EXPOSURE OF NONMIGRATORY PIGEONS TO MANCOZEB: A SENTINEL MODEL FOR HUMANS

The use of pesticides in agriculture has increased over the last decade. Their widespread, often uncontrolled use causes thousands of people to be daily exposed to environmental agricultural chemicals, resulting in acute and chronic health effects. At present there is a paucity of data on the potential adverse effects of exposure to low levels of mancozeb for prolonged periods. In order to investigate the effects of mancozeb exposure on pulmonary wildlife populations, tracheas and lungs of nine 1- to 7- yr-old nonmigratory pigeons raised near peach orchards and vineyards repeatedly sprayed with the fungicide were examined. The experimental situation allowed us to evaluate the long-term natural toxicity of mancozeb as a sentinel for human populations occupationally exposed to fungicides. The use of nonmigratory pigeons may serve as an important biological source from which helpful data may be obtained for assessing risks to human health and gaining new insight into pathogenetic mechanisms.     

A SMALL ANIMAL PLETHYSMOGRAPH/EXPOSURE TUBE FOR DETERMINATION OF RESPIRATORY MECHANICS DURING EXPOSURE,USING A NONINVASIVE METHOD TO MEASURE INTRAPLEURAL PRESSURE

The real-time measurement of changes in respiratory mechanics, primarily dynamic compliance (C dyn) and airway resistance (R L) , is often used to assess the pulmonary toxicity of inhaled materials, irritants thought to cause reactivity response in the airways. Simple volume displacement plethysmography for measurement of ventilation in spontaneously breathing animals can be adapted for the determination of C dyn and R L by including measurement of intrapleural pressure (Ppl). Accurate estimates of Ppl can be obtained by measurement of esophageal pressure (Pes) using transoral insertion of a water-filled catheter. Measurement of Pes does not require surgical intervention as is often required for the measurement of Ppl directly. However, the use of conventional head-out plethysmography to measure ventilation and respiratory mechanics during exposure usually precludes the use of a transoral esophageal catheter to measure Pes. Thus, invasive methods must be used to measure Ppl. The combination headout plethysmograph/nose-only exposure tube (PET), described in this article is suitable for the measurement of R L and C dyn using transoral catheterization for the determination of Pes during exposure. In addition to avoidance of surgical intervention, use of the PET does not interfere with the animal's normal breathing or require extraordinary procedures for connection to a nose-only exposure chamber. Ventilation, breath waveform, and respiratory mechanics measurements in 36 Long-Evans rats demonstrated that neither short-term restraint in the PET nor subsequent insertion of the esophageal catheter significantly altered ventilation or individual breath structure. R L and C dyn measured in normal rats using the PET did not differ from R L and C dyn determined using more traditional plethysmographic methods.     

ENVIRONMENTAL COPPER: ITS DYNAMICS AND HUMAN EXPOSURE ISSUES

This article provides an overview of the environmental patterns and dynamics of copper from the perspective of issues that affect our ability to examine current human exposures. It presents selected sum mary information on the levels of copper found in various media and exposure pathways from a variety of information sources, and discusses the breadth and the limitations of this information. The analysis presented focuses on the ability to provide quantitative values for both external metrics of exposures (microenvironmental levels) and internal biological markers of exposure. The status of the current information on environmental copper is placed within a conceptual framework that can be used to identify data gaps, assess the utility of current biological markers of exposure, and examine the need for systematic and consistent data-gathering studies to improve our ability to com plete exposure assessments. A primary concern is the exposure to copper through potable water supplies; this is considered within a framework that examines copper levels and distribution in food, soil, air and sedim ents, as well as the levels found in biological media such as urine, blood, and hair. An existing water consumption model for copper and associated exposure factors is briefly discussed. This type of model will eventually be valuable within a total exposure analysis modeling framework that can consider and prioritize exposures from multiple routes and differentiate levels of concern for both excesses and deficiencies in exposure, an important issue, since copper is an essential nutrient. Finally, this review attempts to examine the needs for better information using as a basis the concerns briefly mentioned in the recent NRC report "Copper in Drinking Water" (National Research Council, 2000).     

GUIDELINES FOR COLLECTION OF HUMAN MILK SAMPLES FOR MONITORING AND RESEARCH OF ENVIRONMENTAL CHEMICALS

This article addresses sample collection protocols for monitoring and research of environmental chemicals in human milk. The process of milk synthesis and secretion and variations in contents of constituents that may impact measurement of environmental chemicals are presented. Possible sources of variation include parity, stage of lactation, method of sampling, maternal nutritional status, and dietary intake. General principles regarding how and when to collect milk samples are provided. For any previously unstudied environmental chemical in milk, all sources of variance must be assessed before a meaningful sampling protocol can be devised.     

CHARACTERIZATION OF RESPIRATORY EXPOSURE TO AND EFFECTS OF COLD-AIR HYPERVENTILATION IN GUINEA PIGS

The purpose of this study was to characterize the respiratory effects of single and repeated controlled exposures to clean warm humid and cold dry air in a new model of anesthetized, mechanically ventilated guinea pigs, and to compare findings with known effects in humans. Intratracheal air (T_tr) and retrotracheal tissue (T_oe) temperatures and peak expiratory airflow (PEF), tidal volume (V_T), heart rate, and blood pressure of hyperventilating animals were measured continuously. Four consecutive 10-min exposures to warm humid air (n = 7) produced slight airway warming and minimal lung function changes during the exposure. In a single 10-min exposure to cold dry air (n = 39), T_tr     

METALS AND METALLOTHIONEIN IN THE LIVER OF RACCOONS: UTILITY FOR ENVIRONMENTAL ASSESSMENT AND MONITORING

Previous studies with low-pH montmorillonite (LPHM) clay exchanged with alkylammonium compounds showed that these organo clays were quite effective in sorbing the estrogenic mycotoxin zearalenone (ZEN) from aqueous solution. The potential toxicity of these types of clays, in particular hexadecyltrimethylammonium (HDTMA) LPHM, led to the investigation of the sorption efficacy of clay exchanged with a less toxic primary amine analog, hexadecylamine (HDA). Isothermal analysis studies showed that HDA LPHM was able to bind ZEN, but less effectively than HDTMA LPHM as evidenced by a significantly lower Freundlich K (63,900 vs. 845). The in vivo effectiveness of these two clays to bind ZEN was tested utilizing the mouse uterine weight bioassay. At a dietary inclusion level of 0.25%, the clays did not have a negative impact on overall animal health as measured by final body weight; however, they did not protect the animals from the estrogenic effects induced by 35 mg ZEN/kg in the feed (i.e., the uterine weights were not reduced in comparison to ZEN alone). In fact, the HDTMA LPHM group showed an increase in uterine weight that was more than the ZEN treatment group. When the animals were fed 0.5% clay, both exchanged clays (i.e., HDTMA LPHM and HDA LPHM) resulted in decreased body weight gain. The uterine weights of ZEN-fed animals (either alone or in combination with clays) were not significantly different from each other. In contrast, the uterine:body weight ratio showed a dramatic increase in the groups fed exchanged clay + ZEN compared to ZEN alone. These results suggest that alkylamine groups may assist the transport or uptake of ZEN and result in an enhanced toxicity from contaminated feed. The findings from this study clearly demonstrate the need for careful testing of all mycotoxin-binding agents before their inclusion in the diet.     

SHORT COMMUNICATION: CATECHOLAMINE CONCENTRATIONS DURING EXPOSURE OF RESTING MAN TO THE HEAT OF A STANDARD SWEAT TEST

1. Normal subjects were heated for 45 min with a heat cradle under the conditions used to investigate sweating clinically. 2. Skin temperatures on the chest and in the external auditory meatus rose but concentrations of noradrenaline and adrenaline decreased during heating. 3. There was no change in adrenoceptor affinity or number as a result of the heat exposure. 4. There was little change in blood pressure and heart rate and no dysrhythmias were observed with an electrocardiogram. 5. It is concluded that heating with a heat cradle is generally not stressful and that there is a reduction in sympathetic nervous activity involving noradrenergic or adrenergic transmission during the procedure.     

GENETIC AND ENVIRONMENTAL DETERMINANTS OF SUSCEPTIBILITY TO ALCOHOL-INDUCED LIVER DISEASE

Although there is an overall relationship between cumulative alcohol intake and the severity of alcohol-related liver damage, there is considerable variation in individual susceptibility to the hepatotoxic effects of alcohol. In this review I shall discuss what factors appear to influence susceptibility. Women develop liver disease after a shorter period of excessive drinking and at a lower alcohol intake than men. This is partly related to differences in body size and composition between the sexes which result in women having preportionately higher blood alcohol levels than men after a standard drink; this probably explains why women are more susceptible to a variety of alcohol-related problems. Other genetic determinants of susceptibility have until recently proved elusive, but certain HLA types, such as HLA-B8, have been shown to increase the risk of chronic liver damage by up to 50%. No genetic variations in the enzymes responsible for alcohol metabolism have been definitely associated with predisposition to liver damage. The more severe lesions — alcoholic hepatitis and cirrhosis — are more common in regular daily drinkers compared with intermittent or ‘qbinge’ drinkers and in moderately dependent patients compared with those who have severe alcohol-withdrawal symptoms. No exogenous agents such as hepatitis viruses of chemicals have yet been shown to contribute to the development of any of the morphological abnormalities of alcoholic liver disease. At the present time there is insufficient information for us to be able to tailor our advice about drinking to the individual patient. We recommend that men should on no account drink more than 80 g alcohol per day and that women should keep below half this amount. People whose intakes approach these amounts should have two alcohol-free days every week. In the future it may be possible to screen specifically for markers of susceptibility to liver damage in populations known to be at risk of alcohol problems.     

RELATIVE CONTRIBUTIONS OF VOLUNTARY APNOEA, EXPOSURE TO COLD AND FACE IMMERSION IN WATER TO DIVING BRADYCARDIA IN HUMANS

1. Diving or face immersion bradycardia is a well recognized but incompletely understood reflex which occurs in man and other mammals. 2. In order to investigate the contributions made by voluntary apnoea, face immersion in water and cold exposure, 18 normal subjects were exposed to these challenges separately and in various combinations. 3. Tested individually, cold and apnoea caused significant reductions in heart rate (P<0.01 and 0.002, respectively). Face immersion in thermoneutral water had no effect on heart rate. 4. The bradycardic effect of apnoea at maximal inspiration may be due to stimulation of pulmonary stretch receptors. 5. Cold exposure and voluntary apnoea applied simultaneously caused a summative effect but when tested with face immersion in water there was a synergistic response greater than the sum of individual responses. 6. The results confirm the bradycardic effect of apnoea and cold exposure, whereas immersion in thermoneutral water had little effect, a finding which has been disputed in the literature.     

USE OF RESPONSE BIOMARKERS IN MILK FOR ASSESSING EXPOSURE TO ENVIRONMENTAL CONTAMINANTS: THE CASE FOR DIOXIN-LIKE COMPOUNDS

Screening for environmental contaminants in milk is generally conducted by chemical analysis, yet such an approach may be time-consuming and expensive, and is not indicative of the physiological consequences of such exposure. The focus of this review is to summarize those constituents of milk that may be altered by maternal exposure to one of the most biologically active environmental pollutants, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and to develop the case for their use as biomarkers of response. Several chemical and/or cellular components of milk are potentially useful as biomarkers, and may be developed as convenient, biologically relevant indicators of maternal exposure to dioxinlike compounds.     

COLONIZATION AND CLEARANCE OF ENVIRONMENTAL MICROBIAL AGENTS UPON INTRANASAL EXPOSURE OF STRAIN C3H/HeJ MICE

Environmental dissemination of biotechnology agents is becoming a common practice. Most applications use historically innocuous species; however, potential health effects of individual products are not scrutinized unless they contain genetically engineered microorganisms. In order to investigate possible health concerns, four surrogate microbial agents were studied in vivo. Male C3H/ HeJ (endotoxin-resistant) mice were administered intranasally (i.n.) with ~107 Pseudomonas aureofaciens, Burkholderia cepacia, P. fluorescens, or P. putida. To determine clearance of the dosed bacterial strains, lungs, small intestine, large intestine, cecum, mesenteric lymph nodes ( MLN) , spleen, and liver were homogenized individually, plated, and dilutions inoculated onto selective media. Pseudomonas fluorescens and P. putida were eliminated from the lungs by 2 d posttreatment, and P. aureofaciens was not detected in the lungs by 5 d posttreatment. Burkholderia cepacia was reisolated from the lungs and cecum for the experimental duration (14 d). Translocation to extraintestinal sites (MLN, spleen, and liver) also occurred. Burkholderia cepacia was recovered from the MLN for 10 d after treatment of mice. Pulmonary exposure to several bacterial strains resulted in unexpected mortality. Pseudomonas aureofaciens was lethal at the lowest dose (8.26 x 106 CFU/ mouse) , while P. fluorescens and B. cepacia were fatal at higher doses ( 6.15 x 108 CFU/mouse and 1.34 x 108 CFU/mouse, respectively). By using the model described in this study, human safety issues can be more easily addressed and evaluated.     

ATTENUATION AND RECOVERY OF PULMONARY INJURY IN RATS FOLLOWING SHORT-TERM,REPEATED DAILY EXPOSURE TO OZONE

Controlled human and epidemiology studies have demonstrated that during repeated exposure to ozone (O 3) attenuation of lung function responses may occur. It is yet unknown whether inflammatory and biochemical effects in lower airways of humans, as observed upon single O 3 exposure, also show a diminutive response following repeated exposure to O 3. The aim of this study was to investigate inflammatory, permeability, and histopathological responses in lungs of rats following repeated daily O 3 exposure and to study the time course of attenuation and recovery of these effects using single O 3 challenges at various postexposure times. To aid in animal-to-human extrapolation, this study and a previously reported human study (Devlin et al., 1997) were designed with similar protocols. Wistar rats were exposed for 5 consecutive days to 0.4 ppm O 3 for 12 h/night. Subsequently, the time course of postexposure recovery was determined by a single challenge of 12 h to 0.4 ppm O 3 after a 5-, 10-, 15-, or 20-day recovery period. Broncho-alveolar lavage (BAL) examination and histopathology were performed 12 h after this O 3 challenge. To quantify the magnitude of the O 3 response, results were compared with a group exposed only once for 12 h to 0.4 ppm O 3 and sacrificed simultaneously. The results demonstrate that a single exposure of 0.4 ppm O 3 causes marked permeability and inflammatory responses in lower airways of rats, as evidenced by enhanced BAL fluid levels of proteins, fibronectin, interleukin (IL)-6, and inflammatory cells. However, 5 days of exposure to 0.4 ppm O 3 for 12 h/night resulted in a complete disappearance of these responses, resulting in BAL fluid values that were not different from those observed in unexposed controls. Postexposure analyses of pulmonary response to O 3 challenges demonstrated that these attenuated responses show a gradual recovery. The data indicate that with respect to BAL fluid levels of albumin, IL-6, and number of macrophages and neutrophils, the period for lung tissue to regain its full susceptibility and responsiveness to O 3 following a 5-day preexposure period is approximately 15-20 days. Remarkably, the total protein and fibronectin responses in BAL fluid still exhibited an attenuated response to an O 3 challenge at 20 days postexposure. Morphometry (number of BrdU-labeled cells in terminal bronchiolar epithelium, and number of alveolar macrophages) showed that after a recovery of 5-10 days following a 5-day preexposure the response to a challenge was identical to that after a single exposure. These results suggest that complete repair from lower airway inflammation caused by short-term, repeated exposure to O 3 may take longer than previously assumed.     

DEVELOPMENT OF AN INHALATION SYSTEM FOR THE SIMULTANEOUS EXPOSURE OF RAT DAMS AND PUPS DURING DEVELOPMENTAL NEUROTOXICITY STUDIES

Due to mass flux constraints, the exposure of pups along with dams to particles cannot be easily done in traditional whole-body inhalation systems. Typical inhalation developmental neurotoxicity studies rely on maternal separation during exposure, resulting in pup stress that may alter behavioral development, thereby confounding study results. We developed an individual-rat, whole-body inhalation exposure cylinder that allows for the simultaneous exposure of rat dams and their pups to vapors, aerosols, and particles. We evaluated pup growth and development following gestational and lactational 6-h/ day exposures to HEPA-filtered air using the novel exposure cylinder, in which dams and pups were maintained together, versus rat pups for which only the dams were exposed or control animals that remained in the domiciliary cage with the dams. Rat pups that were separated from their dams during neonatal exposure to HEPA-filtered air demonstrated significant delays in several developmental landmarks such as surface righting, negative geotaxis, and eye opening, as well as decreased terminal body and brain weights. Increased spontaneous motor activity was observed on postnatal day (PND) 13, 17, and 60 in pups that were separated from their dams. Malnutrition is the likely cause for the observed hyperactivity and delayed development. We then compared maternal blood levels of tertiary amyl methyl ether (TAME) and its metabolite tertiary amyl alcohol (TAA) in the 2 exposure systems following exposure to 500 ppm TAME for 6 h. Dams exposed in the novel exposure cylinder had higher blood levels of TAME compared with those exposed in stainless steel caging. We also compared levels of particulate manganese phosphate within the novel exposure cylinder to determine if levels achieved within the exposure cylinder were similar to levels generated within a 1-m3 chamber. The novel exposure cylinder is an ideal system for exposure of dams and pups to particles, due to the high horizontal flow rates, which result in an adequate mass flux flowing past the breathing zone of the animals with retained normal growth and development.     

青少年期尼古丁暴露对成年大鼠饮酒行为和腹侧被盖区nACh受体表达水平的影响

目的:观察大鼠青少年期尼古丁暴露对成年期大鼠饮酒行为的影响,检测青少年期尼古丁暴露和成年期大鼠饮酒行为对大鼠腹侧被盖区(VTA脑区)烟碱型尼古丁受体(nAChR)部分亚单位mRNA表达的影响。探讨VTA区nAChR受体参与青少年期吸烟和成年期酒依赖形成的可能机制。方法:39只Wistar大鼠出生后35 d(PN35)开始为期10 d的尼古丁(1.0 mg.kg-1/day salt)皮下注射(尼古丁处理组,N组n=20),以生理盐水作为对照处理(生理盐水对照组,C组n=19)。完成后各组随机抽取6只作为空白对照(E)组(分别为CE组n=6,NE组n=6),断头取脑分离VTA区提取mRNA,Real Time-PCR定量检测nAChR受体α4、α5、α7和β2亚单位mRNA。两组余下大鼠作为酒依赖模型(A)组(分别为NA组n=14,CA组n=12)于大鼠出生后60 d(PN60)以Samson糖水递减程序诱导建立乙醇双瓶自由选择饮酒行为实验,观测干预对Wistar大鼠乙醇消费量、酒偏好程度、总饮液量的影响。之后相同程序定量检测VTA标本相同指标。结果:青少年期尼古丁干预对成年期饮酒行为的各项行为学指标无明显影响(P>0.05)。VTA区nAChR亚单位mRNA的表达:未建立酒依赖模型两处理组间α4、α5、α7和β2亚单位mRNA表达无差异(P>0.05);建立酒依赖模型两处理组间α4、α5、α7和β2亚单位mRNA表达都有不同程度的显著性差异(P<0.05或P<0.001),其中尼古丁处理组α4、α5和β2表达上调,生理盐水处理组α7表达下调。因素分析显示:两因素对α4和α5亚单位表达都有调节作用;酒依赖模型因素对β2表达有调节作用;对α5、α7和β2亚单位表达两因素有交互作用。结论:(1)青少年期尼古丁干预可以调节VTA区nAChR亚单位α4、α5、α7、β2的表达,其效应在一定时间后才出现;没有发现青少年期尼古丁干预对成年期酒依赖形成行为学的促进作用,考虑可能有深层的内在原因相继造成了人类青少年期吸烟和此后酒依赖的形成。(2)VTA区多种包含有α4、α5、α7、β2亚单位的nAChR亚型是尼古丁和乙醇共同作用点,推测是众多推动酒依赖形成的因素之一。     

烟焦油急慢性暴露及戒断后对涡虫精神运动活性的影响

目的:本实验主要探究烟焦油对涡虫的精神运动活性的影响作用。方法:通过毒理实验确定烟焦油对涡虫的半致死浓度为0.1274mg·ml~(-1)及安全浓度为≤0.0882 mg·ml~(-1)。在安全浓度范围内设定3组浓度为0.0294 mg·ml~(-1)、0.0490 mg·ml~(~(-1))、0.0686 mg·ml~(-1)的烟焦油溶液处理组,分别对涡虫进行急性处理与慢性处理,通过戒断反应体现涡虫在不同浓度烟焦油中的运动速度变化,进一步探究烟焦油对涡虫的精神运动活性作用。结果:急性处理、慢性处理后涡虫在不同浓度烟焦油中运动速度均有明显变化且差异显著(P<0.01):于低浓度烟焦油处理后转入高浓度烟焦油中涡虫的运动速度上升,高浓度烟焦油处理后转入低浓度烟焦油中涡虫的运动速度下降,并与在中浓度烟焦油中涡虫的运动速度形成鲜明的对比。结论:实验表明烟焦油急慢性暴露及戒断后对涡虫精神运动活性的影响显著。     

INHALATION OF POORLY SOLUBLE PARTICLES. I. DIFFERENCES IN INFLAMMATORY RESPONSE AND CLEARANCE DURING EXPOSURE

Results from animal studies have indicated some uncertainties over the validity of a single general occupational control limit for all types of ''particulates (insoluble) not otherwise classified'' (PNOC) (ACGIH, 2000). Therefore, to examine the extent to which a given control limit may be valid for nontoxic dusts with different physical characteristics, this study compared the pulmonary effects in rats of inhalation exposure to two poorly soluble dusts of similar density and with relatively low toxicity: titanium dioxide and barium sulfate. The objectives were to compare the dusts in (a) their buildup and clearance in the lungs during inhalation; (b) their transfer to lymph nodes; (c) the changes, with time, in the lavageable cell population; and (d) the pathological change from histology. The exposure aerosol concentrations were selected to achieve similar mass and volume lung burdens for both dusts and to attain ''overload'' over the common exposure periods of about 4 mo and 7 mo. Despite obtaining similar lung burdens for both dusts, there was significantly more translocation of TiO2 to the hilar lymph nodes than with BaSO4. It was also found that clearance of TiO2 was retarded whereas clearance of BaSO4 was not. Trends in these data were clarified by the use of a simple model of particle clearance. Retardation of particle clearance and translocation to the lymph nodes are markers of the condition known as ''overload'' in which the alveolar macrophage-based clearance of particles from the deep lung is impaired. In addition, bronchoalveolar lavage showed that TiO2 caused significantly more recruitment of inflammatory neutrophils to lungs than BaSO4. These differences between the dusts were not due to differences in toxicity, solubility, or lung deposition. The explanation that the different responses are due to the different particle size distributions of the two dust types is examined in a companion paper (Tran et al., this issue).     

EFFECTS OF HCFC-123 EXPOSURE TO MATERNAL AND INFANT RHESUS MONKEYS ON HEPATIC BIOCHEMISTRY,LACTATIONAL PARAMETERS AND POSTNATAL GROWTH

ABSTRACT

Peroxisome proliferators are a class of nongenotoxic rodent hepatocarcinogens that cause peroxisome proliferation and liver tumors when administered to rats and mice; but other species, including guinea pigs, dogs, and primates are less sensitive or refractory to the induction of peroxisome proliferation. Therefore, rodent peroxisome proliferators are not believed to pose a hepatocarcinogenic hazard to humans. Some peroxisome proliferators produce developmental toxicity in rats that is expressed as suppressed postnatal growth. To evaluate the relevance of the rat developmental effect to primates, groups of 4 lactating female Rhesus monkeys and their infants were exposed for 6 h/day, 7 days/week for 3 weeks to air or 1000 ppm HCFC-123. Animals were evaluated for clinical signs, body weights, clinical pathology parameters, and biochemical and pathological evaluations of liver biopsy samples. The effect of HCFC-123 exposure on milk quality (protein and fat concentration) was evaluated. The concentrations of HCFC-123 and the major metabolite, trifluoroacetic acid (TFA), were measured in the blood of the mothers and infants and in the milk. Exposure of monkeys to 1000 ppm HCFC-123 did not result in exposure-related clinical observations, or changes in body weight, appetence and behavior. There were no exposure-related effects on serum triglycerides, cholesterol, or glucose levels. HCFC-123 and TFA were present in milk, although maternal HCFC-123 exposure did not affect milk protein and fat content. In general, HCFC-123 was not detected in maternal or infant blood. TFA was detected in the majority of the mothers and TFA levels in infants ranged from 2 to 6 times higher than levels in the corresponding maternal blood. A pharmacokinetic analysis in a maternal animal indicated a peak concentration of TFA at approximately 1 h post-exposure, with a half-life of approximately 20 h. Liver microsomal P450 and peroxisome oxidase activities showed exposure-related decreases in CYP4A1 and CYP2E1 and acyl-CoA oxidase for animals exposed to HCFC-123. Microscopic evaluation of maternal liver from HCFC-123 exposed animals revealed mild to moderate centrilobular hepatocyte vacuolation, trace to mild centrilobular necrosis, and trace to mild subacute inflammation. The histopathological damage and altered hepatic biochemical activities produced by HCFC-123 in monkeys are not consistent with the HCFC-123 peroxisome proliferation response observed in rat livers. These findings demonstrate that HCFC-123 is not a peroxisome proliferator in adult Rhesus monkeys and postnatal exposure to HCFC-123 does not affect body weight of nursing infant monkeys.