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Endpoint summary

Description of key information

In order to evaluate the acute oral toxicity property of Dodicor V5654, an OECD 423 GLP conform study in female Wistar rats is provided.

In order to evaluate the acute dermal toxicity property of Dodicor V5654, an OECD 402 GLP conform study in female Sprague Dawley rats is provided.

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:

2007-05-02 to 2007-05-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted December 17, 2001

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

April 29, 2004

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: 07SK021
- Description: Liquid, dark brownish
- Expiration date of the lot/batch: n.a.
- Purity test date: 94%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (range of 20 ± 5° C), light protected
- Solubility and stability of the test substance in the solvent/vehicle: unknown in PEG 300

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Fuellinsdorf / Switzerland
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 11-12 weeks
- Weight at study initiation: at Day1 of treatment about 178- 208 g
- Fasting period before study: 18-19 hours
- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30-70 % (values above 70 % during cleaning process possible)
- Air changes (per hr): 10-15
- Photoperiod: 12 hrs dark / 12 hrs light

Route of administration:

oral: gavage

Vehicle:

other: Polyethylene glycol 300 (PEG 300)

Doses:

2000 mg/kg bw
dosing volume was 10 mL/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
Frequency of observations:
- Mortality/Viability and Clinical signs: during acclimatization and during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 and twice daily during days 2-15
- Frequency of weighing: On test days 1 (prior to administration), 8 and 15
- Necropsy of survivors performed: yes

Key result

Sex:

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: A slightly ruffled fur was observed in all treated females at the 1 or 2 hours post-dose and persisted up to the 5-hour reading in one female and up to test day 2 in five females. Additionally, all females expressed a hunched posture at the 2-hour evaluat

Gross pathology:

No macroscopic findings were recorded at necropsy

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of Dodicor V 5654 after single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight

Executive summary:

In order to evaluate the acute oral toxicity property of Dodicor V5654, an OECD 423 GLP conform study was performed in female Wistar rats.

Two groups of 3 rats were treated with Dodicor V 5654 by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle PEG 300 at a concentration of 0.2 g and administered at a dosing volume of 10 mL. The animals were examined for mortality, viability and clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. At end of observation period, all animals were necropsied and examined macroscopically.

All animals survived until the end of the study period. A slightly ruffled fur was observed in all treated females at the 1 or 2 hours post-dose and persisted up to the 5-hour reading in one female and up to test day 2 in five females. Additionally, all females expressed a hunched posture at the 2-hour evaluation which persisted up to the 5-hour observation. Otherwise, no clinical signs were observed in any animal at any time at any observation. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy.

Based on the results of this study, he median lethal dose of Dodicor V 5654 after single oral administration to female rats, observed over a period of 14 days is: LD50 (female rat): greater than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

GLP-conform OECD study, well documented.

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:

2019-09-27 to 2019-11-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

Fixed Dose Procedure” adopted on 09 October 2017

Deviations:

no

Principles of method if other than guideline:

- Principle of test:
The objective of this study was to assess the toxic potential of the test item Dodicor V 5654 when applied by dermal route to female Sprague Dawley rats at one or more defined dose.
This also gives details on classification and labelling of chemical for safety and risk ssessment and LD50 value

- Short description of test conditions:
The study was performed in two phases i.e. range finding study and main study. Range finding study was performed with three female rats (one rat per each dose) and main study was performed with two female rats.

- Parameters analysed / observed:
No skin reaction at the treatment site was observed at 24, 48 and 72 hours after removal of test item using draize method. No mortality and clinical signs were noted. No treatment related changes in body weight and percent change in body weight with respect to day 1 were noted. Normal increase in body weights were noted during the observation period.
No treatment related gross pathological changes were noted in any of the range finding study and main study animals during necropsy.

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
Batch produced by : Clariant Ibérica Producción, S.A.
- Lot No.: ESD0033040 (dried substance)
- Liquid brownish
- Purity: ca 97%
- Expiration date of the lot/batch: August 2021

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient (21 to 29⁰C)
- Stability under test conditions: The stability of the test item was not established under this study.
- Solubility and stability of the test substance in the solvent/vehicle: Not Applicable

FORM AS APPLIED IN THE TEST - As such (undiluted)

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: In-house bred
- Females- nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 9 weeks
- Weight at study initiation: Females: 215.24 - 248.80 g
- Housing: Animals were housed in a standard polypropylene cage (size: L 430 x B 285 x H 150 mm) with stainless steel mesh top grill having facilities for holding pelleted food and drinking water in water bottle fitted with stainless steel sipper tube. Clean sterilized paddy husk was provided as bedding material.
- Diet (e.g. ad libitum): Altromin maintenance diet for rats and mice (manufactured by Altromin Spezialfutter GmbH & Co. KG) was provided ad libitum to the animals throughout the acclimatization and experimental period.
- Water (e.g. ad libitum): Water was provided ad libitum throughout the acclimatization and experimental period. Deep bore-well water passed through Reverse Osmosis Unit was provided in plastic water bottles with stainless steel sipper tubes.
- Acclimation period: Animals were acclimatized for a period of seven (200 mg/kg body weight dose), ten days (1000 mg/kg body weight dose) and thirteen days (2000 mg/kg body weight dose) for range finding study respectively and sixteen days for main study animals to laboratory conditions prior to dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 to 23.8 degree celcius
- Humidity (%): 47 to 68%
- Air changes (per hr): 12 to 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light and 12 hours dark cycle

IN-LIFE DATES: From: 01 October 2019 To: 31 October 2019

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorso-lateral area of the trunk of animals
- % coverage: approximately 10% of the total body surface area
- Type of wrap : Exposure area was covered with cotton gauze and held in place with non-irritating adhesive tape. The whole area was wrapped with a suitable semi- occlusive dressing (crepe bandage).

REMOVAL OF TEST SUBSTANCE
- Washing : At the end of the contact period, the residual test item was washed using distilled water and dried with absorbent cotton
- Time after start of exposure:The contact period of test item was 24 hours.

TEST MATERIAL
- Amount(s) applied (volume with unit):
Range Finding Study: For 200 mg/kg=0.05 mL, 1000 mg/kg=0.24 mL, 2000 mg/kg=0.50 mL
Main Study: 2000 mg/kg=0.54 and 0.48 mL

VEHICLE - Not Applicable

Duration of exposure:

24 hours

Doses:

Range Finding Study:
200 mg/kg
1000 mg/kg
2000 mg/kg

Main Study:
2000 mg/kg

No. of animals per sex per dose:

Range Finding Study:
200 mg/kg= 1 animal
1000 mg/kg= 1 animal
2000 mg/kg= 1 animal

Main Study:
2000 mg/kg= 2 animals

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All the animals were observed for clinical signs of toxicity and mortality at 20 to 30 mins, 1 hr (±10 mins), 2 hrs (±10 mins), 4 hrs (±10 mins) and 6 hrs (±10 mins) post dosing on Day 1 and thereafter once daily for clinical signs of toxicity and twice daily for mortality during the 14 days observation period.
Weighing of animals were done on day of receipt of animals, day of treatment and weekly once upto termination.
- Necropsy of survivors performed: yes
- Other examinations performed:
- Clinical signs: All the animals were observed for clinical signs of toxicity and mortality at 20 to 30 mins, 1 hr (±10 mins), 2 hrs (±10 mins), 4 hrs (±10 mins) and 6 hrs (±10 mins) post dosing on Day 1 and thereafter once daily for clinical signs of toxicity and twice daily for mortality during the 14 days observation period.
- Body weight: Individual animal body weight was recorded at receipt, on day 1 before test item application, on day 8 and 15 during the experimental period.
- Organ weights: Not Applicable
- Histopathology: Histopathological examination was not carried out as there were no gross pathological findings in any of the animals.

Statistics:

Not Applicable

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No treatment related mortality were observed in both range finding study and main study animals.

Clinical signs:

other: No treatment related clinical signs of toxicity were observed in both range finding study and main study animals. No skin reactions were observed in the treatment sites at 24, 48 and 72 hours after removal of test item.

Gross pathology:

No treatment related gross pathological changes were observed in any of the animals in both range finding study and main study.

Other findings:

Not Applicable

Table: Grading of Skin Reactions

1. Erythema and Eschar Formation	Score
No erythema..................................................................................................	0
Very slight erythema (barely perceptible)……………………………….....	1
Well defined erythema……………………………………………………..	2
Moderate to severe erythema........................................................................                              ..	3
Severe erythema (beet redness) to eschar formation preventing grading of erythema........................................................................................................	4
Maximum possible score: 4

 

2. Oedema Formation	Score
No oedema    .	0
Very slight oedema (barely perceptible).........................................................	1
Slight oedema (edges of area well defined by definite rising)    .	2
Moderate oedema (raised approximately 1 millimetre)    .	3
Severe oedema (raised more than 1 millimetre and extending beyond area of exposure)    .	4
Maximum possible score: 4

The above table was used to observe the skin reactions in the treatment sites at 24, 48 and 72 hours after removal of test item.

Interpretation of results:

GHS criteria not met

Conclusions:

No skin reaction at the treatment site was observed at 24, 48 and 72 hours after removal of test item using draize method. According to the OECD guideline the LD 50 cut-off is greater 2000 mg/kg bw.

Executive summary:

The objective of this study was to assess the toxic potential of the test item Dodicor V 5654 when applied by dermal route to female Sprague Dawley rats at one or more defined dose levels according to OECD Guideline 402. 

The study was performed in two phases i.e. range finding study and main study. Range finding study was performed with three female rats (one rat per each dose, i.e. 200, 1000 and 2000 mg/kg bw). Main study was performed with two female rats at a dose of 2000 mg/kg bw. The contact period of test item was 24 hours followed by a 14-day observation period.

All the animals were observed for clinical signs of toxicity and mortality at 20 to 30 mins, 1 hr (±10 mins), 2 hrs (±10 mins), 4 hrs (±10 mins) and 6 hrs (±10 mins) post dosing on Day 1 and thereafter once daily for clinical signs of toxicity and twice daily for mortality during the 14 days observation period. Individual animal body weight was recorded at receipt, on day 1 before test item application, on day 8 and 15 during the experimental period.

No mortality and clinical signs were noted. No treatment related changes in body weight and percent change in body weight with respect to day 1 were noted. Normal increase in body weights were noted during the observation period. No treatment related gross pathological changes were noted in any of the range finding study and main study animals during necropsy. No skin reaction at the treatment site was observed at 24, 48 and 72 hours after removal of test item using draize method.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006 the test substance Dodicor V5654 has not to be classified for acute oral toxicity nor for acute dermal toxicity.