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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 February to 17 March 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Proprietary GLP guideline-compliant study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solution
Details on test material:
The test material was dichromium tris(chromate) 25% solution, batch no. RCAJ29F1TOX, described as a dark brown liquid. The batch had an expiry date of November 2010, and was stored at room temperature.
All concentrations were expressed as active ingredient.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
The animals were young, healthy adult female CRL:(WI) BR SPF rats obtained from Toxi Coop Ltd (Budapest). The rats were 9-11 weeks old at dosing, weighed 217-234 g, and were nulliparous and non-pregnant. They were acclimatised to the laboratory for at least 22 days. Only healthy (certified by a veterinary surgeon) animals were used for the study.
The rats were housed in groups of 3, in Type II polypropylene/polycarbonate cages with Lignocel Bedding (a copy of the certificate of analysis was retained by the test facility). The temperature in the animal room was 22±3°C, relative humidty was 30-70%, there were 15-20 air changes per hour and light was provided for 12 hours daily.
Animals were fed ssniff SM R/M-Z+H "Autoclavable complete feed for rats and mice - breeding and maintenance" (ssniff Spezialdiaten GmbH, Germany) ad libitum. Tap water from the municipal supply was provided ad libitum.
Individuals were identified by indelible ink markings on the tail.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Details on oral exposure:
The test substance was administered in a single oral dose by gavage, to rats fasted overnight. Water was not withheld prior to dosing. Animals were weighed immediately prior to treatment. Food was returned 3 hours after dosing.
The dose volume was 10 ml/kg bw. The test item was freshly formulated at a concentration of 0.127 and 0.021 ml/ml in the vehicle on the day of administration. The formulation was stirred continuously during administration, to ensure the syringe was filled from a homogenous liquid.
The test item was expected to have toxic effects (based on Sponsor information), therefore the starting dose chosen was 300 mg/kg of active ingredient.
Initially, three females (group 1) were treated at the 300 mg/kg dose level. Mortality was observed in these animals, so a further three rats (group 2) were treated with 50 mg/kg bw. No mortality occurred in group 2, so a confirmatory group (group 4) were also treated at 50 mg/kg.
Doses:
50 and 300 mg/kg bw
No. of animals per sex per dose:
3 females per group
Control animals:
no
Details on study design:
The rats were observed for 14 days following dosing. Clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing, and daily thereafter. Individual observations were performed and cinluded the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was given to the observation of tremors, convulsions, saliation, diarrhoea, lethargy, sleep and coma.
Body weights were recorded the day prior to dosing, the day of dosing, and weekly thereafter. All rats were subject to gross necropsy. Surviving animals were saccrificed by exsanguination under pentobarbital anaesthesia. The rats were examined externally, and then the cranial, thoracic and abdominal cavities were opened and the organs and tissues examined macroscopically for abnormalities.
Statistics:
Not applicable.

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
50 - 300 mg/kg bw
Based on:
act. ingr.
Mortality:
All 3 animals dosed with 300 mg/kg died within 6 hours of dosing.
Clinical signs:
Decreased activity, hunched posture, dyspnoea, piloerection and soft faeces were observed in all 3 animals administered 300 mg/kg. No adverse effects were noted in the animals dosed with 50 mg/kg.
Body weight:
There were no treatment-related effects on body weight in surviving animals.
Gross pathology:
Necropsy of the animals dosed with 300 mg/kg revealed dark/brown discolouration of the oesophagus, stomach ad/or digestve content as well as dark/brown discolouration of the lungs associated with yellow liquid in the trachea or nasal cavity. No macropscopic findings were noted in the 500 mg/kg groups.
Other findings:
No other findings reported.

Any other information on results incl. tables

No further details.

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute oral LD50 of dichromium tris(chromate) was between 50 and 300 mg active ingredient/kg bw in female rats.
Executive summary:

The acute oral toxicity of Dichromium tris(chromate), tested as a water dilution (25% corresponding to 23.6% active ingredient) was evaluated in female CRL:(WI) BR rats, according to the acute toxic class method (OECD 423).

The test substance was administered in a single oral dose by gavage, rats were observed for 14 days post-administration and necropsies were performed on all animals. The first group of 3 females were dosed with 300 mg active ingredient/kg bw. All 3 rats died within 6 hours of dosing, therefore the second group of 3 females were dosed with 50 mg active ingredient/kg bw. No mortalities occurred, so a confirmatory group of 3 females were also dosed with 50 mg active ingredient/kg bw.

Clinical signs observed in all 3 animals administered 300 mg/kg were decreased activity, hunched posture, dyspnoea, piloerection, soft faeces and death. No mortalities occurred in the animals administered 50 mg/kg, and no clinical signs of toxicity were observed in these animals.

Necropsy of the animals dosed with 300 mg/kg revealed dark/brown discolouration of the oesophagus, stomach and/or digestive content, as well as dark/brown discolouration of the lungs associated with yellow liquid in the trachea or nasal cavity. There were no abnormal findings in the 50 mg/kg animals.

The acute oral LD50 of dichromium tris(chromate) was between 50 and 300 mg active ingredient/kg bw in female rats. Based on the results of the study, Dichromium tris(chromate) should be classified as Toxicity Category 3 according to UN GHS and Regulation (EC) No 1272/2008.