Reaction mass of glycerol 1,3-di(acetate) and glycerol acetate and triacetin

Endpoint summary

Description of key information

Acute toxicity: Oral LD50 (rat, m/f): > 2000 mg/kg bw (OECD 401, GLP)
Acute toxicity: Inhalation LC50 (rat, m/f): > 1.7 mg/L (OECD 403, GLP)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

17 Feb - 2 Mar 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP - Guideline study, tested with the source substance Triacetin (CAS No. 102-76-1). 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 401 (Acute Oral Toxicity)

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: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: 8 weeks
- Weight at study initiation: 120-250 g
- Fasting period before study: animals were fasted overnight prior to administration.
- Housing: animals were housed individually in polycarbonate cages with sawdust bedding.
- Diet: RMH-B (Hope Farms, Woerden, The Netherlands), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1.72 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: animals were observed on the day of dosing once every two hours and once daily thereafter.
- Necropsy of survivors performed: yes
- Body weight: weekly

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

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:

Necropsy revealed no substance-related findings.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Study period:

1985

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study with acceptable restrictions. Lack of details on the test substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

lack of details on the test substance

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Wistar Bor: WISW (SPF-Cpb)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 160-220 g
- Housing: animals were housed in groups of 5 per Makrolon type III cage.
- Diet: Altromin 1324 (Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 40-60
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindric inhalation chamber with a baffle
- Exposure chamber volume: 20 L
- Method of holding animals in test chamber: restraining tube for head/nose-only exposure
- Source and rate of air: a compressed air supplying device (600 kPa) delivered the air at a rate of 10 L/min
- Method of conditioning air: continuous infusion pump
- System of generating particulates/aerosols: 200 µL/minute of the test substance were dispersed into the chamber
- Method of particle size determination: Aerodynamic Particle Sizer with Laser-Velocimeter (TSI-APS 3300)

TEST ATMOSPHERE
- Brief description of analytical method used: GC (FI-detector) to measure the test substance concentration (mg/m³ air)
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 100 % of the particles were ≤ 5µm
- 1054845 particles per ccm
- MMAD: 1.69 µm

Time to chamber equilibration (t95): 6 minutes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

20 mg/L (nominal concentration)
1.7 mg/L (analytical concentration)

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: twice daily
- Body weights: the animals were weighed before exposure and weekly thereafter.
- Necropsy of survivors performed: yes

Statistics:

mean values were calculated

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1 721 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1.721 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

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.

Body weight:

No effect on body weight was noted.

Gross pathology:

There were no local irritation of the visible mucous membranes of the respiratory tract.

Other findings:

Air-exposed negative control animals showed no clinical symptoms during the study.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute toxicity

Justification for grouping of substances and read-across

There are no data available on the acute toxicity of "Reaction mixture of glycerol-1,3-di(acetate), glycerol acetate and triacetin".

In order 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, read-across from a structurally related substance is conducted.

In accordance with 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).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical and toxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

Overview of Acute toxicity

#	EC 905-964-4	CAS 102-76-1
Chemical name	"Reaction mixture of glycerol-1,3-di(acetate), glycerol acetate and triacetin"	Triacetin
Molecular weight	134.13 - 218.20 g/mol	218.20 g/mol
Acute toxicity oral	RA: CAS 102-76-1	LD50 > 2000 mg/kg bw
Acute toxicity inhalation	RA: CAS 102-76-1	LC50 > 1.7 mg/L

The above mentioned substances are considered to be similar on the basis of the structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for "Reaction mixture of glycerol-1,3 -

di(acetate), glycerol acetate and triacetin".

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Acute toxicity: oral

No studies are available investigating the acute toxicity via the oral route of "Reaction mixture of glycerol-1,3-di(acetate), glycerol acetate and triacetin".

In order to fulfil the standard information requirements set out in Annex VII, 8.5.1, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related analogue substance Triacetin (CAS 102-76-1) is conducted.

An acute oral toxicity study (limit test) with Triacetin (CAS 102-76-1) was performed according to OECD Guideline 401 and GLP (Reijnders, 1988). The test substance was administered by oral gavage at a concentration of 2000 mg/kg bw to groups of five male and female young adult Wistar rats. The animals were observed for 14 days following administration. No mortalities occurred during the study period. No clinical signs of toxicity and no changes in body weight were reported. Necropsy at the end of the 14-day study period did not reveal any substance related findings. The acute oral LD50 was found to be greater than 2000 mg/kg bw for Triacetin.

Acute toxicity: inhalation

No studies are available investigating the acute toxicity via the inhalation route of "Reaction mixture of glycerol-1,3-di(acetate), glycerol acetate and triacetin".

In order to fulfil the standard information requirements set out in Annex VIII, 8.5.2, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related analogue substance Triacetin (CAS 102-76-1) is conducted.

An acute nose/head only inhalation toxicity study was performed with Triacetin (CAS 102-76-1) similarly to OECD Guideline 403 and under GLP conditions (Pauluhn, 1985). Five male and five female Wistar rats were exposed for 4 hours to the maximum attainable Triacetin aerosol concentration of 1.7 mg/L (analytical concentration). The nominal concentration used in this study was 20 mg/L. Samples taken from the breathing zone were used to measure the actual Triacetin concentration. 100 % of the aerosol particles were found to be smaller than 5 µm and the MMAD was 1.69 µm. All treated animals survived and no signs of systemic toxicity were observed throughout the 14-day observation period. No local irritation of the visible mucous membranes of the respiratory tract was seen at gross pathology analysis. The acute inhalatory LC50 in rats was found to be greater than the maximum attainable aerosol concentration of 1.7 mg/L Triacetin. This concentration is above the maximum saturated vapour concentration of Triacetin, which is 0.5986 mg/L at 20°C.

Conclusion for acute toxicity

In summary, one acute oral toxicity study conducted with the source substance Triacetin (CAS 102-76-1) showed no effects and resulted in an oral LD50 value greater than 2000 mg/kg bw. A read-across study from Triacetin (CAS 102-76-1) investigating the acute toxicity via inhalation showed no effects of toxicity, as well. The LC50 value for rats was found to be greater than the maximum attainable aerosol concentration of 1.7 mg/L. Thus, the available data indicated a very low level of acute toxicity for

"Reaction mixture of glycerol-1,3-di(acetate), glycerol acetate and triacetin" and therefore, no hazard for acute oral and inhalative toxicity was identified.

Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details)

Justification for selection of acute toxicity – inhalation endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details)

Justification for classification or non-classification

Based on read-across from the source substance Triacetin following an analogue approach, the available data on acute and inhalation toxicity of "Reaction mixture of glycerol-1,3-di(acetate), glycerol acetate and triacetin"

do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and the data are therefore conclusive but not sufficient for classification.