Chromium tris((2-ethylhexanoate)

Endpoint summary

Description of key information

ORAL ROUTE

According to the key study (Richeux, 2017) conducted in accordance with the O.E.C.D. test guideline n° 423, the LD50 of

the test item is higher than 2000 mg/kg body weight by oral route in the rat.

DERMAL ROUTE

According to the key study (Richeux, 2017) conducted in accordance with the O.E.C.D. test guideline n°402, the LD50 of

the test item is higher than 2000 mg/kg body weight by dermal route in the rat.

INHALATION ROUTE

The pure substance is a paste. As a consequence, the study need not be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and the possibility of exposure to aerosols, particles or droplets of an inhalable size.

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:

2017-01-20 to 2017-03-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

dated December 17th, 2001

Deviations:

yes

Remarks:

Environmental parameters : relative humidity lower than 30% (minimum = 18%) and temperature higher than 25°C (maximum= 29°C) reported - these deviations are considered without impact on the conclusion of the study.

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Remarks:

dated October 23rd, 2015

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER LABS, Le Genest St Isle, France
- Age at study initiation: 8 weeks old at the beginning of the study
- Weight at study initiation: 189 - 212 g
- Fasting period before study: Food was removed o day 1 and then redistributed 4 hours after adminsitration of the test item.
- Housing: Animals were housed by group of three in solid-bottomed clear plycarbonate cages with a stainless steel mesh lid. Each cage contains sawdust and was installed in conventional air conditioned animal husbandry
- Diet (ad libitum): Envigo - 2016
- Water: ad libitum
- Acclimatization period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 25 °C
- Relative humidity: 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12
- Rate of air exchange : at least 10 changes per hour

Route of administration:

oral: gavage

Vehicle:

other: ethanol in olive oil (2/8, w/w)

Details on oral exposure:

In the first step of the study, 2.9515 g of the test item were weighted and the formulation ethanol (2.36 g) / olive oil (9.45 g) was added to obtain a preparation weighing 14.76 g.
In the second step of the study, 2.1164 g of the test item were weighted and the formulation ethanol (1.69 g) / olive oil (6.77 g) was added to obtain a preparation weighing 10.58 g.
The preparations were stirred magnetically and by vortex to obtain green homogeneous emulsions just before the administration.
Each preparation was administered under a volume of 10 mL/kg body weight using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:

2000 mg/kg

No. of animals per sex per dose:

2000 mg/kg: 3 + 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Daily examination: Systematic examination were carried out to identify any behavioural or toxic effects on the major physiological functions during 14 days following the administration of the test item. These observations were compared to historical control data. Clinical observations and mortality were recorded every day for 14 days.
- Periodical examinations: The animals were weighed on D0 (just before administering the test item) then on D2, D7 and D14. Weight changes were calculated and recorded.
- Examination at the end of the test: On D14, the animals were anesthetised with sodium pentobarbital (Dolethal). Macroscopic observations were entered on individual autopsy sheets. Only those organs likely to be modified in cases of acute toxicity were examined. No organ was removed and preserved in view to microscopic examinations.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured during the study.

Clinical signs:

other: other: No clinical signs related to the administration of the test item were observed during the study.

Gross pathology:

The macrosscopic examination of the animals at the end of the study did not reveal treatment related changes.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item is higher than 2000 mg/kg body weight by oral route in the rat.
The test item does not have to be classified in accordance with the Regulation EC n° 1272/2008 on classification, labelling and packaging of substances and mixtures. No signal word or hazard statement is required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 ng/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017-01-20 to 2017-03-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 24 February 1987

Deviations:

yes

Remarks:

Environmental parameters : relative humidity lower than 30% (minimum = 18%) and temperature higher than 25°C (maximum = 29°C) reported - these deviations are considered without impact on the conclusion of the study.

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

dated 30 May 2008

GLP compliance:

yes (incl. QA statement)

Remarks:

Certificate dated 23 Cctober 2015

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Janvier Labs, Le Genest St Isle, France
- Age at study initiation: approximately 7 (male) to 8 (female) weeks
- Weight at study initiation: 200 to 298 g prior to dosing
- Housing: During the treatment the animals were kept in individual cages. IN accordance with the principles of animal welfare, the animal were put into threir cage by 5, on day 1. The rats were kept in bottomed clear polycarbonate cages with a stainles seelt mesh lid.
- Diet (ad libitum): ENVIGO 2016
- Water (ad libitum): domestic quality potable water
- Acclimation period: at least 5 days prior to the start of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled to remain within target range of 19°C to 25°C
- Humidity (%): controlled to remain within target range of 30% to 70%
- Air changes (per hr): at least 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 h/12h

Type of coverage:

other: topical application under non occlusive porous gauze dressing, gauze dressing removed after 24-hour exposure period

Vehicle:

other: ethanol in liquid paraffin (2/8, w/w)

Details on dermal exposure:

Approximately 24 hours before the treatment, fur was removed from the dorsal area of the trunk of the tes animals by clipping. At leat 10% of the ody surface was clear for the application of the test item.
Ethanol in liquid paraffin (2/8, w/w) was chosen as it produced the most suitable formulation at the requested concentration.
6.4147 g of the test item was weighted and 25.66g of the vehicle was added to obtain a preparation weighing of 3207 g. The preparation was stirred manually and by vortex to obtai a green homogeneous emulsion just before the administration.
Animals from treated group received by topical application, under non-occlusive porous gauze dressing (50 mm * 50 mm non woven swab of 4-layer patch from MEDISTOCK) secured in position with a strip of surgical adhesive tape (50 mm wides hypoallergenic micropore adhesive tapefrom 3M), an effective dose of 2000 mg/Kg body weight administered under a volume of 10 mL/Kg body weight, during 24 hours. After 24-hour exposure period, the gauze dressings were removed.

Duration of exposure:

24-hour exposure period

Doses:

2000 mg/kg bodyweight

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 after dosing
* Daily examination: Systemic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions during 14 days following the administration of the test item. This examination focuses particularly on a list of symptoms, recorded as present of absent on the observation sheet. These observations were compared to historical data. Observations and a mortality report were carried out every day for 14 days.
* Periodical examinations: The animal were weighed on day 0 (just before adminstering the test item) then on day 2, day 7 and day 14. Wieght changes were calculated and recorded.
* Examination at the end of the test: On day 14, the animals were anesthesised with sodium pentoarbital (Dolethal). Macroscopic observations were entered on individual autopsy sheets. Only those organs likely to be modified in cases of acute toxicity were examined. Those presenting macroscopic anomalies can be removed and preserved in view to microscopic examinations.

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occured during the study.

Clinical signs:

other: other: Neither cutaneous reactions, nor systemic clinical signs related to the administration of the test item were observed. Green coloratino was noted on the areas at 24 and 48 hours post dose.

Gross pathology:

The macroscopic examination of the animals at the end of the study did not reveal treatment-related changes.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test item is higher than 2000 mg/kg body weight by dermal route in the rat.
The test item does not have to be classified in accordance with the Regulation EC n° 1272/2008 on classification, labelling and packaging of substances and mixtures. No signal word or hazard statement is required.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Value:

> 2 000 ng/kg bw

Justification for classification or non-classification

The test item does not have to be classified in accordance with the Regulation EC n° 1272/2008 on classification, labelling and packaging of substances and mixtures. No signal word or hazard statement is required.