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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:
For in-life testing -- Start : 23 April 2013 Completion : 07 May 2013
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study without deficiencies. The study was conducted on a close structural analog of alkylnaphthalene.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
Identification: Alkylated Naphthalene
Description: Clear amber slightly viscous liquid
Batch: 18515
Purity/Composition: UVCB 100%

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Species: Rat, Wistar strain, Crl:WI (outbred, SPF-Quality).
Source: Charles River Deutschland, Germany.
Number of animals 5 males and 5 females (females were nulliparous and non-pregnant).
Age and body weight: Young adult animals (approx. 10 weeks old) were selected.
Body weight variation did not exceed +/- 20% of the sex mean.
Identification Tail mark.
Health inspections were conducted 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.
Conditions
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Clipping: One day before exposure (Day -1) an area of approximately 5x7 cm on
the back of the animal was clipped.
Application: The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze (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).
Frequency: Single dosage, on Day 1.
Dose level (volume) 2000 mg/kg (2.273 mL/kg) body weight.
Dose volume calculated as dose level (g/kg) / specific gravity.
Application period: 24 hours, after which dressings were removed and the skin cleaned of residual test substance using tap water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 male and 5 female per dose
Control animals:
no
Details on study design:
Frequency: Single dosage, on Day 1.
Dose level (volume): 2000 mg/kg (2.273 mL/kg) body weight (Dose volume calculated as dose level (g/kg) / specific gravity).
Application period: 24 hours, after which dressings were removed and the skin cleaned of residual test substance using tap water.

Observations
Mortality/Viability: Twice daily. The time of death was recorded as precisely as possible.
Body weights: Days 1 (pre-administration), 8 and 15.
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).

Necropsy: All animals were sacrificed by oxygen/carbon dioxide procedure on Day 15. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.
Statistics:
None required

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities occurred.
Clinical signs:
Chromodacryorrhoea at the snout was noted in two males and three females on Days 1 and 2 only.
Scabs were seen in one female on Days 7 and 8 only.
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.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value of alkylated naphthalene in Wistar rats was established to exceed 2000 mg/kg body weight.
Based on these results, alkylated naphthalene does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) and the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.
Executive summary:

An assessment of acute dermal toxicity was conducted with Alkylated Naphthalene in the rat. The study was carried out based on the guidelines described in:

OECD No.402 (1987) "Acute Dermal Toxicity", Commission Regulation (EC) No 440/2008, B3: "Acute Toxicity (Dermal)"

EPA, OPPTS 870.1200. (1998), "Acute Dermal Toxicity", JMAFF Guidelines (2011); including the most recent revisions.

Alkylated Naphthalene was administered to five rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight.

Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

Results

No mortality occurred.

Chromodacryorrhoea at the snout was noted in two males and three females on Days 1 and 2 only.

Scabs were seen in one female on Days 7 and 8 only.

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 Alkylated Naphthalene in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, Alkylated Naphthalene does not have to be classified and has no obligatory labelling requirement for

acute dermal toxicity according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011),

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.