A mixture of: cis-tetrahydro-2-isobutyl-4-methylpyran-4-ol; trans-tetrahydro-2-isobutyl-4-methylpyran-4-ol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 10 Jan 1985 to 24 Jan 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to OECD Guideline Study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

6 rabbits (4 males, 2 females) were used for this study. Skin application site was abraded on 50% of the animals to enhance dermal penetration

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

A mixture of: cis-tetrahydro-2-isobutyl-4-methylpyran-4-ol; trans-tetrahydro-2-isobutyl-4-methylpyran-4-ol

EC Number:

405-040-6

EC Name:

A mixture of: cis-tetrahydro-2-isobutyl-4-methylpyran-4-ol; trans-tetrahydro-2-isobutyl-4-methylpyran-4-ol

Cas Number:

63500-71-0

Molecular formula:

C10 H20 O2

IUPAC Name:

4-methyl-2-(2-methylpropyl)oxan-4-ol

Details on test material:

- Name of test material (as cited in study report): MT-178
- Substance type: pure active substance
- Lot/batch No.:
- Expiration date of the lot/batch:
- Storage condition of test material: The test article was stored at ambient room temperature

Test animals

Species:

rabbit

Strain:

other: albino rabbits

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals USA
- Age at study initiation: no data
- Weight at study initiation: 2.2 - 2.5 kg
- Fasting period before study:
- Housing: animals were housed 2/cage in suspended wire mesh cages. Bedding was placed beneath the cages.
- Diet (e.g. ad libitum): ad libitum, Fresh Purina Rabbit Chow (Diet #53-21)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: 10 Jan 1985 To: 24 Jan 1985

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: abdomen
- % coverage: ca. 10 % of body surface
- Type of wrap if used: The test article was covered with a gauze patch and gentle pressure was applied to the gauze to aid the distribution of the test article over the prepared site. The torso was wrapped with plastic which was secured with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): application site was wipped
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.0 g/kg bw
- Constant volume or concentration used: yes

Duration of exposure:

24 hours

Doses:

2000 mg/kg (male and female)

No. of animals per sex per dose:

4 males + 2 females

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animal were observed daily. Bodyweights were recorded pretest and at termination of the test.
- Necropsy of survivors performed: yes
- Other examinations performed: toxicity and pharmacological effects, body weight, gross pathology

Statistics:

The LD 50 and 95% Confidence were calculated, if possible, by the method of Litchfield, J.T. Jr., & F. Wilcoxon JPET 96:99, 1949 or Horn, H.J. Biometric.s 12:311, 1956.

Results and discussion

Preliminary study:

Not Applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no death

Clinical signs:

other: There were no signs of toxicity. Physical signs: Three animals were normal during the 14 day observation period. Instances of few feces and yelllow nasal discharge were noted in the remaining three animals.

Gross pathology:

All animals were normal

Any other information on results incl. tables

Table 1: bodyweight, dose volume and dermal reactions

Rabbit # & sex	Dose volume cc	Weight (kg) day 0	Weight (kg) day 14	Day 1		Day 7		Day 14		% remaining
				R	E	R	E	R	E
1-M ab	5.3	2.5	2.9	2	2	0 f	0	0	0	20
2-M	4.7	2.2	2.6	2	2	4	0	0	0	20
3-M ab	4.9	2.3	2.5	2 gb	2	4	2	0	0	20
4-M	4.9	2.3	2.7	2	0	0 f	0	0	0	20
5-F ab	4.9	2.3	2.7	3	2	4	1	0 f	0	20
6-F	4.7	2.2	2.8	2	2	0	0	0	0	20
Codes used: R =erythema(redness) E. =edema ab=abraded b = brown areas f =flaking skin g =green areas % remaining = the amount of material remaining on the skin, gauze and occlusive binding at 24 hours, after the occlusive binding was removed.

 

DERMAL SCORING CODE for EVALUATION OF SKIN REACTIONS

 

ERYTHEMA & ESCHAR FORMATION:

0             NO ERYTHEMA

1             VERY SLIGHT ERYTHEMA (BARELY PERCEPTIBLE)

2             WELL DEFINED ERYTHEMA

3             MODERATE TO SEVERE ERYTHEMA 3

4             SEVERE ERYTHEMA (BEET REDNESS) TO SLIGHT ESCHAR FORMATION (INJURIES IN DEPTH)

EDEMAFORMATION:

0             NO EDEMA

1             VERY SLIGHT EDEMA (BARELY PERCEPTIBLE)

2             SLIGHT EDEMA (EDGES OF AREA WELL DEFINED BY DEFINITERAISING)

3             HODERATE EDEMA (RAISED APPROXIMATELY 1 MILLIMETER)

4             SEVERE EDEMA (RAI SED MORE THAN 1 MI LLIMETER AND EXTENDING BEYOND THE AREA OF EXPOSURE)

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD 50 is greater than 2.0 g/kg of body weight.

Executive summary:

Purpose of the study. The purpose of this study was to investigate the toxicity of the test article in the albino rabbit. The procedures used were equivalent to the OECD Guideline 402 on Acute Dermal Toxicity with two deviations (see below under Methods).

Method. Six healthy albino rabbits were dosed dermally in a limit test with a unique concentration of test material at a dose level of 2000 mg/kg of body weight.

Two deviations were made from the OECD Guideline: 1.) 6 animals (4 males, 2 females) were used for the study instead of 10; 2.) skin application site was abraded on 50% of the animals to enhance dermal penetration.

The test article was kept in contact with the skin for 24 hours. The animals were observed daily for signs of mortality, toxicity and pharmacological effects. Skin reactions were scored on Days 1, 7 and 14. Body weights were recorded pretest and at termination. All animals were examined for gross pathology.

Results. All animals survived the 2000 mg/kg dermal application. Physical signs of few feces and yellow nasal discharge were noted during the study. Body weight changes were normal. Dermal reactions, slight to moderate on Day 1, were absent to severe on Day 7 and absent on Day 14. Necropsy results were normal.

Discussion. Study was performed using occlusive patch and skin abrasion was used in that study to increase dermal penetration and exposure. As exposure to test substance was not lethal both on more severe conditions (abreded skin, occlusive patch) and as dermal reactions were completely reversible effect after 14 days, it can be concluded that the test substance has no toxic effect on test animals despite a lower number of animals used in the study.

Conclusion. The LD50 is greater than 2000 mg/kg of body weight.