Glycerides, C18-36

Endpoint summary

Description of key information

Oral (OECD 401): LD50 > 2000 mg/kg bw

Dermal (OECD 402): LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Limited information on materials and methods, males only were dosed, no individual animal data, no necropsy, limited observation period.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted Feb 1987

Deviations:

yes

Remarks:

Limited information on materials and methods, mouse species, limited observation period, males only were dosed, no individual animal data, no necropsy.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

mouse

Strain:

other: SPF NMRI

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 19 - 20 g

Route of administration:

oral: gavage

Vehicle:

not specified

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 6 days
- Frequency of observations and weighing: the animals were observed for mortality and morbidity, and the body weight was recorded; the frequency was not reported
- Necropsy of survivors performed: no

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality during the study period.

Clinical signs:

No adverse clinical signs were reported.

Body weight:

The body weight growth was reported to be "normal".

Interpretation of results:

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

Conclusions:

The observation period was only 6 days. However, as no clinical signs were observed and the body weight development was described to be normal, it is unlikely that mortality would have occurred in the time period Day 7-14. The study is therefore considered to be sufficient to meet the data requirement and the LD50 is considered to be > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study, and is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 Sep - 18 Sep 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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.

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:

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

Body weight:

The male rats achieved satisfactory body weight gains throughout the study.
Four female rats showed minimal body weight gain after the first week. One female showed little body weight loss after the first week. At the end of the study, minimal body weight gain was recorded in two female animals and one animal showed no body weight gain. Two female rats achieved satisfactory body weight gains throughout the study. Variation of body weight in this age / body weight range is a physiological finding and not substance-related (see Table 1).

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

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified

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:

03 Sep - 18 Sep 1997

Reason / purpose for cross-reference:

read-across source

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:

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

Body weight:

The male rats achieved satisfactory body weight gains throughout the study.
Four female rats showed minimal body weight gain after the first week. One female showed little body weight loss after the first week. At the end of the study, minimal body weight gain was recorded in two female animals and one animal showed no body weight gain. Two female rats achieved satisfactory body weight gains throughout the study. Variation of body weight in this age / body weight range is a physiological finding and not substance-related (see Table 1).

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

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to endpoint discussion for further details). The selected study 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

Justification for read-across

Data on the acute dermal toxicity of Dub TGI 24 are not available. The assessment of acute dermal toxicity was therefore based on a study conducted with a source substance as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

 

Acute oral toxicity

CAS 91052-08-3

The acute oral toxicity of Dub TGI 24, was assessed in a study performed following a protocol similar to OECD guideline 401 (please refer to IUCLID section 7.2.1). No individual animal data was given. Five male SPF NMRI mice were administered 2000 mg/kg bw by gavage. No mortality was observed during the 6-day observation period. No treatment-related clinical signs were observed. The body weight increase was reported to be ‘normal’. Based on the results, the oral LD50 value for male mice is > 2000 mg/kg bw.

Acute dermal toxicity

CAS 555-43-1

The acute dermal toxicity of glycerol tristearate was investigated in a limit test performed according to OECD guideline 402 and under GLP conditions (please refer to IUCLID section 7.2.3). 2000 mg/kg bw test substance dissolved in corn oil was applied to the shaved skin of 5 Wistar rats/sex for 24 h under semiocclusive conditions. After exposure, residual test substance was removed and animals were observed for a period of 14 days. No mortality occurred and no clinical signs were reported. Four female rats showed minimal body weight gain after the first week. One female had a body weight loss (-3.2%) after the first week. At the end of the study, minimal body weight gain was recorded in two female animals and one animal showed no body weight gain. Two female rats achieved satisfactory body weight gains throughout the study. The observed variation in body weight was limited to less than 10% and not considered to be treatment-related. The body weight gain during the study period of the male animals was within the normal range for this species and strain. No local skin effects were observed at the test site. At necropsy, no substance-related findings were noted. Therefore, the LD50 in male and female rats is > 2000 mg/kg bw.

Acute inhalation toxicity

No data on acute toxicity following inhalation are available. Based on the vapour pressure of the substance and the defined uses, no study needs to be conducted because exposure of humans via inhalation is not likely.

Overall conclusion for acute toxicity

The reliable data available for the target and source substances indicate a very low level of acute toxicity following the oral and dermal route, as LD50 values were greater than the currently applied limit values. Therefore, as the available data did not identify any hazard for acute toxicity, Dub TGI 24 is not expected to be hazardous following acute exposure.

 

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that "substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Dub TGI 24, data will be generated from data available for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

The available data on acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.