Table 2-3, Levels of Significant Exposure to Bromodichloromethane – Oral - Toxicological Profile for Bromodichloromethane

Table 2-3Levels of Significant Exposure to Bromodichloromethane – Oral

Figure key^a	Species (strain) No./group	Exposure parameters	Doses (mg/kg/day)	Parameters monitored	Endpoint	NOAEL (mg/kg/day)	Less serious LOAEL (mg/kg/day)	Serious LOAEL (mg/kg/day)	Effect
ACUTE EXPOSURE
1	Rat (F344) 14 F	GDs 6–10 (GW)	0, 75	CS, BW, OF, DX	Bd wt		75		Body weight on GD 20 reduced 35%
1	Rat (F344) 14 F	GDs 6–10 (GW)	0, 75	CS, BW, OF, DX	Develop			75	62% full-litter resorption rate
Bielmeier et al. 2001
2	Rat (F344) 10–11 F	GDs 8 or 9; or 9 (GW)	0, 75, 100	CS, DX	Repro		75		Reduced serum progesterone
2	Rat (F344) 10–11 F	GDs 8 or 9; or 9 (GW)	0, 75, 100	CS, DX	Develop			75	64% full-litter resorptions
Bielmeier et al. 2001
3	Rat (Sprague-Dawley) 13 F	GDs 6–10 (GW)	0, 75, 100	CS, BW, OF, DX	Develop	100			Full-litter resorption rate was 0%; no information was provided regarding pup weight
Bielmeier et al. 2001
4	Rat (F344) 10–13 F	GDs 6–10, GDs 6–15, or GDs 11–15 (GW)	0, 75	CS, DX	Develop			75	Full-litter resorption in rats dosed on GDs 6–10 and 6–15
Bielmeier et al. 2001
5	Rat (F344) 9–13 F	GDs 6–10 (GW)	0, 75, 100	CS, OF, DX	Repro		75		Decreased serum progesterone and luteinizing hormone on GD 10
5	Rat (F344) 9–13 F	GDs 6–10 (GW)	0, 75, 100	CS, OF, DX	Develop			75	Full-litter resorptions (80%) on GDs 6–10
Bielmeier et al. 2004
6	Rat (F344) NS-F	GDs 6–10 (GW)	0, 100	CS, OF, BI	Repro		100		Significant reductions in serum progesterone and luteinizing hormone on GD 10
Bielmeier et al. 2007
7	Rat (Sprague-Dawley) 10 M, 10 F	Once (GO)	390, 546, 765, 1,071, 1,500	CS, LE	Death			916 M 969 F	LD₅₀ values
Chu et al. 1980
8	Rat (Sprague-Dawley) 10 M, 10 F	Once (GO)	390, 546, 765, 1,071, 1,500	CS, LE	Bd wt	546 M	765 M		Decreases in body weight gain were in males at 765 mg/kg (36% of controls) and 1,071 mg/kg (45%); no alterations were observed in females
					Hemato		390 F		Decreases in hematocrit and red blood cell count in females at ≥390 mg/kg and hemoglobin level at ≥546 mg/kg
					Other noncancer (blood glucose)	1,500
Chu et al. 1982
9	Rat (F344) 6 F	5 days (GW)	0, 75, 150, 300	IX	Immuno		75		Decreased response to the T-cell stimulant, phytohemagglutinin (PHA), in mesenteric lymph node lymphocytes at 75 mg/kg/day
									Decreased response to concanavalin A (Con A) in mesenteric lymph node lymphocytes at 150 mg/kg/day
									Decreased response to Con A and PHA in the splenic lymphocytes and to S. typhimurium in the mesenteric lymph node lymphocytes at 300 mg/kg/day
									Impaired humoral immunity (response to sheep red blood cells) at 300 mg/kg/day
French et al. 1999
10	Rat (Fischer 344) 12 M	Once (G)	0, 20.5, 30.7, 41.0, 81.9, 122.9, 163.8, 245.7	BW, BC, OW	Bd wt	245.7
10	Rat (Fischer 344) 12 M	Once (G)	0, 20.5, 30.7, 41.0, 81.9, 122.9, 163.8, 245.7	BW, BC, OW	Hepatic	163.8	245.7		Increases in ALT (239%), AST (130%), and sorbitol dehydrogenase (378%); significant increases at 81.9, 122.9, and 163.8 mg/kg, but were not considered biologically significant
Keegan et al. 1998
11	Rat (Fischer 344) 6 M	Once (GW)	0, 200, 400	BW, BC, OW, HP	Bd wt	400
					Hepatic	200	400		Vacuolar degeneration and necrosis and alterations in serum enzyme levels
					Renal	200	400		Tubule degeneration 24 and 48 hours post-exposure and tubule necrosis 48 hours post-exposure, increases in urinary glucose and protein levels and decreases in urinary pH and osmolarity; urinary pH and osmolarity decreased at 200 mg/kg
					Other noncancer (blood glucose)	400
Lilly et al. 1994
12	Rat (Fischer 344) 6 M	Once (GO)	0, 200, 400	BW, BC, OW, HP	Bd wt	400
					Hepatic	200	400		Vacuolar degeneration and necrosis and alterations in serum enzyme levels
					Renal	200	400		Tubule degeneration 24 and 48 hours post-exposure and tubule necrosis 48-hours post-exposure, increases in urinary glucose and protein levels and decreases in urinary pH and osmolarity; urinary pH and osmolarity were also decreased at 200 mg/kg
					Other noncancer (blood glucose)	400
Lilly et al. 1994
13	Rat (Fischer 344) 6 M	Once (GW)	0, 200, 400	BW, BC, OW, HP	Bd wt	200	400		12% decrease in body weight
					Hepatic	200	400		Minimal centrilobular necrosis and mild vacuolar degeneration
					Renal		200		Mild to marked proximal tubule necrosis
					Other noncancer (blood glucose)	400
Lilly et al. 1996
Note: Animals were killed 48-hours post exposure.
14	Rat (Fischer 344) 10 M	Once (GW)	0, 122.8, 163.8, 245.7, 327.7, 491.5	BW, BC, UR, OW	Bd wt	327.7	491.5		13% decrease in body weight 48 hours post-exposure
Lilly et al. 1997
15	Rat (F344) 12–14 F	GDs 6–15 (GO), (GW)	0, 25, 50, 75	CS, BW, MX, DX, OF	Bd wt		25	50	Decreased weight gain on GDs 6–8 at 25 mg/kg/day; weight loss at 50 mg/kg/day
15	Rat (F344) 12–14 F	GDs 6–15 (GO), (GW)	0, 25, 50, 75	CS, BW, MX, DX, OF	Develop	25^b		50	Full-litter resorptions; no alterations in gestation length, postnatal viability, or pup weight on PND 1 or 6 in surviving litters BMDL₀₅ of 7.15 mg/kg/day
Narotsky et al. 1997
16	Rat (F344/N) 5 M, 5 F	Once (GO)	0, 150, 300, 600, 1,250, 2,500	LE, CS	Death			600	Deaths occurred in 2/5 males and 1/5 females at 600 mg/kg and in all males and females at 1,250 or 2,500 mg/kg
NTP 1987
17	Rat (F344/N) 5 M, 5 F	14 days (GO)	0, 38, 75, 150, 300, 600	LE, CS, BW	Bd wt	150	300	600	21% decrease in terminal body weights in males at 300 mg/kg/day and weight loss or no weight gain in males and females at 600 mg/kg/day
NTP 1987
18	Rat (Sprague-Dawley) 15 F	GDs 6–15 (GO)	0, 50, 100, 200	CS, BW, HP, MX, DX	Bd wt	100	200		Maternal body weight gain reduced by 38%
					Resp	200
					Cardio	200
					Gastro	200
					Hemato	200
					Musc/skel	200
					Hepatic	200
					Renal	200
					Endocr	200
					Immuno	200
					Neuro	200
					Repro	200
					Develop	100	200		Delayed ossification of the sternebrae
Ruddick et al. 1983
19	Rat (Fischer 344) 6 F	5 days (GW)	0, 75, 150, 300	BW, BC, OW, HP	Death			300	2/6 rats died on day 5
					Bd wt	150	300		16.8% decrease in body weight
					Hepatic	75	150		Hepatocellular vacuolar degeneration
					Renal	75	150		Tubule vacuolar degeneration and tubular degeneration at ≥150 mg/kg/day; tubular necrosis and 8- and 12-fold increases in serum creatinine and urea nitrogen at 300 mg/kg/day
Thornton-Manning et al. 1994
20	Mouse (ICR) 6 M	Once (GW)	Not reported	NX	Neuro		524		ED50 on the screen test was 524 mg/kg
Balster and Borzelleca 1982
21	Mouse (ICR) 8 M	14 days (GW)	0, 1.2, 11.6	NX	Neuro	11.6			No significant alteration in performance on a swimming endurance test
Balster and Borzelleca 1982
22	Mouse (ICR Swiss) NR, M,F	Once (GW)	500–4,000	CS, LE	Death			450 M 900 F	LD₅₀ values
Bowman et al. 1978
23	Mouse (CD-1) 10 M	14 days (GO)	0, 37, 74, 148	CS, BW, BC, HP	Bd wt	148
					Hepatic	37	74		Centrilobular pallor at ≥74 mg/kg/day, focal inflammation at 148 mg/kg/day
					Renal	74	148		Intratubular mineralization, epithelial hyperplasia, and cytomegaly
Condie et al. 1983
24	Mouse (C57BL/6) 6 F	14 days (W)	0, 10, 37, 62	IX	Immuno	62			No alterations in the response to T-lymphocyte or B-lymphocyte stimulants
French et al. 1999
25	Mouse (CD-1) 8–9 M,F	14 day (GW)	0, 50, 125, 250	BW, HE, BC, OW, IX	Bd wt	125	250		20–22% decrease in body weight gain
					Hemato	50	125		Decreases in fibrinogen at 125 (females only) and 250 mg/kg/day
					Hepatic	125	250		Increases in (>800%) in ALT and AST
					Renal	125	250		41% increase in serum urea nitrogen levels
					Immuno	125	250		Alterations in humoral immunity (decreases in antibody forming cells and hemagglutination)
					Other noncancer (blood glucose)	125	250		30% decrease in blood glucose levels in males
Munson et al. 1982
26	Mouse (B6C3F1) 5 M, 5 F	Once (GO)	0, 150, 300, 600, 1,250, 2,500	CS, LE	Death			600	100 and 40% mortality in males and females at 600 mg/kg; 100% mortality in males and females at 1,250 and 2,500 mg/kg
NTP 1987
27	Mouse (B6C3F1) 5 M, 5 F	14 days (GO)	0, 19, 38, 75, 150, 300	CS, LE, BW	Death			150	100% mortality in males at 150 and 300 mg/kg; no deaths related to BDCM exposure in females
NTP 1987
28	Mouse (C57BLl/6J) 6 F	5 days (GW)	0, 75, 150	BW, BC, OW, HP	Bd wt	150
					Hepatic	150
					Renal	150
Thornton-Manning et al. 1994
INTERMEDIATE EXPOSURE
29	Rat (Wistar) 7 M	1 month (F)	0, 20, 60, 180	BW, OW, HE, BC, HP	Bd wt	60	180		19% decrease in body weight gain
					Resp	180
					Cardio	180
					Gastro	180
					Hemato	180
					Hepatic	60	180		Decrease in absolute liver weight, vacuolization, swelling, and necrosis
					Renal	180
					Endocr	180
Aida et al. 1989
Note: BDCM was microencapsulated and added to the diet.
30	Rat (Wistar) 7 M	1 month (GO)	0, 20, 60, 180	BW, OW, HE, BC, HP	Bd wt	60	180		15% decrease in body weight gain
					Resp	180
					Cardio	180
					Gastro	180
					Hemato	180
					Hepatic	20	60		Increases in relative liver weight at 180 mg/kg/day and vacuolization at ≥60 mg/kg/day
					Renal	180
					Endocr	180
Aida et al. 1989
31	Rat (Wistar) 6 M, 6 F	6 months (F)	M: 0, 6.1, 25.5, 138.0 F: 0, 8.0, 31.7, 168.4	CS, WI, BW, OW, HE, BC, HP	Bd wt	25.5	138.0		Decreased body weight gain in males (32%) and females (24%)
					Resp	138.0
					Cardio	138.0
					Gastro	138.0
					Hemato	138.0
					Hepatic		6.1		Increases in absolute and relative weights in males at ≥6.1 mg/kg/day and in females at ≥31.7 mg/kg/day, fatty generation at ≥6.1/8.0 mg/kg/day, bile duct proliferation and cholangiofibrosis at 138.0/168.4 mg/kg/day, and granulomas in females at ≥31.7 mg/kg/day
					Renal	138.0
					Endocr	138.0
					Neuro	138.0
					Repro	138.0
					Other noncancer (blood glucose)	6.1	25.5		Decreased blood glucose levels at ≥25.5/31.7 mg/kg/day
Aida et al. 1992
Note: BDCM was microencapsulated and added to the diet.
32	Rat (Sprague-Dawley) 25 F	GDs 6–21 (W)	0, 2.2, 18.4, 45.0, 82.0	CS, BW, MX, DX	Develop	45	82		Minor ossification delays
Christian et al. 2001a
33	Rat (Sprague-Dawley) 30 F	GDs 6–21 (W)	0, 4.1–12.6, 11.6–40.2, 29.5–109	CS, BW, RX, MX, DX, HP	Repro	51.7			No alterations in reproductive function in a 2-generation study
33	Rat (Sprague-Dawley) 30 F	GDs 6–21 (W)	0, 4.1–12.6, 11.6–40.2, 29.5–109	CS, BW, RX, MX, DX, HP	Develop	94.5			14% decrease in pup’s body weight on PND 22, which was likely due to taste aversion.
Christian et al. 2001b
34	Rat (Sprague-Dawley) 10 M	28 days (W)	0, 0.52, 5.2, 45	CS, HE, BC,HP	Bd wt	45
					Hemato	45
					Hepatic	45
					Renal	45
Chu et al. 1982
35	Rat (F344) 6 M	26 weeks (W)	0, 5, 49	IX	Immuno	5	49		Decreased response to Con A in splenic lymphocytes
French et al. 1999
36	Rat (Eker) 8 M, 8 F	4 or 10 months (W)	M: 0, 3.5 35.0 F: 0, 6.5, 48.0	CS, OW, HP	Bd wt	35.0
					Gastro	35.0
					Hepatic	3.5	35.0		Increases in the incidence of centrilobular swelling and clear cell foci
Hooth et al. 2002
37	Rat (F344) 6 M	5 days/week 4 weeks (GO) or (GW)	0, 100	OW, HP	Renal	100
Lipsky et al. 1993
38	Rat (F344) 5 M	5 days/week 4 weeks (GO)	0, 50, 100	BW, UR, BC, OW, HP	Bd wt	100
38	Rat (F344) 5 M	5 days/week 4 weeks (GO)	0, 50, 100	BW, UR, BC, OW, HP	Renal	100			Decreases in urine pH and increases in formic acid excretion; minimal to slight cytoplasmic vacuolation in cortical tubules of 2/5 rats exposed to 100 mg/kg
Lock et al. 2004
39	Rat (Eker) 8 M, 8 F	10 months (W)	0, 6.5, 48.0	CS, OW, HP	Gastro		6.5		Increase in aberrant crypt foci in colon
39	Rat (Eker) 8 M, 8 F	10 months (W)	0, 6.5, 48.0	CS, OW, HP	Other noncancer (urinary bladder)	48.0
McDorman et al. 2003
40	Rat (Fisher 344) 12 M, 12 F	6 months (W)	M: 0, 9.1, 27.3, 72.9 F: 0, 9.0, 26.9, 71.7	NX, HP	Neuro	71.7			No biologically relevant alterations in FOB tests or histopathological examination of the brain, spinal cord, hindlimb nerves, or optic nerve
Moser et al. 2007
41	Rat (F344/N) 10 M, 10 F	5 days/week 13 weeks (GO)	0, 19, 38, 75, 150, 300	CS, BW, HP	Death			300	5/10 males and 2/10 females died
					Bd wt	75	150	300	Decreases in body weight gain (30 and 12% less than controls) at 150 mg/kg, decrease in body weight gain of 32% in females at 300 mg/kg, no weight gain in males at 300 mg/kg
					Resp	300
					Cardio	300
					Gastro	300
					Hepatic	150 F	300 F		Centrilobular degeneration, mild bile duct hyperplasia, and enlarged hepatocytes (females only)
					Renal	150	300		Degeneration of the proximal tubular epithelial cells
					Endocr	300
					Immuno	150	300		Lymphoid atrophy of the thymus, spleen, and lymph nodes in males; this may have been secondary to the marked decrease in body weight gain
					Repro	150	300		Mild to moderate atrophy of the seminal vesicles and/or prostate at 300 mg/kg
NTP 1987
42	Rat (F344/N) 10 M	22 days (W)	0, 6, 12, 20, 38, 71	CS, WI, BW, OW, HE, BC, HP	Bd wt	20	38		12 and 17% decrease in body weight gain at 38 and 71 mg/kg/day; this is likely secondary to the decrease in water consumption
					Resp	71
					Cardio	71
					Gastro	71
					Hemato	71
					Hepatic	71
					Renal	71
					Endocr	71
					Immuno	71
					Neuro	71
					Repro	71
NTP 2006
43	Mouse (ICR) 16 M	30 days (GW)	0, 100	NX	Neuro	100			No alterations in performance on a passive avoidance learning test
Balster and Borzelleca 1982
44	Mouse (ICR) 6–13 M	60 days (GW)	0, 100, 400	NX	Neuro		100		Alterations in operant behavior
Balster and Borzelleca 1982
45	Mouse (ICR) 6–8 M	90 days (GW)	0, 1.2 11.6	NX	Neuro	11.6			No dose-related alterations on two tests of motor performance or a test of exploratory behavior
Balster and Borzelleca 1982
46	Mouse (C57BL/6) 6 F	16 days (GW)	0, 50, 125, 250	IX	Immuno	250			No alterations in the response to T-lymphocyte or B-lymphocyte stimulants
French et al. 1999
47	Mouse (B6C3F1) 6 M	5 days/week 4 weeks (GO)	0, 25, 50	BW, UR, BC, OW, HP	Bd wt	50
47	Mouse (B6C3F1) 6 M	5 days/week 4 weeks (GO)	0, 25, 50	BW, UR, BC, OW, HP	Renal	50
Lock et al. 2004
48	Mouse (B6C3F1) 10 M, 10 F	5 days/week 13 weeks (GO)	M: 0, 6.25, 12.5, 25, 50, 100 F: 0, 25, 50, 100, 200, 400	CS, BW, HP	Bd wt	100 M 400 F
					Resp	100 M 400 F
					Cardio	100 M 400 F
					Gastro	100 M 400 F
					Hepatic	100 M 100 F	200 F		Enlarged centrilobular hepatocytes and microgranulomas
					Renal	50 M 400 F	100 M		Focal necrosis of the proximal renal tubular epithelium
					Endocr	100 M 400 F
					Immuno	100 M 400 F
					Neuro	100 M 400 F
					Repro	100 M 400 F
NTP 1987
49	Mouse (B6C3F1) 10 M	22 days (W)	0, 6, 10, 16, 29, 51	CS, WI, BW, OW, HE, BC, HP	Bd wt	51
					Resp	51
					Cardio	51
					Gastro	51
					Hemato	51
					Hepatic	51
					Renal	51
					Endocr	51
					Immuno	51
					Neuro	51
					Repro	51
NTP 2006
50	Rabbit (New Zealand white) 25 F	GDs 6–29 (W)	0, 1.4, 13.4, 35.6, 55.3	CS, BW, MX, DX	Develop	55.3
Christian et al. 2001a
CHRONIC EXPOSURE
51	Rat (Wistar) 40 M, 40 F	2 years (F)	M: 0, 6.1, 25.5, 138.0 F: 0, 8.0, 31.7, 168.4	CS, WI, BW, OW, HE, BC, HP	Bd wt	25.5	138.0		Decreased body weight gain in males (23–25%) and females (31–39%)
					Resp	138.0
					Cardio	138.0
					Gastro	138.0
					Hemato	138.0
					Hepatic		6.1^c		Increases in absolute and relative weights at ≥6.1/8.0 mg/kg/day after 12 months of exposure and at ≥31.7 mg/kg/day after 18 months of exposure; fatty generation at ≥6.1 mg/kg/day in males and at ≥31.7 mg/kg/day in females, bile duct proliferation at 31.7 (females only) and 138.0/168.4 mg/kg/day only after 12 months of exposure; cholangiofibrosis at 138.0/168.4 mg/kg/day; and granulomas in females at 31.7 and 168.4 mg/kg/day after 12, 18, or 24 months of exposure and in males at ≥6.1 mg/kg/day only after 24 months of exposure BMDL₁₀ of 0.78 mg/kg/day
					Renal	138.0
					Endocr	138.0
					Neuro	138.0
					Repro	138.0
					Other noncancer (blood glucose)	31.7	168.4		Increase blood glucose levels in males only
					Cancer				No increases in tumor incidence
Aida et al. 1992
Note: BDCM was microencapsulated and added to the diet.
52	Rat (F344) 78 M	104 weeks (W)	0, 3.9, 20.6, 36.3	CS, BW, FI, BC, OW, HP	Bd wt	36.3
					Resp	36.3
					Cardio	36.3
					Gastro	36.3
					Hepatic	36.3
					Renal	20.6	36.3		Renal tubular cell hyperplasia
					Endocr	36.3
					Cancer				No increases in the incidence of tubular cell adenoma or carcinoma
George et al. 2002
53	Rat (F344) 7 M	52 weeks (W)	0, 22, 39	RX, HP	Repro	22	39		Decreases in sperm velocity from the cauda epididymidis; no changes in sperm motility
Klinefelter et al. 1995
54	Rat (F344/N) 50 M, 50 F	5 days/week 2 years (GO)	0, 50, 100	CS, WI, BW, OW, HP	Bd wt	50	100		Decreases in body weight gain; terminal weights 12 and 21% lower in males and females
					Resp	100
					Cardio	100
					Gastro	100
					Hepatic		50		Fatty metamorphosis; increases in clear cell change at ≥50 mg/kg, eosinophilic cytoplasmic change, and focal cell change in females at 100 mg/kg
					Renal	50	100		Tubular epithelial cell cytomegaly in males at ≥50 mg/kg; increased incidence in nephrosis in females at 100 mg/kg
					Endocr	100
					Immuno	100
					Repro	100
					Cancer			50	Adenocarcinomas in the large intestine in males at 50 mg/kg and males and females at 100 mg/kg; renal tubular cell adenocarcinoma at 100 mg/kg
NTP 1987
55	Rat (F344/N) 50 M	2 years (W)	0, 6, 12, 25	CS, WI, BW, OW, HP	Bd wt	25
					Resp	25
					Cardio	25
					Gastro	25
					Hepatic	25
					Renal	25
					Endocr	25
					Immuno	25
					Repro	25
					Cancer				No increases in malignant tumors
NTP 2006
56	Rat (Wistar) 58 M, 58 F	Lifetime (W)	M: 0, 90 F: 0, 190	BW, HP	Bd wt		90 M 190 F		Decreased body weight (approximately 30%) in males and females
					Hepatic	90M	190 F		Increased incidence of hepatic adenofibrosis
					Cancer			190 F	Increased incidence of hepatic neoplastic nodules in females only; no additional description of the tumors was provided
Tumasonis et al. 1985
57	Mouse (B6C3F1) 78 M	104 weeks (W)	0, 8.1, 27.2, 43.3	CS, BW, FI, BC, OW, HP	Bd wt	43.3
					Gastro	43.3
					Hepatic	43.3
					Renal	43.3
					Endocr	43.3
					Cancer				No increases in the incidence of hepatocellular adenomas or carcinomas
George et al. 2002
58	Mouse (B6C3F1) 50 M, 50 F	5 days/week 2 years (GO)	M: 0, 25 50 F: 0, 75, 150	CS, BW, HP	Death			75 F	Decreased survival in females administered 75 or 150 mg/kg; the incidences of non-accidental deaths were 24/50, 37/50, and 35/50 in the 0, 75, and 150 mg/kg groups
					Bd wt	50 M 75 F	150 F		25% lower body weights than controls in females
					Resp	50 M 150 F
					Cardio	50 M 150 F
					Gastro	50 M 150 F
					Hepatic	25 M 150 F	50M		Hepatic fatty metamorphosis
					Renal	150 F	25 M		Renal cytomegaly
					Endocr	25 M	50 M 75 F		Thyroid follicular cell hyperplasia
					Immuno	50 M 150 F
					Repro	50 M 150 F
					Cancer			50 M 75 F	Renal tubular adenomas or adenocarcinomas in males at 50 mg/kg, hepatocellular adenomas or adenoma or carcinomas in females at ≥75 mg/kg
NTP 1987
59	Mouse (B6C3F1) 50 F	2 years (W)	0, 9, 18, 36	CS, WI, BW, OW, HP	Bd wt	36
					Resp	36
					Cardio	36
					Gastro	36
					Hepatic	36
					Renal	36
					Endocr	36
					Immuno	36
					Repro	36
					Cancer				No significant increases in neoplastic lesions

a: The number corresponds to entries in Figure 2-3.
b: Used to derive an acute-duration oral minimal risk level (MRL) of 0.07 mg/kg/day based on the BMDL₀₅ of 7.15 mg/kg/day and an uncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for human variability).
c: Used to derive a chronic-duration oral MRL of 0.008 mg/kg/day based on the BMDL₁₀ of 0.78 mg/kg/day and an uncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for human variability).
: ALT = alanine aminotransferase; AST = aspartate aminotransferase; BC = biochemistry; BDCM = bromodichloromethane; BI = biochemical changes; BW or Bd wt = body weight; Cardio = cardiovascular; CS = clinical signs; Develop = developmental; DX = developmental toxicity; ED₅₀ = dose resulting in a 50% response; Endocr = endocrine; (F) = exposure in feed; F = female(s); FI = food intake; FX = fetal toxicity; G = gavage, neat; Gastro = gastrointestinal; GD = gestation day; GO = gavage in oil vehicle; GW = gavage in water vehicle; HE = hematology; Hemato = hematological; HP = histopathology; Immuno = immunological; LD₅₀ = lethal dose, 50% kill; LE = lethality; LOAEL = lowest-observed-adverse-effect level; M = male(s); MRL = Minimal Risk Level; Musc/skel = musculoskeletal; MX = maternal toxicity; Neuro = neurological; NOAEL = no observed-adverse-effect level; NR = not reported; NS = not specified; NX = neurotoxicity; OF = organ function; OW = organ weight; PND = postnatal day; Repro = reproductive; Resp = respiratory; UR = urinalysis; W = water

From: CHAPTER 2, HEALTH EFFECTS

Toxicological Profile for Bromodichloromethane.

Atlanta (GA): Agency for Toxic Substances and Disease Registry (US); 2020 Mar.

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