Eye Findings in Goats during the 3 Years after Acute Whole-body Neutron and Gamma Irradiation

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INT. J. RADIAT. BIOL., 1967, VOL. 13, NO. 2, 147-153 Eye findings in goats during the 3 years after acute whole- body neutron and gamma irradiation P. W. EDMONDSON and A. L. BATCHELOR Medical Research Council, Radiobiological Research Unit, Harwell, England and J. P. F. LLOYD Oxford Eye Hospital, Oxford, England (Received 9 August 1967) Goats which survived single whole-body exposures in the lethal range were examined at intervals up to 3 years after exposure. Only 2 out of 28 goats receiving fission neutron radiation showed changes in the lens. No radiation- induced lens changes were found after gamma radiation. The low incidence of cataract is similar to that found in dogs and primates exposed to fission neutrons and in human survivors from atomic bombing. There is a systematic change according to body size in the sensitivity of the lens to neutrons. 1. Introduction Cataract is the principal hazard to be considered when determining the maximum permissible dose-rate for exposure of the eye to radiation. In this special case, not only is a quality factor (QF) used as in all other tissues, but when the QF is 10 or greater an additional modifying factor of 3 is employed, as for instance when considering fission neutrons. There is abundant infor- mation on cataract induction in small laboratory animals (Upton, Christenberry, Melville, Furth and Hurst 1956, Bateman, Bond and Rossi 1964), and in this experimental work the RBE for fission neutrons in comparison with x- and gamma-rays has been in the range 3-9. There is little supporting evidence about the RBE of fast neutrons in large animals or indeed about their suscepti- bility to cataract formation. It therefore seemed worthwhile to report some largely negative observations on the lenses of goats exposed to whole-body irradiation by fission neutrons or gamma-rays. 2. Materials and methods The neutrons and gamma-rays employed were of mean energies 0.7 and 2.5 MeV respectively. The sources of radiation, the manner of exposure, the dosimetry and animal husbandry have been described elsewhere (Batchelor and Edmondson 1964). At the time of irradiation the goats were aged between 2 and 3 years and ranged in weight from 120 to 200 pounds. Twelve unirradiated goats of the same sex and comparable in age and size were used to establish the appearances normally encountered in the goat. The lens of the goat is quite unexpectedly easy to see in its entirety either by retro-illumination with the ophthalmoscope viewing through a + 10 or + 12 lens or by focal illumination using a binocular loupe. The pupil stays wide even under illumination, and by either method the equator of the lens can be viewed throughout all meridia except for a small sector above. In some Int J Radiat Biol Downloaded from informahealthcare.com by University of Melbourne on 11/23/14 For personal use only.

Transcript of Eye Findings in Goats during the 3 Years after Acute Whole-body Neutron and Gamma Irradiation

Page 1: Eye Findings in Goats during the 3 Years after Acute Whole-body Neutron and Gamma Irradiation

INT. J. RADIAT. BIOL., 1967, VOL. 13, NO. 2, 147-153

Eye findings in goats during the 3 years after acute whole- body neutron and gamma irradiation

P. W. E D M O N D S O N and A. L. B A T C H E L O R

Medical Research Council, Radiobiological Research Unit, Harwell, England

and J. P. F. L L O Y D

Oxford Eye Hospital, Oxford, England

(Received 9 August 1967)

Goats which survived single whole-body exposures in the lethal range were examined at intervals up to 3 years after exposure. Only 2 out of 28 goats receiving fission neutron radiation showed changes in the lens. No radiation- induced lens changes were found after gamma radiation. The low incidence of cataract is similar to that found in dogs and primates exposed to fission neutrons and in human survivors from atomic bombing. There is a systematic change according to body size in the sensitivity of the lens to neutrons.

1. Introduction Cataract is the principal hazard to be considered when determining the

maximum permissible dose-rate for exposure of the eye to radiation. In this special case, not only is a quality factor (QF) used as in all other tissues, but when the Q F is 10 or greater an additional modifying factor of 3 is employed, as for instance when considering fission neutrons. There is abundant infor- mation on cataract induction in small laboratory animals (Upton, Christenberry, Melville, Fur th and Hurs t 1956, Bateman, Bond and Rossi 1964), and in this experimental work the RBE for fission neutrons in comparison with x- and gamma-rays has been in the range 3-9. There is little support ing evidence about the RBE of fast neutrons in large animals or indeed about their suscepti- bility to cataract formation. It therefore seemed worthwhile to report some largely negative observations on the lenses of goats exposed to whole-body irradiation by fission neutrons or gamma-rays.

2. Materials and methods

The neutrons and gamma-rays employed were of mean energies 0.7 and 2.5 MeV respectively. T h e sources of radiation, the manner of exposure, the dosimetry and animal husbandry have been described elsewhere (Batchelor and Edmondson 1964). At the t ime of irradiation the goats were aged between 2 and 3 years and ranged in weight from 120 to 200 pounds. Twelve unirradiated goats of the same sex and comparable in age and size were used to establish the appearances normally encountered in the goat.

The lens of the goat is quite unexpectedly easy to see in its entirety either by retro-i l lumination with the ophthalmoscope viewing through a + 10 or + 12 lens or by focal illumination using a binocular loupe. Th e pupil stays wide even under illumination, and by either method the equator of the lens can be viewed throughout all meridia except for a small sector above. In some

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animals this sector could not be seen, since the animal's nose got in the way of the observer's head. A mydriatic or anaesthetic agent was never needed. As examination with a full-scale slit lamp would have entailed the use of a general anaesthetic, this was not done. When a hand-held slit lamp was used, it proved very difficult to keep the observer 's head, the microscope and the animals' head in alignment, and the amount of illumination available was not satisfactory. The easily and widely manoeuvrable binocular loupe (magnifi- cation × 2) and focusing pen- torch with a 2 v bulb over-run by a 2.2 V ' N i - C a d ' battery provided a superior view, and despite the lower magnification available this method was adopted as standard. A strict rule was made that no appearances should be noted or even queried as abnormal unless it was felt that they could be recognized again at subsequent examinations.

3 . R e s u l t s

Data concerning the irradiated animals and the times after exposure at which their eyes were examined are shown in table 1. I t is stressed that all radiation doses quoted refer to the dose in air in the middle of the empty con- tainer (Batchelor and Edmondson 1964). Radiation doses to the lens were neither measured nor estimated.

Radiation and dose

Neutrons Gamma 0.7 MeV 2'5 MeV

(rad) (R)

633 600

500-566 533

400-466 400-466

300-366 300-346

200 200-266

100

Number of

animals exposed

2 4

16 2 5 7 3 8 1

2 1

Number of eyes exposed and the intervals after exposure at which they were examined

Days Months

1 - - - ~ - - - ~ V 7 - ~ 2-f~-36 3' '3

1 2

4 2 - - 9 11 13 5

- - % % 110 8 6 - - 1 6 3 7 3

- - - - - - 6 2 4

- - 2 6 12 10 2

. . . . 2 2 - - - - - - 2 4 4

. . . . 1 1

Table 1. Dose of radiation, time after exposure and number of goat eyes examined. When animals were irradiated unilaterally only the eye on the side irradiated is included.

In our goats the L D 50/30 for single bilateral whole-body exposures was 505 rads neutrons and 395 rads gamma (Edmondson and Batchelor 1966), and the L D 50/30's for unilateral exposure were only a little greater (unpublished observations). Thus all but 7 of the 51 irradiated goats examined were survivors f rom potentially killing doses, and 31 had survived doses equal to or in excess of the L D 50/30 (table 1).

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Response of goat lens to neutrons and gamma rays 149

3.1. Findings common to both control and irradiated goats

The lens appeared quite clear when viewed co-axially on retro-illumination, and the frequent presence on the cornea of foreign bodies such as dust and chaff was easily recognized, By viewing obliquely the edge of the lens and the site of the zonule were seen easily. Viewed at this angle the equator, by refraction, showed normally a partial ring clearest at the apex of the observed area. To the central or axial view quite a number of eyes presented a varying appearance of 'nucleus hyper-refringens '. Normally the sutures were not visible by retro-illumination.

By focal illumination the ' shagreen ' of both anterior and posterior capsules were readily observed, the latter showing an irregular pattern. There seemed to be a wide variation in the prominence of both the anterior and posterior sutures. Superficial corneal opacities varying in extent were seen in a few cases, in two instances accompanied by vascularization. Some of these opacities appeared to remain stationary, others to regress over the period of observation. In-turned lashes were seen a number of times, and sometimes they caused superficial corneal opacities. In only a few instances did the corneal opacity preclude an adequate view of the lens.

The eyes of goats, in common with those of many animals in captivity, almost always appeared to carry on their surfaces varying numbers of foreign bodies.

3.2. Findings in irradiated goats not found in unirradiated controls but not considered to be the consequence of irradiation exposure

Two of the goats which had been exposed to neutrons showed abnormalities which were judged to be developmental, in one goat circular plaque opacities about 5 mm in diameter were seen in the posterior capsule of each eye. They were almost symmetrical and showed no change at the four examinations made over a 30-month period. The second animal showed very prominent posterior sutures in both lenses with a ' duplicated ' appearance of the suture line. These appearances did not change in the 2 months which elapsed between examinations.

A partially dislocated lens with much coarse pigment deposited on the anterior surface was seen in a third neutron-irradiated animal. This abnormality was considered to be the consequence of trauma.

3.3. Ocular changes which were considered to result Jrom radiation exposure

Radiation-induced ocular changes were found only in two goats. Both of these had been exposed to neutrons, one receiving a bilateral whole-body exposure to 466 rads and the other a unilateral left-sided exposure to 566 rads. The eyes of the former were examined at 2, 23, 36 and 40 months after irradiation. The first and last examinations revealed no abnormalities, but on the occasion of both the second and third examinations there was a ring of opacities at the equator of each lens which was thought to be the consequence of radiation exposure. The other animal, which had been irradiated on the left side only, was examined at 8, 10 and 14 months. The right eye was normal on each occasion. Two abnormalities were seen in the left eye. An irregularly-shaped area of opacity averaging 5 mm in diameter was originally seen on the anterior

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capsule. This was first thought to consist of remnants of embryonic mesodermal tissue and to be a developmental abnormality. However, at 10 months the lens of this eye showed vacuolation in the equatorial region together with fine crystalline-looking opacities, and by 14 months very extensive opacification was present. The entire posterior sub-capsular region had become almost completely opaque, and the anterior sub-capsular opacity had spread materially with marked vacuolation. The whole substance of the lens was hazy, especially around the sutures. Corneal scarring, assumed to originate from keratitis which had been observed initially, was present but quiescent. The sensitivity to touch of the corneas (corneal reflex) was apparently unimpaired.

4. Discussion

It is commonly supposed that the lens is very sensitive to neutrons. Experi- mental information concerning the effects of neutrons, x- and gamma-rays on the optic lens is collected in table 2, where the LD 50/30 for whole-body exposure is also given for purposes of comparison.

The data in table 2 indicate that detectable lens changes in small animals can be induced by a single sub-lethal whole-body exposure to x- or gamma-rays. However, in dogs, monkeys, goats and man the dose must be in the lethal range. Furthermore it would seem that to induce a more severe grade of cataract sufficient to interfere with vision, whole-body doses of x- or gamma-rays will have to be much in excess of the 50 per cent killing dose in each of these species.

The reported RBE for the induction of visible damage to the lens when fission or 1-2 MeV neutrons are compared with low-LET radiation ranged from 3 to 9 in small animals (table 2). Even so, the neutron dose required to produce a severe grade of cataract in large animals has not been lower than the LD 50. In adult dogs Moses, Linn and Allen (1953) in a 2-year follow-up did not detect changes in the lens after exposures to fast neutron doses from 60-150 N (150 to 375 rads) though ' some vacuolization ' was seen in the lenses of young dogs. In monkeys, Pickering, Williams Melville McDowell, Leffingwelt and Zellmer (1960) found the threshold dose for the induction of minimal lens changes by fission neutrons to be 150 rads to the whole-body. Only one of our own goats surviving acute neutron exposures equal to or in excess of the LD 50 has so far developed gross cataract, and only one other has shown transient early signs of radiation injury to the lens. In fact only one report has been found which suggests that even minimal lens changes can be produced by sub-lethal exposures, that of Brown (1960). He irradiated monkeys with 14 MeV neutrons and reported observations at about 6 years after irradiation, a somewhat longer period than that employed by other workers, including ourselves. The lens changes observed were viewed with the ophthalmoscope but were of a degree unlikely to interfere with vision. Even with 14 MeV neutrons and monkeys, however, it was still true that a whole-body dose in the lethal range was required to produce lens opacities of a degree sufficient to interfere with vision.

Information on the effects of neutrons on the human lens is not abundant. The dose received by humans exposed accidentally or occupationally was not measured at the time, and estimates of either the whole-body or lens dose can only be approximate. Cogan, Martin and Kimura (1949) found no cataracts

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in 948 Japanese who were in the open and between 1 and 2 kilometres away from the hypocentre of atomic bomb explosions. The estimated radiation doses at these ranges, ignoring shielding, are neutrons 0.1 to 192 rads and gamma 2 to 903 fads (Auxier, Cheka, Haywood, Jones and Thorngate 1966). At smaller distances from the hypocentre there were only five radiation cataracts in 231 Japanese (Cogan et al. 1949). Each of these five people had total epilation of the scalp and a history of other signs of severe exposure to radiation. Examin- ations at a much longer interval after exposure were made by Masuda (1967). Lens opacities attributed to the bomb were found in 8-7 per cent of 1101 survivors and lens opacities suspected to have been caused by the bomb were found in a further 11 per cent. The highest incidence of definitely attributable cataract, 19.6 per cent, was in those with a history of epilation. The corres- ponding incidence in Japanese who had "never experienced the atomic bomb" was 9.5 per cent. It is important to note that none of the lens changes seen by Masuda (1967) were of a degree sufficient to require visual correction. The human evidence therefore supports the conclusion of Picketing and Brown (1959) that " t h e localized neutron dose required to produce significant numbers of opacities is greater than, or certainly approaches if administered whole body, the radiation dose considered to be the t,l~'3o for man " ~ 5 0

Ham (1953) surveyed all that was known at the time about the induction of cataract by neutrons and, basing his conclusions very largely on cataract induction in cyclotron workers, considered that " 10 to 20 rep of fast neutrons must be regarded tentatively as sufficient dose to induce lens opacities which may interfere with eyesight". From that time it became generally accepted that the human lens is particularly sensitive to fast neutrons. However in 1953 Ham had recognized that the estimates of neutron dose in the cyclotron workers were " little more than educated guesses " and more recently (Ham t960) he revised his conclusions thus: " it would seem wise to regard a cumulative dose of 75-100 rads as likely to approach the threshold for cataract in man ". There remains nevertheless a marked discrepancy between this conclusion and the fact that in the Japanese survivors the dose necessary to produce cataracts of a degree sufficient to interfere with vision was large enough to be epilatory.

With increasing body-size there appears to be a progressive decrease in lens sensitivity to neutrons (table 2). It may be pertinent that increasing body-size is paralleled by a progressive decrease in the proportion of the eye volume which is taken up by the lens.

ACKNOWLEDGMENTS

We wish to record our indebtedness to Dr. R. H. Mole who planned and guided this investigation and provided much constructive criticism. We wish to thank Mr. II. C. Binstead who, through Messrs. Clement Clarke, kindly lent us the hand-held slit lamp.

Des ch~vres qui avaient surv6cu h une exposi t ion un ique du corps ent ier fi des doses mortel les fu ren t examin6es h des interval les al lant j u s q u ' h trois ans apr~s exposit ion. Seule- m e n t deux des 28 ch~vres qui avaient re~u une i r radiat ion de neu t rons de fission m o n t r ~ r e n t des changemen t s dans la lentille. O n ne t rouva aucun c h a n g e m e n t de la lentille indu i t pa r le r a y o n n e m e n t apr~s l ' i r radia t ion gamma. La faible incidence de cataracte est semblab le fi ceUe q u ' o n t rouve chez les chiens et les p r imates expos6s fi des neu t rons de fission ainsi que chez les survivants d ' u n b o m b a r d e m e n t a tomique. I1 y a une var ia t ion sys t6mat ique de la sensibilit6 de la lentille au r a y o n n e m e n t selon la g randeur du corps.

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Response of goat lens to neutrons and gamma rays 153

Ziegen, die einer einzelnen Bestrahlung des ganzen K6rpers innerhalb t6dlicher Grenzen ausgesetzt waxen, wurden yon Zeit zu Zeit in Zwischenr~iumen bis zu drei Jahren nach der Bestrahlung untersucht. Nur zwei aus 28 Ziegen, welche Bestrahlung mit Spaltungs- neutronerl erhalten hat-ten, zeigten Ver~inderungen der Linse, jedoch keine nach Gamma- Bestrahlung. Das seltene Auftreten von Katarakt ist ~ihnlich wie dies bei Hunden und Primaten, die Spaltungsneutronen ausgesetzt wurden, und bei ~berlebenden von Atombomben gefunden wurde. Es besteht eine systematische Anderung der Bestrahlungs- empfindlichkeit der Linse im Verh~iltnis zur K6rpergrol3e.

REFERENCES

ALLEN, R. G., Jr., BROWN, F. A., LocIE, L. C., ROVNER, D. R., WILSON, S. G., Jr., and ZELLMER, R. W., 1960, Radiat. Res., 12, 532.

AUXIER, J. A., CHEKA, J. S., HAYWOOD, F. F., JONES, W. D., and THORNGATE, J. H., 1966, Hlth Phys., 12, 425.

BATCHELOR, A. L., and EDMONDSON, P. W., 1964, Biological Effects of Neutron and Proton Irradiations, 2, 3 (Vienna: International Atomic Energy Agency).

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