Rhodium

Endpoint summary

Description of key information

No relevant data (human, laboratory animal or in vitro) were identified for rhodium metal.

 

Substance is considered to fall within the scope of the read-across category 'Rhodium and dirhodium trioxide'. Rhodium trioxide did not reveal any skin sensitising properties when tested in a local lymph node assay: BrdU-ELISA assay (OECD442B, GLP compliant). Based on this experimental evidence, rhodium is considered to be void of any skin sensitising properties.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 January 2019 - 26 February 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 442B (Skin Sensitization: Local Lymph Node Assay: BrdU-ELISA)

Version / remarks:

adopted 25 June 2018

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Commission Regulation (EU) No. 640/2012 of 6 July 2012 amending Regulation (EC) No. 440/2008; EC method B.51: Skin Sensitisation, Local Lymph Node Assay: BrdU-ELISA.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA): BrdU-ELISA

Specific details on test material used for the study:

Rh content = 100% Rh2O3 x 0.67 H2O or 95.5% Rh2O3 (based on Rh content of 77.4 wt%)

Species:

mouse

Strain:

CBA:JN

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Janvier Labs, CS 4105 Le Genest, Saint Isle, Saint Berthevin, Cedex 53941, France
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at main study initiation: approx 10 weeks
- Weight at study initiation: 19-25 g
- Housing: Before application the animals were housed in groups of 5 animals in MAKROLON cages (type III) with a basal surface of approximately 39 cm x 23 cm and a height of approximately 15 cm. After application the animals were housed singly in order to prevent them licking off the test item from the ears of the other animals. Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material. The cages were changed and cleaned once a week.
- Diet: Commercial diet ssniff® R/M-H V1534 (sourced from ssniff Spezialdiäten GmbH, 59494 Soest, Germany) was offered ad libitum. Food residue was removed.
- Water: Tap water was offered ad libitum.
- Acclimation period: At least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3 (maximum range)
- Humidity (%): 55 ± 15 (maximum range)
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12 (about 150 lux at approx 1.5m room height)
- in-life date: 21-26 February 2019

Vehicle:

propylene glycol

Remarks:

Acetone/olive oil (4:1, v/v) and N,N-dimethylformamide did not provide suitable suspensions/solutions at higher concentrations. The application formulations were continuously stirred with a magnetic stirrer throughout the entire administration procedure.

Concentration:

Pre-screening test: 10, 25, 50 and 75% (w/w)
Main study: 0, 5, 10 and 25% (w/w)

No. of animals per dose:

5

Details on study design:

PRE-SCREEN (RANGE-FINDING) TESTS:
- Compound solubility: In a preliminary solubility assessment, propylene glycol was selected as it is recommended by the OECD guideline and provided suitable solutions of the test item both for administration and adherence to the mouse ear of such high concentrations. Doses were selected based on the recommendations in the OECD guideline, adjusted to the physical appearance of the test item as solid, with 75, 50, 25 and 10% (w/w). A 25% concentration was the highest concentration of dirhodium trioxide in propylene glycol to obtain an applicable solution.
- Test item adminstration: The test item formulations were administered to the dorsum of both ears of each animal at an application volume of 25 µL/ear.
- Systemic toxicity and Irritation: All mice were observed daily for any clinical signs of systemic toxicity or local irritation at the application site. Body weights were recorded pre-test and prior to termination (Day 6). Both ears of each mouse were observed for erythema and scored on a 0-4 scale (0: no erythema; 1: very slight erythema (barely perceptible); 2: well-defined erythema; 3: moderate to severe erythema; 4: severe erythema (beet redness) to eschar formation preventing grading of erythema).
The following clinical observation would indicate systemic toxicity: changes in nervous system function (e.g. pilo-erection, ataxia, tremors, and convulsions); changes in behaviour (e.g. aggressiveness, change in grooming activity, marked change in activity level); changes in respiratory patterns (i.e. changes in frequency and intensity of breathing such as dyspnoea, gasping, and rales), and changes in food and water consumption. In addition, signs of lethargy and/or unresponsiveness and any clinical signs of more than slight or momentary pain and distress, or a >5% reduction in body weight from Day 1 to Day 6 and mortality would be considered in the evaluation. Moribund animals or animals showing signs of severe pain and distress would have been humanely killed.
- Ear thickness measurements: Ear thickness measurements were taken using a thickness gauge on Day 1 (pre-dose), Day 3 (approximately 48 hours after the first dose), and Day 6. Additionally, on Day 6, ear thickness was determined by ear punch weight determinations, which was performed after the animals were humanely killed. Excessive local irritation is indicated by an erythema score ≥3 and/or ear thickness increase of ≥25% on any day of measurement. The highest dose selected for the main LLNA: BrdU-ELISA study was the next lower dose in the pre-screen concentration series that doses not induce systemic toxicity and/or excessive local skin irritation.

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local lymph node assay BrdU-ELISA
- Criteria used to consider a positive response: Results of each treatment group are expressed as the mean SI. The SI is derived by dividing the mean BrdU luminescence/mouse within each test item group and the positive control group by the mean BrdU luminescence labelling index for the solvent/vehicle control group. The average SI for the vehicle control is then one.
SI = (Mean test item or positive control group)/(Mean negative control group)
The decision process regards a result as positive when SI ≥ 1.6. However, the strength of the dose-response relationship, the statistical significance and the consistency of the vehicle and positive control responses would also be used when determining whether a borderline result (i.e. SI value between 1.6 and 1.9) is declared positive.
For a borderline positive response between an SI of 1.6 and 1.9, it may be necessary to consider additional information such as dose-response relationship, evidence of systemic toxicity or excessive irritation, and where appropriate, statistical significance together with SI values to confirm that such results are positives. Consideration would be also given to various properties of the test item, including whether it has a structural relationship to known skin sensitizers, whether it causes excessive skin irritation in the mouse, and the nature of the dose-response observation.
In addition, the average ear weights per group and the average ear thickness per group were compared to the vehicle control group as an indication for possible irritating properties.

TREATMENT PREPARATION AND ADMINISTRATION: g
•Day 1: The weight of each animal was identified and recorded. Ear thickness of left and right ear of each animal was recorded. Any clinical observation was recorded. 25 µL of the appropriate dilution of the test item, the negative control, the positive control or the vehicle of the positive control were applied to the dorsum of each ear.
•Days 2 and 3: The application procedure carried out on day 1 was repeated.
•Day 4: No treatment.
•Day 5: 0.5 mL (5 mg/mouse) of BrdU (10 mg/mL) solution was injected inter-peritoneally.
•Day 6: The weight of each animal and any clinical observation were recorded. Approximately 24 hours after BrdU injection the animals were humanely killed. The draining auricular lymph nodes from each mouse ear were excised and processed separately in phosphate buffered saline (PBS) for each animal. To further monitor the local skin response in the study, additional parameters such as scoring of ear erythema and ear thickness measurements (obtained by using a thickness gauge and ear punch weight determinations at necropsy) were carried out.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

eugenol (CAS No 97-53-0)

Statistics:

As no concentration-related increased values were observed, no statistical evaluation was carried out.
Comparison to negative control was carried out using Student's t-test.

Positive control results:

Two positive control groups (treated with 25% solutions (v/v) of either α-hexyl cinnamic aldehyde or Eugenol in acetone / olive oil (4 : 1 v/v)) and one group with the vehicle of the positive controls were employed. Treatment with the positive control items α-hexyl cinnamic aldehyde or Eugenol caused the expected increases in the BrdU labelling index and increased ear weight, compared to the negative controls, which reflects a positive sensitisation response. The Stimulation Index of both positive controls was greater than the threshold value of 1.6 over the positive control vehicle group and therefore, the study can be regarded as valid.

Parameter:

SI

Value:

< 1.6

Test group / Remarks:

25%

Remarks on result:

other: Treatment with the test item at concentrations of 5, 10 and 25% (w/w) revealed no dose-related increase in the BrdU labelling index (SI values of 0.830, 0.879 and 1.022, respectively), and none of the SI values exceeded the threshold of 1.6.

Parameter:

SI

Value:

< 1.6

Test group / Remarks:

10%

Remarks on result:

other: Treatment with the test item at concentrations of 5, 10 and 25% (w/w) revealed no dose-related increase in the BrdU labelling index (SI values of 0.830, 0.879 and 1.022, respectively), and none of the SI values exceeded the threshold of 1.6.

Parameter:

SI

Value:

< 1.6

Test group / Remarks:

5%

Remarks on result:

other: Treatment with the test item at concentrations of 5, 10 and 25% (w/w) revealed no dose-related increase in the BrdU labelling index (SI values of 0.830, 0.879 and 1.022, respecitvely), and none of the SI values exceeded the threshold of 1.6.

In the preliminary test of a previous study with Dirhodium trioxide employing two animals per dose, concentrations of 5%, 10% or 25% (w/w) were used. No signs of irritation (erythema score ≥ 3 and/or an ear thickness increase of more than 25%) were noted.

Parameter	Negative control	5% test item	10% test item	25% test tem	Positive control 1 (HCA)	Positive Control 2 (Eugenol)		Vehicle of positive controls
BrdU labelling index	3.063	2.544	2.694	3.132	7.272*	7.111*		4.208
Stimulation index (SI)	1.000	0.830	0.879	1.022	1.728*	1.690*		1.000
Ear weight (mg)	14.7	15.2	15.0	15.6	17.9	15.7		14.4
Difference of ear thickness (mm, TD6)	223.0	225.0	220.0	226.0	248.0	225.0		221.0

  * statistically significant increase compared to negative control at p ≤ 0.01

The stimulation indices of the test item treated groups calculated for the BrdU labelling index did not exceed the threshold value of 1.6. Hence, the test item is classified as not skin sensitising.

There was no death and no systemic clinical signs or effects on body weights were observed during the study.The ear weight (punch biopsies) and the difference of ear thickness on test day 3 and test day 6 compared to the vehicle control were not or only slightly increased, i.e. no skin irritating properties were noted.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the present test conditions, the test item did not reveal any skin sensitising properties in the local lymph node assay: BrdU-ELISA.

Executive summary:

The skin sensitising potential of dirhodium trioxide has been assessed in a GLP mouse local lymph node assay (LLNA): BrdU-ELISA, conducted according to OECD Test Guideline 442B. Following a preliminary range-finding study to assess irritancy, female mice CBA/JN mice (5/group) were treated topically with 0, 5, 10 and 25% test item (in propylene glycol) on three consecutive days. There was no treatment on test days 4, 5 and 6. On day 6, cell proliferation in the local lymph nodes was measured by incorporation of injected 5-bromo-2-deoxyuridine (BrdU) using ELISA. The cell proliferation in the local lymph nodes was determined by measuring the BrdU content with BrdU-ELISA and the values obtained were used to calculate Stimulation Indices (SI).

The stimulation indices of the test item treated groups calculated for the BrdU labelling index did not exceed the threshold value of 1.6. Hence, there was no clear evidence of cell proliferation and the test item is classified as not skin sensitising.

There were no deaths and no systemic clinical signs or effects on body weights were observed during the study. The ear weight (punch biopsies) and the difference of ear thickness on test day 3 and test day 6 compared to the vehicle control were not or only slightly increased, i.e. no skin irritating properties were noted.

Treatment with the positive control items α-hexyl cinnamic aldehyde or Eugenol caused the expected increases in the BrdU labelling index. Therefore, the study can be regarded as valid.

In conclusion, under the present test conditions, the test item dirhodium trioxide did not reveal any skin sensitising properties in the local lymph node assay:BrdU-ELISA.

Reference 2

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

18 January 2019 - 26 February 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Substance is considered to fall within the scope of the read-across category 'Rhodium and dirhodium trioxide'.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 442B (Skin Sensitization: Local Lymph Node Assay: BrdU-ELISA)

Version / remarks:

adopted 25 June 2018

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Commission Regulation (EU) No. 640/2012 of 6 July 2012 amending Regulation (EC) No. 440/2008; EC method B.51: Skin Sensitisation, Local Lymph Node Assay: BrdU-ELISA.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA): BrdU-ELISA

Species:

mouse

Strain:

CBA:JN

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Janvier Labs, CS 4105 Le Genest, Saint Isle, Saint Berthevin, Cedex 53941, France
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at main study initiation: approx 10 weeks
- Weight at study initiation: 19-25 g
- Housing: Before application the animals were housed in groups of 5 animals in MAKROLON cages (type III) with a basal surface of approximately 39 cm x 23 cm and a height of approximately 15 cm. After application the animals were housed singly in order to prevent them licking off the test item from the ears of the other animals. Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material. The cages were changed and cleaned once a week.
- Diet: Commercial diet ssniff® R/M-H V1534 (sourced from ssniff Spezialdiäten GmbH, 59494 Soest, Germany) was offered ad libitum. Food residue was removed.
- Water: Tap water was offered ad libitum.
- Acclimation period: At least 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3 (maximum range)
- Humidity (%): 55 ± 15 (maximum range)
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12 (about 150 lux at approx 1.5m room height)
- in-life date: 21-26 February 2019

Vehicle:

propylene glycol

Remarks:

Acetone/olive oil (4:1, v/v) and N,N-dimethylformamide did not provide suitable suspensions/solutions at higher concentrations. The application formulations were continuously stirred with a magnetic stirrer throughout the entire administration procedure.

Concentration:

Pre-screening test: 10, 25, 50 and 75% (w/w)
Main study: 0, 5, 10 and 25% (w/w)

No. of animals per dose:

5

Details on study design:

PRE-SCREEN (RANGE-FINDING) TESTS:
- Compound solubility: In a preliminary solubility assessment, propylene glycol was selected as it is recommended by the OECD guideline and provided suitable solutions of the test item both for administration and adherence to the mouse ear of such high concentrations. Doses were selected based on the recommendations in the OECD guideline, adjusted to the physical appearance of the test item as solid, with 75, 50, 25 and 10% (w/w). A 25% concentration was the highest concentration of dirhodium trioxide in propylene glycol to obtain an applicable solution.
- Test item adminstration: The test item formulations were administered to the dorsum of both ears of each animal at an application volume of 25 µL/ear.
- Systemic toxicity and Irritation: All mice were observed daily for any clinical signs of systemic toxicity or local irritation at the application site. Body weights were recorded pre-test and prior to termination (Day 6). Both ears of each mouse were observed for erythema and scored on a 0-4 scale (0: no erythema; 1: very slight erythema (barely perceptible); 2: well-defined erythema; 3: moderate to severe erythema; 4: severe erythema (beet redness) to eschar formation preventing grading of erythema).
The following clinical observation would indicate systemic toxicity: changes in nervous system function (e.g. pilo-erection, ataxia, tremors, and convulsions); changes in behaviour (e.g. aggressiveness, change in grooming activity, marked change in activity level); changes in respiratory patterns (i.e. changes in frequency and intensity of breathing such as dyspnoea, gasping, and rales), and changes in food and water consumption. In addition, signs of lethargy and/or unresponsiveness and any clinical signs of more than slight or momentary pain and distress, or a >5% reduction in body weight from Day 1 to Day 6 and mortality would be considered in the evaluation. Moribund animals or animals showing signs of severe pain and distress would have been humanely killed.
- Ear thickness measurements: Ear thickness measurements were taken using a thickness gauge on Day 1 (pre-dose), Day 3 (approximately 48 hours after the first dose), and Day 6. Additionally, on Day 6, ear thickness was determined by ear punch weight determinations, which was performed after the animals were humanely killed. Excessive local irritation is indicated by an erythema score ≥3 and/or ear thickness increase of ≥25% on any day of measurement. The highest dose selected for the main LLNA: BrdU-ELISA study was the next lower dose in the pre-screen concentration series that doses not induce systemic toxicity and/or excessive local skin irritation.

MAIN STUDY

ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local lymph node assay BrdU-ELISA
- Criteria used to consider a positive response: Results of each treatment group are expressed as the mean SI. The SI is derived by dividing the mean BrdU luminescence/mouse within each test item group and the positive control group by the mean BrdU luminescence labelling index for the solvent/vehicle control group. The average SI for the vehicle control is then one.
SI = (Mean test item or positive control group)/(Mean negative control group)
The decision process regards a result as positive when SI ≥ 1.6. However, the strength of the dose-response relationship, the statistical significance and the consistency of the vehicle and positive control responses would also be used when determining whether a borderline result (i.e. SI value between 1.6 and 1.9) is declared positive.
For a borderline positive response between an SI of 1.6 and 1.9, it may be necessary to consider additional information such as dose-response relationship, evidence of systemic toxicity or excessive irritation, and where appropriate, statistical significance together with SI values to confirm that such results are positives. Consideration would be also given to various properties of the test item, including whether it has a structural relationship to known skin sensitizers, whether it causes excessive skin irritation in the mouse, and the nature of the dose-response observation.
In addition, the average ear weights per group and the average ear thickness per group were compared to the vehicle control group as an indication for possible irritating properties.

TREATMENT PREPARATION AND ADMINISTRATION: g
•Day 1: The weight of each animal was identified and recorded. Ear thickness of left and right ear of each animal was recorded. Any clinical observation was recorded. 25 µL of the appropriate dilution of the test item, the negative control, the positive control or the vehicle of the positive control were applied to the dorsum of each ear.
•Days 2 and 3: The application procedure carried out on day 1 was repeated.
•Day 4: No treatment.
•Day 5: 0.5 mL (5 mg/mouse) of BrdU (10 mg/mL) solution was injected inter-peritoneally.
•Day 6: The weight of each animal and any clinical observation were recorded. Approximately 24 hours after BrdU injection the animals were humanely killed. The draining auricular lymph nodes from each mouse ear were excised and processed separately in phosphate buffered saline (PBS) for each animal. To further monitor the local skin response in the study, additional parameters such as scoring of ear erythema and ear thickness measurements (obtained by using a thickness gauge and ear punch weight determinations at necropsy) were carried out.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

eugenol (CAS No 97-53-0)

Statistics:

As no concentration-related increased values were observed, no statistical evaluation was carried out.
Comparison to negative control was carried out using Student's t-test.

Positive control results:

Two positive control groups (treated with 25% solutions (v/v) of either α-hexyl cinnamic aldehyde or Eugenol in acetone / olive oil (4 : 1 v/v)) and one group with the vehicle of the positive controls were employed. Treatment with the positive control items α-hexyl cinnamic aldehyde or Eugenol caused the expected increases in the BrdU labelling index and increased ear weight, compared to the negative controls, which reflects a positive sensitisation response. The Stimulation Index of both positive controls was greater than the threshold value of 1.6 over the positive control vehicle group and therefore, the study can be regarded as valid.

Parameter:

SI

Value:

< 1.6

Test group / Remarks:

25%

Remarks on result:

other: Treatment with the test item at concentrations of 5, 10 and 25% (w/w) revealed no dose-related increase in the BrdU labelling index (SI values of 0.830, 0.879 and 1.022, respectively), and none of the SI values exceeded the threshold of 1.6.

Parameter:

SI

Value:

< 1.6

Test group / Remarks:

10%

Remarks on result:

other: Treatment with the test item at concentrations of 5, 10 and 25% (w/w) revealed no dose-related increase in the BrdU labelling index (SI values of 0.830, 0.879 and 1.022, respectively), and none of the SI values exceeded the threshold of 1.6.

Parameter:

SI

Value:

< 1.6

Test group / Remarks:

5%

Remarks on result:

other: Treatment with the test item at concentrations of 5, 10 and 25% (w/w) revealed no dose-related increase in the BrdU labelling index (SI values of 0.830, 0.879 and 1.022, respectively), and none of the SI values exceeded the threshold of 1.6.

In the preliminary test of a previous study with Dirhodium trioxide employing two animals per dose, concentrations of 5%, 10% or 25% (w/w) were used. No signs of irritation (erythema score ≥ 3 and/or an ear thickness increase of more than 25%) were noted.

Parameter	Negative control	5% test item	10% test item	25% test tem	Positive control 1 (HCA)	Positive Control 2 (Eugenol)		Vehicle of positive controls
BrdU labelling index	3.063	2.544	2.694	3.132	7.272*	7.111*		4.208
Stimulation index (SI)	1.000	0.830	0.879	1.022	1.728*	1.690*		1.000
Ear weight (mg)	14.7	15.2	15.0	15.6	17.9	15.7		14.4
Difference of ear thickness (mm, TD6)	223.0	225.0	220.0	226.0	248.0	225.0		221.0

  * statistically significant increase compared to negative control at p ≤ 0.01

The stimulation indices of the test item treated groups calculated for the BrdU labelling index did not exceed the threshold value of 1.6. Hence, the test item is classified as not skin sensitising.

There was no death and no systemic clinical signs or effects on body weights were observed during the study.The ear weight (punch biopsies) and the difference of ear thickness on test day 3 and test day 6 compared to the vehicle control were not or only slightly increased, i.e. no skin irritating properties were noted.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the present test conditions, the test item did not reveal any skin sensitising properties in the local lymph node assay: BrdU-ELISA.

Executive summary:

The skin sensitising potential of dirhodium trioxide has been assessed in a GLP mouse local lymph node assay (LLNA): BrdU-ELISA, conducted according to OECD Test Guideline 442B. Following a preliminary range-finding study to assess irritancy, female mice CBA/JN mice (5/group) were treated topically with 0, 5, 10 and 25% test item (in propylene glycol) on three consecutive days. There was no treatment on test days 4, 5 and 6. On day 6, cell proliferation in the local lymph nodes was measured by incorporation of injected 5-bromo-2-deoxyuridine (BrdU) using ELISA. The cell proliferation in the local lymph nodes was determined by measuring the BrdU content with BrdU-ELISA and the values obtained were used to calculate Stimulation Indices (SI).

The stimulation indices of the test item treated groups calculated for the BrdU labelling index did not exceed the threshold value of 1.6. Hence, there was no clear evidence of cell proliferation and the test item is classified as not skin sensitising.

There were no deaths and no systemic clinical signs or effects on body weights were observed during the study. The ear weight (punch biopsies) and the difference of ear thickness on test day 3 and test day 6 compared to the vehicle control were not or only slightly increased, i.e. no skin irritating properties were noted.

Treatment with the positive control items α-hexyl cinnamic aldehyde or Eugenol caused the expected increases in the BrdU labelling index. Therefore, the study can be regarded as valid.

In conclusion, under the present test conditions, the test item dirhodium trioxide did not reveal any skin sensitising properties in the local lymph node assay:BrdU-ELISA.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No relevant data (human, laboratory animal or in vitro) were identified for rhodium metal.

Substance is considered to fall within the scope of the read-across category 'Rhodium and dirhodium trioxide'. Rhodium trioxide did not reveal any skin sensitising properties when tested in a local lymph node assay: BrdU-ELISA assay (OECD442B, GLP compliant). Based on this experimental evidence, rhodium is considered to be void of any skin sensitising properties.

Biovailability considerations provide further good support for the conclusion that rhodium is not associated with a concern for skin sensitisation. Rhodium is an inorganic solid (Tremain and Atwal, 2011) and is considered to be non-bioavailable following dermal exposure, and not bioavailable to a significant extent to test cells (in vitro), and thus unable to induce skin sensitisation. Transformation/dissolution testing indicates that rhodium is insoluble, based on a measured metal concentration of 0.00 μg/L in aqueous environmental media following substance loading at 10 and 100 mg/L (for 7 days each) and also at 1 mg/L (in a 28-day test) (Skeaff and Beaudoin, 2011). Further, in bio-elution tests (which are likely to provide more realistic insights into physiological solubility and thus systemic availability) with rhodium sponge, the proportion of metal release (from total metal content) in simulated dermal fluid was nominally insignificant: 0.00003 and 0.00007% after 24 and 168 hours, respectively (Rodriguez, 2012). This lack of solubility/availability indicates that the substance is not dermally bioavailable, given that such bioavailability is constrained by the extent of dissolution in dermal fluid. Since a compound is required to be dermally bioavailable in order to induce skin sensitisation, rhodium is considered incapable of inducing skin sensitisation. Consequently, no further testing for skin sensitisation is considered justified.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

No respiratory tract sensitisation data are available. A new study was not conducted as no standard and validated test method is available and it is not a REACH Standard Information Requirement. Further, rhodium is not expected to reach the lungs in appreciable quantities (based on respiratory tract deposition modelling data). Thus, inhalation will not be a significant route of exposure.

Justification for classification or non-classification

No skin or respiratory tract sensitisation data are available for rhodium. However the substance is considered to fall within the scope of the read-across category 'Rhodium and dirhodium trioxide'. Rhodium trioxide did not reveal any skin sensitising properties when tested in a local lymph node assay: BrdU-ELISA assay (OECD442B, GLP compliant). Based on this data together with bioavailability arguments, there is no evidence to classify rhodium as a skin or respiratory sensitiser according to EU CLP criteria (EC 1272/2008).