Fatty acids, C16-18 and C18-unsatd., esters with propylene glycol

Endpoint summary

Description of key information

Oral: LD50 > 2000 mg/kg bw
Dermal : LD50 > 2000 mg/kg bw
Inhalation: no data available

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:

12 Jun 1991 - 29 Jun 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

Comparable to guideline study with acceptable restrictions. Lack of test material details, no necropsy performed.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

lack of test material details, no necropsy performed

Qualifier:

according to guideline

Guideline:

other: FHSA/CPSC: Federal Hazardous Substances Control Act, 16 CFR 1500.3

Deviations:

no

GLP compliance:

not specified

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: Hilltop Lab Animals, Scottdale, PA, USA
- Age at study initiation: young adult, not further specified
- Weight at study initiation: 184-205 g
- Fasting period before study: 18 h
- Housing: individually in suspended stainless steel caging with mesh floors
- Diet: pelleted Purina Rat Chow #5012, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

2.5%

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25% w/w
- Amount of vehicle (if gavage): 2.0-2.3 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 2.3 mL/kg bw

Doses:

5000 mg/kg bw administered as two doses due to the volume of test material of 2.0-2.3 mL each within 24h.

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: the rats were observed for signs of gross toxicity and mortality at 1, 2, 3, 4, 5 and 24 h post-dosing, and at least once daily thereafter for 14 days. Body weights were recorded initially and at termination (Day 14).
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: administered as two doses within 24 h.

Mortality:

No mortalities occurred.

Clinical signs:

other: No abnormal clinical signs were observed.

Gross pathology:

Not examined.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 was determined to be > 5000 mg/kg bw

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

12 Jun 1991 - 29 Jun 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

Comparable to guideline study with acceptable restrictions. Lack of test material details, no necropsy performed.

Justification for type of information:

Please refer section 13 for read across justification.

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

lack of test material details, no necropsy performed

Qualifier:

according to guideline

Guideline:

other: FHSA/CPSC: Federal Hazardous Substances Control Act, 16 CFR 1500.3

Deviations:

no

GLP compliance:

not specified

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: Hilltop Lab Animals, Scottdale, PA, USA
- Age at study initiation: young adult, not further specified
- Weight at study initiation: 184-205 g
- Fasting period before study: 18 h
- Housing: individually in suspended stainless steel caging with mesh floors
- Diet: pelleted Purina Rat Chow #5012, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

2.5%

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25% w/w
- Amount of vehicle (if gavage): 2.0-2.3 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 2.3 mL/kg bw

Doses:

5000 mg/kg bw administered as two doses due to the volume of test material of 2.0-2.3 mL each within 24h.

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: the rats were observed for signs of gross toxicity and mortality at 1, 2, 3, 4, 5 and 24 h post-dosing, and at least once daily thereafter for 14 days. Body weights were recorded initially and at termination (Day 14).
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: administered as two doses within 24 h.

Mortality:

No mortalities occurred.

Clinical signs:

other: No abnormal clinical signs were observed.

Gross pathology:

Not examined.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 was determined to be > 5000 mg/kg bw

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 Feb - 09 Mar 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

GLP-Guideline study, tested with the source substance Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS No. 68583-51-7). 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:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

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
- Source: Winkelmann, Borchen, Germany.
- Fasting period before study: 16 h
- Housing: 5 animals of the same sex per cage in Makrolon 3 cages.
- Litter: soft wood granulate.
- Diet: Altromin-Haltungsdiät 1324 (Altromin GmbH, Lage, Germany), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 8 days
- Identification of the test animals: Group identification by cage labelling, individual identification by labelling with saturated picric acid solution.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-60
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% (w/v)
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 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: At day of application, animals were observed several times, thereafter 2 times per day until Day 14. Weighing was performed one day before application, directly before application, 48 h after application and at Day 7 and Day 14 after application.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross necropsy and 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: No clinical signs of toxicity were observed at the end of the 14-day observation period.

Gross pathology:

Males: tightly filled urinary bladder in 1/5 males 14 days after application. 4/5 males showed no clinical signs of toxicity at the end of the 14-day observation period.
Females: 4/5 females showed no clinical signs of toxicity. In 1/5 females a mild hydrometra was observed. According to the author the hydrometra was not due to the substance treatment.

Table 1. Mean body weights in g.

Doses	2000 mg/kg bw	2000 mg/kg bw
- 1 d	185	168
0 d	173	159
2 d	194	172
7 d	213	172
14 d	239	182
body weight gain	54	14

d = day of study

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 was determined to be > 2000 mg/kg bw

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

17 Feb - 09 Mar 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

GLP-Guideline study, tested with the source substance Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS No. 68583-51-7). 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.

Justification for type of information:

Please refer section 13 for read across justification.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

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
- Source: Winkelmann, Borchen, Germany.
- Fasting period before study: 16 h
- Housing: 5 animals of the same sex per cage in Makrolon 3 cages.
- Litter: soft wood granulate.
- Diet: Altromin-Haltungsdiät 1324 (Altromin GmbH, Lage, Germany), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 8 days
- Identification of the test animals: Group identification by cage labelling, individual identification by labelling with saturated picric acid solution.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-60
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% (w/v)
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 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: At day of application, animals were observed several times, thereafter 2 times per day until Day 14. Weighing was performed one day before application, directly before application, 48 h after application and at Day 7 and Day 14 after application.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, gross necropsy and 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: No clinical signs of toxicity were observed at the end of the 14-day observation period.

Gross pathology:

Males: tightly filled urinary bladder in 1/5 males 14 days after application. 4/5 males showed no clinical signs of toxicity at the end of the 14-day observation period.
Females: 4/5 females showed no clinical signs of toxicity. In 1/5 females a mild hydrometra was observed. According to the author the hydrometra was not due to the substance treatment.

Table 1. Mean body weights in g.

Doses	2000 mg/kg bw	2000 mg/kg bw
- 1 d	185	168
0 d	173	159
2 d	194	172
7 d	213	172
14 d	239	182
body weight gain	54	14

d = day of study

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 was determined to be > 2000 mg/kg bw

Reference 5

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 Oct - 19 Dec 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

Comparable to guideline study with acceptable restrictions. Lack of test material details.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

lack of test material details

GLP compliance:

yes

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
- Source: Züchter Winkelmann, Borchen, Germany
- Weight at study initiation: 180 g (males), 164 g (females)
- Fasting period before study: 16 h before and 3 h after treatment
- Housing: animals were housed in groups of 5 in Makrolon 3 cages and softwood bedding (Weichholzgranulat, ARWI-Center, Essen, Germany)
- Diet: Altromin-Haltungsdiät 1324 (Fa. Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-60
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% (w/v)
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 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 several times on the application day for symptoms and mortality and thereafter twice daily. Individual body weights were determined one day before application and 48 h, 7 and 14 days after treatment.
- 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 clinical signs of toxicity were observed up to the end of the 14-day observation period in male animals. In one female a slightly coloured red nose was observed 4-24 h after treatment. No further clinical signs were observed until the end of the 14-day

Gross pathology:

Pathology of male animals revealed no substance-related findings. In one female hydrometra was observed but was considered to be not substance-related.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 is determined to be > 2000 mg/kg bw

Reference 6

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

17 Oct - 19 Dec 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

Comparable to guideline study with acceptable restrictions. Lack of test material details.

Justification for type of information:

Please refer section 13 for read across justification.

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

lack of test material details

GLP compliance:

yes

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
- Source: Züchter Winkelmann, Borchen, Germany
- Weight at study initiation: 180 g (males), 164 g (females)
- Fasting period before study: 16 h before and 3 h after treatment
- Housing: animals were housed in groups of 5 in Makrolon 3 cages and softwood bedding (Weichholzgranulat, ARWI-Center, Essen, Germany)
- Diet: Altromin-Haltungsdiät 1324 (Fa. Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-60
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% (w/v)
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 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 several times on the application day for symptoms and mortality and thereafter twice daily. Individual body weights were determined one day before application and 48 h, 7 and 14 days after treatment.
- 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 clinical signs of toxicity were observed up to the end of the 14-day observation period in male animals. In one female a slightly coloured red nose was observed 4-24 h after treatment. No further clinical signs were observed until the end of the 14-day

Gross pathology:

Pathology of male animals revealed no substance-related findings. In one female hydrometra was observed but was considered to be not substance-related.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 is determined to be > 2000 mg/kg bw

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances 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).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole 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

Data waiving:

other justification

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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:

24 Oct - 11 Dec 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

Comparable to guideline study with acceptable restrictions. Analytical purity of test substance not specified and occlusive dressing according to former guideline.

Qualifier:

according to guideline

Guideline:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

analytical purity of test substance not specified and occlusive dressing according to former guideline

GLP compliance:

yes

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
- Source: Züchter Winkelmann, Borchen, Germany
- Weight at study initiation: 251 g (males), 219 g (females)
- Housing: individually housed in Makrolon 2 cages and softwood bedding (Weichholzgranulat, ARWI-Center, Essen, Germany)
- Diet: Altromin-Haltungsdiät 1324 (Fa. Altromin GmbH, Lage, Germany), ad libitum.
- Water: tap water, ad libitum
- Acclimation period: 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-60
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

other: the undiluted test substance was moistened with water on the dressing

Details on dermal exposure:

TEST SITE
- Area of exposure: 6.5 cm x 4 cm clipped skin of the dorsal area of the trunk
- Type of wrap if used: The test material was held in contact with the skin with an adhesive bandage (Hansapor steril, Nr. 2275, Beiersdorf, Germany) and held in place with a 8 cm x 6 cm film (Applica, Nr. 1218, Beiersdorf, Germany) and an adhesive tape (Fixomull stretch, Nr. 2292, Beiersdorf, Germany).

REMOVAL OF TEST SUBSTANCE
- Residual test material was removed (no further details)
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: yes, the undiluted test substance was moistened with water

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: symptoms and mortality were observed several times on the application day and afterwards twice daily. Body weights were observed on the day of application and 48 h, 7 and 14 days after application.

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 clinical signs of toxicity were observed up to the end of the 14-day observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 is determined to be > 2000 mg/kg dw.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

24 Oct - 11 Dec 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

Comparable to guideline study with acceptable restrictions. Analytical purity of test substance not specified and occlusive dressing according to former guideline.

Justification for type of information:

Please refer section 13 for read across justification.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

analytical purity of test substance not specified and occlusive dressing according to former guideline

GLP compliance:

yes

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
- Source: Züchter Winkelmann, Borchen, Germany
- Weight at study initiation: 251 g (males), 219 g (females)
- Housing: individually housed in Makrolon 2 cages and softwood bedding (Weichholzgranulat, ARWI-Center, Essen, Germany)
- Diet: Altromin-Haltungsdiät 1324 (Fa. Altromin GmbH, Lage, Germany), ad libitum.
- Water: tap water, ad libitum
- Acclimation period: 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 45-60
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

other: the undiluted test substance was moistened with water on the dressing

Details on dermal exposure:

TEST SITE
- Area of exposure: 6.5 cm x 4 cm clipped skin of the dorsal area of the trunk
- Type of wrap if used: The test material was held in contact with the skin with an adhesive bandage (Hansapor steril, Nr. 2275, Beiersdorf, Germany) and held in place with a 8 cm x 6 cm film (Applica, Nr. 1218, Beiersdorf, Germany) and an adhesive tape (Fixomull stretch, Nr. 2292, Beiersdorf, Germany).

REMOVAL OF TEST SUBSTANCE
- Residual test material was removed (no further details)
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: yes, the undiluted test substance was moistened with water

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: symptoms and mortality were observed several times on the application day and afterwards twice daily. Body weights were observed on the day of application and 48 h, 7 and 14 days after application.

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 clinical signs of toxicity were observed up to the end of the 14-day observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 is determined to be > 2000 mg/kg dw.

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 Jun - 17 Jul 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

GLP-Guideline study, tested with the source substance Octanoic acid ester with 1,2-propanediol, mono- and di- (CAS No. 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

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

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:

GHS criteria not met

Conclusions:

The LD50 was determined to be > 2000 mg/kg bw.

Reference 4

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Study period:

09 Jun - 17 Jul 1992

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Remarks:

GLP-Guideline study, tested with the source substance Octanoic acid ester with 1,2-propanediol, mono- and di- (CAS No. 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.

Justification for type of information:

Please refer Section 13 for read across justification

Reason / purpose for cross-reference:

read-across source

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

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

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:

GHS criteria not met

Conclusions:

The LD50 was determined to be > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances 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).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is 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

There are no data for acute toxicity available for the target substance. In accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5 read-across from appropriate substances is conducted to fulfill the standard information requirements set out in Regulation (EC) No 1907/2006, Annex VIII, 8.5.

According to Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met”. In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across) “to avoid the need to test every substance for every endpoint”. 

The target substance Fatty acids, C16-18 and C18-unsatd., esters with propylene glycol represents a UVCB substance predominantly comprised of diesters of an aliphatic diol (1,2-propyleneglycol (PG)) chemically linked to mainly oleic acid (C18:1) but as well to palmitic acid (C16), palmitoleic acid (C16:1), stearic acid (C18) and/or linoleic acid (C18:2).

Glycol esters are in general known to be stepwise hydrolysed by gastrointestinal enzymes into the free fatty acid component and the respective alcohol (Long, 1958; Lehninger, 1970; Mattson and Volpenhein, 1972).

Based on the common metabolic fate of glycol esters, the read-across approach is based on the presence of common functional groups, common precursors and the likelihood of common breakdown products via biological processes, which result in structurally similar chemicals, common functional groups, structural similarities and similar physico-chemical, toxicological and toxicokinetic behaviour. For further details on the read-across approach, please refer to the analogue justification in section 13 of the technical dossier.

 

As no data are available on acute toxicity following the oral, dermal or inhalation route of the target substance, read-across to reliable data on the analogue substances Ethylene distearate (CAS 627-83-8), Decanoic acid, mixed diesters with octanoic acid and propylene glycol (CAS 68583-51-7), Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) and Octanoic acid ester with 1,2-propanediol, mono- and di (CAS 31565-12-5) was conducted.

 

Acute oral toxicity

CAS 627-83-8

A study for acute oral toxicity of Ethylene distearate was performed in rats in accordance with OECD guideline 401 (Wnorowski, 1991a). A group of 10 Wistar rats (5 males and 5 females) was treated with the limit dose of 5000 mg/kg bw of the test substance in carboxymethyl cellulose by 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. Therefore, the oral LD50 value in male and female rats was greater than 5000 mg/kg bw.

 

CAS 68583-51-7

A study for acute oral toxicity of Decanoic acid, mixed diesters with octanoic acid and propylene glycol was performed in rats in accordance with EU Method B.1 under GLP conditions (Potokar, 1988). A group of 10 Wistar rats (5 males and 5 females) was dosed with 2000 mg/kg bw of the test material in peanut oil by gavage. 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. No effect on body weight gain was noted. During necropsy, in 1/5 males a tightly filled urinary bladder and in 1/5 females a mild hydrometra was observed. These findings were not considered to be substance-related. Therefore, under the conditions of this study, the oral LD50 value in male and female rats was greater than 2000 mg/kg bw.

 

CAS 151661-88-0

Acute oral toxicity of Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) was tested equivalent to OECD guideline 401 under GLP conditions in a group of 10 Wistar rats (5 males and 5 female), treated with the limit dose 2000 mg/kg bw in peanut oil by gavage Potokar, 1989a). No mortality occurred and no clinical signs of toxicity were observed up to the end of the 14-day observation period in male animals. In one female a slightly coloured red nose was observed 4-24 h after treatment. No further clinical signs were observed. No effect on body weight was noted and pathology of male animals revealed no substance-related findings. In one female hydrometra was observed but was considered to be not substance-related.

Therefore, under the conditions of this study, the oral LD50 value in male and female rats was greater than 2000 mg/kg bw.

 

Conclusion on acute oral toxicity

In summary, based on the available data on acute oral toxicity of the read-across analogue substances, the oral LD50 value of the target substance is considered to be ≥ 2000 mg/kg bw.

 

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 a liquid with low vapour pressure (experimental result: < 1.1E-1 Pa at 20°C (Kintrup, 2015), calculated result <2.67E-10 (Werth, C. 2014)) thereby indicating a low volatility (ECHA, 2012). Therefore, testing for acute toxicity following inhalation is not appropriate and should be avoided for reasons of animal welfare.

 

Acute dermal toxicity

CAS 151661-88-0

Reliable data from the read-across analogue substances Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) and Octanoic acid ester with 1,2-propanediol, mono- and di (CAS 31565-12-5) investigating the acute toxicity via the dermal route are available.

The acute dermal toxicity of Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol was evaluated in rats in accordance with OECD guideline 402 under GLP conditions (Potokar, 1989b). 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 or semiocclusive conditions for 24 h. 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.

 

CAS 31565-12-5

Dermal toxicity of Octanoic acid ester with 1,2-propanediol, mono- and di was established according to OECD guideline 402 and GLP (Mürmann, 1992). 5 rats/sex were exposed to 2000 mg Octanoic acid ester with 1,2-propanediol, mono- and di /kg bw under occlusive or semiocclusive conditions for 24 h followed by an observation period of 14 days.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 (Mürmann, 1992).

 

Conclusion on acute dermal toxicity

The results of the studies of the read-across analogue substances consistently showed no effects at the limit dose of 2000 mg/kg bw. Therefore, the dermal LD50 value of the target substance is considered to be ≥2000 mg/kg bw.

 

Overall conclusion for acute toxicity

In summary, reliable data available for the read-across analogue substances indicate a very low level of acute toxicity as oral and dermal LD50 values were greater than 2000 mg/kg bw.

Thus, as the available data did not identify hazards for acute oral and dermal route, the target substance is not considered as hazardous after acute exposure.

 

References

Agency for Toxic Substances and Disease Registry (ATSDR) (1997). Toxicological Profile for Propylene Glycol. US Department of Health and Human Services. Atlanta, US.

Agency for Toxic Substances and Disease Registry (ATSDR) (2010). Toxicological Profile for Ethylene Glycol. US Department of Health and Human Services. Atlanta, US.

ECHA (2014). Guidance on information requirements and chemical safety assessment, Chapter R.7c: Endpoint specific guidance.

Lehninger, A.L. (1970). Biochemistry. Worth Publishers, Inc.Long, C.L. et al. (1958). Studies on absorption and metabolism of propylene glycol distearate. Arch Biochem Biophys, 77(2):428-439.

Mattson, F.H. and Volpenhein, R.A. (1972). Hydrolysis of fully esterified alcohols containing from one to eight hydroxyl groups by the lipolytic enzymes of the rat pancreatic juice. Journal of Lipid Research 13: 325-328..

Miller, O.N., Bazzano, G. (1965). Propanediol metabolism and its relation to lactic acid -metabolism. Annals of the New York Academy of Sciences 119: 957-973.

Ritchie, A.D. (1927). Lactic acid in fish and crustacean muscle. Journal of Experimental Biology 4:327-332.

Werth, C. 2014. Propyleneglycol dioleate (CAS 105-62-4). EPIsuite 4.11 calculation with 9-Octadecenoic acid (Z)-, 1-methyl-1,2-ethanediyl ester.Dr. Knoell Consult GmbH, Report No. 20140626-Wer-1. 2014-06-26

 

Justification for selection of acute toxicity – oral endpoint: Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details). 

Justification for selection of acute toxicity – inhalation endpoint: No study required as inhalation is not considered as a relevant route of human exposure. In regard to the nature of the test substance and its uses, data on the oral and dermal route are provided thus fulfilling the data requirements according to Regulation (EC) No 1907/2006, Annex VIII, Section 8.5. 

Justification for selection of acute toxicity – dermal endpoint: Hazard assessment is conducted by means of a read-across based on a read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on the 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.