Triacetin

Endpoint summary

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

Toxicity to reproduction - Screening

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 (MHLW, 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 histopathological 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 in rats is considered to be ≥ 1000 mg/kg bw/day for both sexes.

Toxicity to reproduction -Two-generation reproductive toxicity study

There is no Two-generation reproductive toxicity study available for Triacetin (CAS 102-76-1). However, data from a reproduction/developmental screening test with the substance does not indicate any adverse effects on parental fertility and intrauterine development of the offspring up to 1000 mg/kg bw/day (highest dose tested). Data from this study also demonstrate that the substance does not exert any adverse effects on reproductive organs or tissues up to currently applied limit dose of 1000 mg/kg bw/day.

Furthermore, all available studies show that the substance is of low acute toxicity after oral and inhalation exposure. In addition, data on the repeated dose toxicity demonstrate that the substance does not exert adverse systemic effects after repeated oral exposure.

In addition, in vitro studies with the substance and its structural analogue Reaction mixture of Glycerol 1,3- di(acetate), glycerol acetate and triacetin (EC 905-964-4) did not show any potential for genetic toxicity.

Toxicokinetic data indicate that uptake of the substance results in complete metabolisation to free glycerol and acetic acid, which are both systemically absorbed (see IUCLID chapter 7.1 Toxicokinetics, metabolism and distribution). However, based on the fact that acetic acid and glycerol are primordial biomolecules found in all species of living organisms, which are fed into various physiological pathways like the citric acid cycle, sugar synthesis, and lipid synthesis, no risk for human health is anticipated.

Although human exposure to the substance cannot be excluded due to its various uses at industrial sites as well as by professionals and consumers, the substance is expected to exert a low hazard profile upon systemic uptake as observed in all available acute and repeated dose toxicity studies.

In conclusion, based the overall weight of evidence from all available data on the substance and its structural analogue Diacetin (technical) (EC 905-964-4), a Pre-natal developmental toxicity study (OECD 414) with the substance is not required and should be avoided for reasons of animal welfare.

Short description of key information:
In a combined repeated dose and reproductive/developmental toxicity screening test with triacetin performed according to OECD Guideline 422 in male and female rats a oral NOAEL of 1000 mg/kg (highest dose tested) was found for parental fertility.

Justification for selection of Effect on fertility via oral route:
There is only one study available (screening test according to OECD 422).

Effects on developmental toxicity

Description of key information

An oral NOAEL for developmental toxicity and teratogenicity in rats of 1000 mg/kg bw/day was found in a study performed according to OECD Guideline 422.  

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

Developmental toxicity/teratogenicity - Screening

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 (MHLW, 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.

Toxicity to reproduction -Pre-natal development

There are no data available for the prenatal developmental toxicity of Triacetin (CAS 102-76-1). However, data from a reproduction/developmental screening test with the substance does not indicate any adverse effects on parental fertility and intrauterine development of the offspring up to 1000 mg/kg bw/day (highest dose tested). Data from this study also demonstrate that the substance does not exert any adverse effects on reproductive organs or tissues up to currently applied limit dose of 1000 mg/kg bw/day.

Furthermore, all available studies show that the substance is of low acute toxicity after oral and inhalation exposure. In addition, data on the repeated dose toxicity demonstrate that the substance does not exert adverse systemic effects after repeated oral exposure.

In addition, in vitro studies with the substance and its structural analogue Reaction mixture of Glycerol 1,3- di(acetate), glycerol acetate and triacetin (EC 905-964-4) did not show any potential for genetic toxicity.

Toxicokinetic data indicate that uptake of the substance results in complete metabolisation to free glycerol and acetic acid, which are both systemically absorbed (see IUCLID chapter 7.1 Toxicokinetics, metabolism and distribution). However, based on the fact that acetic acid and glycerol are primordial biomolecules found in all species of living organisms, which are fed into various physiological pathways like the citric acid cycle, sugar synthesis, and lipid synthesis, no risk for human health is anticipated.

Although human exposure to the substance cannot be excluded due to its various uses at industrial sites as well as by professionals and consumers, the substance is expected to exert a low hazard profile upon systemic uptake as observed in all available acute and repeated dose toxicity studies.

In conclusion, based the overall weight of evidence from all available data on the substance and its structural analogue Diacetin (technical) (EC 905-964-4), a Pre-natal developmental toxicity study (OECD 414) with the substance is not required and should be avoided for reasons of animal welfare.

Justification for selection of Effect on developmental toxicity: via oral route:
There is only one study available (screening test according to OECD 422).

Justification for classification or non-classification

The available data on toxicity to reproduction of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.