Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral (similar to OECD 401): LD50 m/f rat > 2000 mg/kg bw

Dermal (read across, OECD 404): LD50 m/f rat > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 Jun - 03 Jul 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
lack of details on test item, no pathology, no body weighing at end of study period
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
yes
Remarks:
no pathology, no body weighing at end of study period
Principles of method if other than guideline:
No information on test guidelines was given in the study report.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other:
Remarks:
Ico rats from Iffa-Credo, L'Arbresle, France
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Iffa-Credo, L'Arbresle, France
- Females non-pregnant: yes
- Age at study initiation: 5-7 weeks old
- Weight at study initiation: Mean body weight at study start: 141 g in females and 156 g in males
- Fasting period before study: for 15-20 hours
- Housing: groups of 5 in stainless steel mash cages
- Diet: Rat pelleted complete maintenance feed, ad libitum
- Water: softened and filtered drinking water, ad libitum (bacteriological and chemical control every 6 months)
- Acclimation period: minimum 48 hours

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 09 Jun 1986 - 23 Jun 1986
Route of administration:
oral: gavage
Vehicle:
paraffin oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50% (w/v),
- Purity: sterile Codex liquid paraffin

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: heated at 40 degree Celsius in a water bath
Doses:
5000 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 weighing: immediately before test item administration
- Necropsy of survivors performed: no
Clinical examinations and mortality: at 0.25, 1, 2, and 4 hours after oral gavage and once daily thereafter.
Statistics:
None
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortalities occurred during the study.
Clinical signs:
No abnormal clinical signs were reported.
Body weight:
Body weights were only determined shortly prior to administration.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
Limited documentation on GLP, test item, methods
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted in 1981
Deviations:
yes
Remarks:
limited report details
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted in 1987
Deviations:
yes
Remarks:
limited documentation only
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
mouse
Strain:
NMRI
Sex:
male/female
Route of administration:
oral: unspecified
Vehicle:
maize oil
Details on oral exposure:
At 5000 mg/kg bw the product was a powder mixed with maize oil. At 20 g/kg bw the product was administered as provided.
Doses:
5000 mg/kg bw and 20000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 20 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortality occurred during the study.
Clinical signs:
No clinical signs of systemic toxicity were reported.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate and reliable studies (Klimisch score 2). The selected studies are sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1974
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Qualifier:
no guideline followed
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
occlusive
Vehicle:
water
Remarks:
50% slurry of the ingredient in distilled water
Details on dermal exposure:
TEST SITE
- Area of exposure: not stated
- Type of wrap if used: gauze and impervious material

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not stated

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw of the slurry

VEHICLE
Distilled water
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
10 rabbits, no sex reported
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
5 rabbits with intact skin and 5 with epidermal abrasions
Mortality:
No mortality.
Clinical signs:
Not reported
Body weight:
Not reported
Gross pathology:
Not reported

The slurry caused only a slight dermal irritation with scores of one and two at 24 hours. No deaths occurred during a 14-day period, and it was concluded that the material is not dermally toxic under the conditions of the test.

Interpretation of results:
study cannot be used for classification
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 May - 2 Jun 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The test substance was applied with an occlusive dressing.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
the test substance was applied with an occlusive dressing
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
the test substance was applied with an occlusive dressing
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
the test substance was applied with an occlusive dressing
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No. 8147, November 2000; including the most recent partial revisions
Deviations:
yes
Remarks:
the test substance was applied with an occlusive dressing
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Wistar Crl:WI (Han)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 10 weeks
- Weight at study initiation: 269-284 g (males), 181-194 g (females)
- Housing: animals were housed individually in labelled Makrolon cages (MIII type, height 18 cm) containing sterilised 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, UK). During the acclimation period the animals were housed in groups in Macrolon cages (MIV type).
- Diet: pelleted rodent diet (SM R/M-Z from SSNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6-21.2
- Humidity (%): 39-62
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the back of the animals; approximately 25 cm² for males and 18 cm² for females
- % coverage: 10
- Type of wrap if used: the test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D) covered with aluminium foil and Coben elastic bandage, respectively. A piece of Micropore tape was used to fix the bandage in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was cleaned using tap water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: yes, the dose volume was calculated as dose level (g/kg) / density (g/mL)
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other: an untreated, adjacent skin area served as the control
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed twice daily for mortality; the body weight was recorded on Day 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: yes, on Day 15 the animals were subjected to necropsy and all gross macroscopical abnormalities were recorded
- Other examinations performed: clinical signs were observed at periodic intervals on the day of dosing (day 1) and once daily thereafter, until sacrifice. The time of onset, degree and duration were recorded and the symptoms graded:
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)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality during the study period (see Table 1).
Clinical signs:
Piloerection was observed from 4 h - day 2 after dosing in 2/5 males (see Table 2). Chromodacryorrhoea (excessive secretion of a reddish-brown liquid from the eyes) (grade 1) was observed in 3/5 males 2-4 hours after dosing. No systemic clinical signs of toxicity were observed during the study period in females.
Body weight:
The body weight gains of males and females were within the normal ranges during the study period.
Gross pathology:
The necropsy and histopathological examination did not reveal substance-related findings.
Other findings:
- Other observations: On the treated skin area, erythema was observed for up to 4 days during Day 3-7 in 4/5 females. Scales or scabs (grade 1) were noted on the treated skin area in 5/5 females and 3/5 males for up to 9 days during Day 7-15 of the observation period.

Table 1: Mortality and clinical signs

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

2000

0/5/5

4 h – day 2 

Day 1-3

0

Females

2000

0/0/5

-

Day 1

0

LD50 > 2000 mg/kg bw

* first number = number of dead animals                                 

second number = number of animals with systemic clinical signs         

  third number = number of animals used                 Table 2: Clinical signs, systemic/local

Effect*

Max grade

Male No./duration (hours or day after dosing)

Female No./duration (hours or day after dosing)

 

 

1

2

3

4

5

6

7

8

9

10

Systemic

 

 

 

 

 

 

 

 

 

 

 

Piloerection

 1

4 h - 2 d

 

 

 

4 h - 2 d

 

 

 

 

 

Chromoda-cryorrhoea

 3

 

2 - 4 h

2 - 4 h

4 h

 

 

 

 

 

 

Local

 

 

 

 

 

 

 

 

 

 

 

Erythema, focal

 4

 

 

 

 

 

7 d

 

7 d

3 – 7 d

7 d

Scales

 3

 

 

8 – 10 d

7 – 15 d

 

7 – 8 d, 14 d

8 – 11 d

7 – 9 d

7 – 8 d

7 – 9 d

Scabs

 3

 

7 - 11 d

 

9 - 15 d

 

8 – 13 d

 

 

 

 

* all grade 1

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
12 - 26 Feb 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The test substance was applied using an occlusive dressing.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
occlusive dressing
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
occlusive dressing
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar Crl:(WI)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: 292 ± 13 g (mean ± SD, males); 199 ± 9 (mean ± SD, females)
- Fasting period before study: no
- Housing: animls were individually housed in labelled polycarbonate cages containing purified sawdust as bedding material (Woody SPF, supplied by B.M.I., Helmond, the Netherlands)
- Diet: standard pelleted laboratory animal diet (Carfil Quality BVBA, Oud-Turnhout, Belgium), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 12 Feb 1998 To: 26 Feb 1998
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the test substance was applied to an area of approximately 25 cm² for males and 18 cm² for females, using a gauze patch measuring 5x 5 cm and 3.5 x 5 cm, respectively. The test area was the back of the animal.
- % coverage: approximately 10% of total body surface
- Type of wrap if used: the gauze patch was fixed to aluminium foil and held in place with Coban elastic bandage (with drops of petrolatum). A piece of Micropore tape was used for additional fixation of the dressings in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was removed using a tissue moistened with tap water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw (10 mL/kg bw)
Duration of exposure:
24 h
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 and weighing: the animals were observed twice daily for mortality; clinical signs were observed at periodic intervals during the dosing day and once daily for the rest of the study period; the body weight was measured on Day 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes, the animals were examined for macroscopic abnormalities
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality during the study period (see Table 1).
Clinical signs:
Red staining of the neck fur (score 1 of 3) was observed in 1/5 females on Day 8-13. This is an effect that is frequently seen in rats under stressful conditions and is therefore not considered to be toxicologically relevant. No other clinical signs were noted in any animals during the study period.
Body weight:
The body weight gains were within the normal ranges in males and females during the whole study period.
Gross pathology:
The necropsy and histopathological examination did not revealed any substance-related findings.

Table 1: mortality and clinical signs

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

2000

0/0/5

- 

-

0

Females

2000

0/1/5

Day 8-13 

-

0

Overall LD50 > 2000 mg/kg bw

* first number = number of dead animals                                 

 second number = number of animals with systemic clinical signs         

 third number = number of animals used                               

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate and reliable studies (Klimisch scores 1-2) and additional secondary literature (Klimisch score 4). The selected studies are sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for read-across

Data on the acute inhalation and dermal toxicity of Hexadecyl palmitate (CAS 540-10-3) are not available. The assessment of acute dermal toxicity was therefore based on studies conducted with analogue source substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Acute oral toxicity

CAS 540-10-3

The acute oral toxicity of Hexadecyl palmitate (CAS 540-10-3) was assessed in a GLP study comparable to OECD guideline 401 (key study, 1986). Administration of 5000 mg/kg bw to 5 rats per sex via oral gavage did not cause mortality and no clinical signs were recorded during the 14-day observation period. There were no effects on body weight. The acute oral LD50 value in rats was found to be > 5000 mg/kg bw.

CAS 540-10-3

The acute oral toxicity of Hexadecyl palmitate (CAS 540-10-3) was assessed in a study performed according to OECD guideline 401, and with very limited documentation (supporting study, 1985). Administration of 5000 and 20000 mg/kg bw to 5 NMRI mice per sex via the oral route did not cause mortality and no clinical signs were recorded. The acute oral LD50 value in mice was found to be > 20000 mg/kg bw.

Brief summaries of 4 acute oral toxicity studies performed with Hexadecyl palmitate (Cetyl palmitate) were retrieved from the publication “Final Report on the Safety Assessment of Octyl Palmitate, Cetyl Palmitate and Isopropyl Palmitate”, International Journal of Toxicology, Jan 1, 1990 . In each, adult albino rats were given a single administration of diluted or undiluted Cetyl Palmitate via gavage. In the first study, a 5% dispersion in mineral oil was administered to 10 rats (4M, 6F) at 5000 mg/kg bw. One male died between Days 7 and 14. In the second study undiluted Cetyl Palmitate which had been melted was administered to 10 rats (5M, 5F) at doses of 5 mL/kg bw; one death occurred within 24 hours. In the third study, groups of five male rats each were given 0.464, 1.0, 2.15, 4.64, or 10.0 g of Cetyl Palmitate per kg bw, delivered as a 50% w/v suspension in corn oil. There was no mortality. In the fourth study, doses of 5.0, 7.12, 10.14, and 14.43 g of Cetyl Palmitate per kg bw were administered as a 50% slurry in corn oil to 10 rats at each dosage level. Diarrhoea in one rat at each level was observed three hours following administration. No deaths were reported. As the original study reports are unavailable, the information from the summaries was not taken into consideration for the hazard assessment.

Acute dermal toxicity

CAS 540-10-3

In secondary literature (Cosmetics Ingredient Review) the acute dermal LD50 value for Hexadecyl palmitate (Cetyl palmitate) was reported to be > 2000 mg/kg bw in a total of 10 rabbits (limit test) following 24 hours of exposure under occlusive conditions (supporting, 1982). No mortality was reported during the 14-day observation period.

CAS 3687-46-5

An acute dermal toxicity study (limit test) was performed with Decyl oleate (CAS 3687-46-5) according to OECD guideline 402 (key study, 2010). 2000 mg/kg bw of the test substance was applied to the skin of 5 Wistar rats/sex under an occlusive dressing for 24 hours. No mortality occurred. Clinical signs were observed in all males on Day 1 and/or 2; as piloerection (2/5 males) or chromodacryorrhoea (3/5 males). No clinical signs were noted in females. The body weight increases were within the range expected for rats used in this type of study and no treatment-related findings were reported during the necropsy and histopathological examination. Erythema (grade 1) was observed on the treated skin for up to 4 days during Day 3-7 in 4/5 females. Scales or scabs (grade 1) were noted on the treated skin area in 5/5 females and 3/5 males for up to 9 days during Day 7-15 of the observation period. The LD50 value is considered to be > 2000 mg/kg bw.

CAS 93803-87-3

The dermal effects of 2-octyldodecyl isooctadecanoate were investigated in an acute dermal toxicity GLP study performed similar to OECD guideline 402 (supporting study, 1998). In a limit test 2000 mg/kg bw of the undiluted test substance was applied to the shaved skin of 5 rats/sex for 24 h under occlusive conditions. After the exposure period, residual test substance was removed and the animals were observed for a period of 14 days. No mortality occurred. Red staining of the fur was observed in 1/5 females on Day 8 – 13. As this is a known sign of stress in rats, it was not considered to be a toxicologically relevant effect. Male and female rats showed the expected gain in body weight throughout the study. The necropsy and histopathological examination did not reveal any substance-related findings. Based on these results, the dermal LD50 value for male and female rats is > 2000 mg/kg bw.

Overall conclusion for acute toxicity

The reliable data available for the target and read-across analogue substances indicate a very low level of acute toxicity following the oral and dermal route, as LD50 values were greater than the recommended guideline limit values. Therefore, as the available data did not identify any acute toxicity, Hexadecyl palmitate (CAS 540-10-3) is not considered to be hazardous following acute exposure via the oral and dermal route.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Hexadecyl palmitate (CAS 540-10-3), data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the analogue read-across approach, the available data on acute oral and dermal toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.