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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
repeated dose toxicity: oral
Remarks:
combined repeated dose and reproduction / developmental screening
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: NTP study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: NTP
Principles of method if other than guideline:
NTP combined repeated dose / reproductive toxicity screening study.
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
No further details

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
Animals were exposed for up to 9 weeks
Frequency of treatment:
Continous
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 15, 50, 100, 400 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
0, 1, 3, 6. 24 (M); 0, 1, 3, 7, 28 (F) mg/kg bw/d
Basis:
actual ingested
Remarks:
Doses / Concentrations:
0, 0.4, 1, 2, 8 (M); 0, 0.4, 1, 2, 10 (F) mg/kg bw/d
Basis:
other: Cr (VI) equivalents
No. of animals per sex per dose:
24 males; 48 females
Control animals:
yes, plain diet

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
> 400 ppm
Sex:
male/female
Basis for effect level:
other: No effects of toxicological significance were seen at the highest dose level in this study.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

No deaths or treatment-related clinical signs of toxicity were observed. No effects were seen on body weight, water and food consumption, organ weights and microscopic evaluation of the liver, kidneys and ovaries. During haematological investigations, a statistically significant decrease of 3% and 6% in mean corpuscular volume (MCV) was seen at week 3 in the 400 ppm females and at week 9 in the 400 ppm males, respectively. Although not statistically significant, the MCV values were also decreased by 3% in the 400 ppm females at week 9. This effect returned to normal in all animals after the recovery period. The mean corpuscular haemoglobin (MCH) was also significantly decreased at week 9 in the 400 ppm males (by 5%) and in the 400 ppm females (by 6%). After the recovery period, the MCH was again comparable across groups. Decreases in the MCV and MCH are also considered to be of no toxicological significance since the decreases were small, were stated to be within historical control ranges, and since both the MCV and MCH are derived indices using the haematocrit, erythrocyte count, or haemoglobin concentration and no treatment-related differences were observed in these latter parameters. No alterations in structure or relative cell numbers were found in the testes.

Applicant's summary and conclusion

Conclusions:
Dietary administration of potassium dichromate for 9 weeks to rats did not produce any significant toxicity up to the highest dose level tested of 24 mg/kg/day (8 mg Cr(VI)/kg/day) and 28 mg/kg/day (10 mg Cr(VI)/kg/day) in males and females, respectively.
Executive summary:

Groups of 24 male and 48 female Sprague-Dawley rats were administered in the diet 0, 15, 50, 100 or 400 ppm of potassium dichromate , corresponding to mean dose levels of approximately 0, 1, 3, 6 and 24 mg/kg/day (0, 0.4, 1, 2 and 8 mg Cr(VI)/kg/day) in males, and 0, 1, 3, 7, and 28 mg/kg/day (0, 0.4, 1, 2 and 10 mg Cr(VI)/kg/day) in females, respectively, for 9 weeks. Six males and 12 females from each dose group were then terminated after 3, 6 or 9 full weeks of treatment and after a recovery period of 8 weeks. Investigations of body weight, food and water consumption, organ weights, microscopic evaluation of the liver, kidney and ovaries, haematology, histology of the testis and epididymis for Sertoli nuclei and preleptotene spermatocyte counts in stage X or XI tubules, and chromatin analysis were included. Treatment-related findings were limited to minor effects on haematological parameters in 400 ppm females; findings are not considered to be of toxicological significance.