Yellow PE 3260

Endpoint summary

Description of key information

The LD50 oral of substance registered is greater than 2000 mg/kg bw.  The LD50 dermal was greater than 2000 mg/kg bw. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL Biological Research Laboratories Ltd., Wölferstr. 4, 4414 Füllinsdorf / Switzerland
- Age at study initiation: 8-10 weeks
- Weight at study initiation: females: 178-193g; males: 196-210g
- Fasting period before study: about 21h
- Housing: groups of 5 animals in Makrolon type 4 cages with standard softwood bedding
- Diet (e.g. ad libitum): pelleted standard Kliba 343 rat maintainance diet ad libitum
- Water (e.g. ad libitum): Itingen community tap water ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1996-07-24 To: 1996-08-07

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 g/L
- Amount of vehicle (if gavage): 10 mg/kg bw

Doses:

limit dose of 2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females per dose group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations: 4 times during day 1 and once daily during days 2-15
- Weighting: On days 1 (pre-administration), 8, and 15
- Necropsy of survivors performed: yes

Statistics:

The logit-model for LD50 determination could not be used as no deaths occured.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No clinical signs of toxicity were observed during the study period.

Gross pathology:

No macroscopic findings were observed at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The mean lethal dose of the substance after single oral administration to rats of both sexes, observed over a period of 14 days, could not be estimated. It can therefore be concluded that the LD50 is greater than 2000 mg/kg bw.

Executive summary:

The acute oral toxicity of the substance was determined according to OECD Guidelines for Testing of Chemicals, Section 4, Number 401 "Acute Oral Toxicity", adopted February 24, 1987 and Directive 92/69/EEC, B.1. "Acute Toxicity-Oral", July 31, 1992.

A group of five male and 5 female Wistar rats was treated with the substance at 2000 mg/kg bw by oral gavage. The test article was suspended in vehicle (bi-distilled water) at a concentration of 0.2 g/ml and administered at a volume of 10 ml/kg bw. Four times during day 1 and once daily during days 2-15 the animals were examined for clinical signs. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 before administration and on days 8 and 15. All animals were necropsied and examined macroscopically.

There were no deaths as a result of treatment with the test article. No clinical signs of toxicity were observed during the observation period. The body weight of the animals was within the physiological range of variability known for rats of this strain and age. No macroscopic findings were observed at necropsy.

The mean lethal dose of the substance after single oral administration to rats of both sexes, observed over a period of 14 days, could not be estimated. It can therefore be concluded that the LD50 is greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Study is reliable without restriction (Klimisch 1 study).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996-07-23-1996-08-27

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BRL Biological Research Laboratories Ltd., Wölferstr. 4, 4414 Füllinsdorf / Switzerland
- Age at study initiation: 8-11 weeks
- Weight at study initiation: females: 202-221g; males: 215-251g
- Housing: during acclimatization in groups of 5 animals in Makrolon type-4 cages with standard softwood bedding, during treatment and opbservation individually in Makrolon type-3 cages with standard softwood bedding
- Diet (e.g. ad libitum): pelleted standard Kliba 343 rat maintainance diet ad libitum
- Water (e.g. ad libitum): Itingen community tap water ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1996-07-30 To: 1996-08-13

Type of coverage:

semiocclusive

Vehicle:

other: bi-distilled water

Details on dermal exposure:

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

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4.0 mL/kg bw
- Concentration (if solution): 500 g/L
- Constant volume or concentration used: yes
- For solids, paste formed: no, substance is well soluble in water

Duration of exposure:

24 h

Doses:

limit dose of 2000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations: Four times during test day 1 and once daily during days 2-15.
- Frequency of observations and weighing: On test days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

The LOGIT-Model for determination of LD50 could not be used as no deaths occurred.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the observation period.

Clinical signs:

other: Yellow discoloration of the skin at the application site was evident in all animals after the removal of the dressing on test day 2 and persisted until study termination.

Gross pathology:

No macroscopic organ findings were noted at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 (rat) after single dermal application is greater than 2000 mg/kg.

Executive summary:

The acute dermal toxicity of the substance was determined according to OECD Guidelines for Testing of Chemicals, Section 4, Number 402 "Acute Dermal Toxicity", adopted February 24, 1987 and Directive 92/69/EEC, 6.3. "Acute Toxicity-Dermal", July 31, 1992.

A group of five male and 5 female Wistar rats was treated with the substance at 2000 mg/kg by demal application. The test article was suspended in water at a concentration of 0.2 g/m1 and administered at a volume of 4 ml/kg. Four times during day 1 and once daily during days 2-15 the animals were examined for clinical signs. Mortality/viability were recorded together with clinical signs at the same time intervals. Body weights were recorded on day 1 before administration and on days 8 and 15. All animals were necropsied and examined macroscopically.

No deaths occurred during the study period. Yellow discoloration of the skin at the application site was evident in all animals after the removal of the dressing on test day 2 and persisted until the study termination. The body weight of the animals was within the physiological range of variability known for rats of this strain and age. The slight loss of body weight in one female animal (no. 8) during the first observation week was considered to be a consequence of the semi-occlusive dressing used during treatment. Commonly female animals prove to be more sensitive in relation to the effects on body weight caused by semi-occlusive dressing than male. No macroscopic organ findings were observed at necropsy.

The mean lethal dose of the substance after single dermal administration to rats of both sexes, observed over a period of 14 days, could not be estimated. It can therefore be concluded that the LD50 is greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Reliable without restriction (Klimisch 1 study)

Additional information

Two valid acute toxicity studies, oral and dermal have been conducted with the registration substance.

The mean lethal dose of the substance after single oral administration to rats of both sexes, observed over a period of 14 days, could not be estimated. It can therefore be concluded that the LD50 is greater than 2000 mg/kg bw.

The mean lethal dose of the substance after single dermal administration to rats of both sexes, observed over a period of 14 days, could not be estimated. It can therefore be concluded that the LD50 is greater than 2000 mg/kg.

No study for acute inhalation toxicity is available.

Justification for selection of acute toxicity – oral endpoint
The selected study was performed under GLP and in accordance with OECD TG 401. No other studies are available.

Justification for selection of acute toxicity – dermal endpoint
The selected study was performed under GLP and in accordance with OECD TG 402. No other studies are available.

Justification for classification or non-classification

No adverse effect observed after acute oral application of the test substance at a dose of 2000 mg/kg bw.

No adverse effect observed after acute dermal application of the test substance at a dose of 2000 mg/kg bw.