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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 September 2016 to 06 October 2016
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)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3-(4-isobutyl-2-methylphenyl)propanal
EC Number:
811-285-3
Cas Number:
1637294-12-2
Molecular formula:
C14H20O
IUPAC Name:
3-(4-isobutyl-2-methylphenyl)propanal
Test material form:
liquid
Specific details on test material used for the study:
Name (as stated in the report): GR-88-0778
Lot No: SC00018060
Aspect: Colourless liquid
Expiration date: 28 April 2017 (expiry date)

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI (Han) (outbred, SPF-Quality).
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Number of animals: 5 males and 5 females (females were nulliparous and nonpregnant).
- Age and body weight: Young adult animals (approx. 10-11 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
- Identification: Tail mark with indelible ink.
- Health inspection: At least prior to dosing. It was ensured that the animals were healthy and that the skin to be treated was intact and free from any abnormality.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Remarks:
The test item was dosed undiluted as delivered by the Sponsor
Details on dermal exposure:
The test item 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. The test item 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.
Duration of exposure:
- Frequence: Single dosage, on Day 1.
- Application period: 24 hours, after which dressings were removed and the skin cleaned of residual test item using tap water.
Doses:
- Dose level (volume): 2000 mg/kg (2.10 mL/kg) body weight. Dose volume calculated as dose level (g/kg) / specific gravity (0.9516).
No. of animals per sex per dose:
1 group of 5 males and 5 females / 1 dose per group
Control animals:
no
Details on study design:
Initially, NYMPHEAL was administered to three female Wistar rats by a single dermal application at 2000 mg/kg body weight for 24 hours. Based on results, an additional group of two females and five males were dosed at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was scheduled to be performed after terminal sacrifice (Day 15).

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:
Flat posture, piloerection, lethargy, quick breathing, shallow respiration, pstosis and/or chromodacryorrhoea on the snout were noted for all animals between Days 1 and 5.
Body weight:
The mean body weight gain during the observation period was within the range expected for rats used in this type of study.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of NYMPHEAL in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

The acute dermal toxicity with NYMPHEAL in the rat was assessed according the OECD No.402 (1987) "Acute Dermal Toxicity".

Initially, NYMPHEAL was administered to three female Wistar rats by a single dermal application at 2000 mg/kg body weight for 24 hours. Based on results, an additional group of two females and five males were dosed at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was scheduled to be performed after terminal sacrifice (Day 15).

No mortality occurred.

Flat posture, piloerection, lethargy, quick breathing, shallow respiration, pstosis and/or chromodacryorrhoea on the snout were noted for all animals between Days 1 and 5. The mean body weight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination.

The dermal LD50 value of NYMPHEAL in Wistar rats was established to exceed 2000 mg/kg body weight.