Triammonium hexachlororhodate

Endpoint summary

Description of key information

In a guideline study, to GLP, ammonium hexachlororhodate (III) (0.5 g) was applied to the shaved, intact skin of three rabbits (4-hr semi-occluded) and irritant reactions were assessed 1, 24, 48, and 72 hr after patch removal. No evidence of irritation was apparent and the primary irritation index was 0. No corrosive effects or evidence of systemic toxicity were reported (Jones, 1989a).
In a guideline study, to GLP, instillation of ammonium hexachlororhodate (III) (0.1 mL; 92 mg) to the eye of a single male rabbit caused severe irritation that required sacrifice after 48 hr. The primary irritation index was 65 (out of 110) at this time point (Jones, 1989b).
No relevant respiratory tract irritation data were identified.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31 August 1989 to 03 September 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK.
- Age at study initiation: approximately 12-16 weeks
- Weight at study initiation: 2.52-2.70 kg
- Housing: Individually in suspended metal cages
- Diet (e.g. ad libitum): ad libitum “Rabbit Diet” from Preston Farmers Limited, New Leake, Boston, Lincolnshire, UK
- Water (e.g. ad libitum): ad libitum mains drinking water
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-20
- Humidity (%): 62-68 [relative]
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

Three males

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm [6.25 cm2]
- Type of wrap if used: material was placed under a gauze patch secured in place with a strip of surgical adhesive tape (BLENDERM, approximate size 2.5x4.0 cm). An elasticated corset (TUBIGRIP) was applied over this, around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes (gentle swabbing with cotton wool soaked in distilled water)
- Time after start of exposure: 4 hours

SCORING SYSTEM: Erythema and eschar formation, and oedema formation, were assessed approximately one, 24, 48 and 72 hours after removal of the patches. A primary irritation index was calculated by adding all of the 24- and 72-hour readings (scored using the Draize scale, see “Any other information”) and dividing by the total number of observations (i.e. six). According to the study report, a primary irritation index of zero indicates a “non-irritant”; one of >0-2 indicates a “mild irritant”; one of >2-5 indicates a moderate irritant and one of >5-8 indicates a severe irritant.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24 and 72 hours after patch removal

Score:

0

Max. score:

8

Reversibility:

other: not applicable

Remarks on result:

other: see below

Irritant / corrosive response data:

No evidence of skin irritation. See attchment.

Yellow-orange staining of the skin caused by the test material was observed. Nevertheless, it was reported that this did not prevent accurate assessment of the skin responses, particularly erythema and eschar formation, for which scores of 0 for all rabbits at all time points were recorded. The study was terminated 72 hours after removal of the patches because of the lack of adverse skin reactions.

Other effects:

No other effects or systemic toxicity were reported.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a guideline study, to GLP, ammonium hexachlororhodate produced a primary irritation index of 0 following a 4-hr semi-occlusive application (0.5 g) to the skin of three rabbits. No corrosive effects or evidence of systemic toxicity were reported.

Executive summary:

In an OECD Test Guideline 404 study, ammonium hexachlororhodate was investigated for irritant (and corrosive) effects following a 4-hr (semi-occluded) application (0.5 g) to the shaved, intact skin of three male White Russian rabbits. The test sites were quantitatively and qualitatively assessed for erythema (and eschar) formation and oedema 1, 24, 48 and 72 hrs after removal of the patches.

No erythema or eschar formation, or oedema, was seen at any time point in any animal. A primary dermal irritation index of 0 was calculated using the observations at 24 and 72 hr. Yellow-orange staining of the skin caused by the test material was observed. Nevertheless, it was reported that this did not prevent accurate assessment of the skin responses. No other effects or systemic toxicity were reported.

Based on the results of this study, no classification for skin irritation is required according to EU CLP criteria (EC 1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04 September 1989 to 06 September 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, to GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

(minor (1 deg C) deviation from recommended guideline temperature of animal cage; unlikely to be of significant magnitude to affect test)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK.
- Age at study initiation: “approximately” between 12 and 16 weeks
- Weight at study initiation: 3.06 kg
- Housing: solitary, in a suspended metal cage
- Diet (e.g. ad libitum): ad libitum “Rabbit Diet” from Preston Farmers Limited, New Leake, Boston, Lincolnshire, UK
- Water (e.g. ad libitum): ad libitum mains drinking water
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-20
- Humidity (%): 60-68 [relative]
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Vehicle:

unchanged (no vehicle)

Controls:

other: second eye of treated animal served as concurrent control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml (approximately 92 mg)

Duration of treatment / exposure:

Eyelids were briefly closed for about one second immediately after application and there was no subsequent washing to remove the test material.

Observation period (in vivo):

Severe ocular reaction resulted in humane sacrifice of the animal 48 hours after application of the test material.

Number of animals or in vitro replicates:

One male

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eye was not rinsed.

SCORING SYSTEM: Assessment of damage/irritation was made quantitatively and qualitatively using the Draize scale (see Attachment) at 1, 24 and 48 hours after application of the test substance into the eye. The ocular irritation potential was calculated from this assessment using a modified version of the Kay & Calandra system (see Attachment).

TOOL USED TO ASSESS SCORE: standard ophthalmoscope

Irritation parameter:

cornea opacity score

Basis:

other: single (only) animal

Time point:

other: 1 hr

Score:

0

Reversibility:

other: not applicable

Irritation parameter:

cornea opacity score

Basis:

other: single (only) animal

Time point:

other: 24 hr

Score:

20

Reversibility:

not reversible

Irritation parameter:

cornea opacity score

Basis:

other: single (only) animal

Time point:

other: 48 hr

Score:

40

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

other: single (only) animal

Time point:

other: 1 hr, 24 hr and 48 hr

Score:

5

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

other: single (only) animal

Time point:

other: 1 hr

Score:

12

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

other: single (only) animal

Time point:

other: 24 hr

Score:

18

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

other: single (only) animal

Time point:

other: 48 hr

Score:

20

Reversibility:

not reversible

Remarks on result:

other: Sloughing of the conjunctival membrane was recorded.

Irritation parameter:

overall irritation score

Basis:

other: single (only) animal

Time point:

other: 1 hr

Score:

17

Reversibility:

not reversible

Irritation parameter:

overall irritation score

Basis:

other: single (only) animal

Time point:

other: 24 hr

Score:

43

Reversibility:

not reversible

Irritation parameter:

overall irritation score

Basis:

other: single (only) animal

Time point:

other: 48 hr

Score:

65

Reversibility:

not reversible

Remarks on result:

other: This was the maximum total score reached before the animal was humanely sacrificed.

Irritant / corrosive response data:

Iridial inflammation and moderate conjunctival irritation were seen one hour after application of the test material. Within 48 hours there was persistent iridial inflammation, moderate corneal opacity over most of the cornea, and severe conjunctival irritation (redness, swelling and discharge of the conjunctivae reached a maximum score on the Draize scale and sloughing of the conjunctival membrane was reported at 48 hours; see Table 1 for details.) Thereafter the rabbit was humanely sacrificed.

See attchment

Other effects:

No systemic effects were reported.

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a guideline study, to GLP, instillation of ammonium hexachlororhodate (III) (0.1 mL; 92 mg) to the eye of a single male rabbit caused severe irritation that required sacrifice after 48 hr. No further animals were tested.

Executive summary:

In an OECD Test Guideline 405 study, conducted according to GLP, ammonium hexachlororhodate (III) (0.1 mL; 92 mg) was instilled into the conjunctival sac of a single male New Zealand White rabbit and both lids were briefly closed. The other eye remained untreated and acted as the control. The treated eye was assessed, without rinsing, both quantitatively and qualitatively, for signs of irritation on the cornea, iris and conjunctiva using the Draize scale after 1, 24 and 48 hr post-application.

Severe irritation was observed, with symptoms including iridial inflammation, moderate corneal opacity and severe conjunctival redness, swelling and discharge. After 48 hr, the total irritation score was 65 (out of a maximum possible score of 110, based on the Draize scale) and sloughing of the conjunctival membrane was reported. The animal was humanely sacrificed and no further animals were tested. No systemic toxicity was observed.

As the results were based on only one rabbit, it is not possible to give a definitive interpretation according to EU CLP criteria (EC 1272/2008). However, it is considered prudent to classify the test material for serious eye damage (Category 1), as the severe effects observed are not expected to be reversible.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No relevant irritation/corrosion human data were identified.

In an OECD Test Guideline 404 study, ammonium hexachlororhodate was investigated for irritant (and corrosive) effects following a 4-hr (semi-occluded) application (0.5 g) to the shaved, intact skin of three male White Russian rabbits. The test sites were quantitatively and qualitatively assessed for erythema (and eschar) formation and oedema 1, 24, 48 and 72 hrs after removal of the patches. No erythema or eschar formation, or oedema, was seen at any time point in any animal. A primary dermal irritation index of 0 was calculated using the observations at 24 and 72 hr. Yellow-orange staining of the skin caused by the test material was observed. Nevertheless, it was reported that this did not prevent accurate assessment of the skin responses. No other effects or systemic toxicity were reported (Jones, 1989a).

 

In an OECD Test Guideline 405 study, conducted according to GLP, ammonium hexachlororhodate (III) (0.1 mL; 92 mg) was instilled into the conjunctival sac of a single male New Zealand White rabbit and both lids were briefly closed. The other eye remained untreated and acted as the control. The treated eye was assessed, without rinsing, both quantitatively and qualitatively, for signs of irritation on the cornea, iris and conjunctiva using the Draize scale after 1, 24 and 48 hr post-application. Severe irritation was observed, with symptoms including iridial inflammation, moderate corneal opacity and severe conjunctival redness, swelling and discharge. After 48 hr, the total irritation score was 65 (out of a maximum possible score of 110, based on the Draize scale) and sloughing of the conjunctival membrane was reported. The animal was humanely sacrificed and no further animals were tested. Ammonium hexachlororhodate (III) can therefore be considered to be at least a severe irritant to the rabbit eye. No systemic toxicity was observed (Jones, 1989b).

 

No relevant respiratory tract irritation data were identified.

Justification for selection of skin irritation / corrosion endpoint:
OECD guideline study, and the only skin irritation study available.

Justification for selection of eye irritation endpoint:
OECD guideline study, and the only eye irritation study available.

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on the results of the available and reliable skin irritation study in rabbits, triammonium hexachlororhodate does not require classification for skin irritation, according to EU CLP criteria (EC 1272/2008).

 

As the results of the eye irritation study were based on only one rabbit, it is not possible to give a definitive interpretation according to EU CLP criteria (EC 1272/2008). However, it is considered prudent to classify the test material for serious eye damage (Category 1), as the severe effects observed are not expected to be reversible.