Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2016-04-01 till 2016-06-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
Paris, 1987
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
May 2008, including most recent amendments
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147
Version / remarks:
November 2000; including the most recent partial revisions
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(2,4-dimethylcyclohex-3-en-1-yl)propan-1-ol
EC Number:
944-553-4
Cas Number:
1632042-40-0
Molecular formula:
C11H20O
IUPAC Name:
1-(2,4-dimethylcyclohex-3-en-1-yl)propan-1-ol
Test material form:
solid
Details on test material:
- Substance name as cited in test report: FRET 11-0571
- Phystical state: white solid
- Storage conditions: 15 - 25 °C

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: mean males 283 g, mean females 187 g
- Housing: animals were individually housed in labeled Makrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom)
- Diet: ad libitum, pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: ad libitum, tap water
- Acclimation period: at least 5 days (During the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18 cm))

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: One day before exposure (Day -1) an area of approximately 5x7 cm on the back of each animal was clipped.
- % coverage: The preparation was applied on an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females.
- Type of wrap if used: The preparation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only. Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).

REMOVAL OF TEST SUBSTANCE
- Washing: dressings were removed and the skin cleaned of residual test item using tap water
- Time after start of exposure: 24 hours

VEHICLE
- Amount(s) applied (volume or weight with unit): 10 mL/kg bw
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: twice daily for mortality/viability
- Frequency of weighing: days 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales: Maximum grade 4: grading slight (1) to very severe (4), Maximum grade 3: grading slight (1) to severe (3), Maximum grade 1: presence is scored (1).

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Lethargy, flat posture, hunched posture, uncoordinated movements, quick breathing, slow breathing, shallow respiration, piloerection, chromodacryorrhoea, ptosis, red secretion of the vagina and/or hypothermia were noted for the animals on Days 1 and/or 2.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
LOCAL EFFECTS
Focal erythema, erythema maculate, scales and/or scabs were seen in the treated skin-area of the animals during the observation period. These local effects were considered not to have affected the conclusion of the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions (OECD 402, GLP) the LD50 of the test substance is >2000 mg/kg bw.
Executive summary:

In a GLP compliant acute dermal study, according to OECD guideline 402, five Wistar rats per sex were exposed to the test substance. The test substance was administered by a single dermal application of 2000 mg/kg bw for 24 hours. After an observation period of 14 days animals were necropsied. No mortality occurred. Lethargy, flat posture, hunched posture, uncoordinated movements, quick breathing, slow breathing, shallow respiration, piloerection, chromodacryorrhoea, ptosis, red secretion of the vagina and/or hypothermia were noted for the animals on Days 1 and/or 2. The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of the test substance in Wistar rats was established to exceed 2000 mg/kg body weight.