Dodecanoic acid, ester with 1,2,3-propanetriol

Endpoint summary

Description of key information

Oral (read-across OECD 401): LD50 > 5000.0 mg/kg bw

Inhalation (read-across OECD 403): LC50 > 1.86 mg/L air (analytical)

Dermal (read-across OECD 402): LD50 > 2000.0 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:

08 Feb - 22 Feb 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Lack of details on test material

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 24 Feb 1987

Deviations:

yes

Remarks:

lack of details on test material

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bantin & Kingman Ltd., Grimston, Aldborough, Hull, UK
- Age at study initiation: 5-8 weeks
- Weight at study initiation: 145-160 g (males), 139-151 g (females)
- Fasting period before study: overnight
- Housing: groups of up to five by sex in solid-floor polypropylene cages with sawdust bedding
- Diet: Rat and Mouse Expanded Diet No. 1 (Special Diet Services Ltd., Witham, Essex, UK), ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 40-65
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 500 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: For the purpose of the study, the test material was freshly prepared as a solution/suspension at the appropriate concentration in arachis oil B.P. The preparation was warmed to aid solubilisation.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed 1 and 4 h after dosing and subsequently once daily for 14 days. Deaths and evidence of overt toxicity were recorded at each observation. Individual body weights were recorded on the day of treatment (Day 0) and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No overt signs of toxicity were noted during the study.

Gross pathology:

No abnormalities were noted at necropsy of animals killed at the end of the study.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

National guideline study

Qualifier:

according to guideline

Guideline:

other: "Appraisal of the safety of chemicals in foods, drugs and cosmetics" by the Staff of the Division of Pharmacology", FDA, 1959

Deviations:

not specified

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Zucht Winkelmann, Paderborn, Germany
- Weight at study initiation: 120-145 g (males), 115-145 g (females)
- Fasting period before study: 16 h
- Housing: single caging
- Diet: standard laboratory diet (Ssniff/Intermast), ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 45-55
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50%
- Amount of vehicle (if gavage): 20 and 40 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 40 mL/kg bw

DOSAGE PREPARATION: The test substance was diluted in olive oil to a final concentration of 50%.

- Rationale for the selection of the starting dose: Based on a range-finding study (not further described), dose levels of 10 and 20 g/kg bw were selected for the determination of the LD50 value.

Doses:

10,000 and 20,000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: animals were observed for clinical signs at 20 min, 1, 3, 24 and 48 h and 7 days post administration. Individual body weights were determined at study initiation (Day 0) and at the end of the observation period (Day 7).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 20 000 mg/kg bw

Based on:

test mat.

Mortality:

10,000 mg/kg bw: 0/5 males and 0/5 females died.
20,000 mg/kg bw: 1/5 males and 1/5 females were found dead at 48 h post-dose.

Clinical signs:

other: At both 10,000 and 20,000 mg/kg bw, slight staggering, ataxia and piloerection were observed 1 and 3 h post-dose (number of animals not specified). Effects were reversible within 24 h.

Gross pathology:

Gross necropsy of dead and sacrificed animals revealed no changes of the examined organs (brain, lung, heart, stomach, intestines, liver, spleen, kidneys, serous membrane/vessels, lymph nodes and gonads).

Table 1. Table for acute oral toxicity
Dose [mg/kg bw]	Mortalities [No. of animals/No. in group]	Time of death (post-administration)	Mortality [%]	Clinical signs / Duration
Males
10,000	0/5	-	0	Staggering, ataxia, piloerection / 1-3 h post-dose
20,000	1/5	48 h	20	Staggering, ataxia, piloerection / 1-3 h post-dose
Females
10,000	0/5	-	0	Staggering, ataxia, piloerection / 1-3 h post-dose
20,000	1/5	48 h	20	Staggering, ataxia, piloerection / 1-3 h post-dose

 

Table 2. Body weight and body weight gain
Animal number	Body weight on Day 0 [g]	Body weight on Day 7 [g]	Body weight gain [%]
Males (10,000 mg/kg bw)
1	130	155	19
2	135	160	19
3	120	135	13
4	140	150	7
5	145	165	14
Mean	134	153	14
Feales (10,000 mg/kg bw)
1	120	145	21
2	115	130	13
3	130	155	19
4	120	145	21
5	140	160	14
Mean	125	147	18
Males (20,000 mg/kg bw)
1	140	- (dead)	-
2	145	155	7
3	135	120	-11
4	140	145	4
5	145	155	7
Mean*	141.25	143.75	2
Females (20,000 mg/kg bw)
1	135	160	19
2	135	150	11
3	145	105	-28
4	140	- (dead)	-
5	145	160	10
Mean*	140	143.74	3

 *Calculations based only on surviving animals

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Lack of details on test material.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted 24 Feb 1987

Deviations:

yes

Remarks:

lack of details on test material

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: A. Tuck and Sons Limited, Battlesbridge, Essex, UK.
- Weight at study initiation: 220-265 g (males), 180-265 (females).
- Fasting period before study: animals were fasted 16-20 h prior to administration.
- Housing: by sex in suspended metal cages (370 x 360 x 180 mm) with mesh floors. A maximum of 5 animals were housed in each cage.
- Diet: Rat Diet (Nottingham University, School of Agriculture, Sutton Bonington, Near Loughborough, Leicestershire, UK), ad libitum.
- Water: tap water, ad libitum.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Air changes (per hr): min. 20
- Photoperiod (hrs dark / hrs light): 10/14

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 500 mg/mL
- Amount of vehicle (if gavage):
Range finder study: 2, 4, 10, 20 and 40 mL/kg bw
Main study: 40 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 40 mL/kg bw

Doses:

Range finder study: 1000, 2000, 5000, 10,000 and 20,000 mg/kg bw
Main study: 20,000 mg/kg bw

No. of animals per sex per dose:

Range finder study: 1
Main study: 5

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Range finder study: after dosing, animals were observed daily for 5 days, or until any evidence of toxicity had subsided, whichever was the longer, and any mortalities were recorded.
Main study: animals were observed 30 min, 1, and 4 h after dosing and once daily thereafter for 14 days. Any mortalities or evidence of overt toxicity were recorded. Body weights of all animals were recorded at Day 0 and at Day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy

Preliminary study:

No mortality occurred in the range finder study at any of the tested dose levels (1, 2, 5, 10 and 20 mg/kg bw). Clinical signs of toxicity were not reported.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 20 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Evidence of overt toxicity was confined to subdued activity and pilar erection within 1 h of dosing. Animals had recovered at 4 h. No further symptoms of toxicity were observed throughout the 14-day observation period, in any of the test animals.

Gross pathology:

Gross necropsy of all survivors at termination of the study revealed no abnormal macroscopic lesions.

Interpretation of results:

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) and consistent studies from three 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 studies are thus 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

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

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 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted: 12 May 1981

Deviations:

yes

Remarks:

only male animals tested; lack of details on test substance

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted: 7 Sep 2009

Deviations:

yes

Remarks:

only male animals tested; lack of details on test substance

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Willi Gassner, Sulzfeld, Germany
- Weight at study initiation: approximately 170 g
- Housing: 2 animals per Makrolon Type 3 cage with Vermiculite pad
- Diet: standard pelled diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 60 ± 5

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindric inhalation chamber "INBIFO-MAKROLON-Tierrohre Typ 1" with stainless steel head cones, according to KIMMERLE apparatus with 20 animal tubes
- Exposure chamber volume: 40 L
- Method of holding animals in test chamber: cylindric tube
- Source and rate of air: 7.11 L air flow/min
- Method of conditioning air: 0.2 mL of test substance per min was pumped using a dosing pump (BRAUN, Melsungen, Germany)
- System of generating particulates/aerosols: aerosol nozzle, nozzle orifice 0.15 mm (BUNDSCHUH, Griesheim, Germany)
- Measured test substance concentration in inhalation chamber: 28.1 µL/ L air

"Zyklon" (BCRIA sampler) was used to sample precipitated particles with a particle size > 5 µm
A cambridge filter was used to sample respirable particles.
Gravimetric analyses were performed to determine the respirable test substance concentration.

TEST ATMOSPHERE
- Brief description of analytical method used: during exposure every hour the aerosol concentration was measured in the inhalation chamber directly in the area of animals noses (head cones)
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.97 µL test substance / L air was < 5 µm diameter

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gravimetric analyses were performed to determine the respirable test substance concentration.

Duration of exposure:

6 h

Concentrations:

28.1 µL/L air (calculated concentration)
measured respirable test substance concentration: 1.97 µL/ L air (< 5 and < 10 µm diameter particle size)

No. of animals per sex per dose:

10

Control animals:

other: yes, sham-exposed

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: during exposure, after exposure and thereafter daily
- Frequency of weighing: at beginning, directly after exposure and at the end of 14 days observation period
- Necropsy of survivors performed: yes, 3 test animals and 1 control animal were euthanized 1 h after exposure, all other animals were necropsied 14 days after exposure
- Other examinations performed: Trachea and lungs of all animals were histopathologically analysed.

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 1.97 other: µL/L air (analytical)

Based on:

test mat.

Exp. duration:

6 h

Remarks on result:

other: max. attainable concentration

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 1.86 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

6 h

Remarks on result:

other: converted from µL/L by using a mean specific gravity value of 0.947

Mortality:

No mortality occured during the study period.

Clinical signs:

other: No clinical signs toxicity were observed in any of the animals during the 14-day observation period.

Body weight:

No effect on body weight was noted.

Gross pathology:

No abnormal findings.

Other findings:

Histopathology: No abnormal findings in lungs or tracheae.
Microscopically no deposits of oily test substance could be detected in the respiratory tissues.

According to the descriptions in this study report it can be assumed that the maximum attainable concentration of the test substance was used for aerosol inhalation exposure.

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 an adequate, reliable (Klimisch score 2) and consistent study from a reference substance 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 dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

22 Mar - 07 Apr 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted in 1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Bor: WISW

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Weight at study initiation: 250-260 g (males), 209-238 g (females)
- Housing: up to 5 animals per cage in Makrolon type III
- Diet: Ssniff R 10 - Complete feed for rats (Ssniff, Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsum
- % coverage: 10%
- Type of wrap if used: gauze and acrylastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: residual test material was removed with warm water and gauze
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2.08 cm³/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: several times on Day 0, thereafter daily
- Frequency of weighing: Days 0, 7 and 14
- Necropsy of survivors performed: yes

Key result

Sex:

male/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 signs of systemic toxicity observed.

Gross pathology:

Necropsy revealed no substance-related findings.

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:

key study

Study period:

16 Dec - 30 Dec 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(1987)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

Commission Regulation (EC) No 440/2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

(1998)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No. 8147, November 2000

Version / remarks:

(2000)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Wistar Crl:WI (Han) (outbred, SPF-Quality)

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: approx. 10 weeks
- Weight at study initiation: 277 - 304 g (males) and 184 - 202 g (females)
- Housing: individually housed in labelled Macrolon cages (Mlll type) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Nonham Mill Ltd), Surrey, UK).
- Diet: pelleted rodent diet (SM R/M-Z from SSNlFF® Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0 ± 3.0
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

polyethylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: approx. 25 cm² on the dorsal area (males) and 18 cm² (females), respectively
- % coverage: 10%
- Type of wrap if used: dressing consisting of a surgical gauze patch (Surgy 1D, Laboratoires Stella sa., Liege, Belgium), successively covered with aluminum foil and Coban elastic bandage (3M, St. Paul, MN, USA.). A piece of Micropore tape (3M, St. Paul, MN, USA) was additionally used for fixation of the bandages in females only.

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg bw
- Concentration (if solution): 200 mg/mL

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed twice daily for mortality and viability, and individual body weights were determined at Day 1 (pre-administration), 8 and 15; clinical signs were determined at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/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: Flat posture was noted among all animals on Day 1. Chromodacryorrhoea was observed in 3/5 males and in 2/5 females on Day 1. Ptosis was determined in 2/5 males and in 4/5 females. 3/5 females showed restless behaviour on Day 1. Scales and scabs of the rig

Gross pathology:

Necropsy revealed no substance-related findings.

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, reliable (Klimisch score 1) and consistent studies from two 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 studies are 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

No data on the acute inhalation and dermal toxicity ofDodecanoic acid, ester with 1,2,3-propanetriol (CAS 37318-95-9)are available. The assessment of acute 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 No. 91744-28-4

The acute oral toxicity of Glycerides, C12-18 di- and tri- was investigated in a GLP-conform study performed according to OECD guideline 401 (Key, 1989). Groups of 5 Sprague Dawley rats per sex received the undiluted test substance via gavage at a limit dose of 5000 mg/kg bw. No mortality and no signs of toxicity occurred during the 14-day observation period. All animals showed the gain in body weight expected for this species and strain. Macroscopic examination of animals at termination did not reveal any treatment-related findings. Based on the results of the study, the oral LD50 value for male and female Sprague Dawley rats is > 5000 mg/kg bw.

 

CAS No. 142-18-7

The acute oral toxicity of 2,3-dihydroxypropyl laurate was investigated in Wistar rats according to the national FDA guideline "Appraisal of the safety of chemicals in foods, drugs and cosmetics" (Supporting, 1977). In this experiment, 2 groups of 5 animals per sex and dose were administered the test material in the vehicle (corn oil) by gavage at doses of 10000 and 20000 mg/kg bw, respectively. One of the 5 males and 1/5 female treated with 20000 mg/kg bw died 48 h after test substance administration. No mortality was observed at 10000 mg/kg bw during the 7-day observation period. At both dose levels, slight staggering, ataxia and piloerection were observed 1 and 3 h post-administration (number of animals not specified). The observed clinical signs were reversible within 24 h. Body weight gains were reduced in the surviving males and females of the 20000 mg/kg bw group from Day 0 to Day 7. This effect was mainly attributed to a strong decrease in body weight in 1/4 males and 1/4 females at study termination (ca. -11 and -28%, respectively). The body weight gain of the remaining 3 animals per sex ranged from 4 to 7% (males) and 10 to 19% (females). The body weight gain of male and female animals treated with 10000 mg/kg bw was within the normal range for this species and strain. The mean group body weight gain was about 14 and 18% for males and females, respectively. Necropsy revealed no substance-related findings in the examined organs (brain, lung, heart, stomach, intestine, liver, spleen, kidneys, serous membrane/vessels, lymph nodes and gonads). Based on the results, the oral LD50 value for male and female Wistar rats is > 20000 mg/kg bw.

 

CAS No. 555-43-1

In an acute oral toxicity study performed similar to OECD guideline 401, 5 male and 5 female Sprague Dawley rats were administered Glycerol tristearate diluted in arachis oil at a limit dose of 20000 mg/kg bw via gavage (supporting, 1980). No mortality occurred up to the end of the 14-day observation period. Evidence of overt toxicity was confined to subdued activity and piloerection within 1 h of dosing, but these effects were fully reversible within 4 h after test substance administration. No significant effect on body weight (gain) was observed. Gross necropsy revealed no abnormal macroscopic lesions. Under the conditions of this experiment, the oral LD50 value for male and female Sprague Dawley rats is > 20000 mg/kg bw.

Acute inhalation toxicity

CAS No. 73398-61-5

The acute inhalation toxicity of Triglycerides, mixed decanoyl and octanoyl was studied in rats according to OECD guideline 403 and in compliance with GLP (Key, 1976). A group of 10 male rats was exposed to a calculated concentration of 28.1 µL/L air for 6 h using a nose only exposure system. The measured respirable test substance concentration was 1.97 µl/L (particles with a diameter below 10 µm) corresponding to an atmosphere concentration of the test aerosol of 1.86 mg/L. This was considered the maximum attainable concentration of respirable particles. 10 male control animals were sham-exposed. No mortality and no clinical signs of toxicity were observed in any of the animals during exposure and the 14-day observation period. The Body weight (gain) observed was within the range expected for this species and strain. At necropsy, no abnormalities were noted. Microscopic examination did not reveal any abnormal findings in lungs or tracheae and no deposits of the oily test substance in the respiratory tissues were detected. Based on these results, the inhalation LC50 value for male rats is > 1.86 mg/L.

Acute dermal toxicity

CAS No. 91052-13-0

The acute dermal toxicity of Glycerides, C8-18 and C18-unsatd. mono- and di-, acetates was investigated in a limit test according to OECD guideline 402 and in compliance with GLP (Key, 2010). In this study, 5 male and 5 female rats were treated with the test substance at a dose of 2000 mg/kg bw. The test substance was dissolved in polyethylene glycol at a concentration of 200 mg/mL and applied onto the shaved skin of the test animals (10 mL/kg bw) for 24 h under occlusive conditions. After exposure, residual test substance was removed and animals were observed for a period of 14 days. No mortalities occurred and body weight gain of all animals was within the normal range during the whole study period. Flat posture was noted in all animals on Day 1. On the same day, chromodacryorrhoea was observed in 3/5 males and in 2/5 females. Ptosis was seen in 2/5 males and in 4/5 females, and 3/5 females showed restless behaviour on Day 1. Scales and scabs of the right flank and/or treated skin were observed among 3/5 males and 1/5 females between Days 4 and 15. Effects on skin were reversible within 15 days, except of 1 male, where scales remained up to day 15. At necropsy, no substance-related findings were noted. Therefore, the dermal LD50 value in male and female rats is > 2000 mg/kg bw.

 

CAS No. 620-67-7

The acute dermal toxicity of propane-1,2,3-triyl trisheptanoate was tested in accordance with OECD guideline 402 and in compliance with GLP (Supporting, 1993). In this study, 5 male and 5 female rats were exposed to the test substance at a limit dose of 2000 mg/kg bw for 24 h. The test substance was applied unchanged to the shaved skin of the test animals under semiocclusive conditions. After 24-h exposure, residual test substance was removed and animals were observed for 14 days. No treatment-related mortalities occurred and no signs of systemic toxicity were observed. All animals showed the gain in body weight expected for this species and strain. No skin irritation was observed in the application zone. No test substance-related abnormalities were found at macroscopic post-mortem examination of the animals. 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 source substances indicate a very low level of acute toxicity following the oral, inhalation and dermal route, as LD50 and LC50 values were greater than the currently applied limit values. Therefore, as the available data did not identify any hazard for acute toxicity, Dodecanoic acid, ester with 1,2,3-propanetriol is not expected to be hazardous following acute exposure.

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 Dodecanoic acid, ester with 1,2,3-propanetriol (CAS 37318-95-9), data will be generated from information on 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 target substance information and 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.