Lead poisoning in jewellery enamellers in Birmingham has been described both at the beginning of this century and again in recent years. The condition arises from the habit of some workers of placing the enamel applicator in the mouth. The history of the hazard is reviewed and an investigation described.

The absorption of ethylbenzene through the skin of the hand and the forearm in men was investigated experimentally. Both the absorption of liquid ethylbenzene and the absorption from aqueous solutions were studied. The rate of absorption of liquid ethylbenzene was 22 to 33 mg./cm.2/hr, and the rates from aqueous solutions were 118 and 215 μg./cm.2/hr from mean concentrations of 112 and 156 mg./litre.

The mandelic acid excreted in urine was equivalent to about 4·6% of the absorbed dose—much less than after lung absorption. Urinary mandelic acid does not provide a reliable index of absorption when there is simultaneous skin and lung exposure.

In order to characterize further the minialbumins (molecular weight 5,000 to 20,000) found in cadmium-poisoned men and animals, the tryptophan content of albumins found in the serum and urine of cadmium-poisoned monkeys was measured by two methods and compared with that of serum albumin (molecular weight 66,000) of normal animals. Normal serum albumin of the monkey was found to contain 2 residues of trytophan per molecule of the protein, whereas all albumins in the poisoned monkeys, whether of normal size or low-molecular weight, contained less tryptophan, this amino acid being absent entirely in the minialbumins of both serum and urine. Serum albumin of the usual molecular weight (66,000) in the cadmium-poisoned monkeys contained approximately 30% less tryptophan than its normal counterpart in untreated animals.

Taken in conjunction with previous observations on the behaviour of minialbumins, which aggregate readily in low-salt media including isotonic saline, it is concluded that approximately 30% of the circulating serum albumin in the poisoned monkeys arose by aggregation of minialbumin molecules. On the basis of the close similarity in amino acid composition, in nearly all other respects, between the various albumins, it is suggested that minialbumin comprises a mixture of peptides derived by fission of the normal albumin molecule along its whole chain length, and that subsequently a peptide containing both tryptophan residues is either deleted metabolically or excluded in the preparation procedures.

Breakdown of ethylene glycol dinitrate (EGDN) in blood in vitro results in the liberation of inorganic nitrite and ethylene glycol mononitrate (EGMN). The nitrite is oxidized to inorganic nitrate but the EGMN is more resistant to further degradation.

Similar metabolites are produced during the metabolism of EDGN in vivo. The nitrate is excreted in the urine and accounts for 60% of the injection. The EGMN released is almost completely metabolized, since only 1·5% of the injection can be detected as EGMN in the urine. Breakdown of EGMN in vivo is confirmed when the compound is injected; less than 0·5% is recovered as EGMN in the urine. Nitrite is released and oxidized to nitrate which is then excreted in the urine and accounts for 57% of the injection.

An injection of EGDN or EGMN causes a fall in blood pressure lasting several hours, EGDN being more effective. Since the fall in blood pressure and the concentrations of EGDN and its metabolites in the blood have been determined simultaneously, a correlation between blood pressure and blood concentrations has been attempted. It is suggested that the fall in blood pressure after an injection of EGDN could be the resultant of the actions of EGDN, EGMN, and nitrite. The initial fall in blood pressure may be due to the intact molecule of EGDN followed in turn by the effects of nitrite and EGMN released during the breakdown of the EGDN molecule.

In experiments on mice, rabbits, and piglets the distribution of uranium was studied at different times after exposure. Uranium was administered by inhalation (mice) and through the skin (rabbits and piglets).

These investigations show that the uptakes of uranium in different organs of the three species are highly dependent on the amounts administered. There seems to be a saturation effect in the spleen and bone tissue whenever the uranium concentration in the blood exceeds a certain level. The effect in the kidney is completely different. If, in a series of animals, the quantity of uranium is continuously increased, the uptakes by the kidneys increase more rapidly than the quantities administered. This observation seems to be consistent with the toxic effects of uranium on the capillary system in the renal cortex.

Polyphloretin phosphate, a compound which reduces permeability, was investigated with respect to its effect on the uptake of uranium deposited in skin wounds in rabbits and piglets. It significantly reduced the absorption of uranium, even from depots in deep wounds.

The findings are discussed with reference to the routine screening of persons exposed to uranium at AB Atomenergi.

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The distribution of uranium in mice following intravenous and intraperitoneal injections of uranyl nitrate and uranyl tricarbonate was studied by autoradiographic and fluorometric methods at different times after administration. The investigations revealed a higher retention of uranium in the spleen and bone than in other organs, including the kidneys.

We have been able to show that even very small amounts of uranium give rise to ischaemia in the kidney. A higher initial uptake was found in the juxtamedullary zone than in the more peripheral parts of the renal cortex. The retention, however, was higher in the peripheral cortex. This may explain the fact that the first observable damage in the kidney appears in the juxtamedullary zone. The connexion between blood supply and uranium uptake and retention in different zones of the renal cortex is discussed with special regard to the toxicological consequences of uranium incorporation and to the possibility of accelerating the excretion of uranium.

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This investigation was undertaken primarily to examine the possibility of hearing damage from industrial ultrasonic equipment. In the factory concerned, ultrasonic washers and drills were used at a number of different locations, and girls working 12 ft (3·6 m.) away from one bank of three small washers complained of unpleasant subjective effects which included fatigue, persistent headaches, nausea, and tinnitus.

As personnel working in the vicinity of similar washers in other parts of the factory did not complain of these effects, it seemed possible that the noise had been transmitted along a column of air in a bank of dryboxes. Enclosure of these washers by a sliding screen of Perspex had completely abated the trouble.

Sound pressure level measurements taken in the positions occupied by the operators indicated that, when the effects occur, they are probably caused by high sound levels at the upper audio-frequencies present with the ultrasonic noise, and this was supported by a limited laboratory investigation. Audiometric investigation showed that hearing damage due to noise from these industrial ultrasonic devices is unlikely. However, extrapolations of currently accepted hearing damage risk criteria may be valid in predicting the occurrence of these subjective effects.

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Urinary δ-aminolaevulinic acid (ALA) is commonly estimated by the method of Mauzerall and Granick (1956). In that method porphobilinogen (PBG) and ALA are successively separated from the urine by ion exchange resins.

A simplified procedure, omitting the initial separation of PBG, was investigated. Urine samples from 39 lead workers and controls were estimated for ALA by both the original procedure and by this simplified procedure. A correlation coefficient of 0·99 was obtained.

It was concluded that the simplified procedure may be used for screening lead workers so long as the possibility of false high readings is borne in mind.

Some sources of variation in standardizing the original procedure are also discussed.

A dry ashing method is described for the determination of lead in whole blood. Within the range of 16-200 μg. lead per 100 ml. blood recoveries were 82 to 100%. The method agreed with a standard wet method and is more convenient. Possible sources of error and the uses of the ashing aid are discussed.

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The output of δ-aminolaevulinic acid (ALA) and of creatinine was determined in lead workers. Values from 24-hour specimens were compared with values from specimens voided at the time of examination. Highly significant positive correlations were found between the output of ALA and of creatinine in both sets of specimens. The individual spreads, however, were considerable.

Values for ALA in mg./100 ml. urine and ALA in mg./g. creatinine were strongly correlated in fresh specimens as well as in 24-hour specimens. When values for ALA in mg./100 ml. urine were compared with ALA in mg./g. creatinine, an approximate relationship of 1:5 was found in the range 1.0-3.0 mg. ALA/100 ml. urine, i.e., the mean urinary concentration of creatinine was 0.2 g./100 ml.

It is concluded that the collection of 24-hour specimens is not necessary and also that reference to creatinine appears to have no advantage over the simple expression of ALA in mg./100 ml. urine. This must be due to the fact that the influence of the metabolic activities of lead has a greater effect on the urinary concentration of ALA than has the concentration of urine in the kidneys.

In 16 workers with lead poisoning of varying degrees, a comparison was made between the therapeutic efficacy of sodium calciumedetate (Ca-EDTA) and penicillamine (PCA), administered intravenously and orally. The question of comparable dosages of ligands, forming metal complexes in different ways, is discussed. With the dosages given, intravenous Ca-EDTA promoted the greatest output of lead in the urine, followed by intravenous and oral PCA. These three agents also had a very satisfactory effect on the output δ-aminolaevulinic acid (ALA) in urine. Oral Ca-EDTA was found to be greatly inferior in both these respects.

In order to study the absorption of the agents and the renal excretion of the formed lead complexes, the urine was collected quantitatively and fractionated in consecutive 4-hour periods, after which the lead excretion during each period was determined. It was found that the oral absorption of PCA was rapid and quantitatively great, whereas the oral absorption of Ca-EDTA was very slow and quantitatively small. The possible resorption of ligand-lead complexes is discussed and indications were found of resorption of the Ca-EDTA-lead complex but not of the PCA-lead complex. The renal excretion of the different ligand-lead complexes was very effective and reached its maximal level within four hours. However, in some subjects excretion of the Ca-EDTA-lead complex showed some delay. An investigation, in four subjects, of a blocking effect of probenecid on the renal excretion of PCA and/or PCA-lead complexes gave no conclusive results. It is concluded that oral PCA is satisfactory in most cases of lead poisoning. However, in more severe cases intravenous treatment is preferable. Which agent should be chosen, Ca-EDTA or PCA, appears to be unimportant as both are quite satisfactory from the point of view of treatment, but it seems that Ca-EDTA may cause more serious side-effects. Oral Ca-EDTA is quite unsatisfactory and there is good evidence to indicate that the agent causes a resorption of Ca-EDTA-lead complexes from the gastro-intestinal tract.

The management of the mine at Mount Isa, Queensland, Australia decided to enquire into the following questions with regard to men working underground in hot conditions:

(a) Which of the various heat stress indices predicts most accurately the effects on workmen of the various heat stress factors which occur in the mine at Mount Isa?

(b) How best should the limits of heat stress be judged at which the normal 8-hour shift should be reduced to a 6-hour shift, or at which work should be stopped?

With these objects in mind, oral temperatures were measured on 86 workmen after three hours of ordinary work in the mine and also on 36 occasions on 29 volunteers after three hours of stepping on and off a stool at a work rate of 1,560 ft. lb./min. These men were studied in different environmental heat stresses over the range that occurs in the mine. Dry bulb air temperatures (D.B.), wet bulb temperatures (W.B.), velocity of air movements, and globe temperatures (G.T.) were measured in the micro-climate in which each man worked. An estimate was made of the work rate of the 86 workmen. From these estimates and measurements, the predicted 4-hourly sweat rate (P4SR) and corrected effective temperature (C.E.T.) values were determined for each heat stress condition. P4SR values varied between 0·9 and 6·5 and C.E.T. between 70° and 95°F.

Correlation coefficients were calculated between oral temperatures and W.B.s, C.E.T.s, and P4SRs and are 0·51, 0·64, and 0·75 respectively. Further analysis was confined to C.E.T. and P4SR. Plots of oral temperature on P4SR for conditions where G.T. was more than 10°F. above D.B. were found to fall well below the rest of the plots, indicating that P4SR exaggerates the effect of mean radiant temperature. These data were therefore excluded from the rest of the analysis. Regression equations were calculated for oral temperature on P4SR and for oral temperature on C.E.T. for (a) men `on the job', for (i) conditions where D.B. was more than 10°F. above W.B. and (ii) for conditions where D.B. was less than 10°F. above W.B., and (b) for men `stepping'. This analysis showed that one overall regression line can be used for all three conditions for oral temperature on P4SR, but for oral temperature on C.E.T. at least two different regression lines would be needed. Also the correlation coefficients between oral temperature and P4SR were generally higher than between oral temperature and C.E.T. For the prediction of oral temperature in the mine at Mount Isa the P4SR index is to be preferred to the C.E.T. scale.

These results indicate that the emphasis given to G.T. in the P4SR index is too great. A multi-variance analysis of the P4SR index shows that, in the middle of the range of heat stress conditions examined, a unit change in P4SR would be obtained by about the same change in W.B. and G.T. This is at variance with the present results and also with the experimental findings of the M.R.C. Climatic Physiology Unit at Singapore. It appears, therefore, that the P4SR index should be revised in this regard.

When it came to setting limits of heat stress for a 6-hour shift and for `stop-work', it was decided to base the limit for the 6-hour shift on a 1:100 probability of men reaching an oral temperature of 100·5°F. (rectal temperature of 101·5°F.) and to base the `stop work' limit on a 1:2,000 probability of reaching an oral temperature of 101·5°F. (rectal temperature of 102·5°F.). The reasons for this choice of physiological criteria are given in full in the paper. P4SR values at which these limits are reached were determined by calculating 1:100 and 1:2,000 probability belts to the overall regression line of oral temperature on P4SR. The P4SR value at the intersection of the 1:100 probability limit and the oral temperature of 100·5°F. is 3·8 and the P4SR value at the intersection of the 1:2,000 probability limit and the oral temperature of 101·5°F. is 5·0. These then are the limits of heat stress in the mine at Mount Isa for a 6-hour shift and for `stop-work'.

A simple graphical method has been developed and is in use in the mine for determining when the level of work and environmental heat stress have reached either a P4SR value of 3·8, when the shift is reduced to six hours; or, when the heat stress has reached a P4SR value of 5·0, when work is stopped.