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EC number: 905-964-4 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- 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.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Crj: CD(SD) IGS
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: (P) 9 weeks
- Weight at study initiation: (P) Males: 371-375 g; Females: 203-240 g
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-25
- Humidity (%): 31-62
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- other: 3 % gum arabic in purified water
- Details on mating procedure:
- - M/F ratio per cage: 1/1
- Length of cohabitation: up to 7 days
- Proof of pregnancy: vaginal plug or sperm in vaginal smear - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- (P) Males: 44 days from 2 weeks before mating.
(P) Females: 41-48 days from 14 days before mating to Day 3 postpartum. - Frequency of treatment:
- once daily, 7 days/week
- Remarks:
- Doses / Concentrations:
40, 200 and 1000 mg/kg bw/day
Basis:
actual ingested - No. of animals per sex per dose:
- 12
- Control animals:
- yes, concurrent vehicle
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: the general condition was observed once a day.
BODY WEIGHT: Yes
- Time schedule for examinations: body weight was determined on Day 0, 3, 7 and 14 of administration and once a week thereafter. For pregnant females, body weight was determined on the Day 0, 14 and 20 of gestation and on Day 0 and 4 of lactation.
FOOD CONSUMPTION: Yes
Food consumption was determined on the same day when body weight was measured.
OTHER:
Haematology and biochemistry for males conducted only at time of necropsy after 44 days of exposure (for further details refer to 7.5.1 Repeated dose toxicity). - Oestrous cyclicity (parental animals):
- Estrous cycle lengths were evaluated by vaginal smears, which were stained with Giemsa and microscopically observed.
- Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: all surviving animals were sacrificed the day after the last administration.
- Maternal animals: all surviving animals were sacrificed on Day 4 of lactation.
HISTOPATHOLOGY / ORGAN WEIGHTS
Microscopic examination of all animals in the control and the 1000 mg/kg bw/day group and unfertilized animals in the remaining groups: brain, spinal cord, pituitary gland, eyeball, thyroid gland (including parathyroid gland), thymus, heart, trachea, lung, liver, kidney, adrenal, spleen, stomach, small intestine, large intestine, pancreas, urinary bladder, bone marrow, sciatic nerve, lymph node, testes, epididymis, prostate, seminal vesicle, ovary, uterus, vagina, mammary gland and any organs, which might be expected to have histopathological changes and thymus and lung of dead animals.
Organ weight: brain, pituitary gland, thyroid gland, heart, liver, kidney, spleen, adrenal, thymus, and in addition for males, testes and epididymis. - Postmortem examinations (offspring):
- GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations. - Statistics:
- Regarding quantitative data (body weight, gain of body weight, food consumption, organ weight, haematology, clinical chemistry, number of corpora lutea, number of implantation sites and total number of offspring), Bartlett test was used. In case of equal variance and unequal variance, ANOVA and Kruskal-Wallis test was applied, respectively. If there was a significant difference, Dunnett test or Dunnett multiple-comparison was used. For day of conceiving, number of estrous, gestation length, implantation index, delivery index, viability index at Day 0 and Day 4, Bartlett test and Kruskal-Wallis test was used. If a significant difference was found, Dunnett multi-comparison test was applied. For histopathology findings, Chi-square was used. If a significant difference was observed, Chi-square of Armitage test was used between control and administration group. Regarding copulation index, fertility index, gestation index and sex ratio of offspring was tested with Fisher’s exact test.
- Reproductive indices:
- Copulation index (%): Number of copulated females/number of pairs x 100
Fertility Index (%): Number of pregnant females/numer of copulated females x 100
Gestation index (%): Number of pregnant animals delivered live offspring/ numer of pregnant animals x 100
Delivery index (%) and implantation index (%) - Offspring viability indices:
- Viability index at Day 0 and 4 were determined.
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Other effects:
- not examined
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
- Reproductive effects observed:
- not specified
- Conclusions:
- The test material had no effect on reproductive performance.
Reference
No dose-related changes in general clinical signs.
One male at 1000 mg/kg bw/day was dead 32 days after the administration started.
BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
For both sexes, no statistically significant difference from controls was observed in body weight and body weight gain during administration period. For both sexes, no statistically significant difference from controls was observed in food consumption during administration period.
ORGAN WEIGHTS (PARENTAL ANIMALS)
No dose-related changes in organ weight.
GROSS PATHOLOGY (PARENTAL ANIMALS)
No changes in gross pathology in both sexes.
HISTOPATHOLOGY (PARENTAL ANIMALS)
Tissue pathology revealed no alteration of tissues even in the highest dose groups for both sexes.
No effects on viability were observed.
CLINICAL SIGNS (OFFSPRING)
No effects were described.
BODY WEIGHT (OFFSPRING)
No effects were observed.
GROSS PATHOLOGY (OFFSPRING)
No abnormalities were found in scheduled sacrificed offsprings in all groups. One dead offspring showed pyelectasis at dosing of 40 mg/kg bw/day.
Table 1. Reproductive performance (P).
Group /Dose level |
Fertility Index in % (P) |
Copulation Index in % (P) |
Group 1 (control) |
90.9 |
91.7 |
Group 2 (40 mg/kg bw) |
100 |
100 |
Group 3 (200 mg/kg bw |
100 |
100 |
Group 4 (1000 mg/kg bw) |
100 |
100 |
Table 2. Delivery data (P).
Parameter [mean] |
Group 1 0 mg/kg bw |
Group 2 40 mg/kg bw |
Group 3 200 mg/kg bw |
Group 4 1000 mg/kg bw |
Number of corpora lutea |
16.6 |
16.3 |
16.3 |
16.8 |
Number of Implantations sites |
15.3 |
16.0 |
14.7 |
15.8 |
Total number of offsping |
14.4 |
15.3 |
14.3 |
14.6 |
Implantation Index (%) |
90.15 |
98.17 |
89.49 |
93.84 |
Delivery Index (%) |
94.83 |
95.11 |
90.17 |
92.62 |
Gestation Index (%) |
100 |
100 |
91.7 |
100 |
Table 3. Litter size and viability index (F1).
Parameter |
Group 1 0 mg/kg bw |
Group 2 40 mg/kg bw |
Group 3 200 mg/kg bw |
Group 4 1000 mg/kg bw |
Total number of offspring at birth |
14.4 |
15.3 |
15.6 |
14.6 |
Total number of live offspring at birth |
14.2 |
15.3 |
15.5 |
14.6 |
Number of live offspring on Day 4 |
14.1 |
14.8 |
15.2 |
14.5 |
Viability index (%) Day 0 Day 4 |
98.71 99.38 |
100 97.17 |
98.86 98.3 |
100 99.41 |
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 toxicity to reproduction 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
Link to relevant study records
- Endpoint:
- developmental toxicity
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- 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.
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- other: Crj: CD(SD) IGS
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: (P) 9 weeks
- Weight at study initiation: (P) Males: 371-375 g; Females: 203-240 g - Route of administration:
- oral: gavage
- Vehicle:
- other: 3 % gum arabic in purified water
- Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - M/F ratio per cage: 1/1
- Length of cohabitation: up to 7 days
- Proof of pregnancy: vaginal plug or sperm in vaginal smear - Duration of treatment / exposure:
- 44 days (males) from 2 weeks prior to mating.
41-48 days (females) from 14 days before mating to day 3 postpartum. - Frequency of treatment:
- daily
- Duration of test:
- Day 14 before mating to Day 3 postpartum
- Remarks:
- Doses / Concentrations:
40, 200 and 1000 mg/kg bw/day
Basis:
actual ingested - No. of animals per sex per dose:
- 12
- Control animals:
- yes, concurrent vehicle
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: The general condition was observed once a day.
BODY WEIGHT: Yes
- Time schedule for examinations: Body weight was determined on Day 0, 3, 7 and 14 of administration and once a week thereafter. For pregnant females, body weight was determined on the Day 0, 14 and 20 of gestation and on Day 0 and 4 of lactation.
FOOD CONSUMPTION: Yes
Food consumption was determined on the same day when body weight was measured.
HISTOPATHOLOGY / ORGAN WEIGHTS
Microscopic: all animals in control and 1,000 mg/kg bw group, and unfertilized animals in other groups: brain, spinal cord, pituitary gland, eyeball, thyroid gland (including parathyroid gland), thymus, heart, trachea, lung, liver, kidney, adrenal, spleen, stomach, small intestine, large intestine, pancreas, urinary bladder, bone marrow, sciatic nerve, lymph node, testes, epididymis, prostate, seminal vesicle, ovary, uterus, vagina, mammary gland and any organs, which might be expected to have histopathological changes and thymus and lung of dead animals.
Organ weight: for both sexes, brain, pituitary gland, thyroid gland, heart, liver, kidney, spleen, adrenal, thymus, and in addition for males, testes and epididymis.
OTHER:
Haematology and biochemistry for males conducted only at time of necropsy after 44 days of exposure (for further details refer to 7.5.1 Repeated dose toxicity). - Ovaries and uterine content:
- - Number of corpora lutea: Yes
- Number of implantations: Yes - Fetal examinations:
- Numbers of offspring or live offspring, the sex ratio, the live birth index, the viability index and body weights, external features, clinical signs and necropsy.
Gross necropsy consisted of external and internal examination. - Statistics:
- Regarding quantitative data (body weight, gain of body weight, food consumption, organ weight, haematology, clinical chemistry, number of corpora lutea, number of implantation sites and total number of offspring), Bartlett test was used. In case of equal variance and unequal variance, ANOVA and Kruskal-Wallis test was applied, respectively. If there was a significant difference, Dunnett test or Dunnett multiple-comparison was used. For day of conceiving, number of estrus, gestation length, implantation index, delivery index, viability index at Day 0 and Day 4, Bartlett test and Kruskal-Wallis test was used. If a significant difference was found, Dunnett multi-comparison test was applied. For histopathology findings, Chi-square was used. If a significant difference was observed, Chi-square of Armitage test was used between control and administration group. Regarding copulation index, fertility index, gestation index and sex ratio of offspring was tested with Fisher’s exact test.
- Indices:
- Copulation index (%): Number of copulated females/number of pairs x 100
Fertility Index (%): Number of pregnant females/numer of copulated females x 100
Gestation index (%): Number of pregnant animals delivered live offspring/ numer of pregnant animals x 100
Delivery index (%) and implantation index (%) were given.
The gestation index, gestation length, parturition and maternal behavior. Effects at gross pathology and microscopic evaluation of the reproductive organs. - Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
No dose-related changes in general clinical signs. One male at 1000 mg/kg bw/day was dead 32 days after the administration started.
BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
For both sexes, no statistically significant difference from controls was observed in body weight and body weight gain during administration period. For both sexes, no statistically significant difference from controls was observed in food consumption during administration period.
ORGAN WEIGHTS (PARENTAL ANIMALS)
No dose-related changes in organ weight were observed.
GROSS PATHOLOGY (PARENTAL ANIMALS)
No changes in gross pathology in both sexes were observed.
HISTOPATHOLOGY (PARENTAL ANIMALS)
Tissue pathology revealed no alteration of tissues even in the highest dose groups for both sexes.
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
On examination of neonates, there were no significant differences in numbers of offspring or live offspring, the sex ratio, the live birth index, the viability index or body weights. No abnormal findings ascribable to the compound were found for external features, clinical signs or necropsy of the offspring. One dead offspring showed pyelectasis at dosing of 40 mg/kg bw/day. - Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- The test substance had no effect on intrauterine development.
Reference
Table 1. Delivery data (P).
Parameter [mean] |
Group 1 0 mg/kg bw |
Group 2 40 mg/kg bw |
Group 3 200 mg/kg bw |
Group 4 1000 mg/kg bw |
Number of corpora lutea |
16.6 |
16.3 |
16.3 |
16.8 |
Number of Implantations sites |
15.3 |
16.0 |
14.7 |
15.8 |
Total number of offsping |
14.4 |
15.3 |
14.3 |
14.6 |
Implantation Index (%) |
90.15 |
98.17 |
89.49 |
93.84 |
Delivery Index (%) |
94.83 |
95.11 |
90.17 |
92.62 |
Gestation Index (%) |
100 |
100 |
91.7 |
100 |
Table 2. Litter size and viability index (F1).
Parameter |
Group 1 0 mg/kg bw |
Group 2 40 mg/kg bw |
Group 3 200 mg/kg bw |
Group 4 1000 mg/kg bw |
Total number of offspring at birth |
14.4 |
15.3 |
15.6 |
14.6 |
Total number of live offspring at birth |
14.2 |
15.3 |
15.5 |
14.6 |
Number of live offspring on Day 4 |
14.1 |
14.8 |
15.2 |
14.5 |
Viability index (%) Day 0 Day 4 |
98.71 99.38 |
100 97.17 |
98.86 98.3 |
100 99.41 |
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 developmental 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.Additional information
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