Registration Dossier

Administrative data

Description of key information

Acute oral LD50 > 5000 mg/kg bw (according to the OECD 423 guideline, as no mortality was observed at 2000 mg/kg the LD50 is considered to be greater than 5000 mg/kg).
Acute dermal LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Start : 17 April 2013 Completion : 03 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 alkyl naphthalene.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
6 Females (nulliparous and non-pregnant) were used. Each dose group consisted of 3 animals.
Animals were young adult animals (approx. 10 weeks old).
Body weight variation did not exceed +/- 20% of the sex mean.
Identification was by Earmark and tail mark.
Health inspections were conducted at least prior to dosing. It was ensured that the animals were healthy and without any abnormality that might affect the study integrity.

Animal husbandry
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.

Accommodation:
Group housing of 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
Acclimatization period was at least 5 days before start of treatment under laboratory conditions.

Diet:
Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).

Water:
Free access to tap water.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Method: Oral gavage, using plastic feeding tubes.
Fasting: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum.
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.
Doses:
Single dose at 2000 mg/kg
No. of animals per sex per dose:
Two groups of 3 females received the test material at 2000 mg/kg body weight.
Control animals:
no
Details on study design:
Observations:

Mortality/Viability - Twice daily.
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 symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
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 - At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
The oral LD50 value of the test substance was ranked within the following ranges: 0-5, 5-50, 50-300 or 300-2000 mg/kg b.w. or as exceeding 2000 mg/kg b.w. The LD50 cut-off value was established based on OECD guideline 423. No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Preliminary study:
LD50 greater than 5000 mg/kg.
No mortality observed at a dose of 2000 mg/kg in 6 treated female rats.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
None observed.
Clinical signs:
Hunched posture was seen in three females on Days 1 and/or 2.
Body weight:
The weight gain shown by the animals over the study period was considered to be similar to that
expected of normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
not classified
Remarks:
Migrated information According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight. Based on these results, the test substance does not have to be classified Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of alkylated naphthalene in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Based on these results, alkylated naphthalene does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.
Executive summary:

An assessment of acute oral toxicity with Alkylated naphthalene was conducted in the rat (Acute Toxic Class Method). The study was carried out based on the guidelines described in: OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method" Commission Regulation (EC) No 440/2008, B1 tris: "Acute Oral Toxicity, Acute Toxic Class Method" EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity" JMAFF guidelines (2011) including the most recent partial revisions.

Alkylated naphthalene was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred. Hunched posture was seen in three females on Days 1 and/or 2. The weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of Alkylated naphthalene in Wistar rats was established to exceed 2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight. Based on these results, alkylated naphthalene does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The studies are recently conducted GLP guideline studies without deficiencies.
The database is considered of high quality.
A substance with same EC number (410-190-0) identified during the Inquiry Process reported a rat acute oral toxicity study with and LD50 greater than 5000 mg/kg. Though a full study report is not available for review for this substance, the reported result strongly supports the result of the testing with the analog Alkylated Naphathalene.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
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.
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
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.
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
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
The studies are recently conducted GLP guideline studies without deficiencies.
The database is considered of high quality.
A substance with same EC number (410-190-0) identified during the Inquiry Process reported a rat acute dermal toxicity study with and LD50 greater than 2000 mg/kg. Though a full study report is not available for review for this substance, the reported result strongly supports the result of the testing with the analog Alkylated Naphathalene.

Additional information

An acute oral and an acute dermal toxicity study were conducted for alkylated naphthalene. Both studies were recent (2013) GLP studies following OECD guidelines. In the acute oral study, two groups of 3 female rats received 2000 mg/kg bw by oral gavage. No mortalities occurred. An acute dermal toxicity study was conducted with the material in which 5 male and 5 female rats received a single dose of 2000 mg/kg bw that was covered with an occlusive patch. None of the rats died following the treatment.

Both finding are supported by equivalent findings with another surrogate substance (EC 410 -190 -0).

Alkylated naphthalene has as very low vapor pressure and the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and no acute inhalation test was performed.


Justification for selection of acute toxicity – oral endpoint
GLP guideline study. Alkylated Naphthalene, EC 700-826-8 is a close structural analog of alkylnaphthalene as and the available acute toxicity testing can be used as read-across to the alkylnaphthalene .

Justification for selection of acute toxicity – dermal endpoint
GLP Guideline study. Alkylated Naphthalene, EC 700-826-8 is a close structural analog of alkylnaphthalene as and the available acute toxicity testing can be used as read-across to the alkylnaphthalene .

Justification for classification or non-classification

According to the OECD 423 test guideline, the acute oral LD50 cut-off value was considered to exceed 5000 mg/kg body weight. Based on these results, alkylated naphthalene does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

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.

Data for inhalative acute toxicity are not available.

Neither in the acute oral or acute dermal toxicity study specific target organ toxicity effects were seen thus not leading to classification for STOT SE (specific target organ toxicity, single exposure) according to GHS or CLP.

As the substance is a slightly viscous hydrocarbon, classification for aspiration hazards according to GHS respectively CLP is also not required.