Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

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 IX, 8.7, 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 toxicity to reproduction.

CAS #

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

Toxicity to reproduction

RA CAS 102-76-1

Experimental result:

NOAEL ≥ 1000 mg/kg bw/day (m, f)

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).

Since no studies are available investigating the toxicity to reproduction of "Reaction mixture of glycerol-1,3-di(acetate), glycerol acetate and triacetin", the available data from the structurally related analogue substance Triacetin (CAS 102 -76 -1) was

considered for assessment and read-across is conducted based on an analogue approach.

A Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test was performed with Triacetin (CAS 102-76-1) according to OECD Guideline 422 and under GLP conditions (JECDB, 1998). Groups of twelve CD rats received oral gavage doses of 40, 200 and 1000 mg/kg bw/day of Triacetin in 3% gum arabicum in purified water for 44 days from 2 weeks prior to mating for males and for 41- 48 days from 14 days before mating to day 3 postpartum for females. Concurrent control animals received the vehicle.

Triacetin had no effects on clinical signs, body weight, food consumption, and organ weight or necropsy findings. No abnormalities in haematological or blood chemical parameters in males were found. No effects on reproductive parameters were observed including mating index, fertility index, gestation length, numbers of corpora lutea and implantations, implantation index, gestation index, delivery index, parturition and maternal behaviour at delivery and lactation. Gross pathology and histopathologic evaluation of the reproductive organs revealed no abnormalities. No histopathological changes were observed in either sex. Only one male animal of the 1000 mg/kg bw/day dose group died 32 days after start of the study. The death was not considered to be treatment related. Thus, the NOAEL for reproductive toxicity is considered to exceed 1000 mg/kg bw/day for both sexes.

Conclusion for toxicity to reproduction

A Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening study with the source substance Triacetin (CAS 102-76-1) is available. The substance had no effect on reproductive parameters including mating index, fertility index, gestation length, numbers of corpora lutea and implantations, implantation index, gestation index, delivery index, parturition and maternal behaviour at delivery and lactationand thus the NOAEL for reproduction toxicity was considered to be above 1000 mg/kg bw/day (m, f).


Justification for selection of Effect on fertility via oral route:
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).

Effects on developmental toxicity

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

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 developmental toxicity.

CAS #

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

Developmental toxicity

RA CAS 102-76-1

Experimental result:

NOAEL ≥ 1000 mg/kg bw/day (m, f)

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).

Since no studies are available investigating the developmental toxicity of "Reaction mixture of glycerol-1,3-di(acetate), glycerol acetate and triacetin" the avaiable data from the structurally related analogue substance Triacetin (CAS 102 -76 -1) was

considered for assessment and read-across is conducted based on an analogue approach.

A Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test was performed with Triacetin (CAS 102-76-1) according to OECD Guideline 422 and under GLP conditions (JECDB, 1998). Groups of twelve CD rats received oral gavage doses of 40, 200 and 1000 mg/kg bw/day of Triacetin in 3% gum arabicum in purified water for 44 days from 2 weeks prior to mating for males and for 41- 48 days from 14 days before mating to day 3 postpartum for females. Control animals received the concurrent vehicle. Triacetin had no effects on clinical signs, body weight, food consumption, and organ weight or necropsy findings in parental animals. There were no statistically significant differences from the control in numbers of offspring or live offspring, the sex ratio, the live birth index, and the viability index or body weight. No abnormal findings ascribable to the compound were found for external features, clinical signs or necropsy of the offspring. Thus, the NOAEL for maternal and developmental toxicity is considered to exceed 1000 mg/kg bw/day.

Conclusion for developmental toxicity

A Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening study with the source substance Triacetin (CAS 102-76-1) is available and did not show any treatment related effects up to the highest tested dose level. Thus, no hazard for developmental toxicity was identified and a NOAEL for developmental toxicity is considered to be above the highest dose level (≥ 1000 mg/kg bw/day (m,f)).


Justification for selection of Effect on developmental toxicity: via oral route:
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

The available data on toxicity to reproduction / developmental toxicity of "Reaction mixture of glyceol-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.