1,2-epoxycyclohexane

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not reported.

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed in accordance with generally accepted scientific principles, with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

publication

Title:

Absorption, Disposition Kinetics, and Metabolic Pathways of Cyclohexene oxide in the Male Fischer 344 Rat and Female B6C3F1 Mouse

Author:

Sauer J M, Bao J, Smith R L, McClure T D, Mayersohn M, Pillai U, Cunningham M L & Spies I G

Year:

1997

Bibliographic source:

Drug Metabolism and Disposition, 25: 3 371-378

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Groups of rats and mice were exposed topically to test material at 60, 30, 15, 7.5, 3.75 or 0 (vehicle control) mg/kg. During the study animals were weighed weekly. At sacrifice organ weights were determined and a histopathological evaluation was performed on the heart, ovary and skin. These organs were evaluated because they demonstrated possible lesions of interest at gross pathology.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,2-epoxycyclohexane

EC Number:

206-007-7

EC Name:

1,2-epoxycyclohexane

Cas Number:

286-20-4

Molecular formula:

C6H10O

IUPAC Name:

7-oxabicyclo[4.1.0]heptane

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): cyclohexene oxide

Test animals

Species:

other: rat & mice

Strain:

other: see the field "details on test animals and environmental conditions".

Sex:

male/female

Details on test animals or test system and environmental conditions:

FEMALE RATS F-344
- Housed in groups of 5 per cage.
- Source: Hilltop Lab Animals, Inc. Scottsdale, PA, USA

MALE AND FEMALE MICE B6C3F1
-Males housed individually and females in groups of 5 per cage.
- Source: Harlan Sprague-Dawley, Inc. Indianapolis IN, USA.

TEST ANIMALS
- Diet (e.g. ad libitum): Teklad 4% Mouse-rat diet, Teklad, Madison, WI, USA. ad libitum.
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: 14 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Controlled.
- Photoperiod (hrs dark / hrs light): 12 hrs light/ 12 hr dark.

Administration / exposure

Type of coverage:

not specified

Vehicle:

acetone

Details on exposure:

60, 30, 15, 7.5 or 0 (vehicle control) mg/kg test material. Each dose concentration remained constant, and the volume, 2mL/kg for rats, 0.5 mL/kg for mice, was adjusted weekly to maintain accurate mg/kg body weight.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Performed by capillary GC and found to be within 10% of the target concentration.

Doses / concentrations

Remarks:

Doses / Concentrations:
60, 30, 15, 7.5 and 3.75 mg/kg
Basis:
analytical per unit body weight

No. of animals per sex per dose:

5 animals per sex per species per dose.

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

- Animals were weighted on the first day of administration, once weekly and at sacrifice.

Sacrifice and pathology:

- Post mortem the following organs were weighed for all animals; liver, thymus, right kidney, right testicle, heart and lungs.
- Histopathological evaluation was performed on the following organs; heart, ovary and skin.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

not specified

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

Lesions: some lesions were noted, however they were not thought to be related to treatment with test material.

Effect levels

Dose descriptor:

NOEL

Effect level:

60 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no effects were seen at this level

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1. Weight gain and relative organ weights for rats and mice after dermal exposure to 60 mg/kg of Test Material

Test Animal	Body weight	Organ Weights % of control
	% of control	Liver	Heart	Kidney	Lung
Rats F-344
Male	100	99 ± 5	104 ± 4	101 ± 3	99 ± 8
Female	97	102 ± 4	99 ± 5	102 ± 3	95 ± 6
Mice B6C3F1
Male	99	99 ± 4	105 ± 4	101 ± 6	85 ± 15
Female	101	100 ± 4	97 ± 5	100 ± 5	100 ± 13

Applicant's summary and conclusion

Conclusions:

The study revealed no evidence of systemic toxicity at treatment with test material up to 60 mg/kg. No potential target organs were identified and no sexual differences were seen. The test concludes that after dermal exposure the test material is so volatile and absorbed so slowly that very little test material penetrates the skin, thus only a small amount of the test material will enter the body with less entering the target organ.

Executive summary:

Both male and female rat and mice were topically exposed to 60, 30, 15, 7.5, and 3.75 mg/kg of the test material during the study. Under the conditions of the study, no evidence of systemic toxicity at treatment with test material up to 60 mg/kg was seen. No potential target organs were identified and no sexual differences were seen. The test concludes that after dermal exposure the test material is so volatile and absorbed so slowly that very little test material penetrates the skin, thus only a small amount of the test material will enter the body with less entering the target organ.

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