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Biomedical subjects

M S Christian

Publications and source records attributed to M S Christian.

At least 37 records · Page 2Linked to original sources
PubMed1993

Developmental toxicity of acrolein in New Zealand white rabbits.

Pregnant New Zealand white rabbits (20 per group) were treated via stomach tube with 0.0, 0.1, 0.75, or 2.0 mg/kg/day from Days 7 through 19 of presumed gestation and subjected to cesarean sectioning on Day 29. Throughout the period of treatment, clinical observations, feed consumption, and body weights were recorded. At the termination of the study, reproductive and fetal parameters were measured. Three does died during the study, and transient effects on body weight gains and feed consumption were noted, with a subsequent rebound effect reflected in both fetal and maternal weights in the high-dose group (2 mg/kg/day). Resorptions were elevated in the high-dose group, but the effect was not statistically significant. Fetal malformations were distributed evenly among groups, and incidences were consistent with historical control data on the same strain and at the same laboratory. Higher dosage levels (range-finding study, 4.0 and 6.0 mg/kg/day) produced high incidences of maternal mortality, spontaneous abortion, resorptions, clinical signs, gastric ulceration, and/or sloughing of the gastric mucosa. Acrolein was not found to be a developmental toxicant or teratogen at doses not toxic to the does under the conditions employed in this study.

Abnormalities, Drug-Induced↗
PubMed1993

Is there any place for nonmammalian in vitro tests?

In vitro developmental toxicity testing procedures have two potential uses: 1) prediction of Adult/Developmental Ratios (A/D Ratios); and 2) study of the mechanisms of embryo development. Historically there has been an incorrect emphasis on malformation as the most relevant endpoint of developmental toxicity, as well as an incorrect assumption that this endpoint alone could be identified by an in vitro procedure. The literature is filled with tests that have later been shown to be inaccurate predictors of mammalian developmental toxicity. In addition, industrial experience with in vitro tests used to predict bimodal responses (e.g., potential carcinogenicity) has produced a basic mistrust of the results of these tests and an unwillingness to perform a test because of fear of inappropriate delays in the regulatory process. Because no single test has been identified as one that can replace mammalian testing procedures, there is also little need seen for these procedures, although some tests are used, not necessarily correctly, to prioritize testing. Better understanding of the utility of these tests would increase their use in the prioritizing process, possibly allow their use when remarkable acute environmental hazards occur, and assist in identifying the mechanism underlying the observed effect.

Abnormalities, Drug-Induced↗
PubMed1992

A decade of rabbit fertility data: study of historical control animals.

Reproductive data for 1795 artificially inseminated Hra: (NZW)SPF control rabbits in 93 developmental toxicity studies conducted from 1980 through 1989 were summarized. Data were obtained during terminal Caesarean-sectioning procedures performed on animals which survived to day 29 of gestation and during postmortem evaluation of does which aborted, delivered prematurely, or were found dead. Significant seasonal variation was not observed. Average pregnancy rate, percentage of rabbits that aborted, and percentage of rabbits that delivered prematurely throughout the decade were 86, 2.0, and 1.6%, respectively. Average numbers of corpora lutea, implantations, live fetuses, dead fetuses, early resorptions, and late resorptions for each doe that survived to scheduled termination were 10.8, 7.8, 7.1, 0.02, 0.49, and 0.15, respectively. The various vehicles used, routes of administration, and a variety of maternal and paternal factors were compared with the fertility data, and no correlations were observed. Rabbits that aborted earlier in gestation had fewer implantations than does which aborted late or delivered prematurely. Does which resorbed 100% of their conceptuses had fewer corpora lutea and implantations when compared with rabbits in the remainder of the population. Rabbits pregnant at scheduled termination which had a low number of corpora lutea or implantation sites had higher than expected pre- and postimplantation losses relative to the population as a whole. Does with a high number of corpora lutea had significantly higher preimplantation loss relative to the general population. This may indicate the presence of a "ceiling value" for the number of ova that can become fertilized and/or implant when the ovulation rate is high and which probably varies according to strain as well as a number of factors related to the individual rabbit. Based upon the results of this study and the work of a previous author, a minimum of four corpora lutea may be necessary for the successful maintenance of pregnancy in the New Zealand white rabbit. The minimum number of corpora lutea required may be strain dependent and may bear a relationship to the normal litter size of the strain.

Abortion, Veterinary↗
PubMed1989

Reduction in accident injury severity in rear seat passengers using restraints.

A prospective study of 441 rear seat occupants seen following road traffic accidents compared injury severity in the 411 unrestrained and 30 restrained subjects. Using ridit analysis, the injury severity score showed far less injury among restrained subjects (P = 0.0001). All 11 deaths and 176 of the 178 most severe injuries occurred in the unrestrained group. One restrained (3 per cent) subject was admitted overnight and 64 unrestrained (16 per cent) subjects required admission; two-thirds required a prolonged admission (mean = 13 days). Fractures, major bruises, abrasions and lacerations were almost confined to unrestrained passengers, 221 events compared with two among restrained passengers. Twenty-three unrestrained subjects were ejected, nine of whom were killed. We conclude that the use of rear seat restraints greatly reduces injury severity and should be compulsory for rear seat occupants as it is for front seat occupants.

Accidents, Traffic↗
PubMed1989

Determination of the developmental toxicity potential of butoxypropanol in rabbits after topical administration.

The developmental toxicity (embryofetotoxicity or teratogenicity) and maternal toxicity of butoxypropanol, a propylene glycol ether, was evaluated in New Zealand White rabbits. Dosages of 0 (water), 10, 40 or 100 mg/kg/day, selected on the basis of the water solubility of butoxypropanol and the results of a pilot study, were administered percutaneously to groups of artificially inseminated (Day 0) female rabbits on Days 7 through 18 of gestation. The dosage volume was 2 ml/kg. The control group contained 17 does and each test group contained 19 does. Does were observed for signs of test substance effect on abortion or premature delivery, body weight, and feed consumption. On Day 29, they were euthanized and examined for pregnancy, number and placement of implantations, early and late resorptions, and live fetuses. Pregnancy occurred in 15 control does (88%) and in 16 does in each test group (84%). There were no statistically significant differences between test and control groups for maternal body weight gain, feed consumption, number of corpora lutea per ovary, implantations, live fetuses, early and late resorptions, fetal body weights, gender, or gross external changes. There were no visceral or skeletal fetal alterations at any dose tested. No signs of maternal toxicity were observed; however, mild erythema occurred at the site of application at the 100 mg/kg/day dose level. The developmental no-effect level was greater than 100 mg/kg/day.

Administration, Topical↗
PubMed1988

Incidence and implications of natural deaths of road users.

A prospective study was carried out over the 10 years 1978-87 to determine the incidence and implications of sudden death in road users--that is, drivers, pedestrians, cyclists, and motorcyclists. During the study period 30,000 patients were seen in the same accident and emergency departments of East Berkshire after road traffic incidents or accidents, of whom 267 either were brought in dead or died within two hours after arrival. Of these patients, 64 (24%) were found to have died of natural causes due to pre-existing disease or to have been killed in an incident that occurred as a result of a medical or psychiatric condition. Twelve of the patients sustained physical injury; all 64 came to necropsy. Only one incident resulted in the death of another person in addition to the natural death of a patient. It is concluded that sudden natural death occurring in road users does not present an appreciable hazard to other road users.

Accidents, Traffic↗
PubMed1988

Developmental variation of the diaphragm and liver in Fischer 344 rats.

The nature and frequency of a developmental variation of the diaphragm and liver in Fischer 344 rats are described. Totals of 20, 98 and 55 (25 for caesarean-sectioning and 30 for natural delivery) mated female rats were used for Experiments 1, 2, and 3, respectively. Each rat was intubated (gavage) with either an aqueous suspension of 0.2% METHOCEL, 0.25% methyl cellulose, or distilled water as a single daily dose from days 6 through 15 (inclusive) of gestation. On the 20th day of gestation, a caesarean-section was performed, and the uterine contents of each rat were examined. A gross necropsy was performed on the pups of 30 mated female rats on day 21 postpartum. The visceral examinations conducted on these fetuses and pups included an evaluation of a developmental variation in the diaphragm and liver. The variation consisted of a thin fibrous central tendon of the diaphragm with an area of liver (0.5-3 mm diameter) that protruded within the thin central tendon of the diaphragm. The incidence (mean % of fetuses affected per litter) of the diaphragm/liver developmental variation was 9% and 11% for METHOCEL- and water-treated groups, respectively. A thin central tendon was present in the diaphragm of all fetuses of methyl cellulose-treated dams; these fetuses did not have a raised area of the liver present within the diaphragm's central tendon. However, in a few weaned pups of the Fischer 344 rats in this study, liver protruded within the central tendon of the diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Developmental toxicology investigation of tellurium.

The developmental toxicity of tellurium was evaluated in Crl Sprague-Dawley rats and New Zealand white rabbits by means of standard segment II-type studies. Groups of pregnant rats were fed a diet containing 0, 30, 300, 3000, or 15,000 ppm of tellurium on Days 6 through 15 of gestation (microscopic detection of sperm in a smear of vaginal contents considered as Day 0), and artificially inseminated rabbits were fed a diet containing 0, 17.5, 175, 1750, and 5250 ppm of tellurium during Days 6 through 18 of gestation (day of insemination considered as Day 0). Signs of maternal toxicity were observed during the treatment period in a statistically significant and dose-related manner at dietary concentrations of 300 ppm and greater in rats and 1750 ppm and greater in rabbits. Exposure of these pregnant rats and rabbits to tellurium had no effect upon reproduction as measured by pregnancy rate, litter size, dead or resorbed implantations, or fetal sex ratio. Both skeletal (primarily skeletal maturational delays) and soft tissue malformations (primarily hydrocephalus) were noted in the offspring of pregnant rats exposed to the highest levels (3000 and 15,000 ppm) of tellurium. Rabbit fetuses of the highest dosage group (5250 ppm) had a slightly elevated evidence of skeletal delays and nonspecific abnormalities. Since maternal toxicity was observed at dosages that did not affect the developing conceptus, there were no indications of unique developmental susceptibility upon exposure of pregnant rats or rabbits to tellurium.

Abnormalities, Drug-Induced↗
PubMed1987

Currently used alternatives to the Chernoff-Kavlock short-term in vivo reproductive toxicity assay.

The Chernoff-Kavlock assay was initially designed to identify developmental toxins within a relatively short time frame, using a mammalian system. Although it has been used for initial prioritization of multiple agents studied concurrently or for dosage-range evaluations, it has not gained wide usage in a commercial setting. As proposed, use of the Chernoff-Kavlock assay in an industrial setting is relatively inefficient, in terms of animal usage and data produced, when compared with available alternative study designs. Only a single dosage level was studied, and the data obtained from the assay do not provide sufficient information to meet the minimum requirements of safety evaluations submitted for regulatory review. For these reasons, other methods of prioritization are generally used. Alternate methods used for initial screening and prioritization at our laboratory are: 1) the hydra developmental toxicity assay; and 2) a dosage-range study in rats. When the results of several pilot and definitive developmental toxicity assays performed in rats were compared, it appeared that the described pilot study served the dual functions of predicting and prioritizing the developmental hazard of the test agent and providing a dosage-range study that identified the appropriate dosages to be tested in the definitive study.

Animals↗
PubMed1987

Use of the adult developmental relationship in prescreening for developmental hazards.

The overwhelming majority of chemicals already in commerce or brought into use each year have not been evaluated for their potential to adversely affect in utero development. Data from those that have been evaluated thus far in pregnant laboratory animals establish that most, but not all, were no more hazardous to the conceptus than they were to adult homeostasis. Most did not need standard developmental toxicity testing because avoidance of adult toxic exposure levels would have precluded abnormal in utero development. The six general principles of teratology when modified, expanded, and placed into this type of context of contemporary developmental toxicology allow an updating of the present testing sequence which was devised prior to 1966. The developmental hazard index (A/D ratio) calculated from the adult and developmental NOELs of standard Segment II evaluations is predicted by in vitro means. This determination, when coupled with adequate considerations of exposure can be used to prioritize chemicals for more elaborate developmental toxicity tests. Those chemicals with large ratios, i.e., disruptive of embryogenesis at treatment levels too low to produce overt effects in the mother and/or with significant concern regarding exposure, can be identified and tested in pregnant laboratory animals as high priority items. Those with low ratios and those for which there is a low level of concern regarding exposure potential also can be identified and are not high priority items for testing in pregnant animals. The proposed tier system establishes priorities of testing based on exposure and the concept of target organ toxicity applied to the embryo. It provides intensive in vivo evaluations of those chemicals for which developmental effects testing is most needed and avoids use of resources and animals for unnecessary testing of agents that do not pose threats to the conceptus.

Animals↗
PubMed1986

The developmental toxicity of xylene and xylene isomers in the Hydra assay.

Two laboratories tested multiple forms of xylene for their developmental toxicity hazard potential (A/D ratio) by means of the hydra assay. The three isomers, as well as a solution of mixed xylenes, all interfered with development (D) at or near to concentrations that also were toxic to adult (A) hydra. The A/D ratios ranged from 1 to 2 in hydra as they had in conventional tests made in pregnant laboratory animals. Each testing laboratory concluded that xylenes were not primary developmental hazards but coaffective agents capable of disrupting development only at or near to concentrations also toxic to adults. In each instance every xylene tested interfered with the same stage or developmental sequence and in a concentration-related manner. The hydra assay may be useful for establishing priorities to test agents in a more elaborate system, but substances less soluble than xylene may exceed the test's applicability.

Animals↗
PubMed1984

Morbidity and mortality of car occupants: comparative survey over 24 months.

The severity of injuries sustained by 2577 car occupants in road traffic accidents in the catchment area of one district accident service during February 1982 to January 1984 inclusive was assessed using the injury severity score system. In the first 12 months the mean injury severity score for front seat occupants injured in a road traffic accident was 4.94 and in the second 12 month period, after the implementation of the seat belt law, the mean injury severity score of all injured front seat occupants was 2.80. These figures indicated a reduction in injury severity of front seat occupants of 53.4% on the previous 12 month figures. The severity of injury sustained by unbelted front seat occupants and back seat passengers showed no significant change over the two years. The number of front seat occupants killed or sustaining serious injuries (injury severity score greater than 12) showed a reduction of 54% in the 12 months beginning February 1983. Front seat occupants requiring admission for injuries sustained showed a decline of 42% in the 12 months after the introduction of the seat belt law, and deaths among front seat occupants fell by 27% compared with the previous 12 months. After the implementation of seat belt legislation those front seat occupants killed or sustaining serious injuries included a significantly higher proportion of victims who were not wearing their seat belts or showed positive evidence of alcohol intake at the time of the accident. This series suggests that the incidence of serious injury or deaths among front seat occupants of cars has decreased substantially since the seat belt law became effective on 31 January 1983.

Accidents, Traffic↗
PubMed1984

Reproductive toxicity and teratology evaluations of naltrexone.

Reproductive toxicology and teratology studies of naltrexone are reviewed. Naltrexone produced behavioral changes in rats at doses below those which affected body weight. Excitatory signs and increased production of seminal plugs occurred in male rats. Prolonged administration to female rats resulted in excitatory signs and impaired maternal activity. Estrus cycling and fertility were decreased in female rats at doses that depressed body weight gain. Higher doses given to pregnant rats for shorter periods of time did not impair fertility or produce embryo or fetal toxicity. In rabbits, there was no evidence of behavioral changes. The highest dosage administered produced transient weight depression and possibly increased resorption. These data are consistent with a report of transient changes in some normal men given single doses of naltrexone. These effects may be mediated via hypothalamic and pituitary mechanisms involved in the control of luteinizing hormone levels.

Animals↗
PubMed1980

Confirmation of death.

A working party set up to study the problems surrounding the confirmation of death investigated current practice by means of a questionnaire sent to a random sample of accident and emergency departments in district general hospitals. Of the 38 replying, 24 said that bodies were examined in the ambulance, four in the accident and emergency department, and 10 in both. Answers to the other questions also suggest that the present procedures are in general unsatisfactory, and some dissatisfaction was expressed by departments. The individuals and organisations consulted were unanimous that confirmation of death should not be carried out in the ambulance. A change of practice would, however, create practical problems. The working party recommends therefore that the standard practice should be for all bodies to be properly examined by a doctor in the accident and emergency department, and that funds should be made available for any building alterations and increase in staff made necessary by such changes.

Ambulances↗