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Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

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

Test material

Test material information

1

Reference substance name:

Reaction products of DL-methionine and C18 unsaturated fatty acid chloride and isopropanol

Molecular formula:

not applicable (UVCB)

IUPAC Name:

Reaction products of DL-methionine and C18 unsaturated fatty acid chloride and isopropanol

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)

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels

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

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.