed to similar exposure levels. However, on certain working operations the concentration gradients were quite marked so that a slight change in the position of the operators head might give quite different individual exposure values (no values specified).

Evaluation:
Possible correlations of eye effects with age of employees, length of employment, particular job and location in the plant were investigated.
Hematological parameters of workers with eye effects were compared with the data of all HQ-exposed workers as well as with a control group of unexposed subjects and evaluated for statistical significance. The significance value was calculated by the difference of the means of the exposed and the control subjects divided by the standard error of the difference between the means. Values less than 3 are considered to be not significant.

Results and discussion

Results:

SYSTEMIC EFFECTS:
No indication of systemic effects from physical examination and haematological parameters.

ACUTE EFFECTS EYE EFFECTS:
Symptoms of acute eye irritation were attributed to exposure to benzoquinone vapors. Discomfort of the workman included symptoms as conjunctivitis, photophobia, moderate lacrymation, burning sensation. After acute exposure to very high concentrations corneal edema and ulceration appeared associated with a considerable loss of visual acuity. As this acute condition subsided, the vision improved (no data on exposure levels available).

LONG-TERM EFFECTS EYE EFFECTS:
No indications of systemic disease were noted on annual physical examinations; no significant changes of haematological parameters when comparing the groups of eye injury cases or of all HQ/BQ-exposed workmen with a control group of unexposed subjects.
Eye effects due to external contact with the eye:
Conjunctival lesion: pigmentation varying from slight diffuse brownish tinge to dense brownish-black globular particles. The lesions tend to locate in the interpalpebral fissure or “lid closure zone”. Relatively slight reaction of the tissue to the foreign material.
Cornea lesions: diffuse greenish-brown stain chiefly in the superficial layers of the cornea, but traceable in diminishing intensity into the deeper portions, confined to the interpalpebral fissure; greyish-white opacities varying in size and involving all the layers of the cornea.

Relationship between degree of eye injury and exposure parameters:
Positive correlation only to the length of exposure as the workers circulated between different workplaces. Individual exposures could be different at the same workplaces (no values of exposure levels available).
- At least 2 yrs: necessary for development of the brownish tinge, conjuncitve may appear slightly dried and have an attached white frothy foam-like deposit, no corneal involvement
- At least 4 yrs: more dryness of the conjunctiva, diffuse stain now agglomerated into small discret dark brown particles located in all of the layers of the conjunctiva; some slight pigmentation possible on the cornea
- At least 5 yrs: definite increase in the size, number and intensity of the conjunctival globular stain; cornea may show a variable number of greyish-white opacities, corneal stain and opacities may become more marked so that there is some interference with vision

Correlation with exposures at certain working operations:
- Operations of packaging the final product: Several workmen who spent the majority of their work time on packaging HQ showed slight pigmentation and corneal opacity. Following accidental contamination of the eyes with particles of HQ, there have been several instances of corneal ulceration.
- Exposure to BQ vapors during early stages of manufacture (most operations): operations leading to greater eye injury.

Reversibility of effects after removal from exposure:
Considerable improvement with regard to diminishing pigmentation of conjunctiva, no improvement of visual acuity due to corneal opacities

Nature of pigment deposits in conjunctiva:
Quinone may undergo further oxidation to hydroxyquinone in alkaline solution (e.g. in the alkaline aqueous medium of the tears), tending to polymerise to a brownish to blackish material, possibly favoured by sunlight or the specific action of intracellular oxidase with production of a melanin-like material. Alternatively, a polymer may be formed from quinhydrone (dimer composed of quinone and hydroquinone) as intermediate product. The relative lack of tissue reaction agrees with the low chemical reactivity of the polymer.

Nature of corneal opacities:
Appear to be modified corneal tissue possibly a protein precipitate as a result of denaturation by the action of HQ or BQ. There appears to be little absorption of these scar-like bodies, but there is no indication that these lesions progress once the exposure has been terminated and the corneal ulceration and edema subsided. It seems likely that both BQ and HQ with appreciable solubility in both water and fat can penetrate the corneal epithelium and the stroma underlying the epithelium, that both act as a barrier either to water or fat soluble materials.

Applicant's summary and conclusion

Conclusions:

Repeated thorough physical examinations and haematological investigation failed to reveal any systemic effects in the exposed workers even at exposures sufficient to cause the local eye injuries.
The relative contribution of BQ vapor or HQ dust to the production of the eye lesions is difficult to assess. However, based on observations in workmen with predominant exposure to HQ, contact of the eyes with particles of HQ produces eye injuries, that are conjunctival pigmentary changes and corneal opacity.

Executive summary:

Health surveys of workmen, exposed to BQ vapors and HQ dust during the manufacture of HQ, included annual physical examinations and investigations of hematological parameters, and were supplemented by ophthalmoscopic examinations of the eyes after a first case of characteristic eye injuries had been recognized in 1946. There was no indication of systemic effects from physical examinations and hematological parameters.

Exposure-related changes in the cornea were found to consist primarily of a stain varying from a diffuse brownish tinge to large brownish black globular particles. The lesions tended to locate in the interpalpebral fissure or “lid closure zone”. There was a relatively slight reaction of the tissue to the foreign material. The corneal injury was of two types: one a typical superficial greenish brown stain, and the other, greyish white opacities varying in size and involving all the layers of the cornea. In a few cases there had been a considerable loss of vision.

Eye injuries apparently developed gradually over a period of years with no serious cases in employees of less than five years plant experience. Removal from exposure resulted in considerable improvement in the staining but a questionable effect on corneal opacities.

Contact with BQ vapor was the probable major factor in the production of the more severe lesions. Less severe eye injuries were found in workmen with almost exclusive exposure to HQ dust during packaging of the final product HQ. Exposure to HQ also includes exposure to BQ as the oxidation-reduction system BQ-HQ is relatively labile, so that HQ is converted into the more volatile BQ in the presence of moisture. The conjunctival and corneal stains were considered to represent end products of the oxidation and subsequent polymerisation of BQ or hydroxyquinone. These processes may be favoured by sunlight or the specific action of intracellular oxidase with production of a melanin-like material. The corneal opacities probably were due to the precipitation of corneal protein or a scar-forming effect. Repeated thorough physical examinations and hematological investigation failed to reveal any systemic effects in the exposed workers even at exposures sufficient to cause the local eye injuries. The relative contribution of BQ vapor or HQ dust to the production of the eye lesions is difficult to assess. However, based on observations in workmen with predominant exposure to HQ, contact of the eyes with particles of HQ produces eye injuries, that are conjunctival pigmentary changes and corneal opacity. From the underlying publications it is not possible to derive any individual effect levels as the workers circulated between different workplaces. Individual exposures could be different at the same workplaces dependent on distance to emission sources (no values for individual exposure levels available). Measured air concentrations of HQ dust in the packaging area, were exposure was almost exclusively to HQ, were given with 25-30 mg HQ/m³ in 1944 and declined to ca. 1-4 mg HQ/m³ in 1946 by installation of measures to reduce exposure. A positive correlation was reported to exist to the length of exposure (Sterner et al., 1947). Based on measured air levels and observed eye effects, a maximum permissible workplace level to prevent eye injuries of 2-3 mg HQ/m³ (in the presence of 0.4 mg/m³= 0.1 ppm BQ) was suggested (Oglesby et al., 1947).