Reaction mass of 2-hydroxyethyl laurate and ethylene dilaurate

Endpoint summary

Description of key information

Oral (OECD 420): LD50 rat > 2000 mg/kg bw

Inhalation (Read-across, similar to OECD 403): LC50 rat, guinea pig > 2.9 mg/L air (nominal)

Dermal (Read-across, similar to OECD 402): LD50 rat > 2000 mg/kg bw

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the glycol esters category will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.

For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the glycol esters category.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 Jan - 15 Feb 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

adopted in 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Medicines & Healthcare products Regulatory Agency, United Kingdom

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK.
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 151 - 173 g (range)
- Fasting period before study: yes, overnight
- Housing: housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: 2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK, ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

The experimenter had information indicating that the test material was likely to be nontoxic

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: the test item did not dissolve/suspend in distilled water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

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
- Necropsy of survivors performed: yes, all animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
- Clinical observations were made 30 min, 1, 2, and 4 h after dosing and then daily for 14 days.
- Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays.
- Body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.

Statistics:

No statistics required

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 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 period.

Clinical signs:

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

Gross pathology:

No abnormalities were noted at necropsy.

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 and reliable study (Klimisch score 1). The selected study is 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:

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

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

key study

Justification for type of information:

Refer to analogue justification provided in IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male

Dose descriptor:

LC50

Remarks:

rat

Effect level:

> 2.916 mg/L air (nominal)

Based on:

test mat.

Remarks:

aerosol

Exp. duration:

6 h

Remarks on result:

other: Source: CAS 68583-51-7

The available in vivo data on testing of decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583 -51 -7) in rats was selected as key data as the rat is the preferred species under the current OECD guideline. Additional data with this source substance was available for guinea pigs; in guinea pigs the LC50 value (aerosol) was also > 2.916 mg/L air.

Interpretation of results:

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

Conclusions:

The read across approach is justified in the analogue justification. The target and source substance are considered unlikely to differ in their acute toxicity potential. The liquid test substance decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) was sprayed into the air to yield a concentration of 200 ppm. Respirable particles of the test material with sizes ≤ 5 µm as aerosol were produced and measured every 30 minutes during a 6-hour exposure. The acute inhalation LC50 was found to be > 200 ppm. Based on the molecular weight of the test substance the LC50 was > 2.916 mg/L air, which is above limit testing of liquid aerosols. Therefore, an acute LC50 value of > 2.916 mg/L air was considered for the hazard assessment and C&L purposes for the target substance Reaction mass of 2-hydroxyethyl laurate and ethylene dilaurate (EC 908-917-6).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate and reliable (Klimisch score 2) studies from reference substances with a common mode of action. Read-across is justified based on different compounds having the same type of effect(s) as described in scenario 2 of the Read-Across Assessment Framework (Read-Across Assessment Framework (RAAF), European Chemicals Agency, Helsinki, Finland, 2017), (please refer to the Analogue Justification for further details provided in IUCLID section 13). 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 dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

key study

Justification for type of information:

Refer to analogue justification provided in IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Source: CAS 151661-88-0

The acute dermal toxicity study with the source substance fatty acids, C18 and C18 unsatd., epoxidized, ester with ethylene glycol (CAS 151661-88-0) was selected as key result for reasons of structural similarity and data reliability. Supporting in vivo data on acute dermal toxicity is given for the source substance 1,2 -propanediol-mono/di-octanoate (CAS 31565 -12 -5), for which the acute dermal LD50 value in rats was > 2000 mg/kg bw.

Interpretation of results:

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

Conclusions:

The read across approach is justified in the analogue justification. The target and source substances are considered unlikely to differ in their acute toxicity potential. The acute dermal LD50 value was >2000 mg/kg bw in male and female rats for the source substance fatty acids, C18 and C18 unsatd., epoxidized, ester with ethylene glycol (CAS 151661-88-0). Therefore, an acute dermal LD50 value of > 2000 mg/kg bw was considered for the hazard assessment and C&L purposes for the target substance Reaction mass of 2-hydroxyethyl laurate and ethylene dilaurate (EC 908-917-6).

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 a common mode of action. Read-across is justified based on different compounds having the same type of effect(s) as described in scenario 2 of the Read-Across Assessment Framework (Read-Across Assessment Framework (RAAF), European Chemicals Agency, Helsinki, Finland, 2017), (please refer to the Analogue Justification for further details provided in IUCLID section 13). 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.

Additional information

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the glycol esters category will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.

For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the glycol esters category.

 

Acute oral toxicity

Reaction mass of 2 -hydroxyethyl laurate and ethylene dilaurate

An acute oral toxicity study (fixed dose method) was performed in female rats in accordance with OECD guideline 420 and under GLP conditions with Reaction mass of 2 -hydroxyethyl laurate and ethylene dilaurate (key study, 2017). A group of 5 female Wistar rats was treated with the limit dose of 2000 mg/kg bw of the test substance in arachis oil by oral gavage. The observation period following administration was 14 days. During the study period, no mortality and no clinical signs of toxicity were observed in any animal. All test animals showed normal body weight gain. No abnormalities were detected during gross necropsy. Therefore, the oral LD50 value in female Wistar rats was greater than 2000 mg/kg bw.

 

Acute inhalation toxicity

CAS 68583-51-7

The acute inhalation toxicity of decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7) was evaluated in two studies similar to OECD guideline 403 in a limit test (key study, 1978). A group of 10 male Sprague-Dawley rats and a group of 10 male and female guinea pigs were exposed whole body to aerosol at 200 ppm (equivalent to 2.916 mg/L air) for 6 h. Three control animals per sex and per species were included in the study. The animals were observed for a period of 7 days following administration.

No mortality occurred and no clinical signs of toxicity were apparent during the study period in any animal. Necropsy revealed no substance-related findings in both studies.

Therefore, the LC50 value for male rats and male and female guinea pigs was greater than 200 ppm (2.916 mg/L air (nominal)).

 

Acute dermal toxicity

CAS 151661-88-0

Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) was evaluated in rats in a study performed equivalent to OECD guideline 402 under GLP conditions (key study, 1989). Groups of 10 rats (5 males and 5 females) were treated with the undiluted test substance at the limit dose of 2000 mg/kg bw under occlusive conditions for 24 h. The animals were observed for a period of 14 days following administration. During the study period, no mortality was observed and no clinical signs of toxicity occurred in any animal. Furthermore, no effects on body weight were noted. The LD50 value was greater than 2000 mg/kg bw.

 

Overall conclusion for acute toxicity

In summary, reliable data available for the target substance and read-across source substances indicate a very low level of acute toxicity following the oral, inhalation or dermal route. Thus, Reaction mass of 2-hydroxyethyl laurate and ethylene dilaurate is not expected to be hazardous after 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 Reaction mass of 2-hydroxyethyl laurate and ethylene dilaurate 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. The available data on acute toxicity do not meet the classification criteria according to Regulation (EC) No. 1272/2008 and are therefore conclusive but not sufficient for classification.