Could knee joint mechanics during the golf swing be contributing to chronic knee injuries in professional golfers?

Full three-dimensional movements and external moments in golfers' knees and the possible involvement in injuries have not been evaluated using motion capture at high sample frequencies. This study measured joint angles and external moments around the three anatomical axes in both knees of 10 professional golfers performing golf drives whilst standing on two force plates in a motion capture laboratory. Significant differences were found in the knee joint moments between the lead and trail limbs for the peak values and throughout all stages during the swing phase. A significantly higher net abduction moment impulse was seen in the trail limb compared with the lead limb (-0.518 vs. -0.135 Nms.kg-1), indicating greater loading over the whole swing, which could contribute to knee lateral compartment or anterior cruciate ligament injuries. A significant correlation (r = -0.85) between clubhead speed at ball contact and maximum joint moment was found, with the largest correlations being found for joint moments at the top of the backswing event and at the end of the follow-through. Therefore, although knee moments can contribute to high clubhead speeds, the large moments and impulses suggest that they may also contribute to chronic knee injuries or exacerbate existing conditions.

Which Phases of the Stroke Cycle Are Propulsive in Front Crawl Swimming?

Purpose: The aim of this study was fourfold: (1) to quantify acceleration, velocity, and phase overlap for each phase of the stroke cycle (SC) during 200 m front crawl; (2) for each variable, to identify any differences between the four SC phases; (3) to investigate changes in variables during the 200 m; (4) to explore any association between performance and each variable. Methods: Ten swimmers performed a 200 m maximum swim. Four SCs were analyzed, one for each 50 m, using three-dimensional methods. Each SC was split into four phases: entry, pull, push, and recovery. Center of mass (CM) acceleration; maximum, minimum, and average CM velocity; phase duration, and, overlap of a phase of one arm with each phase of the opposite arm were calculated. Results and Conclusion: Phase velocities were positively correlated with performance and decreased during the 200 m. The acceleration data showed high within and between-swimmer variability. When the entry of one arm overlapped with the pull, and sometimes push, phase of the opposite arm, it was propulsive for the whole body. The pull was the slowest phase and overlapped predominantly with the opposite arm's recovery. The push phase was often propulsive for the whole body, regardless of the overlaps with the other arm, and together with the entry were the fastest phases. The recovery of each arm was mostly resistive for the whole body, except the short period of overlap with the opposite arm's push phase.

Peak power, force, and velocity during jump squats in professional rugby players.

Training at the optimal load for peak power output (PPO) has been proposed as a method for enhancing power output, although others argue that the force, velocity, and PPO are of interest across the full range of loads. The aim of this study was to examine the influence of load on PPO, peak barbell velocity (BV), and peak vertical ground reaction force (VGRF) during the jump squat (JS) in a group of professional rugby players. Eleven male professional rugby players (age, 26 ± 3 years; height, 1.83 ± 6.12 m; mass, 97.3 ± 11.6 kg) performed loaded JS at loads of 20-100% of 1 repetition maximum (1RM) JS. A force plate and linear position transducer, with a mechanical braking unit, were used to measure PPO, VGRF, and BV. Load had very large significant effects on PPO (p < 0.001, partial η² = 0.915); peak VGRF (p < 0.001, partial η² = 0.854); and peak BV (p < 0.001, partial η² = 0.973). The PPO and peak BV were the highest at 20% 1RM, though PPO was not significantly greater than that at 30% 1RM. The peak VGRF was significantly greater at 1RM than all other loads, with no significant difference between 20 and 60% 1RM. In resistance trained professional rugby players, the optimal load for eliciting PPO during the loaded JS in the range measured occurs at 20% 1RM JS, with decreases in PPO and BV, and increases in VGRF, as the load is increased, although greater PPO likely occurs without any additional load.

The WATER study: Which AquaTic ExeRcises increase muscle activity and limit pain for people with low back pain?

OBJECTIVE: Aquatic exercise therapy is used for the treatment and management of chronic low back pain (CLBP). However, to the authors' knowledge, no studies to date have compared muscle activity between different aquatic exercises performed by people with CLBP. As such, this study assessed and compared muscle activity, pain, perceived exertion and exercise intensity between different rehabilitative aquatic exercises. DESIGN: Cross-sectional. SETTING: A 25-m indoor swimming pool within a university building. PARTICIPANTS: Twenty participants with non-specific CLBP. ASSESSMENT: Twenty-six aquatic exercises in shallow water (1.25-m depth). Muscle activity was quantified bilaterally for the erector spinae, multifidus, gluteus maximus and medius, rectus abdominis, and external and internal obliques. MAIN OUTCOMES: Mean and peak muscle activity, pain (visual analogue scale), perceived exertion (Borg scale) and exercise intensity (heart rate). RESULTS: Hip abduction/adduction and extension/flexion exercises produced higher activity for gluteal muscles. Variations of squat exercises increased the activity of back extensors. Higher abdominal muscle activity was produced with exercises that made use of buoyancy equipment and included leg and trunk movements while floating on the back, and with some proprioceptive and dynamic lower limb exercises. Pain occurrence and intensity were very low, with 17 exercises being pain free. CONCLUSIONS: This study provides evidence on trunk and gluteal muscle activity, pain, intensity and perceived exertion for people with CLBP performing aquatic exercises. The findings may be useful when prescribing exercises for rehabilitation, as physiotherapists seek to implement progression in effort and muscle activity, variation in exercise type, and may wish to target or avoid particular muscles. CONTRIBUTION OF THE PAPER.

Muscle Activity During Aquatic and Land Exercises in People With and Without Low Back Pain.

BACKGROUND: Chronic low back pain (CLBP) is the most prevalent musculoskeletal disorder. Aquatic exercises are commonly used by physical therapists for CLBP treatment and management; however, there are no data on trunk muscle activation during aquatic exercises in people with CLBP. OBJECTIVE: We quantified activation of trunk and gluteal muscles, exercise intensity, pain, and perceived exertion in people with and without CLBP when performing water and land exercises. DESIGN: The study used a cross-sectional design. METHODS: Twenty participants with nonspecific CLBP and 20 healthy participants performed 15 aquatic exercises and 15 similar land exercises. Mean and peak muscle activation were measured bilaterally from erector spinae, multifidus, gluteus maximus, gluteus medius, rectus abdominis, external oblique, and internal oblique using waterproof and wireless surface electromyography. Exercise intensity (heart rate), perceived exertion (Borg scale), and, for the CLBP group, pain (visual analog scale) were recorded. RESULTS: There were no significant between-group differences. Significant between-environment differences were found in heart rate (always higher on land), exertion (higher in the water for 3 exercises and on land for 6 exercises), and muscle activation (higher on land in 29% and in the water in 5% of comparisons). Pain levels were low, but pain was reported more than twice as frequently on land than in water (7.7% vs 3.7%, respectively). LIMITATIONS: People with high levels of disability and CLBP classification were not included. CONCLUSIONS: People with mild-to-moderate CLBP had similar exercise responses to healthy controls. Aquatic exercise produced sufficient muscle activation, intensity, and exertion, and should not be assumed to be less strenuous or less effective in activating trunk and pelvic muscles than exercise on land. These data can be used to inform design and prescription of rehabilitation programs and interventions.

Re-examining the effects of verbal instructional type on early stage motor learning.

The present study investigated the differential effects of analogy and explicit instructions on early stage motor learning and movement in a modified high jump task. Participants were randomly assigned to one of three experimental conditions: analogy, explicit light (reduced informational load), or traditional explicit (large informational load). During the two-day learning phase, participants learned a novel high jump technique based on the 'scissors' style using the instructions for their respective conditions. For the single-day testing phase, participants completed both a retention test and task-relevant pressure test, the latter of which featured a rising high-jump-bar pressure manipulation. Although analogy learners demonstrated slightly more efficient technique and reported fewer technical rules on average, the differences between the conditions were not statistically significant. There were, however, significant differences in joint variability with respect to instructional type, as variability was lowest for the analogy condition during both the learning and testing phases, and as a function of block, as joint variability decreased for all conditions during the learning phase. Findings suggest that reducing the informational volume of explicit instructions may mitigate the deleterious effects on performance previously associated with explicit learning in the literature.

Dominant lethal assay of chlordecone and its distribution in the male reproductive tissues of the rat.

Male rats received 3.6 or 11.4 mg/kg/day of chlordecone orally for 5 days. Some statistically significant events were seen in the reproductive data of females mated to males receiving chlordecone. However, these events did not follow a consistent pattern and do not suggest the conclusion that chlordecone causes dominant lethal effects. Male rats received a single oral dose (40 mg/kg) of chlordecone and were killed at 1, 2, 3, 5, 7, 14 or 21 days. Chlordecone was distributed throughout the reproductive tract. The descending order of concentration was seminal vesicular fluid greater than prostate greater than vas deferens greater than seminal vesicle greater than unwashed sperm greater than washed sperm. It is concluded that chlordecone is well distributed throughout the reproductive tract of the male rat, appears in the ejaculate, and does not appear to produce dominant lethal effects.

A combined reproduction, neonatal development, and neurotoxicity study with 1,6-hexamethylene diisocyanate (HDI) in the rat.

1,6-Hexamethylene diisocyanate (HDI), a chemical widely used in commercial polyurethane products, was evaluated in a combined reproductive/developmental/neurotoxicity study. Sprague-Dawley rats (n = 120; 15 per sex/dose group) were administered via whole-body inhalation exposure either 0, 0.005, 0.05, or 0.3 ppm HDI for 6 h/day during a 14-day premating phase, up to a 14-day mating phase, and a 21-day gestation phase. The dams and their litters were maintained for a 4-day lactation phase during which exposure to HDI was discontinued. Neurobehavioral testing (automated measures of activity and a functional observational battery) was conducted before exposure, after the premating phase, and before termination. Body weight and clinical observations were recorded throughout the study. Terminal examinations included a gross necropsy, hematology, and clinical chemistry. Tissues retained for microscopic examination included the reproductive organs, neural tissues, nasal turbinates (multiple sections), trachea, larynx, and lung. The animals were also evaluated for effects on mating, fertility, gestation length, litter size, pup sex ratio, and pup viability. In the 0.300 ppm dose group a statistically significant decrease in body weight was observed in the females on day 4 of the study. Also observed at this dose level, in both males and females, were microscopic alterations in the nasal cavity, primarily epithelial hyperplasia, squamous metaplasia, chronic-active inflammation, and more seriously, degeneration of the olfactory epithelium. Similar microscopic effects were also observed, albeit to a lesser extent, in the males and females of the 0.05 ppm dose level. No histopathologic effects were observed in the 0.005 ppm dose level. No effects on any reproductive or neurotoxicologic parameters, hematology, clinical chemistry, or any effects on pup growth and development were observed at any exposure level.

Subchronic toxicity, mutagenicity and allergenicity studies of a cultured dextrose food product.

MicroGARD(R) 200 is a fermented dextrose product used to extend food shelf-life by inhibiting spoilage due to Gram-negative bacteria, selected yeast and molds. The present studies were conducted to evaluate the safety of this food ingredient for determination of GRAS status. MicroGARD 200 was subjected to a bacterial reverse mutation assay, a subchronic oral toxicity study and an oral antigenicity study. It showed no evidence of mutagenic potential or toxicity in four strains of Salmonella typhimurium or in Escherichia coli strain WP2 uvrA with and without metabolic activation. MicroGARD 200 was orally administered to rats for 13 consecutive weeks at dietary concentrations of 0, 0.5, 2.0 or 5.0%. Water consumption and urinary excretion of sodium were slightly increased in both sexes at the high dose due to the sodium content of the test substance (about 6%). Increases in fasting glucose and decreased plasma creatinine were not accompanied by treatment-related histopathological changes and were within the normal range for historical controls. The potential antigenic properties of MicroGARD 200 were investigated via gavage in guinea pigs using an active systemic anaphylaxis (ASA) challenge [Annals of Allergy 67 (1991) 400; Allergy 49 (1994) 361]. There was no evidence of any anaphylactic sensitizing properties for MicroGARD 200.

Toxicological review of inorganic phosphates.

Inorganic phosphate salts are widely used as food ingredients and in a variety of commercial applications. The United States Food and Drug Administration (FDA) considers inorganic phosphates "Generally Recognized As Safe" (GRAS) (FDA, 1973a, 1979) [FDA: Food and Drug Administration 1973a. GRAS (Generally Recognized as Safe) food ingredients-phosphates. NTIS PB-221-224, FDA, Food and Drug Administration, 1979. Phosphates; Proposed Affirmation of and Deletion From GRAS Status as Direct and Human Food Ingredients. Federal Register 44 (244). 74845-74857, 18 December (1979)] and the European Union (EU) allows inorganic phosphates to be added directly to food (EU Directive 95/2/EC as amended by 98/72/EC). In this review, data on the acute, subchronic and chronic toxicity, genotoxicity, teratogenicity and reproductive toxicity from the published literature and from unpublished studies by the manufacturers are reviewed. Based on the toxicity data and similar chemistry, the inorganic phosphates can be separated into four major classes, consisting of monovalent salts, divalent salts, ammonium salts and aluminum salts. The proposed classification scheme supports the use of toxicity data from one compound to assess the toxicity of another compound in the same class. However, in the case of eye and skin irritation, the proposed classification scheme cannot be used because a wide range of responses exists within each class. Therefore, the eye and skin hazards associated with an individual inorganic phosphate should be assessed on a chemical-by-chemical basis. A large amount of toxicity data exists for all four classes of inorganic phosphates. The large and comprehensive database allows an accurate assessment of the toxicity of each class of inorganic phosphate. Overall, all four classes of inorganic phosphates exhibit low oral, inhalation and dermal toxicities. Based on these data, humans are unlikely to experience adverse effects when the daily phosphorus consumption remains below 70 mg/kg/day (JECFA, 1964, 1982a) [JECFA (Joint FAO/WHO Expert Committee on Food Additives 1964. Specifications for the Identity and Purity of Food Additives and their Toxicological Evaluation) Emulsifiers, Stabilizers, Bleaching, and Maturing Agents. Technical Report Series of the World Health Organization 281; ECFA (Joint FAO/WHO Expert Committee on Food Additives 1982a. Phosphoric Acid and Phosphate Salts. ICS/FA/82)].

Dental appliances for snoring and obstructive sleep apnoea: construction aspects for general dental practitioners.

The medical and dental aspects of management for patients diagnosed with snoring and obstructive sleep apnoea are well documented. However, guidance for treatment by the general dental practitioner is lacking. This article reviews aspects of appliance provision and presents the use of a silicone material in an attempt to improve the longevity of a recognized prosthesis.

Use of an audio-paced incremental swimming test in young national-level swimmers.

PURPOSE: To evaluate the reliability and sensitivity to training of an audio-paced incremental swimming test. METHODS: Eight young national-level male swimmers (age 15 +/- 1 year) performed a 7 x 200-m incremental swimming test (velocities 1.19, 1.24, 1.28, 1.33, 1.39, and 1.45 m/s and maximal sprint pace) using an audio-pacing device. The same test was performed 4 times by each participant, 1 wk apart to assess reliability (WK1, WK2) and after 9 and 20 wk of training (WK9, WK20). Blood lactate concentration ([La-]) and heart rate (HR) were recorded after each stage. Outcome measures were the velocity (v) and HR at lactate markers of 2 mM, 4 mM, and 1 mM. RESULTS: Velocities at the lactate markers proved to be more reliable than HR, with typical errors ranging from 0.66% to 2.30% and 1.28% to 4.50%, respectively (shifts in mean ranged -0.91% to 0.73% and -0.84% to 1.79%, respectively). Across WK1, WK9, and WK20 there were significant improvements in peak velocity (P < .001) and each of the velocities associated with the lactate markers (P < .05), whereas only HR at 1mM improved (P < .05). CONCLUSIONS: This article demonstrates that an audiopaced incremental swimming test is reliable for use with junior swimmers and is sensitive to changes observed after training. The postswimming measurement of HR in the pool was comparatively less reliable.

A three-dimensional examination of the planar nature of the golf swing.

Previous planar models of the downswing in golf have suggested that upper limb segments (left shoulder girdle and left arm) move in a consistent fixed plane and that the clubhead also moves only in this plane. This study sought to examine these assumptions. Three-dimensional kinematic analysis of seven right-handed golfers of various abilities (handicap 0- 15) was used to define a plane (named the left-arm plane) containing the 7th cervical vertebra, left shoulder and left wrist. We found that the angles of this plane to the reference horizontal z axis and target line axis (parallel to the reference x axis) were not consistent. The angle to the horizontal z axis varied from a mean of 133 degrees (s = 1 degrees) at the start of the downswing to 102 degrees (s = 4 degrees) at impact, suggesting a "steepening" of the left-arm plane. The angle of the plane to the target line changed from - 9 degrees (s = 16 degrees) to 5 degrees (s = 15 degrees) during the same period, showing anticlockwise (from above) rotation, although there was large inter-individual variation. The distance of the clubhead from the left-arm plane was 0.019 m (s = 0.280 m) at the start at the downswing and 0.291 m (s = 0.077 m) at impact, showing that the clubhead did not lie in the same plane as the body segments. We conclude that the left arm and shoulder girdle do not move in a consistent plane throughout the downswing, and that the clubhead does not move in this plane. Previous models of the downswing in golf may therefore be incorrect, and more complex (but realistic) simulations should be performed.

Narcotics and diabetes. I. The effects of streptozotocin-induced diabetes on the antinociceptive potency of morphine.

The antinociceptive potency of morphine as determined by the tail-flick test was significantly decreased in streptozotocin (STZ)-induced diabetic mice and mice pretreated with hypertonic dextrose or fructose. STZ-induced diabetic rats and spontaneously diabetic mice were also significantly less sensitive to the antinociceptive effects of morphine in the tail-flick test. Hypoglycemic mice were significantly more sensitive to morphine. Insulin-reversal of dextrose- and STZ-induced diabetic hyperglycemia returned sensitivity to morphine-induced antinociception to control values. Pretreatment with hypertonic 3-O-methylglucose (a nonmetabolizable sugar) had no effect on morphine potency. The ability of morphine to inhibit phenylquinone-induced writhing was attenuated in STZ-induced diabetic mice. Mice receiving various pretreatments (STZ-induced diabetes, STZ-induced diabetes plus insulin, dextrose, fasting or fasting plus insulin) were subjected to analyses of their serum glucose levels, serum insulin levels and brain glucose lvels. From these data, it appeared that only hyper- or hypoglycemia correlated (inversely) with changes in the potency of morphine. It is hypothesized that the diabetes-induced hyperglycemia is responsible for selectively affecting the potency of morphine.

Luxatio erecta: persistent displacement of the greater tuberosity after reduction.

The case of a 36-year-old man who sustained a luxatio erecta dislocation of his shoulder is reported. He had persistent displacement of a fracture of the greater tuberosity after closed reduction of the shoulder. The two-part fracture required operative treatment. This is the first occurrence of this complication reported in the literature.

Narcotics and diabetes. II. Streptozotocin-induced diabetes selectively alters the potency of certain narcotic analgesics. Mechanism of diabetes: morphine interaction.

The antinociceptive potencies of phenazocine and levorphanol were altered similarly to that of morphine in streptozotocin (STZ)-induced diabetic and transiently hyper- or hypoglycemic mice, but the potencies of methadone, propoxyphene and meperidine were not altered by changes in serum glucose levels. The acute, s.c. LD50 of morphine in STZ-induced diabetic mice was significantly lower than in the control mice, but the acute s.c. LD50 of methadone was not altered by STZ-induced diabetes. By using morphine as the prototype drug for subsequent experiments, it was demonstrated that the potency of naloxone in antagonizing the effects of morphine in te tail-flick test was not altered in diabetics. Levels of morphine in the brains of STZ-induced diabetic mice were not significantly different from control mice. The durations of action of morphine in STZ-induced diabetes and control mice were similar. We conclude that changes in serum glucose levels can selectively alter the potency of certain narcotic analgesics. The interaction between STZ-induced diabetes and morphine-induced antinociception does not appear to be due to differences in the absorption, distribution or elimination of morphine between diabetic and nondiabetic mice.

Clubfeet and tarsal coalition.

Tarsal coalition was noted in 18 cases of rigid equinovarus deformity. Sixteen cases were encountered at surgery and two at morbid dissection. There were 14 patients in the series; six had associated pathologic conditions that might have caused their clubfeet to be deemed "teratologic," whereas eight did not and were considered to have congenital clubfeet. Four patients in the series had bilateral coalitions. Preoperative radiographs demonstrated the coalition in only one case. A presurgical magnetic resonance image (MRI) clearly showed the coalition in another case. Nonoperative treatment was unsuccessful. Two patients with tibial dysplasia had ankle disarticulations. The remaining 16 feet required extensive soft-tissue releases, internal fixation, and coalition excision. The vast majority of cases showed cartilaginous subtalar coalition at the medial facet. The patients were followed for an average of 6 years, and two recurrences were noted. Remaining feet were painless and plantargrade, but were rather stiff. This anomaly may be more common than previously described. It is usually not suspected preoperatively and may likewise be difficult to recognize at surgery. A preoperative MRI scan may also be helpful.

Effects of coumarin following perinatal and chronic exposure in Sprague-Dawley rats and CD-1 mice.

Coumarin, a naturally occurring substance most frequently used as a fragrance enhancer and stabilizer, was administered in the diet of Sprague-Dawley rats at dose levels of 0, 333, 1000, 2000, 3000, and 5000 ppm or in the diet of CD-1 mice at dose levels of 0, 300, 1000, or 3000 ppm. Rats receiving 333, 1000, and 2000 ppm coumarin were exposed to these dose levels in utero and during the lactational period, then chronically following weaning. Rats in the 3000- and 5000-ppm dose groups and all mice received only postweaning chronic exposure. All male rats were terminated after 104 weeks of postweaning exposure; female rats were terminated after 110 weeks: Male mice were terminated at Week 101 and female mice at Week 109. Among rats, survival was decreased at 333 ppm, but significantly increased among rats in the 3000- and 5000-ppm dose groups. Dramatic dose-related decreases in body weight gain were recorded for rats receiving 2000, 3000, and 5000 ppm, clearly indicating that the MTD (maximum tolerated dose, as indicated by a body weight decrement of greater than 10-15%) was exceeded. Food consumption also was decreased at the three highest dose levels, although body weight decrement was disproportionately large compared to changes in food consumption. Treatment-related decreases in hemoglobin were recorded from Week 6 onward. Minimal treatment-related changes in hematology and clinical chemistry were recorded. Increased liver weights were observed for male and female rats receiving 3000 or 5000 ppm and for females only at 1000 and 2000 ppm. Increased incidences of cholangiofibroma, cholangiocarcinoma, and parenchymal liver cell tumors were observed among male and female rats receiving 5000 ppm. One male rat receiving 3000 ppm developed a cholangiocarcinoma; no tumor increase was observed in males or females at 2000 ppm or below. Coumarin, at a dose clearly exceeding the MTD can, therefore, induce liver tumors in rats, although survival, relative to controls, was increased at the same dose levels. Among mice, a decrease in body weight gain was reported for males in the 1000- and 3000-ppm dose groups during the first 52 weeks of the study. No dose-related abnormalities in clinical signs, clinical pathology, hematology, or gross or microscopic pathology were noted.

Worker exposure and protective clothing performance during manual seed treatment with lindane.

Twelve workers were monitored for exposure to 18.75% lindane dust formulation during manual wheat seed treatment. The mean total actual exposure rate was 32.89 mg/hr. Potential respiratory exposure averaged 0.0057 mg/hr (less than 1% of the total), with seven workers receiving no measurable respiratory exposures. Mean hand exposure was 1.84 mg/hr (5.6%). Dermal exposure to the head and neck averaged 4.28 mg/hr (13%). Exposure measured beneath the workshirt and workpants averaged 26.8 mg/hr (81.4%). The workshirt and workpants provided 3.4-fold and 11.5-fold protection factors, respectively. Forearm exposure measured beneath the workshirt represented more than 40% of total actual exposure. The small contribution of hand exposure to total dermal exposure was consistent with the use of chemical-resistant gloves by all workers. Total dermal exposure could be reduced substantially by wearing coveralls over regular work clothing, and by the use of guantlet-type gloves. It is recommended that worker education concerning personal hygiene and the appropriate use of protection clothing be made essential components of exposure reduction programs.

Developmental toxicity of 1,6-hexamethylene diisocyanate (HDI) in the Sprague-Dawley rat.

BACKGROUND: 1,6-Hexamethylene diisocyanate (HDI), a widely used chemical in commercial polyurethane manufacture, has been shown to affect the respiratory tract of experimental animals. However, its potential to affect neonatal development, particularly after inhalation exposure, is less well described. The present study was conducted to assess the developmental toxicity of HDI. METHODS: Gravid Sprague-Dawley rats were exposed to concentrations of 0, 0. 005, 0.050, or 0.300 ppm HDI via inhalation (whole-body exposure) on days 0-19 of gestation. Maternal toxicity, as demonstrated by clinical signs and changes in body weight gain during gestation, was characterized. Dams were sacrificed on gestation day 20, at which time fetuses were removed by cesarean section, the uterus was examined, and a gross maternal necropsy was performed. Maternal evaluation also included lung weight and a detailed histopathologic assessment of the nasal turbinates, larynx, trachea, and lungs. All fetuses were evaluated for external anomalies. Approximately one-half of each litter was examined for visceral effects, the other half underwent a skeletal (bone and cartilage) examination. RESULTS: Maternal toxicity was demonstrated in the 0.300- and, to a lesser extent, in the 0.050-ppm exposure groups. No maternal effects were noted in the 0.005-ppm group. Test compound-related maternal effects were restricted to histopathological findings and included acanthosis, hyperkeratosis, inflammation of the nasal turbinates, and, more seriously, degeneration of the olfactory epithelium. No pathological alterations were noted in the larynx, trachea, or lungs in any dose group. No test compound-related effects were observed on any reproductive parameters, or any embryonic endpoints, including pre/postimplantation loss and resorption. There were no effects on litter size or the number of fetuses per implantation site and no effects on fetal or placental weights were observed. No test compound-related fetal external, visceral, or skeletal findings were observed. No effect on the fetal or litter incidence of total malformations or variations was observed, and there was no difference in the incidence of malformations between males and females. CONCLUSIONS: Administered as described in this study, 1, 6-HDI produced maternal effects (nasal turbinate histopathology) at concentrations of 0.050 and 0.300 ppm with no developmental toxicity observed at any concentration.