Early lead exposure effects on an auditory threshold task in the rhesus monkey (Macaca mulatta).

Behavioral thresholds to pure tones were obtained from adult rhesus monkeys that had been exposed to lead during early development and unexposed cohort controls. Thresholds were elevated (by 2-9 dB) for the previously lead exposed monkeys at all frequencies tested (125-8,000 Hz in octave steps). Although the magnitude and direction of the differences were similar to significant effects reported for children, the more difficult task and much smaller sample sizes in this study of monkeys may have precluded obtaining significant differences at the same magnitude of effects observed in children. Thresholds for one lead-exposed monkey were significantly elevated at midrange frequencies in agreement with electrophysiological results obtained in another study [Lasky, Maier, Snodgrass, Hecox, and Laughlin [1995] Neurotoxicology and Teratology, 17, 633-644]. Behavioral measurements during the threshold task indicated less engagement for lead exposed monkeys than for controls. In addition, the lead exposed monkeys completed testing at significantly fewer frequencies and were significantly more difficult to test than control monkeys by tester ratings. These results are consistent with reports concerning the behavior of lead exposed children.

Developmental lead exposure induces tactile defensiveness in rhesus monkeys (Macaca mulatta).

BACKGROUND: Tactile defensiveness in children is associated with difficult social relations, emotional dysregulation, and inattention. However, there are no studies of lead exposure and tactile defensiveness in children or animals in spite of the fact that lead exposure is also associated with inattention and emotional dysregulation. OBJECTIVES: In this study we tested whether lead exposure induces tactile defensiveness in rhesus monkeys. METHODS: We tested 61 monkeys from a 3 (no lead, 1-year lead, 2-year lead) x 2 (succimer chelation or not) factorial experiment for tactile defensiveness at 4 years of age. Lead-treated monkeys had been orally administered lead in a daily milk solution from 8 days of life to either 1 or 2 years of age to produce blood lead levels of 35-40 mg/dL. Succimer chelation therapy or placebo was administered at 1 year of age. We measured tactile defensiveness using six repeated trials of each of three textures as a swipe to the cheek and neck. RESULTS: Lead-exposed monkeys showed higher negative responses to repeated tactile stimulation compared with controls. Blood lead during the first 3 months of life was positively correlated with the negative response on the tactile defensiveness test. There was an interaction of lead exposure x succimer chelation x trials, but it is not clear that succimer chelation was beneficial with respect to tactile defensiveness. CONCLUSIONS: This is the first report to implicate lead as a potential cause of tactile defensiveness. Research should examine whether lead exposure is associated with tactile defensiveness in children.

Postnatal lead effects on the development of visual spatial acuity in rhesus monkeys (Macaca Mulatta).

High lead levels adversely affect visual function in humans and laboratory animals. The effects of lower lead levels are less certain. This study compared the development of photopic spatial acuity in rhesus monkeys exposed to lead (n = 43) with monkeys (n = 23) not exposed to lead. Lead exposure began at Day 8 postpartum and continued daily throughout the first 26 weeks of postnatal life achieving target blood lead levels of 35-40 microg/dl by about 15 weeks. Photopic spatial acuity was evaluated by a preferential looking technique used clinically to assess spatial acuity in human infants. Acuity increased rapidly over the first few postnatal weeks achieving the maximum acuity level assessed (26.3 c/deg) by 7 weeks of age for most monkeys. Postnatal lead exposure at the dosages and durations studied did not affect the development of photopic spatial acuity.

Sensory processing disorders in a nonhuman primate model: evidence for occupational therapy practice.

Evaluation of sensory processing function serves as a critical component of treatment planning and implementation of intervention in pediatric occupational therapy practice. We developed a Sensory Processing Scale for Monkeys (SPS-M), based on human tests, that measures behavioral responses to a series of tactile stimuli. This assessment has been used to assess sensory processing in adult rhesus monkeys exposed to prenatal alcohol, stress, or postnatal lead. Control monkeys from undisturbed pregnancies showed a habituation pattern, prenatally stressed monkeys showed sensitization, and prenatal alcohol-exposed monkeys showed relatively high responsiveness without habituation across trials. Lead-exposed monkeys showed sensitization compared to nonlead-exposed controls, and chelation reduced the sensitization in lead-exposed animals. Aversive responsiveness was associated with up-regulated striatal dopamine receptor binding measured with positron emission tomography.

The effects of early lead exposure on the brains of adult rhesus monkeys: a volumetric MRI study.

Little is known about direct effects of exposure to lead on central nervous system development. We conducted volumetric MRI studies in three groups of 17-year-old rhesus monkeys: (1) a group exposed to lead throughout gestation (n = 3), (2) a group exposed to lead through breast milk from birth to weaning (n = 4), and (3) a group not exposed to lead (n = 8). All fifteen monkeys were treated essentially identically since birth with the exception of lead exposure. The three-dimensional MRI images were segmented on a computer workstation using pre-tested manual and semi-automated algorithms to generate brain volumes for white matter, gray matter, cerebrospinal fluid, and component brain structures. The three groups differed significantly in the adjusted (for total brain size) volumes of the right cerebral white matter and the lateral ventricles. A significant reduction was noted in right cerebral white matter in prenatally exposed monkeys as compared to controls (p = 0.045). A similar reduction was detected in the white matter of the contralateral hemisphere; however, this difference did not achieve statistical significance (p = 0.143). Prenatally exposed monkeys also had larger right (p = 0.027) and left (p = 0.040) lateral ventricles. Depending on the timing of exposure during development, lead may exhibit differential effects with resultant life-long alterations in brain architecture.

Inguinal hernias, endometriosis, and other adverse outcomes in rhesus monkeys following lead exposure.

The Harlow Center for Biological Psychology (HCBP) has a cohort of rhesus monkeys that were exposed to low concentrations of lead acetate in utero or as infants. The lead-exposed animals have been followed for 19 years and have developed four cases of inguinal hernia (males), three cases of endometriosis (females), and one case of immunoblastic lymphoma (male). Retrospective analysis of the data from the original lead-exposed cohort indicates that there is a significant association between lead exposure and the development of inguinal hernia (P=.04). Endometriosis was not significantly associated with lead exposure (P=.36). A case control study also was done to determine the significance of neonatal lead exposure as a risk factor for the development of inguinal hernia and endometriosis. The risk of developing inguinal hernia was significantly increased in lead-exposed animals (OR=20.0, P=.009). The association between endometriosis and lead exposure was also strong (OR=10.13, P<.001). No unmatched variables were associated with inguinal hernia, including body weight, history of diarrhea, constipation, or intussusception. No unmatched variables were highly associated with endometriosis, including body weight, age at first parity, and history of stillbirths. However, parity and the number of stillbirths were associated with lead exposure (P=.011 and P=.041, respectively). There was an association between endometriosis and a history of hysterotomy (OR=2.09) but it was not statistically significant (P=.38). No other cases of lymphoma in unexposed animals were identified using HCBP animal health records. These data indicate that early lead-exposed rhesus monkeys may develop illnesses later in life, especially inguinal hernia and endometriosis, more frequently than unexposed monkeys. Studies of human populations with early lead exposure are warranted to determine their incidence of inguinal hernia, endometriosis, and hematologic neoplasia.