Chromium trinitrate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1997

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: one of soluble inorganic chorium (III) salts, CrCl3, as a similar structural analogue of chromic nitrate, can be used for read-across.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Concise International Chemical Assessment Document 76 INORGANIC CHROMIUM(III) COMPOUNDS

Author:

Dr Tiina Santonen, Dr Antti Zitting, and Dr Vesa Riihimäki

Year:

2009

Bibliographic source:

International Programme on Chemical Safety (IPCS)

Reference 2

Reference Type:

publication

Title:

Chromium as an essential nutrient for humans

Author:

Anderson RA

Year:

1997

Bibliographic source:

Regulatory Toxicology and Pharmacology, 26:S35–41, 1997

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

20 weeks of exposure rather than only 13 weeks

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Chromium chloride

IUPAC Name:

Chromium chloride

Constituent 2

Reference substance name:

Chromium trichloride

EC Number:

233-038-3

EC Name:

Chromium trichloride

Cas Number:

10025-73-7

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

N/A

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

Four-week-old male Harlan Sprague-Dawley rats (eight per group)

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Details on oral exposure:

CrCl3 was fed a diet supplemented with 0, 5, 25, 50, or 100 mg Cr/kg as chromium chloride for a period of 20 weeks.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

20 weeks

Frequency of treatment:

once daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 5, 25, 50, or 100 mg Cr/kg as chromium chloride, Daily Cr3+ intakes can be estimated to correspond to 0.35–7 mg/kg
Basis:
nominal in diet

No. of animals per sex per dose:

8

Control animals:

yes

Details on study design:

Four-week-old male Harlan Sprague-Dawley rats (eight per group) were fed a diet supplemented with 0, 5, 25, 50, or 100 mg Cr/kg as chromium chloride for a period of 20 weeks (Ander son et al., 1997). Daily Cr3+ intakes can be estimated to correspond to 0.35–7 mg/kg bw (estimated on the basis of default reference values given in Appendix VI of European Commission [2003]). If 200 g is used as a mean body weight, the highest dose corresponds to 7 mg chromium/kg bw.

Positive control:

N/A

Examinations

Observations and examinations performed and frequency:

Effects on body weights, selected organ weights, and the histology of liver and kidneys were evaluated.

Sacrifice and pathology:

Histopathological examination was performed on four high-dose and four control rats. Haematology and biochemical analyses of blood (serum glucose, cholesterol, triglycerides, liver enzymes, blood urea nitrogen, total protein, and creatinine) were performed on animals at 11, 17, and 24 weeks of age.

Other examinations:

N/A

Statistics:

N/A

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

Some sporadic, statistically significant changes were seen in some clinical chemistry parameters (lactate dehydrogenase, aspartate aminotransferase, serum creatinine levels).

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Details on results:

No changes in body or organ weights, no general signs of toxicity, and no changes in liver or kidney histopathology were seen.
Some sporadic, statistically significant changes were seen in some clinical chemistry parameters (lactate dehydrogenase, aspartate aminotransferase, serum creatinine levels), but because these changes did not show any dose or time dependency, they were not considered to be treatment related.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

> 7 mg/kg bw/day (actual dose received)

Based on:

element

Remarks:

chromium

Sex:

male

Basis for effect level:

other: see 'Remark'

2

Dose descriptor:

NOAEL

Effect level:

> 21.3 mg/kg bw/day (actual dose received)

Based on:

test mat.

Remarks:

chromium chloride

Sex:

male

3

Dose descriptor:

NOAEL

Effect level:

> 32 mg/kg bw/day (actual dose received)

Based on:

other: chromium trinitrate

Sex:

male

Basis for effect level:

other: results converted by molecular weight to reference substance intake

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Based on these results, the highest dose level (7 mg chromium III/kg bw/day ) can be considered as a no-observed-adverse-effect level (NOAEL) for repeated dose toxicity (using 200 g as a mean body weight). Accordingly, this relates to a NOAEL of >32 mg/kg bw/d based on chromium trinitrate.

Executive summary:

This study was conducted to evaluate the toxicity of chromium chloride in rats exposed to 0, 5, 25, 50, or 100 mg Cr/kg chromium trichloride in the diet for 20 weeks (estimated to correspond to 0.35–7 mg/kg bw). No morphological changes of liver and renal damage were observed based on histopathological examination of kidneys and did not result in significant alterations in body weight gain at level of 15 mg chromium (III)/kg bw/day. However, in calculations, they used a rat body weight of only 100 g, which seems exceptionally low, because the normal weight of adult Sprague-Dawley rats is between 200 and 300 g. If 200 g is used as a mean body weight, the highest dose corresponds to 7 mg chromium/kg bw. Moreover no alterations in testers or epididymis weights were observed in rats at the highest dose.

Therefore, the no-observed-adverse-effects-level(NOAEL) of chromium trichloride is estimated to be 7 mg chromium (III)/kg bw/day. This value can be converted to a NOAEL of > 32 mg/kg bw/d based on molecular mass of chromium trinitrate.