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EC number: 242-901-3 | CAS number: 19234-20-9
- 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 2-(1-Methylethoxy)ethanol (CAS No. 109-59-1). 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 421 (Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Japan, Inc. Atsugi
- Fasting period before study: 18 h
- Housing: animals were housed individually in metallic cages with wire mesh bottoms.
- Diet: ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-25
- Humidity (%): 40-75
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on mating procedure:
- - M/F ratio per cage: 1/1
- Length of cohabitation: 2 weeks
- Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as Day 0 of pregnancy - Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- Males: 48 days
Females: from 14 days prior to mating, during mating and 3 days of lactation (41-47 days) - Frequency of treatment:
- daily, 7 days/week
- Remarks:
- Doses / Concentrations:
8, 30 and 125 mg/kg bw/day
Basis:
actual ingested - No. of animals per sex per dose:
- 13
- Control animals:
- yes, concurrent vehicle
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All males and females were observed once per day every day during before administration period, twice per day every day during the administration period.
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations:
Male: On administration days 1, 8, 15, 22, 29, 36, 43 and autopsy day.
Female: On administration days 1, 8, 15 and 22, After confirmation of mating, on gestation days 0, 7, 14 and 20, and after delivery, lactation days 0 and 4 and autopsy day. In females mating, on administration days 36, 43, 50 and autopsy day.
FOOD CONSUMPTION: Yes
- Food consumption:
Male: On administration days 1-2, 8-9, 15-16, 36-37 and 43-44.
Female: Before mating, on administration days 1-2, 8-9 and 14-15, and after confirmation of mating, on gestation days 0-1, 7-8, 14-15 and 20-21, and after delivery, lactation days 3-4.
WATER CONSUMPTION: No - Oestrous cyclicity (parental animals):
- The estrous cycles in all female were determined daily by vaginal smears from acclimation period to mating.
- Sperm parameters (parental animals):
- Parameters examined in P male parental generations:testis weight, epididymis weight
- Litter observations:
- PARAMETERS EXAMINED
The following parameters were examined in F1 offspring: number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioral abnormalities.
GROSS EXAMINATION OF DEAD PUPS:
external and internal abnormalities; possible cause of death was determined for found dead. - Postmortem examinations (parental animals):
- Male animals were sacrificed and necropsied on day following day 48, and the organs were removed for spleen, testis, epididymis, ventral prostate, coagulation gland and seminal vesicle. Of these, spleen, testis, epididymis were weighed. All females delivered were sacrificed and necropsied on day 4 of lactation, and the organs were removed for spleen, ovary, uterus and vagina. Spleen was weighed. The numbers of uterine implantation sites and corpora lutea were counted and implantation index was calculated. Histopathological examination was conducted for testis and epididymis of all male specimens and for ovary of all female specimens in the control and high dose groups.
- Postmortem examinations (offspring):
- Live pups were weighed on day 0 and 4 of lactation, and were necropsied on day 4 of lactation
- Statistics:
- Statistical analyses were conducted by Mann-Whitney U-test, Fischer’s exact probability test, Dunnett’s test, and Kruskal-Wallis rank sum test.
- Reproductive indices:
- Copulation index = (Number of copulated pairs/Number of mated pairs) x 100%
Fertility index = (Number of pregnant animals/Number of copulated pairs) x 100% - Offspring viability indices:
- Delivery index = (Number of pups born/Number of implantation sites) x 100%
Birth index = (Number of live pups on day 0/ Number of implantation sites) x 100%
Live birth index = (Number of live pups on day 0/ Number of pups born) x 100%
Sex ratio on day 0 = (Number of male pups/ Number of female pups) x 100%
Viability index = (Number of live pups on day 4/ Number of live pups on day 0) x 100% - Clinical signs:
- effects observed, treatment-related
- 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:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Other effects:
- no effects observed
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEL
- Remarks:
- systemic
- Effect level:
- 8 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: haematuria
- Dose descriptor:
- NOAEL
- Remarks:
- systemic
- Effect level:
- 30 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: haematuria
- Dose descriptor:
- NOAEL
- Remarks:
- reproduction
- Effect level:
- 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No test substance related effects were observed any reproductive parameters up to the highest dose tested.
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not specified
- Dose descriptor:
- NOAEL
- Remarks:
- developmental
- Generation:
- F1
- Effect level:
- 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects observed
- Reproductive effects observed:
- not specified
Reference
Table 1. Results on reproductive performance.
Dose (mg/kg bw/day) |
Control |
8 |
30 |
125 |
Number of females examined |
13 |
13 |
13 |
13 |
Mean length of estrous cycle [days] |
4.0 ± 0.0 |
4.0 ± 0.0 |
4.0 ± 0.1 |
4.1 ± 0.4 |
Number of animals showing each type of cycle during pre-treatment period |
13 |
13 |
12 |
13 |
Changes of oestrous cycle after treatment |
13 |
13 |
12 |
12 |
Mean times of oestrous during mating |
1.0 ± 0.0 |
1.0 ± 0.0 |
1.0 ± 0.0 |
1.1 ± 0.3 |
Number of mated pairs |
13 |
13 |
13 |
13 |
Copulation indexin % |
100.0 |
100.0 |
100.0 |
100.0 |
Number of pregnant animals |
13 |
12 |
12 |
13 |
Fertility indexin % |
100.0 |
92.3 |
92.3 |
100.0 |
Paring days until copulation |
2.5 ± 1.1 |
2.4 ± 1.0 |
2.5 ± 1.1 |
2.5 ± 1.5 |
Number of pregnant females with live pups |
13 |
12 |
12 |
13 |
Gestation index % |
100.0 |
100.0 |
100.0 |
100.0 |
Gestation length in days |
22.3 ± 0.5 |
22.3 ± 0.5 |
22.3 ± 0.5 |
22.8 ± 0.4* |
Number of corpora lutea |
15.0 ± 1.9 |
15.4 ± 1.9 |
14.8 ± 1.2 |
15.9 ± 2.4 |
Number of implantation sites |
14.7 ± 2.0 |
14.8 ± 1.8 |
13.9 ± 2.4 |
14.9 ± 2.7 |
*: p <0.05, **: p<0.01
Table 2. Developmental parameters of offspring.
Dose (mg/kg bw/day) |
Control |
8 |
30 |
125 |
Day 0 of lactation |
||||
Number of pups born |
13.8 ± 1.9 |
13.9 ± 2.49 |
13.2 ± 2.4 |
13.3 ± 3.2 |
Delivery index (%) |
94.3 ± 4.3 |
93.9 ± 7.3 |
94.4 ± 6.4 |
88.3 ± 12.0 |
Number of live pups |
13.8 ± 1.9 |
13.9 ± 2.4 |
12.9 ± 2.4 |
13.2 ± 3.1 |
Birth index (%) |
94.3 ± 4.3 |
93.9 ± 7.3 |
92.7 ± 6.8 |
87.8 ± 11.6 |
Live birth index (%) |
100.0 ± 0.0 |
100.0 ± 0.0 |
98.2 ± 4.4 |
99.5 ± 1.6 |
Sex ratio on Day 0 (%) |
49.72 ± 16.0 |
54.4 ± 15.7 |
48.7 ± 15.8 |
49.3 ± 10.8 |
Day 4 of lactation |
||||
Number of live pups |
13.8 ± 2.0 |
13.9 ± 2.4 |
12.6 ± 2.4 |
13.2 ± 3.0 |
Viability index (%) |
99.4 ± 2.1 |
100.0± 0.0 |
97.6 ± 6.3 |
99.5 ± 1.6 |
Sex ratio on Day 4 |
49.5 ± 15.8 |
54.4 ± 15.7 |
49.3 ± 16.6 |
49.5 ± 10.6 |
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 125 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on structural similarity between the source and target substance, the source substance being a product of the hydrolysis of the target substance (refer to endpoint discussion for further details).
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 / developmental toxicityof 2-(1-methylethoxy)ethyl acetate (CAS 19234-20-9). In order to fulfil the standard information requirements set out in Annex IX, 8.6, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances 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 physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, 2-isopropoxy-ethanol (CAS 109-59-1) and acetic acid (CAS 64-19-7) are selected as reference substances for assessment of the repeated dose toxicity of 2-(1-methylethoxy)ethyl acetate.
The read-across is based on the metabolism of 2-(1-methylethoxy)ethyl acetate, in particular on the fact that the substance undergoes enzymatic ester hydrolysis resulting in the formation of 2-isopropoxy-ethanol and acetic acid. A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).
Overview of toxicity to reproduction
CAS # |
19234-20-9 |
109-59-1 |
64-19-7 |
Chemical name |
2-(1-methyl-ethoxy)ethyl acetate |
2-isopropoxy-ethanol |
Acetic acid |
Molecular weight |
146.18 |
104.15 |
60.05 |
Toxicity to reproduction |
RA: CAS 109-59-1 and data waiving |
Experimental result: NOAEL (fertility) = 125 mg/kg bw/d |
-- |
(a) The substance subject to registration is indicated in bold font.
(b) Reference (read-across) substances are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.
A reproductive and developmental toxicity screening test was conducted under OECD TG421 in compliance with GLP (MHLW, 2003). 2-(1-methylethoxy) ethanol was administered orally by gavage to rats (13 animals/sex/group) at 0 (vehicle control), 8, 30 and 125 mg/kg bw/day. Males were dosed from 14 days before mating to the day before scheduled sacrifice through the mating period (total 48 days). Females were dosed from 14 days before mating to 3 days after delivery through mating and gestation periods (total 41-47 days). Males were sacrificed and necropsied on day 49. Females and all live F1 pups were sacrificed and necropsied on day 4 of lactation. With regard to reproductive toxicity, no treatment-related change was observed in estrous cyclicity and copulation results (indices for copulation index, fertility index, paring days until copulation). Statistically significant prolongation of gestation length was found in the group at 125 mg/kg bw/day. The values expressed in days were 22.3, 22.3, 22.3 and 22.8 for control, 8, 30, and 125 mg/kg bw/day, respectively. Since all pregnant animals delivered on gestation day (GD) 22 or GD23, this was concluded an accidental change and a meaningless significant difference. There were no changes between control and treated groups in gestation index, number of corpora lutea, number of implantation sites and implantation index. No abnormalities were observed in delivery and lactation for dams in each group. Based on these results, NOAEL for reproductive toxicity was considered to be 125 mg/kg bw/day.
Conclusion for toxicity to reproduction
In a reproductive and developmental toxicity screening test, reproductive performance in parental animals was not affected up to 125 mg/kg bw/day. No abnormalities were observed in delivery and lactation for dams in each group. In F1 offspring, no abnormalities were found for the indices of development and growth up to 125 mg/kg bw/day. Based on these results, NOAELs for reproductive and developmental toxicity were considered to be 125 mg/kg bw /day.
In addition, a substance-tailored exposure-driven testing was followed for the hazard assessment of toxicity to reproduction. No significant exposure is expected throughout all relevant exposure scenarios according to Annex XI, section 3.2(a) (i), therefore testing for developmental toxicity is omitted in accordance with Annex VIII column 2 section 8.6.1. The justification is based on an exposure assessment in accordance with section 5 of Annex I.
Further details are given in the endpoint itself , as well as in the chapter "Toxicological information" and in chapter 9 and 10 of the CSR.
Short description of key information:
Based on read-across from 2-isopropoxyethanol (CAS No. 109-59-1):
NOAEL systemic, female = 8 mg/kg bw/d
NOAEL systemic, male = 30 mg/kg bw/d
NOAEL reproduction, male and female = 125 mg/kg bw/d
Justification for selection of Effect on fertility via oral route:
Hazard assessment is conducted by means of read-across from structural analogues/surrogates. 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
Description of key information
Based on read-across from 2-isopropoxyethanol (CAS No. 109-59-1):
NOAEL systemic maternal = 8 mg/kg bw/d
NOAEL developmental toxicity = 125 mg/kg bw/d
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 2-(1-Methylethoxy)ethanol (CAS No. 109-59-1). 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:
- Crj: CD(SD)
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Japan, Inc. Atsugi
- Fasting period before study: 18 h
- Housing: animals were housed individually in metallic cages with wire mesh bottoms.
- Diet: ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-25
- Humidity (%): 40-75
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- yes
- Details on mating procedure:
- - M/F ratio per cage: 1:1
- Length of cohabitation: up to 2 weeks
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy - Duration of treatment / exposure:
- Males: 48 days
Females: from 14 days prior to mating, during mating and 3 days of lactation (41-47 days) - Frequency of treatment:
- daily, 7 days/week
- No. of animals per sex per dose:
- 13
- Control animals:
- yes, concurrent vehicle
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule:All males and females were observed once per day every day during before administration period, twice per day every day during the administration period.
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations:
Male: On administration days 1, 8, 15, 22, 29, 36, 43 and autopsy day.
Female: On administration days 1, 8, 15 and 22, After confirmation of mating, on gestation days 0, 7, 14 and 20, and after delivery, lactation days 0 and 4 and autopsy day. In females mating, on administration days 36, 43, 50 and autopsy day.
FOOD CONSUMPTION: Yes
- Food consumption:
Male: On administration days 1-2, 8-9, 15-16, 36-37 and 43-44.
Female: Before mating, on administration days 1-2, 8-9 and 14-15, and after confirmation of mating, on gestation days 0-1, 7-8, 14-15 and 20-21, and after delivery, lactation days 3-4.
WATER CONSUMPTION: No
POST-MORTEM EXAMINATIONS: Yes
Male animals were sacrificed and necropsied on day following day 48, and the organs were removed for spleen, testis, epididymis, ventral prostate, coagulation gland and seminal vesicle. Of these, spleen, testis, epididymis were weighed. All females delivered were sacrificed and necropsied on day 4 of lactation, and the organs were removed for spleen, ovary, uterus and vagina. Spleen was weighed. The numbers of uterine implantation sites and corpora lutea were counted and implantation index was calculated.Histopathological examination was conducted for testis and epididymis of all male specimens and for ovary of all female specimens in the control and high dose groups. - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of implantations: Yes - Fetal examinations:
- - External examinations: Yes: all per litter
- Soft tissue examinations: No
- Skeletal examinations: No
- Head examinations: No - Statistics:
- Statistical analyses were conducted by Mann-Whitney U-test, Fischer’s exact probability test, Dunnett’s test, and Kruskal-Wallis rank sum test.
- Indices:
- Delivery index = (Number of pups born/Number of implantation sites) x 100%
Birth index = (Number of live pups on day 0/ Number of implantation sites) x 100%
Live birth index = (Number of live pups on day 0/ Number of pups born) x 100%
Sex ratio on day 0 = (Number of male pups/ Number of female pups) x 100%
Viability index = (Number of live pups on day 4/ Number of live pups on day 0) x 100% - Details on maternal toxic effects:
- Maternal toxic effects:yes. Remark: haematuria
Details on maternal toxic effects:
As a clinical sign, reddish urine (hematuria) was observed after approximately 4 hrs after dosing on the first administration day. All females in the group at 125 mg/kg bw/day, and one female in the group at 30 mg/kg bw/day showed reddish urine until before administration of the next day. No hematuria was found after day 2. Absolute and relative weights of spleen were increased in male and female groups at 125 mg/kg bw/day. - Dose descriptor:
- NOEL
- Remarks:
- systemic
- Effect level:
- 8 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: haematuria
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
The treatment did not affect the indices of birth index, number of pups born, delivery index, number of live pups, live birth index, number of live pups on day 4 of lactation, viability index and sex ratio on postnatal day 4. - Dose descriptor:
- NOEL
- Remarks:
- developmental
- Effect level:
- 125 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No test substance related effects were observed any developmental parameters up to the highest dose tested.
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
Reference
Table 1. Developmental parameters of offspring.
Dose (mg/kg bw/day) |
Control |
8 |
30 |
125 |
Day 0 of lactation |
||||
Number of pups born |
13.8 ± 1.9 |
13.9 ± 2.49 |
13.2 ± 2.4 |
13.3 ± 3.2 |
Delivery index (%) |
94.3 ± 4.3 |
93.9 ± 7.3 |
94.4 ± 6.4 |
88.3 ± 12.0 |
Number of live pups |
13.8 ± 1.9 |
13.9 ± 2.4 |
12.9 ± 2.4 |
13.2 ± 3.1 |
Birth index (%) |
94.3 ± 4.3 |
93.9 ± 7.3 |
92.7 ± 6.8 |
87.8 ± 11.6 |
Live birth index (%) |
100.0 ± 0.0 |
100.0 ± 0.0 |
98.2 ± 4.4 |
99.5 ± 1.6 |
Sex ratio on Day 0 (%) |
49.72 ± 16.0 |
54.4 ± 15.7 |
48.7 ± 15.8 |
49.3 ± 10.8 |
Day 4 of lactation |
||||
Number of live pups |
13.8 ± 2.0 |
13.9 ± 2.4 |
12.6 ± 2.4 |
13.2 ± 3.0 |
Viability index (%) |
99.4 ± 2.1 |
100.0± 0.0 |
97.6 ± 6.3 |
99.5 ± 1.6 |
Sex ratio on Day 4 |
49.5 ± 15.8 |
54.4 ± 15.7 |
49.3 ± 16.6 |
49.5 ± 10.6 |
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 125 mg/kg bw/day
- Quality of whole database:
- The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on structural similarity between the source and target substance, the source substance being a product of the hydrolysis of the target substance (refer to endpoint discussion for further details).
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 toxicity to reproduction / developmental toxicityof 2-(1-methylethoxy)ethyl acetate (CAS 19234-20-9). In order to fulfil the standard information requirements set out in Annex IX, 8.6, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances 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 physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, 2-isopropoxy-ethanol (CAS 109-59-1) and acetic acid (CAS 64-19-7) are selected as reference substances for assessment of the repeated dose toxicity of 2-(1-methylethoxy)ethyl acetate.
The read-across is based on the metabolism of 2-(1-methylethoxy)ethyl acetate, in particular on the fact that the substance undergoes enzymatic ester hydrolysis resulting in the formation of 2-isopropoxy-ethanol and acetic acid. A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).
Overview of developmental toxicity
CAS # |
19234-20-9 |
109-59-1 |
64-19-7 |
Chemical name |
2-(1-methyl-ethoxy)ethyl acetate |
2-isopropoxy-ethanol |
Acetic acid |
Molecular weight |
146.18 |
104.15 |
60.05 |
Developmental toxicity |
RA: CAS 109-59-1 and CAS 64-19-7 and data waiving |
Experimental result: NOAEL (development) = 125 mg/kg bw/d |
Experimental result: NOAEL = 1600 mg/kg bw/d |
(a) The substance subject to registration is indicated in bold font.
(b) Reference (read-across) substances are indicated in normal font.
A reproductive and developmental toxicity screening test was conducted under OECD TG421 in compliance with GLP (MHLW, 2003). 2-(1-methylethoxy) ethanol was administered orally by gavage to rats (13 animals/sex/group) at 0 (vehicle control), 8, 30 and 125 mg/kg bw/day. Males were dosed from 14 days before mating to the day before scheduled sacrifice through the mating period (total 48 days). Females were dosed from 14 days before mating to 3 days after delivery through mating and gestation periods (total 41-47 days). Males were sacrificed and necropsied on day 49. Females and all live F1 pups were sacrificed and necropsied on day 4 of lactation. There were no changes between control and treated groups in gestation index, number of corpora lutea, number of implantation sites and implantation index. No abnormalities were observed in delivery and lactation for dams in each group. The treatment did not affect the indices for development and growth of F1 pups (birth index, live birth index, number of pups born, delivery index, number of live pups, live birth index, number of live pups on day 4 of lactation, viability index, sex ratio on postnatal day 4, and morphological examinations). Based on these results, NOAEL for developmental toxicity was considered to be 125 mg/kg bw/day.
A developmental toxicity study was conducted similar to EU Method B.31 (MHLW, 2003). Acetic acid was administered orally by gavage to 25 pregnant rats, 25 pregnant mice or 12 pregnant rabbits for 10 consecutive days (days 6-15 of gestation) with doses of 0, 16, 74.3, 345 and 1600 mg/kg bw/day. Females and all live F1 pups were subjected to caesarean section where they were sacrificed on day 20 (rats), 17 (mice), or 20 (rabbits). The administration of up to 1600 mg/kg bw/d of the test material to rats, mice or rabbits had no clearly discernible effect on nidation or on maternal or foetal survival. The number ab abnormalities seen either in soft or skeletal tissues of the test group did not differ from the number of occurring spontaneously in the sham-treated controls. Based on these results, NOAEL for developmental toxicity was considered to be 1600 mg/kg bw/day.
Conclusion for developmental toxicity
In a reproductive and developmental toxicity screening test, reproductive performance in parental animals was not affected up to 125 mg/kg bw/day 2-(1-methylethoxy) ethanol. No abnormalities were observed in delivery and lactation for dams in each group. In F1 offspring, no abnormalities were found for the indices of development and growth up to 125 mg/kg bw/day (highest dose tested). Based on these results, NOAELs for reproductive and developmental toxicity were considered to be 125 mg/kg bw /day.
In a developmental toxicity study the NOAEL for developmental toxicity of Acetic acid was considered to be 1600 mg/kg bw/day (highest dose tested).
In addition, a substance-tailored exposure-driven testing was followed for the hazard assessment of developmental toxicity. No significant exposure is expected throughout all relevant exposure scenarios according to Annex XI, section 3.2(a) (i), therefore testing for developmental toxicity is omitted in accordance with Annex VIII column 2 section 8.6.1. The justification is based on an exposure assessment in accordance with section 5 of Annex I.
Further details are given in the endpoint itself, as well as in the chapter "Toxicological information" and in chapter 9 and 10 of the CSR.
Justification for selection of Effect on developmental toxicity: via oral route:
Hazard assessment is conducted by means of read-across from structural analogues/surrogates. 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 the available data on toxicity to reproduction/developmental toxicity of the breakdown products of hydrolysis, the data is insufficient for classification and labelling according to the classification criteria of Regulation (EC) 1272/2008 or Directive 67/548/EEC, and therefore the conclusion is data lacking
Additional information
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