1m - 2: Through port	80.4	77.8	81.4

1m - 3: Door open	78.5	77.1	73.9

1m - 3: Through port	80.0	79.1	79.9

1m - 4: Door open	79.2	73.8	70.8

1m - 4: Through port	81.2	76.5	76.8

O2 Level: (%)

	(Reading upon removal)	No Alarm	No Alarm	No Alarm

1m - 1	20.7	20.6	20.6

1m - 2	20.7	20.7	20.6

1m - 3	20.7	20.5	20.5

1m - 4	20.7	20.5	20.7

	a - Instrument only measures to 0.1 fc.  Correct measurement is unknown.

1m-1, 1m-2, 1m-3, 1m-4 are exposure chamber designations.

fc = foot candles (measured with an Omega HHLM-2 Light Meter)

db = decibels (measured using an Omega HHSL-1 Sound Meter)

% = % oxygen (measured using a Biosystems Oxy Plus Single Sensor Gas Detector with an alarm at 19.5% O2)

I-20

APPENDIX I  -  INHALATION EXPOSURE DATA (CONT'D)

TABLE  I-6 - PARTICLE SIZE DATA

0 MG/M3

 PRIVATE  IMPACTOR

STAGE	STAGE CONSTANT

(um)	FILTER WEIGHT

DIFFERENCE (UG)	PERCENT IN

SIZE RANGE

FILTER	0.30	0	0

8	0.54	0	0

7	0.84	0	0

6	1.50	0	0

5	2.60	0	0

4	4.10	0	0

3	6.80	10	100

2	17.0	0	0

1	28.0	0	0

TOTAL = 10

	PARTICLE CONCENTRATION = 0.5 MG/M3

	PARTICLE SIZE DETERMINED WITH A SIERRA SERIES 210 CASCADE IMPACTOR

	CONDITIONS:

		SAMPLE FLOWRATE (Liters/Minute):  4		SAMPLE DURATION (Minutes):  5

		CALCULATION OF PARTICLE CONCENTRATION:

		SAMPLE VOLUME = SAMPLE FLOW RATE*SAMPLE DURATION

		PARTICLE CONCENTRATION =

		((TOTAL FILTER WEIGHT DIFFERENCE [ug]/1000 [ug/mg])/(SAMPLE VOLUME [L]))*1000 [L/M3]

I-21

APPENDIX I  -  INHALATION EXPOSURE DATA (CONT'D)

TABLE  I-6 - PARTICLE SIZE DATA (CONT'D)

20,000 MG/M3 TARGET

 PRIVATE  IMPACTOR

STAGE	STAGE CONSTANT

(um)	FILTER WEIGHT

DIFFERENCE (UG)	PERCENT IN

SIZE RANGE

FILTER	0.30	0	0

8	0.54	0	0

7	0.84	0	0

6	1.50	0	0

5	2.60	0	0

4	4.10	10	100

3	6.80	0	0

2	17.0	0	0

1	28.0	0	0

TOTAL = 10

	CONCENTRATION OF PARTICLES = 0.5 MG/M3

	PARTICLE SIZE DETERMINED WITH A SIERRA SERIES 210 CASCADE IMPACTOR

	CONDITIONS:

		SAMPLE FLOWRATE (Liters/Minute):  4		SAMPLE DURATION (Minutes):  5

		CALCULATION OF PARTICLE CONCENTRATION:

		SAMPLE VOLUME (Liters) = SAMPLE FLOW RATE*SAMPLE DURATION

		PARTICLE CONCENTRATION =

		((TOTAL FILTER WEIGHT DIFFERENCE/1000 ug/mg)/(SAMPLE VOLUME))*1000 L/M3

I-22

TABLE  I-7 – CHAMBER TEMPERATURES AND HUMIDITIES

CHAMBER TEMPERATURES (ºF) - 0 mg/m3 Target Concentration

	Time from Start of Exposure (Hours)

	0	0.5	1	1.5	2	2.5	3	3.5	4	4.5	5	5.5	6

31-Aug-02	66	70	70	70	70	70	70	70	70	70	70	70	70

1-Sep-02	66	68	68	68	68	68	68	68	68	68	68	68	68

2-Sep-02	68	70	72	72	72	72	72	72	72	72	72	72	72

3-Sep-02	66	72	72	72	72	72	72	72	72	72	72	72	72

4-Sep-02	68	72	72	72	72	72	72	72	72	72	72	72	72

5-Sep-02	68	72	72	72	72	72	72	72	72	72	72	74	74

6-Sep-02	68	72	74	74	74	74	74	74	74	74	74	74	74

7-Sep-02	68	70	71	71	71	71	71	71	71	71	71	71	71

8-Sep-02	70	72	72	72	72	72	72	72	72	72	72	72	72

9-Sep-02	68	70	72	72	72	72	72	72	72	74	74	74	74

10-Sep-02	70	72	74	74	74	74	74	74	74	74	74	74	74

11-Sep-02	70	72	74	74	74	74	74	74	74	74	74	74	74

12-Sep-02	70	72	74	74	76	75	75	75	75	75	75	75	75

13-Sep-02	72	74	74	74	76	76	76	76	76	76	76	76	76

14-Sep-02	68	70	70	70	74	74	74	74	74	74	74	74	74

15-Sep-02	70	74	74	74	74	74	74	74	74	74	74	74	74

16-Sep-02	67	70	72	72	72	73	74	74	74	74	74	74	74

17-Sep-02	70	72	74	74	74	74	74	74	74	74	74	74	74

18-Sep-02	68	68	72	72	74	74	74	74	74	74	74	74	74

19-Sep-02	70	70	72	72	72	72	72	72	72	72	72	72	72

20-Sep-02	68	70	72	72	72	72	72	72	72	72	72	72	72

21-Sep-02	68	72	72	72	72	72	72	72	72	72	72	72	72

22-Sep-02	68	70	70	72	72	72	72	72	72	72	72	72	72

23-Sep-02	68	72	72	72	72	74	74	74	74	74	74	74	74

24-Sep-02	70	70	70	70	70	74	74	74	74	74	74	74	74

25-Sep-02	68	70	70	70	72	72	72	72	72	72	72	72	72

26-Sep-02	68	70	70	70	72	72	72	72	72	72	72	72	72

I-23

TABLE  I-7 – CHAMBER TEMPERATURES AND HUMIDITIES (CONT’D)

CHAMBER TEMPERATURES (ºF) - 2000 mg/m3 Target Concentration

	Time from Start of Exposure (Hours)

	0	0.5	1	1.5	2	2.5	3	3.5	4	4.5	5	5.5	6

31-Aug-02	66	68	70	70	70	70	70	70	70	70	70	70	70

1-Sep-02	66	70	70	70	70	70	70	70	70	70	70	70	70

2-Sep-02	68	70	70	70	70	70	70	70	70	70	70	70	70

3-Sep-02	66	70	70	70	70	70	70	70	70	70	70	70	70

4-Sep-02	68	72	72	72	72	72	72	72	74	74	74	74	74

5-Sep-02	68	70	72	72	72	72	72	72	72	72	74	74	74

6-Sep-02	70	72	72	72	72	72	72	72	72	72	72	72	72

7-Sep-02	70	70	70	70	70	70	70	70	70	70	70	70	70

8-Sep-02	70	72	72	72	72	72	72	72	72	72	72	72	72

9-Sep-02	68	70	70	70	70	70	70	70	70	74	74	74	74

10-Sep-02	70	70	73	74	74	74	74	74	74	74	74	74	74

11-Sep-02	70	72	74	74	74	74	74	76	76	76	76	76	76

12-Sep-02	70	70	74	74	74	74	74	74	74	74	74	74	74

13-Sep-02	70	74	74	74	76	76	76	76	76	76	76	76	76

14-Sep-02	68	70	70	72	72	73	73	73	73	73	73	73	73

15-Sep-02	70	74	74	74	74	74	74	74	74	74	74	74	74

16-Sep-02	68	72	72	72	72	70	74	74	74	74	74	74	74

17-Sep-02	70	70	74	74	74	74	74	74	74	74	74	74	74

18-Sep-02	70	72	72	72	74	74	74	74	74	74	74	74	74

19-Sep-02	70	72	72	72	72	72	72	72	72	72	72	72	72

20-Sep-02	68	70	70	70	72	72	72	72	72	72	72	72	72

21-Sep-02	66	70	70	70	70	70	70	72	72	72	72	72	72

22-Sep-02	68	70	70	70	70	70	70	70	70	70	70	70	70

23-Sep-02	68	70	72	72	72	72	72	72	72	72	72	72	72

24-Sep-02	70	70	72	72	72	72	72	72	72	72	72	72	72

25-Sep-02	68	70	70	70	70	70	70	70	72	72	72	72	72

26-Sep-02	68	70	70	72	72	72	72	72	72	72	72	72	72

I-24

TABLE  I-7 – CHAMBER TEMPERATURES AND HUMIDITIES (CONT’D)

CHAMBER TEMPERATURES (ºF) – 10,000 mg/m3 Target Concentration

	Time from Start of Exposure (Hours)

	0	0.5	1	1.5	2	2.5	3	3.5	4	4.5	5	5.5	6

31-Aug-02	68	72	74	74	74	74	74	74	74	74	74	74	74

1-Sep-02	66	72	72	72	72	72	72	72	72	72	72	72	72

2-Sep-02	66	72	74	74	74	74	74	74	74	74	74	74	74

3-Sep-02	66	74	74	74	74	74	74	74	74	74	74	74	74

4-Sep-02	68	74	74	76	76	76	76	76	76	76	76	76	76

5-Sep-02	68	74	76	76	76	76	76	76	76	76	76	78	78

6-Sep-02	70	74	74	74	76	76	76	76	76	76	76	76	76

7-Sep-02	70	73	73	73	73	73	73	73	73	73	73	73	73

8-Sep-02	70	72	72	74	74	74	74	74	74	74	74	74	74

9-Sep-02	68	72	74	76	76	76	76	76	76	78	78	78	78

10-Sep-02	70	74	76	78	78	78	78	78	78	78	78	78	78

11-Sep-02	68	74	76	76	76	78	78	78	78	78	78	78	78

12-Sep-02	70	74	76	78	78	78	78	78	78	78	78	78	78

13-Sep-02	70	74	76	78	78	78	78	78	78	78	78	78	78

14-Sep-02	68	73	76	76	76	76	76	76	76	76	76	76	76

15-Sep-02	70	72	74	74	74	74	74	74	74	74	74	74	74

16-Sep-02	66	72	74	76	76	76	78	78	78	78	78	78	78

17-Sep-02	70	73	76	76	78	78	78	78	78	78	78	78	78

18-Sep-02	70	74	76	76	78	78	78	78	78	78	78	78	78

19-Sep-02	70	72	74	74	76	76	78	78	78	78	78	78	78

20-Sep-02	70	74	76	76	76	76	76	78	78	78	78	78	78

21-Sep-02	68	72	74	74	76	76	76	78	78	78	78	78	78

22-Sep-02	68	72	74	76	76	76	76	76	76	76	76	76	76

23-Sep-02	66	74	76	76	76	78	78	78	78	78	78	78	78

24-Sep-02	70	74	76	76	76	76	76	76	78	78	78	78	78

25-Sep-02	70	74	74	74	76	76	76	76	76	76	76	76	76

26-Sep-02	70	74	74	76	76	76	76	76	76	76	76	76	76

I-25

TABLE  I-7 – CHAMBER TEMPERATURES AND HUMIDITIES (CONT’D)

CHAMBER TEMPERATURES (ºF) – 20,000 mg/m3 Target Concentration

	Time from Start of Exposure (Hours)

	0	0.5	1	1.5	2	2.5	3	3.5	4	4.5	5	5.5	6

31-Aug-02	66	68	70	70	70	70	70	70	70	70	70	70	70

1-Sep-02	66	68	72	72	72	72	72	72	72	72	72	72	72

2-Sep-02	66	70	70	70	70	70	70	70	70	70	70	70	70

3-Sep-02	66	70	70	70	70	70	70	70	70	70	70	70	70

4-Sep-02	68	70	72	72	72	72	72	74	74	74	74	74	74

5-Sep-02	68	70	72	72	72	72	72	74	74	74	74	74	74

6-Sep-02	68	72	72	74	74	74	74	74	74	74	74	74	74

7-Sep-02	68	70	72	72	72	72	72	72	72	72	72	72	72

8-Sep-02	70	70	74	74	74	74	74	74	74	74	74	74	74

9-Sep-02	68	70	72	74	74	74	74	74	74	74	74	74	74

10-Sep-02	68	70	72	74	74	74	74	74	76	76	76	76	76

11-Sep-02	68	70	72	74	74	74	74	76	76	76	76	76	76

12-Sep-02	68	71	72	74	74	74	74	74	74	74	74	74	74

13-Sep-02	70	72	74	74	74	74	74	74	74	74	76	76	76

14-Sep-02	68	70	72	72	72	72	72	72	72	72	72	72	72

15-Sep-02	70	72	72	72	72	72	72	72	72	72	72	72	72

16-Sep-02	66	68	70	70	72	72	74	74	74	74	74	74	74

17-Sep-02	68	70	72	74	74	74	74	74	74	74	74	74	74

18-Sep-02	68	70	72	72	72	72	74	74	74	74	74	74	74

19-Sep-02	68	70	70	72	72	72	72	74	74	74	74	74	74

20-Sep-02	66	70	72	72	72	72	72	74	74	74	74	74	74

21-Sep-02	66	70	72	72	72	72	72	74	74	74	74	74	74

22-Sep-02	68	70	72	72	72	72	72	72	72	72	72	72	72

23-Sep-02	66	70	70	70	72	72	72	74	74	74	74	74	74

24-Sep-02	68	70	72	72	72	72	72	72	72	72	72	72	72

25-Sep-02	68	70	70	70	72	72	72	72	72	72	72	72	72

26-Sep-02	68	70	70	70	70	70	70	70	70	72	72	72	72

I-26

TABLE  I-7 – CHAMBER TEMPERATURES AND HUMIDITIES (CONT’D)

CHAMBER HUMIDITIES (%RH) - 0 mg/m3 Target Concentration

	Time from Start of Exposure (Hours)

	0	0.5	1	1.5	2	2.5	3	3.5	4	4.5	5	5.5	6

31-Aug-02	71	64	64	64	64	64	64	64	64	64	64	64	64

1-Sep-02	71	72	72	72	72	72	72	72	72	72	72	72	72

2-Sep-02	72	64	57	57	57	57	57	57	57	57	57	57	57

3-Sep-02	80	65	65	65	65	65	65	65	65	65	65	65	65

4-Sep-02	72	65	65	65	65	65	65	65	65	65	65	65	65

5-Sep-02	72	65	65	65	65	65	65	65	65	65	65	58	58

6-Sep-02	72	57	58	58	58	58	58	58	58	58	58	58	58

7-Sep-02	67	64	64	64	64	64	64	64	64	64	64	64	64

8-Sep-02	72	65	65	65	65	65	65	65	65	65	65	65	65

9-Sep-02	72	68	65	65	65	65	65	65	65	58	58	58	58

10-Sep-02	72	69	58	58	58	58	58	58	58	58	58	58	58

11-Sep-02	72	65	58	58	58	58	58	58	58	58	58	58	58

12-Sep-02	64	57	51	51	45	48	48	48	48	48	48	48	48

13-Sep-02	57	58	58	58	52	52	52	52	52	52	52	52	52

14-Sep-02	81	72	72	72	72	72	72	72	72	72	72	72	72

15-Sep-02	72	58	58	58	58	58	58	58	58	58	58	58	58

16-Sep-02	95	90	82	82	82	78	66	66	66	66	66	66	66

17-Sep-02	72	65	58	58	58	58	58	58	58	58	58	58	58

18-Sep-02	72	72	65	65	58	58	58	58	58	58	58	58	58

19-Sep-02	64	64	57	57	57	57	57	57	57	57	57	57	57

20-Sep-02	72	64	57	57	57	57	57	65	65	65	65	65	65

21-Sep-02	72	65	65	65	65	65	65	65	65	65	65	65	65

22-Sep-02	72	64	64	57	57	57	57	57	57	57	57	57	57

23-Sep-02	64	57	57	57	57	58	58	58	58	58	58	58	58

24-Sep-02	57	57	57	57	57	57	57	57	57	57	57	57	57

25-Sep-02	64	57	57	57	57	57	57	57	57	57	57	57	57

26-Sep-02	64	64	64	64	64	64	64	64	64	64	64	64	64

I-27

TABLE  I-7 – CHAMBER TEMPERATURES AND HUMIDITIES (CONT’D)

CHAMBER HUMIDITIES (%RH) - 2000 mg/m3 Target Concentration

	Time from Start of Exposure (Hours)

	0	0.5	1	1.5	2	2.5	3	3.5	4	4.5	5	5.5	6

31-Aug-02	71	72	64	64	64	64	64	64	64	64	64	64	64

1-Sep-02	71	64	64	64	64	64	64	64	64	64	64	64	64

2-Sep-02	72	64	64	64	64	64	64	64	64	64	64	64	64

3-Sep-02	71	64	64	64	64	64	64	64	64	64	64	64	64

4-Sep-02	72	65	65	65	65	65	65	65	58	58	58	58	58

5-Sep-02	72	72	65	65	65	65	65	65	65	65	65	65	65

6-Sep-02	64	57	57	65	65	65	57	57	57	57	57	65	65

7-Sep-02	57	64	68	68	68	68	68	68	68	68	68	68	68

8-Sep-02	72	65	65	65	65	65	65	65	65	65	65	65	65

9-Sep-02	72	68	68	68	68	68	68	68	68	58	58	58	58

10-Sep-02	72	72	61	66	66	66	66	66	66	66	66	66	66

11-Sep-02	72	65	58	58	58	58	58	52	52	52	52	52	52

12-Sep-02	64	64	51	51	51	51	51	51	51	51	51	51	51

13-Sep-02	64	58	58	58	52	52	52	52	52	52	52	52	52

14-Sep-02	72	72	72	69	69	69	69	69	69	69	69	69	69

15-Sep-02	72	58	58	58	58	58	58	58	58	58	58	58	58

16-Sep-02	90	73	73	73	73	72	66	66	66	66	66	66	66

17-Sep-02	72	72	58	58	58	58	58	58	58	58	58	58	58

18-Sep-02	64	65	65	65	58	58	58	58	58	58	58	58	58

19-Sep-02	64	65	65	65	65	65	65	65	65	65	65	65	65

20-Sep-02	72	64	64	64	57	57	57	65	65	65	65	65	65

21-Sep-02	90	81	81	81	72	72	72	65	65	65	65	65	65

22-Sep-02	64	64	64	64	64	64	64	64	64	64	64	64	64

23-Sep-02	64	64	57	57	57	57	57	57	57	57	57	57	57

24-Sep-02	57	57	57	57	57	57	57	57	57	50	50	50	50

25-Sep-02	64	57	57	57	57	57	57	57	57	57	57	57	57

26-Sep-02	64	64	64	57	57	57	57	57	57	57	57	57	57

I-28

TABLE  I-7 – CHAMBER TEMPERATURES AND HUMIDITIES (CONT’D)

CHAMBER HUMIDITIES (%RH) – 10,000 mg/m3 Target Concentration

	Time from Start of Exposure (Hours)

	0	0.5	1	1.5	2	2.5	3	3.5	4	4.5	5	5.5	6

31-Aug-02	64	57	58	58	58	58	58	58	58	58	58	58	58

1-Sep-02	71	57	57	57	57	57	57	57	57	57	57	57	57

2-Sep-02	71	65	58	58	58	58	58	58	58	58	58	58	58

3-Sep-02	80	58	58	58	58	58	58	58	58	58	58	58	58

4-Sep-02	72	58	58	59	59	59	59	59	59	59	59	59	59

5-Sep-02	72	58	59	59	59	59	59	59	59	59	59	53	53

6-Sep-02	64	58	58	58	52	52	52	52	52	52	52	52	52

7-Sep-02	64	61	65	65	65	65	65	65	65	65	65	65	65

8-Sep-02	76	65	65	58	58	58	58	58	58	58	58	58	58

9-Sep-02	72	65	58	56	56	56	56	56	56	53	53	53	53

10-Sep-02	72	62	56	53	53	53	53	53	53	53	53	53	53

11-Sep-02	72	58	59	59	59	53	53	53	53	53	53	53	53

12-Sep-02	57	51	45	46	46	46	46	46	46	46	46	46	46

13-Sep-02	64	58	52	53	53	53	53	53	53	53	53	53	53

14-Sep-02	72	65	59	59	59	59	59	59	59	59	59	59	59

15-Sep-02	72	65	66	66	66	66	66	66	66	66	66	66	66

16-Sep-02	90	82	74	67	67	67	57	57	57	53	53	53	53

17-Sep-02	72	61	59	59	53	53	53	53	53	53	53	53	53

18-Sep-02	64	58	59	59	53	53	53	53	53	53	53	53	53

19-Sep-02	81	73	66	66	59	59	53	53	53	53	53	53	53

20-Sep-02	64	58	52	52	52	52	52	53	53	53	53	53	53

21-Sep-02	72	65	66	66	59	59	59	53	53	53	53	53	53

22-Sep-02	64	61	58	52	52	52	52	52	52	52	52	52	52

23-Sep-02	71	58	52	52	52	52	52	52	52	52	52	52	52

24-Sep-02	57	51	45	52	52	52	52	52	46	46	46	46	46

25-Sep-02	57	51	51	51	52	52	52	52	52	52	52	52	52

26-Sep-02	64	58	58	52	52	52	52	52	52	52	52	52	52

I-29

TABLE  I-7 – CHAMBER TEMPERATURES AND HUMIDITIES (CONT’D)

CHAMBER HUMIDITIES (%RH) – 20,000 mg/m3 Target Concentration

	Time from Start of Exposure (Hours)

	0	0.5	1	1.5	2	2.5	3	3.5	4	4.5	5	5.5	6

31-Aug-02	71	72	64	64	64	64	64	64	64	64	64	64	64

1-Sep-02	71	72	57	57	57	57	57	57	57	57	57	57	57

2-Sep-02	71	64	64	64	64	64	64	64	64	64	64	64	64

3-Sep-02	71	72	72	72	72	72	72	72	72	72	72	72	72

4-Sep-02	72	72	65	65	65	65	65	58	58	58	58	58	58

5-Sep-02	72	72	65	65	65	65	65	58	58	58	58	58	58

6-Sep-02	81	65	65	58	58	58	58	58	58	58	58	58	58

7-Sep-02	64	72	65	65	65	65	65	65	65	65	65	65	65

8-Sep-02	72	72	58	58	58	58	58	58	58	58	58	58	58

9-Sep-02	72	77	65	58	58	58	58	58	58	58	58	58	58

10-Sep-02	72	77	65	58	58	58	58	58	59	59	59	59	59

11-Sep-02	72	72	65	58	58	58	58	52	52	52	52	52	52

12-Sep-02	55	57	57	51	51	51	51	51	51	51	51	51	51

13-Sep-02	57	57	51	58	58	58	58	58	58	58	52	52	52

14-Sep-02	72	64	65	69	69	69	69	69	69	69	69	69	69

15-Sep-02	72	65	65	65	65	65	65	65	65	65	65	65	65

16-Sep-02	90	90	81	81	73	73	66	66	66	58	58	58	58

17-Sep-02	72	72	65	58	58	58	58	58	58	58	58	58	58

18-Sep-02	72	72	65	65	65	65	58	58	58	58	58	58	58

19-Sep-02	72	64	64	65	65	65	65	58	58	58	58	58	58

20-Sep-02	71	64	57	57	57	57	65	58	58	58	58	58	58

21-Sep-02	71	72	65	65	65	65	65	58	58	58	58	58	58

22-Sep-02	64	64	61	61	61	61	61	61	61	61	61	61	61

23-Sep-02	71	64	64	64	57	57	57	58	58	58	58	58	58

24-Sep-02	64	64	57	57	57	57	57	57	57	57	57	57	57

25-Sep-02	64	64	64	64	57	57	57	57	57	57	57	57	57

26-Sep-02	64	64	64	64	64	64	64	64	64	57	57	57	57

I-30

	APPENDIX J- ANALYTICAL CHEMISTRY REPORT

	SUMMARY

Charcoal tube sorbent tube samples were received by the Analytical Chemistry Laboratory from  inhalation chamber exposures and were characterized for hydrocarbon distribution using capillary gas chromatography with flame ionization detection (GC/FID).  Sorbent tube samples were stored in a freezer pending analysis.

	SAMPLE PREPARATION

The front and back sections of each charcoal sample tube were desorbed and analyzed separately to

assess potential sampling breakthrough.  The charcoal tube sections were desorbed with 3.0 mL  5% 2-propanol / 95% carbon disulfide (5% 2-PrOH/95% CS2) for at least 30 minutes.  Aliquots were then analyzed by GC-FID.

	STANDARDIZATION

A standard mixture was prepared in CS2 containing each of the 18 target hydrocarbons plus TBA oxygenate.  Analysis of the standard mixture was used to confirm the relative retention times of each target hydrocarbon and was not used for quantitative purposes.

CHARACTERIZATION

Characterization of the neat MRD-00-718 (gasoline vapor condensate with TBA) was performed separately and will be reported as part of EMBSI Study 167490. Neat test substance characterization included a similar analysis of the relative distribution of target hydrocarbons and oxygenate as was performed for the chamber sorbent tube samples.

J-1

APPENDIX J- ANALYTICAL CHEMISTRY REPORT

INSTRUMENT CONDITIONS FOR MRD-00-718

ON CHARCOAL SORBENT TUBE

The following GC conditions and equipment were used to determine the hydrocarbon distribution of test substance on chamber characterization sorbent tubes:

GC	Perkin Elmer XL Autosystem

FID Range	FID (2^5)

Detector Temperature; (gas flows)	225°C (H2 45 mL/min; Air  450 mL/min)

Injector Temperature (Split ratio)	200°C (split injection 20:1)

Injection Volume	0.2µL or 0.5µL*

Analytical Column C-32	Supleco Petrocol DH 150 fused silica capillary column (150 m x 250 µm; 1.0 µm film thickness)

Oven Temperature Program	35(C (hold 130 minutes); ramp @ 2(C/minute to 200(C

Data Collection	Perkin Elmer Nelson Turbochrom (TC4) version 4.1.2

Carrier Gas Program	65 psi (He)

*0.2µL injected of 10,000mg/m3 and 20,000mg/m3 samples, 0.5µL injected of 2000mg/m3 samples.

RESULTS

Hydrocarbon characterization was performed on an area percent basis for each of the 18

target hydrocarbons and TBA oxygenate. Results are listed in Table J-1.

The relative distribution of hydrocarbons and oxygenate measured on the chamber characterization charcoal tubes was in good agreement with that measured in the characterization of neat MRD-00-718 test substance.

D. J. Letinski, Analytical Chemist			Date

J-2

APPENDIX J- ANALYTICAL CHEMISTRY REPORT

TABLE J - 1

MRD-00-718 CHAMBER CHARACTERIZATION - SORBENT TUBES HYDROCARBON DISTRIBUTION

Sample Date

4-Sep-02	10-Sep-02	17-Sep-02

25-Sep-02

Inhalation ID

1	2	3	4	5	6	7	8	9

10	11	12

 target mg/m3	target  mg/m3	target  mg/m3

target  mg/m3

2000	10,000	20,000	2000	10,000	20,000	2000	10,000	20,000	2000	10,000 20,000

Compound

RESULTS   ARE   in   "AREA %"  of   TARGET   HYDROCARBONS

isobutane

2.1	2.0	2.0	2.2	2.2	0.3	2.2	2.0	2.0

2.2	2.0	2.1

n-butane

9.6	9.4	9.3	10.1	9.8	3.1	9.8	9.5	9.4

10.1	9.5	9.6

isopentane

25.9	26.1	26.5	26.3	26.2	21.4	25.9	26.1	26.2

26.6	25.7	25.9

n-pentane

12.0	12.1	12.3	12.1	12.1	11.8	12.0	12.1	12.2

12.3	12.0	12.0

trans-2-pentene

2.2	2.2	2.2	2.2	2.2	2.3	2.2	2.2	2.2

2.2	2.2	2.2

TBA

14.9	15.7	15.9	14.6	15.5	19.9	15.0	15.7	16.1

15.4	16.1	16.1

2-methyl-2-butene

3.3	3.3	3.4	3.3	3.3	3.6	3.3	3.3	3.4

3.3	3.3	3.3

2,3-dimethylbutane

1.9	1.9	1.9	1.9	1.9	2.3	1.9	1.9	1.9

1.9	1.9	1.9

2-methylpentane

6.4	6.4	6.4	6.3	6.3	7.8	6.3	6.4	6.3

6.3	6.3	6.3

3-methylpentane

4.0	4.0	3.9	3.9	3.9	5.0	3.9	4.0	3.9

3.9	4.0	3.9

n-hexane

3.5	3.5	3.4	3.5	3.4	4.5	3.4	3.5	3.4

3.4	3.5	3.5

methylcyclopentane

1.7	1.7	1.7	1.7	1.6	2.2	1.7	1.7	1.7

1.7	1.7	1.7

2,4-dimethylpentane

1.1	1.1	1.1	1.1	1.1	1.5	1.1	1.1	1.1

1.0	1.1	1.1

benzene

2.5	2.1	2.1	2.4	2.1	2.9	2.5	2.1	2.1

2.4	2.2	2.2

2-methylhexane

1.4	1.3	1.3	1.3	1.3	1.8	1.4	1.3	1.3

1.2	1.4	1.3

2,3-dimethylpentane

1.3	1.3	1.2	1.3	1.3	1.7	1.3	1.3	1.2

1.2	1.3	1.3

3-methylhexane

1.6	1.5	1.5	1.5	1.5	2.0	1.6	1.5	1.5

1.3	1.5	1.5

isooctane

1.6	1.6	1.5	1.5	1.6	2.1	1.6	1.6	1.5

1.3	1.6	1.5

toluene

3.0	2.9	2.6	2.8	2.9	4.0	3.0	2.9	2.6

2.4	2.9	2.8

Sum

100	100	100	100	100	100	100	100	100

100	100	100

	        No hydrocarbon target compounds were detected on the back section of the sorbent tubes analyzed.

J-3

APPENDIX K – STATISTICIAN’S REPORT

Analysis of Fetal Data from a Whole-Body Inhalation Developmental Toxicity

Study in Rats with Gasoline with TBA Vapor Condensate (MRD-00-718)

This report details the statistical analysis of fetal body weight and anomaly data from ExxonMobil Study 171834.  The study was conducted to evaluate the potential developmental toxicity of Gasoline with TBA Vapor Condensate (GTVC).  GTVC was administered via whole-body inhalation exposure to pregnant rats during the period of major organogenesis and fetal growth.  GTVC was administered by whole-body inhalation exposure to 25 confirmed-mated CD® (SD) IGS BR female rats at target exposures of 0 (air control) 2000, 10,000, and 20,000 mg/m3 for six hours (plus the theoretical equilibration time) daily from Gestation Day (GD) 5 through GD 20.

The fetal body weight was analyzed by a mixed model analysis of variance that provides an accurate statistical model of the biology.  The analysis used the litter as the basis for analysis and effectively used the litter size as a covariate.  Two alternative models were used: one model considered exposure group, litter size, and fetal sex as explanatory variables while the other model used these variables and included the corpora lutea (CL) as an additional covariate.  When the overall effect of exposure, or the interactions with exposure, were statistically significant the exposure groups means were tested pairwise vs. the control group using least squares means.  The least squares means allows comparisons that account for differences in litter size and sex.  The mathematical model is based on a paper by Chen, et al (1996).  The analysis was run using SAS with code suggested in Little, et al (1997).

The number of implants per dam, the litter size per dam, and the dam uterine weight were analyzed by a standard analysis of variance with CL as a covariate.  When the overall effect of exposure, or the interactions of exposure with CL, was statistically significant the exposure groups’ means were tested pairwise vs. the control group using least squares means (Snedecor and Cochran, 1989).

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APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

The analysis of anomalies (malformations or variations) was based on a Generalized Estimating Equation (GEE) application of the linearized model, Ryan (1992).  The model used the litter as the basis for analysis and considered correlation among littermates by incorporating an estimated constant correlation and the litter size as a covariate.  When the overall effect of exposure, or the exposure by sex effect, was statistically significant the exposure groups were tested pairwise vs. the control group using least squares means.  The least squares means allows comparisons that account for differences in litter size.  There were three categories of anomalies tested, and within each category specific anomalies were also tested.  In addition to the category specific anomalies a series of combined analyses were performed within each category:

Combined Malformations and Variations for All Fetuses

Combined Malformations and Variations for Alive Fetuses

Combined Malformations and Variations for Dead Fetuses

Malformations for All Fetuses

Malformations for Alive Fetuses

Malformations for Dead Fetuses

Variations for All Fetuses

Variations for Alive Fetuses

Variations for Dead Fetuses

In some cases there were no dead fetuses in a category.

Table I lists the four categories and corresponding sub-categories.  Within each category several subcategories were combined into a group of similar anomalies.  For example in the Category Skeletal the separate sub-categories of “Bifid vertebral centra” and “Dumbbell-shaped vertebral centra” were combined into a sub-category “Hypoplastic vertebral centra”.  In this combined category an animal is counted once when he, or she, exhibits more than one characteristic.  The sub-categories that were combined are listed in the Sub-categories Combined column of Table 1 by the sub-category number.  The analyses were run using SAS.

K-2

APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

Table I

Malformation Categories and Corresponding Sub-categories

Category	Sub-Category	Sub-categories combined

Head	1 - Retinal fold; Left

	External	1 - Adactyly forepaw; Bilateral

2 - Cleft palate

3 - Ectrodactyly hindpaw; Bilateral (2 digits on each paw)

4 - Hooked tail

5 - Malrotated hindpaw

6 – Microcephaly

7 - Protruding tongue

8 - Short tail

	Abdomen/Thorax	1 - Malpositioned kidney; Bilateral

2 - Umbilical artery arises from left side of urinary bladder

	Skeletal	1 - Multiple paw bones absent

2 Ribs - Fused; Right

3 Ribs - Multiple bones malformed

4 - Rudimentary supernumerary ribs

5 - Short last rib

6 Skull - Multiple bones malformed

7 Sternebrae – Bifid

8 Sternebrae – Fused

9 - Asymmetric sternebrae

10 - Hypoplastic sternebrae

11 - Unossified sternebrae

12 - Presacral vertebrae

13 - Bifid vertebral centra

14 - Dumbbell-shaped vertebral centra

15 - Dumbbell-shaped vertebral centra anlage

16 - Malformed vertebral arch

17 Vertebrae - Multiple bones malformed

18 - Delayed ossification of the sternebrae	10, 11

	19 - Hypoplastic vertebral centra	13, 14

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APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

RESULTS:

BODY WEIGHT ANALYSIS

Based on the bodyweight analysis that did not consider CL count, there was no statistically significant difference in the mean fetal litter weights among the exposure groups.  The exposure by sex interaction was not statistically significant; therefore only the group means are presented.  Table II shows the mean fetal weight and the least squares mean fetal weight.

Table II

Mean fetal weight, the least squares mean fetal weight not considering CL count

Exposure Group

(mg/m3)	n litters 	n fetuses	observed fetus mean (gm)	Least squares fetus mean (gm)

0	25	385	5.29	5.32

2,000	23	302	5.33	5.29

10,000	23	327	5.29	5.29

20,000	24	345	5.13	 5.16

The bodyweight analysis that included CL count and a CL by exposure interaction indicated a statistically significant difference in the mean fetal litter weights among the exposure groups and an exposure by CL count interaction (p<0.0025 and p<0.0005 respectively); the 20,000 mg/m3 exposure group was different from the 0 exposure group (p<0.02).  When the model as fit without the exposure by CL count interaction there was not a significant difference in fetal weights among the exposure groups (p<0.14).  Table III shows the mean fetal weight and the least squares mean fetal weight based on the two models.

Table III

Mean fetal weight, the least squares mean fetal weight considering CL count

Exposure Group

(mg/m3)	n litters 	n fetuses	n CL	observed fetus mean (gm)	Least squares fetus mean (gm)

with CL*exposure	Least squares fetus mean (gm)

without CL*exposure

0	25	385	16.3	5.29	5.31	5.31

2,000	23	302	14.0	5.33	5.36	5.30

10,000	23	327	14.9	5.29	5.26 	5.29

20,000	24	345	15.1	5.13	 5.15 *	5.16

               * statistically significantly different from control, p<0.02

K-4

APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

IMPLANTS, LITTER SIZE, AND UTERINE WEIGHT ANALYSES

The number of implants per dam, the litter size per dam, and the dam uterine weight analyses that included a CL and an exposure by CL interaction indicated statistically significant differences in the exposure related means for all three measures. However, only the uterine weight analyses indicated a statistically significant difference between the control and an exposed group.  Table IV shows the means the least squares means for these three measures.  When the analyses were repeated with a model that did not include an exposure by CL interaction term there were no statistically significant exposure related effects.

Table IV

Mean number of implants, litter size, and uterine weight, and the

corresponding least squares means considering CL count and an exposure by CL interaction

	Observed Means	Least Squares Means

Exposure Group

(mg/m3)	n litters

	n

CL	n implants	Litter Size	Uterine Weight	n implants	Litter Size	Uterine Weight

0	25	16.3	15.68	15.40	114.3	14.73	14.58	109.2

2,000	23	14.0	13.30	13.13	100.6	14.35	14.17	107.7

10,000	23	14.9	14.61	14.22	105.5	14.82	14.44	106.6

20,000	24	15.1	14.71	14.38	104.1	14.71	14.38	103.7*

* statistically significantly different from control, p<0.02

MALFORMATION ANALYSES

Of the 31 anomaly analyses the count of skeletal rudimentary supernumerary ribs, count of combined skeletal variations and malformations and count of combined skeletal variations indicated a statistically significant differences among the exposure groups (p<0.05).  Individual comparisons indicated the high exposure group (20,000 mg/m3) had a large incidence of rudimentary supernumerary ribs than the control group.  None of the other measures indicated statistically significant differences among the exposure groups.   See Table V for the incidences of skeletal rudimentary supernumerary ribs.

Statistically significant differences in counts between control and 20,000 mg/m3 for count of combined skeletal variations and malformations and count of combined skeletal variations can be explained by difference in counts for skeletal rudimentary supernumerary ribs. Differences between exposure groups become insignificant when the skeletal count of rudimentary supernumerary ribs are removed from the definitions of count of combined skeletal variations and malformations and count of combined skeletal variations.

Incidence tables for all measures are provided in the appendix.

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APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

Table V

Skeletal Count of Rudimentary Supernumerary Ribs

Numbers in parenthesis are percents

Exposure Group (mg/m3)	Dams

Examined	Fetuses Examined	Dams  Affected	Fetuses  Affected

0  	25	193	12 (48)	16 (8)

2000  	23	153	8 (35)	11 (7)

10000  	23	165	7 (30)	8 (5)

20000  	24	170	16 (67)	29*  (17)

		* statistically significantly different from control, p<0.05

DISCUSSION:

The analyses for fetal body weight, number of implants per dam, the litter size per dam, and the dam uterine weight are complicated.  The analyses that did not include CL count were not statistically significant, those that included a term for CL and no exposure by CL interaction terms were not statistically significant, but when there was a CL term and an interaction term there were statistically significant exposure effects (only the fetal weight and uterine weight endpoints indicated a difference between an exposure group and the 0 exposure group).  Supplementary diagnostics indicate that the changing pattern is due to complex relationships among the endpoints, the exposure, and the CL count.  The models for fetal weight indicate that at low CL counts the bodyweight increases with increasing exposure, for moderate CL count (in the 12 to 14 count range) there is no change in fetal weight as exposure changes, and for high CL count (above 14 CL per dam) the fetal weight decreases with increasing exposure (the rate of decrease in weight becoming sharper as the CL count increases).  The specific least squares analysis uses the overall mean CL count of 15.1, so the model predicts a decrease in fetal weight with increasing exposure.  Because of these complexities and the confounding of CL count and exposure it is not clear that exposure is directly linked with adverse effects

CONCLUSION:

Based on these findings, administration of the test substance at the exposures tested is associated with an increased incidence of skeletal rudimentary supernumerary ribs in the 20,000 mg/m3 exposure group relative to the control group.  Analyses of mean litter fetal body weight and uterine weight are complex with equivocal results; observed effects may be due to a confounding with CL count.  The confounding effect may also apply to the number of implants per dam and the litter size, but that has not been clearly shown with these data

K-6

APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

Mark J. Nicolich, Ph.D.			Date

Statistician

ExxonMobil Biomedical Sciences, Inc

1545 Route 22 East

PO Box 971

Annandale, NJ 08801-0971

George Bukhbinder, Ph.D.			Date

Consultant

References:

Chen, Gaylor, and Laborde, “Dose-response modeling of growth for developmental toxicity”, Environmetrics, vol 7, pg 135-144, 1996.

Little, Milliken, Stroup, and Wolfinger, “SAS System for Mixed Models“, SAS Institute, Cary, NC, 1997, section 5.6.2, pg 203.

Ryan, L., “The use of generalized estimating equations for risk assessment in developmental toxicity”, Risk Analysis, 12(3), pg 439-447, 1992.

SAS/STAT, V8.02, copyright © 1999-2001, SAS Institute, Inc., Cary, NC.

Snedecor, G.W. and Cochran, W.G., Statistical Methods, 8th Edition, Iowa State University Press, Ames, Iowa, 1989.

K-7

APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

APPENDIX

Anomaly Counts

Study # 171834

                                       head - individual

                               VISCERAL/HEAD:  Retinal fold; Left

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          192          0           0

                   2000 MG/M3       22          149          0           0

                  10000 MG/M3       23          162          0           0

                  20000 MG/M3       24          175          1           1

                       External Variations and Malformations - combined

                                          All Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          385          1           1

                   2000 MG/M3       23          302          2           3

                  10000 MG/M3       23          327          1           2

                  20000 MG/M3       24          345          0           0

                       External Variations and Malformations - combined

                                         Alive Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          384          1           1

                   2000 MG/M3       23          302          2           3

                  10000 MG/M3       23          327          1           2

                  20000 MG/M3       24          345          0           0

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APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

                       External Variations and Malformations - combined

                                          Dead Fetuses

                                 dams       fetuses      dams       fetuses

                     DOSE      examined    examined    affected   affected

                    0 MG/M3        1           1           0           0

                               External Malformations - combined

                                          All Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          385          1           1

                   2000 MG/M3       23          302          1           2

                  10000 MG/M3       23          327          1           2

                  20000 MG/M3       24          345          0           0

                               External Malformations - combined

                                         Alive Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          384          1           1

                   2000 MG/M3       23          302          1           2

                  10000 MG/M3       23          327          1           2

                  20000 MG/M3       24          345          0           0

                               External Malformations - combined

                                          Dead Fetuses

                                 dams       fetuses      dams       fetuses

                     DOSE      examined    examined    affected   affected

                    0 MG/M3        1           1           0           0

K-9

APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

                                     external - individual

                             EXTERNAL: Adactyly forepaw; Bilateral

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          385          0           0

                   2000 MG/M3       23          302          1           1

                  10000 MG/M3       23          327          0           0

                  20000 MG/M3       24          345          0           0

                                     external - individual

                                     EXTERNAL: Cleft palate

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          385          0           0

                   2000 MG/M3       23          302          1           1

                  10000 MG/M3       23          327          0           0

                  20000 MG/M3       24          345          0           0

                                     external - individual

		                EXTERNAL: Ectrodactyly hindpaw; Bilateral

						(2 digits on each paw)

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          385          0           0

                   2000 MG/M3       23          302          1           1

                  10000 MG/M3       23          327          0           0

                  20000 MG/M3       24          345          0           0

                                     external - individual

                                     EXTERNAL: Hooked tail

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          385          0           0

                   2000 MG/M3       23          302          1           1

                  10000 MG/M3       23          327          0           0

                  20000 MG/M3       24          345          0           0

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APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

                                     external - individual

                                  EXTERNAL: Malrotated hindpaw

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          385          1           1

                   2000 MG/M3       23          302          1           2

                  10000 MG/M3       23          327          1           2

                  20000 MG/M3       24          345          0           0

                                     external - individual

                                     EXTERNAL: Microcephaly

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          385          0           0

                   2000 MG/M3       23          302          1           1

                  10000 MG/M3       23          327          0           0

                  20000 MG/M3       24          345          0           0

                                     external - individual

                                  EXTERNAL: Protruding tongue

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          385          0           0

                   2000 MG/M3       23          302          2           2

                  10000 MG/M3       23          327          0           0

                  20000 MG/M3       24          345          0           0

                                     external - individual

                                      EXTERNAL: Short tail

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          385          0           0

                   2000 MG/M3       23          302          1           1

                  10000 MG/M3       23          327          0           0

                  20000 MG/M3       24          345          0           0

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APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

                       Visceral Variations and Malformations - combined

                                          All Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          192          1           1

                   2000 MG/M3       23          151          1           1

                  10000 MG/M3       23          162          1           1

                  20000 MG/M3       24          175          0           0

                       Visceral Variations and Malformations - combined

                                         Alive Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          191          1           1

                   2000 MG/M3       23          151          1           1

                  10000 MG/M3       23          162          1           1

                  20000 MG/M3       24          175          0           0

                       Visceral Variations and Malformations - combined

                                          Dead Fetuses

                                 dams       fetuses      dams       fetuses

                     DOSE      examined    examined    affected   affected

                    0 MG/M3        1           1           0           0

                                     visceral - individual

                        ABDOMEN/THORAX:  Malpositioned kidney; Bilateral

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          192          0           0

                   2000 MG/M3       23          151          1           1

                  10000 MG/M3       23          162          0           0

                  20000 MG/M3       24          175          0           0

K-12

APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

                                     visceral - individual

			          ABDOMEN/THORAX:  Umbilical artery arises from

					left side of urinary bladder

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          192          1           1

                   2000 MG/M3       23          151          0           0

                  10000 MG/M3       23          162          1           1

                  20000 MG/M3       24          175          0           0

                       Skeletal Variations and Malformations - combined

                                          All Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193         15          24

                   2000 MG/M3       23          153         13          21

                  10000 MG/M3       23          165         13          15

                  20000 MG/M3       24          170         20          38

                       Skeletal Variations and Malformations - combined

                                         Alive Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193         15          24

                   2000 MG/M3       23          153         13          21

                  10000 MG/M3       23          165         13          15

                  20000 MG/M3       24          170         20          38

				    Skeletal Variations and Malformations -

				combined,without Rudimentary Supernumarary Ribs

                                          All Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          7           9

                   2000 MG/M3       23          153          8          10

                  10000 MG/M3       23          165          8           8

                  20000 MG/M3       24          170          6          10

K-13

APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

				    Skeletal Variations and Malformations -

				combined,without Rudimentary Supernumarary Ribs

                                         Alive Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          7           9

                   2000 MG/M3       23          153          8          10

                  10000 MG/M3       23          165          8           8

                  20000 MG/M3       24          170          6          10

                                Skeletal Variations - combined

                                          All Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193         15          24

                   2000 MG/M3       23          153         13          21

                  10000 MG/M3       23          165         13          15

                  20000 MG/M3       24          170         20          38

                                Skeletal Variations - combined

                                         Alive Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193         15          24

                   2000 MG/M3       23          153         13          21

                  10000 MG/M3       23          165         13          15

                  20000 MG/M3       24          170         20          38

			             Skeletal Variations - combined,without

						Rudimentary Supernumarary Ribs

                                          All Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          7           9

                   2000 MG/M3       23          153          8          10

                  10000 MG/M3       23          165          7           7

                  20000 MG/M3       24          170          6          10

K-14

APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

			             Skeletal Variations - combined,without

						Rudimentary Supernumarary Ribs

                                         Alive Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          7           9

                   2000 MG/M3       23          153          8          10

                  10000 MG/M3       23          165          7           7

                  20000 MG/M3       24          170          6          10

                               Skeletal Malformations - combined

                                          All Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          2           2

                   2000 MG/M3       23          153          1           1

                  10000 MG/M3       23          165          1           1

                  20000 MG/M3       24          170          1           1

                               Skeletal Malformations - combined

                                         Alive Fetuses

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          2           2

                   2000 MG/M3       23          153          1           1

                  10000 MG/M3       23          165          1           1

                  20000 MG/M3       24          170          1           1

                                     skeletal - individual

                            SKELETAL/PAW: Multiple paw bones absent

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          0           0

                   2000 MG/M3       23          153          1           1

                  10000 MG/M3       23          165          0           0

                  20000 MG/M3       24          170          0           0

K-15

APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

                                     skeletal - individual

                           SKELETAL/RIBS (T1-2 anlage): Fused; Right

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          1           1

                   2000 MG/M3       23          153          0           0

                  10000 MG/M3       23          165          0           0

                  20000 MG/M3       24          170          0           0

                                     skeletal - individual

                            SKELETAL/RIBS: Multiple bones malformed

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          0           0

                   2000 MG/M3       23          153          1           1

                  10000 MG/M3       23          165          0           0

                  20000 MG/M3       24          170          0           0

                                     skeletal - individual

                         SKELETAL/RIBS: Rudimentary supernumerary ribs

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193         12          16

                   2000 MG/M3       23          153          8          11

                  10000 MG/M3       23          165          7           8

                  20000 MG/M3       24          170         16          29

                                     skeletal - individual

                                 SKELETAL/RIBS: Short last rib

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          3           3

                   2000 MG/M3       23          153          1           1

                  10000 MG/M3       23          165          1           1

                  20000 MG/M3       24          170          0           0

K-16

APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

                                     skeletal - individual

                            SKELETAL/SKULL: Multiple bones malformed

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          0           0

                   2000 MG/M3       23          153          1           1

                  10000 MG/M3       23          165          0           0

                  20000 MG/M3       24          170          0           0

                                     skeletal - individual

                               SKELETAL/STERNEBRAE (I, II): Bifid

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          0           0

                   2000 MG/M3       23          153          1           1

                  10000 MG/M3       23          165          0           0

                  20000 MG/M3       24          170          0           0

                                     skeletal - individual

                               SKELETAL/STERNEBRAE (IV-VI): Fused

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          1           1

                   2000 MG/M3       23          153          0           0

                  10000 MG/M3       23          165          0           0

                  20000 MG/M3       24          170          0           0

                                     skeletal - individual

                          SKELETAL/STERNEBRAE:  Asymmetric sternebrae

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          0           0

                   2000 MG/M3       23          153          2           2

                  10000 MG/M3       23          165          1           1

                  20000 MG/M3       24          170          1           1

K-17

APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

                                     skeletal - individual

                          SKELETAL/STERNEBRAE:  Hypoplastic sternebrae

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          1           1

                   2000 MG/M3       23          153          1           1

                  10000 MG/M3       23          165          0           0

                  20000 MG/M3       24          170          1           2

                                     skeletal - individual

                          SKELETAL/STERNEBRAE:  Unossified sternebrae

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          1           1

                   2000 MG/M3       23          153          4           6

                  10000 MG/M3       23          165          4           4

                  20000 MG/M3       24          170          1           1

                                     skeletal - individual

                          SKELETAL/VERTEBRAE (L): Presacral vertebrae

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          0           0

                   2000 MG/M3       23          153          0           0

                  10000 MG/M3       23          165          0           0

                  20000 MG/M3       24          170          1           1

                                     skeletal - individual

                          SKELETAL/VERTEBRAE:  Bifid vertebral centra

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          3           4

                   2000 MG/M3       23          153          0           0

                  10000 MG/M3       23          165          0           0

                  20000 MG/M3       24          170          3           3

K-18

APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

                                     skeletal - individual

                     SKELETAL/VERTEBRAE:  Dumbbell-shaped vertebral centra

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          1           1

                   2000 MG/M3       23          153          0           0

                  10000 MG/M3       23          165          0           0

                  20000 MG/M3       24          170          2           2

                                     skeletal - individual

               SKELETAL/VERTEBRAE:  Dumbbell-shaped vertebral centra anlage

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          1           2

                   2000 MG/M3       23          153          1           1

                  10000 MG/M3       23          165          1           1

                  20000 MG/M3       24          170          3           4

                                     skeletal - individual

                         SKELETAL/VERTEBRAE:  Malformed vertebral arch

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          1           1

                   2000 MG/M3       23          153          0           0

                  10000 MG/M3       23          165          1           1

                  20000 MG/M3       24          170          1           1

                                     skeletal - individual

                          SKELETAL/VERTEBRAE: Multiple bones malformed

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          0           0

                   2000 MG/M3       23          153          1           1

                  10000 MG/M3       23          165          0           0

                  20000 MG/M3       24          170          0           0

K-19

APPENDIX K – STATISTICIAN’S REPORT (CONT/D)

                                      skeletal - combined

               SKELETAL/STERNEBRAE:  Delayed ossification of the sternebrae

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          2           2

                   2000 MG/M3       23          153          5           7

                  10000 MG/M3       23          165          4           4

                  20000 MG/M3       24          170          2           3

                                      skeletal - combined

                       SKELETAL/VERTEBRAE:  Hypoplastic vertebral centra

                                   dams       fetuses      dams       fetuses

                     DOSE        examined    examined    affected   affected

                      0 MG/M3       25          193          3           4

                   2000 MG/M3       23          153          0           0

                  10000 MG/M3       23          165          0           0

                  20000 MG/M3       24          170          4           5

K-20

APPENDIX L - HISTORICAL CONTROL DATA FOR ANNANDALE, NJ FACILITY

TESTING FACILITY – ANNANDALE, NJ

SUPPLIER: Charles River Laboratories, Inc.

FEED: PMI Certified Rodent Chow (5002 Meal)

STUDY          NUMBER	STUDY DATES	SUPPLIER LOCATION/AREA	SPECIES/STRAIN NUMBER OF LITTERS/FETUSES	% PREGNANT	DOSING ROUTE/CARRIER

9A	May 9, 2000 –

June 2, 2000	Raleigh, NC/R04	Crl:CD®(SD)IGSBR VAF/Plus	25/398	100 Oral/Corn Oil

9B	May 9, 2000 –

June 2, 2000	Raleigh, NC/R04	Crl:CD®(SD)IGSBR VAF/Plus	25/401	100 Oral/Corn Oil

10	May 19, 2001 –

June 15, 2001	Raleigh, NC/R04	Crl:CD®(SD)IGSBR VAF/Plus	24/359	96 Inhalation/Air

11	August 19, 2001 –

September 18, 2001	Raleigh, NC/R04	Crl:CD®(SD)IGSBR VAF/Plus	24/358	96 Inhalation/Air

12	November 18, 2001 -December 20, 2001	Raleigh, NC/R04 Crl:CD®(SD)IGSBR VAF/Plus	25/389	100	Inhalation/Air

13	February 3, 2002 –

March 8, 2001	Raleigh, NC/R04	Crl:CD®(SD)IGSBR VAF/Plus	25/374	100 Inhalation/Air

14	April 22, 2002 –

May 22, 2002	Raleigh, NC/R04	Crl:CD®(SD)IGSBR VAF/Plus	25/353	100 Inhalation/Air

15	June 17, 2002 –

July 17, 2002	Raleigh, NC/R04	Crl:CD®(SD)IGSBR VAF/Plus	22/316	88 Inhalation/Air

L-1

APPENDIX L - HISTORICAL CONTROL DATA FOR ANNANDALE, NJ FACILITY (CONT’D)

 (UTERINE IMPLANTATION DATA)

	NUMBER

OF

LITTERS

LIVE

MALE

FEMALE

RESORPTIONS

IMPLANTS

CORPORA LUTEA

DEAD

FETUS/ IMPLANTS

RESORPTIONS/ IMPLANTS

F/I TRANSFORMED

HIGH

16.04	7.92	8.36	0.72	16.48	17.16	0.04	0.98	0.05	80.376320

LOW

14.12	6.88	7.24	0.32	14.56	15.50	0	0.95	0.02	77.306160

STUDY #

	15	22	14.36	7.09	7.27	0.36	14.73	15.50	0	0.98	0.02	79.881591

STD

1.89	1.80	1.72	0.66	2.00	1.82	0	0.04	0.04	4.499537

(N)

22	22	22	22	22	22	22	22	22	22

14	25	14.12	6.88	7.24	0.40	14.56	15.88	0.04	0.95	0.04	78.128760

STD

3.11	2.44	2.15	0.58	3.00	1.54	0.2	0.10	0.10	8.029518

(N)

25	25	25	25	25	25	25	25	25	25

13	25	14.96	7.36	7.60	0.72	15.68	15.96	0	0.95	0.05	77.306160

STD

3.12	2.45	2.42	0.84	3.09	3.18	0	0.07	0.07	6.507916

(N)

25	25	25	25	25	25	25	25	25	25

12	25	15.56	7.92	7.64	0.32	15.88	16.40	0	0.98	0.02	80.376320

STD

2.92	2.64	2.38	0.56	2.88	2.99	0	0.04	0.03	3.947106

(N)

25	25	25	25	25	25	25	25	25	25

11	24	14.92	7.17	7.75	0.63	15.54	16.04	0	0.96	0.04	78.114083

STD

2.19	2.57	2.27	0.77	1.82	1.94	0	0.05	0.05	5.545914

(N)

24	24	24	24	24	24	24	24	24	24

10	24	14.96	7.54	7.42	0.58	15.50	16.42	0	0.97	0.04	78.883958

STD

3.07	2.90	2.55	0.83	3.18	3.41	0	0.05	0.05	5.408551

(N)

24	24	24	24	24	24	24	24	24	24

9(B)	25	16.04	7.84	8.20	0.44	16.48	17.16	0	0.97	0.03	79.840760

STD

2.24	1.57	1.91	0.77	2.02	1.93	0	0.05	0.05	5.232909

(N)

25	25	25	25	25	25	25	25	25	25

9(A)	25	15.92	7.56	8.36	0.52	16.44	16.88	0	0.97	0.03	79.294360

STD

1.53	1.69	1.60	0.71	1.42	1.48	0	0.04	0.04	4.836482

(N)

25	25	25	25	25	25	25	25	25	25

L-2

APPENDIX L - HISTORICAL CONTROL DATA FOR ANNANDALE, NJ FACILITY (CONT’D)

 (UTERINE IMPLANTATION DATA)

	NUMBER

OF

LITTERS

R/I TRANSFORMED

D/I TRANSFORMED

DEAD/ IMPLANTS	PRE IMPLANT LOSS	POST IMPLANT LOSS

MALFORMATIONS

VARIATIONS

AFFECTED

HIGH

12.694280	8.238	0	7.9	5.1	0.28	1.70	1.00

LOW

9.624000	7.103	0	1.6	2.0	0.08	0.00	0.40

STUDY #

	15	22	10.118955	7.545	0	4.4	2.3	0.27	0.50	0.60

STD

4.499552	0.595	0	10.9	4.3	0.46	0.80	0.70

(N)

22	22	22	22	22	22	22	22

14	25	11.588840	8.238	0	7.9	4.6	0.28	1.70	0.70

STD

8.074369	2.934	0	17.7	10.2	0.46	1.20	0.70

(N)

25	25	25	25	25	25	25	25

13	25	12.694280	7.473	0	1.6	5.1	0.24	1.40	1.00

STD

6.507867	1.521	0	2.7	6.7	0.52	1.60	1.00

(N)

25	25	25	25	25	25	25	25

12	25	9.624000	7.326	0	3.0	2.0	0.10	1.40	0.40

STD

3.947128	0.905	0	3.9	3.4	0.30	1.20	0.60

(N)

25	25	25	25	25	25	25	25

11	24	11.886500	7.324	0	3.0	4.2	0.25	1.10	0.90

STD

5.545880	0.446	0	3.9	5.4	0.53	1.10	1.10

(N)

24	24	24	24	24	24	24	24

10	24	11.402500	7.455	0	5.1	3.3	0.17	0.70	0.80

STD

5.349722	1.087	0	12.6	5.4	0.38	0.80	0.80

(N)

24	24	24	24	24	24	24	24

9(B)	25	10.159600	7.117	0	3.9	2.8	0.08	0.00	0.50

STD

5.232766	0.478	0	7.0	5.0	0.40	0.00	0.80

(N)

25	25	25	25	25	25	25	25

9(A)	25	10.706120	7.103	0	2.5	3.1	0.12	0.10	0.60

STD

4.836645	0.318	0	4.3	4.3	0.33	0.40	0.70

(N)

25	25	25	25	25	25	25	25

L-3

APPENDIX L - HISTORICAL CONTROL DATA FOR ANNANDALE, NJ FACILITY (CONT’D)

 (FETAL BODY WEIGHTS)

	NUMBER

OF

LITTERS

MALE

FEMALE

HIGH

5.75	5.50

LOW

5.41	5.16

STUDY #

	15	22	5.60	5.33

STD

0.41	0.38

(N)

156	160

14	25	5.46	5.18

STD

0.41	0.39

(N)

172	181

13	25	5.49	5.17

STD

0.33	0.37

(N)

184	190

12	25	5.59	5.36

STD

0.36	0.32

(N)

198	191

11	24	5.52	5.25

STD

0.38	0.45

(N)

172	186

10	24	5.75	5.50

STD

0.35	0.34

(N)

181	178

9(B)	25	5.41	5.16

STD

0.45	0.39

(N)

196	205

9(A)	25	5.61	5.31

STD

0.38	0.37

(N)

189	209

L-4

APPENDIX L - HISTORICAL CONTROL DATA FOR ANNANDALE, NJ FACILITY (CONT’D)

 (EXTERNAL DATA)

STUDY #	15	14	13	12	11	10	9(B)	9(A)

NUMBER OF LITTER	22	25	25	25	24	24	25	25

NUMBER OF FETUSES	316	353	374	389	358	359	401	398

% STUNTED - F	0.63	0.85	0.27	0.26	0.84	0	1.25	0

% STUNTED - L	9.09	12.00	4.00	4.00	8.33	0	16.00	0

% EXT. VAR. - F	0	0	0	0	0	0	0	0

% EXT. VAR. - L	0	0	0	0	0	0	0	0

% EXT. MAL - F	0.94	0.85	0.53	0.26	0.56	0.28	0	0.50

% EXT. MAL. - L	13.64	12.00	8.00	4.00	8.33	4.17	0	8.00

Domed head - F

0.28

Domed head - L

4.00

Malrotated hindpaw - F	0.94	0.57	0.53	0.26	0.28	0.28

0.50

Malrotated hindpaw - L	13.64	8.00	8.00	4.00	4.17	4.17

8.00

Filamentous tail - F

	0.28

	Filamentous tail - L

	4.17

	NOTE:    F - Fetus

                L - Litter

	Blank entries for an observation indicate that the observation was not present in that study

L-5

APPENDIX L - HISTORICAL CONTROL DATA FOR ANNANDALE, NJ FACILITY (CONT’D)

 (INTERNAL DATA)

STUDY #	15	14	13	12	11	10	9(B)	9(A)

NUMBER OF LITTER	22	25	25	25	24	24	25	25

NUMBER OF FETUSES	158	177	182	195	181	178	197	201

% VIS. VAR. - F	1.27	2.26	0.55	0	0	0	0	1.00

% VIS. VAR. - L	9.09	12.00	4.00	0	0	0	0	4.00

% VIS. MAL. - F	1.9	2.26	2.19	0.51	2.21	1.69	1.02	0.50

% VIS. MAL. - L	9.09	16.00	12.00	4.0	16.67	12.50	4.00	4.00

Olfactory bulb: Misshapen  - F

0.51

Olfactory bulb: Misshapen - L

4.00

Microphthalmia - F

	0.51

	Microphthalmia - L

	4.00

	Retinal fold  - F

0.56	1.64

	1.12

Retinal fold - L

4.00	8.00

	8.33

Carotid artery: Malpositioned  - F

0.56

Carotid artery: Malpositioned - L

4.00

Innominate artery: Absent - F

0.56

Innominate artery: Absent - L

4.00

Subclavian artery: Malpositioned - F

0.56

Subclavian artery: Malpositioned - L

4.00

NOTE:    F - Fetus

               L - Litter

	Blank entries for an observation indicate that the observation was not present in that study

L-6

APPENDIX L - HISTORICAL CONTROL DATA FOR ANNANDALE, NJ FACILITY (CONT’D)

 (INTERNAL DATA)

STUDY #	15	14	13	12	11	10	9(B)	9(A)

NUMBER OF LITTER	22	25	25	25	24	24	25	25

NUMBER OF FETUSES	158	177	182	195	181	178	197	201

Spleen: Small - F	0.63

	Spleen: Small - L	4.55

	Kidney(s): Large - F	0.63

	Kidney(s): Large - L	4.55

	Hydronephrosis - F	1.26	1.13

	1.66

	Hydronephrosis - L	9.09	8.00

	12.50

	Ureter(s): Convoluted  - F

1.00

Ureter(s): Convoluted - L

4.00

Hydroureter - F	1.26	1.13

	0.55	0.56	0.51	0.50

Hydroureter - L	9.09	8.00

	4.17	4.17	4.00	4.00

Umbilical artery: Left of urinary bladder - F	1.26	2.26	0.55

	Umbilical artery: Left of urinary bladder - L	9.09	12	4.00

	Testis(es): Malpositioned  - L

	0.55

	Testis(es): Malpositioned - F

	4.00

	NOTE:    F - Fetus

               L - Litter

L-7

APPENDIX L - HISTORICAL CONTROL DATA FOR ANNANDALE, NJ FACILITY (CONT’D)

 (SKELETAL DATA)

STUDY #	15	14	13	12	11	10	9(B)	9(A)

NUMBER OF LITTER	22	24	25	25	24	24	$	$

NUMBER OF FETUSES	157	176	192	194	177	181	$	$

% SKEL. VAR. - F	5.10	21.60	17.80	15.46	15.25	8.84	$	$

% SKEL. VAR. - L	27.27	70.83	76.00	60.00	54.17	50.00	$	$

% SKEL. MAL. - F	0	0.57	0	0	1.13	0	$	$

% SKEL. MAL. - L	0	4.17	0	0	8.33	0	$	$

Forepaw anlage: Misshapen - F

0.57

Forepaw anlage: Misshapen - L

4.17

Sternebrae: Advanced - F

2.84	1.05

	Sternebrae: Advanced - L

16.67	8.00

	Sternebrae: Bifid - F

	0.52

	Sternebrae: Bifid - L

	4.00

	Sternebrae: Hypoplastic - F

1.03

Sternebrae: Hypoplastic - L

4.00

Sternebrae: Unossified - F	0.64	1.70	1.05

1.7	1.10

Sternebrae: Unossified - L	4.55	12.5	8.00

8.33	8.33

Sternebral anlage: Hypoplastic - F

	2.82

	Sternebral anlage: Hypoplastic - L

	12.50

	Vertebrae: Absent multiple - F

	0.56

	Vertebrae: Absent multiple - L

	4.17

	Vertebral centra: Bifid- F	0.64	3.98	5.76	10.82	6.78	1.10

Vertebral centra: Bifid- L	4.55	25.00	36.00	48.00	29.17	8.33

L-8

APPENDIX L - HISTORICAL CONTROL DATA FOR ANNANDALE, NJ FACILITY (CONT’D)

 (SKELETAL DATA)

STUDY #	15	14	13	12	11	10	9(B)	9(A)

NUMBER OF LITTER	22	24	25	25	24	24	$	$

NUMBER OF FETUSES	157	176	192	194	177	181	$	$

Vertebral centra: Dumbbell/8-shaped - F

1.14	0.52	0.52

1.10

Vertebral centra: Dumbbell/8-shaped - L

8.33	4.00	4.00

8.33

Vertebral centra: Misshapen - F

	0.56

	Vertebral centra: Misshapen- L

	4.17

	Vertebral centra: Unossified - F

	0.56

	Vertebral centra: Unossified - L

	4.17

	Vertebrae: Supernumerary presacral Lumbar - F

	0.52

0.56

	Vertebrae: Supernumerary presacral Lumbar - L

	4.00

4.17

	Vertebral centra anlage: Bifid - F

	0.52

	Vertebral centra anlage: Bifid - L

	4.00

	Vertebral centra anlage: Dumbbell/8 shaped - F

6.82	5.24	1.55

Vertebral centra anlage: Dumbbell/8 shaped - L

33.33	28.00	12.00

Vertebral centra anlage: Hypoplastic - F

	1.69

	Vertebral centra anlage: Hypoplastic - L

	12.50

	Vertebral centra anlage: Misshapen - F

	0.56

	Vertebral centra anlage: Misshapen - L

	4.17

	Rib(s): Cervical - F

0.57

Rib(s): Cervical  - L

4.17

Rib(s): Rudimentary lumbar - F	3.18	9.66	8.90	4.12	1.70	5.52

Rib(s): Rudimentary lumbar - L	22.73	37.50	40.00	24.00	12.50	25.00

Rib(s): Rudimentary thoracic - F

	0.52

	Rib(s): Rudimentary thoracic - L

	4.00

	Rib(s): Well formed lumbar - F

	0.52

	Rib(s): Well formed lumbar - L

	4.00

	Rib(s): Short last thoracic - F	0.64	1.14

Rib(s): Short last thoracic - L	4.55	8.33

Rib(s): Thick/wavy - F

Rib(s): Thick/wavy - L

L-9

APPENDIX L - HISTORICAL CONTROL DATA FOR ANNANDALE, NJ FACILITY (CONT’D)

 (SKELETAL DATA)

STUDY #	15	14	13	12	11	10	9(B)	9(A)

NUMBER OF LITTER	22	24	25	25	24	24	$	$

NUMBER OF FETUSES	157	176	192	194	177	181	$	$

Rib(s): Cervical anlage - F

0.57

Rib(s): Cervical anlage - L

4.17

Rib(s) anlage: Fused - F

0.57

Rib(s) anlage: Fused - L

4.17

Rib(s) anlage: Hypoplastic - F

	2.82

	Rib(s) anlage: Hypoplastic - L

	12.50

	Rib(s) anlage: Site of ossification - F

	1.13

	Rib(s) anlage: Site of ossification - L

	4.17

	Calcaneus: Advanced - F

0.57

Calcaneus: Advanced - L

4.17

NOTE:    F - Fetus

               L - Litter

               $ - Not examined

L-10

APPENDIX M – FEED AND WATER ANALYSES

FEED ANALYSIS

M-1

APPENDIX M – FEED AND WATER ANALYSES (CONT’D)

FEED ANALYSIS

M-2

APPENDIX M – FEED AND WATER ANALYSES (CONT’D)

FEED ANALYSIS

M-3

APPENDIX M – FEED AND WATER ANALYSES (CONT’D)

FEED ANALYSIS

M-4

APPENDIX M – FEED AND WATER ANALYSES (CONT’D)

FEED ANALYSIS

M-5

APPENDIX M – FEED AND WATER ANALYSES (CONT’D)

FEED ANALYSIS

M-6

APPENDIX M – FEED AND WATER ANALYSES (CONT’D)

FEED ANALYSIS

M-7

APPENDIX M – FEED AND WATER ANALYSES (CONT’D)

FEED ANALYSIS

M-8

APPENDIX M – FEED AND WATER ANALYSES (CONT’D)

FEED ANALYSIS

M-9

APPENDIX M – FEED AND WATER ANALYSES (CONT’D)

FEED ANALYSIS

M-10

WHOLE-BODY INHALATION DEVELOPMENTAL TOXICITY STUDY IN RATS

WITH GASOLINE WITH TBA VAPOR CONDENSATE MRD-00-718: 171834

 PAGE

Page   PAGE  2  of   NUMPAGES  268

Page   PAGE  99  of   NUMPAGES  268

WHOLE-BODY INHALATION DEVELOPMENTAL TOXICITY STUDY IN RATS

WITH GASOLINE WITH TBA VAPOR CONDENSATE MRD-00-718: 171834

WHOLE-BODY INHALATION DEVELOPMENTAL TOXICICTY STUDY IN RATS

WITH GASOLINE VAPOR CONDENSATE WITH TBA (MRD-00-718:  171834)

 PAGE

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[Federal Register Volume 76, Number 71 (Wednesday, April 13, 2011)]
[Notices]
[Pages 20686-20688]
[FR Doc No: 2011-8895]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-D-0164]

Draft Guidance for Industry on Safety Labeling Changes;
Implementation of the Federal Food, Drug, and Cosmetic Act;
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a draft guidance for industry entitled ``Safety
Labeling Changes--Implementation of Section 505(o)(4) of the Federal
Food, Drug, and Cosmetic Act.'' The Food and Drug Administration
Amendments Act of 2007 (FDAAA) added new provisions to the Federal
Food, Drug, and Cosmetic Act (the FD&C Act) authorizing FDA to require
certain drug and biological product application holders to make safety
related labeling changes based upon new safety information that becomes
available after the drug or biological product is approved under the
FD&C Act or the Public Health Service Act (the PHS Act). This draft
guidance provides information on the implementation of the new
provisions, including a description of the types of safety labeling
changes that ordinarily might be required under the new legislation,
how FDA plans to determine what constitutes new safety information, the
procedures involved in requiring safety labeling changes, and
enforcement of the requirements for safety labeling changes.

DATES: Although you can comment on any guidance at any time (see 21 CFR
10.115(g)(5)), to ensure that the Agency considers your comment on this
draft guidance before it begins work on the final version of the
guidance, submit written or electronic comments on the draft guidance
by July 12, 2011.

ADDRESSES: Submit written requests for single copies of this guidance
to the Division of Drug Information, Center for Drug Evaluation and
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, Rm. 2201, Silver Spring, MD 20993-0002; or the Office of
Communication, Outreach and Development (HFM-40), Center for Biologics
Evaluation and Research (CBER), Food and Drug Administration, 1401
Rockville Pike, Rockville, MD 20852-1448. The guidance may also be
obtained by mail by calling CBER at 1-800-835-4709 or<PHONE_NUMBER>.
Send one self-addressed adhesive label to assist the office in
processing your requests. Submit written comments on the guidance to
the Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
Submit electronic comments to http://www.regulations.gov. See the
SUPPLEMENTARY INFORMATION section for electronic access to the draft
guidance document.

FOR FURTHER INFORMATION CONTACT: Kristen Everett, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 6228, Silver Spring, MD 20993-0002, 301-
796-5400, or Stephen Ripley, Center for Biologics Evaluation and
Research (HFM-17), Food and Drug Administration, 1401 Rockville Pike,
Rockville, MD 20852-1448,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry
entitled ``Safety Labeling Changes--Implementation of Section 505(o)(4)
of the Federal Food, Drug, and Cosmetic Act.'' In the past, FDA has
requested that holders of applications for approved products make
labeling changes related to safety after approval to address serious
risks. FDA learned of the potential for such serious risks from a
variety of sources. In most cases, application holders responded to
these requests by negotiating appropriate language with FDA staff to
address the concerns, and then submitting a supplement or amended
supplement to obtain approval of the change. Negotiations were often
protracted, and FDA had few tools available at its disposal to end
negotiations and require the changes. Congress recognized the
limitations of FDA's authority in this area and, in FDAAA, gave FDA new
authority to require safety labeling changes in certain circumstances.
    Title IX, section 901 of FDAAA (Pub. L. 110-85) amended the FD&C
Act by adding new section 505(o)(4) (21 U.S.C. 355(o)(4)). Section
505(o)(4) authorizes FDA to require, and if necessary, order labeling
changes if FDA becomes aware of new safety information that FDA
believes should be included in the labeling of certain prescription
drug and biological products approved under section 505 of the FD&C Act
or section 351 of the PHS Act (42 U.S.C. 262). Specifically, section
505(o)(4) of the FD&C Act applies to prescription drug products with an
approved new drug application (NDA) under section 505(b) of the FD&C
Act, biological products with an approved biologics license application
(BLA) under section 351 of the PHS Act, or prescription drug products
with an approved abbreviated new drug application (ANDA) under section
505(j) of the FD&C Act if the reference listed drug (RLD) with an
approved NDA is not currently marketed. FDAAA imposes timeframes for
application holders to submit and FDA staff to review such changes, and
gives FDA new enforcement tools to bring about timely and appropriate
labeling changes. This draft guidance provides information on the
implementation of the new provisions, including a description of the
types of safety labeling changes that ordinarily

might be required under the new legislation, how FDA plans to determine
what constitutes new safety information, the procedures involved in
requiring safety labeling changes, and enforcement of the requirements
for safety labeling changes.
    This draft guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The draft guidance, when
finalized, will represent the Agency's current thinking on the
implementation of section 901 of FDAAA on safety labeling changes. It
does not create or confer any rights for or on any person and does not
operate to bind FDA or the public. An alternative approach may be used
if such approach satisfies the requirements of the applicable statutes
and regulations.

II. Comments

    Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) either electronic or written comments regarding this
document. It is only necessary to send one set of comments. It is no
longer necessary to send two copies of mailed comments. Identify
comments with the docket number found in brackets in the heading of
this document. Received comments may be seen in the Division of Dockets
Management between 9 a.m. and 4 p.m., Monday through Friday.

III. Paperwork Reduction Act of 1995

    Under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C.
3501-3520), Federal agencies must obtain approval from the Office of
Management and Budget (OMB) for each collection of information that
they conduct or sponsor. ``Collection of information'' is defined in 44
U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or
requirements that members of the public submit reports, keep records,
or provide information to a third party. Section 3506(c)(2)(A) of the
PRA, 44 U.S.C. 3506(c)(2)(A), requires Federal agencies to provide a
60-day notice in the Federal Register for each proposed collection of
information before submitting the collection to OMB for approval. To
comply with this requirement, FDA is publishing this notice of the
proposed collection of information set forth in this document.
    With respect to the collections of information associated with this
draft guidance that were not previously approved by OMB, described
below, FDA invites comments on the following topics: (1) Whether the
proposed information collected is necessary for the proper performance
of FDA's functions, including whether the information will have
practical utility; (2) the accuracy of FDA's estimated burden of the
proposed information collected, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information collected; and (4) ways to
minimize the burden of information collected on the respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
    This draft guidance provides information on the implementation of
section 901 of FDAAA, which authorizes FDA to require certain drug and
biological product application holders to make safety related labeling
changes based upon new safety information that becomes available after
the drug or biological product is approved under the FD&C Act or the
PHS Act. FDA plans to request safety labeling changes by sending a
notification letter to the application holder. Under section
505(o)(4)(B), the application holder must respond to FDA's notification
by submitting a labeling supplement or notifying FDA that the applicant
does not believe the labeling change is warranted and submitting a
statement detailing the reasons why the application holder does not
believe a change is warranted (a rebuttal statement).
    The submission of rebuttal statements may result in the collection
of information that is not already approved by OMB. Based on FDA's
experience thus far with safety labeling changes requirements under
section 505(o)(4), FDA estimates that approximately six application
holders will elect to submit approximately one rebuttal statement each
year and that each rebuttal statement will take approximately 6 hours
to prepare.
    In addition, in the draft guidance, the agency states that new
labeling prepared in response to a safety labeling change notification
should be available on the application holder's Web site within 10
calendar days of approval, which may result in the collection of
information that is not already approved by OMB. FDA estimates that
approximately 197 application holders will post new labeling one time
each year in response to a safety labeling change notification and that
the posting of the labeling will take approximately 4 hours to prepare.
    FDA estimates the burden of the collections of information that
have not already been approved by OMB, is as follows:

                                                     Table 1--Estimated Annual Reporting Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                Number of
                                                                        Number of      responses per        Total          Hours per       Total hours
                                                                       respondents       respondent       responses         response
--------------------------------------------------------------------------------------------------------------------------------------------------------
Rebuttal statement.................................................               6                1                6                6               36
                                                                    ------------------------------------------------------------------------------------
    Total..........................................................  ...............  ...............  ...............  ...............              36
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this information collection.

                                               Table 2--Estimated Annual Third Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                Annual
                         Type of submission                             Number of      frequency per     Total annual      Hours per       Total hours
                                                                       respondents       disclosure      disclosures       disclosure
--------------------------------------------------------------------------------------------------------------------------------------------------------
Post approved labeling on application holder's Web site............             197                1              197                4              788
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this information collection.

    This draft guidance also refers to previously approved collections
of information. Specifically, the draft guidance describes: Labeling
supplements for NDAs, ANDAs, and BLAs submitted under 21 CFR 314.70,

314.71, 314.97 and 601.12; and the content and format of prescription
drug labeling submitted under 21 CFR 201.56 and 201.57. These
collections of information are subject to review by OMB under the PRA
act and are approved under OMB control numbers 0910-0001, 0910-0338,
and 0910-0572. Section V of the draft guidance refers to the guidance
entitled ``Formal Dispute Resolution: Appeals Above the Division
Level,'' which describes collections of information approved under OMB
control number 0910-0430.

IV. Electronic Access

    Persons with access to the Internet may obtain the document at
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, or
http://www.regulations.gov.

    Dated: April 7, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-8895 Filed 4-12-11; 8:45 am]
BILLING CODE 4160-01-P


[Federal Register Volume 88, Number 20 (Tuesday, January 31, 2023)]
[Notices]
[Page 6251]
[FR Doc No: 2023-01871]

-----------------------------------------------------------------------

DEPARTMENT OF ENERGY

Federal Energy Regulatory Commission

[Docket No. IN13-15-000]

BP America Inc., BP Corporation North America Inc., BP America
Production Company, and BP Energy Company; Updated Notice of
Designation of Commission Staff as Non-Decisional

    With respect to orders issued by the Commission in the above-
captioned docket, with the exceptions noted below, the staff of the
Office of Enforcement are designated as non-decisional in deliberations
by the Commission in this docket. Accordingly, pursuant to 18 CFR
385.2202 (2022), they will not serve as advisors to the Commission or
take part in the Commission's review of any offer of settlement.
Likewise, as non-decisional staff, pursuant to 18 CFR 385.2201 (2022),
they are prohibited from communicating with advisory staff concerning
any deliberations in this docket.
    Exceptions to this designation as non-decisional are:

Grace Kwon
Laura Vallance
Jennifer Gordon
Joseph Cleaver
David Mason
Erin Melly

    Dated: January 24, 2023.
Kimberly D. Bose,
Secretary.
[FR Doc. 2023-01871 Filed 1-30-23; 8:45 am]
BILLING CODE 6717-01-P