Chronic maternal methanol inhalation in nonhuman primates (Macaca fascicularis): reproductive performance and birth outcome

Burbacher, Thomas M.; Grant, Kimberly S.; Shen, Danny D.; Sheppard, Lianne; Damian, Doris; Ellis, Sean; Liberato, Noelle

doi:10.1016/j.ntt.2004.06.001

Cited by 26 publications

(22 citation statements)

References 33 publications

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“…The hypothesis was that methanol formed by the metabolism of aspartame might lead to preterm delivery, because methanol has been shown to decrease gestational length in primates (30,31).…”

Section: Discussionmentioning

confidence: 99%

Association between intake of artificially sweetened and sugar-sweetened beverages and preterm delivery: a large prospective cohort study

Englund‐Ögge¹,

Brantsæter²,

Haugen³

et al. 2012

The American Journal of Clinical Nutrition

121

102

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“…The hypothesis was that methanol formed by the metabolism of aspartame might lead to preterm delivery, because methanol has been shown to decrease gestational length in primates (30,31).…”

Section: Discussionmentioning

confidence: 99%

Association between intake of artificially sweetened and sugar-sweetened beverages and preterm delivery: a large prospective cohort study

Englund‐Ögge¹,

Brantsæter²,

Haugen³

et al. 2012

The American Journal of Clinical Nutrition

121

102

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show abstract

“…In a study by Burbacher et al (2004), Macaque monkeys (11-12 females per dose group) were exposed to 0, 200, 600 or 1800 ppm methanol vapour for 2.5 hours/day for 7 days a week (corresponding to oral doses of 0, 21, 61 and 185 mg/kg bw/day (Alexander et al, 2008)) prior to breeding and throughout pregnancy (approximately 120 days). The mothers remained healthy during the study and tests to evaluate motor incoordination, vision loss, and/or respiratory effects were negative.…”

Section: Monkeysmentioning

confidence: 99%

Scientific Opinion on the re‐evaluation of aspartame (E 951) as a food additive

2013

EFS2

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The EFSA ANS Panel provides a scientific opinion on the safety of aspartame (E 951). Aspartame is a sweetener authorised as a food additive in the EU. In previous evaluations by JECFA and the SCF, an ADI of 40 mg/kg bw/day was established based on chronic toxicity in animals. Original reports, previous evaluations, additional literature and data made available following a public call were evaluated. Aspartame is rapidly and completely hydrolysed in the gastrointestinal tract to phenylalanine, aspartic acid and methanol. Chronic and developmental toxicities were relevant endpoints in the animal database. From chronic toxicity studies in animals, a NOAEL of 4000 mg/kg bw/day was identified. The possibility of developmental toxicity occurring at lower doses than 4000 mg/kg in animals could not be excluded. Based on MoA and weight‐of‐evidence analysis, the Panel concluded that developmental toxicity in animals was attributable to phenylalanine. Phenylalanine at high plasma levels is known to cause developmental toxicity in humans. The Panel concluded that human data on developmental toxicity were more appropriate for the risk assessment. Concentration‐response modelling was used to determine the effects of aspartame administration on plasma phenylalanine using human data after phenylalanine administration to normal, PKU heterozygote or PKU homozygote individuals. In normal and PKU heterozygotes, aspartame intakes up to the ADI of 40 mg/kg bw/day, in addition to dietary phenylalanine, would not lead to peak plasma phenylalanine concentrations above the current clinical guideline for the prevention of adverse effects in fetuses. The Panel concluded that aspartame was not of safety concern at the current aspartame exposure estimates or at the ADI of 40 mg/kg bw/day. Therefore, there was no reason to revise the ADI of aspartame. Current exposures to aspartame ‐ and its degradation product DKP ‐ were below their respective ADIs. The ADI is not applicable to PKU patients.

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“…There were no differences between exposed and control infants in early visual acuity (demonstration of 20/800 Snellen required to resolve the visual elements in the test stimuli). Using a similar longitudinal study design, Burbacher and colleagues examined the infant neurobehavioral consequences of fetal exposure to methanol through maternal inhalation (Burbacher et al , 1999, 2004). Methanol exposed monkey infants, also screened for visual deficits, were able to solve recognition problems with simple test stimuli (bold, geometric patterns) but failed to provide evidence of memory on more difficult test problems (social stimuli) when compared to controls.…”

Section: Visual Recognition Memory In Neurotoxicant-exposed Infant Mamentioning

confidence: 99%

Measuring infant memory: Utility of the visual paired-comparison test paradigm for studies in developmental neurotoxicology

Burbacher

Grant

2012

Neurotoxicology and Teratology

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The assessment of brain function and behavior in young infants is central to understanding the effects of chemical exposure on central nervous system development. One approach to infant cognitive assessment, based on the direct observation of infant eye movements, is known as the Visual Paired-Comparison task. The Visual Paired-Comparison test methodology uses selective visual attention as a vehicle to study emerging recognition memory skills. The utility of this procedure to study visual recognition memory has been well established in both human and nonhuman primate infants. The primary outcome measure produced by this assessment technique is known as the Novelty Preference Score, reflecting the amount of time the infant spends actively looking at novel rather than familiar test stimuli. Visual recognition memory testing has demonstrated a strong sensitivity to conditions that may place infants at risk for poor developmental outcome (e.g. preterm birth, Down syndrome) and in humans; performance is significantly related to later measures of I.Q. and language competency. This assessment methodology has been successfully applied to the study of neurobehavioral effects after fetal neurotoxicant exposure. Field and laboratory studies have used tests of visual recognition memory to better understand the effects of compounds such as lead, methylmercury and polychlorinated biphenyls on emergent cognitive processing. The Visual Paired-Comparison paradigm and its capacity to measure recognition memory in preverbal infants provide a valid and theoretically meaningful approach to neurobehavioral assessment for studies in developmental toxicology and teratology.

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Chronic maternal methanol inhalation in nonhuman primates (Macaca fascicularis): reproductive performance and birth outcome

Cited by 26 publications

References 33 publications

Association between intake of artificially sweetened and sugar-sweetened beverages and preterm delivery: a large prospective cohort study

Association between intake of artificially sweetened and sugar-sweetened beverages and preterm delivery: a large prospective cohort study

Scientific Opinion on the re‐evaluation of aspartame (E 951) as a food additive

Measuring infant memory: Utility of the visual paired-comparison test paradigm for studies in developmental neurotoxicology

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