California enacts Safe Cosmetics Act.

Californians frustrated with what they consider the FDA’s loose control over cosmetic safety have taken matters into their own hands with the country’s first state cosmetics regulatory act, which takes effect in January 2007. The California Safe Cosmetics Act of 2005 will require manufacturers to report the use of potentially hazardous ingredients to the state Department of Health Services (DHS), which in turn will alert consumers. The DHS has the authority to investigate whether the product could be toxic under normal use and to require that manufacturers submit health effects data. Manufacturers that continue marketing products deemed unsafe in California could face legal action. 
 
“The legislation’s sponsors believe that the basis of the law is the public’s right to know,” says Kevin Reilly, DHS deputy director of prevention services. The new law uses the list of toxicants drawn up under California’s Proposition 65, which mandates that the governor publish a list, updated at least yearly, of chemicals that are known to the state of California to cause cancer, birth defects, or other reproductive harm. 
 
Although the new act applies only in California, its effects are likely to reverberate nationwide. Consumer advocates predict that manufacturers seeking to avoid negative publicity will remove, rather than report, suspect ingredients. Those formulas would then be marketed coast to coast. 
 
Impetus for the law stems from consumers’ concerns over long-term exposure to certain cosmetic ingredients. Cosmetic use has not been linked to chronic illnesses, but some products do contain carcinogens (such as formaldehyde, used in nail treatments), teratogens (such as lead acetate, used in two hair dyes), and other reproductive toxicants (such as di-n-butyl phthalate, used in nail treatments and dandruff shampoos). 
 
Studies in recent years have shown that humans absorb and inhale sometimes surprisingly high levels of toiletry ingredients. In the November 2005 issue of EHP, a team led by Susan M. Duty of the Harvard School of Public Health demonstrated that urine concentrations of phthalate metabolites increased by 33% with each personal care product—hair gel or spray, lotion, deodorant, cologne, aftershave—that subjects used. 
 
Historically, cosmetics safety has been in the hands of manufacturers; the FDA requires no premarket testing. Each year, an expert panel convened by the industry-funded Cosmetic Ingredient Review (CIR) identifies priority ingredients for which it conducts literature reviews and analyses to determine safety. The panel—made up of independent academic researchers and representatives from industry, consumer interests, and the FDA—has declared 9 of the 1,286 ingredients reviewed since 1976 unsafe for normal cosmetic use. But manufacturers are not obligated to eliminate any ingredients—at least one ingredient identified as unsafe by CIR, hydroxyanisole, is still used. 
 
Safety advocates see evidence of any harm in any use as reason enough for a ban. “Ingredients suspected of causing cancer shouldn’t be used in cosmetics,” says spokesman Kevin Donegan of the Breast Cancer Fund, a San Francisco–based nonprofit that promoted the California bill. 
 
F. Alan Andersen, director and scientific coordinator of CIR, counters that the dose creates the danger. “We don’t subscribe to the notion that if there’s ever an adverse effect, [a chemical] must not be in a product people use,” he says. “It doesn’t make sense to us to apply the precautionary principle. Instead, we use a risk assessment approach, and the wide margins of safety that we have found for chemicals such as phthalates using this approach assure us that actual use of cosmetics is safe.” 
 
The law drew fierce opposition from individual companies and the Cosmetic, Toiletry, and Fragrance Association (CTFA) as it worked its way through the California legislature. “CTFA supports strong federal regulation by the FDA,” says Kathleen Dezio, executive vice president of public affairs and communications for the association. “For this reason, CTFA has generally opposed state-specific legislation that would undermine this national approach and lead to an unworkable state-by-state patchwork of rules . . . or unjustified, extreme requirements that are well beyond those placed on any other category of food, beverages, drugs, or consumer products.” She adds that CTFA has met with the DHS and “pledged our cooperation in accomplishing the requirements” of the law. 
 
Some manufacturers have already ceded to public pleas for safer products. In the past two years, almost 350 of them signed a pledge promoted by the Campaign for Safe Cosmetics, a coalition of health and environmental groups, to use no chemicals linked to cancer or birth defects. Industry leaders L’Oreal and Revlon broke new ground last year when they promised that products they sold in the United States would meet more stringent European Union standards. In 2004 Europe enacted a ban on suspected carcinogens, mutagens, and reproductive toxicants in personal care products. 
 
“We’re definitely seeing a shift in the attitude of manufacturers,” Donegan says. “They’re starting to see the benefits of removing anything that could cause cancer.”

The successful management of patients with malignant lymphoma is dependent upon accurate staging and an appropriate treatment regime. Although the chest is a frequent site of involvement (Chabner, 1977;Filly et al., 1976;Kaplan, 1980;Peckham, 1973;Rosenberg, 1961), investigation has relied upon the plain chest X-ray (CXR) and tomography (Tomo) until the introduction of computed tomographic scanning (CT scan).
Prognosis has been found to correlate with the presence of very bulky disease in the chest, and even moderate amounts of intrathoracic lymphoma have been associated with a worse response to treatment than would be expected for other sites of involvement (Lee et al., 1980;Mauch et al., 1978). CT has been found to detect more mediastinal and pulmonary disease (Fong et al., 1982;Muhm et al., 1979;Osbourne et al., 1982;Underwood et al., 1979) in patients with thymoma and bronchial carcinoma, and it has been suggested that it may improve the staging of intrathoracic lymphoma (Ellert & Kreel, 1980). Comparison has not previously been made with conventional radiography, therefore a prospective study was undertaken to determine the role of thoracic CT in the management of patients with lymphoma.

Patients
One hundred consecutive, previously untreated patients with biopsy proven malignant lymphoma were studied over an 18-month period ( Table I).
The histological diagnosis was established in all cases by Dr A.G. Stansfeld and the patients were (a) Chest X-ray: posteroanterior (PA), lateral and penetrated PA views. (b) Tomograms: PA and lateral tomograms of the mediastinum and hila at 1 cm intervals. (c) CT scan: CT scan was performed with contiguous 1.3cm sections from the sternal notch to the diaphragm using an EMI 5005 CT body scanner. Intravenous contrast was given to 14 patients to enhance the major vessels when findings were equivocal by plain scan.
In the second half of the study a further 50 patients were examined by PA, penetrated and lateral CXR and CT scan only. For these patients the CT scan included the lung bases only when abnormalities were present in the upper part of the chest (19/50).
Follow up At the completion of treatment all patients were reexamined with repeat PA, lateral and penetrated CXR. CT scan was repeated in all those in whom it was previously abnormal or equivocal.
All patients have had monthly clinical follow up for 24-42 months from the completion of treatment, with further CXRs and CT scans.

Analysis
At the completion of the study the CXR and tomograms (AKT) and CT scans (IKF, FEW) were reported independently. All cases in which the findings differed were then reviewed together with the X-rays taken following treatment and with the knowledge of the patient's clinical course and response to therapy.
Soft tissue masses in the mediastinal and hilar regions were reported as lymphadenopathy. Parenchymal lymphoma was only diagnosed in the presence of discrete nodules or infiltrates and in the absence of clinical evidence of infection. Histological confirmation of parenchymal lymphomas was achieved in 6 patients. Shadows radiating from the hila were not accepted as evidence of lymphomatous infiltration as they could not be distinguished from vascular or lymphatic congestion. Equivocal findings were recorded as negative and post radiation fibrosis was disregarded.
Statistical analysis was made using the Chi squared test with Yates' correction and Student's t test.

Definitions
True positive abnormalities Those confirmed histologically (15 patients), and those showing resolution on repeat examination following successful lymphoma treatment without antibiotic therapy, or progression in association with other sites of disease upon the failure of treatment. One patient in whom histological confirmation was not obtained for the chest abnormalities died of lymphoma during 'treatment. All the radiological findings in this case were in agreement and were assumed to represent a true positive.
False positive abnormalities Those initially thought to be due to lymphoma, but subsequently shown on clinical and radiological follow up not to represent disease (see Results).
True negative investigations Those which were normal at presentation and remained so at follow up examination with no clinical evidence of disease elsewhere.
False negative investigations Those which were contradicted by other radiological findings which fulfilled the true positive criteria.

Results
Comparison of the results from CXR, tomography and CT scan In all instances CT scan proved to be the most sensitive and CXR the least sensitive method for detecting intrathoracic lymphoma. The results of conventional tomography were intermediate between those of CXR and CT scan but never significantly more sensitive than the CXR. Tomography was therefore stopped after the first 50 patients (Table II). The findings from CXR and CT scan differed most significantly in the mediastinum (P<0.001 for 100 patients (Figure 1; Tables III and IV)). The increased detection by the CT scan was particularly   Table V). CT scan, although more sensitive than CXR, was no more accurate at detecting hilar lymphadenopathy than tomography (Table IV). This was due to the difficulty experienced with all methods in differentiating enlarged nodes from hilar vessels.
False positives in the mediastinum (Tables II and  III) were due to prominent vessels in all four cases as shown by i.v. contrast enhancement of the CT scans (Figure 2). Similarly at the hilum four of the false positives were due to vessels and one, on tomography, to a large anterior mediastinal mass which was wrongly interpreted as involving the hila.
Pulmonary parenchymal disease was detected with greater sensitivity by the CT scan compared with the CXR (P<0.05, Table IV). All 4 patients in whom CT scanning detected occult parenchymal disease had NHL with no other evidence of extranodal spread (Figure 3). Biopsy confirmation was obtained in 2 of these 4 patients.
Effect of CT scanning on staging and treatment Thirty-nine patients had evidence of Stage IV disease prior to CT scanning and thus neither stage nor the treatment was affected by the CT scan.
There was a change in stage in 10/61 patients with Stage I-III disease (16%) due to information solely available from the CT scan. The stage was increased in 9 patients: 4 from II-IV by the detection of parenchymal deposits (2 confirmed on biopsy), 3 from I-IT, and 2 from II-III by the detection of intrathoracic lymphadenopathy. Stage was decreased in one patient from III-I when the CT scan demonstrated that a mediastinal shadow was due to normal vascular structures.   Thirty-two Stage 1-111 patients had either B symptoms or very large intrathoracic masses for which chemotherapy is our current treatment of choice, and treatment was not therefore affected by CT scan results. Treatment was changed in 11 of the remaining 29 patients (38%). Four required chemotherapy for parenchymal deposits and one (downgraded from III to I) received involved field radiotherapy for an inguinal deposit. Six other patients receiving radiotherapy to the involved field for NHL had the field changed by CT scanning (includes one patient in whom the stage was not changed). No change was made in those with localised HD as all received mantle field radiation which adequately covered any additional sites.
CT scanning and remission assessment (Table VI) Complete remission was achieved by CXR criteria in 28/46 patients with intrathoracic lymphoma, although the CT scan returned to normal in only 18. There have been 9 relapses from the 28 with normal CXR (32%) of which 6 were correctly identified by the remission CT scan as having residual disease after treatment. In comparison, only 3/18 (17%) in whom the CT scan became normal have relapsed.
However, a positive CT scan following treatment did not always represent residual disease. Eight of the 28 in whom the CT scan was still positive have not relapsed in 2 years. A post treatment laparotomy was performed in one patient ( Figure  4) with marked residual abnormalities, but only fibrotic and hylanised tissue was found.

Discussion
With the introduction of any new staging technique the two principal questions that must be answered are: how does it compare with current practice and what is the clinical relevance of any additional findings? We have attempted to answer these questions in a series of one hundred consecutive and previously untreated patients as a representative sample of our general lymphoma practice. The addition of CT scanning to the investigation of the chest increased the frequency with which intrathoracic lymphoma could be detected to 46% in newly diagnosed patients, greater than hitherto reported (Chabner et al., 1977;Filly et al., 1976;Kaplan, 1980;Peckham, 1973;Rosenberg, 1961).
CT scan was shown to be the most sensitive technique in the assessment of mediastinal and parenchymal disease particularly in patients with NHL but also in HD. However CT scan displayed only a small advantage over CXR or tomography at the hilum as has been found for other tumours within the chest (Fong et al., 1982;Muhm et al., 1979;Osbourne et al., 1982;Underwood et al., 1979;Baron et al., 1981). The low incidence of pericardial and pleural infiltration reflects the early stage in the disease at which most of these patients had been diagnosed.
The additional information from CT scan changed the stage in 10 patients and the treatment in 11. The relative importance of these numbers, however, becomes more apparent when the size of the group "at risk" is taken into account; i.e. change in stage 10/61 (16%), change in treatment 11/29 (38%). This compares favourably with the yield from other staging procedures such as lymphography or bone marrow biopsy (Chabner et al., 1977;Kaplan, 1980). The value of CT scanning at remission assessment was more difficult to quantify, particularly as relapse was the only positive criterion available. The return of the CT scan to normal was a better prognostic factor than CXR. However, residual abnormalities on CT scan after treatment did not always represent active disease, as has been found at post treatment laparotomy (Sutcliffe et al., 1982).
In conclusion, the greater sensitivity and specificity of the chest CT scan produced changes in staging and treatment which were most relevant to the management of those patients with localised disease or only minor abnormalities by conventional chest radiology. Further follow up will be necessary to assess the relevance of CT scan at remission assessment. The difficulty in providing a CT scanning service for the routine staging of these patients with malignant lymphoma argues for the greater concentration of lymphoma treatment in specialist centres.