1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31 Aug 2010 to 14 Sep 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

February 24, 1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August 1998

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May, 2008

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole

EC Number:

262-104-4

EC Name:

1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole

Cas Number:

60207-90-1

Molecular formula:

C15H17Cl2N3O2

IUPAC Name:

1-{[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl}-1H-1,2,4-triazole

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RjHan:(WI)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult rats
- Weight at study initiation: Between 208 g and 247 g
- Housing: individual caging, type II polypropylene/polycarbonate; odents are housed with deep wood sawdust bedding to allow digging and other normal rodent activities
- Diet: complete feed for rats and mice, ad libitum
- Water: tap water from municipal supply, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.4 - 24.1
- Humidity (%): 35 - 93
- Air changes: 15-20 air exchanges per hour
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m

IN-LIFE DATES: 31 Augt 2010 to 14 Sep 2010

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: 10
- Type of wrap: gauze pads kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi-occlusive plastic wrap.

REMOVAL OF TEST SUBSTANCE
- Washing: washing using body temperature water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 5000 mg/kg body weight

Duration of exposure:

24 hours

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical examination performed on the day of treatment, at 1 and 5 hours after the application of the test item, and once each day for 14 days thereafter; body weight of all animals was recorded on Day 0 (beginning of the experiment) and on Days 7 and 14
- Necropsy of survivors performed: yes
- Clinical signs including body weight: Observations included the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behaviour pattern. Particular attention was directed to the observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Postmortem examniations: All animals were subjected to gross macroscopic examination. All animals were anaesthetised and exsanguinated. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. Any gross macroscopic findings were recorded.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

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

Mortality:

None

Clinical signs:

other: No adverse clinical signs were observed after treatment with the test item or during the 14 day observation period

Gross pathology:

Enlargement of the thymus was noted in 5/10 animals treated. No other findings were observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of the test substancei n an acute dermal toxicity study performed in compliance with GLP and following the OECD 402 guideline, after single dermal administration was found to be greater than 5000 mg/kg bw in male and female RjHan:(WI) Wistar rats.

Executive summary:

In an acute dermal toxicity study performed in compliance with GLP and following the OECD 402 guideline, a group of five male and five female, young adult, RjHan:(WI) Wistar rats was exposed by a single semi-occlusive dermal application of 5000 mg/kg of test substance for 24 hours to approximately 10% of the total body surface. Animals were observed for 14 days. Body weight was measured on Day 0 (before treatment) and on Days 7 and 14. A clinical examination was performed on the day of treatment, at 1 and 5 hours after the application of the test item, and once each day for 14 days thereafter. All animals were examined macroscopically at the end of the study. 

There were no deaths. There were no clinical signs or effect on body weight. Enlargement of the thymus was noted in 5/10 animals treated. No other findings were observed at necropsy.  The acute dermal LD50 of the test substance was greater than 5000 mg/kg bw in male and female RjHan:(WI) Wistar rats.