CGL 210

Endpoint summary

Description of key information

Acute oral and dermal toxicity was evaluated in GLP-conform studies according OECD guideline 401 and 402. Neither oral nor dermal administration of the test article at concentrations of 2000 mg/kg bw to rats caused unscheduled deaths. Thus, the LD50 for single oral and dermal administration is considered to be higher 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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

- weight of animals not mentioned

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: HanBrl: Wist (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Biotechnology and Animal Breeding Division CH-4414 Fullinsdorf / Switzerland
- Age at study initiation: 8-10 weeks
- Weight at study initiation: not mentioned
- fastened for 16-20h, access to water
- Housing: In groups of three per sex in Makrolon type-4 cages with wire mesh tops and standardized softwood bedding ('Lignocel' Schill AG, CH-4132 Muttenz/Switzerland).
- Diet (e.g. ad libitum): maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst/ Switzerland) ad libitum. The females received from the 24-OCT-2001 until the 30-OCT-2001 batch no. 73/01, then to the end of the study batch no. 74/01. The male rats received batch no. 74/01. Results of analyses for contaminants are archived at RCC Ltd, Itingen.
- Water (e.g. ad libitum): Community tap-water, from Itingen ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd, Itingen.
- Acclimation period: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES:
Delivery of Animals 24-OCT-2001 (females), 26-OCT-2001 (males)
Acclimatization 24-OCT to 30-OCT-2001 (females), 26-OCTto 1-NOV-2001 (males)
Treatment (first dose) 31-OCT-2001 (females, 2000 mg/kg), 2-NOV-2001 (males, 2000 mg/kg)
Observation 31-OCTto14-NOV-2001 (females), 2-NOVto16-NOV-2001 (males)

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/ml
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial performed before experimental starting date.
- Lot/batch no. (if required): 424718/113701

DOSAGE PREPARATION (if unusual):
The preparations were made shortly before each dosing.
The test item was weighed into a tared glass beaker on a suitable precision balance and the
vehicle added (weight:volume). The mixtures were prepared using a ultra sound bath then a
magnetic stirrer.
Homogeneity of the test item in the vehicle was maintained during administration using a
magnetic stirrer.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 males
3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation for mortality/viability daily during acclimatization, then twice daily during days 1-15, for clinical signs daily during acclimatization and then 5 times on day 1, daily during days 2-15, body weighing days 1, 8,15
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was used.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No death occurred during the study.

Clinical signs:

Slightly ruffled fur was evident in two females at 2000 mg/kg on the fist test day.

Body weight:

The body weight of the animals was within the range commonly recorded for this strain and
age.

Gross pathology:

No macroscopic findings were observed at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of the test item after single oral administration to rats of both sexes, observed over a period of 14 days is: LD50 (rat) >2000 mg/kg bodyweight

Executive summary:

One group of three male or three female HanBrl: WIST (SPF) rats was treated by oral gavage with the test substance at 2000 mg/kg body weight. The test item was suspended in vehicle (PEG 300) at a concentration of 0.2 g/ml and administered at a volume of 10 ml/kg. The animals were examined for clinical signs daily during the acclimatization period, four times during test day 1 and once daily during test days 2-15. Mortality/viability was recorded daily during the acclimatization period and together with clinical signs at the same time intervals on test day 1 and twice daily on test days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period. Slightly ruffled fur was evident in two females at 2000 mg/kg on the fist test day. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

according to GLP and OECD guideline 401

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:

2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

other: HanBrl: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd., Biotechnology and Animal Breeding Division, CH-4414 Fullinsdorf / Switzerland
- Age at study initiation: 9-11 weeks
- Weight at study initiation: not mentioned
- fastened for 16-20h, access to water
- Housing: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH- 4132 Muttenz) during treatment and observation.
- Diet (e.g. ad libitum): maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst/ Switzerland) ad libitum. The females received from the 24-OCT-2001 until the 30-OCT-2001 batch no. 73/01, then to the end of the study batch no. 74/01. The male rats received batch no. 74/01. Results of analyses for contaminants are archived at RCC Ltd, Itingen.
- Water (e.g. ad libitum): Community tap-water, from Itingen ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd, Itingen.
- Acclimation period: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES:
Experimental starting date 21-NOV-2001
Experimental completion date 12-DEC-2001
Delivery of animals 21-NOV-2001 (males and females)
Acclimatization 21-NOV to 27-NOV-2001 (males and females)
Treatment 28-NOV-2001 (males and females , 2000 mg/kg)
Observation 28-NOV to 12-DEC-2001

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: 10

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin was flushed with lukewarm tap water and dried with disposable paper towels. Thereafter, the reaction sites were assessed.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
- Constant volume or concentration used: yes
- concentration in vehicle: 0.5 g/ml

VEHICLE
- Amount(s) applied: 4 ml/kg bw
- Lot/batch no. (if required): 02938667

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: for mortality/viability: Daily during acclimatization and twice daily during days 1-15, for weighing: On test days 1 (pre-administration), 8 and 15, for clinical signs: Daily during acclimatization and at least four times (see table of Mortality/Clinical Signs) on test day 1 after the test item administration. Once daily during days 2-15. All abnormalities were recorded.
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was used.

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:

Slight erythema on the back was evident in three males and one female on test day 2 in an other female on test day 2 and 3. All other animals were without clinical signs.

Body weight:

The body weight of the animals was within the range commonly recorded for this strain and
age.

Gross pathology:

No macroscopic findings were observed at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose after single dermal administration to rats of both sexes, observed over a period of 14 days is: LD50 (rat) >2000 mg/kg bodyweight

Executive summary:

A group of five male and five female HanBrl: WIST (SPF) rats was treated with the test item at 2000 mg/kg by dermal application. The test item was diluted in vehicle (corn oil) at a concentration of 0.5 g/ml and administered at a volume of 4 ml/kg. The animals were examined for clinical signs four times during test day 1 and once daily during test days 2-15. Mortality/viability was recorded together with clinical signs at the same time intervals on test day 1. During test days 2-15 it was recorded two times a day. Body weights were recorded on day 1 prior to administration and on days 8 and 15. All animals were necropsied and examined macroscopically. No deaths occurred during the study. Slight erythema on the back was evident in three males and one female on test day 2 additionally in an other female on test day 2 and 3. All other animals were without clinical signs. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

according to GLP and OECD guideline 402

Additional information

Performance and Observation

To evaluate acute oral and dermal toxicity of the test substance, two studies according OECD guideline 401 (CIBA 2001a) and 402 (CIBA 2001b) were performed.

 

In the first study, a group of three male or three female HanBrl: WIST (SPF) rats was treated by oral gavage with the test substance at 2000 mg/kg body weight. The test item was suspended in vehicle (PEG 300) at a concentration of 0.2 g/ml and administered at a volume of 10 ml/kg. All animals survived until the end of the study period. Slightly ruffled fur was evident in two females at 2000 mg/kg on the first test day. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy.

 

In the second study, a group of five male and five female HanBrl: WIST (SPF) rats was treated with the test item at 2000 mg/kg by dermal application. The test item was diluted in vehicle (corn oil) at a concentration of 0.5 g/ml and administered at a volume of 4 ml/kg. No deaths occurred during the study. Slight erythema on the back were evident in three males and one female on test day 2 additionally in another female on test day 2 and 3. All other animals were without clinical signs. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy.

 

Discussion

Oral or dermal application of the test substance did not induce mortalities or any signs of toxicity. Also, body weight gain, food consumption and viability were unaffected. Application of the test item onto skin induced slight erythema. All symptoms resolved within the post observation period.

 

The test item is a viscous liquid and not inhalable. On account of this, a test of acute inhalative toxicity was not performed.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. No mortality occurred at the limit dose of 2000 mg/kg bw. As a result, the substance is not considered to be classified for acute oral or dermal toxicity under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.