Registration Dossier

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

Reference
Name:
Unnamed

Test animals

Species:
rat
Strain:
other: DCF
Sex:
male/female
Details on test animals 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 / concentrationsopen allclose all
Dose / conc.:
17 mg/m³ air (analytical)
Dose / conc.:
54 mg/m³ air (analytical)
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 animals)

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
Description (incidence and severity):
mean absolute and relative lung/trachea weights statistically significant increased
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Gray lung discoloration was commonly observed in animals exposed to basic chromium sulfate at the mid- and high-exposure levels. The degree of discoloration with both materials increased with exposure level.
Neuropathological findings:
not specified
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.