Phosphoric acid, chromium(3+) salt (1:2.5)

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

other: read-across from constituent CrIII

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Thirteen-week subchronic rat inhalation toxicity study with a recovery phase of trivalent chromium compounds, chromic oxide, and basic chromium sulfate

Author:

Derelanko MJ, Rinehart WE, Hilaski RJ, Thompson RB, Loser E

Year:

1999

Bibliographic source:

Toxicological Sciences 52: 278-288

Materials and methods

Principles of method if other than guideline:

Fertility was assessed by measuring sperm parameters during a 90-day inhalation study. The study was performed according to OECD TG 413.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

1

Reference substance name:

Chromium (III) oxide

EC Number:

215-160-9

EC Name:

Chromium (III) oxide

Cas Number:

1308-38-9

Molecular formula:

Cr2O3

Test animals

Species:

rat

Strain:

other: DCF

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female CDF (Fischer 344)/Crl BR VAF/Plus rats, approximately 5 weeks of age, were obtained from Charles River Laboratories (Raleigh, NC).

Following 3 days of group housing, animals were individually housed in stainless steel, suspended wire-mesh cages and given free access to commercial laboratory feed (Purina Certified Rodent Chow No. 5002) and tap water during the non-exposure periods.

Animal rooms were maintained on a 12-h light/dark cycle; temperature range was maintained at 21 ±2°C, and the relative humidity range was 43 ±11%.

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure (if applicable):

nose only

Vehicle:

unchanged (no vehicle)

Details on exposure:

Rats were exposed in stainless steel and acrylic nose-only inhalation chambers operated with at least 12 chamber air changes per h.

Details on mating procedure:

Not applicable

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Basic chromium sulfate particles were generated using an auger dust feeder and an air micronizer. Chamber samples were determined once per h by standard gravimetric methods, with periodic analysis for Cr(III) and Cr(VI). Particle-size measurements were made from each exposure level using a cascade impactor once per day for the first two weeks and weekly thereafter.

Duration of treatment / exposure:

6 hours/day

Frequency of treatment:

5 days/week

Details on study schedule:

Doses basic chromium sulfate (17, 54, or 168 mg/m 3 ). The desired exposure levels were selected to be multiples of the threshold limit value (TLV) for trivalent chromium and set at chromium equivalents of 3, 10, and 30 mg/m3 for each test article.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

17 mg/m³ air (analytical)

Doses / concentrations 2

Dose / conc.:

54 mg/m³ air (analytical)

Doses / concentrations 3

Dose / conc.:

168 mg/m³ air (analytical)

No. of animals per sex per dose:

15

Control animals:

yes, concurrent no treatment

Examinations

Parental animals: Observations and examinations:

Performed according to OECD TG 413

Oestrous cyclicity (parental animals):

Not applicable

Sperm parameters (parental animals):

In a 13-week nose-only inhalation study, sperm samples from male rats were collected at necropsy and were used for automated evaluation of sperm motility, count and morphology.
Sperm evaluation: At necropsy, sperm samples from the left caudal epididymis of 10 males per group were used for automated evaluation of sperm motility, count, and morphology. The concentration and morphology of the sperm were evaluated using visual methods. Two hundred intact sperm were evaluated from each animal for morphology. Intact sperm were evaluated as normal or abnormal. The number of disarticulated sperm in each field was also assessed.

Litter observations:

Not applicable

Postmortem examinations (parental animals):

Performed according to OECD TG 413

Postmortem examinations (offspring):

Not applicable

Statistics:

one-way analysis of variance
Bartlett’s test for homogeneity of variance
Dunnett’s t-test
Welch t-test with Bonferonni correction
Kruskal-Wallis analysis of variance
Mann-Whitney U test
level for statistical significance: p<0.05

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

reduced mean body weights in mid- and high dose group

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

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Chronic inflammation was observed involving the alveoli of all exposure-level groups, consisting of alveolar spaces filled with macrophages, neutrophils, lymphocytes, and cellular debris.

Histopathological findings: neoplastic:

not specified

Other effects:

no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

not examined

Effect levels (P0)

Dose descriptor:

NOAEC

Effect level:

> 168 mg/m³ air (analytical)

Based on:

test mat.

Basis for effect level:

other: No effects observed at the highest dose level

Remarks on result:

other: For CrIII the NOAEC is >30 mg/m3

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:

not examined

Mortality:

not examined

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

not examined

Results: F1 generation

General toxicity (F1)

Clinical signs:

not examined

Mortality / viability:

not examined

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Urinalysis findings:

not examined

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Other effects:

not examined

Effect levels (F1)

Remarks on result:

not determinable due to absence of adverse toxic effects

Overall reproductive toxicity

Reproductive effects observed:

no

Any other information on results incl. tables

Sperm motility or morphology was not affected in rats with nose-only exposures to chromium hydroxide sulphate dust at 17, 54, or 168 mg/m3 for 6 h/day, 5 days/week for 13 weeks. Ovary and testes weights were also unaffected by treatment.

Applicant's summary and conclusion

Conclusions:

Negative, no effects on sperm parameters and reproductive organ weights.

Executive summary:

Sperm parameters were assessed in male rats exposed to chromium (III) oxide and chromium (III) hydroxy sulfate in a 90-day inhalation (concentrations of 0, 17, 54 or 168 mg/m3). No treatment-related effects on fertility parameters (sperm parameters) were observed.