Lithium phosphorodifluoridate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

CRL:(WI) rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult rats
- Weight at study initiation: Males between 259g and 293g, Females between 205g and 256g
- Fasting period before study: none
- Housing :Individual caging (Cage type: Type II. polypropylene/polycarbonate Bedding: Laboratory bedding:
Lignocel Hygienic Animal Bedding produced by J. Rettenmaier & Söhne GmbH+Co.KG
- Diet (e.g. ad libitum): ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest, Germany ad libitum
- Water (e.g. ad libitum): tap water from the municipal supply, as for human consumption from 500 ml bottle ad libitum.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.1 - 25°C
- Humidity (%): 30-51%
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12h dark' / 12h light

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back of each animal
- % coverage: 10
- Type of wrap if used: semi-occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24h

TEST MATERIAL
- For solids, paste formed: moisten with water when applied to skin

Duration of exposure:

20 hours

Doses:

Sighting study: 50, 200, 1000, 2000 mg/kg bw
Main study: 1000 mg/kg bw

No. of animals per sex per dose:

Sighting study: 1 animal per dose
Main study: 4 females, 5 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed on the day of treatment at 1 and 5 hours after application of the test item and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. The body weights were recorded on Day 0 (before test item administration) and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

None

Preliminary study:

As the animal treated at a dose level of 2000 mg/kg bw in the sighting period, showed severe signs of a corrosive effect, the animal was euthanized and the dose level for the main period was defined as 1000 mg/kg bw.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 1 000 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Administration of the test item at a dose level of 1000 mg/kg body weight did not cause mortality, however due to the severe corrosive effects caused by the administration of the test item, two male animals were euthanized due to ethical reasons.

Clinical signs:

other: No systemic clinical signs were observed after treatment with the test item or during the 14-day observation period. Piloerection observed in case of 2 animals is suspected to be associated with the general bad condition of the animal caused by the severe

Gross pathology:

Test-item related, diffuse, grey discoloration of the skin at the site of application could be detected in 2/3 male and 1/5 female rats. In 1/5 male and 4/5 female rats, there was no evidence of the test item-related observations at a dose level of 1000 mg/kg bw at necropsy.

Other findings:

LOCAL DERMAL SIGNS
Administration of the test item at a dose level of 1000 mg/kg bw caused necrotic skin surface, wounds, scabs, erythema, oedema and scaled skin. Full recovery of the local signs was observed in case of 1/5 male and 4/5 females. Local signs were irreversible within the observation period in case of one female and two males. In case of two male animals, necrotic tissues on an extended surface was observed on the exposed skin area, therefore the animals were euthanized for animal welfare reasons in consultation with the clinical veterinarian.

Severe corrosive effects were seen in the 2000 mg/kg bw test group and irreversible local effects on the skin within the observation period in case of one female and two males (1000 mg/kg bw).

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute dermal median lethal dose (LD50) of the test item was found to be higher than 1000 mg/kg body weight in male and female CRL:(WI) rats. Severe corrosive effects were seen in the 2000 mg/kg bw test group and irreversible local effects on the skin was observed.

Cross-reference 2

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

no

Species:

rabbit

Strain:

other: Japanese White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kitayama LABES Co., Ltd
- Age at study initiation: 11 weeks old
- Weight at study initiation: 2.51 - 2.64 kg
- Housing: Hanging type aluminium cages (32W x 48D x 33H cm, stainless steel mesh flooring)
- Diet (e.g. ad libitum): Pellet diet, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 1 day after 7 day quarantine period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.9 - 24.1°C
- Humidity (%): 45.1 - 63.0 %
- Air changes (per hr): 6 - 20
- Photoperiod (hrs dark / hrs light): 12h dark, 12h light

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: olive oil

Controls:

yes, concurrent vehicle

Amount / concentration applied:

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

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.15 mL
- Lot/batch no. (if required): 70910

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: dorsal area of the trunk
- coverage: approx 6cm2
- Type of wrap if used: semi-occlusive elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours

OBSERVATION TIME POINTS
1, 24, 48, 72 hours then 7, 10, 14 days

SCORING SYSTEM:
- Method of calculation: following the OECD guideline

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

not reversible

Remarks:

eschar formation was observed after 7 days and did not reverse by the end of the 14 day observation period

Remarks on result:

probability of severe irritation

Remarks:

Max score achieved on Day 7, 10 and 14 observations

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

no effect

Other effects:

- Other adverse local effects: Irreversible effects to the skin was observed in one animal during the study

No irritation was seen in the control animals (treated with olive oil) all scores zero.

Interpretation of results:

Category 1 (corrosive) based on GHS criteria

Conclusions:

The substance is concluded to be corrosive/severly irritating to skin and therefore a classification of Skin Corrosion Category 1 is applied.