Chromium trinitrate

Toxicity to reproduction

Administrative data

Endpoint:

fertility, other

Remarks:

based on test type (migrated information)

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-standard study design

Data source

Reference

Reference Type:

publication

Title:

Long-term exposure of male and female mice to trivalent and hexavalent chromium compounds: effect on fertility

Author:

Elbetieha A & Al-Hamood MH

Year:

1997

Bibliographic source:

Toxicology 116, 39-47

Materials and methods

Test guideline

Qualifier:

no guideline followed

Deviations:

not applicable

Principles of method if other than guideline:

The effects on fertility were investigated following the administration of chromium (III) chloride to male and female mice for 12 weeks before mating.
Treated males were mated with untreated females; treated females were mated with untreated males. Females were sacrificed one week following
mating.

GLP compliance:

no

Remarks:

Published study

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:

No further details

Test animals

Species:

mouse

Strain:

Swiss

Sex:

male/female

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

water

Details on mating procedure:

1 treated male: 2 untreated females
1 untreated male: 3 treated females

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Treated males or females were mated with untreated animals following exposure for 12 weeks.

Frequency of treatment:

Continuous.

Details on study schedule:

The effects of chromium chloride on male and female fertility were investigated in sexually mature (7 weeks old) Swiss mice administered this trivalent chromium compound in drinking water. Groups of 9-20 males were administered 0, 2000 or 5000 mg/l chromium chloride for 12 weeks and then mated for ten days, 1 male to 2 untreated females. The exposed males were then removed and 1 week later the females were terminated. Similarly, groups of 11-18 females were administered 0, 2000 or 5000 mg/l chomium chloride for 12 weeks and then mated for ten days, 3 females to 1 untreated male. One week after the removal of the males, the females were terminated. Number of pregnant females, total implantations, viable fetuses and resorptions were recorded. In addition, satellite groups of 10-13 males and 8-10 females administered chomium chloride for 12 weeks were sacrificed at the end of the treatment. Body and reproductive organ weights were recorded in these animals.

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 2000, 5000 mg/l (males)
Basis:
nominal in water
chromium (III) chloride

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 2000, 5000 mg/l (females)
Basis:
nominal in water
chromium (III) chloride

No. of animals per sex per dose:

9-20 males; 11-18 females

Control animals:

yes, concurrent no treatment

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

1

Dose descriptor:

LOAEL

Effect level:

2 000 mg/L drinking water

Based on:

element

Remarks:

chromium III

Sex:

male/female

2

Dose descriptor:

LOAEL

Effect level:

ca. 5 mg/kg bw/day

Based on:

element

Remarks:

chromium III

Sex:

male/female

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

Exposed males

Bodyweights were significantly reduced by exposure to 2000 and 5000 mg/l chromium chloride, however a dose-response relationship is not apparent. Testes weights were significantly increased in both treated groups of males, however relative weights only are reported and there is no relationship to dose. Relative seminal vesicle weight was significantly lower at 5000 mg/l. Relative preputial gland weight was significantly lower at 2000 and 5000 mg/l, however there is no relationship to dose level.

Fertility was significantly (p<0.005) reduced in males exposed to 5000 mg/l chromium chloride. The number of succesful matings was significantly lower for males exposed to 5000 mg/l. Numbers of implantations and viable foetuses were lower for females mated to males exposed to 2000 and 5000 mg/l. Resportions were increased for females mated to males exposed to 2000 mg/l and the number of dead foetues was increased in females mated to males exposed to 5000 mg/l.

Exposed females

Bodyweights were unaffected by treatment with 2000 or 5000 mg/l. Relative ovary weight was significantly increased and relative uterus weight was significantly decreased in females exposed to 5000 mg/l. Implantation numbers were significantly reduced in females exposed to 2000 and 5000 mg/l; numbers of viable foetuses were also significantly reduced, although there is no relationship to treatment. The numbers of resorptions were increased in both treatment groups.

Parameter		Males exposed			Females exposed
		M			F
		Controls	2000 mg/l	5000 mg/l	Controls	2000 mg/l	5000 mg/l
Bodyweight	(g)	35.7	30.6*	33.4**	34.6	nr	34.2
Testes weight	(mg/10 g bw)	50.72	61.8**	61.2*
Seminal vesicle weight	(mg/10 g bw)	44.5	42.2	35.4**
Preputial gland weight	(mg/10 g bw)	18.7	10.1***	15.0*
Ovary weight	(mg/10 g bw)				2.21	nr	3.63*
Uterus weight	(mg/10 g bw)				23.75	nr	13.90**
Pregnant females	(#, %)	33/40 (82.5%)	18/20 (90%)	8/18 (44%***)	17/18 (94.4%)	10/14 (71.4%)	10/12 (83.3%)
Implantations	(#)	8.18	7.47	7.33	9.00	6.30**	5.70**
Viable foetuses	(#)	8.18	7.33	6.00	8.76	5.55**	5.85**
Resorptions	(#)	0	6	1	4	12	16
Animals with resorptions	(#, %)				2/18 (11%)	4/14 (28%)	4/12 (33%)
Dead foetuses	(#)	0	0	12	0	0	0

Applicant's summary and conclusion

Conclusions:

The findings of this study indicate that administration of high levels of water-soluble Cr (III) compounds in the drinking water to male and female mice might have negative effects on fertility. However the US Department of Health and Human Services in its Toxicological Profile for Chromium, September 2012, states that the results should be interpreted with caution due to concerns regarding experimental methods, including decreased water consumption in the higher concentration group (resulting in a potential overestimate of exposure and uncertainty regarding daily dose calculations). Also sperm counts wee not conducted and no standard mating protocol was used.

Executive summary:

Male and female Swiss mice were administered chromium chloride in drinking water for 12 weeks prior to mating with untreated animals. Female mice were sacrificed one week following treatment; the numbers of pregnant animals, total implantations, viable foetuses and resorptions were recorded. Satellite groups of animals were also treated for 12 weeks (without mating) and the weights of the reproductive organs recorded.

There were no deaths or signs of toxicity; slightly reduced bodyweights were seen in both groups of treated males but without any relationship to dose. Relative testes weights were significanlty increased in both satellite groups, however findings may be secondary to bodywieght effects. Relative seminal vesicle and preputial gland weights were significantly lower, however the toxicological significance of these findings is unclear in the absence of histopathology. Relative ovary and uterus weight was increased in females at 5000 mg/l. Mean numbers of implantation sites were lower in treated groups.

Due to some shortcomings in study design, these finding should be interpreted with caution and considering the high doses applied should not become overestimated.