Pattern of limb malformations in mice induced by methoxyacetic acid

The present study investigated the pattern of limb malformations induced in mice by methoxyacetic acid (MAA), one of di(2-methoxyethyl) phthalate (DMEP) metabolites. Pregnant Jcl:ICR mice were given orally at gestational day (gd) 10.5, 11.0, or 11.5 (vaginal plug = gd 0) a single dose of MAA 10 mmol/kg of body weight. Fetuses were examined at gd 15.5 for external and skeletal malformations. Limb defects were maximum in frequency and severity after administration at gd 11.5. Forelimbs had greater susceptibility than hindlimbs. Treatment at gd 10.5 produced cutaneous or osseous syndactyly between digits I and II, II and III, and ectrodactyly of digit II or digit I. Intercalary defects in the forelimbs were also detected. No hindlimb malformations were induced. Treatment at gd 11.0 induced ectrodactyly of digit II and digit I in the forelimbs, as well as osseous syndactyly or intercalary defects of the metacarpals or phalanges, and the frequency became increased. Hindlimb malformations were also detected in a small number with syndactyly between digits I and II or ectrodactyly in digit I. Treatment at gd 11.5 induced ectrodactyly in the forelimbs. Half of the forelimbs showed ectrodactyly with four missing digits (digits I, II, III, and V) and the remaining limbs showed ectrodactyly with a similar frequency with one, two, or three missing digits, either in the pre- or postaxial area. In the hindlimbs ectrodactyly with one, two, or three missing digits was the most common malformation observed. Syndactyly between digits I and II was also induced in a small percentage.