1011 ultrafiltratable (non-protein bound). The milk:serum nonprotein bound 35S activity ratio remained fairly constant during the 24 h period, being 1.05 for the carbimazole study and 0.55 for the propylthiouracil study. 320 ml of milk was collected in 24 h from the mother who received 35S carbimazole and 0.47% of the given radioactive dose was found in this volume of milk. 500 ml of milk was collected from the mother who received 35S-propylthiouracil and 0-077% of the given dose was excreted in milk in 24 h. We measured 35S activity rather than the actual concentration of methimazole or propylthiouracil because of the low dose of radioisotope used. Even if all the radioactivity were in the form of unmetabolised drug, the percentage of a given dose of either methimazole or propylthiouracil excreted in milk in 24 h seems small. Both methimazole and propylthiouracil are weak acids and breast milk is generally of a lower pH than plasma, and the pH partition theory4 would predict that the concentration of these two drugs would be lower in milk than in plasma. The percentage of a given dose of propylthiouracil excreted in milk is lower compared to that of methimazole and this can be accounted for by the difference in the protein binding of the two drugs in plasma. The advantages of breast-feeding are well known and since breast milk contains a significant quantity of thyroid hormones,5 the question of breast-feeding by mothers while on antithyroid therapy should be reviewed. Although we cannot make any definite recommendation after only two studies, we do feel that antithyroid drug therapy should not be an absolute contraindication to breast-feeding provided that the mother is on a small dose of antithyroid drug and that the circulating thyroid hormones of the baby are closely monitored. The benefits of breast-feeding have to be balanced against the risks of interference with the infant’s thyroid function and the possible haematological side-effects of these drugs.1 If mothers on antithyroid drugs do breast-feed, propylthiouracil should be preferred to carbimazole or methimazole. was

Letters

the Editor

to

EXCRETION OF CARBIMAZOLE AND PROPYLTHIOURACIL IN BREAST MILK

SiR,-Standard teaching has

it that mothers taking antishould not breast-feed.’ This advice is based on the work of Williams et al. who reported that the concentration of thiouracil in two samples of human milk was three times higher than that in whole blood taken at the same time.2 Since there is no information on the excretion of modern antithyroid drugs in milk, we present here results of a study in two lactating mothers who were given 35S-labelled propylthiouracil or carbimazole. The first patient took a single oral dose of 10 mg carbimazole containing 100 fLCi of the 35S-labelled drug and the other

thyroid drugs

University Department of Medicine, Gardiner Institute, Western Infirmary,

Glasgow G11

6NT

L. C. K. Low J. LANG W. D. ALEXANDER

COSMETIC TALC AND OVARIAN CANCER I

5

I

I

10

15

I

I

20

24

Hours after orol dose

SIR,-We would not argue with the right of Dr Roe (Oct. 6, p. 744) to place different interpretations on the data on talc.

point of our Aug. 18 article was that the data are not clear enough either to indict or to absolve talc from a role in the pathogenesis of ovarian cancer. What is disturbing is that a consultant to the cosmetic industry feels that further research on the biological effects of talc "merits little priority". We pointed out that many questions about talc are still unanswered. We hoped that the cosmetic industry would lead the search for answers. Consumers have a right to expect that manufacturers will investigate potential risks to ensure that conventional use of their proThe

358 activity in

serum

and breast milk.

(a) After 10 mg carbimazole. (b) After 100 mg propylthiouracil.

patient

took 100 mg of propylthiouracil

radiolabelled drug. Breast milk

containing

100

ILCi of

expressed mechanically at regular times over a 24 h period and blood-samples were taken at the time of breast emptying. The 35S activity in the milk and serum samples was measured by liquid scintillation counting. These samples were then subjected to ultrafiltration.3 The total 35S activity in the milk samples was lower than that of the corresponding serum samples for both drugs (figure), 35S activity being expressed as a percentage of the was

radioactive dose given per ml of serum or milk. Even though carbimazole was given to the first patient, methimazole was measured.’ Although the milk:serum ratio of the total 35S activity for the two drugs varied with time, it appeared to be directly related to the percentage of the serum 35S activity that 1. Knowels JA. Breast milk: a source of more than nutrition for the neonate. Clin Toxicol 1974; 7: 69-82. 2. Williams RH, Kay GA, Jandorf BJ. Thiouracil. Its absorption, distribution and excretion. J Clin Invest 1944; 23: 613-27. 3. Marchant B. The metabolism of 35S-antithyroid drugs. PH.D. thesis, University of Glasgow, 1971.

ducts is not hazardous. How is adherence to the Cosmetic Toiletry and Perfumery Association’s voluntary guidelines for making asbestos-free talc monitored? We hope that the opinion of this consultant to the C.T.P.A. is not widespread in the industry ; if research on talc risks merits little priority in the cosmetic industry, the scientific community and the consumer cannot drop the discussion with the confidence that more is likely to be done. Talc is known to elicit potent inflammatory responses in man when found in the lungs, pleural cavity, and peritoneal 4. Williams V, Shirkey HC. In: Avery GS, ed. Drug treatment: Principles and practice of clinical pharmacology and therapeutics. Edinburgh: Churchill Livingstone, 1976: 83-89. 5. Bode HH, Vanjonack WJ, Crawford JD. Mitigation of cretinism by breast feeding. Pediatrics 1978: 62: 13-16.