Table 3-2, Levels of Significant Exposure to Dibromochloromethane - Oral - Toxicological Profile for Bromoform and Dibromochloromethane

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Toxicological Profile for Bromoform and Dibromochloromethane. Atlanta (GA): Agency for Toxic Substances and Disease Registry (US); 2005 Aug.

Toxicological Profile for Bromoform and Dibromochloromethane.

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Table 3-2Levels of Significant Exposure to Dibromochloromethane - Oral

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Key to^a Figure	Species (Strain)	Exposure/Duration/Frequency (Route)	System	NOAEL (mg/kg/day)		LOAEL
Key to^a Figure	Species (Strain)	Exposure/Duration/Frequency (Route)	System	NOAEL (mg/kg/day)		Less Serious (mg/kg/day)			Serious (mg/kg/day)			Reference Chemical Form

ACUTE EXPOSURE
Death
1	Rat (Sprague-Dawley)	1 d (GO)							848	F	(LD50)	Chu et al 1982a
2	Rat (Sprague-Dawley)	(G)							1186	M	(LD50)	Chu et al. 1980
	Rat (Sprague-Dawley)								848^b	F	(LD50)
3	Rat (Sprague-Dawley)	1 d (GO)							3700	M	(100% mortality)	Hewitt et al 1983
4	Rat (Fischer- 344)	1 d (GO)							1250	M	(4/5 died)	NTP 1985
5	Rat (Fischer- 344)	14 d 1×/d (GO)							500		(8 of 10 died)	NTP 1985
6	Mouse (ICR)	1 d (GW)							800^b	M	(LD50)	Bowman et al 1978
									1200	F	(LD50)
7	Mouse (B6C3F1)	1 d (GO)							630	M	(3/5 died)	NTP 1985
8	Mouse (B6C3F1)	14 d 1×/d (G)							500		(7 of 10 died)	NTP 1985
9	Hamster (Golden Syrian)	1 d (G)							145	M	(LD50)	Korz and Gatterman 1997
Systemic
10	Rat (Sprague-Dawley)	1 d (GO)	Hepatic			2500	M	(increased SGPT and OCT levels)				Hewitt et al 1983
			Renal	2500	M
11	Rat (Fischer- 344)	14 d 1×/d (GO)	Hepatic	250		500		(mottled liver)				NTP 1985
			Renal	250		500		(darkened renal medullae)
			Bd Wt	125	M				250	M	(45% decrease body weight gain)
12	Rat	1 d (G)	Hepatic	1220								Plaa and Hewitt 1982a
13	Rat (Fischer- 344)	7 d (GW)	Endocr	160	M	310	M	(decreased serum testosterone)				Potter et al 1996
			Bd Wt	160	M	310	M	(14% decrease in body weight)
14	Mouse (B6C3F1)	9 doses in 11 day period (GO)	Hepatic			100	F	(hepatocellular ballooning and proliferation)				Coffin et al 2000
15	Mouse (B6C3F1)	11 days (W)	Hepatic			170	F	(hepatocellular ballooning)				Coffin et al 2000
16	Mouse (CD-1)	14 d 1×/d (GO)	Hepatic			37^c	M	(hepatocellular vacuolization)				Condie et al 1983
			Renal			37	M	(mesangial hyperplasia)
			Bd Wt	147	M
17	Mouse (CD-1)	14 d 1×/d (GW)	Hepatic	125	F	250	F	(increased relative and absolute liver weight, decreased serum glucose, and increased SGPT and SGOT)				Munson et al 1982
18	Mouse (B6C3F1)	14 d 1×/d (GO)	Renal	250		500		(reddened renal medullae)				NTP 1985
Immuno/ Lymphoret
19	Mouse (CD-1)	14 d 1×/d (GW)		50	F	125	F	(impaired humoral immunity)				Munson et al 1982
Neurological
20	Rat (Fischer- 344)	14 d 1×/d (GO)		250					500		(lethargy, ataxia)	NTP 1985
21	Rat (Fischer- 344)	1 d (GO)		160		310		(lethargy)				NTP 1985
22	Mouse (ICR)	14 days daily (GW)		10	M							Balster and Borzelleca 1982
23	Mouse (ICR)	1 d (GW)				454	M	(ED50 for impaired motor performance)				Balster and Borzelleca 1982 Chlorodibromomethane
24	Mouse (ICR)	1 d (GW)							500		(sedation, anesthesia)	Bowman et al 1978
25	Mouse (B6C3F1)	14 d 1×/d (GO)		250					500		(lethargy, ataxia, and labored breathing)	NTP 1985
Developmental
26	Rat (Sprague-Dawley)	9 d Gd 6–15 (GO)		200								Ruddick et al 1983
INTERMEDIATE EXPOSURE
Death
27	Rat (Fischer- 344)	13 wk 5d/wk (G)							250		(18/ 20 died)	NTP 1985
Systemic
28	Rat (Wistar)	30 d (F)	Hepatic	18.3	M	56.2	M	(heptocellular vacuolation)				Aida et al 1992
			Bd Wt	173.3	M
29	Rat (Sprague-Dawley)	28 d (W)	Hemato	12	M							Chu et al 1982a
			Hepatic	12	M
			Renal	12	M
			Bd Wt	12	M
30	Rat (Sprague-Dawley)	90 d (GO)	Resp	200								Daniel et al. 1990
			Cardio	200
			Gastro	200
			Hemato	200
			Hepatic			50		(hepatocellular vacuolization)
			Renal	50		100		(tubular degeneration)
			Endocr	200
			Dermal	200
			Ocular	200
			Bd Wt	50					200		(55% decrease in body weight gain)
31	Rat (Fischer- 344)	13 wk 5d/wk (GO)	Resp	250								NTP 1985
			Cardio	250
			Gastro	250
			Musc/skel	250
			Hepatic	30	M	60	M	(hepatocellular vacuolization)
			Renal	125		250		(toxic nephropathy)
			Endocr	250
			Dermal	250
			Bd Wt	125	M				250	M	(47% decreased body weight gain)
			Other			250		(salivary gland hyperplasia)
32	Mouse (B6C3F1)	3 wk 5 d/wk (GO)	Hepatic	50	F	192	F	(hepatocyte hydropic degeneration)				Melnick et al 1998
						100^b	F	(increased relative liver weight)
			Bd Wt	417	F
33	Mouse (B6C3F1)	13 wk 5d/wk (GO)	Resp	250								NTP 1985
			Gastro	250
			Hepatic	125	M	250	M	(hepatocellular vacuolization)
			Renal	125	M	250	M	(toxic nephropathy)
			Endocr	250
			Dermal	250
			Bd Wt	250
Immuno/ Lymphoret
34	Rat (Sprague-Dawley)	90 d (GO)		100		200		(34–40% decr. in thymus wt.)				Daniel et al. 1990
Neurological
35	Rat (Sprague-Dawley)	90 d (GO)		50	F	100	F	(decreased absolute brain weight)				Daniel et al. 1990
36	Mouse (ICR)	60 d 1×/d (GW)		100	M	400	M	(decreased response rate in operant behavior test)				Balster and Borzelleca 1982
37	Mouse (ICR)	30d 1×/d (GW)		100	M							Balster and Borzelleca 1982 Chlorodibromomethane
Reproductive
38	Rat (Sprague-Dawley)	90 d (GO)		100								Daniel et al. 1990
39	Rat (Fischer- 344)	13 wk 5d/wk (GO)		250								NTP 1985
40	Rat (Sprague-Dawley)	15 d (W)		47.8	F							NTP 1996
41	Rat (Sprague-Dawley)	28–34 d (W)		28.2	M							NTP 1996
	Rat (Sprague-Dawley)			46	F
42	Mouse (ICR)	2 generations (continuous) (W)		170	F				685	F	(decreased fertility)	Borzelleca and Carchman 1982
43	Mouse (B6C3F1)	13 wk 5d/wk (GO)		250								NTP 1985
Developmental
44	Mouse (ICR)	2 generations (continuous) (W)		685								Borzelleca and Carchman 1982
CHRONIC EXPOSURE
Death
45	Mouse (B6C3F1)	105 wk 5d/wk (GO)							100	M	(decreased survival)	NTP 1985
Systemic
46	Rat (Fischer- 344)	2 yr 5d/wk (GO)	Resp	80								NTP 1985
			Cardio	80
			Gastro	80
			Musc/skel	80
			Hepatic			40^d		(fatty change)
			Endocr	80
			Dermal	80
			Bd Wt	80
47	Rat (Wistar)	2 year (F)	Hepatic	20	M	85	M	(yellowing of liver; hypertrophy)				Tobe et al 1982
			Bd Wt	20	M	85	M	(10% decrease in body weight gain)	540	M	(marked decrease in body weight gain)
48	Mouse (B6C3F1)	105 wk 5d/wk (GO)	Resp	100								NTP 1985
			Cardio	100
			Gastro	100
			Musc/skel	100
			Hepatic			50	F	(fatty metamorphosis)
			Renal			100	M	(nephrosis)
			Endocr			50	F	(thyroid follicular cell hyperplasia)
			Dermal	100
			Bd Wt	50		100		(14–17% decreased terminal body weight)
Reproductive
49	Rat (Fischer- 344)	2 yr 5d/wk (GO)		80								NTP 1985
50	Mouse (B6C3F1)	105 wk 5d/wk (GO)		100								NTP 1985
Cancer
51	Mouse (B6C3F1)	105 wk 5d/wk (GO)							100		(CEL: hepatocellular adenoma or carcinoma)	NTP 1985

a: The number corresponds to entries in Figure 3-2.
b: Differences in levels of health effects and cancer effects between male and females are not indicated in Figure 3-2. Where such differences exist, only the levels of effect for the most sensitive gender are presented.
c: Used to derive an acute-duration oral MRL of 0.1 mg/kg/day; dose divided by an uncertainty factory of 300 (3 for use of a minimal LOAEL, 10 for extrapolation from animals to humans, and 10 for human variability).
d: Used to derive a chronic-duration oral MRL of 0.09 mg/kg/day; dose adjusted for intermittent exposure and divided by an uncertainty factory of 300 (3 for use of a minimal LOAEL, 10 for extrapolation from animals to humans, and 10 for human variability).
: Bd Wt = body weight; CNS = central nervous system; d = day(s); F = female; (F) = food; (G) = gavage; Gd = gestation day; Gastro = gastrointestinal; LD50 = lethal dose, 50% kill; LOAEL = lowest-observed-adverse-effect level; M = male; NOAEL = no-observed-adverse-effect level; (W) = water; wk = week(s); × = time(s)

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Toxicological Profile for Bromoform and Dibromochloromethane. Atlanta (GA): Agency for Toxic Substances and Disease Registry (US); 2005 Aug. Table 3-2, Levels of Significant Exposure to Dibromochloromethane - Oral.
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Table 3-2, Levels of Significant Exposure to Dibromochloromethane - Oral - Toxic...
Table 3-2, Levels of Significant Exposure to Dibromochloromethane - Oral - Toxicological Profile for Bromoform and Dibromochloromethane
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