In-Life:

Physical Observations:

(Methodology and References, Appendix A). Twice daily (morning and afternoon) for signs of pharmacologic or toxicologic effects and mortality. Physical observations for abnormal signs were performed once during each exposure for all animals as a group starting on the second exposure day. In addition, each female was given a detailed physical examination or. Days 0, 6-18, 24 and 30 of gestation. On Days 6-18 of gestation, the detailed physical examinations were conducted after all animals had been removed from the chamber following exposures.

Body Weights:

(Methodology and References, Appendix A)

Recorded on Days 0, 6, 9, 12, 15, 18, 24, and 30 of gestation. Day 30 gestation body weights are presented as actual and corrected (the actual Day 30 gestation body weight minus the weight of the gravid uterus).

Food Consumption:

(Methodology and References, Appendix A)

Recorded for the following intervals during gestation: 0-1, 5-6, 6-7, 7-8, 8-9, 9-10, 10-11, 13-14, 16-17, 18-19, 19-20, 24-25 and 29-30.

Postmortem:

Maternal Evaluations:

Gross Postmortem Examinations:

Complete gross postmortem examinations were performed on all study rabbits. External surface, all orifices, the cranial cavity, carcass, the external surface of the spinal cord and sectioned surfaces of the brain, nasal cavity and paranasal sinuses, the thoracic, abdominal and pelvic cavities and their viscera and the cervical tissues and organs were examined for all animals.

The carcass of each female was discarded at completion of the gross postmortem evaluation.

Organs Weighed:

(Methodology and References, Appendix A)

The liver was weighed for all females at gestation Day 30 sacrifice, and both absolute and relative weight data are presented. The latter was presented relative to the corrected Day 30 gestation weights.

Animals Killed:

Day 30 of gestation.

Method:

Intravenous injection of Sodium Pentobarbital via the marginal ear vein.

Dates:

28 through 30 January 1991.

Reproductive System:

The intact uterus (ovaries attached) was removed from the abdominal cavity, weighed and the number and location of the following were recorded for each uterine horn; live fetuses; dead fetuses (no evidence of tissue degeneration); late resorptions (recognizable dead fetus undergoing degeneration regardless of size); early resorptions (evidence of implantation but no recognizable fetus:); implantation sites; The ovaries were dissected free from the uterus and evaluated fur the presence and number of corpora lutea. When no uterine implants were grossly apparent, the uterus was stained with ammonium sulfide (method of Salewski see Appendix A. page A-2). When no foci were visualized post-staining, the female was considered not pregnant.

Fetal Evaluations:

All fetuses were given a gross examination for external malformations variations to include observation for palatal defects. Subsequently, each fetus was weighed, humanely sacrificed via an intraperitoneal injection of pentobarbital sodium and discarded.

Late Resorptions:

Late resorptions were weighed, examined grossly for external malformations and discarded.

Statistical Analysis:

Due to the small group sizes involved, data were not evaluated statistically.

Protocol Deviations:

The following protocol deviations were not considered to have adversely effected animal health and were not considered to have compromised the validity or integrity of the study. Temperature and relative humidity values within the animal quarters and exposure chambers were outside of the desired range on some occasions."

F1 Male and Female New Zealand Rabbits