Strain-dependent differences in the metabolism of 3-methylcholanthrene by maternal, placental, and fetal tissues of C57BL/6J and DBA/2J mice.

C57BL/6J (B6) and DBA/2J (D2) mice have different susceptibilities to developmental toxicity and transplacental carcinogenesis induced by in utero exposure to polycyclic aromatic hydrocarbons, which has been associated with polycyclic aromatic hydrocarbon metabolism and inducibility at the Ah locus. The distribution of total 3-methylcholanthrene (3-MC)-associated radioactivity in maternal, placental, and fetal tissues of beta-naphthoflavone-pretreated pregnant B6 and D2 mice was determined up to 12 h after p.o. exposure to [6-14C]-3-MC (63 mg/kg, 20 mu Ci) on gestational day 17. 3-MC-associated radioactivity in maternal plasma was not significantly different in the two strains. However, D2 tissue homogenates had consistently higher levels of 3-MC-associated radioactivity, which included both bound and free parent compound and metabolites. Increased metabolism of 3-MC by B6 maternal liver was suggested by the induced levels of aryl hydrocarbon hydroxylase activity in that tissue and by the observation that levels of total radioactivity decreased more rapidly in B6 tissues than in D2 tissues. The D2 fetal lung, the target tissue for 3-MC-induced transplacental carcinogenesis, appeared to accumulate 3-MC-associated radioactivity for a longer period of time than either the D2 fetal liver or the B6 fetal tissues. This study suggests that the genetic differences in fetal susceptibility to the developmental toxicity and transplacental carcinogenesis of 3-MC may be related to the presystemic elimination of the compound from both maternal and fetal tissues.

Amniotic fluid microviscosity determined by fluorescence polarization: methodology and relation to gestational age.

The fluorescence polarization of 116 amniotic fluid specimens obtained from 22 isoimmunized pregnant women was determined. The degree of fluorescence polarization of amniotic fluid provides an index of microvisocity in lipid aggregates that is dependent on the lecithin-to-sphingomyelin ratio and the degree of saturation of fatty acid side chains. We confirmed the reproducibility of the measurement of amniotic fluid microviscosity (coefficient of variation, 2.0%). The measurements are not effected by bilirubin concentration of amniotic fluid dilution. The pattern of change of amniotic fluid microviscosity during gestation parallels the expected development of the surfactant system. Amniotic fluid microviscosity is high during early gestation and abruptly and sequentially decreases between the 28th and 36th week of gestation. Since the measurements are an accurate reflection of the biochemical properties of amniotic fluid lipids and parallel the development of the surfactant system, we conclude that amniotic fluid microviscosity may well serve as an indicator of the process of fetal lung maturation.

Manual micromethods for bilirubin determination in sera of adults and children and investigation of reasons for observed differences.

This study compared three micromanual methods for determining bilirubin concentration. The two microchemical methods for total bilirubin, a Jendrassik-Grof procedure and a Unopette procedure, using dimethyl sulfoxide as an accelerator and protein solubilizer, gave comparable results in sera of adults and children. A microspectrophotometric method and the microchemical methods for total bilirubin gave similar results in plasmas of newborns with physiologic hyperbilirubinemia and in sera of older children with no hepatic abnormality. However, the microspectrophotometric method gave higher values in normal and hyperbilirubinemic adult sera. The results obtained with the Jendrassik-Grof and Unopette microchemical methods for direct bilirubin in sera of adults and children showed the values determined by the Unopette to be higher. Using the presently accepted normal range, this difference is significant enough to preclude recommendation of the use of the Unopette method for distinguishing normal from elevated levels of direct bilirubin. Direct bilirubin in newborn serum measured by the Unopette method is considerably higher than that measured by the Jendrassik-Grof method. An investigation to determine the reason for the difference in the direct bilirubin results indicated that the Unopette direct method measures diconjugated bilirubin in amounts similar to those measured by the Jendrassik-Grof method but significantly more monoconjugated bilirubin than the Jendrassik-Grof method.

Evaluation of the developmental toxicity of isoeugenol in Sprague-Dawley (CD) rats.

Isoeugenol, used as a perfumery and flavoring agent, was evaluated for developmental toxicity. Timed-pregnant CD((R)) outbred albino Sprague-Dawley rats received isoeugenol (250, 500, or 1000 mg/kg/day) or vehicle (5 ml/kg corn oil) by gavage on gestational days (gd) 6 through 19. Maternal food and water consumption, body weight, and clinical signs were monitored at regular intervals throughout gestation. At termination (gd 20), confirmed-pregnant females (23-25 per group) were evaluated for gestational outcome. All live fetuses were weighed and examined for external malformations, and approximately 50% were evaluated for visceral or skeletal malformations. There were no treatment-related maternal deaths. Clinical signs associated with isoeugenol exposure included dose-related evidence of sedation and aversion to treatment (rooting behavior) in all isoeugenol groups, as well as an increased incidence of piloerection at >/= 500 mg/kg/day. Maternal body weight, weight gain, and gestational weight gain (corrected for gravid uterine weight) were reduced at all doses in a dose-related manner. Gravid uterine weight was significantly decreased at the mid and high doses, whereas maternal relative liver weight was increased at all three dose levels. During treatment (gd 6 to 20), maternal relative food consumption was significantly decreased at the high dose, and maternal relative water consumption was elevated in the mid- and high-dose groups. Prenatal mortality (resorption or late fetal death) was unaffected. At 1000 mg/kg/day, average fetal body weight/litter was decreased by 7% (male) or 9% (female). Incidences of fetal morphological anomalies were statistically equivalent among groups, except for an increase in the incidence of unossified sternebra(e), a skeletal variation, at the high dose. In summary, the maternal toxicity lowest observed adverse effect level (LOAEL) was 250 mg/kg/day based primarily on reduced body weight and gestational weight gain (corrected for gravid uterine weight), and the maternal toxicity no observed adverse effect level (NOAEL) was not determined in this study. The developmental toxicity LOAEL was 1000 mg/kg/day based on intrauterine growth retardation and mildly delayed skeletal ossification. The developmental toxicity NOAEL was 500 mg/kg/day.

Evaluation of the developmental toxicity of formamide in Sprague-Dawley (CD) rats.

Timed-pregnant CD(R) outbred albino Sprague-Dawley rats received formamide (50, 100, or 200 mg/kg/day) or vehicle (5 ml/kg deionized/distilled water, po) on gestational days (gd) 6 through 19. Maternal food and water consumption (absolute and relative), body weight, and clinical signs were monitored at regular intervals throughout gestation. At termination (gd 20), confirmed-pregnant females (21-23 per group) were evaluated for clinical status and gestational outcome; live fetuses were examined for external, visceral, and skeletal malformations and variations. There were no maternal deaths and no dose-related clinical signs. At 200 mg/kg/day, maternal body weight on gd 20, weight gain, and gravid uterine weight were significantly decreased. Maternal weight gain, corrected for gravid uterine weight, liver weight (absolute or relative), and food and water consumption (absolute or relative), were not affected. Formamide did not affect prenatal viability or incidences of fetal malformations or variations. Average fetal body weight/litter was decreased at 100 and 200 mg/kg/day. Fetal body weight was affected at lower daily doses than in previously published studies, possibly due to the longer total exposure period and/or lack of a recovery period between cessation of exposure and termination. In summary, the maternal toxicity no-observed-adverse-effect level (NOAEL) was 100 mg/kg/day and the low observed adverse effect level (LOAEL) was 200 mg/kg/day under the conditions of this study. Similarly, the developmental toxicity NOAEL was 50 mg/kg/day and the LOAEL was 100 mg/kg/day.

Evaluation of the developmental toxicity of methacrylamide and N,N'-methylenebisacrylamide in Swiss mice.

Timed-pregnant CD-1 outbred albino Swiss mice received either methacrylamide (MAC; 0, 60, 120, or 180 mg/kg/day) or N,N'-methylenebisacrylamide (BAC; 0, 3, 10, or 30 mg/kg/day) p.o. in distilled water on gestational days (GD) 6 through 17. Maternal clinical status was monitored daily. At termination (GD 17), confirmed-pregnant females (27-30 per group, MAC; 24-25 per group, BAC) were evaluated for clinical status and gestational outcome; live fetuses were examined for external, visceral, and skeletal malformations. For MAC, no treatment-related maternal mortality was observed. Maternal body weight on GD 17, maternal weight gain during treatment and gestation, and corrected maternal weight gain were reduced at the high dose. Relative maternal food and water intake was not adversely affected; neurotoxicity was not observed. Relative maternal liver weight was increased at > or = 120 mg/kg/day; gravid uterine weight was decreased at 180 mg/kg/day. The maternal no-observed adverse effect level (NOAEL) was 60 mg/kg/day. The NOAEL for developmental toxicity was also 60 mg/kg/day. At > or = 120 mg/kg/day, mean fetal body weight was reduced. At 180 mg/kg/day, increased postimplantation death per litter was observed. Morphological development was not affected. The maternal NOAEL for BAC was 10 mg/kg/day. At 30 mg/kg/day, decreased maternal body weight on GD 17, maternal body weight change during treatment and gestation, corrected maternal body weight, and gravid uterine weight were observed. Relative maternal liver weight increased at 30 mg/kg/day. The developmental NOAEL was 3 mg/kg/day BAC. Mean fetal body weight was reduced at 30 mg/kg/day. At > or = 10 mg/kg/day, an increased incidence of fetal variations (extra rib) was observed, although fetal malformation rate was unaffected. MAC and BAC were not teratogenic to Swiss mice at the doses tested. BAC was more potent than MAC in causing adverse maternal and developmental effects.

Non-exercise VO2max estimation for physically active college students.

This study sought to develop a maximal oxygen consumption (VO2max) regression model derived strictly from self-reported non-exercise (N-EX) predictor variables. The VO2max (mean +/- SD; 44.05 +/- 6.6 ml.kg-1.min-1) of 100 physically active college students (50 females, 50 males), aged 18 to 29 yr, was measured using a treadmill protocol and open circuit calorimetry. Questionnaire-based predictor variables used in the N-EX regression model included (a) the subject's perceived functional ability (PFA) to walk, jog, or run given distances, (b) habitual physical activity (PA-R) data, (c) body mass index (BMI), and (d) gender. BMI (kg.m-2) was computed from self-reported body weight in pounds and self-reported body height in feet and inches. The questionnaire-based N-EX regression model (R = 0.85, SEE = 3.44 ml.kg-1.min-1) developed in this study exceeded the accuracy of previously developed N-EX regression models and is comparable to many exercise-based regression models in the literature. Cross-validation using PRESS (predicted residual sum of squares) statistics demonstrated minimal shrinkage (R = 0.84, SEE = 3.60 ml.kg-1.min-1) of the present regression model. The PFA data were useful in explaining observed VO2max variance (squared partial r2 = 0.155, P < 0.0001) and enhanced the ability of the N-EX regression model to accurately predict criterion VO2max. These results suggest that a questionnaire-based N-EX regression model provides a valid and convenient method for predicting VO2max in physically active college students.

Stroke volume does not plateau during graded exercise in elite male distance runners.

UNLABELLED: Stroke volume (SV) responses during graded treadmill exercise were studied in 1) elite male distance runners (N = 5), 2) male university distance runners (N = 10), and 3) male untrained university students (N = 10). METHODS: Cardiac output (Q) and SV were determined by a modified acetylene rebreathing procedure. RESULTS: There were no differences in SV responses among the three groups during the transition from rest to light exercise (P > 0.05). However, the rates of change of SV during light to maximal exercise in untrained subjects (slope = -0.1544 mL x beat(-1)) and university distance runners (slope = 0.1041) did not change, whereas it dramatically increased (P < 0.001) in elite distant runners (slope = 0.6734). Moreover, the elite distance runners showed a further slope increase in SV when heart rate was above 160 bpm, which resulted in an average maximal SV of 187 +/- 14 mL x beat(-1) compared with 145 +/- 8 and 128 +/- 14 mL x beat(-1) in the university runners and untrained students, respectively (P < 0.001). Similarly, max Q reached 33.8 +/- 2.3, 26.3 +/- 1.7, and 21.3 +/- 1.5 L x min(-1) in the three groups, respectively (P < 0.001). On the other hand, there was a nonsignificant tendency for maximal arteriovenous oxygen content difference to be lower in the elite athletes compared with the other groups. CONCLUSION: Results from university distance runners and untrained university students support the classic observation that SV plateaus at about 40% of maximal oxygen consumption despite increasing intensity of exercise. In contrast, stroke volume in the elite athletes does not plateau but increases continuously with increasing intensity of exercise over the full range of the incremental exercise test.

Development of a submaximal treadmill jogging test for fit college-aged individuals.

The purpose of this study was to develop a single-stage submaximal treadmill jogging test for the estimation of maximal oxygen uptake (VO2max). VO2max was measured in 129 relatively fit individuals (males = 84, females = 45), 18-29 yr, using a maximal treadmill protocol (mean +/- SD; VO2max = 48.3 +/- 6.2 ml.kg-1 x min-1, range = 35.6 to 62.3 ml.kg-1 x min-1). The treadmill test required subjects to sustain a comfortable, submaximal jogging pace (4.3-7.5 mph; level grade) until a steady-state heart rate was achieved (approximately 3 min). To help ensure that a submaximal level of exertion was realized for the treadmill jogging test, treadmill speed and exercise HR criteria were established that restricted treadmill speed to < or = 7.5 mph for males and < or = 6.5 mph for females and steady-state exercise HR < or = 180 bpm. Multiple regression analysis (N = 66) to estimate VO2max from the treadmill jogging test yielded the following validation (V) model (r(adj) = 0.84, SEE = 3.2 ml.kg-1 x min-1): VO2max = 54.07 + 7.062 * GENDER (0 = female; 1 = male) - 0.1938 * WEIGHT (kg) + 4.47* SPEED (miles.h-1) - 0.1453 * HEART RATE (bpm). Cross-validation (CV) of the treadmill jogging test comparing observed and estimated VO2max (N = 63) resulted in r(adj) = 0.88, SEE = 3.1 ml.kg-1 x min-1. The results indicate that this submaximal single-stage treadmill jogging test based on multiple linear regression provides a valid and convenient method for estimating VO2max.

VO2max estimation from a submaximal 1-mile track jog for fit college-age individuals.

The primary purpose of this study was to develop a submaximal field test for the estimation of maximal oxygen uptake (VO2max) using a 1-mile track jog. A second purpose was to determine the accuracy of the 1.5-mile run in estimating VO2max for both male and female subjects. VO2max was measured in 149 relatively fit college students (males = 88, females = 61) 18-29 yr using a treadmill protocol (mean +/- SD; VO2max = 47.7 +/- 6.3 ml.kg-1 x min-1). Multiple regression analysis (N = 54) to estimate VO2max from the submaximal, steady-state 1-mile track jog yielded the following validation (V) model (r(adi) = 0.87, SEE = 3.0 ml.kg-1 x min-1): VO2max = 100.5 + 8.344* GENDER (0 = female; 1 = male) - 0.1636* BODY MASS (kg) - 1.438* JOG TIME (min.mile-1) - 0.1928* HEART RATE (bpm). To help ensure that a submaximal level of exertion was realized for the 1-mile track jog, elapsed jog time was restricted to > or = 8.0 min for males and > or = 9.0 min for females and exercise HR to < or = 180 bpm. Cross-validation (CV) of the 1-mile track jog comparing observed and estimated VO2max (N = 52) resulted in radj = 0.84, SEE = 3.1 ml.kg-1 x min-1. Multiple regression analysis (N = 50) to estimate VO2max from the 1.5-mile run (V:N = 49, radj = 0.90, SEE = 2.8 ml.kg-1 x min-1; CV: N = 47, radj = 0.82, SEE = 3.9 ml.kg-1 x min-1), used elapsed run time, body mass, and gender as independent variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of model vascular trauma on the hepatic drug-metabolizing enzymes of the neonatal rat.

Abdominal aorta ligation in neonatal rats was used as a model for pediatric traumatic injury. Short-term ischemic trauma (24 h) was found to have significant effect on plasma corticosterone levels, and on the specific activity of the drug-metabolizing enzymes FAD-containing monooxygenase and glucuronyl transferase in hepatic microsomes. Ischemic injury was determined to cause a decrease in FAD-containing monooxygenase activity in pre-weaning animals. Glucuronyl transferase activity was increased by this surgical procedure in animals less than 12 days age, and after weaning; however, glucuronyl transferase activity was decreased by this model in rats between 14 days of age and weaning.

Developmental toxicity evaluation of 1,2,3,4-butanetetracarboxylic acid in Sprague Dawley (CD) rats.

1,2,3,4-butanetetracarboxylic acid (BTCA), proposed as a formaldehyde substitute in the treatment of permanent press fabrics, was evaluated for developmental toxicity. Timed-mated CD rats (25 per group) received BTCA 250, 500, or 1000 mg/kg/day or vehicle (deionized/distilled water) by gavage on gestational days (gd) 6 through 19. Maternal feed and water consumption, body weight, and clinical signs were monitored throughout gestation. At termination (gd 20), confirmed-pregnant females (21 to 25 per group) were evaluated for clinical status and gestational outcome; live fetuses were examined for external, visceral, and skeletal malformations. One maternal death, reduced body weight, and reduced weight gain were noted at the high dose; confirmed pregnancy rates were 84 to 100% for each group. There were no treatment-related effects on fetal growth, survival, or morphologic development. The maternal toxicity NOAEL and LOAEL are 500 and 1000 mg/kg/day, respectively. The developmental toxicity NOAEL is > or = 1000 mg/kg/day, and the LOAEL was not established in this study.

Formamide and dimethylformamide: reproductive assessment by continuous breeding in mice.

Reproductive toxicity in Swiss mice, during chronic exposure to formamide (FORM) or dimethylformamide (DMF), was evaluated using the Reproductive Assessment by Continuous Breeding Protocols. FORM administered in drinking water at 0, 100, 350, and 750 ppm (approximately 20 to 200 mg/kg/d) reduced fertility and litter size in F0 animals without generalized toxicity at 750 ppm FORM. Crossover matings suggested that females were the affected sex. After F1 mating, FORM reduced F2 litter size, increased days to litter, reduced relative ovarian weight, and lengthened estrous cycles at 750 ppm. The No-Observed-Adverse-Effect-Level for generalized toxicity was 750 ppm for the F0 and 350 ppm for the F1 generation. Reproductive performance was normal at 350 ppm for both F0 and F1 mice. Chronic exposure to DMF in drinking water at 0, 1000, 4000, and 7000 ppm (approximately 200 to 1300 mg/kg/d) reduced fertility by the first litter at 4000 ppm, reduced body weight in F0 females at 7000 ppm, and increased liver weights at all doses in both sexes. A crossover mating at 7000 ppm identified F0 females as the affected sex. F1 postnatal survival was reduced at > or =4000 ppm DMF. F1 mating reduced F2 litter size and live pup weight at > or =1000 ppm. At necropsy, body weight of F1 males and females was reduced at > or =4000 ppm. DMF-treated pups (both F1 and F2) and F1 adults had cranial and sternebral skeletal malformations. Only DMF caused overt developmental toxicity. A No-Observed-Adverse-Effect-Level for DMF was not established.

Navy review of nasopharyngeal radium treatments of submarine candidates.

From approximately 1945 through 1960 nasopharyngeal radium treatments were used to treat barotrauma incurred during submarine escape training by submarine candidates. Concern has been expressed that the treatments placed submarine candidates at significantly increased risk of having brain cancer develop. The concern is based on brain cancer incidence rates reported in a study of Washington County children. Using comparable populations' risk coefficients and secondary brain tumor incidence rates, the excess number of brain cancers per 10,000 subjects during the 42.5 years after treatment was calculated to be 0.5 to 2.8 cases and 1 case, respectively. Personnel records of a sample of those treated and others whose treatment status was unknown were reviewed to determine the feasibility of an epidemiologic study to confirm the cancer risk. The records indicated treatments were not consistently documented to confirm who was treated. In addition, social security numbers are not known to aid in determination of vital status. In conclusion, nasopharyngeal irradiation does not appear to pose a significant risk to submariners, and it is not feasible to use the submariner population to do a meaningful epidemiologic study to clarify the cancer risk.

Coincident resection-recession (tenectomy-recession) of the medial rectus muscle, bilaterally, for the treatment of esotropia: results in 18 cases.

PURPOSE: To study the effect of preceding tenectomy of the medial rectus tendon on the results of medial rectus muscle recession. SUBJECTS AND METHODS: Eighteen consecutive cases of incomitant esotropia were retrospectively reviewed. The average preoperative esotropia was 35 PD with an incomitant deviation between 10 PD and 30 PD. All patients underwent 7 mm bilateral medial rectus muscle recession after 4 mm tenectomy of the anterior medial rectus muscle. RESULTS: Fourteen patients (78%) had "satisfactory" results (within 10 PD static esodeviation and 12 PD dynamic deviation [incomitance]). Four (22%) were undercorrected. One showed a postoperative consecutive exotropia of 4 PD at distance only. CONCLUSIONS: Tenectomy of the anterior muscle tendon preceding large recessions of the medial rectus was effective in reducing the frequency of overcorrection (consecutive exotropia). Undercorrection did not appear to be more common.

Molecular dynamics of the compensatory response to myocardial infarct.

Myocardial infarct via occlusion of the left anterior descending coronary in rats caused overriding depression in transcription, signal transduction, inflammation and extracellular matrix pathways in the infarct zone within 24 h. In contrast, remote zone gene expression was reciprocally activated during the immediate post-infarct period. Infarct zone signal transduction occurred primarily through TGFbeta1 induction while the remote zone exhibited elevated WNT, NOTCH, GPCR and transmembrane signaling. A minimal day 1 acute phase, inflammatory response was detected in the infarct zone while interleukins (IL1alpha, IL1beta, IL6, IL12alpha, IL18) and the TNFalpha superfamily were activated in the remote zone. Different cytochrome subsets were activated in each left ventricular region on day 1 while anti-oxidant genes were elevated only in the remote zone. The infarct zone exhibited mixed early transcription factor activation across all binding domains with a balance favoring constitutive gene activation and differentiation pathways as opposed to cell proliferation. In contrast, the remote zone exhibited activation of extensive developmental transcription factors involved in specification of cell phenotype, tissue-specific interactions and position-specific cell proliferation on day 1. The day 28 infarct zone response mirrored the day 1 remote zone response including activation of genes associated with matrix remodeling (metallothionein and metalloproteinase 9, 12, 23), as well as genes associated with cell proliferation and phenotype specification (MYC, EGR2, ATF3, HOXA1) recapitulating developmental histogenesis programs.

Prediction of ice skating performance with off-ice testing in women's ice hockey players.

Off-ice predictors of skating performance have not been investigated for women's hockey players. The purpose of this study was to identify the off-ice variables associated with high-performance skating acceleration, speed, agility, and on-ice anaerobic capacity and power in women's ice hockey players. Sixty-one women's ice hockey players between the ages of 8 and 16 years (x age = 12.18 +/- 2.05 years, x playing experience = 4.68 +/- 2.69 years) participated in the study. Subjects were 1-4 months postseason. Some players were continuing to play once per week during the off-season. Skating tests (ST) included (a) 6.10-m acceleration, (b) 47.85-m speed, (c) agility cornering S turn, and (d) modified repeat skate test (MRS). Two trials of each ST were measured with a photoelectric timing system (except MRS, which was measured with 1 trial). The off-ice variables that were evaluated included age, years of playing experience, height, body mass, predicted fat percentage, sit-and-reach flexibility, vertical jump height, 40-yd dash time, and 1-minute timed sit-ups and push-ups. The results of this study show that 40-yd dash time is the strongest predictor of skating speed in women's hockey players ages 8-16 years old. From the regression procedure the best prediction equation was speed = 4.913 - (0.0107 x kilograms) + (0.4356 x 40-yd dash time).

Effect of metoclopramide on gastric function in man.

The effects of metoclopramide on gastric emptying and gastric secretion have been assessed in man using the double sampling test meal. Metoclopramide increases the rate of emptying of the stomach. The magnitude of the effect is directly related to the initial emptying time. Metoclopramide has no effect on the acid response to a water test meal.

Reproductive toxicity of tricresyl phosphate in a continuous breeding protocol in Swiss (CD-1) mice.

The effects of a mixture of tricresyl phosphate isomers on reproductive performance in Swiss (CD-1) mice were evaluated using a continuous breeding protocol. Tricresyl phosphate (TCP) was mixed into the feed at 0, 0.05, 0.1, and 0.2% by weight. Although the fertility index was not changed in the animals consuming the high-concentration feed, the number of litters per pair decreased in a dose-related fashion, and the proportion of pups born alive, and their weight, was significantly decreased in the high-dose group. A crossover mating trial found impaired fertility in both males and females exposed to 0.2% TCP, with a greater effect in females. Histopathology of the F0 pairs revealed dose-related seminiferous tubule atrophy, and decreased testis and epididymal weights in the high-dose males, while the female reproductive tract showed no histopathologic changes. There were dose-related changes in the adrenals of both sexes, and body weight was depressed in both sexes at the highest concentration. The last litter born in the 98-day breeding phase was reared to age 74 days and then mated within the control and two of the treatment groups (0.0, 0.05, and 0.1% TCP; there were too few offspring in the 0.2% group). There was a decrease in the fertility index in the 0.1% TCP group, and a decreased proportion of liveborn and number of liveborn pups per litter. In the F1 males at necropsy, sperm concentration and morphology were normal at termination, although motility was decreased in both the 0.05% and the 0.1% groups compared to controls. These data show that TCP impaired fertility in both sexes of mice in the F0 generation and affected sperm motility at even the lowest dose in F1 males.