Health effects due to inhalation of oilseed rape emissions

THE LANCET

COMMENTARY

Indications for investigation of suspected precocious puberty (1) Girls with pubic hair or breast development before age 6 yr (2) Boys with any sign of puberty before age 7 yr (3) Boys before age 9 yr and girls before age 8 yr with any sign of puberty who appear to be developing more rapidly than is usual or who exhibit an acceleration in linear growth or skeletal maturation (4) Boys or girls with contrasexual precocious puberty (development appropriate for opposite sex) (5) Boys with signs of precocious puberty without testicular enlargement

is indicated. If gonadotropins are low, luteinisinghormone-releasing hormone (LHRH) (100 µg subcutaneously) may be given and gonadotropins measured 45 min later.5 If the response to that test is pubertal, treatment with an LHRH analogue should be given; such therapy preserves adult height only if it is started before skeletal maturation has advanced significantly.6

M Joycelyn Elders, Carla R Scott, J Paul Frindik, Stephen F Kemp University of Arkansas for Medical Sciences, Arkansas Children’s Hospital, Little Rock, AR 72202-3591, USA 1

but boys are probably entering puberty at an earlier age too. The physical picture of puberty has been changing quickly and society’s views must now catch up. Previously, the onset of menses signalled a young woman’s readiness for marriage; as menarche came earlier in life, it signalled readiness for dating. Today the girl may be only aged 9 or 10. Are schools ready to counsel girls at such a young age? Are parents prepared? Girls do not get education about sexual contact early enough. In almost all teenage pregnancies the father is an adult,3,4 so men need to understand that girls entering puberty today are not emotionally ready to behave as women. Public-health policies need to protect children and provide the education and services required to prevent early pregnancies and sexually transmitted diseases. We cannot go back to the “good old days” and leave to chance the education of children in respect to the development of their bodies. And it is sensible also to revise views of the circumstances in which apparent precocious puberty merits investigation. The purpose of investigating precocious puberty is to distinguish between conditions that are benign (precocious thelarche or precocious adrenarche) and those that require treatment (gonadal tumour, congenital adrenal hyperplasia, or central precocious puberty); to forestall premature epiphyseal closure; and to prevent the very young child from having to face the psychosocial issues associated with puberty. Most children seen by primary-care physicians will not require extensive evaluation. The indications for investigations are set out in the panel. In girls with breast development only, and with no acceleration of growth or skeletal maturation (precocious thelarche), the physician should inquire about a history of exposure to exogenous oestrogen and check serum luteinising hormone, follicle-stimulating hormone, and oestradiol concentrations, as well as bone age. Pelvic ultrasound can be considered if the laboratory tests are abnormal. If there is precocious adrenarche—ie, girls or boys with early pubic hair but without acceleration of growth or skeletal maturation—a history of exposure to exogenous androgen needs to be sought, testosterone dehydroepiandrostane (or its sulphate) and possibly androstenedione measured, and bone age determined. If signs of precocious puberty in a girl or boy are associated with accelerated growth and bone maturation, the physician should inquire about a history of exposure to an exogenous sex steroid and should check gonadotropin and sex-steroid concentrations. If gonadotropins are pubertal, a magnetic resonance scan of the hypothalamus 458

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Herman-Giddens ME, Slora EJ, Wasserman RC, et al. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the pediatric research in office settings network. Pediatrics 1997; 99: 505–12. Cutler GB Jr. Precocious puberty. In: Hurst JW, ed. Medicine for the practicing physician, 2nd ed. Boston: Butterworth, 1992: 577–81. Alan Guttmacher Institute. Sex and America’s teenagers. New York: Alan Guttmacher Institute, 1994. Males MA. Adult involvement in teenage childbearing and STD. Lancet 1995; 346: 64–65. Eckert KL, Wilson DM, Bachrach LK, et al. A single-sample, subcutaneous gonadotropin-releasing hormone test for central precocious puberty. Pediatrics 1996; 97: 517–19. Oerter KE, Manasco P, Barnes KM, Jones J, Hill S, Cutler GB. Adult height in precocious puberty after long-term treatment with deslorin. J Clin Endocrinol Metab 1991; 73: 1235–40.

Health effects due to inhalation of oilseed rape emissions Allergy to inhalable particles emitted from oilseed rape among people living in close vicinity to rape crops has been a concern the UK, so late last year the UK Medical Research Council’s Institute for Environment and Health held a workshop on this issue based on a systematic review of the literature. A report1 has now been published. The conclusion that “only a few, mainly atopic, individuals in populations which are in close proximity to oilseed rape are likely to be affected and there appears to be no exceptional public health problem in comparison with responses to other pollen allergen sources” is well justified but deserves some additional considerations. There are four main species of Brassica cultivated for their oils. In Europe the most cultivated spice is B napus L, commonly known as oilseed rape. The oil extracted from rape has different uses, ranging from being a foodstuff for human beings to use in industrial production of photographic products and cosmetics. In 1996 Germany, France, and the UK were the largest cultivators of oilseed rape in Europe: Germany had about 1 million hectares under cultivation, about twice as much as in the UK..1 The area under cultivation has greatly increased during the past 20 years as a result of European Community subsidies. As pointed out by Hemmer et al,2 despite 20 years of increasing production and industrial use, only a few studies have been conducted on oilseed-rape allergy, most of them in the UK. The results of these studies have shown that a proportion of people living in close proximity to rape crops is likely to be sensitised and/or have respiratory and irritative symptoms. In most studies a sample of individuals with allergic or respiratory symptoms living in the vicinity of rape crops has been assayed for allergy to oilseed rape, either by skin

Vol 350 • August 16, 1997

THE LANCET

COMMENTARY testing or by RAST. Rape sensitisation has been confined mostly to atopic individuals, the rates of sensitisation among selected groups of atopics ranging from 26% in Dundee3 to 5% (4/81) in a study of children in Aberdeen.4 The only study assessing a well-defined large general population was conducted by Soutar et al in Scotland and it showed that, among individuals with symptoms related to the flowering seasons of rape, 41% were atopic and about 10% of them showed sensitisation to oilseed rape.5,6 Whether sensitisation to rape has a clinical expression is a different question. Fell et al7 have shown that a nasal provocation test based on oilseed rape extract was negative in 4 non-symptomatic, non-atopic controls but was positive all 5 symptomatic people sensitised to oilseed rape. In the Soutar study5 Grampian, an area in Scotland, with large crops was compared with an urban area with no apparent exposure. In the rape-exposed area the excess risk of seasonal symptoms in the general population in spring varied from 1·2% for cough to 2% for headache, with no increased risk for rhinitis (derived from table 4 in reference 5). If the association between seasonal cough and headache and exposure is assumed to be causal, an assumption that is still premature, then seasonal effects due to rape exposure could have affected up to about 2% of the general population. In favour of a true association is the fact that, among those in Grampian with symptoms in May and June, 75% showed an increased bronchial responsiveness during the rapeflowering season, compared with 47% of those without seasonal symptoms (p<0·001).6 Since only two individuals were found to be allergic to oilseed rape, the authors raised the possibility that other allergens or other chemicals released by the rape crops may be important. Many different volatile organic compounds have been identified in the emissions from rape crops, and some of these compounds may be involved in some of the symptoms reported.8 An important finding in the study by Fell et al7 was that the prevalence of rape allergy may be high in occupationally exposed people. Among 27 workers complaining of symptoms potentially related to rape exposure, 16 were atopic and 9 were positive to oilseed rape allergen. Occupational asthma studies have been a helpful source of learning about asthma. In addition, causality is more likely to be established if an association between occupational exposure to rape emissions and symptoms is found. Thus the need for further occupational studies involving populations exposed to oilseed rape should be incorporated into the list of research needs recommended in the MRC report. Although all these findings need corroboration in future studies, the existing evidence does not allow the public health importance of medical effects of oilseed rape emissions to be dismissed. In particular, the fact that clear-cut clinical allergy to rape in monosensitised people has been shown to occur only rarely should not be interpreted as meaning that the importance of raperelated symptoms is negligible. The magnitude of the problem is proportional to the size of the exposed populations, but how many people are exposed is not known. Hemmer et al2 have recently shown that in Vienna the yearly average of oilseed-rape pollen counts per cubic metre has increased from about 50 in the

Vol 350 • August 16, 1997

1970s to about 300 in the 1990s, closely paralleling the increase in area of rape under cultivation. Low exposure to pollens in large urban populations is likely to be more important than expected, according to findings reported by Knox et al that both meteorological conditions and air pollution9 may directly increase the respirable fraction of airborne biological proteins. So far, most environmental health problems have been addressed in a reactive way. As described by Colborn,10 research often comes from serendipitous observations by scientists engaged in unrelated fields or from science reacting to damage in heavily contaminated areas. The case of health effects resulting from exposure to either particulate or volatile emission from oilseed rape crops illustrates once more the urgent need of a proactive approach based on large longitudinal studies able to evaluate which changes in quality of life and function will result from transformations in agriculture or industrial processes.

Josep M Antó Respirator y and Environmental Health Research Unit, Institut Municipal d’Investigació Mèdica, E-08003 Barcelona, Spain 1

Medical Research Council Institute for Environment and Health. IEH assessment on oilseed rape: allergenicity and irritancy. Leicester: Institute for Environment and Health, 1997. 2 Hemmer W, Focke M, Wantke F, Jäger S, Götz M, Jarisch R. Oilseed rape is a potentially relevant allergen. Clin Exp Allergy 1997; 27: 156–61. 3 Parratt D, Thomson G, Saunders C, McSharry C, Cobb S. Oilseed rape as a potent antigen. Lancet 1990; 335: 121–22. 4 Ninan TK, Milne V, Russell G. Oilseed rape not a potent antigen. Lancet 1990; 336: 808. 5 Soutar A, Harker C, Seaton A, Brooke M, Marr I. Oilseed rape and seasonal symptoms: epidemiological and environmental studies. Thorax 1994; 49: 352–56. 6 Soutar A, Harker C, Seaton A, Packe G. Oilseed rape and bronchial reactivity. Occup Environ Med 1995; 52: 575–80. 7 Fell PJ, Soulsby S, Blight MM, Brostoff J. Oilseed rape - a new allergen? Clin Exp Allergy 1992; 22: 501–05. 8 Butcher RD, Goodman BA, Deighton N. Evaluation of the allergic/irritant potential of air pollutants: detection of proteins modified by volatile organic compounds from oilseed rape (Brassica napus ssp oleifera) using electrospray ionization-mass spectometry. Clin Exp Allergy 1995; 25: 985–92. 9 Knox RB, Suphioglu C, Taylor P, et al. Major grass pollen allergen Lo1 p 1 binds to diesel exhaust particles: implications for asthma and air pollution. Clin Exp Allergy 1997; 27: 246–51. 10 Colborn T. Pesticides - How research has succeeded and failed to translate science into policy: endocrinological effects on wildlife. Environ Hlth Perspect 1995; 103 (suppl 6): 81–86.

Trinucleotide repeats not the only cause of anticipation Anticipation, in the genetic context, refers to the tendency of familial disorders to occur earlier in the younger than in the older generations of a family. The disorder may also be more severe in the later generations, probably from the well-known correlation of early onset with severity The English geneticist Lionel Penrose, in a report he wrote in 1945 when he was a war refugee in Canada, found anticipation of mental illness in the families of psychiatric inpatients.1 He pointed out that anticipation is “very characteristic of mental hospital data”, which in the past had been attributed to “a tendency for progressive degeneration”. He wrote that such an explanation is “not in accordance with the concepts of modern genetics” and suggested that a more likely 459