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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.