Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from a sparingly water soluble chromate. Follows OECD guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Strontium Chromate L203E

Test animals

Species:
rat
Strain:
other: albino (RccHanTM:WIST(SPF))
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V.
- Age at study initiation: males 9-10 weeks, females 9-11 weeks
- Weight at study initiation: males 258-321 g, females 179-225 g
- Housing: in groups of 5 of the same sex in Makrolon type-IV cages with wire mesh tops and standard softwood bedding including paper enrichment
- Diet (e.g. ad libitum): ad libidum except during the restraining period in exposure tubes, pelleted standard Harlan Teklad 2914C rat maintenance diet
- Water (e.g. ad libitum): community tap water ad libidum, except during the restraining period
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+-3
- Humidity (%): 30-70
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: The low of air at each tube was 1.0 L/min.
- Method of holding animals in test chamber: Separately in restraint tubes; flow-past, nose-only exposure system
- System of generating particulates/aerosols: A dust aerosol was generated from the test item using a CR3020 rotating brush aerosol generator connected to a micronizing jet mill. The aerosol generated was discharged into exposure chamber through a 63Ni charge neutralizer.
- Method of particle size determination: Using a Mercer 7 stage cascade Impactor

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD in all groups between 2.76 um and 3.80 um; GSD within the target range 1.5-3
Duration of exposure:
4 h
Concentrations:
target concentrations 0.25, 0.5, and 1 mg/L air (gravimetrically determined mean aerosol concentration 0.27, 0.51 and 0.81 mg/L air, respectively)
No. of animals per sex per dose:
5 M / 5 F
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Viability/mortality - test day 1 (before exposure), three times during exposure, immeadiately and 1 h after exposure on test day 1 and twice daily during the observation period; Body weights - on day 1 (before exposure), and on day 2, 4, 8 and 15 (before necropsy)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Clinical signs - three times during exposure, immeadiately and 1 h after exposure on test day 1 and once daily during the observation period
Statistics:
No statistical analysis were performed due to the high death rates.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
0.27 - 0.51 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
With concentrations 0.81 mg/L and 0.51 mg/L, eight eanimals died withing 5 days and two animals were killed due to severe body weight loss on day 8. Two males of 0.27 mg/L group were found dead on day 3 and 4, respectively.
Clinical signs:
Tachypnea and ruffled fur with all doses; decreased activity with concentrations 0.81 mg/L and 0.51 mg/L; excitement with 0.27 mg/L in most of the animals during exposure and immediately after exposure end.
Body weight:
Slight to marked body weight loss in all animals with concentration 0.81 mg/L (from test day 1 to 2) and 0.51 mg/L (from day 1 to 4), and slight body weight loss in four males and three females with 0.27 mg/L (from day 1 to 2). With the 0.81 and 0.51 mg/L concentrations, further body weight loss in the rats until death or killing (when body weight loss was more than 20%). With 0.27 mg/L, further body weight loss in four males and one female until day 4 and one female until day 8. Body weight loss also in one male and one female from day 4 to 8. Thereafter normal body weight development in the surviving animals.
Gross pathology:
0.81 mg/L - dark red discoloration, dark red foci and/or not or incompletely collapsed lung in all animals, beginning autolysis in one rat;
0.51 mg/L - dark red discoloration and/or not or incompletely collapsed lung in all animals;
0.27 mg/L - hardened, pale or dark red discolored lung in all animals, irregular surface of the lung in all survivors, reddish discoloration of the thymus in one male.
Other findings:
No indication of relevant sex-related differences.

Applicant's summary and conclusion

Interpretation of results:
highly toxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
LC50 between 0.27 and 0.51 mg/L. Strontium chromate falls into category 2 in CLP classification and labelling, signal word 'danger', hazard statement 'H330: Fatal if inhaled'.
Executive summary:

Harlan Laboratories (2010) conducted an acute inhalation toxicity study on strontium chromate (Strontium Chromate L203E, purity 97%). Male and female albino rats were exposed four 4-hours nose-only to target concentrations 0.25, 0.5 and 1 mg/L air of strontium chromate (analytical concentrations were 0.27, 0.51 and 0.81 mg/L air, respectively), and observed for 14 days after the exposure. At the concentrations of 0.51 and 0.81 mg/L, all animals died within eight days. The 0.27 mg/L concentration resulted in the death of two animals. Tachypnea and ruffled fur as well as body weight loss were seen at all aerosol concentrations. Treatment related changes were discoloration and incompletely collapsed lungs, as well as hardened and pale lungs. The LC50of strontium chromate was considered to be between 0.27 and 0.51 mg/L air.