Fatty acids, C16-18 (even numbered), esters with 1,2-propanediol

Endpoint summary

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 5000 mg/kg bw (EU Method B.1)
Acute toxicity: Dermal LD50 (rat, m/f): > 2000 mg/kg bw (OECD 402, GLP, category approach)
Acute toxicity: Inhalation: No study available

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

no data on individual body weights available

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

limited data available (no data on individual body weights available)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: SPF Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Paderborn, Germany
- Weight at study initiation: 120 g
- Fasting period before study: animals were fasted for approx. 16 h prior to administration
- Housing: randomized into 2 groups in macrolon plastic cages bedded with wood chips (Ssniff/bedding, Intermast, Soest, Germany)
- Diet: pellets (Ssniff/Intermast, Soest, Germany)
- Water: ad libitum
- Acclimation period: 7 days

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

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25%
- Amount of vehicle (if gavage): the amount of vehicle administered was based on body weight (4.81, 4.83, 9.75 or 9.58 mL for 2500 or 5000 mg/kg bw test substance in males and females, respectively).

MAXIMUM DOSE VOLUME APPLIED: 9.75 mL

Doses:

2500 and 5000 mg/kg bw
(10 000 and 20 000 mg/kg bw test item solution containing 25% test substance)

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were weighed prior to substance administration and at the end of the observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

Group mean values of body weights were calculated.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed until the end of the treatment period.

Clinical signs:

other: Lightly decreased activity and slight disturbances of coordination were observed about 20 min after substance administration and held for 2 h. Afterwards, all animals appeared normal.

Body weight:

other body weight observations

Remarks:

Animals gained weight during the observation period (average body weight gain: 23.3 and 23.7 g for the low- and high-dose group, respectively).

Gross pathology:

No gross pathological findings were identified at termination of the study.

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

Dose descriptor:

LD50

Value:

> 5 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, 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

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:

09 Jun-25 Jun 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

GLP-Guideline study, tested with the source substance Octanoic acid ester with 1,2-propanediol, mono- and di- (CAS 31565-12-5). According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (Dec 2012)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Bor: WISW (SPF Cpb)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Weight at study initiation: 247 - 259 g (males) and 231 - 252 g (females)
- Housing: animals were housed individually in Makrolon III cages.
- Diet: Ssniff R 10 (Alleindiät für Ratten, 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: clipped skin of the dorsal area of the trunk
- % coverage: 10
- Type of wrap if used: The test material was held in contact with the skin with an acrylastic bandage.

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.06 cm³/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed 30 min, 1, 2, 3, 4, 5 and 6 h post application and subsequently once daily. Individual body weights were determined on the day of application (Day 0) and on Day 7 and 14.
- 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:

other: 48 h after application 2 male and 1 female animal showed scaling. Scales were not apparent at the 72 h observation time point.

Body weight:

other body weight observations

Remarks:

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

Gross pathology:

Necropsy revealed no substance-related findings. One male animal showed a slight swelling of the spleen possibly due to the termination of the study.

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

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2 due to read-across) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s), common precursors/breakdown products and similarities in PC/ECO/TOX properties (refer to 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

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

CAS 1323-39-3/29013-28-3

Acute toxicity of Octadecanoic acid, monoester with 1,2-propanediol (CAS 1323-39-3) and Palmitic acid, monoester with propane-1,2-diol (CAS 29013-28-3) was tested in SPF Wistar rats (International Bio-Research, 1976). The test substance was dissolved in arachis oil at a concentration of 25%. Groups of 10 male and 10 female rats each were exposed to 2500 or 5000 mg/kg bw (equivalent to 10 000 and 20 000 mg/kg bw test item solution containing 25% test substance) via gavage. No mortality was observed until the end of the observation period of 14 days. 20 min after substance administration, lightly decreased activity and slight disturbances of coordination were observed which held for 2 h. Afterwards, all animals appeared normal. Furthermore, expected body weight gain was observed at study termination. No gross pathological findings were identified. Thus, a LD50 > 5000 mg/kg bw was derived.

Moreover, Propylene Glycol Stearate did not induce adverse effects after gavage in an acute toxicity study and hence, a LD50 > 5000 mg/kg bw was derived (Cosmetic Ingredient Review, 1983).

 

Acute inhalation toxicity

No data on acute toxicity following inhalation are included in the dossier as exposure to humans via the inhalation route is considered negligible, especially as the test substance is used only as pellets or pastilles with diameters far above the inhalable size (> 100 µm). Moreover, the test substance has a low vapour pressure (< 2.6E-06 Pa at 25 °C) which indicates a negligible volatility. Therefore, testing for acute toxicity following inhalation is not appropriate and should be avoided for reasons of animal welfare.

 

Acute dermal toxicity

CAS 31565-12-5

Ten rats (5 males and 5 females) were treated with Octanoic acid-1,2-propandiol-monoester by dermal application according to OECD 402 and GLP at the limit dose of 2000 mg/kg bw under semiocclusive conditions for 24 h (Hüls AG, 1992). The animals were observed for a period of 14 days following administration. During the study period, no mortality and no clinical signs of toxicity occurred in any animal. Furthermore, no effects on body weight were noted. No substance-related findings during necropsy were observed in any animal. In 3 animals, scaling was observed after 48 h, being no longer apparent at the 72 h observation time point. Thus, a dermal LD50 > 2000 mg/kg bw was derived.

 

Moreover, Propylene Glycol Stearate applied in a product formulation was non-toxic in an acute dermal toxicity study (Cosmetic Ingredient Review, 1983).

Overall conclusion on acute toxicity

In summary, reliable data available for Octadecanoic acid, monoester with 1,2-propanediol (CAS 1323-39-3) and Palmitic acid, monoester with propane-1,2-diol (CAS 29013-28-3) and for the read-across analogue substance indicate a very low level of acute toxicity following the oral or dermal route as oral and dermal LD50 values were greater than the currently applied limit values. Thus, as the available data did not identify any hazard for acute oral and dermal toxicity, Octadecanoic acid, monoester with 1,2-propanediol (CAS 1323-39-3) and Palmitic acid, monoester with propane-1,2-diol (CAS 29013-28-3) is not considered as hazardous after acute exposure.

Justification for classification or non-classification

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

No data on acute inhalation toxicity is available.