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Keywords:

  • trinitrotoluene (TNT);
  • cataract;
  • TNT exposure;
  • toxic cataract

Abstract.

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. References

Purpose: To compare the prevalence of cataract in workers exposed to trinitrotoluene (TNT) to the prevalence in a group of unexposed workers, matched on age and sex, using Tiukina's description and grading of TNT-induced cataract.

Methods: A total of 23 TNT-exposed and 44 unexposed workers underwent an eye examination performed by an ophthalmologist who did not know the exposure status of the subjects. All lens opacities matching Tiukina's description were classified as TNT cataract and graded on Tiukina's scale of stages 1–4.

Results: Four cases of TNT-induced cataract were identified among the 23 TNT-exposed workers and none in the unexposed group (p < 0.01).

Conclusion: Exposure to TNT may cause a unique type of cataract, which a general ophthalmologist, using Tiukina's description and grading scale, will be able to distinguish from other cataracts.


Introduction

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. References

Trinitrotoluene (TNT) is an important explosive because it is cheap, easy to produce and has an inherently low volatility. It has been in use since the early 20th century and became widely used during World War I. It is still used extensively today.

Occupational exposure has been associated with various clinical manifestations including toxic hepatitis, dermatitis, aplastic anaemia and cataract (Grant & Schuman 1993).

Early in the 20th century, Reis (1922) discovered retrobulbar neuritis in two patients working with TNT. Another presumed ocular effect of TNT was reported in a 23-year-old patient, who developed punctate and flame-shaped retinal haemorrhages (Aiello 1946).

Glezerow (1953) reported that, in the Soviet Union, cataracts with a particular form had been associated with industrial exposure to TNT since 1932. The TNT-induced cataracts were described as initially consisting of a small dark ring of turbidity in the pupil, usually about half the size of the pupil. This was accompanied by the development of spoke-like opacities in the equator of the lens. These opacities were said to appear after only 4–5 years of TNT exposure, although the dark ring in the pupil might be observed after only 2–3 years. Eventually the opacities in the equator tended to extend and meet the axial opacities (Glezerow 1953).

Kroll & Kolevatykh (1965) agreed that TNT produced a unique type of lens opacity, occurring at any age after exposure of 3 or more years, and consisting at first of opacities at the equator of the lens which did not interfere with vision and could only be detected with the pupil widely dilated.

Tiukina (1967) carried out several hundred eye examinations on TNT-exposed ammunition workers. By examining the same workers several times with years in between, she created an opportunity to observe changes in the TNT-induced cataract over the course of time. In 1967 Tiukina published drawings of the ophthalmoscopic appearance of TNT-induced cataract and described the four stages of development. The TNT-induced cataract is bilateral and symmetrical in all stages (Tiukina 1967).

Hassman & Juran (1968) detected a remarkably high incidence of cataract in people handling TNT. They reported that 26 out of 61 people showed the characteristic peripheral cataract, and most had no other indications of any adverse effects of TNT. Average exposure was 8.4 years.

The prevalence of TNT-induced cataract in exposed groups has been found to vary from 0% to 90%. An annual examination from 1977 to 1987 of Polish workers exposed to TNT disclosed cataract in 143 cases (34.6%), amounting to 88.4% in those exposed for more then 20 years (Zhou 1990). According to Zhou (1990), examination of more than 26 000 TNT-exposed workers in China showed an average prevalence of TNT-induced cataract of 17.9% (range 7.6–85.2%). No details are available on these investigations. In a study from Finland, examination of 12 workers chronically exposed to TNT revealed TNT-induced cataract in six cases (Harkonen et al. 1983).

The big differences in prevalences of TNT cataract in the studied populations probably reflect differences in exposure. In general, estimation of exposure is difficult due to various routes of uptake and because information on exposure is often limited as to duration (Manoilova 1968; Zhou 1990; Lewis-Younger et al. 2000). In one study, however, a more exact dose− effect relation was established in a small group of workers (Liu et al. 1995).

All the studies mentioned above were uncontrolled case series. Lewis-Younger et al. (2000) presented the first large study including a control group. They discovered that 63% of the workers (n = 61) had anterior cortical lens opacification in a pattern of peripheral flecks. Surprisingly similar changes were found in 14% of subjects in the control group. A possible explanation could be misclassification as some of the presumed unexposed workers chosen for the control group actually reported previous TNT exposure, or the diagnostic criteria used might not have been specific to TNT-induced cataract. Despite the classification problems, TNT exposure was the only risk factor significantly associated with cataract.

As a potential mechanism behind the induction of cataract by TNT, one theory proposes that increased oxidative stress resulting from reductive activation of TNT may be involved. In support of this theory, zeta-crystallin is found in bovine lenses. This enzyme is identical to TNT reductase (Kumagai et al. 2000). The lens has several well developed oxidative defence systems (Lou 2003). The fact that activity in these systems decreases with age (Lou & Dickerson 1992) may explain why TNT-induced cataract seems to develop in older subjects. Exposure to TNT may become more damaging with age, not only because of accumulation of the toxin but also because of a less efficient defence system.

Our study was initiated to compare the prevalence of cataract in workers exposed to TNT to the prevalence in a group of non-exposed workers matched on age and sex. We used Tiukina's description of TNT cataract and grading scale to make the diagnoses. The paper by Tiukina (1967) is, in our opinion, the only one published that thoroughly describes the appearance of TNT-induced cataract.

Material and Methods

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. References

Material

The plant at which our study was carried out has for many years produced a wide range of material for military purposes. It is divided into several factories, each of which manufactures different products. One of these is the only TNT ammunition factory in Denmark. It has been in production for about 25 years, but those 25 years have involved large variations in production intensity and several periods without any production. The production processes have mainly consisted of melting and pressing TNT-granulate, steampipe melting out of TNT from old shells, and crushing and moulding new ammunition. There has been no systematic monitoring of the work environment, but according to a number of site reports, the work environments at several of the work sites, particularly those where crushing and moulding takes place, have been problematic, with exposure to TNT from steam and dust, and contamination of the skin because of poor hygiene. For these reasons the exact level of exposure of the individual worker is impossible to determine.

As a consequence of this study the work environments have been considerably improved.

The study group comprised all 25 workers actually working (summer 2001) at the TNT ammunition factory. Of these, 23 workers agreed to participate. As a control group we selected 44 blue-collar workers, matched on age and sex, from a nearby naval base. None of them had any known history of TNT exposure.

Methods

The study design was cross-sectional. It was carried out in spring 2002.

All 67 persons went through the following programme.

Interview-based questionnaire

Two senior registrars who were aware of exposure status asked about health status, including actual or former eye disease or trauma, the use of drugs, smoking habits and ultraviolet (UV) light exposure from welding. The exposed subjects were asked about the extent of TNT exposure and symptoms of TNT poisoning. Concerning the degree of TNT exposure, the exposed subjects were asked about the number of years and with which production processes they had been working with TNT. Questionnaires and medical history were obtained prior to examination by the ophthalmologist.

Blood samples

All 67 persons underwent a thorough clinical examination. Blood samples were taken for measuring different haematological and liver variables (haemoglobin,[EVF],[MCV], lactate dehydrogenase [LDH],[ASAT],[ALAT], bilirubin, gamma glutamyl transpeptidase, alkaline phosphatase).

Eye examination

A standard eye examination was carried out by an ophthalmologist who was unaware of the exposure status of the subjects. The lens was evaluated with a slit-lamp biomicroscope following pupillary dilatation with tropicamid 1% and phenylephine 10%. Direct ophthalmoscopic evaluation of the lens and fundus was performed.

The lens was classified as follows:

  • • 
    A = normal lens, and
  • • 
    B = TNT cataract, and
  • • 
    C = any other cataract.

Cataracts induced by TNT exposure were graded according to Tiukina as follows:

  • • 
    stage 1 is characterized by a ring of dust-like opacities in the lens equator; the outer demarcation is sharp to the extreme periphery, which is always clear, and towards the centre there is a gradual transition to clear lens;
  • • 
    in stage 2 the dust-ring becomes more intense and fragmented, and the edges of the fragments gradually grow in a pattern, forming triangles;
  • • 
    stage 3 is characterized by growth of the triangles and the formation of the outer ring again; the apices of the triangles stretch towards the centre of the lens, and
  • • 
    stage 4 represents a further development of stage 3; the apices of the triangles now reach the centre of the lens.

Visual acuity is normal in stages 1–3 but subnormal in stage 4. Stages 1 and 2 can only be detected in maximum mydriasis and are consequently easily overlooked. An additional ring of opacities may or may not form more centrally in all stages.

Slit-lamp photos of the lens were obtained in retroillumination with a Zeiss model 40SL/P (Zeiss, Aalen, Germany). Slit-lamp photography was used for documentation only, not for grading.

Results

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. References

The average age for both the control group and the exposed group was 48 years (range 34–58 years). According to the questionnaire, the two groups differed in frequency on former eye ailment. The five cases in the exposed group had involved eyelid operation, iritis, strabismus, operation for cataract (right eye), and conjunctivitis. The eight cases in the reference group contained seven cases of smaller foreign body trauma and one case of unilateral amblyopia due to major astigmatism. There were more cases of UV light exposure from welding in the reference group (Table 1).

Table 1.  Patient characteristics in the TNT-exposed group and the control group.
 Exposed groupReference group
 n(%)n(%)
Male19(83)36(82)
Female4(17)8(18)
Eye disease/trauma5(21)8(18)
UV exposure from welding9(39)14(57)
Diabetes0 0 
Corticosteroids3(13)5(12)
Smoker8(35)16(36)

The eye examination revealed TNT-induced cataract in four exposed subjects and none in the unexposed group (Tables 2 and 3). The difference in prevalence between the two groups was statistically significant (p < 0.01; Mantel-Haenszel's chi-squared test). All TNT-induced cataracts were symmetrical and bilateral, matching Tiukina's description (Fig. 1). The TNT cataract did not cause any reduction in visual acuity. No other eye diseases were diagnosed. In this study the risk of developing TNT-induced cataract was found to be connected to working with moulding, but not to age, duration or other working processes (Table 4).

Table 2.  The TNT-exposed subjects.
Case no.SexAgeYears exposed to TNTTNT cataract
2F4725No
9M5118No
21M4418No
20M5216No
10M5215Stage 2
13M4915No
19M4915No
16F4215No
14M3914No
3F5412No
7M3812Stage 1
12M5610Stage 3
15M5210Stage 3
18F4710No
23M4610No
6M4010No
11M345No
22M444No
4M574No
1M533No
8M483No
5M542No
17M581No
Table 3.  Mantel-Haenszel's chi-squared test.
 TNT cataractNo TNT cataractTotal
  1. χ = 8.14; p < 0.01.

TNT exposed41923
Unexposed04444
Total46367
image

Figure 1. (A) Case 7, stage 1. (B) Case 10, stage 2. (C) Case 12, stage 3. (D) Case 15, stage 3.

Download figure to PowerPoint

Table 4.  Characteristics of TNT-exposed group.
 Without TNT cataract mean (range)With TNT cataract mean (range)
  1. * anova p = 0.02.

Age (years)48(34–58)50(38–56)
Years of employment18(6–31)22(15–29)
Years working with TNT11(1–25)12(10–15)
Years working with pressing3.4(0–22)2.5(0–10)
Years working with steampipe melting2.7(0–10)3(0–9)
Years working with moulding4.5(0–15)10.5(8–15)*

General health examination revealed no toxic effects from TNT. All blood samples were normal.

Discussion

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. References

We used Tiukina's description and grading of TNT cataract because it is precise and easy to use. Several uncontrolled case series of TNT-exposed workers suggest that TNT exposure causes a unique type of cataract (Kroll & Kolevatykh 1965; Tiukina 1967; Hassman & Juran 1968; Harkonen et al. 1983). The diagnostic criteria are nearly the same, but the grading scales differ to some extent.

Only one previous cross-sectional study used a control group and controlled for confounding factors (Lewis-Younger et al. 2000). Surprisingly, they found TNT-like cataract (peripheral flecks) in 14% of the presumed unexposed workers. In our opinion this may be due to misclassification of exposure and cataract. The unexposed subjects in the study were selected from the same factory, and misclassification of exposure might have taken place. Furthermore, they used a classification system that was not specific to TNT-induced cataract (LOCS III system) and might thereby have included other kinds of cataract. This is supported by the higher prevalence of cataract found in that study despite exposure levels that were probably comparable to or lower than those in our study.

The strength of our study as compared to previous studies relies on the use of a truly unexposed control group and a well described TNT cataract grading scale. The groups were comparable and there were no reasons to believe that the increased prevalence of cataract among TNT-exposed workers was caused by confounding.

We found that the prevalence of TNT-induced cataract in the exposed group was 17.4%. This result is consistent with the Chinese studies reported by Zhou (1990). Other studies have found TNT-induced cataract in about 50% of exposed subjects (Manoilova 1968; Harkonen et al. 1983). The reason for this difference in prevalence may be differences in intensity and duration of exposure.

Although our data on exposure are poor, we find that this study supports the theory that exposure intensity plays a role in the development of TNT-induced cataract, whereas we found no relation to age or duration of exposure.

By comparing the prevalence of TNT cataract in the two groups, we conclude that TNT exposure may cause a unique cataract, and that a general ophthalmologist, using Tiukina's grading scale, will be able to identify it among other cataracts without special training.

References

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. References
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