Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: LD50 > 5000 mg/kg bw (equivalent or similar to OECD 401; GLP compliant)

Acute inhalation toxiciy: LC50 > >5.41 mg/L (analytical; OECD 403; GLP compliant)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25/8/1988-8/9/1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: storage at room temperature
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen
- Females nulliparous and non-pregnant: yes
- Age at study initiation: males: ca. 9 weeks; females ca. 14 weeks
- Weight at study initiation(mean): males: 175 g: females: 172 g
- Fasting period before study: ca. 16 hours before test item administration and up to 4 hours after test item administration food was withdrawn.
- Housing: five animals/cage; Macrolon cage Typ III with dustfree wood pelletes (manufacturer: Firma Ssniff, Soest/Westfalen)
- Diet (ad libitum, for exception please refer to "Fasting period before study" above): "fixed-formula"- standard diet AltrominR1324 pellets (Manufacturer: Altromin GmbH, Lage)
- Water (ad libitum): drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Relative humidity: 50 ± 10 %
- Air changes: ca. 10 air changes/h
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
DOSAGE PREPARATION:
The test material was suspended in water at room temperature. The test material was formulated prior to administration. A homogeneous mixture was accomplished by stirring.
Animals were dosed using a constant application volume of 20 mL/kg bw.
The application volume was calculated based in the individual body weight of the animals determined prior to test item application.
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on the day of the application, the animals were inspected several times and during the following 14-day observation period twice a day (once on weekends and holidays). The type, onset, duration and intensity of the clinical symptoms were recorded and any dead animals were removed. The time of death was recorded. At the end of the experiment animals were randomly selected for necropsy.
At application day, day 7 and at the end of the 14-day observation period, the surviving animals were individually weighed.
- Necropsy performed: yes, all deceased and surviving animals were macroscopically examined..
Statistics:
Statistical analysis not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred.
Clinical signs:
Clinical signs were limited to piloerection (one male and one female) and salivation (all animals) starting 15 minutes following dosing; signs had resolved within 8 hours.
Body weight:
Slight weight loss was apparent in two females during the second week of the study. The body weight of the males was not effected.
Gross pathology:
There were no findings attributable to treatment.
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 (male rats) > 5000 mg/kg
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the oral route.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 April to 21 May 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
1981-05-12
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: sealed container, at room temperature
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
The animals were male and female Han Wistar rats, obtained from Harlan UK Ltd. The animals were weight matched to 200 g ± 15% on arrival and were less than 12 weeks of age at the start of the study.
The animals were housed in groups of five. The room provided a minimum of 15 air changes per hour, temperature was maintained at 19 to 25°C and relative humidity was maintained at 40 to 70 %. The animals were removed from this environment during acclimatisation to tube restraint and during test article exposure. Fluorescent lighting was provided on a 12 hour light/dark cycle.
The rats were provided with wooden 'Aspen' chew blocks as enrichment. They were fed SQC Rat and Mouse Maintenance Diet No.1, Expanded (SDS Ltd., UK) ad libitum. Mains water was provided ad libitum.
All animals were examined for ill health on arrival. They underwent 9 days acclimatisation, the final 3 days of which they underwent acclimatisation to restraint tubes.
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
2.22 µm
Geometric standard deviation (GSD):
2.36
Remark on MMAD/GSD:
88.3 - 89.8 % ofthe particles were below 3.5 μm in diameter.
Details on inhalation exposure:
TEST ATMOSPHERE / CHAMBER DESCRIPTION
- System of generating particulates/aerosols: test aerosol was generated from chromium (III) oxide using a Rotating Brush Generator that fed into a flow-through (nose-only) exposure chamber with an internal volume of approximately 40 L. The air flow was 35 L/min and was sufficient to provide a minimum of 12 air changes per hour.
- Method of particle size determination: the particle size distribution of the aerosol was measured gravimetrica!ly using a Marple 298 Cascade impactor by sampling the aerosol from inside the chamber at a flow rate of 2L/min. The weight of test article collected on each weighed substrate was used to calculate the mass median aerodynamic diameter and geometric standard deviation. A total of three samples were collected during exposure.
- Temperature, humidity, pressure in air chamber: the temperature, relative hurnidity, air flow and oxygen concentration inside the exposure chamber were monitored continuously and recorded approximately hourly during the animal exposure.
During the animal exposure the mean temperature and relative humidity within the chamber were 21.5 ± 0.283 °C and 10.9 ± 0.150 % respectively. The low relative humidity was due to a combination of the dried air supply necessary for the consistent aerosol generation of a powder and the effect of the dry powder aerosol itself. The low humidity level is to be expected with a dry powder aerosol and has no detrimental effect on the outcome ofthe study. Oxygen concentration remained stable at 20.9 % v/v throughout the animal exposure. The air flow was 35 L/min and was sufficient to provide a minimum of 12 air changes/hour.

TEST ATMOSPHERE
- Brief description of analytical method used: the achieved aerosol concentration in the exposure chamber was measured gravimetrically prior to and at approximately half-hourly intervals throughout the exposure.
During the exposure additional aerosol samples were taken for the purposes of monitoring aerosol stability when the aerosol generator was changed once the powder reservoir in the generator was depleted.
The chamber aerosol concentration was sampled onto weighed glass-fibre filters. After sampling (ca 1 L/min), the filters were then re-weighed. U sing the collected weight and volume of air sampled, the gravimetric chamber aerosol concentration was calculated.
- Samples taken from breathing zone: yes

The rats had Vaseline petroleum jelly smeared over their closed eyelids prior to test article exposure as a precautionary measure to avoid adverse irritant effects to the eye.GENERATION OF
Analytical verification of test atmosphere concentrations:
yes
Remarks:
The achieved aerosol concentration was measured gravimetrically prior to and at approximately half-hourly intervals throughout the exposure.
Duration of exposure:
4 h
Concentrations:
Nominal concentration = 17.6 mg/L.
Mean achieved concentration = 5.41 ± 0.744 mg/L, with a range of 4.57 to 6.84 mg/L.
No. of animals per sex per dose:
5 males / 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: all animals were observed daily (for 14 days post-exposure) for signs of ill health or overt toxicity. Animals were observed approximately hourly during the exposure period and for the remainder of the exposure day. Individual body weights were recorded before and after exposure on Day 1, and on Days 2, 8 and 15. Additional body weights were recorded on Days 3, 4 and 5.
- Necropsy of survivors performed: all animals were subject to a gross necropsy. The gross necropsy procedure included inspection of the nasal cavity and respiratory tract.
Statistics:
Not performed.
Preliminary study:
Not applicable.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.41 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No animals died during the study.
Clinical signs:
other: Adverse treatment related clinical signs were increased breathing rate in 4 females and 2 males during exposure, and hunched posture in one female. No adverse clinical signs were observed immediately following exposure or during the remainder of the obser
Body weight:
All animals lost body weight during exposure, but regained their pre-exposure body weight by day 5. As a result of the initial loss, the body weight gain seen during the first week of the study was less than expected for most animals of this age and strain. Animals generally gained more weight during the second week (especially females) and weight gain during this week was more comparable with other rats of this strain and age.
Gross pathology:
Macroscopic findings included green areas in the lung and lymph nodes in the majority of animals. Reddened nasal cavity, mandibular lymph nodes and thymus were also noted in several animals. One animal had a pale urinary bladder, however this was not considered to be treatment-related.
Interpretation of results:
GHS criteria not met
Conclusions:
LC50 (rats; 4 hours) > 5.41 mg/L air (actual concentration)
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the inhalation route.
Executive summary:

Male and female Han Wistar rats underwent a single 4 hour nose-only inhalation exposure to chromium (III) oxide at a mean atmospheric exposure level of 5.41 mg/L. Exposure to the test compound was well tolerated and no mortalities occurred. Clinical signs were limited to increased breathing rate during exposure. Adverse clinical signs did not persist into the 14 day observation period. Necropsy revealed green staining in the lung and lymph nodes and reddening of the nasal cavity and mandibular lymph nodes. The LC50 is therefore considered to be in excess of 5.41 mg/L.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity

The key study described by Bomhard (1988; equivalent or similar to OECD 401; GLP) is reliable without restrictions. Male and female Wistar rats were exposed to dichromium trioxide via gavage. No deaths occurred, resulting in a LD50 of chromium dioxide above 5000 mg/kg bw.

 

Acute inhalation toxicity

The key study by Gaunt (2009; OECD 403 (1981; GLP) is reliable without restrictions. Male and female Wistar rats were exposed to a mean concentration of dichromium trioxide of 5.41 mg/L via nose only inhalation for 4 hours No deaths occurred, resulting in a LC50 above 5.41 mg/L air (actual concentration).

 

Acute dermal toxicity

No information is available on acute dermal toxicity, however based on the very low acute oral toxicity and very low dermal absorption of dichromium trioxide, toxicity by this route can confidently be predicted to be very low. Local effects were not observed in an in vivo skin irritation study according to OECD 404. Consequently any additional testing is not believed not contribute to the overall negative database and is therefore not foreseen.

Justification for classification or non-classification

Acute oral toxicity

Dichromium trioxide is not acutely toxic via the oral route, showing a LD50 above 5000 mg/kg bw. The classification criteria according to Regulation (EC) No 1272/2008 are therefore not met, no classification required.

 

Acute inhalation toxicity

Dichromium trioxide is not acutely toxic via the inhalation route, showing a LC50 above 5.41 mg/L. The classification criteria according to Regulation (EC) No 1272/2008 are therefore not met, no classification required.

 

Acute dermal toxicity

Taking into account the lack of acute systemic toxicity in acute oral and inhalation toxicity study, the lack of local skin effects in in vivo skin irritation studies, one may safely assume that dichromium trioxide does not require a classification for acute dermal toxicity in accordance with Regulation (EC) 1272/2008.