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EC number: 246-613-9 | CAS number: 25103-09-7
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- other information
- Study period:
- From December 7, 2004 to September 2, 2005
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Meets generally accepted scientific standards, well documented
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 005
- Report date:
- 2005
Materials and methods
Test guideline
- Qualifier:
- no guideline required
- Principles of method if other than guideline:
- The objective of the study was to determine dosage levels of substance to be evaluated in a reproductive/developmental toxicity screening study in rats.
Therefore, when compared to relevant OECD Guidelines for repeated short-term studies (OECD 407), it suffers limitations, as haematology, clinical chemistry, histopathology and neurobehavioural examinations were not conducted. - GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 2-ethylhexyl mercaptoacetate
- EC Number:
- 231-626-4
- EC Name:
- 2-ethylhexyl mercaptoacetate
- Cas Number:
- 7659-86-1
- Molecular formula:
- C10H20O2S
- IUPAC Name:
- 2-ethylhexyl sulfanylacetate
- Details on test material:
- - Name of test material (as cited in study report): 2-ethylhexyl mercaptoacetate (EHMA)
- Physical state: colorless liquid
- Stability under test conditions: considered stable
- Storage condition of test material: stored at room temperature under nitrogen
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Crl:CD (SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, North Carolina
- Age at study initiation:
Male: 59 days
Female: 82 days
- Weight at study initiation:
Males: 253.9 - 285.0 g
Females: 242.5 - 272.5 g
- Fasting period before study: not reported
- Housing: individually
- Diet: rodent diet ad libitum
- Water: filtered tap water ad libitum
- Acclimation period: 7 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.7 - 23.0
- Humidity (%): 22.8 - 56.1
- Air changes (per hr): approximately 28
- Photoperiod (hrs dark / hrs light): not reported
IN-LIFE DATES: From: January 4 To: January 18, 2005
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: weekly
VEHICLE
- Justification for use and choice of vehicle (if other than water): no
- Amount of vehicle (if gavage): 4 mL/kg
- Purity: 100% - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Duplicate samples (1 mL each) from top, middle and bottom strata of the pre-initiation formulations prepared at concentrations bracketing those used in the study (1 and 50 mg/mL) were used for homogeneity and concentration determinations. Duplicate samples (1 mL each) for concentration analysis were collected from the middle stratum of the first preparation of each dosing formulation (including the control group).
- Duration of treatment / exposure:
- 14 Days
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 10, 50 & 150 mg/kg bw/d
Basis:
other: nominal in gavage solution
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Post-exposure period: none
- Dose selection rationale: Results of the 7-day study of 1992 - Positive control:
- No
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: daily
FOOD CONSUMPTION : Yes
- Time schedule for examinations: daily
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: No
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Gross necropsies were conducted on the 150 mg/kg/day female found dead and all other surviving animals on study day 14. Animals were euthanized by carbon dioxide inhalation at the scheduled necropsy. The necropsies included, but were not limited to, examination of the external surface, all orifices, and the cranial, thoracic, abdominal and pelvic cavities, including contents. Tissues were not retained, and the carcasses were discarded. (See Table 1 for details on organ weights examination) - Statistics:
- Mean body weight, body weight change, food consumption (of each interval) and organ weight data were subjected to a parametric one-way analysis of variance (ANOVA) (Snedecor and Cochran, 1980) to determine intergroup differences. If the ANOVA revealed statistically significant (p<0.05) intergroup variance, Dunnett's test (Dunnett, 1964) was used to compare the test article-treated groups to the control group.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Details on results:
- CLINICAL SIGNS AND MORTALITY
One female in the 150 mg/kg/day group was found dead on study day 2. This female had clear material around the mouth noted on study day 1 approximately 1 hour following dose administration and lost 28.6 g during study days 0-1. This female was internally normal. The death of this female was considered test article-related due to effects on mean body weight seen in the other 150 mg/kg/day females and the mortalities seen at 200 mg/kg/day in the previous 7 day toxicity study (See study: Worell (1992)/Oral 7 day repeated 03). All other animals survived to their scheduled necropsy.
Decreased defecation was noted in three of the 150 mg/kg/day females; noted for one female during study days 2-4 and the other two females during study days 8-11. This finding was not noted in the 150 mg/kg/day males. Clear material around the mouth was observed in four males and in the four surviving females in the 150 mg/kg/day group approximately 1 hour after dose administration. This finding was noted in the majority of these animals as early as study day 2 and continued throughout the remainder of the study. Other clinical findings noted at the daily examinations or approximately 1 hour following dosing including hair loss on various body surfaces, lacrimation, swollen eyelids, clear material on the forelimbs and salivation, occurred primarily in single animals in the 150 mg/kg/day group and therefore were not considered to be test article-related.
BODY WEIGHT AND WEIGHT GAIN
When the overall treatment period (study days 0-14) was evaluated, mean male and female body weight gains in the 150 mg/kglday group were slightly lower (not statistically significant) than the respective control groups.
In this group, in both males and females, lower mean body weight gains were observed for the first-week period of the study. In males, the difference was statistically significant during study days 4-5 (p<0.01) and in females during study days 1-2 and 4-5 (p<0.05).
For the second-week period of the study, mean body weight gains in the 150 mg/kg/day group male and females were generally similar to the control group values.
Mean male and female body weights in the 150 mg/kg/day group were similar to the control group from study days 0 through 4.
However, from study days 5 through 12, mean male and female body weights were 5.1% to 9.2% and 6.0% to 11.9% lower than the control group values, respectively.
By the end of the study (study days 13 and 14), mean male and female body weights in the 150 mg/kglday group were similar to the control group.
The only statistically significant (p<0.05) differences noted were lower mean female body weights during study days 5, 8 and 9.
Mean body weights and body weight changes in the 10 and 50 mglkg/day male and female groups were similar to the respective control group values. Differences were slight and not statistically significant; no dose-dependent trends were evident.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
Mean male food consumption in the 10, 50 and 150 mg/kg/day groups was generally similar to the control group throughout the study (days 0-14). The only statistically significant (p<0.05 or p<0.01) differences noted in any intervals for the male animals on study were increased food consumption in the 150 mg/kg/day group males during study days 10-11 and 12-13.
With the exception of study days 3-4, mean female food consumption in the 150 mg/kg/day group females was lower than the control group from the start of dose administration through study days 10-11; the differences were statistically significant (p<0.05) during study days 2-3 and 4-5. Because of the increases in food consumption during the last 3 days of treatment, mean food consumption in this group was similar to that in the control group when the entire treatment period (study days 0-14) was evaluated.
Food consumption in the 10 and 50 mg/kg/day female groups was similar to that in the control group. The only statistically significant (p<0.05) differences from the control group values were transient increases in the 10 mg/kg/day group females (study days 3-4 and 11-12).
ORGAN WEIGHTS
Mean absolute and relative (to final body weight) liver weights were increased by 14.3% (absolute) in the 50 mg/kg/day males as well as by 25.4 and 25.7% (absolute) in the 150 mg/kg/day male and female groups compared to control group values, respectively. The differences from the control group values for mean relative liver weights at 150 mg/kg/day were statistically significant (p<0.01).
Mean absolute and relative kidney weights were increased by 9.0 and 12.0% (absolute) in the 50 and 150 mg/kg/day males compared to control group values.
Slightly decreased mean absolute and relative thymus and thyroid/parathyroid weights were noted in the 150 mglkg/day group males (14.3 and 16.5% absolute, respectively) and females (17.8 and 23.1% absolute, respectively) compared to the control group values; the difference in mean relative thyroid/parathyroid weight in the males was statistically significant (p<0.05).
No other test article-related effects were noted on organ weights for the 50 and 150 mg/kg/day groups.
No test article-related effects on mean absolute and relative organ weights were observed in the 10 mg/kg/day group males and females. A statistically significant (p<0.05) decrease in mean absolute brain weight was noted in the 10 mg/kg/day group females; this decrease did not occur in a dose-related manner and is not considered to be treatment-related.
GROSS PATHOLOGY
One female from the 150 mg/kg/day group was found dead on study day 2. This female was internally normal. All other animals survived to their scheduled necropsy.
At the scheduled necropsy on study day 14, one male in the control group had white contents in the pericardium and one male in the 50 mg/kg/day group had a dilated renal pelvis. No other gross pathology findings were noted in males or females.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 50 mg/kg bw/day (nominal)
- Sex:
- male/female
- Dose descriptor:
- LOAEL
- Effect level:
- 150 mg/kg bw/day (nominal)
- Sex:
- male/female
- Basis for effect level:
- other: Death of one female and clinical signs associated
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 2 Mean Body Weights changes (g) – Most relevant changes
Exposure Group |
Control |
10 mg/kg/d |
50 mg/kg/d |
150 mg/kg/d |
Males |
||||
Day 4-5 |
9.2 +/- 3.2 |
5.4 +/- 3.2 |
4.9 +/- 2.2 |
-6.6 +/- 13.4** |
Females |
||||
Day 7-14 |
11.7 +/- 6.9 |
8.7 +/- 4.3 |
7.6 +/- 6.4 |
23.8 +/- 4.3* |
*Statistically significant difference from the control group (p0.05) using Dunnett’s test.
**Statistically significant difference from the control group (p0.01) using Dunnett’s test.
Table 3 Food consumption (g/animal/d) – Most relevant changes
Exposure Group |
Control |
10 mg/kg/d |
50 mg/kg/d |
150 mg/kg/d |
Females |
||||
Day 0-7 |
16.0 +/- 2.2 |
18.0 +/- 2.0 |
16.8 +/- 0.8 |
12.5 +/- 2.7* |
*Statistically significant difference from the control group (p0.05) using Dunnett’s test.
Table 4 Organ Weights (g) – Most relevant changes
Exposure Group |
Control |
43 mg/kg/d |
84 mg/kg/d |
170 mg/kg/d |
Males |
||||
Absolute organ Weight (g) |
||||
Liver |
14.6 +/- 1.69 |
15.0 +/- 2.53 |
16.7 +/- 1.78 |
18.3 +/- 3.14 |
Kidney |
3.01 +/- 0.30 |
3.03 +/- 0.20 |
3.28 +/- 0.34 |
3.37 +/- 0.59 |
Relative organ Weight (g) to bodyweight |
||||
Liver |
4.10 +/- 0.21 |
4.27 +/- 0.47 |
4.62 +/- 0.45 |
5.31 +/- 0.52* |
Kidney |
0.84 +/- 0.07 |
0.87 +/- 0.05 |
0.91 +/- 0.11 |
0.98 +/- 0.09 |
Thyroids/para |
0.007 +/- 0.0 |
0.007 +/- 0.0 |
0.006 +/- 0.0015 |
0.007 +/- 0.0005 |
Females |
||||
Absolute organ Weight (g) |
||||
Liver |
11.2 +/- 2.07 |
11.5 +/- 1.76 |
10.1 +/- 1.16 |
14.0 +/- 1.41 |
Brain |
1.88 +/- 0.09 |
1.77 +/- 0.03* |
1.90 +/- 0.05 |
1.83 +/- 0.06 |
Relative organ Weight (g) to bodyweight |
||||
Liver |
4.01 +/- 0.50 |
4.19 +/- 0.58 |
3.64 +/- 0.42 |
5.26 +/- 0.56** |
*Statistically significant difference from control group (p0.05) using Dunnett’s test.
**Statistically significant difference from control group (p0.01) using Dunnett’s test.
Applicant's summary and conclusion
- Conclusions:
- In this limited 14-day repeated dose toxicity study by gavage in rats, as it was designed to select dose to be used in a screening reproduction toxicity study, the NOAEL should be derived at 50 mg/kg bw/d, based on the death of a female at 150 mg/kg bw/d and associated clinical findings observed at this level.
- Executive summary:
The objective of the study was to determine dosage levels of 2-ethylhexyl mercaptoacetate to be evaluated in a reproductive/developmental toxicity screening study in rats.
2-ethylhexyl mercaptoacetate, in the vehicle, corn oil, was administered orally by gavage to three groups of five Crl:CD (SD) rats/sex/dose once daily for 14 days. Dosage levels were 10, 50 and 150 mg/kg/day administered at a dosage volume of 4 mL/kg. A concurrent control group composed of five animals/sex received the vehicle on a comparable regimen. All animals were observed twice daily for mortality and moribundity. Clinical observations, body weights and food consumption were recorded daily. On study day 14, each surviving animal was subjected to a gross necropsy and selected organs were weighed.
One female in the 150 mg/kg/day group was found dead on study day 2. Decreased defecation was observed in three females in the 150 mg/kg/day group.
Body weight losses and associated slight decrease in feed consumption were observed in the 150 mg/kg/day group males and females during the first week of dose administration. Nevertheless, when the overall treatment period (study days 0-14) was evaluated, mean male and female body weight gains in the 150 mg/kg/day groups were found to be only slightly lower (not statistically significant) than the respective control groups.
Increased absolute and relative (to final body weight) liver weights were observed in the 50 mg/kg/day (males) and the 150 mg/kg/day (males and females) groups. Absolute and relative kidney weights were increased in the 50 and 150 mg/kg/day males compared to control group values. Absolute and relative thymus gland and thyroid/parathyroid gland weights in the 150 mg/kg/day males and females were slightly reduced compared to the control animals.
Based on the results of this study, dosage levels of 10, 50 and 150 mg/kg/day were selected for a reproduction/developmental toxicity screening study of 2-ethlyhexyl mercaptoacetate administered orally by gavage to rats.
The NOAEL of this 14-day study in rats should be derived at 50 mg/kg bw/d, based on the death of a female at 150 mg/kg bw/d and associated clinical findings observed at this level. As increases in kidney and liver weight observed in animals dosed at 50 mg/kg bw/d were not found to be statistically significant and because of the absence of gross pathology findings at this dose, these effects should be considered as not toxicologically relevant.
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