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Biomedical subjects

J Cocker

Publications and source records attributed to J Cocker.

At least 37 records · Page 2Linked to original sources
PubMed1997

A biological monitoring study of 1-methoxy-2-propanol: analytical method development and a human volunteer study.

1-Methoxy-2-propanol (M2P) is finding increasing industrial use as a less toxic alternative to the short-chained ethylene glycol ethers. Like most glycol ethers, M2P is readily absorbed through the skin and biological monitoring is therefore appropriate in assessing occupational exposure. An analytical method, suitable for routine monitoring, was developed for the determination of free M2P in urine. The method involves solvent extraction, gas chromatography-mass spectrometry and is sensitive (detection limit 1 mumol/l), specific and reproducible (intra- and inter-assay coefficients of variation 5% and 9%, respectively). A human volunteer study, involving six volunteers, was also conducted. Volunteers were exposed to 100 ppm M2P for 8 h (the occupational exposure standard in the UK) including a 30-min break. Post-exposure levels of free M2P in urine were found to reach up to 110 mumol/l). Levels of M2P were also monitored in blood (maximum 103 mumol/l) and exhaled air samples (up to 252 nmol/l). The volunteer study showed that M2P is rapidly excreted in urine with a half-life of less than 2.6 h.

Adult↗
PubMed1997

A novel device for capturing breath samples for solvent analysis.

We have developed a novel breath sampling device suitable for capturing a portion of end-tidal air. This breath sample is then transferred onto a Perkin Elmer automated thermal desorption (ATD) sampling tube which is subsequently analysed by ATD-gas chromatography-mass spectrometry (GCMS). The breath sampler has been evaluated in the laboratory, in brief field trials and in human volunteer studies. The method is sensitive with a typical detection limit of 1 nmol/l and reproducible with an overall coefficient of variation between 5% and 15% for collection and analysis of breath samples from volunteers. The field trials used the sampler to assess exposure to solvents in several industries including the shoe manufacturing industry, the inks and coatings industry and at dry cleaning establishments. The sampler was found easy to use and reliable. Solvents detected include ethyl acetate (6.4-25.5 nmol/l), propan-2-ol (3.4-39.3 nmol/l), 2-butanone (0-6.6 nmol/l) and tetrachloroethene (0-557 nmol/l). The breath sampler was also used to monitor the elimination of solvents in breath from human volunteers after exposure chamber studies. More than 500 breath samples have been analysed from 24 volunteers in exposures to 10 different solvents (toluene, trimethyl benzene, tetrachloroethene, tetrahydrofuran, acetone, propan-2-ol, xylene, 2-butanone, 1-methoxy-2-propanol and n-hexane). The breath sampler allowed the rapid and non-invasive collection of data on elimination of solvents.

Absorption↗
PubMed1996

Occupational exposure to permethrin during its use as a public hygiene insecticide.

Permethrin is an active ingredient found in many public hygiene insecticide products and exposure to it was assessed in a survey of 45 professional users. The exposures measured were over a wide range, with more than a 100-fold difference between average levels and the highest levels. Dermal contamination was evident on 93% of the operators, the highest contamination resulting from the use of leaking application equipment, demonstrating that proper maintenance of equipment is vital. Where the insecticide was applied at ground level most contamination was on the legs, indicating the importance of appropriate footwear. Contamination of the hands occurred despite the use of protective gloves, higher levels of contamination occurring when liquids were used. Dermal contamination was not always the principle route of exposure, and high airborne concentrations were linked with use in confined areas. Airborne concentrations were also associated with the physical form of the product used and the treatment method. To help in assessing the effectiveness of protective clothing and control measures, biological monitoring was carried out. Monitoring of metabolites in urine showed that systemic uptake occurred but evidence from toxicological studies indicates that the levels found were well below those considered to cause harm.

Environmental Monitoring↗
PubMed1994

A biological monitoring assessment of exposure to methylene dianiline in manufacturers and users.

This paper describes a cross sectional study in which biological monitoring was used to assess exposure to methylene dianiline (MDA) in a selection of United Kingdom industries that manufacture or use MDA. Samples of urine were collected from 411 workers, representing 45 factories engaged in various activities. All urine samples were analysed for MDA and its acetyl metabolites and results are reported as total MDA. In this study, 91% of postshift urine samples and 88% of preshift samples had less than 50 nmol MDA/mmol creatinine. Some evidence was obtained which showed that when exposure to MDA was through inhalation (as solid material or contaminated dust), postshift urine samples had higher MDA concentrations than samples taken preshift the next day. When exposure was most likely to be through the dermal route, urine samples taken preshift next day tended to have higher MDA concentrations than urine samples collected immediately postshift on the day of exposure. Therefore a biological monitoring sampling strategy for MDA must take account of the route of entry into the body. If exposure is likely to be via inhalation, postshift samples should be collected and if exposure is likely via the skin, preshift samples next day are more appropriate. The results show that in most factories, regardless of the route of exposure, it is possible to keep urinary MDA concentrations below 50 nmol/mmol creatinine. In the absence of a health based or hygiene based standard, the use of a "yardstick" as a target to aim for, which has been derived from good working practice across the industry, may be a useful way of helping to control exposure.

Administration, Cutaneous↗
PubMed1992

Human inhalation pharmacokinetics of chlorodifluoromethane (HCFC22).

Two groups of three male volunteers were exposed to atmospheric concentrations of either 327 or 1833 mg m-3 chlorodifluoromethane (HCFC22) for 4 h. Blood, urine and expired air samples were taken during and after the exposure period and analysed for HCFC22. Urine samples were also analysed for fluoride ion. During the exposure period, blood concentrations of HCFC22 approached a plateau, and the average peak blood concentrations of 0.25 and 1.36 micrograms cm-3 were proportional to dose. HCFC22 concentrations in expired air were similar to the exposure concentration during the exposure period. The ratio between venous blood and breath concentrations of HCFC22 towards the end of the exposure period was on average 0.77, which is consistent with in vitro estimates of the partition coefficient. In the post-exposure period, three phases for the elimination of HCFC22 were identified, with estimated half-lives of 0.005, 0.2 and 2.6h. HCFC22 was detected in urine samples taken in the post-exposure period, and the rate of decline was consistent with the terminal rate of elimination estimated from blood and breath measurements. On average 2.1% of the inhaled HCFC22 was recovered in breath within 26 h of exposure. This is consistent with the low solubility in blood and fat. Minimal changes in fluoride ion concentrations in urine following exposure indicate that HCFC22 is unlikely to be metabolised to a significant extent. Following inhalational exposure HCFC22 is poorly absorbed and is rapidly eliminated from the body. Possible biological monitoring strategies could be based on measurements of HCFC22 in urine or breath samples collected after the end of an exposure period.

Adult↗
PubMed1990

Biological monitoring of a worker acutely exposed to MBOCA.

A 30 year-old male polyurethane worker was exposed to an accidental spill of 4,4'-methylene-bis-2-chloroaniline (MBOCA) at a plant producing MBOCA-cured plastic products. Exposure to MBOCA is significant in that this compound is a known animal carcinogen and a suspected human carcinogen. The employee was sprayed over his upper body and extremities with molten MBOCA while cleaning out a clogged hose from a MBOCA and polymer mixing machine. The subsequent environmental and medical evaluation of this episode included serial urinary MBOCA samples from the worker over a 2 week period to allow the calculation of a biological half-life for this compound. This worker experienced a very high dose of MBOCA as judged by his urinary MBOCA levels (peak value of 1,700 ppb 4 hours after exposure). There were no acute symptoms or other laboratory abnormalities noted. The kinetic evaluation resulted in a biological half-life for MBOCA in urine of approximately 23 hours. Assuming a one-compartment model, approximately 94% of an initial MBOCA dose will be eliminated within four days. This is the first report of kinetic analysis on urinary MBOCA excretion in humans. This information suggests that biological monitoring of the urine MBOCA concentrations in exposed workers may miss peak levels following an acute exposure unless the analyses of the urinary MBOCA are performed in a timely fashion. Recommendations to the company included: 1) installation of a warning system or lock-out device on the mixing machine to prevent the opening of the MBOCA hose prior to the release of pressure; and 2) annual medical surveillance of this individual for bladder cancer with urinalysis and urine cytology.

Accidents, Occupational↗
PubMed1990

Evidence that a beta-N-glucuronide of 4,4'-methylenebis (2-chloroaniline) (MbOCA) is a major urinary metabolite in man: implications for biological monitoring.

Urine samples from workers exposed to 4,4'-methylenebis (2-chloroaniline) (MbOCA) contain a labile metabolite(s) that, on hydrolysis, yields the parent compound at concentrations two to three times those of free MbOCA. Evidence has now been obtained that the major labile metabolite is an N-glucuronide of MbOCA. The N-glucuronide of MbOCA was synthesised chemically, characterised by thermospray mass spectrometry, and found to have a pseudomolecular (M + 1) ion at m/z 443/445. MbOCA and [14C] uridine diphosphoglucuronic acid [( 14C]UDPGA) were incubated with liver microsomes from rats induced with polychlorinated biphenyls. The stoichiometry of the reaction product was about 1:1 (MbOCA:UDPGA). This product, the chemically synthesised glucuronide, and the labile urinary metabolite had identical chromatographic and hydrolytic (heat and beta-glucuronidase) properties. These studies show that the major labile conjugate of MbOCA in the urine of workers exposed to this compound is probably the mono N-glucuronide. In view of the lability of this compound and the fact that its concentration in urine is two to three times that of free MbOCA, it is essential that any strategy for the biological monitoring of exposed workers takes into account the N-glucuronide.

Benzhydryl Compounds↗
PubMed1988

Determination of the N-acetyl metabolites of 4,4'-methylene dianiline and 4,4'-methylene-bis(2-chloroaniline) in urine.

A sensitive and specific gas chromatographic/mass spectrometric assay is described for the determination of N-acetyl 4,4'-methylene dianiline (N-acetyl MDA) and N-acetyl 4,4'-methylene-bis(2-chloroaniline) (N-acetyl MbOCA) in urine. The method is based on the solvent extraction of the compounds together with deuterium-labelled internal standards, the compounds being separated and detected by capillary gas chromatography/mass spectrometry as their pentafluoropropyl derivatives. The method has been applied to the detection of N-acetyl MbOCA and N-acetyl MDA in the urine of workers occupationally exposed to MbOCA and MDA. The results show that whilst N-acetyl MbOCA is a relatively minor urinary metabolite a significant proportion of MDA is excreted as the N-acetylated compound.

Acetanilides↗
PubMed1986

Assessment of occupational exposure to 4,4'-diaminodiphenylmethane (methylene dianiline) by gas chromatography-mass spectrometry analysis of urine.

A new specific and sensitive method has been used to monitor workers from five different factories where 4,4'-diaminodiphenylmethane (methylene dianiline) (DDM) was being used. The isolation and identification of an N-acetyl conjugate of DDM, a major metabolite of DDM found in human urine, is reported for the first time. The use of this biological monitoring method will allow the assessment of the absorption of DDM and help in monitoring improvements in work practices, particularly where exposure may occur through pathways other than inhalation.

Acetanilides↗
PubMed1985

The metabolic activation of 4,4'-methylene-bis-(2-chlorobenzeneamine) to a bacterial mutagen by hepatic postmitochondrial supernatant from human and other species.

4,4'-Methylene-bis-(2-chlorobenzeneamine) (MbOCA) is a commercially important industrial chemical that is carcinogenic in three animal species and mutagenic in the Ames test. The ability of hepatic postmitochondrial supernatant from humans, dogs, mice, and rats to activate MbOCA to a bacterial mutagen has been investigated using the Ames plate incorporation test and a bacterial fluctuation test. In the Ames plate test, hepatic S9 preparations from mice and Aroclor 1254-induced rats only were sufficiently active to produce a significant mutagenic response. Preincubation of MbOCA with S9 from human liver produced a slight increase in the number of revertants but not a doubling as compared to controls. However, using the more sensitive bacterial fluctuation test, liver S9 from all species activated MbOCA to a bacterial mutagen. The responses produced were dose-related and, for at least part of the dose range, were double the background levels observed in controls. The increases in the mutagenicity of MbOCA produced by liver S9 from humans, dogs, and rats were significant at the 0.1% level of probability. Liver S9 preparations from all species in which MbOCA is carcinogenic have now been demonstrated to be capable of activating this compound to a bacterial mutagen. The finding that S9 from human liver can also activate MbOCA to a mutagen increases the concern that it may be a human carcinogen.

Animals↗
PubMed1981

Search for benzidine and its metabolites in urine of workers weighing benzidine-derived dyes.

Urinary benzidine and conjugates have been used to assess the extent of occupational exposure to benzidine-based azo dyes. The aim of the present study was to investigate the presence of benzidine and its conjugates in the urine of workers exposed to benzidine-derived dyes. Urine samples were collected from 29 workers in three textile dyehouses, two tanneries, and two dyestuff quality control laboratories in West Yorkshire and Lancashire. In 200 samples, obtained over a period of 15 months and analysed by gas chromatography/mass spectrometry, no free benzidine or monoacetylbenzidine was detected. Nevertheless, after strong acid hydrolysis of urine samples taken on two separate occasions from textile dye weighers where the standard of hygiene appeared below average, trace amounts of benzidine were detected suggesting the excretion of a benzidine derived dye or a metabolite thereof.

Benzidines↗
PubMed1979

The time course of mandelic and phenylglyoxylic acid excretion in workers exposed to styrene under model conditions.

Urinary excretion of mandelic and phenylglyoxylic acids by two technicians building glass-reinforced plastic boats has been measured over a 7-day period. Peak excretion of both metabolites occurred several hours after the end of exposure. There was little relationship between urinary mandelic acid concentrations measured at the end of shift and the maximum excretion observed in samples collected after this time. It is suggested that sampling strategies devised to monitor workers exposed to styrene should reflect maximum excretion rates of urinary mandelic acid.

Environmental Exposure↗
PubMed1968

Consistency in the histological diagnosis of epithelial abnormalities of the cervix uteri.

A group of pathologists, all working in the same laboratory and all applying the same diagnostic criteria to the diagnosis of epithelial abnormalities in the uterine cervix, have studied the consistency with which they have applied these criteria. Epithelial abnormalities were ranked, and a series of sections were diagnosed separately by each pathologist at various times over a number of years. Both consistency and trend were studied by a graphed statistical method and it was shown that not only were there serious inconsistencies in diagnosis between the various pathologists but also between the diagnoses made by individual pathologists studying the same section at various times. It is suggested that this inconsistency in the application of agreed diagnostic criteria is of importance when considering discrepancies between reported series of cervical epithelial abnormalities and that the type of study described is of value in assessing both variations in diagnostic criteria between different laboratories and the consistency of pathologists in training. Any slight change in the application of diagnostic criteria for any individual pathologist with the passage of time may also be detected by this technique.

Analysis of Variance↗