Butanal, 4-(heptyloxy)-3-methyl-

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between 25 February 2014 and 02 April 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was considered to be a reliability 1 as it has been conducted according to OECD Test Guideline 402 using a fixed dose method and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

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

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-(heptyloxy)-3-methylbutanal

EC Number:

802-100-7

Cas Number:

1093653-57-6

Molecular formula:

C12H24O2

IUPAC Name:

4-(heptyloxy)-3-methylbutanal

Test material form:

other: Liquid

Details on test material:

Identification: TM 09-0217
Chemical name: 4-(heptyloxy)-3-methyl butanal
CAS number: 1093653-57-6
Intended use: Industrial fragrance
Appearance: Liquid
Storage conditions: Room temperature in the dark
Supplier: Sponsor
Sample receipt: 12 February 2014

Test animals

Species:

rat

Strain:

other: CD (Crl:CD ‘SD’)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Animal supply, acclimitisation and allocation
Healthy male and female (nulliparous and non-pregnant) CD (Crl:CD ‘SD’) albino rats were obtained from a reputable supplier.
The animals were allocated without conscious bias to cages within the treatment group. They were housed individually from Day -1 until Day 13 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. Each cage contained a quantity of autoclaved wood flake bedding. Cages, food hoppers, water bottles and bedding were changed at appropriate intervals.

Each animal was assigned an alpha-numeric code and identified uniquely within the study by tail marking. Each cage label was colour-coded and was identified uniquely with the study number, dose level and animal mark.

The animals were allowed to acclimatise to the conditions described below for 6 days before treatment. For those animals selected for this study, their body weights were in the range 347 to 388 g for males and 246 to 271 g for females and they were approximately eight to twelve weeks of age prior to dosing (Day 1).

Animal housing, diet and water supply
Animals were housed inside a barriered rodent facility (Building F21, Room 044/045). The facility was designed and operated to minimise the entry ofexternal biological and chemical agents and to minimise the transference of such agents between rooms.

The animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated. The temperature and relative humidity controls were set to maintain the range of 19 to 23 °C and 40 to 70% respectively. Any minor deviations from these ranges would not have had an adverse effect on the animals and would not affect the integrity or validity of the study. Artificial lighting was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per 24 hours. Environmental parameters are archived with the departmental raw data.

Periodic checks were made on the number of air changes in the animal rooms. Temperature and humidity were monitored daily.
Alarms were activated if there was any failure of the ventilation system, or temperature limits were exceeded. A stand-by electricity supply was available to be automatically brought into operation should the public supply fail.

The animals were allowed free access to a standard rodent diet (Rat and Mouse No. 1 Maintenance Diet). This diet contained no added antibiotic or other chemotherapeutic or prophylactic agent.

Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.
Each cage of animals was provided with an Aspen chew block for environmental enrichment. Chew blocks were provided throughout the study and were replaced when necessary. Each cage of animals was provided with a plastic shelter for environmental enrichment, which was replaced at the same time as the cages.

Each batch of diet was analysed routinely by the supplier for various nutritional components and chemical and microbiological contaminants. Supplier’s analytical certificates were scrutinised and approved before any batch of diet was released for use. The quality of the water supply is governed by regulations published by the Department for Environment, Food and Rural Affairs. Certificates of analysis were received routinely from the water supplier. Certificates of analysis were received routinely from the supplier of the chew blocks. Since the results of these various analyses did not provide evidence of contamination that might have prejudiced the study, they are not presented.

No other specific contaminants that were likely to have been present in the diet or water were analysed, as none that may have interfered with or prejudiced the outcome of the study was known.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

A group of ten rats (five males and five females) was treated at 2000 mg/kg body weight.

One day prior to treatment, hair was removed from the dorso-lumbar region of each rat with electric clippers taking care to avoid damaging the skin, exposing an area equivalent to approximately 10% of the total body surface area.

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.

Treatment in this manner was performed on Day 1 (day of dosing) of the study only.

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), to remove any residual test substance. The treated area was blotted dry with absorbent paper.

A record of the weight of the test substance dispensed and the amount remaining after dosing was made. The balance of these two weights was compared with the predicted usage as a check that the doses had been administered correctly.

TM 09-0217 was administered, as supplied, at a dose volume of 2000 mL/kg body weight. The specific gravity, as measured by this laboratory, was 0.872 g/mL. The absorption of the test substance was not determined. Determination of the homogeneity, stability and purity of the test substance was not undertaken as part of this study.

Duration of exposure:

24 hours

Doses:

Single dose 2000 mg/kg

No. of animals per sex per dose:

5 female and 5 male per dose

Control animals:

no

Details on study design:

Serial 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). The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation. All animals were observed for 14 days after dosing.

Bodyweight:
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 and macropathology
Method of kill:
All animals were humanely killed on Day 15 by carbon dioxide asphyxiation

Macroscopic pathology:
All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.

Statistics:

The computer systems that were used on this study to acquire and quantify data include:

System name: Xybion Pristima*
System Function: Used for Pharmacy test substance management

* All version numbers of the system are maintained by Huntingdon Life Sciences

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths and no systemic response to treatment in any animal.

Clinical signs:

other: Very slight to well-defined erythema was seen in one male (An. No. A4) and four females (An. Nos A7 to A10). These reactions had resolved by Day 9. In addition, eschar/scab formation was seen in one female (An. No. A9) from Day 7, resolving completely b

Gross pathology:

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

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute median lethal dermal dose (LD50) to rats of TM 09-0217 was demonstrated to be greater than 2000 mg/kg body weight.

Executive summary:

The acute dermal toxicity potential of the test material, TM 09-217 was assessed and gave an LD₅₀ of > 2000 mg/kg body weight according to OECD Test Guideline 402, using a fixed dose method.