Lauric acid, ester with hydroxypropanediyl diacetate

Endpoint summary

Description of key information

Oral: LD50 = > 2000 mg/kg bw 
Inhalation: LC50 > 9.65 mg/L (time-extrapolated value, corresponding to 1.86 mg/L after 6 h exposure)
Dermal: LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

16 Dec 2009 - 05 Jan 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP-Guideline study, tested with the source substance Glycerides, C8-18 and C18-unsatd. mono- and di-, acetates (CAS 91052-13-0). According to the ECHA guidance document 'Practical guide 6: How to report read-across and categories' (ECHA, 2012), the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-aross substance.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

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:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: young adult animals (approx. 9-10 weeks old)
- Weight at study initiation: 160-190 g, body weight variation did not exceed ± 20% of the sex mean
- Fasting period before study: animals were deprived of food overnight prior to dosing and until 3-4 h after administration of the test substance, water was available
- Housing: group housing of 3 animals per cage in labeled Macrolon 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, UK).
- Diet: pelleted rodent diet (SM R/M-Z from SSNlFF® Spezialdiaten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3 (actual range: 18.4- 21.8)
- Humidity (%): 40-70 (actual range: 31 - 88)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: the vehicle was selected based on trial formulations performed at the testing labotatory and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: according to OECD guideline 423

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality: twice daily; clinical observations: daily; bodyweight: Day 1, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: According the OECD test guideline 423, Annex 2b, the LD50 was considered to exceed 5000 mg/kg body weight.

Mortality:

No mortality occurred during the study period.

Clinical signs:

Hunched posture and/or piloerection was observed among all females on Day 1.

Body weight:

The body weight gain of the treated 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:

Necropsy revealed no substance-related findings.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified

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 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 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:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given (comparable to guideline study).

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

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.

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

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:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable (Klimisch score 2) 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

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

16 - 30 Dec 2009

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP-Guideline study, tested with the source substance Glycerides, C8-18 and C18-unsatd. mono- and di-, acetates (CAS 91052-13-0). According to the ECHA guidance document 'Practical guide 6: How to report read-across and categories' (ECHA, 2012), the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-aross substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

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:

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 right flank and/or treated skin were observed among a 3/5 males and one female between Days 4 and 15.

Body weight:

Body weight gains of all dose groups were within the normal ranges in males and females during the whole study period.

Gross pathology:

Necropsy revealed no substance-related findings.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified

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 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 Lauric acid ester with hydroxypropanediyl diacetate (CAS 30899-62-8) are not available. The assessment of acute toxicity was therefore based on studies conducted with 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 91052-13-0

The acute oral toxicity of Glycerides, C8-18 and C18-unsatd. mono- and di-, acetates, was assessed in a study performed according to OECD guideline 423 and under GLP conditions (Otterdijk, 2010a). A total of 3 female Wistar rats were exposed to a limit dose of 2000 mg/kg bw in a stepwise procedure (3 rats per step). No mortality was observed up to the end of the 14-day observation period. Hunched posture and/or piloerection were noted in all females on Day 1 of the observation period. All animals showed the expected gain in body weights during the study and necropsy revealed no substance-related findings. Based on the results, the oral LD50 value for female Sprague Dawley rats is > 2000 mg/kg bw. In accordance with OECD guideline 423, the oral LD50 cut-off of the test substance is considered to be 5000 mg/kg bw.

CAS 97593-30-1

A study was conducted according to OECD guideline 423 (acute toxic class method) and under GLP conditions to assess the acute oral toxicity potential of C12: Glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates (Gillissen, 2008). A total of 6 female HsdCpb:Wu rats were administered a limit dose of 2000 mg/kg bw. In two sequential steps, 3 animals each received formulations of test substance in corn oil via gavage. During the study period, no animals died and no clinical signs were observed. The body weights were not affected by treatment and no substance-related findings were noted during the necropsy at study termination. Therefore, the oral LD50 value for rats is > 2000 mg/kg bw. In accordance with OECD guideline 423, the oral LD50 cut-off of the test substance is considered to be 5000 mg/kg bw.

 

Acute inhalation toxicity

CAS 73398-61-5

The acute inhalation toxicity of triglycerides, mixed decanoyl and octanoyl was assessed according to OECD guideline 403 and in compliance with GLP (Reminghaus, 1976). A group of 10 male rats was exposed to a calculated concentration of 28.1 µL/L air (undiluted test substance) 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 to be 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, or during the 14-day observation period. The body weight was not affected during the study. 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 LC50 value for male rats is > 1.86 mg/L air (analytical) for 6-h exposure. It is possible to extrapolate the result to a 4-h exposure period, according to Regulation (EC) 1272/2008 and the ECHA ‘Guidance on information requirements and chemical safety assessment Chapter R.7a: Endpoint specific guidance’ (2015):

Applying Haber’s Law (Cⁿx t = k), with a conservative default n = 3, (1.863 [mg/L] x 6 h = c [mg/L] x 4h) a time-extrapolated LC50 value of > 9.65 mg/L is reached. 

Acute dermal toxicity

CAS 91052-13-0

The acute dermal toxicity of Glycerides, C8-18 and C18-unsatd. mono- and di-, acetates was investigated in a limit test performed according to OECD guideline 402 and under GLP conditions (Otterdijk, 2010b). 2000 mg/kg bw test substance dissolved in polyethylene glycol at a concentration of 200 mg/mL was applied to the shaved skin of 5 Wistar Crl:WI (Han) rats/sex (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 mortality occurred and the body weight gain during the study period of the animals was within the normal range for this species and strain. 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. At necropsy, no substance-related findings were noted. Therefore, the LD50 in male and female rats is > 2000 mg/kg bw.

CAS 736150-63-3

The dermal effects of Glycerides, castor-oil mono, hydrogenated, acetates were investigated in an acute dermal toxicity study performed according to OECD guideline 402 and in compliance with GLP (Ott, 2003). 2000 mg/kg bw of the test substance in corn oil (0.5 g/mL) was applied to the shaved skin of 5 HanBrl: WIST rats/sex for 24 h under semi-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 and no clinical signs were observed during the observation period. Male and female rats showed the expected gain in body weight. At necropsy, no substance-related findings were observed. No local skin effects were reported. The dermal LD50 value for male and female rats is considered to be > 2000 mg/kg bw.

Overall conclusion for acute toxicity

The reliable data available for the source substances indicate a very low level of acute toxicity following the oral, inhalation and dermal route, as LD50 values were greater than the currently applied limit values. The LC50 value was the maximum attainable concentration. Therefore, as the available data did not identify any hazard for acute toxicity, Lauric acid ester with hydroxypropanediyl diacetate is not expected to be hazardous following acute exposure.

Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is most adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – inhalation endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is most adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is most adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

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 Lauric acid ester with hydroxypropanediyl diacetate (CAS 30899-62-8), data will be generated from information available 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 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.