Reaction mass of 3-(3,3-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal and 3-(1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal and 3-(1,1-dimethyl-2,3-dihydro-1H-inden-4-yl)propanal

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 26 to March 17, 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute dermal toxicity (2-1-2), 12 Nousan No 8147, Agricultural Production Bureau, November 24, 2000.

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Compliance Programme (inspected on July 01-03, 2014/ signed on September 15, 2014)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-(3,3-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal

Cas Number:

173445-65-3

Molecular formula:

C14H18O

IUPAC Name:

3-(3,3-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal

Constituent 2

Reference substance name:

3-(1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal

Cas Number:

173445-44-8

Molecular formula:

C14H18O

IUPAC Name:

3-(1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal

Constituent 3

Reference substance name:

3-(1,1-dimethyl-2,3-dihydro-1H-inden-4-yl)propanal

Molecular formula:

C14H18O

IUPAC Name:

3-(1,1-dimethyl-2,3-dihydro-1H-inden-4-yl)propanal

Test material form:

liquid

Details on test material:

- Physical state: Colourless liquid
- Storage condition of test material: Room temperature in the dark under nitrogen

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS: RccHan®:WIST rat
- Source: Harlan (UK) Ltd.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: ca. 8–9 weeks
- Weight at study initiation: 245-257 g for males and 174-183 g for females
- Fasting period before study: None
- Housing: Animals were housed individually from Day -1 until Day 4 when they were returned to group housing (in groups of five rats of the same sex). The cages were solid bottomed polycarbonate cages with a stainless steel mesh lid.
- Diet: Standard rodent diet (Harlan Teklad 2014C Diet), ad libitum
- Water: Drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23 °C
- Humidity: 40-70%
- Air changes: at least 15 air changes per hour
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: February 26 to March 17, 2015

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 10% of the total body surface area
- Type of wrap if used: The test substance was applied by spreading it evenly over the prepared skin. The treatment area (approximately 50 mm x 50 mm) was covered with porous gauze held in place with a non-irritating dressing, and further covered by a waterproof dressing encircled firmly around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing: At the end of the 24 hours exposure period the dressing was carefully removed and the treated area of skin was washed with warm water (30 - 40°C) containing a mild detergent solution, to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Test item was administered, as supplied, at a dose volume of 2 mL/kg bw.
- The specific gravity, as measured by this laboratory, was 0.997 g/mL.
- Concentration (if solution): Undiluted
- Constant volume or concentration used: Yes

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:
- Mortality: Cages of rats were checked at least twice daily for any mortalities.
- Clinical observations: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only).
- Dermal reactions: Local dermal irritation at the treatment site was assessed daily for 14 days.
- Frequency of weighing: The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly body weight changes and group mean body weights were calculated.
- Necropsy of survivors performed: Yes; All animals were humanely killed on Day 15 by carbon dioxide asphyxiation and were subjected to a macroscopic examination.

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

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 mortality was observed.

Clinical signs:

other: No systemic response to treatment was observed.

Gross pathology:

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Other findings:

Dermal reactions: No dermal reactions were observed in any animal during the study. However, bandage reaction/sticky residue was noted around but not on the dose site and was a result of the bandage adhesive sticking to the skin during the application period. This is a normal finding seen in this type of study and not considered to be associated with the test substance.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Dermal LD50 Combined > 2000 mg/kg bw. Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In an acute dermal toxicity study (limit study) performed according to the OECD guideline No. 402, a group of ten RccHan^®:WIST albino rats (five males and five females) received a single topical application of the test substance at a dose level of 2000 mg/kg bw, for a duration of 24 hours. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

There were no deaths and no systemic response to treatment in any animal throughout the study. No dermal reactions were observed in any animal during the study. All animals were considered to have achieved satisfactory bodyweight gains throughout the study. No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15. 

 

Dermal LD50 Combined > 2000 mg/kg bw.

 

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.