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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study. Lack of details on test material (analytical purity), no data on GLP. Refer to endpoint summary Acute toxicity and IUCLID Section 13 for reporting and justification of the analogue approach.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982
Reference Type:
secondary source
Title:
European Union Risk Assessment Report: Cyclohexane; CAS No: 110-82-7; EINECS No: 203-806-2
Author:
EUROPEAN COMMISSION - European Chemicals Bureau
Year:
2004
Bibliographic source:
European Chemical Bureau - Institute for Health and Consumer Protection

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
lack of details on test material (analytical purity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Cyclohexane
- Molecular formula: C6H12
- Molecular weight: 84.16
- Smiles notation: C1CCCCC1
- InChl: 1S/C6H12/c1-2-4-6-5-3-1/h1-6H2
- Analytical purity: no data

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Laboratory Animals, Inc.
- Age at study initiation: young adults
- Weight at study initiation: 2645-3125 g (males); 2640-3000 g (females)
- Housing: individual
- Diet: Purina Lab Rabbit Chow(R), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the test material was applied to the shaved back.
- % coverage: 10
- Type of wrap if used: the test material was held in contact with the skin by means of a non-absorbent binder.

REMOVAL OF TEST SUBSTANCE
- Washing: the exposed area was wiped (but not washed) to remove any test material remaining.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: ca. 6.86-8.12 mL (as calculated from the reported body weight data and a density of 0.77 g/cm³ (EC –ECB, 2004)
- Constant volume or concentration used: no
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality and gross pharmacological and toxicological signs were recorded immediately after dosing, at 1 and 4 h, and twice daily thereafter. Individual body weights were recorded just prior to initiation and on Days 7 and 14. Skin sites were evaluated for signs of irritation on Days 1, 3, 7, 10 and 14 according to the Draize scoring system.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy, skin irritation scoring.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred among the test animals during the study.
Clinical signs:
With the exception of phonation upon application, all rabbits appeared normal throughout the study.
Body weight:
All six rabbits gained weight between initiation and termination.
Gross pathology:
No observable gross pathology findings were noted in any of the rabbits upon necropsy.
Other findings:
Erythema on Day 1 ranged from very slight in 2 males and 2 females to well-defined in 1 female. Erythema on Day3 was noted as very slight in 2 males and 2 females and had cleared by Day 7.
Edema on Day 1 ranged from very slight in 1 male and 3 females to slight in 1 male and cleared by Day 3. Epidermal scaling was noted in 1 female on Day 10. Refer to Table 1.

Any other information on results incl. tables

Table 1. Individual dermal irritation scores

Animal No.

Erythema score

Edema score

Day

Day

1

3

7

10

14

1

3

7

10

14

Males

1

1

1

0

0

0

2

0

0

0

0

2

0

0

0

0

0

0

0

0

0

0

3

1

1

0

0

0

1

0

0

0

0

Females

1

1

1

0

0

0

1

0

0

0

0

2*

2

1

0

0

0

1

0

0

0

0

3

1

0

0

0

0

1

0

0

0

0

 

* This animal showed epidermal scaling on Day 10.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Cyclohexane was tested for acute dermal toxicity in rabbits (3 males and 3 females) in a study conducted following a protocol equivalent to OECD 402. The test substance was applied at 2000 mg/kg bw to an area of shaved dry skin covering approx. 10% of the total body surface, and held in contact with the skin for 24 h. Animals were observed for mortality and clinical signs for a period of 14 days following application. Body weights were determined weekly and skin reactions were evaluated according to the Draize scoring system 24 and 72 h and 7, 10 and 14 days post-application. No mortality occurred and the only clinical sign reported was phonation upon application. Animals showed normal body weight development and necropsy revealed no treatment-related changes. In 5/6 animals, very slight to slight erythema was observed at the 24 and 72 h reading time points, and very slight to slight edema was seen only at 24 h. Skin redness was fully reversible within 7 days post-application. One animal showed epidermal scaling on Day 10. Based on the study results, the dermal LD50 in male and female rabbits is greater than 2000 mg/kg bw.

In this study, no mortality and no signs of systemic toxicity were observed. Therefore, the results do not fulfil the classification criteria for acute toxicity by the dermal route according to Regulation (EC) No 1272/2008 and Directive 67/548/EEC.

CLP: not classified
DSD: not classified