- Email: [email protected]
Passive smoke exposure in children: Relationship between urine cotinine levels and parental report of exposure
314 release. That this effect may be preferentially mediated in the nucleus accumbens is indicated by corresponding increases in D2 receptor density in this region. By comparison, a functional subsensitivity to the GLU antagonist MK-801 is produced by PW exposure, as is a corresponding and selective inhibition of MK-801 binding in hippocampus. Current evidence suggests that the GLU system, but not DA system changes may be implicated in Pb-induced learning deficits, whereas DA effects may be related to Pb-induced changes in Fixed Interval (FI) schedule controlled behavior. Specifically, DA agonists do not differentially affect accuracy of learning in control vs. Pb-exposed rats, whereas the effects of MK-801 are attenuated and those of NMDA potentiated by Pb exposure. In contrast, Pb exposed rats show supersensitivity to the changes in Fixed Interval response rates invoked by D2 agonists whereas comparable FI response rate changes are noted in response to MK-801 and NMDA. ES05903, ES05017 and ES01247.
NBTS 4 LEVIN, E.D., N. CHRISTOPHER*, S. BRIGGS*, C.S. HENDRIX* AND M.E. STANTON, Dept of Psychiatry, Duke University Med. Ctr., Durham, North Carolinia and Neurotoxicology Div., USEPA, Research Triangle Park, North Carolinia. Prenatal Nicotine Ext)osure and Functioqal Recovery from Medial Frontal Cortical Lesions: Insult. Injury and the Neuronlastic Resnonse. This study examined the effect of prenatal nicotine exposure on functional recovery from neonatal frontal cortical lesions. Since we previously found that prenatal nicotine exposure blunts noradrenergic responsiveness which is important for neuroplasticity, it was hypothesized that prenatal nicotine exposure would impair recovery after neonatal frontal cortical lesions. Pregnant Sprague-Dawley rats were given 2 mg/kg/day of nicotine via osmotic minipumps from GD 4 until parturition. Either medial frontal cortical excisions or sham surgeries were performed on the offspring on PN Day 7. In adulthood, the offspring were tested for spatial alternation in a Tmaze. Delays of 0, 10, 20 and 40 seconds were interposed between trials. With 9 sessions of testing, there was a significant linear (p<0.01) decrease of choice accuracy with increasing delays. There was a significant nicotine x lesion interaction (p<0.05) with regard to this linear decay. At the longest delay the nicotine-treated lesioned rats showed a significant (p<0.05) deficit relative to nicotinetreated sham operated rats. In contrast, the salinetreated lesioned rats showed no such deficit. Toxicant exposure which impairs recovery from other insults such as brain lesions may explain the heterogeneity of response which is seen after
NEUROBEHAVIORAL TERATOLOGY SOCIETY ABSTRACTS prenatal nicotine and many other types of toxicant exposure. (Supported by the March of Dimes Ftd.)
NBTS 5 DAVIS, J.M., Environmental Criteria and Assessment Office, U.S. EPA, RTP, NC. Risk Assessment I~sues for Neqrotoxicoloqists. The use of neurobehavioral effects in the assessment of health risks by agencies such as the U.S. Environmental Protection Agency has been increasing. Although efforts have been devoted to formalizing the assessment process for neurotoxicological effects, some issues that are of particular relevance to neurobehavioral phenomena remain to be considered more f u l l y by researchers and risk assessors alike. Many of these issues are related to a fundamental problem of defining what is an adverse (neurotoxicological) effect. For example, how severe does a neurobehavioral dysfunction or impairment have to be to warrant the designation "adverse" by a risk assessor? How does the persistence or i r r e v e r s i b i l i t y of an effect bear upon such a designation? How should a risk assessor treat "subclinical" effects or effects that are not readily measurable in individual subjects but are evident on a population scale? How should multiple effects be interpreted when they are not necessarily consistent with one another? When can a neuro-chemical, -physiological, or -anatomical alteration be considered a valid biomarker of neurotoxicity? What are the limits to generalizing from one species to another? How should compensatory mechanisms and effects be taken into consideration? Neurotoxicologists may be able to provide valuable empirical information that can help answer these questions.
NBTS 6 FRIED, P.A. 1, B. WATKINSON .1, and S.L. PERKINS .2 Department of Psychology, Carleton University, Ottawa, Canada1; Division of Biochemistry, Ottawa Civic Hospital, Ottawa, Canada 2. Passive smoke exoosure in children: Relationship between urine cotinine levels and parental reoort of exposure. A paramount difficulty in interpreting, in offspring, the long term consequences of exposure to teratogenic agents is the determination and evaluation of possible confounding postnatal factors.
NEUROBEHAVIORAL TERATOLOGY SOCIETY ABSTRACTS In the area of in utero cigarette exposure the issue of secondhand smoke is a key concem. In the present report, 109 six to eleven year old children from predominantly middle class families served as subjects. The parental report of passive smoke exposure both in and out of the home was compared to the child's urine cotinine results. Compared to extant literature, a high degree of concordance was noted between the two ways of measuring passive exposure. A dose-response relationship with little overlap in cotinine values between parental reported exposed and non-exposed children was observed. Considering secondhand smoke exposure outside the home, in addition to the household, improved the correlation only when the former exposure was heavy. The merits of adjusting the biochemical parameter to take into account such factors as urine concentration and the age and sex of the child will be discussed. In addition, aspects of our study design that may have contributed to and other aspects that may have limited the correlation between the parental report and the urine cotinine values will be described. Supported by grant DA04874 to PAF from NIDA.
NBTS 7 JACOBSON, S.W., H.C. KO', B.L. YAO', J.L. JACOBSON, F.M. CHANG', and C.C. HSU°, Department of Psychology, Wayne State University, Detroit, Michigan, and Departments of Psychiatry and Obstetrics and Gynecology, National Cheng Kung University Medical College, Tainan, Taiwan. preliminary findings confirming effects of prenatal pCB exposure on infant recognition memory. In 1979, over 2000 Taiwanese residents ingested cooking oil contaminated with polychlorinated biphenyls (PCBs) and dibenzofurans (PCDFs). Many developed Yu-cheng ("oil disease"), characterized by chloracne, hyperpigmentation, and related symptoms. Children born to exposed women exhibited similar signs, growth retardation, and poorer performance on standardized IQ tests. Because these chemicals are lipophilic and difficult to excrete, they persist in human tissue, affecting offspring of Yu-cheng women even after maternal exposure has ceased. Nine infants recently bom to Yucheng exposed women and 31 non-exposed controls were administered the Fagan visual recognition memory (VRM) test at 6.5 months. Yu-cheng offspring showed significantly poorer VRM, as indicated by poorer novelty preference, after controlling for potential confounders (57% vs. 65% for controls). Smaller head circumference and a higher incidence of illnesses, also detected in these Yu-cheng infants, partially mediated the effects on recognition memory. These findings are the first to confirm VRM
deficits previously seen in Michigan infants prenatally exposed to PCBs, due primarily to maternal consumption of contaminated fish. Supported by a grant from the National Science Council, Taiwan.
NBTS 8 STRUPP, B.J., S. ALBER*, D.A. LEVITSKY*, and T. MEYER*. Div. of Nut. Sci. & Department of Psychology, Cornell Univ., Ithaca, New York. Chronic oost-weanino lead (Pb) exoosure Imoairs performance on a delayed a l t e r n a t i o n task. Despite the increasing evidence that low-level Pb exposure lowers IQ, the specificity o f the impairment is
unknown. Animal studies have provided some insight into this issue, but have generally employed exposure regimens that produce relatively high blood lead (BPb) levels. The present study was designed to assess the e f f e c t s of lowlevel exposure on s p e c i f i c aspects of f u n c t i o n i n g , using a delayed a l t e r n a t i o n task. Pb acetate was administered c h r o n i c a l l y a f t e r weaning, y i e l d i n g median BPb l e v e l s of O, 19, and 36 pg/dL in the three treatment groups. The performance of both Pb-treated groups was s i g n i f i c a n t l y i n f e r i o r to c o n t r o l s , but the impairment was constant across the four delays. This pattern renders a memory d e f i c i t u n l i k e l y . Analyses of the types of errors committed, using l o g t s t i c regression techniques, w i l l also be discussed. The present r e s u l t s demonstrate that low-level Pb exposure
impairs cognition even after the major period of brain development, questioning the current level of concern for occupational exposure (40 pg/dL). Supported by grants from NIEHS and the March of Dimes B i r t h Defects Foundation.
NBTS 9 Goldey, E.S., L.S. Kehn*, and K.M. Crofton, Neurotoxicology Division, U.S. BPA and *ManTech Environ, Tech. Inc., RTP, NC. Effects of chemicalinduced hypothyroidismon auditory and motor function: Pi'eliminarv comoarison of PTU and PCBs. Because the developing auditory system may be sensitive to the effects of hypothyroidism, we conducted studies with propylthiouracil (PTU) or Aroclor 1254, a thyrotoxic poly.chlorinated biphenyl
315
NBTS 4 LEVIN, E.D., N. CHRISTOPHER*, S. BRIGGS*, C.S. HENDRIX* AND M.E. STANTON, Dept of Psychiatry, Duke University Med. Ctr., Durham, North Carolinia and Neurotoxicology Div., USEPA, Research Triangle Park, North Carolinia. Prenatal Nicotine Ext)osure and Functioqal Recovery from Medial Frontal Cortical Lesions: Insult. Injury and the Neuronlastic Resnonse. This study examined the effect of prenatal nicotine exposure on functional recovery from neonatal frontal cortical lesions. Since we previously found that prenatal nicotine exposure blunts noradrenergic responsiveness which is important for neuroplasticity, it was hypothesized that prenatal nicotine exposure would impair recovery after neonatal frontal cortical lesions. Pregnant Sprague-Dawley rats were given 2 mg/kg/day of nicotine via osmotic minipumps from GD 4 until parturition. Either medial frontal cortical excisions or sham surgeries were performed on the offspring on PN Day 7. In adulthood, the offspring were tested for spatial alternation in a Tmaze. Delays of 0, 10, 20 and 40 seconds were interposed between trials. With 9 sessions of testing, there was a significant linear (p<0.01) decrease of choice accuracy with increasing delays. There was a significant nicotine x lesion interaction (p<0.05) with regard to this linear decay. At the longest delay the nicotine-treated lesioned rats showed a significant (p<0.05) deficit relative to nicotinetreated sham operated rats. In contrast, the salinetreated lesioned rats showed no such deficit. Toxicant exposure which impairs recovery from other insults such as brain lesions may explain the heterogeneity of response which is seen after
NEUROBEHAVIORAL TERATOLOGY SOCIETY ABSTRACTS prenatal nicotine and many other types of toxicant exposure. (Supported by the March of Dimes Ftd.)
NBTS 5 DAVIS, J.M., Environmental Criteria and Assessment Office, U.S. EPA, RTP, NC. Risk Assessment I~sues for Neqrotoxicoloqists. The use of neurobehavioral effects in the assessment of health risks by agencies such as the U.S. Environmental Protection Agency has been increasing. Although efforts have been devoted to formalizing the assessment process for neurotoxicological effects, some issues that are of particular relevance to neurobehavioral phenomena remain to be considered more f u l l y by researchers and risk assessors alike. Many of these issues are related to a fundamental problem of defining what is an adverse (neurotoxicological) effect. For example, how severe does a neurobehavioral dysfunction or impairment have to be to warrant the designation "adverse" by a risk assessor? How does the persistence or i r r e v e r s i b i l i t y of an effect bear upon such a designation? How should a risk assessor treat "subclinical" effects or effects that are not readily measurable in individual subjects but are evident on a population scale? How should multiple effects be interpreted when they are not necessarily consistent with one another? When can a neuro-chemical, -physiological, or -anatomical alteration be considered a valid biomarker of neurotoxicity? What are the limits to generalizing from one species to another? How should compensatory mechanisms and effects be taken into consideration? Neurotoxicologists may be able to provide valuable empirical information that can help answer these questions.
NBTS 6 FRIED, P.A. 1, B. WATKINSON .1, and S.L. PERKINS .2 Department of Psychology, Carleton University, Ottawa, Canada1; Division of Biochemistry, Ottawa Civic Hospital, Ottawa, Canada 2. Passive smoke exoosure in children: Relationship between urine cotinine levels and parental reoort of exposure. A paramount difficulty in interpreting, in offspring, the long term consequences of exposure to teratogenic agents is the determination and evaluation of possible confounding postnatal factors.
NEUROBEHAVIORAL TERATOLOGY SOCIETY ABSTRACTS In the area of in utero cigarette exposure the issue of secondhand smoke is a key concem. In the present report, 109 six to eleven year old children from predominantly middle class families served as subjects. The parental report of passive smoke exposure both in and out of the home was compared to the child's urine cotinine results. Compared to extant literature, a high degree of concordance was noted between the two ways of measuring passive exposure. A dose-response relationship with little overlap in cotinine values between parental reported exposed and non-exposed children was observed. Considering secondhand smoke exposure outside the home, in addition to the household, improved the correlation only when the former exposure was heavy. The merits of adjusting the biochemical parameter to take into account such factors as urine concentration and the age and sex of the child will be discussed. In addition, aspects of our study design that may have contributed to and other aspects that may have limited the correlation between the parental report and the urine cotinine values will be described. Supported by grant DA04874 to PAF from NIDA.
NBTS 7 JACOBSON, S.W., H.C. KO', B.L. YAO', J.L. JACOBSON, F.M. CHANG', and C.C. HSU°, Department of Psychology, Wayne State University, Detroit, Michigan, and Departments of Psychiatry and Obstetrics and Gynecology, National Cheng Kung University Medical College, Tainan, Taiwan. preliminary findings confirming effects of prenatal pCB exposure on infant recognition memory. In 1979, over 2000 Taiwanese residents ingested cooking oil contaminated with polychlorinated biphenyls (PCBs) and dibenzofurans (PCDFs). Many developed Yu-cheng ("oil disease"), characterized by chloracne, hyperpigmentation, and related symptoms. Children born to exposed women exhibited similar signs, growth retardation, and poorer performance on standardized IQ tests. Because these chemicals are lipophilic and difficult to excrete, they persist in human tissue, affecting offspring of Yu-cheng women even after maternal exposure has ceased. Nine infants recently bom to Yucheng exposed women and 31 non-exposed controls were administered the Fagan visual recognition memory (VRM) test at 6.5 months. Yu-cheng offspring showed significantly poorer VRM, as indicated by poorer novelty preference, after controlling for potential confounders (57% vs. 65% for controls). Smaller head circumference and a higher incidence of illnesses, also detected in these Yu-cheng infants, partially mediated the effects on recognition memory. These findings are the first to confirm VRM
deficits previously seen in Michigan infants prenatally exposed to PCBs, due primarily to maternal consumption of contaminated fish. Supported by a grant from the National Science Council, Taiwan.
NBTS 8 STRUPP, B.J., S. ALBER*, D.A. LEVITSKY*, and T. MEYER*. Div. of Nut. Sci. & Department of Psychology, Cornell Univ., Ithaca, New York. Chronic oost-weanino lead (Pb) exoosure Imoairs performance on a delayed a l t e r n a t i o n task. Despite the increasing evidence that low-level Pb exposure lowers IQ, the specificity o f the impairment is
unknown. Animal studies have provided some insight into this issue, but have generally employed exposure regimens that produce relatively high blood lead (BPb) levels. The present study was designed to assess the e f f e c t s of lowlevel exposure on s p e c i f i c aspects of f u n c t i o n i n g , using a delayed a l t e r n a t i o n task. Pb acetate was administered c h r o n i c a l l y a f t e r weaning, y i e l d i n g median BPb l e v e l s of O, 19, and 36 pg/dL in the three treatment groups. The performance of both Pb-treated groups was s i g n i f i c a n t l y i n f e r i o r to c o n t r o l s , but the impairment was constant across the four delays. This pattern renders a memory d e f i c i t u n l i k e l y . Analyses of the types of errors committed, using l o g t s t i c regression techniques, w i l l also be discussed. The present r e s u l t s demonstrate that low-level Pb exposure
impairs cognition even after the major period of brain development, questioning the current level of concern for occupational exposure (40 pg/dL). Supported by grants from NIEHS and the March of Dimes B i r t h Defects Foundation.
NBTS 9 Goldey, E.S., L.S. Kehn*, and K.M. Crofton, Neurotoxicology Division, U.S. BPA and *ManTech Environ, Tech. Inc., RTP, NC. Effects of chemicalinduced hypothyroidismon auditory and motor function: Pi'eliminarv comoarison of PTU and PCBs. Because the developing auditory system may be sensitive to the effects of hypothyroidism, we conducted studies with propylthiouracil (PTU) or Aroclor 1254, a thyrotoxic poly.chlorinated biphenyl
315