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5018644 
Journal Article 
Evaluation Of The Developmental Toxicity Of Alpha-Methyl-3,4-Methylenedioxyhydrocinnamic Aldehyde In Rats 
Letizia, C; Api, A; Lewis, EM; Hoberman, AM; Christian, MM; Diener, RM 
2006 
1 
Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929 
90 
English 
The developmental toxicity of alpha-Methyl-3,4-methylene-dioxyhydrocinnamic aldehyde (MMDHCA), a widely used fragrance ingredient, was evaluated in rats. MMDHCA or the vehicle, corn oil, were administered orally (gavage) to one-hundred pregnant rats (25 rats/group) once daily on days 7 through 17 of gestation at doses of 0 (vehicle), 62, 125 and 250 mg/kg/day. The rats were observed for viability twice daily and clinical observations and observations for abortions, premature deliveries and deaths were conducted daily. On day 21, all rats were sacrificed and a gross necropsy of the thoracic, abdominal and pelvic viscera was performed. The uteri were removed and examined for pregnancy, number and distribution of implantation sites, early and late resorptions and fetal mortality. Each fetus was examined for gross external alterations. Approximately one half of each litter was examined for soft tissue alterations and the remaining fetuses were examined for skeletal alterations. No deaths occurred. No gross changes attributable to MMDHCA were observed at necropsy. Excessive salivation occurred in all groups, but the incidence was increased at the 250 mg/kg/day dose level. The highest dose level also produced a significant increase in the incidences of a clear, red or yellow perioral and/or red perivaginal substance and significant reductions in mean feed consumption and body weight gains during the entire dosage period. No adverse effects on embryofetal development were observed in this study. Caesarean-sectioning or litter parameters, as well as fetal alterations, were not affected by dosages of MMDHCA as high as 250 mg/kg/day. On the basis of this data, the maternal no observable adverse effect level (NOAEL) of MMDHCA is 125 mg/kg/day and the developmental NOAEL is greater than 250 mg/kg/day.