The myth of the final hazard assessment

Hazard assessment is a basic tool used in the evaluation and regulation of chemicals, but in spite of this there are many different interpretations of the scope and function of a hazard assessment. Starting from a discussion of the essential elements and conceptual frames involved, an attempt is made to identify the sources of uncertainty that are inherent in a hazard assessment. Problems identified include unambiguous identification of the chemical source, the routes of exposure, and the possible targets to be considered. Inadequacies in effects data are frequent, but unlike many of the other sources of uncertainty, these are often compensated for by the use of safety factors when setting quantitative limits for human or environmental exposure. The inherent uncertainties in the process make periodic revisions of any hazard assessment process inevitable, as new knowledge on routes of exposure and targets becomes available.     

Exteroceptive suppression periods in jaw-closing muscles. Variability and relation to experimental pain and sustained muscle contraction

The duration of the late exteroceptive suppression period (ES₂) of temporal muscle EMG activity has been reported to be reduced in patients suffering from chronic tension-type headache. Methods of recording and analysing ES₂ have varied between centers and reproducibility of results within subjects , although insufficiently studied, has generally been poor. ES₂ was investigated in 30 healthy subjects, using a computerized technique of recording, rectifying and averaging the EMG signals. Hour to hour and week to week variations of ES₂ durations were calculated, and the influence of pain during a cold pressor test and of sustained muscle contraction on ES₂ durations was investigated. The intra-individual variation of ES₂ durations was 16.0% from hour to hour and 20.7% from week to week. The inter-individual variation was 36.7%. The present method for analysis of ES₂ periods proved to be reliable, as the intra-observer variation was 4.2% and the inter-observer variation 4.6%. ES₂ periods were significantly shorter on the first compared to the second day of examination ( p = 0.006) and during experimental pain ( p = 0.0005). We recommend the use of the computerized averaging technique in future studies and caution against the dependence of results upon factors such as conditioning and pain.     

Isolated leukemic choroidal relapse in a child with acute lymphoblastic leukemia one year off therapy, diagnosed through transvitreal retino-choroidal biopsy

A serous retinal detachment and choroidal hemorrhagic infiltration developed in a 17-year-old girl with acute lymphoblastic leukemia one year after cessation of therapy without concurrent bone marrow (BM) or central nervous system relapse. A choroidal biopsy through a sclerotomy with simultaneous release of subretinal fluid revealed no malignant cells. Accordingly, she was treated with prednisone, topical corticosteroid and atropine with normalisation of vision and clinical findings. Five months later the retinal detachment and choroidal infiltration recurred. In order to re-attach the retina once more and obtain a representative choroidal biopsy, a pars plana vitrectomy followed by a retinotomy with removal of subretinal tissue was done revealing leukemic infiltration of the choroid. Simultaneously a BM relapse was diagnosed.     

Case-control study of risk factors for cervical neoplasia in Denmark. II. Role of sexual activity,reproductive factors,and venereal infections

Sexual, reproductive and venereal risk factors for cervical neoplasia were investigated in a population-based case-control study of 586 women with histologically verified, cervical squamous-cell carcinoma in situ, and 59 women with invasive squamous-cell cervical cancer, diagnosed from 1985 to 1986 in Copenhagen. Cases were identified from the computerized Danish Cancer Registry. An age-stratified control group (n=614) was drawn at random from the female population in the study area by means of the Danish Central Population Register. A structured questionnaire was mailed to cases as well as controls. Increasing number of sexual partners exerted a significant effect on the risk both for carcinoma in situ, and invasive cancer, independently of age at first intercourse and other potential confounders. Conversely, the association with early age at first intercourse became statistically insignificant after allowance for other risk factors, although an increasing risk was still observed with decreasing age at sexual debut. Early age at first episode with genital warts was a significant risk factor for carcinoma in situ, perhaps indicating a possible increased susceptibility of the cervix epithelium during adolescence. A history of genital warts was a good predictor of risk for carcinoma in situ, whereas a history of previous gonorrhea was associated with an increased risk for invasive carcinoma. Women with multiple births had a significantly increased adjusted risk, especially for carcinoma in situ, although some association was also observed with invasive cervical cancer. The study supports the hypothesis of cervical neoplasia being a sexually transmitted disease, and that carcinoma in situ and invasive cervical carcinoma, to a high degree, have similar patterns of risk factors.Drs Kjaer, Engholm, and Lynge are with the Danish Cancer Registry. Dr Dahl is with the Department of Surgery, Slagelse Hospital, Denmark. Dr Bock is with the Department of Gynecology, Rigshospitalet, Copenhagen, Denmark. Dr Jensen, formerly with the Danish Cancer Registry, is deceased. Address correspondence to Dr Kjaer, Danish Cancer Registry, Institute of Cancer Epidemiology, Danish Cancer Society, Rosenvengets Hovedvej 35, Box 839, Copenhagen. Denmark. The Danish Cancer Society supported this study through grants.     

Immunocytochemical characterization of large granular lymphocytes in normal cervix and HPV associated disease.

A quantitative immunocytochemical study of large granular lymphocytes (LGLs) in the normal cervix and in human papillomavirus (HPV) associated disease was performed using a panel of monoclonal antibodies which included those for LGL surface markers CD56, CD16, and CD57. Only CD56-positive cells were found within the ectocervical epithelium and these cells increased in number in cervical intraepithelial neoplasia (CIN) in comparison with normal cervix. Examination of serial sections and double labelling suggests that these cells are CD3+, CD8+, CD56+, CD16+. The observed increase in number of this subset was not associated specifically with HPV infection but was related to CIN. Lymphocytes expressing all three LGL markers were found in the stroma and CD16(+)-positive cells clustered around endocervical glands with occasional cells extending into the endocervical epithelium. These results indicate that a small subset of LGLs which express T-cell markers is increased in number in CIN. Cells expressing classical NK markers are restricted to the stroma and are not found within the ectocervical epithelium.     

Clinical results of piezoelectric gallstone lithotripsy.

The safety and efficacy of piezoelectric extracorporeal shockwave lithotripsy in the treatment of symptomatic gallbladder stones were evaluated in 53 consecutively treated patients. All treatments were performed as outpatients without anesthesia; over 95 per cent of 109 treatments were performed without analgesia or sedation. Ursodeoxycholic acid was administered post-treatment. Seventy per cent of patients had multiple sessions. Cumulative stone-free rates of 38 per cent at 6 months, 65 per cent at 12 months, and 75 per cent at 15 months were achieved. There was no difference in eventual stone clearance between patients with single stones less than 20 mm diameter, single stones greater than or equal to 20 mm diameter, or multiple (two or three) stones, although patients with single smaller stones required significantly fewer total shocks to become stone-free (P = .02). Stone clearance correlated with estimated stone volume. Biliary pain occurred in 62 per cent of patients after treatment but ceased in stone-free patients. Biliary complications of pancreatitis (7.5%) and choledocholithiasis (3.8%) were successfully treated by endoscopic papillotomy. Nonbiliary complications were virtually nonexistent. Three patients (5.7%) had elective cholecystectomy. Results indicate that piezoelectric lithotripsy is a safe, minimally painful treatment that, in conjunction with oral bile acids, can produce stone-free rates of 75 to 100 per cent in selected patients.     

Occupational exposure of deck crews to carcinogenic agents on crude oil tankers

Occupational exposure to carcinogenic agents on the decks on six Norwegian crude oil tankers was examined in five harbors. The purpose of the study was to evaluate the need for improving the working environment on deck on these tankers. Technical arrangments and the work itself on the deck were observed during loading or unloading. Occupational monitoring was performed by active sampling of benzene, polyaromatic hydrocarbons, and some aldehydes. The crew answered a questionnaire concerning their work, use of protective equipment, and occurrence of acute symptoms. The levels of air-borne carcinogenic agents were low, probably due to closed loading systems on all tankers. However, the seamen reported discomfort during the work that may be related to other chemical agents in the cargo. The seamen were frequently painting with lead chromate paint without using personal protective equipment. This type of chemical exposure should be evaluated.