Evaluation of the developmental toxicity of methyl dihydrojasmonate (MDJ) in rats.
Methyl dihydrojasmonate (MDJ) is a widely used fragrance ingredient. MDJ was evaluated for developmental toxicity in presumed pregnant Sprague-Dawley rats (25/group) at oral dosages of 0, 40, 80 or 120 mg/kg/day in corn oil administered on gestational days 7-20. Dams were observed for viability, clinical signs, body weights, and feed consumption. Caesarean-sectioning and necropsy occurred on gestational day 21. Fetuses were weighed and examined for gender, gross external changes, and soft tissue or skeletal alterations. No maternal or fetal deaths occurred. MDJ-related maternal clinical signs included an increased incidence of sparse hair coat and ungroomed appearance at 120 mg/kg/day. Two dams in this group also had tan areas in the liver and a pale spleen. The 120 mg/kg/day dosage also caused reduced mean maternal body weight gains and body weights during the dosage period and reduced absolute and relative maternal feed consumption for the entire dosage period. No Caesarean-sectioning or litter parameters were affected by dosages of MDJ as high as 120 mg/kg/day, although at the highest dosage a tendency toward slightly reduced, but not statistically significant, fetal mean body weight was observed. No fetal gross external, soft tissue or skeletal changes were attributable to dosages of MDJ as high as 120 mg/kg/day. Based on these data, maternal No-Observable-Adverse-Effect-Level (NOAEL) of 80 and developmental NOAEL of equal to or greater than 120 mg/kg/day were established for MDJ. It is concluded that MDJ is not a developmental toxicant in rats under the conditions of this study.
Research Institute for Fragrance Materials, Inc., Woodcliff Lake, New Jersey 07677, USA. vpolitano@rifm.org
Valerie T
VT
Politano
Elise M
EM
Lewis
Alan M
AM
Hoberman
Mildred S
MS
Christian
Robert M
RM
Diener
Anne Marie
AM
Api
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003517:Cyclopentanes / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D015394:Molecular Structure; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000737:chemistry / Q000633:toxicity*
D003517:Cyclopentanes; D013723:Teratogens; C501952:methyldihydrojasmonate