Toxicological Profile for ChromiumResp 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)

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)

LOAEL

Serious (mg/kg/day)

Reference Chemical Form Comments


daily 20 wk (F)

Hepatic 9 Anderson et al. 1997b Cr picolinate (III)

Renal

Bd Wt

9

9


12 wk (W)

Bd Wt 40 (24% lower final body weight)


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


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)


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


Exposure/ LOAEL Duration/

a Key to Figure

Species (Strain)

Frequency (Route)

System NOAEL


(mg/kg/day) Serious (mg/kg/day)


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)


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


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)


Serious (mg/kg/day)


1415 M

1415 M

1415 M

1415 M

1415 M

1415 M

1415 M

1415 M

1415 M





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


a Key to Figure

Species (Strain)

Exposure/ Duration/

Frequency (Route)

System NOAEL


(mg/kg/day)

LOAEL

Serious (mg/kg/day)


22 Rat (Fischer- 344)

14 wk (F)



14 wk ad lib (F)



90 d (F)



38 wk (F)


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)




14 wk (F)



90 d (F)


3. HE

ALTH

EFFE

CTS

155

5141

0.25

5058

5

5

5112

1415

469.1

92

1806

500574



a Key to Species Figure (Strain)


31 Mouse (Swiss)

32 Mouse (B6C3F1)

33 Mouse (BALB/c)

Developmental 34 Rat

(BD)

35 Mouse (BALB/c)

Frequency (Route)

System NOAEL



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)


Shara et al. 2007 Cr nicotinate (III)

Elbetieha and Al-Hamood 1997 CrCl3 (III)


Zahid et al. 1990 Cr2(SO4)3 (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


LOAEL

System NOAEL



25

Resp 2040

Cardio 2040

Gastro 2040

Hepatic 2040

Renal 2040

Hemato 3.6

Hepatic 3.6

Renal 3.6

Bd Wt 3.6


Bailey et al. 2008b NOAEL is for standard neurodevelopmentalCr picolinate (III) end points.


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


a Key to Figure

Species (Strain)

Exposure/ Duration/

Frequency (Route)

System NOAEL


(mg/kg/day)

LOAEL

Serious (mg/kg/day)



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


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


a Key to Figure

Species (Strain)

Exposure/ Duration/

Frequency (Route)

System


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)


Serious (mg/kg/day)



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


a Key to Figure

Species (Strain)

Exposure/ Duration/

Frequency (Route)

System NOAEL


(mg/kg/day)

LOAEL

Serious (mg/kg/day)


Immuno/ Lymphoret 43 Rat

(Fischer- 344) 2 yr (F)



52 wk (F)


45 Mouse (B6C3F1)

Neurological 46 Rat

2 yr (F)

2 yr 5 d/wk (F)

781 M

2040


Ivankovic and Preussmann 1975 Cr III


2 yr (F)



52 wk (F)


49 Mouse (B6C3F1)

2 yr (F)

Reproductive 50 Rat

(Fischer- 344) 2 yr (F)

781 M

313 F




52 wk (F)


CH

RO

MIU

M

3. HE

ALTH

EFFE

CTS

160

5118

781

510755



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

Documents

Toxicological Profile for ChromiumResp 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)