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271
2365
267
200
183
5099
506
518133.6
5182
33.6
5223
25
5022
9
9
9
CH
RO
MIU
M
Table 3-5 Levels of Significant Exposure to Chromium Ill - Oral
a Key to Figure
Species (Strain)
Exposure/ Duration/
Frequency (Route)
ACUTE EXPOSURE Death 1 Rat
(NS) once (GW)
System NOAEL
(mg/kg/day) Less Serious
(mg/kg/day)
LOAEL
Serious (mg/kg/day)
2365 (LD50)
Reference Chemical Form
Smyth et al. 1969 Cr(CH3COO)3H2O (III)
Comments
2 Rat (Sprague-Dawley)
once (G)
200 M (LD50)
183 F (LD50)
Vernot et al. 1977 Cr(NO3)3.9H2O (III)
Systemic 3 Rat
(Fischer- 344) 3 d (F)
Reproductive 4 Rat
(NS) 3 d Gd 1-3 (G)
Hemato 506 F
33.6 F (decreased number of pregnancies)
NTP 2008b Cr picolinate (III)
Bataineh et al. 2007 CrCl3 (III)
5 Rat (NS)
3 d Gd 4-6 (G)
33.6 F Bataineh et al. 2007 CrCl3 (III)
Developmental 6 Mouse
(CD-1) 11 d Gd 6-17 1 x/d (F)
25 Bailey et al. 2008a Cr picolinate (III)
NOAEL is for standard developmental end points.
INTERMEDIATE EXPOSURE Systemic 7 Rat
(Sprague-Dawley)
daily 20 wk (F)
Hepatic 9 Anderson et al. 1997b CrCl3 (III)
Renal 9
Bd Wt 9
3. HE
ALTH
EFFE
CTS
150
5024
9
9
9
501640
95
1806
1806
1806
1806
1806
1806
CH
RO
MIU
M
Table 3-5 Levels of Significant Exposure to Chromium Ill - Oral (continued)
a Key to Figure
Species (Strain)
Exposure/ Duration/
Frequency (Route)
System NOAEL
(mg/kg/day) Less Serious
(mg/kg/day)
LOAEL
Serious (mg/kg/day)
Reference Chemical Form Comments
8 Rat (Sprague-Dawley)
daily 20 wk (F)
Hepatic 9 Anderson et al. 1997b Cr picolinate (III)
Renal
Bd Wt
9
9
9 Rat (Sprague-Dawley)
12 wk (W)
Bd Wt 40 (24% lower final body weight)
Bataineh et al. 1997 CrCl3 (III)
10 Rat (BD)
90 d 5 d/wk (F)
Resp
Cardio
Gastro
Hemato
Hepatic
Renal
1806
1806
1806
1806
1806
1806
Ivankovic and Preussmann 1975 Cr2O3 (III)
3. HE
ALTH
EFFE
CTS
151
5100
506
506
506
506
506
506
506
506
506
5134
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
Table 3-5 Levels of Significant Exposure to Chromium Ill - Oral (continued)
Exposure/ Duration/
a FrequencyKey to Species (Route)Figure (Strain) System
11 Rat 14 wk Resp(Fischer- 344) (F)
Cardio
Gastro
Hemato
Hepatic
Renal
Endocr
Ocular
Bd Wt
12 Rat 90 d Resp(Sprague- (F) Dawley)
Cardio
Gastro
Hemato
Hepatic
Renal
Endocr
Bd Wt
LOAEL
NOAEL (mg/kg/day)
Less Serious (mg/kg/day)
Serious (mg/kg/day)
Reference Chemical Form Comments
506 F NTP 2008b Cr picolinate (III)
506 F
506 F
506 F
506 F
506 F
506 F
506 F
506 F
1.5 F Shara et al. 2005 Cr nicotinate (III)
1.5 F
1.5 F
1.5 F
1.5 F
1.5 F
1.5 F
1.5 F
CH
RO
MIU
M
3. HE
ALTH
EFFE
CTS
152
5138
0.25
0.25
0.25
0.25
0.25
0.25
0.25
5131
165
140
5059
14
5
Table 3-5 Levels of Significant Exposure to Chromium Ill - Oral (continued)
Exposure/ LOAEL Duration/
a Key to Figure
Species (Strain)
Frequency (Route)
System NOAEL
(mg/kg/day) Less Serious
(mg/kg/day) Serious (mg/kg/day)
13 Rat (Sprague-Dawley)
38 wk (F)
Resp
Cardio
Gastro
Hemato
Hepatic
Renal
Endocr
0.25 F
0.25 F
0.25 F
0.25 F
0.25 F
0.25 F
0.25 F
14 Mouse BDF1
210 d (W)
Bd Wt 165 M
140 F
15 Mouse (Swiss)
12 wk (W)
Bd Wt 14 F 5 M (14% decrease in body weight gain)
Reference Chemical Form Comments
Shara et al. 2007 Cr nicotinate (III)
De Flora et al. 2006 CrK(SO4)2 (III)
Elbetieha and Al-Hamood 1997 CrCl3 (III)
CH
RO
MIU
M
3. HE
ALTH
EFFE
CTS
153
5110
1415
1415
1415
1415
1415
1415
1415
1415
1415
5101
506
5135
1.5
5139
0.25
5111
1415
91
1806
16
Table 3-5 Levels of Significant Exposure to Chromium Ill - Oral (continued)
Exposure/ Duration/
a Key to Species Frequency Figure (Strain) (Route)
Mouse 14 wk (B6C3F1) (F)
Immuno/ Lymphoret 17 Rat 14 wk
(Fischer- 344) (F)
18 Rat 90 d (Sprague-Dawley)
(F)
19 Rat 38 wk (Sprague- (F) Dawley)
20 Mouse 14 wk (B6C3F1) (F)
Neurological 21 Rat 90 d
5 d/wk (F)
System
Resp
Cardio
Gastro
Hemato
Hepatic
Renal
Endocr
Ocular
Bd Wt
LOAEL
NOAEL (mg/kg/day)
Less Serious (mg/kg/day)
Serious (mg/kg/day)
Reference Chemical Form Comments
1415 M
1415 M
1415 M
1415 M
1415 M
1415 M
1415 M
1415 M
1415 M
NTP 2008b Cr picolinate (III)
506 F NTP 2008b Cr picolinate (III)
1.5 F Shara et al. 2005 Cr nicotinate (III)
0.25 F Shara et al. 2007 Cr nicotinate (III)
1415 M NTP 2008b Cr picolinate (III)
1806 Ivankovic and Preussmann 1975 Cr III
CH
RO
MIU
M
3. HE
ALTH
EFFE
CTS
154
5108
506
5109
506
5136
1.5
5140
0.25
5114
1415
500340
5102
506
5137
1.5
CH
RO
MIU
M
Table 3-5 Levels of Significant Exposure to Chromium Ill - Oral (continued)
a Key to Figure
Species (Strain)
Exposure/ Duration/
Frequency (Route)
System NOAEL
(mg/kg/day) Less Serious
(mg/kg/day)
LOAEL
Serious (mg/kg/day)
Reference Chemical Form Comments
22 Rat (Fischer- 344)
14 wk (F)
506 F NTP 2008b Cr picolinate (III)
23 Rat (Fischer- 344)
14 wk ad lib (F)
506 F NTP 2008b Cr picolinate (III)
24 Rat (Sprague-Dawley)
90 d (F)
1.5 F Shara et al. 2005 Cr nicotinate (III)
25 Rat (Sprague-Dawley)
38 wk (F)
0.25 F Shara et al. 2007 Cr nicotinate (III)
26 Mouse (B6C3F1)
Reproductive 27 Rat
(Sprague-Dawley)
14 wk ad lib (F)
12 wk (W)
1415 M
40 (altered sexual behavior, decreased absolute testes, seminal vesicles, and preputial gland weights)
NTP 2008b Cr picolinate (III)
Bataineh et al. 1997 CrCl3 (III)
28 Rat (Fischer- 344)
14 wk (F)
506 F NTP 2008b Cr picolinate (III)
29 Rat (Sprague-Dawley)
90 d (F)
1.5 F Shara et al. 2005 Cr nicotinate (III)
3. HE
ALTH
EFFE
CTS
155
5141
0.25
5058
5
5
5112
1415
469.1
92
1806
500574
Table 3-5 Levels of Significant Exposure to Chromium Ill - Oral (continued)
Exposure/ LOAEL Duration/
a Key to Species Figure (Strain)
30 Rat (Sprague-Dawley)
31 Mouse (Swiss)
32 Mouse (B6C3F1)
33 Mouse (BALB/c)
Developmental 34 Rat
(BD)
35 Mouse (BALB/c)
Frequency (Route)
System NOAEL
(mg/kg/day) Less Serious
(mg/kg/day) Serious (mg/kg/day)
38 wk (F)
0.25 F
12 wk (W)
5 M (increased testes and decreased preputial gland weights)
5 F (decreased number of implantations and viable fetuses; increased ovarian and decreased uterine weights)
14 wk (F)
1415 M
7 wk 7 d/wk (F)
9.1 M (decreased spermatogenesis)
90 d 5 d/wk (F)
1806
Gd 12- Ld 20 (W)
74 (reduced ovary and testis weights in offspring and impaired fertility in female offspring)
Reference Chemical Form Comments
Shara et al. 2007 Cr nicotinate (III)
Elbetieha and Al-Hamood 1997 CrCl3 (III)
NTP 2008b Cr picolinate (III)
Zahid et al. 1990 Cr2(SO4)3 (III)
Ivankovic and Preussmann 1975 Cr2O3 (III)
Al-Hamood et al. 1998 CrCl3 (III)
CH
RO
MIU
M
3. HE
ALTH
EFFE
CTS
156
5222
25
99
2040
2040
2040
2040
2040
19
3.6
3.6
3.6
3.6
38
Table 3-5 Levels of Significant Exposure to Chromium Ill - Oral (continued)
LOAEL
System NOAEL
(mg/kg/day) Less Serious
(mg/kg/day) Serious (mg/kg/day)
25
Resp 2040
Cardio 2040
Gastro 2040
Hepatic 2040
Renal 2040
Hemato 3.6
Hepatic 3.6
Renal 3.6
Bd Wt 3.6
Reference Chemical Form Comments
Bailey et al. 2008b NOAEL is for standard neurodevelopmentalCr picolinate (III) end points.
Ivankovic and Preussmann 1975 Cr2O3 (III)
MacKenzie et al. 1958 CrCl3 (III)
a Key to Species Figure (Strain)
36 Mouse (CD-1)
CHRONIC EXPOSURE Systemic 37 Rat 2 yr
(BD) 5 d/wk (F)
Rat 1 yr (Sprague- (W) Dawley)
Exposure/ Duration/
Frequency (Route)
Gd 6-21 Ld 1-21 ad lib (F)
CH
RO
MIU
M
3. HE
ALTH
EFFE
CTS
157
5103
313
313
313
313
313
313
313
313
90
0.46
0.46
0.46
0.46
CH
RO
MIU
M
Table 3-5 Levels of Significant Exposure to Chromium Ill - Oral (continued)
a Key to Figure
Species (Strain)
Exposure/ Duration/
Frequency (Route)
System NOAEL
(mg/kg/day) Less Serious
(mg/kg/day)
LOAEL
Serious (mg/kg/day)
Reference Chemical Form Comments
39 Rat (Fischer- 344)
2 yr (F)
Resp
Cardio
Gastro
Hepatic
Renal
Endocr
Ocular
Bd Wt
313 F
313 F
313 F
313 F
313 F
313 F
313 F
313 F
NTP 2008b Cr picolinate (III)
40 Rat (Long- Evans)
2-3 yr 7 d/wk (W)
Cardio 0.46 Schroeder et al. 1965 Cr(CH3COO)3 (III)
Hepatic
Renal
Bd Wt
0.46
0.46
0.46
3. HE
ALTH
EFFE
CTS
158
5142
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.22
0.25
5115
781
781
781
781
781
781
781
781
Table 3-5 Levels of Significant Exposure to Chromium Ill - Oral (continued)
a Key to Figure
Species (Strain)
Exposure/ Duration/
Frequency (Route)
System
41 Rat (Sprague-Dawley)
52 wk (F)
Resp
Cardio
Gastro
Hemato
Hepatic
Renal
Endocr
Bd Wt
42 Mouse (B6C3F1)
2 yr (F)
Resp
Cardio
Gastro
Hepatic
Renal
Endocr
Ocular
Bd Wt
LOAEL
NOAEL (mg/kg/day)
Less Serious (mg/kg/day)
Serious (mg/kg/day)
Reference Chemical Form Comments
0.25 F Shara et al. 2007 Cr nicotinate (III)
0.25 F
0.25 F
0.25 F
0.25 F
0.25 F
0.25 F
0.22 M (14.9% decrease in body weight)
0.25 F (9.6% decrease in body weight)
781 M NTP 2008b Cr picolinate (III)
781 M
781 M
781 M
781 M
781 M
781 M
781 M
CH
RO
MIU
M
3. HE
ALTH
EFFE
CTS
159
5104
313
5143
0.25
5116
781
97
2040
5106
313
5144
0.25
5117
781
5105
313
5145
0.25
Table 3-5 Levels of Significant Exposure to Chromium Ill - Oral (continued)
a Key to Figure
Species (Strain)
Exposure/ Duration/
Frequency (Route)
System NOAEL
(mg/kg/day) Less Serious
(mg/kg/day)
LOAEL
Serious (mg/kg/day)
Reference Chemical Form Comments
Immuno/ Lymphoret 43 Rat
(Fischer- 344) 2 yr (F)
313 F NTP 2008b Cr picolinate (III)
44 Rat (Sprague-Dawley)
52 wk (F)
0.25 F Shara et al. 2007 Cr nicotinate (III)
45 Mouse (B6C3F1)
Neurological 46 Rat
2 yr (F)
2 yr 5 d/wk (F)
781 M
2040
NTP 2008b Cr picolinate (III)
Ivankovic and Preussmann 1975 Cr III
47 Rat (Fischer- 344)
2 yr (F)
313 F NTP 2008b Cr picolinate (III)
48 Rat (Sprague-Dawley)
52 wk (F)
0.25 F Shara et al. 2007 Cr nicotinate (III)
49 Mouse (B6C3F1)
2 yr (F)
Reproductive 50 Rat
(Fischer- 344) 2 yr (F)
781 M
313 F
NTP 2008b Cr picolinate (III)
NTP 2008b Cr picolinate (III)
51 Rat (Sprague-Dawley)
52 wk (F)
0.25 F Shara et al. 2007 Cr nicotinate (III)
CH
RO
MIU
M
3. HE
ALTH
EFFE
CTS
160
5118
781
510755
Table 3-5 Levels of Significant Exposure to Chromium Ill - Oral (continued)
Exposure/ LOAEL Duration/
a Key to Species Frequency NOAEL Less Serious Serious Reference
(Route)Figure (Strain) System (mg/kg/day) (mg/kg/day) (mg/kg/day) Chemical Form Comments
52 Mouse 2 yr 781 M NTP 2008b (B6C3F1) (F) Cr picolinate (III)
Cancer 53 Rat 2 yr 55 M (equivocal evidence for NTP 2008b
(Fischer- 344) (F) prepubital gland Cr picolinate (III)adenoma)
a The number corresponds to entries in Figure 3-4.
ad lib = ad libitum; Bd Wt = body weight; Cardio = cardiovascular; d = day(s); Endocr = endocrine; (F) = feed; F = female; (G) = gavage; Gastro = gastrointestinal; Gd = gestational day; (GW) = gavage in water; Hemato = hematological; Immuno/Lymphoret = immunological/lymphoreticular; Ld = lactation day; LD50 = lethal dose, 50% kill; LOAEL = lowest-observed-adverse-effect level; M = male; NOAEL = no-observed-adverse-effect level; NS = not specified; Resp = respiratory; x = time(s); (W) = drinking water; wk = week(s); yr = year(s)
CH
RO
MIU
M
3. HE
ALTH
EFFE
CTS
161