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T Lawlor

Publications and source records attributed to T Lawlor.

At least 19 recordsLinked to original sources

Photoclastogenicity-an improved protocol, its validation, and investigation of the photogenotoxicity of DMBA.

An improved protocol was developed to detect light-induced clastogenic photoproducts in Chinese hamster ovary (CHO) cells. Dishes (60 mm) containing cells and the test material or vehicle control in 3 mL of phosphate-buffered saline were exposed to light using a SUNTEST CPS solar simulation unit. Importantly, cells were exposed at about 25 cm from the light source, thereby allowing a short exposure time of 2 min. With this exposure the assay was conducted with lids removed during the UV exposure with minimal risk of contamination. After preliminary experiments an exposure of 165.6 mJ/cm(2) UVA: 17.0 mJ/cm(2) UVB was selected for treatments with the different phototoxins. Under these exposure conditions about 10-15% aberrant cells were induced in vehicle control cultures with no or minimal cytotoxicity. The well-known photoclastogens 8-methoxypsoralen (8-MOP) and chlorpromazine (CLZ) were tested. In agreement with published data, 8-MOP and CLZ were clastogenic (lowest observed effect level, LOEL, was 0.0159 microg/mL and 1.03 microg/mL, respectively). In the absence of UV, 8-MOP was clastogenic at a much higher concentration (LOEL 251 microg/mL without UV vs. 0.0159 microg/mL with UV) while CLZ was negative up to a toxic concentration of 35 microg/mL. 7,12-Dimethylbenz[a]anthracene (DMBA), which is photomutagenic in bacteria, was clastogenic at > or =0.005 microg/mL with UV light (without S9) and at > or =2.53 microg/mL with S9 (without UV light). These results demonstrate the utility of the protocol for the detection of photoclastogenicity and expand the characterization of DMBA's photogenotoxic activity.

9,10-Dimethyl-1,2-benzanthracene↗

Evaluation of the in vitro genetic toxicity of 4-(2, 4-dichlorophenoxy)butyric acid.

The herbicide 4-(2,4-dichlorophenoxy)butyric acid (2,4-DB) is principally used in the USA on peanuts, soybeans and alfalfa. In Europe, it is used on undersown spring barley and grassland (with clover). The genetic toxicity in vitro of the dimethylamine salt of 2,4-DB was examined by employing a range of end points including gene mutation in bacteria (Ames test) and mammalian cell cultures (CHO/HGPRT assay), cytogenetic abnormalities in mammalian cells (CHO/chromosomal aberration assay), and induction of DNA damage and repair in rat hepatocytes. There were no indications of genotoxic potential for 2,4-DB in the first three of these assays. One of the two criteria for a positive response in the UDS assay was exceeded but the increases did not exceed the second criteria for a positive response. The test material was therefore evaluated as weakly active in this assay. The weight of the evidence clearly indicates that 2, 4-DB is not genotoxic to mammals and are consistent with the reported lack of carcinogenic potential for 2,4-DB in both mice and rats.

2,4-Dichlorophenoxyacetic Acid↗

In vitro genotoxicity testing of ARASCO and DHASCO oils.

ARASCO and DHASCO oils are microbially-derived triglycerides rich in arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acids, respectively. Both oils were tested for mutagenic activity in three different in vitro mutagenesis assays. All assays were conducted with and without metabolic activation. Neither ARASCO nor DHASCO oil was mutagenic in the Ames reverse mutation assay using five different Salmonella histidine auxotroph tester strains, nor were the oils mutagenic in the mouse lymphoma TK(+/-) forward mutation assay. The oils showed no clastogenic activity in chromosomal aberration assays performed with Chinese hamster ovary cells. Based on these assays, neither ARASCO nor DHASCO oils appear to have any genotoxic potential.

Animals↗

The efficacy of involuntary outpatient treatment in Massachusetts.

One means to address some of the unintended consequences of the shift of treatment for individuals with serious mental illness from hospitals to communities has been involuntary outpatient treatment (IOT). Using Massachusetts data, 19 patients with court orders for IOT were matched to all and to best fits on demographic and clinical variables, and then to individuals with the closest fit on utilization before the IOT date. Outcomes indicated the IOT group had significantly fewer admissions and hospital days after the court order. The full impact of IOT requires more study, particularly directed toward IOT's effects on insight and quality of life.

Adult↗

Mutagenic activity of a series of synthetic and naturally occurring heterocyclic amines in Salmonella.

26 synthetic and naturally occurring heterocyclic amines were tested in the Salmonella/microsome assay (Ames test) using tester strains TA98 and TA100 in the presence of an Aroclor-induced rat-liver S9 fraction. 9 of the compounds were protein-pyrolysis products which had previously been shown to be mutagenic. Mutagenic potencies similar to previously reported values were demonstrated for these compounds with the exception that Trp-P-1 was only mutagenic in strain TA98 in our study, although it had previously been reported to be weakly mutagenic in strain TA100. 17 structurally diverse heterocyclic amines were synthesized and tested for mutagenicity. The structural diversity of these synthetic heterocyclic amines will enhance the sensitivity of future quantitative structure-activity relationship (QSAR) studies by demonstrating the structural characteristics essential for mutagenicity. The results of this study provide a large data base for the mutagenicity of this important class of compounds.

Amines↗

Salmonella mutagenicity tests: V. Results from the testing of 311 chemicals.

311 chemicals were tested under code, for mutagenicity, in Salmonella typhimurium; 35 of the chemicals were tested more than once in the same or different laboratories. The tests were conducted using a preincubation protocol in the absence of exogenous metabolic activation, and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters. Some of the volatile chemicals were also tested in desiccators. A total of 120 chemicals were mutagenic or weakly mutagenic, 3 were judged questionable, and 172 were non-mutagenic. The remaining 16 chemicals produced different responses in the two or three laboratories in which they were tested. The results and data from these tests are presented.

Animals↗

A prospective, multicenter study of patients' refusal of antipsychotic medication.

Refusal of treatment with antipsychotic medication was studied prospectively in a sample of 1434 psychiatric patients admitted to four acute inpatient units in state-operated mental health facilities in Massachusetts during a 6-month period. Compared with a control group of patients who accepted prescribed antipsychotic treatment, the 103 patients who refused were older, of a higher social class, and less likely to have been prescribed antiparkinsonian medications. On admission, prior to refusal of medication, patients who refused were found to have significantly higher Brief Psychiatric Rating Scale scores than compliant patients and more negative attitudes regarding their hospitalization and past, present, and future treatment. Treatment refusal had negative effects on the hospital milieu and on the patient; refusers were more likely to require seclusion or restraint and had longer hospitalizations than treatment acceptors. Most refusal episodes ended with voluntary acceptance of treatment. In 23% of cases medications were discontinued. Only 18% of the sample reached formal, judicial review, and in every case that did, involuntary treatment was ordered. The policy implications of these findings are discussed.

Adult↗

Mutagenicity studies on ketone solvents: methyl ethyl ketone, methyl isobutyl ketone, and isophorone.

3 ketone solvents (methyl ethyl ketone (MEK), methyl isobutyl ketone (MiBK), and isophorone) were tested for potential genotoxicity. The assays of MEK and MiBK included the Salmonella/microsome (Ames) assay, L5178Y/TK+/- mouse lymphoma (ML) assay, BALB/3T3 cell transformation (CT) assay, unscheduled DNA synthesis (UDS) assay, and micronucleus (MN) assay. Only the ML, UDS, and MN assays were conducted on samples of isophorone. No genotoxicity was found for MEK or isophorone. The presence of a marginal response only at the highest, cytotoxic concentration tested in the ML assay, the lack of reproducibility in the CT assay, and clearly negative results in the Ames assay, UDS and MN assays, suggest that MiBK is unlikely to be genotoxic in mammalian systems.

Animals↗

Salmonella mutagenicity tests: IV. Results from the testing of 300 chemicals.

Three hundred chemicals were tested for mutagenicity, under code, in Salmonella typhimurium, using a preincubation protocol. All tests were performed in the absence of exogenous metabolic activation, and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters. The results and data from these tests are presented.

Animals↗

Salmonella mutagenicity tests: III. Results from the testing of 255 chemicals.

The results and data from the testing of 255 chemicals for mutagenicity in Salmonella are presented. All chemicals were tested under code using a preincubation modification of the Salmonella/microsome test in the absence of exogenous metabolic activation and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters.

Animals↗

Comparative mutagenicity of aliphatic epoxides in Salmonella.

37 aliphatic epoxides comprising 6 subclasses (unsubstituted aliphatic epoxides, halogenated aliphatic epoxides, glycidyl esters, glycidates, glycidyl ethers and diglycidyl ethers) were tested, under code, for mutagenicity in Salmonella strains TA98, TA100, TA1535 and TA1537 and/or TA97 with and without metabolic activation using a standardized protocol. The 4 halogenated aliphatic epoxides and the 4 diglycidyl ethers were all mutagenic. The 2 glycidates were negative in all strain/activation systems used while all 5 glycidyl esters were mutagenic. 3 of the 8 unsubstituted aliphatic epoxides and 11 of the 12 glycidyl ethers were mutagenic. Glycidol also was mutagenic whereas 9,10-epoxyoctadecanoic acid, 2-ethylhexyl ester was not mutagenic. Of the 28 mutagenic compounds, all but neodecanoic acid, 2,3-epoxypropyl ester and 2-ethylhexyl glycidyl ether were detected in TA100 without activation. The latter two were detected only with activation in TA100 and TA1535. The majority of the other 26 chemicals were also mutagenic in TA1535 without activation. Good intra- and interlaboratory reproducibility was seen in the results of each of the 4 chemicals tested in more than one set of experiments. The current results confirm and extend the observations of other investigators regarding structural effects on the mutagenicity of members of the aliphatic epoxide class of chemicals.

Animals↗

Salmonella mutagenicity tests: II. Results from the testing of 270 chemicals.

This publication includes data of Salmonella mutagenicity results on 270 coded chemicals, encompassing 329 tests performed by three laboratories under contract to the National Toxicology Program (NTP). The preincubation modification of the Salmonella/mammalian microsome assay was used to test chemicals in up to five Salmonella strains in the presence and absence of rat and hamster liver S-9. With a few exceptions, inter- and intralaboratory reproducibility was good.

Animals↗

Serum cholesterol and triglycerides in relation to ponderal index and age in two contrasting populations.

One hundred and seventy six mentally retarded adult patients had their serum cholesterol, triglycerides and ponderal index determined during a seven week period and compared with those of a normal group of business executives being routinely screened by the same laboratory. A comparison of cholesterol and triglyceride levels showed those of the former group to be significantly lower, as dealt with in a previous paper by Lawlor, O'Hara and Birtwistle (1974). The values in mentally subnormal males showed no correlations with ponderal index, whereas the normal males showed highly significant correlations throughout. Both the normal and subnormal females showed highly significant correlations of cholesterol with triglyceride levels, and of age with cholesterol concentration, but not of ponderal index with either cholesterol or triglyceride levels.

Administrative Personnel↗