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Toxicological information

Repeated dose toxicity: dermal

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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

Reference
Name:
Unnamed
Type:
Constituent
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 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.