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Endpoint summary

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 2000 mg/kg bw (OECD 401, GLP)

Read across from source substances 1,2,3 -propanetriol, homopolymer, diisooctadecanoate (CAS 63705-03-3) and 2,3-dihydroxypropyl octadec-9-enoate (CAS 111-03-5)

Acute toxicity: Dermal LD50 (rat, m/f): > 2000 mg/kg bw (OECD 402, GLP)

Read across from source substances 1,2,3 -propanetriol, homopolymer, diisooctadecanoate (CAS 63705-03-3) and glycerol tristearate (CAS 555-43-1)

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:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc., Yokohama, Japan
- Age at study initiation: 6 weeks
- Weight at study initiation: 123-125 g
- Fasting period before study: 16 h
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25
- Humidity (%): 42-51
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Lot/batch no. (if required): CER5860

DOSAGE PREPARATION:
After the test substance was heated and melted at 37 °C, it was diluted in the vehicle. This preparation was performed two days before administration and stored in the dark.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Because the acute oral toxicity of the test substance was expected to be very low, a dose level of 2000 mg/kg bw was chosen. No mortality was observed during step 1. Therefore, the dose level in step 2 was also 2000 mg/kg bw.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 females

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were performed once a day. Animals were weighed on Days 0, 1, 2, 3, 7, 10 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: No clinical signs were reported.

Gross pathology:

There were no abnormalities during test period.

Interpretation of results:

not classified

Conclusions:

DSD: not classified
CLP: not classified

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study with acceptable restrictions. Lack of data on test substance.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Lack of data on test substance.

Qualifier:

equivalent or similar 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
- Weight at study initiation: about 168 g (males) and 150 g (females)
- Fasting period before study: 16 h
- Housing: the animals were housed in groups of 5 in Makrolon 3 cages with a bedding of softwood granules.
- Diet: Altromin 1324, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 7 d

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

IN-LIFE DATES:
From: 15 Mar 1988
To: 29 Mar 1988

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50% (w/v)
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

5000 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: there was a repeated observation of the animals on the application day. During the 14 d observation period, the animals were observed twice daily. Individual body weights were recorded the day prior to application, the day of application and on Days 2, 7 and 14 of the observation period.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 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 d observation period.

Gross pathology:

Necropsy revealed no substance-related findings.

Interpretation of results:

not classified

Conclusions:

CLP: not classified
DSD: not classified

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

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

Remarks:

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

Adequacy of study:

key study

Justification for type of information:

refer to the analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

Source CAS 111-03-5

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

Source CAS 63705-03-3

Interpretation of results:

not classified

Conclusions:

As detailed in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in acute toxicity potential. The oral LD50 value for both source substances is > 2000 mg/kg bw. Therefore the target substance is also expected to have a very low level of acute oral toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

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:

supporting study

Study period:

03 Sep - 18 Sep 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted in 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted in 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Ministerium für Umwelt, Raumordnung und Landwirtschaft des Landes Nordrhein-Westfalen, Düsseldorf, Germany

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Wistar (Hsd/Win:WU/SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Weight at study initiation: 261 - 278 g (males), 202 - 220 g (females)
- Housing: individually housed in Makrolon type III cages on soft wood bedding
- Diet: Ssniff R 10 diet in pellet form (laboratory standard rat diet, Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

corn oil

Details on dermal exposure:

TEST SITE
- Area of exposure: 50 x 50 mm on the dorsolumbar region
- % coverage: 10%
- Type of wrap if used: the treated skin was covered with gauze which was held in place with a semiocclusive dressing encircled firmly around the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated area of skin was cleaned with corn oil and absorbent paper.
- Time after start of exposure: 24 h

PREPARATION OF DOSING SOLUTION
- Preparation: the powdery substance was suspended in corn oil.
- Amount(s) applied (volume or weight with unit): 5 cm³/kg bw
- Concentration: 40 g/100 cm³

Duration of exposure:

24 h

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: rats were checked at least twice daily for mortality. Animals were observed for clinical signs 30 min after dosing and at hourly intervals on Day 0, thereafter daily.
- Frequency of weighing: on Days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: local dermal irritations were recorded daily.

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.

Gross pathology:

The macroscopical examination on Day 14 revealed no abnormalities.

Other findings:

After removal of the dressings 24 h post-application until the end of the study, no skin irritations were noticed.

Table 1. Body weight.

Animal No.	Body weight on Day (g)			Body weight gain (g)
	0	7	14	Week 1	% body weight gain	Week 2	% body weight gain
Males
1	278	296	305	18	6.5	9	3.0
2	261	278	305	17	6.5	27	9.7
3	260	278	306	18	6.9	28	10.1
4	272	298	321	26	9.6	23	7.7
5	269	294	313	25	9.3	19	6.5
Females
1	202	209	209	7	3.5	0	0.0
2	212	213	217	1	0.5	4	1.9
3	220	213	223	-7	-3.2	10	4.7
4	220	234	250	14	6.4	16	6.8
5	208	210	215	2	1.0	5	2.4

Interpretation of results:

not classified

Conclusions:

CLP: not classified
DSD: not classified

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 - 24 Oct 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

LANDESANSTALT FÜR UMWELT, MESSUNGEN UND NATURSCHUTZ BADEN-WÜRTTEMBERG, Karlsruhe, Germany

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Wistar Crl:WI (Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: approx. 9 weeks (males), approx. 13 weeks (females)
- Weight at study initiation: 282.6 g (males), 212.4 g (females)
- Housing: the animals were housed individually in Makrolon cages, type III with bedding H 15005-29 (Ssniff, Spezialitäten GmbH (Experimental Animal Diets Inc., Soest, Germany)) and environmental enrichment NGM E-022 (ABEDD® LAB & VET Service GmbH, Wien, Austria).
- Diet: VRF1(P) (SDS Special Diets Services, Altrip, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 09 Oct 2012 To: 23 Oct 2012

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: about 40 cm² clipped skin of the dorsal and dorsolateral parts of the trunk
- % coverage: ca. 10
- Type of wrap if used: the application site was covered with a semi-occlusive dressing (4 layers of absorbent gauze; Ph. Eur. (Lohmann GmbH & Co., KG)) and stretch bandage (Fixomull® Stretch (adhesive fleece) (Beiersdorf AG)).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the application site was rinsed with warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5.2 mL/kg bw

Duration of exposure:

24 h

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for clinical signs several times on the day of administration and at least once daily thereafter each workday for the individual animals. A check for mortalities was made at least once each workday. Scoring of skin reaction according to Draize was performed 30-60 minutes after removal of the semi-occlusive dressing (after 24 h), weekly thereafter and on the last day of observation. Individual body weights were determined shortly before administration (Day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, scoring of skin reactions

Statistics:

Mean values and standard deviations of body weights were determined.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No systemic clinical signs were observed during clinical examination.

Gross pathology:

No macroscopic pathologic abnormalities were noted at necropsy.

Other findings:

- Other observations: no local effects were observed in the male and female animals after administration.

Interpretation of results:

not classified

Conclusions:

CLP: not classified
DSD: not classified

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

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

Remarks:

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

Adequacy of study:

key study

Justification for type of information:

refer to the analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

CAS 63705-03-3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

CAS 63705-03-3

Interpretation of results:

not classified

Conclusions:

As detailed in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in acute toxicity potential. The oral LD50 value for both source substances is > 2000 mg/kg bw. Therefore the target substance is also expected to have a very low level of acute dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

No acute toxicity data are available on Fatty acids, C16-18 (even numbered), esters with glycerol oligomers. However, in EFSA's scientific opinion on the re-evaluation of polyglycerol esters of fatty acids (PEPA, E 475), as a food additive, it is stated that rats given single doses of 7, 14 or 29 g/kg bw of a polyglycerol ester via gavage did not show any signs of toxic effects. Similarly, rabbits given single doses of 10–29 g/kg bw via gavage showed no toxic effects (as described by JECFA, 1974a). The available data thus indicated a low acute oral toxicity of PEFA (EFSA, 2017)

The registrants are currently trying to get hold of the acute toxicity studies mentioned in the aforementioned EFSA report. Therefore, as an interim measure, the acute oral toxicity hazard of the registered substance was assessed based on the available data from the source substances 1,2,3 -propanetriol, homopolymer, diisooctadecanoate (CAS 63705-03-3) and 2,3-dihydroxypropyl octadec-9-enoate (CAS 111-03-5). In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and following the Read across assessment framework (RAAF, ECHA 2017) read across from analogue substances have been applied to support the human health hazard assessment of Fatty acids, C16-18 (even numbered), esters with glycerol oligomers. 

 

Acute toxicity: oral

 

CAS 63705-03-3

 

For the source substance 1,2,3 -propanetriol, homopolymer, diisooctadecanoate (CAS 63705-03-3), an acute oral toxicity study (limit test) according to OECD TG 401 (Potokar, 1988) and conducted under GLP condition is available. Groups of 5 female Wistar rats received doses of 5000 mg /kg bw of test substance by gavage. The animals were observed for 14 days. No mortality, signs of systemic toxicity and abnormalities during necropsy were observed. No effect on body weight was noted. Thus, the acute oral LD 50 in rats was determined to be greater than 5000 mg/kg bw.

 

CAS 111 -03 -5

 

For the source substance 2,3-dihydroxypropyl octadec-9-enoate (CAS 111-03-5), an acute oral toxicity study (limit test) according to OECD TG 423 (MHLW, 2005) and conducted under GLP condition is available. 3 female Sprague-Dawley rats received doses of 2000 mg /kg bw of test substance by gavage. The animals were observed for 14 days. No mortality, signs of systemic toxicity and abnormalities during necropsy were observed. No effect on body weight was noted. Thus, the acute oral LD 50 in rats was determined to be greater than 2000 mg/kg bw.

 

Acute toxicity: dermal

 

CAS 63705-03-3

 

The acute dermal toxicity potential of the source substance 1,2,3 -propanetriol, homopolymer, diisooctadecanoate (CAS 63705-03-3) was investigated in a limit test performed according to OECD Guideline 402 (Cords, 2012) and under GLP conditions. The dorsal and dorsolateral parts of the trunk of five male and female rats were treated semiocclusively with the test material at 5000 mg/kg bw. 24 hours after application, the treated area of skin was rinsed with warm water. No mortality occurred and no clinical signs of systemic toxicity were observed in any of the animals during the 14-day observation period. The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weights of the female animals did not significantly change during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range. Finally no macroscopic pathologic abnormalities were noted at necropsy. Thus, the dermal LD50 after treatment with 1,2,3-Propanetriol, homopolymer, diisooctadecanoate in male and female rats was found to be > 5000 mg/kg bw.

 

CAS No. 555-43-1

 

In an acute dermal toxicity study, the source substance glycerol tristearate was investigated in rats in accordance with OECD guideline 402 and in compliance with GLP (Krueger, 1998). The animals (5 per sex) were dermally exposed to the test substance at a limit dose of 2000 mg/kg bw. The powdery test substance was suspended in corn oil at a concentration of 40 g/100 m³ and applied onto the shaved skin of the test animals (5 cm³/kg bw) for 24 h under semiocclusive conditions. After exposure, residual test substance was removed and animals were observed for a period of 14 days. No treatment-related mortalities occurred and no signs of systemic toxicity were observed during the study. Male rats showed the expected gain in body weight throughout the study. Minimal body weight gain was recorded in 2/5 females, whereas 1/5 females showed no gain in body weight. However, this finding was not considered to be treatment-related, since it was considered a physiological finding in rats of this age. At necropsy, macroscopic examination revealed no test substance-related abnormalities. Based on these results, the dermal LD50 value for male and female rats is > 2000 mg/kg bw.

 

Conclusion for acute toxicity

 

The reliable data available for the source substances indicate a very low level of acute toxicity via the oral and dermal route, as LD50 values were greater than the administered limit values. Therefore, as the available data did not identify any acute toxicity, the registration substance is not expected to be hazardous following acute exposure via the oral and dermal route.

Justification for classification or non-classification

Based on read-across from structurally similar substances, the available data on oral and dermal toxicity do not meet the classification criteria according to Regulation (EC) No. 1272/2008 (CLP), and are therefore conclusive but not sufficient for classification.