Dodecyl laurate

Endpoint summary

Description of key information

Oral (similar to OECD 401, read across): LD50 rat > 5000 mg/kg bw

Dermal (OECD 402, read across): LD50 rat > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Basic data given. The analytical purity of the test substance was not reported.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

the analytical purity of the test substance is not reported

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 176-296 g
- Fasting period before study: overnight
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50%
- Amount of vehicle (if gavage): 5 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

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 observations and weighing: observations of mortality and signs of toxicity were made 1, 3, 4, 6 and 24 h after administration and daily thereafter; animals were weighed prior to dosing and prior to necropsy.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

One male rat died on day 4 after administration. No information on the cause of death was provided.

Clinical signs:

other: No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Gross pathology:

No substance-related findings were noted during the necropsy.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

20 Dec 1995 - 03 Jan 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

: only basic data given, test substance purity not specified

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

mouse

Strain:

Swiss

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 20 g (medium weight)

Route of administration:

oral: gavage

Vehicle:

not specified

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs of toxicity were observed.

Gross pathology:

No effects were observed.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

12 - 18 Mar 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Principles of method if other than guideline:

To determine the LD50 of the test substance, 5000 mg/kg bw was administered to 5 female mice orally. The mice were observed for mortality and signs of toxicity for 6 days after dosing. The body weights were recorded on day 0 prior to dosing and on day 6.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

mouse

Strain:

other: NMRI EOPS

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 19-20 g
- Fasting period before study: 4 h

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 6 mL/kg bw

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 6 days
- Frequency of observations and weighing: the animals were observed for mortality and signs of toxicity daily; the body weight was recorded on day 0 prior to dosing and on day 6
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, mortality, body weight

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No signs of toxicity were observed.

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 (RL2) from reference substances with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 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

Reference

Reference 1

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:

other: 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:

other: 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

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

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Secondary literature only. Few details on the study protocol were reported, no necropsy was performed, the analytical purity of the test substance was not specified, observation period was not reported.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

few details on study protocol reported, no necropsy performed, observation period not reported, no individual data

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

other: albino

Sex:

not specified

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

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

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

10 per dose

Control animals:

no

Details on study design:

- Necropsy of survivors performed: no
- Other examinations performed: mortality, clinical signs, local skin irritation effects

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality during the study period.

Clinical signs:

other: No signs of toxicity were observed during the study period.

Other findings:

- Other observations: the maximum skin irritation scores noted were well defined erythema (grade 2 of 4) and very slight edema (grade 1 of 4)

Interpretation of results:

study cannot be used for classification

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate and reliable study data (RL1) and secondary source data (RL4) from reference substances with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 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 oral, inhalation and dermal toxicity of Lauryl laurate (CAS 13945-76-1) are not available. The assessment of acute oral and dermal toxicity was therefore based on studies conducted with analogue 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 3234-85-3

The acute oral toxicity of Tetradecanoic acid, tetradecyl ester (CAS 3234-85-3) was assessed in a study comparable to OECD guideline 401 (key study, 1976). 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 in rats was found to be > 5000 mg/kg bw.

CAS 95912-86-0

The acute oral toxicity of Fatty acids, C8-10, C12-18-alkyl esters (CAS 95912-86-0) was assessed in a study comparable to OECD guideline 401 (supporting study, 1991). Administration of 5000 mg/kg bw to 5 female NMRI mice via the oral route did not cause mortality and no clinical signs were recorded during the 6-day observation period. There were no effects on body weight. The acute oral LD50 in mice was found to be > 5000 mg/kg bw.

CAS 20292-08-4

The acute oral toxicity of 2-ethylhexyl laurate (CAS 20292-08-4) was assessed in a study comparable to OECD guideline 401 (supporting study, 1996). Administration of 2000 mg/kg bw to 5 female mice 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 in female mice was found to be > 2000 mg/kg bw.

Acute dermal toxicity

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 is considered to be > 2000 mg/kg bw.

CAS 3234-85-3

A summary of an acute dermal toxicity study is available in a CIR review (supporting study, 1982). Ten (10) rabbits were exposed to 2000 mg/kg bw tetradecyl myristate (CAS 3234-85-3) by dermal application for 24 h. There was no mortality during the study period (unknown duration) and no treatment -related clinical signs were observed. The maximum skin irritation scores reported were well-defined erythema (score 2) and very slight oedema (score 1). No details were given regarding the duration and number of animals with skin irritation effects. The LD50 was > 2000 mg/kg bw.

Overall conclusion for acute toxicity

The reliable data available for the 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 currently applied limit values. Therefore, as the available data did not identify any hazard for acute toxicity, Lauryl laurate 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 Lauryl laurate, 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 toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.