Ammonium wolframate

Endpoint summary

Description of key information

In a skin irritation study conducted on rabbits according to OECD 404, ammonium paratungstate elicited no dermal irritation. In an eye irritation study conducted on rabbits according to OECD 405, instillation of ammonium paratungstate into the rabbit elicited corneal opacification, iridial inflammation and considerable irritation in one animal. Reactions in the two remaining rabbits were confined to transient well-defined conjunctival irritation only.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-02-25 to 1998-02-28 28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Well documented, scientifically sound study that was conducted in accordance to GLP and OECD guideline 404 with no deviation to the protocol.

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: Harlan UK Ltd Bicester, Oxon, England
- Age at study initiation: 10 to 11 weeks
- Weight at study initiation: 2.2 to 2.6 kg
- Housing: Individually in metal cages with perforated floors
- Diet (eg ad libitum): STANRAB (P) SQC Rabbit Diet- ad libitum
- Water (eg ad libitum): ad libitum
- Acclimation period: Acclimated, but period not stated.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22.5
- Humidity (%): 39 to 56%
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12/12 artificial light (0700 - 1900)

IN-LIFE DATES: From: 1998-02-25 To: 1998-02-28

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test substance was applied under a 25 mm x 25 mm gauze pad.

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL distilled water

Duration of treatment / exposure:

4 hours

Observation period:

4 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing an area of skin approximately 100 mm x 100 mm.
- Type of wrap if used: Semi-occlusive dressing and gauze pad.
- Each treatment site was covered with "Elastoplast" elastic adhesive dressing for four hours. The animals were not restrained during the exposure period and were returned to their cages immediately after treatment. At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washed with warm water (35 °C) and area blotted dry with absorbent paper.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Local dermal irritation was scored according to Draize.

CLINICAL SIGNS:
All animals were observed daily for signs of ill health or toxicity.

DERMAL RESPONSES:
Examination of the treated skin was made on Day 1 (ie approximately 60 minutes after removal of the dressings) and on Days 2, 3, and 4 (equivalent to 24, 48 and 72 hours after exposure).

Irritation parameter:

erythema score

Basis:

mean

Remarks:

mean score for all 3 male rabbit

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

No erythema

Irritation parameter:

edema score

Basis:

mean

Remarks:

mean score for all 3 male rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

No edema

Irritant / corrosive response data:

No dermal response to treatment was observed in any animal throughout the study.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

A single semi-occlusive application of ammonium paratungstate to intact rabbit skin for four hours elicited no dermal irritation.

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:

1998-03-02 to 1998-03-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Well documented, scientifically sound study that was conducted in accordance to GLP and OECD guideline 405 with no deviation to the protocol.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England
- Age at study initiation: 10 to 16 weeks
- Weight at study initiation: 2.3 to 3.6 kg
- Housing: Individually in metal cages with perforated floors.
- Diet (eg ad libitum): STANRAB (P) SQC Rabbit Diet ad libitum
- Water (eg ad libitum): ad libitum
- Acclimation period: Acclimated, but period not stated.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 22.5
- Humidity (%): 38 to 65%
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12/12 artificial light (0700 - 1900 hours)

IN-LIFE DATES: From: 1998-03-02 To: 1998-03-23

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
- In compliance with the study guideline, the weight of the test substance, which when gently compacted occupied a volume of 0.1 mL, was measured: 219, 205, 218 mg (Weight of 0.1 mL test material (mg)).

Duration of treatment / exposure:

Single instillation

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3

Details on study design:

- The eyes of each animal were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial or conjunctival inflammation.
- One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed.
- In compliance with the study guideline, the weight of the test substance, which when gently compacted occupied a volume of 0.1 mL, was measured.
- A volume of 0.1 mL of test substance exceeded 100 mg, therefore in accordance with the protocol 100 mg was placed into the lower inverted lid of one eye of each animal.
- The eyelid was then gently held together for one second before releasing. The contralateral eye remained untreated.

OBSERVATIONS:
- Clinical Signs: All animals were observed daily for signs of ill health or toxicity.
- Ocular Responses: Examination of the eyes was made after 1 hour and 1, 2 and 3 days after instillation (approximately 24, 48 and 72 hours). Additional observations were made 4 days after instillation in two animals and 5 through 21 days after instillation in one animal.
SCORING SYSTEM: Ocular irritation was assessed using the prescribed numerical system with respect to the Cornea, Iris, Conjuctivae and Chemosis.

TOOL USED TO ASSESS SCORE: Handheld light

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of weak irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

density

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.6

Max. score:

3

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of weak irritation

Remarks:

redness

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of weak irritation

Remarks:

redness

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.6

Max. score:

3

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of weak irritation

Remarks:

redness

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.6

Max. score:

4

Reversibility:

fully reversible within: 21 days

Remarks on result:

probability of mild irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Corneal opacification (Grade 2) and iridial inflammation (Grade 1) was observed in one animal. Vascularization of the cornea was observed 14 days after instillation. A beefy red colouration of the conjuctivae, swelling with eyelids about half closed and a white discharge was also noted in this animal. Ocular reactions gradually ameliorated and the eye was normal 21 days after instillation.

Responses in the remaining two animals were transient in nature and confined to a diffuse crimson colouration to the conjuctivae, with above normal swelling of the eyelids in one of the rabbits. These reactions had resolved by either three or four days after instillation.

Other effects:

Clinical signs: There were no signs of toxicity or ill health in any rabbit during the observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

Instillation of ammonium paratungstate into the rabbit eye elicited corneal opacification, iridial inflammation and considerable conjunctival irritation in one animal. Reactions in the two remaining rabbits were confined to transient well-defined conjunctival irritation only.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

All three rabbits in the skin irritation study received a score of 0 for both erythema and oedema over the course of 24, 48 and 72 hours. A classification is not warranted under CLP. One animal received a mean eye irritation score of 2.6 for conjunctiva redness, while the 2 other animals received a score of 1 after 24, 48 and 72 hours and was reversible after 21 days. The minimum eye score that would dictate a Category 2 classification for eye irritation under CLP for conjunctival redness is >= 2 in 2/3 animals. One animal out of the three received scores greater than or equal to the cut-off value for CLP classification for cornea opacity, iritis and conjunctiva oedema (chemosis), but the remaining two animals received a score of 0, and as a result would not dictate a CLP classification. Therefore, a classification is not warranted for the eye irritation endpoint.