Decanoic acid, mixed diesters with octanoic acid and propylene glycol

Endpoint summary

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 2000 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 LC50 (rat, m/f): > 2.916 mg/L air (OECD 403, category approach)

 

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:

17 Feb - 02 Mar 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

no

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.

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: 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:

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 adequate, reliable (Klimisch score 1-2) and consistent studies, 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

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Basic data given.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

duration of exposure 6 h, purity of the test material not specified, guinea pig is unusual species for acute inhalation toxicity tests

GLP compliance:

no

Test type:

traditional method

Limit test:

yes

Species:

guinea pig

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adults
- Weight at study initiation: 285 - 465 g
- Housing: individually housed in mesh bottom cages
- Diet: ad libitum
- Water: ad libitum

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 75 L
- Method of particle size determination: every 30 min using a Bausch and Lomb particle counter (model 40-1A)

- Each group of rats was placed in a 75 L chamber equipped with an air supply of 10 L per minute. After the test animals became accustomed to the chamber conditions, the material was sprayed into the air supply at a rate calculated to yield the required concentration of 200 ppm.
- The chamber temperature was recorded every 30 min.
- The control group was exposed only to air for the same length of time.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Particle counts were performed every 30 min using a Bausch and Lomb particle counter (model 40-1A)

Duration of exposure:

6 h

Concentrations:

200 ppm
equivalent to a concentration of 2.916 mg/L air (based on a molecular weight of 356.55 g/mol)

No. of animals per sex per dose:

3 (control), 4 (test group A), 6 (test group B)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: all major tissues and organs were preserved and the lungs and grossly abnormal organs were examined microscopically.

Sex:

male

Dose descriptor:

LC50

Effect level:

> 200 ppm

Based on:

test mat.

Exp. duration:

6 h

Sex:

male

Dose descriptor:

LC50

Effect level:

> 2.916 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

6 h

Remarks on result:

other: based on a molecular weight of 356.55 g/mol

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs of toxicity were observed up to the end of the 7-day observation period.

Gross pathology:

Necropsy examination revealed no substance-related findings.

According to the authors, respirable particles of the test material (≤5 µm) were produced.

Interpretation of results:

other: inconclusive

Conclusions:

CLP: inconclusive

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Basic data given.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

duration of exposure 6 h, purity of the test material not specified, only male animals were used.

GLP compliance:

no

Test type:

traditional method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Blue Spruce Farms, Inc., Altamont, NY, USA
- Age at study initiation: young adults
- Weight at study initiation: 145 - 195 g
- Housing: individually housed in mesh bottom cages
- Diet: ad libitum
- Water: ad libitum

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 75 L
- Method of particle size determination: every 30 min using a Bausch and Lomb particle counter (model 40-1A)

- Each group of rats was placed in a 75 L chamber equipped with an air supply of 10 L per minute. After the test animals became accustomed to the chamber conditions, the material was sprayed into the air supply at a rate calculated to yield the required concentration of 200 ppm.
- The chamber temperature was recorded every 30 min.
- The control group was exposed only to air for the same length of time.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Particle counts were performed every 30 min using a Bausch and Lomb particle counter (model 40-1A)

Duration of exposure:

6 h

Concentrations:

200 ppm
equal to 2.916 mg/L air (MW = 356.55 g/mol)

No. of animals per sex per dose:

3 (controls), 10 (test substance groups)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Other examinations performed: all major tissues and organs were preserved and the lungs and grossly abnormal organs were examined microscopically.

Sex:

male

Dose descriptor:

LC50

Effect level:

> 200 ppm

Based on:

test mat.

Exp. duration:

6 h

Sex:

male

Dose descriptor:

LC50

Effect level:

> 2.916 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

6 h

Remarks on result:

other: based on a molecular weight of 356.55 g/mol

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No clinical signs of toxicity were observed up to the end of the 7-day observation period.

Gross pathology:

Necropsy examination revealed no substance-related findings.

According to the authors, respirable particles of the test material (≤ 5 µm) were produced.

Interpretation of results:

other: inconclusive

Conclusions:

CLP: inconclusive

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 2.916 mg/L air

Physical form:

inhalation: aerosol

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) and consistent studies, 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 dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Study period:

24 Oct - 07 Nov 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

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.

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: other: No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Interpretation of results:

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

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

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 No. 31565-12-5). According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, 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: 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:

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

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Study period:

09 Dec - 27 Dec 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

GLP-Guideline study, tested with the source substance Butylene glycol dicaprylate / dicaprate (CAS No. 853947-59-8). According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, 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 - 273 g (males) and 225 - 243 g (females)
- Housing: animals were housed individually in type III Makrolon cages
- Diet: Ssniff R 10 complete feed for rats (Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: drinking water (Gelsenwasser, Haltern, Germany), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- 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 dorsal skin of the animals
- % coverage: 10%
- Type of wrap if used: The test material was covered with a mull patch and fixed with a semi-occlusive dressing and a strip of plaster.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw, 2.2 mL/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were weighed on the day of administration, on Day 7 and at the end of the study period (Day 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: other: No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Gross pathology:

The necropsies at the end of the study revealed no macroscopic changes to organs, nor were there any abnormalities in the skin and subcutaneous tissue in the application area.

Other findings:

The animals showed no dermal reactions 24 h after administration and up to the end of the observation period.

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 adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (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.

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 627-83-8

The acute toxicity via the oral route of ethylene distearate has been investigated in rats and mice in several studies (CAS 627-83-8).

A study for acute oral toxicity of ethylene distearate was performed in rats in accordance with OECD guideline 401 (Product Safety Labs, 1991). 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 in male and female rats was greater than 5000 mg/kg bw.

Further studies in which the acute oral toxicity of ethylene distearate was studied in rats and mice similar to OECD guideline 401 are available. The test material was administered by gavage at doses of 5000 or 2000 mg/kg bw (Product Safety Labs, 1991; Siege Social-Laboratoire, 1995). No mortalities were observed and no abnormalities in body weight were recorded during the 14-day observation period in the studies. No signs of toxicity were observed in the studies by Siege Social-Laboratoire and Product Safety Labs (1995, 1991).

Furthermore, four independent acute oral toxicity studies in doses up to 16000 mg/kg bw in rats with glycol distearate are reported (HPV, 1982). Doses above 13000 mg/kg bw were noted to produce diarrhoea, wet oily coats and nasal haemorrhage being reversible within 10 days. In one study, at gross necropsy the stomach contained residues which appeared to be the test material.

In summary, the oral LD50 of ethylene distearate is greater than 5000 mg/kg bw.

CAS 68583-51-7

Several studies investigating the acute toxicity via the oral route of Decanoic acid mixed diesters with octanoic acid and propylene glycol are available (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 (Henkel, 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 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 in male and female rats was greater than 2000 mg/kg bw.

Further studies are available, in which the acute oral toxicity of Decanoic acid, mixed diesters with octanoic acid and propylene glycol was studied in rats and mice according to OECD guideline 401.

In each case, the test material was administered by gavage at a dose of 5000 mg/kg bw or 5 mL/kg bw (Safepharm Laboratories, 1989; Safepharm Laboratories, 1988; Consultox Laboratories Ltd., 1972; EVic-CEBA Laboratory, 1985). No mortalities were observed during the 14-day study periods. No substance related signs of toxicity were observed in the studies. Moreover, no abnormalities in body weight (gain) were observed during the observation period and macroscopic examinations at termination revealed no treatment-related changes (Safepharm Laboratories, 1989; Safepharm Laboratories, 1988).

In summary, the oral LD50 of Decanoic acid mixed diesters with octanoic acid and propylene glycol is greater than 2000 mg/kg bw.

CAS 84988-75-0

No studies are available investigating the acute oral toxicity of Fatty acids, C14-18 and C16-18-unsatd., esters with propylene glycol. In order 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 read-across from the structurally related category members ethylene distearate (CAS 627-83-8), Decanoic acid, mixed diesters with octanoic acid and propylene glycol; CAS 68583-51-7) and Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) was conducted.

In addition to the already discussed studies from the category members ethylene distearate, Decanoic acid, mixed diesters with octanoic acid and propylene glycol (described under the respective CAS numbers), an additional study evaluating the acute oral toxicity of Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) is available (Henkel, 1989). The study was performed 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 of the test substance in peanut oil by gavage. 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 in male and female rats was greater than 2000 mg/kg bw.

In summary, based on the available data on acute oral toxicity of the category members, the oral LD50 of Fatty acids, C14-18 and C16-18-unsatd., esters with propylene glycol is considered to be greater than 2000 mg/kg bw.

CAS 624-03-3

No studies are available investigating the acute oral toxicity of ethane-1,2-diyl palmitate. In order 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 read-across from the structurally related category members ethylene distearate (CAS 627-83-8) and Decanoic acid, mixed diesters with octanoic acid and propylene glycol; CAS 68583-51-7) was conducted.

The studies from the category members ethylene distearate and Decanoic acid, mixed diesters with octanoic acid and propylene glycol are already described under the respective CAS numbers.

Based on the available data on acute oral toxicity of the category members the oral LD50 of ethane-1,2-diyl palmitate is considered to be greater than 2000 mg/kg bw.

Acute inhalation toxicity

CAS 627-83-8, CAS 68583-51-7, CAS 84988-75-0 and CAS 624-03-3

For acute inhalation toxicity, two studies are available within the Glycol ester category and were considered for assessment of all category members by read-across and a weight of evidence approach. 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 (Food and Drug Research Laboratories, 1978 a,b). A group of 10 male Sprague-Dawley rats and a group of 10 male and female guinea pigs and 3 control animals, respectively, were exposed whole body to 200 ppm (equivalent to 2.916 mg/L air) for 6 h. 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 for male rats and male and female guinea pigs was greater than 200 ppm (2.916 mg/L).

Acute dermal toxicity

CAS 627-83-8, CAS 68583-51-7, CAS 84988-75-0 and CAS 624-03-3

Data from the category members Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0), Butylene glycol dicaprylate / dicaprate (CAS 853947-59-8) 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 and were considered for assessment of all category members by read-across and weight of evidence approach.

The acute dermal toxicity of Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol, Butylene glycol dicaprylate / dicaprate and Octanoic acid ester with 1,2-propanediol, mono- and di were evaluated in rats in accordance with OECD guideline 402 under GLP conditions (Henkel, 1989; Hüls AG, 1992a and b).

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.

No substance-related findings during necropsy were observed in any animal (Hüls AG 1992a and b). In 3 animals, scaling was observed after 48 h, being no longer apparent at the 72 h observation time point (Hüls AG, 1992b).

The results of the three studies of the category substances consistently showed no effects at the limit dose 2000 mg/kg bw. Therefore, the dermal LD50 is considered to be greater than 2000 mg/kg bw.

Conclusion for acute toxicity

In summary, 14 studies are available studying the acute oral toxicity of Glycol Ester category members resulting in oral LD50 values greater than 2000 mg/kg bw. For acute inhalation toxicity, two studies are available within the Glycol Ester category. From these studies a LC50 value for male rats and male and female guinea pigs of greater than the limit dose of 200 ppm (2.916 mg/L) was obtained. Acute dermal toxicity data from three category members consistently showed no effects at the limit dose 2000 mg/kg bw.

Thus, the available data indicate a very low level of acute toxicity for the category members and thus no hazard for acute oral, inhalative and dermal toxicity was identified.

 

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.

Gubicza, L., Kabiri-Badr, A., Keoves, E., Belafi-Bako, K. (2000): Large-scale enzymatic production of natural flavour esters in organic solvent with continuous water removal. Journal of Biotechnology 84(2): 193-196.

Heymann, E. (1980): Carboxylesterases and amidases. In: Jakoby, W.B., Bend, J.R. & Caldwell, J., eds., Enzymatic Basis of Detoxication, 2nd Ed., New York: Academic Press, pp. 291-323.Gubicza, L. et al. (2000). Large-scale enzymatic production of natural flavour esters in organic solvent with continuous water removal. Journal of Biotechnology 84(2): 193-196.

International Programme on Chemical Safety (IPCS) (2001): Ethylene Glycol. Poisons Information Monograph. PIM 227.

Lilja, J. et al. (2005). Esterification of propanoic acid with ethanol, 1-propanol and butanol over a heterogeneous fiber catalyst. Chemical Engineering Journal, 115(1-2): 1-12.

Liu, Y. et al. (2006). A comparison of the esterification of acetic acid with methanol using heterogeneous versus homogeneous acid catalysis. Journal of Catalysis 242: 278-286.

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.

Radzi, S.M. et al. (2005). High performance enzymatic synthesis of oleyl oleate using immobilised lipase from Candida antartica. Electronic Journal of Biotechnology 8: 292-298.

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

Stryer, L. (1994): Biochemie. 2nd revised reprint, Heidelberg; Berlin; Oxford: Spektrum Akad. Verlag.

Tocher, D.R. (2003): Metabolism and Functions of Lipids and Fatty Acids in Teleost Fish. Reviews in Fisheries Science 11(2), 107-184.

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Zhao, Z. (2000). Synthesis of butyl propionate using novel aluminophosphate molecular sieve as catalyst. Journal of Molecular Catalysis 154(1-2): 131-135.

 

Justification for selection of acute toxicity – oral endpoint
The selected study is the most adequate and reliable study based on overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – inhalation endpoint
Hazard assessment is based on the weight of evidence from all avalable studies.

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-across based on a category approach. 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

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 group concept is applied to the members of the Glycol Ester Category, data will be generated from representative reference substance(s) within the category to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labeled on this basis.

Therefore, based on the group concept, all available data on acute oral and dermal toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

Since the available acute inhalation studies provided LC50 values for male rats and male and female guinea pigs of greater than the limit dose of 200 ppm (2.916 mg/L), the data is inconclusive according to the classification criteria of Regulation (EC) 1272/2008 or Directive 67/548/EEC.