Strontium chromate

Toxicity to reproduction

Administrative data

Endpoint:

fertility, other

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Read-acros from soluble chromates. Acceptabe study report which meets basic scientific principles.

Data source

Reference

Reference Type:

publication

Title:

Embryo- and fetotoxicity of chromium in pregestationally exposed mice.

Author:

Junaid, M., R. C. Murthy, et al.

Year:

1996

Bibliographic source:

Bull Environ Contam Toxicol.57(2): 327-34.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The effect of pregestational exposure to chromium was studied in female mice. The mice were given potassium chromate in drinking water for 20 days, after which they were mated with unexposed males. Signs of general toxicity, and numbers of implantations, corpora lutea and pre-implantation losses were followed.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Potassium dichromate

EC Number:

231-906-6

EC Name:

Potassium dichromate

Cas Number:

7778-50-9

Details on test material:

Potassium dichromate. No details presented.

Test animals

Species:

mouse

Strain:

Swiss

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Industrial Toxicology Research Centre
- Age at study initiation: (P) x 4 months
- Weight at study initiation: (P) ; Females: 30 ± 5 g
- Fasting period before study: no data
- Housing: individual cages until day 20 when matched with utreated males
- Diet (e.g. ad libitum): feed pellets from Lipton India ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22°C
- Humidity (%): 50 ±5%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 h

Administration / exposure

Route of administration:

oral: drinking water

Details on exposure:

250, 500, or 750 ppm in drinking water for 20 days before mating

Details on mating procedure:

Females were checked for pregnancy the next morning after mating. The day that the vaginal plug was found was degnated at day 0 of gestation.
After becoming pregnant the females were kept individually in plastic cages.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Calculated from water consuption.

Duration of treatment / exposure:

20 days

Frequency of treatment:

Daily ad libitum in water

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 250, 500, 750 ppm
Basis:
nominal in water

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 63, 119, 174 mg Cr(VI)/kg/day
Basis:
actual ingested

No. of animals per sex per dose:

15

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: Based on an earlier study (Trivedi et al 1989), average Cr intake of humans in drinking water is ca 200 µg/day.

- Actual exposure calculated based on water intake: 0, 63, 119 and 174 mg Cr(VI)/kg/day.

Positive control:

No

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data


BODY WEIGHT: Yes


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: no data

OTHER:

Oestrous cyclicity (parental animals):

No data

Sperm parameters (parental animals):

No

Litter observations:

10 pregnant animals/group were sacrificed on day 19 of gestation. Total implantations/litter, number of live/dead foetuses, crown-rump length, number of resoprtions, foetus and placenta weights were recorded.

Postmortem examinations (parental animals):

SACRIFICE
- Maternal animals: Day 19 of gestation.

GROSS NECROPSY
- No data

HISTOPATHOLOGY / ORGAN WEIGHTS: placentae

Postmortem examinations (offspring):

Foetuses were examined for gross external abnormalities. 1/3 of the foetuses were fixed in Bouin's fluid for examination of visceral abnormalities; 2/3 fixed in 95% ethanol and stained by the Alizarin red S method in order to enable examination skeletal deformities.

Statistics:

One-way Anova followed by Student's t-test; Fischer's Exact test.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

3 mothers died in the highest dose group

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

not specified

Other effects:

no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not specified

Reproductive function: sperm measures:

not examined

Reproductive performance:

effects observed, treatment-related

Description (incidence and severity):

reduced number of implantations, increased numbers of pre-implantation losses

Details on results (P0)

General toxicity was observed as 3 mothers in the highest dose group died.
Fertility effects were observed in the highest dose group (174 mg Cr(VI)/kg/day, where no implantation were seen and the number of corpora lutea was significantly decreased. Also at the concentration 119 mg Cr(VI)/kg/day could reduced numbers of implantations and increases in pre-implantation losses be observed.

Effect levels (P0)

1

Dose descriptor:

NOAEL

Effect level:

119 other: mg Cr(VI)/kg/day

Sex:

female

Basis for effect level:

other: General toxicity for mothers

2

Dose descriptor:

NOAEL

Effect level:

63 other: mg Cr(VI)/kg/day

Sex:

female

Basis for effect level:

other: Female fertility effects

Results: P1 (second parental generation)

Effect levels (P1)

Remarks on result:

other: not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:

effects observed, treatment-related

Mortality / viability:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

crown-rump length

Histopathological findings:

not specified

Details on results (F1)

Presented under 7.8.2 Developmental toxicity

Effect levels (F1)

Remarks on result:

other: not specified

Results: F2 generation

Effect levels (F2)

Remarks on result:

other: not specified

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Pregestational exposure to potassium dichromate in drinking water caused general toxicity in the mothers (NOAEL 119 mg Cr(VI)/kg/day). Female fertility effects (decreased numbers of implantations and corpora lutaea, increases in pre-implantation losses) were significant, and NOAEL for these effects was 63 mg Cr(VI)/kg/day.

Executive summary:

The effect of pregestational exposure to chromium was studied in adult female Swiss albino mice(Junaid et al 1996b). Groups of 15 mice were administered daily 0, 250, 500 or 750 ppm heaxavalent chromium, as potassium dichromate in drinking water for 20 days, after which they were mated with unexposed males. On day 19 of gestation, 10 pregnant females from each group were randomly selected and sacrificed. Based on water intake and the reported body weight of 30 g, the chromium exposures of the rats can be calculated as 0, 63, 119 and 174 mg Cr(VI)/kg/day.

No clinical signs of toxicity could be detected in the treated mothers. At the highest dose level (174 mg Cr(VI)/kg/day ) 3 deaths occurred among the 15 mice in the group. Autopsy did not establish the cause of death, but as all cases were in the high exposure group, the deaths were likely to be connected to the exposure. No implantations (100% loss) were seen in the highest exposure group, and the number of corpora lutea was significantly decreased at this concentration. Pregestational treatment with 119 mg Cr(VI)/kg/day also reduced the number of implantations. At 119 mg/kg/day there was also a statistically significant increase in pre-implantation losses. A NOAEL of 119 mg Cr(VI)/kg/day can be identified for general toxicity. The NOAEL for female fertility effects appears to be 63 mg Cr(VI)/kg/day. Developmental effects of the foetuses are reported under "Developmental toxicity".