Hexadecylnaphthalene

Endpoint summary

Description of key information

For the analogue the following data are available:

Acute oral LD50 > 2000 mg/kg bw
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:

experimental study

Adequacy of study:

key study

Study period:

Start : 17 April 2013 Completion : 03 May 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study without deficiencies.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system 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:

GHS criteria not met

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 Naphthalenedoes 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 Naphthalenewas 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

Value:

2 000 mg/kg bw

Quality of whole database:

data based on structural analogue

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:

experimental study

Adequacy of study:

key study

Study period:

For in-life testing -- Start : 23 April 2013 Completion : 07 May 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study without deficiencies

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system 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:

GHS criteria not met

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),
- 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

Value:

2 000 mg/kg bw

Quality of whole database:

data based on structural analogue

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.

Justification for classification or non-classification

Based on the available data the substance does not need to be classified for acute toxicity according to the criteria given in Regulation (EC) No 1272/2008.