Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 431-090-3 | CAS number: 190085-41-7
- 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
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- September 06 to November 05, 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2013
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- 2-ethylhexyl salicylate
- EC Number:
- 204-263-4
- EC Name:
- 2-ethylhexyl salicylate
- Cas Number:
- 118-60-5
- IUPAC Name:
- 2-ethylhexyl salicylate
- Test material form:
- other: liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: RccHanTM: WIST(SPF)
- Details on test animals or test system and environmental conditions:
- Animals: Rat, RccHanTM: WIST(SPF)
Rationale: Recognized by international guidelines as a recommended test system.
Breeder: Harlan Laboratories, B.V. Kreuzelweg 53 5961 NM Horst / Netherlands
Number of Animals: 44 males: 11 per group 44 females: 11 per group
Age (at Start of Treatment): 11 weeks
Body Weight Range
(at Start of Treatment): Males: 312 to 351 g Females: 208 to 244 g
Identification: Cage card and individual animal number (ear tattoo).
Pups: On day 1 post partum, pups were individually tattooed with Indian ink.
Randomization: Performed after at least three days of acclimatization using a computer-generated random algorithm. Body weights (recorded on the day of allocation) were taken into consideration in order to ensure similar mean body weights in all groups.
Acclimatization: Under test conditions after health examination. Only animals without any visible signs of illness were used for the study.
Husbandry
Room Numbers, Füllinsdorf: E0441A (acclimatization) and E0441 (after acclimatization) Conditions: Standard laboratory conditions. Air-conditioned with 10 - 15 air changes per hour, continuously monitored environmental conditions (temp. range: 22 ± 3 °C; relative humidity range: 30 - 70%). Values outside of these ranges occasionally occurred, usually following room cleaning, which was considered not to have any influence on the study. These data were not reported but were retained in the raw data. There was 12-hour fluorescent light / 12-hour dark cycle with music during the light period.
Accommodation: In groups of three to five animals in Makrolon type-4 cages with wire mesh tops up to the day of ran-domization and afterwards individually in Makrolon type-3 cages with wire mesh tops and sterilized standard softwood bedding (‘Lignocel’ J. Rettenmaier & Söhne GmbH & CoKG, 73494 Rosenberg/Germany, imported by Provimi Kliba SA, 4303 Kaiseraugst / Switzerland) with paper enrichment (ISO-BLOX from Harlan Laboratories B.V., Netherlands), batch/ lot nos. 100099. During the pre-pairing period, cages with males were interspersed amongst those holding females to promote the development of regular estrus cycles.
Diet: Pelleted standard Harlan Teklad 2018C (batch no. 43/12) rodent maintenance diet (Provimi Kliba SA, 4303 Kaiseraugst / Switzerland) was available ad libitum. .
Water: Community tap-water from Füllinsdorf was available ad libitum in water bottles.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- Four groups of 11 males and 11 females were treated by gavage with Neo Heliopan OS once daily. Males were treated over a 14-day pre-pairing period and during the pairing period up to one day before necropsy. Females were treated throughout the pre-pairing, pairing, gestation and lactation period up to the day 3 post partum.
Vehicle and Control Item
Identification: Corn oil
Source: Carl Roth GmbH
Batch Number: 292189296
Expiry Date (Retest Date): 02-Aug-2017
Storage Conditions: Room temperature (20 ± 5 °C) - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- On the first treatment day samples from the control group as well as three samples (top, middle and bottom) of about 1 g of each concentration were taken prior to dosing for analysis of concentration and homogeneity. To confirm the stability (8 days) samples of about 1 g of each concentration were taken from the middle of each aliquot used on day 7 of the treatment. During the last week of the treatment, samples were taken from the middle to confirm concentration.
The aliquots for analysis of dose formulations were frozen (-20 ± 5 °C) and delivered on dry ice to B. Bürkle (Harlan Laboratories Ltd., Zelgliweg 1, 4452 Itingen / Switzerland) and stored there at -20 ± 5 °C until analysis.
The samples were analyzed by GC coupled to an FID detector following an analytical procedure provided by the Sponsor and adapted at Harlan Laboratories. The test item was used as the analytical standard. Analyzed samples were not discarded without written consent from the study director.
In conclusion, the results indicate the accurate use of the test item and corn oil as vehicle during this study. Application formulations were found to be homogeneously prepared and sufficient formulation stability under storage conditions was approved. - Details on mating procedure:
- During the pairing period, females were housed with sexually mature males (1:1) until evidence of copulation was observed. The females were removed and housed individually if:
- the daily vaginal smear was sperm positive, or
- a copulation plug was observed.
The day on which a positive mating was determined (copulation plug or sperm) was designated day 0 post coitum. - Duration of treatment / exposure:
- Males: 28 days Females: Approximately 7 weeks
- Frequency of treatment:
- Once daily
- Duration of test:
- Approximately 7 weeks
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 25, 80, 250 mg/kg/day
Basis:
actual ingested
- No. of animals per sex per dose:
- 11
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Method: Oral, by gavage
Rationale for Method: Administration by gavage is a common and accepted route of exposure for this type studies.
Frequency of Administration: Once daily
Target Dose Levels: Group 1: 0 mg/kg/day (control group)
Group 2: 25 mg/kg/day
Group 3: 80 mg/kg/day
Group 4: 250 mg/kg/day
Rationale for Dose Level Selection: The dose levels were selected based on a previous dose range-finding toxicity study in Han Wistar rats, Harlan Laboratories Study D54872, using dose levels of 0, 100, 300 and 1000 mg/kg/day, resulting in mortality and adverse toxic effects at the dose level
of 1000 mg/kg bw/day and adverse toxic effects at the dose level of 300 mg/kg bw/day.
Dose Volume: 4 mL/kg body weight
Dose Concentrations: Group 1: 0.00 mg/mL
Group 2: 6.25 mg/mL
Group 3: 20.00 mg/mL
Group 4: 62.50 mg/mL
Duration of Acclimatization Period: Minimum 5 days
Duration of Treatment Period: Males: 28 days Females: Approximately 7 weeks
Examinations
- Maternal examinations:
- Viability / Mortality: Twice daily
Clinical Signs: Daily cage-side clinical observations (once daily, during acclimatization and up to day of necropsy). Additionally females were observed for signs of difficult or prolonged parturition, and behavioral abnormalities in nesting and nursing.
Food Consumption: Males: Pre-Pairing period days 1 - 4, 4 - 8, 8 - 11 and 11 - 14; after pairing period weekly.
Females: Pre-Pairing period days 1 - 4, 4 - 8, 8 - 11 and 11 - 14; gestation days 0 - 7, 7 - 14 and 14 - 21 and days 1 - 4 of the lactation.
No food consumption was recorded during the pairing period.
Body Weights: Recorded daily from treatment start to day of necropsy. - Ovaries and uterine content:
- Ovaries were checked for discoloration and uteri for fetus content and discoloration.
- Fetal examinations:
- Pup Data: The litters were examined for litter size, live births, still births and any gross anomalies. The sex ratio of the pups was recorded. Pups were weighed individually (without identification) on days 0 (if possible), 1 and 4 post partum. Pups and dams were sacrificed on day 4 post partum. All parent animals and pups, except those excessively cannibalized, were examined macroscopically for any structural changes, either at the scheduled necropsy or during the study if death occurred to establish, if possible, the cause of death.
- Statistics:
- The following statistical methods were used to analyze food consumption, body weights and reproduction data:
• Means and standard deviations of various data were calculated.
• The Dunnett-test [see References (2)] (many to one t-test) based on a pooled variance estimate was applied if the variables could be assumed to follow a normal distribution for the comparison of the treated groups and the control groups for each sex.
• The Steel-test [see References (3)] (many-one rank test) was applied instead of the Dunnett-test when the data could not be assumed to follow a normal distribution.
• Fisher's exact-test [see References (4)] was applied if the variables could be dichotomized without loss of information. - Indices:
- Reproductive indices recorded were fertility indices, mean precoital time, post-implantation loss, and offspring viability indices were mean litter size, pup sex ratios and viability indices.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
At 250 mg/kg bw/d slight but non-significant changes on weight gain were noted.
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 80 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
No test item-related effects on mating performance, fertility index (number of females achieving pregnancy as a percentage of females paired), conception rate (number of females achieving pregnancy as a percentage of females mated), corpora lutea count, number of implantations or postnatal loss were noted at any dose level.
Treatment with the test item at the dose levels of 250 and 80 mg/kg bw/day caused a reduction in gestation index (number of females with living pups as a percentage of females pregnant) as well as an increase in incidence of post-implantation loss resulting in a lower litter size. Further, at the dose levels of 250 and 80 mg/kg bw/day, prolonged gestation period was noted. These findings were considered to be test item-related adverse effects.
Effect levels (fetuses)
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 80 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- fetal/pup body weight changes
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
1 Viability / Mortality
At the dose level of 250 mg/kg bw/day, one female (no. 78) was found dead on day 23 of the gestation period. During necropsy, fetuses were found in uterus of this female. A slight body weight loss was noted in this female on day 22 of the gestation period but no other signs and no macroscopical or microscopical findings indicating bad condition of this female were noted. Death of the female was most probably a result of difficult parturition and considered to be test-item related. All remaining animals of P generation survived the scheduled study period.
2 Clinical Signs or Observations
No test item-related findings were noted in males or females at any dose level. In one female (67) at the mid-dose level, hunched posture and ruffled fur were noted from day 2 of the lactation period onwards. Further, slight swelling in axillary region was observed in one female (no. 79) at the high-dose level from day 9 of the gestation period onwards. Because of isolated occurrence, these findings were considered not to be related to the treatment with the test item. No further findings were noted in males or females at any dose level.
3 Food Consumption of Males
The overall differences in mean food consumption at the dose levels of 25, 80 and 250 mg/kg bw/day were respectively: +0.9%, -0.9% and +1.7% during the pre-pairing period (percentages refer to the respective values in the control group).
4 Food Consumption of Females Pre-Pairing, Gestation and Lactation Periods
At the dose levels of 250 and 80 mg/kg bw/day, reduced food consumption was noted during lactation. Mean food consumption was 16.4 and 19.8 g/animal/day at the dose levels of 250 and 80 mg/kg bw/day, respectively and 22.2 g/animal/day in the control group. Although the differences were not statistically significant, they were dose dependent and therefore considered to probably be related to the treatment with the test item. No effects on food consumption were noted at the dose level of 80 mg/kg bw/day. The overall differences in mean food consumption at the dose levels of 25, 80 and 250 mg/ kg bw/day were respectively: -5.6%, -0.6% and -4.4% during the pre-pairing period, -2.4%, +6.2% and +4.8% during the gestation period and +1.4%, -10.8% and -26.1% during the lactation period (percentages refer to the respective values in the control group).
5 Body Weights of Males Pre-Pairing and Pairing Periods
At the dose level of 250 mg/kg bw/day, slight but statistically significant reduction in body weight gain was noted on day 13 of the pre-pairing period. Body weight gain was also slightly lower on further days at the end of this period but without statistical significance. No significant differences in absolute body weights were noted at this dose level. At the dose levels of 25 and 80 mg/kg bw/day, no test item-related effects on absolute body weights or body weight gain were noted. The overall differences in mean body weight gain at the dose levels of 0, 25, 80 and 250 mg/kg bw/day were respectively: +15%, +15%, +13% and +13% during the pre-pairing period and +11%, +9%, +9% and +10% during the pairing period (percentages refer to the body weight gain within the period). At the low- and mid-dose levels, statistically significantly lower body weight gains were noted on individual days during the pairing period. Because the differences were minor and did not follow dose dependency, they were considered not to be related to the treatment with the test item. 6 Body Weights of Females Pre-Pairing, Pairing, Gestation and Lactation Periods At the dose level of 250 mg/kg bw/day, statistically significant reduction in body weight gain was noted on day 4 of the lactation period. No significant differences in absolute body weights were noted at this dose level at any time. At the dose levels of 25 and 80 mg/kg bw/day, no effects on absolute body weights or body weight gain were noted. The overall differences in mean body weight gain at the dose levels of 0, 25, 80 and 250 mg/kg bw/day were respectively: +8%, +7%, +9% and +6% during the pre-pairing period, +51%, +55%, +56% and +48% during the gestation period and +5%, +2%, +2% and ±0% during the lactation period (percentages refer to the body weight gain within the period). Mating Performance and Fertility: No effects on mating performance, fertility index or conception rate were noted at any dose level. No effects on gestation index were noted at the dose level of 25 mg/kg bw/day; it was 100% at this dose level. Duration of Gestation : At the dose levels of 250 and 80 mg/kg bw/day, prolonged gestation period was noted. Mean duration of gestation was 22.6 and 22.0 days at the dose levels of 250 and 80 mg/kg bw/day, respectively, compared to 21.5 days in the control group. Mean prolongation of the gestation at the high- and mid-dose levels was not statistically significant. However, it was dose dependent and the values were beyond the biological background (historical control data included values of gestation length from 21.2 to 21.8 days). Therefore this finding was considered to be test item-related. At the dose level of 25 mg/kg bw/day, mean gestation of duration was the same like the control value; 21.5 days and therefore not affected by the treatment. Corpora Lutea Count : No effects on corpora lutea count were observed at any dose level. Implantation Rate and Post-Implantation Loss : Number of implantations was not affected by the treatment with the test item at any dose level. At the dose level of 25 mg/kg bw/day, no effects on post-implantation loss were noted.
Applicant's summary and conclusion
- Conclusions:
- Because of reduced absolute body weights of pups at the dose level of 250 mg/kg bw/day NOEL for developmental toxicity was considered to be 80 mg/kg bw/day.
- Executive summary:
Because of reduced absolute body weights of pups at the dose level of 250 mg/kg bw/day NOEL for developmental toxicity was considered to be 80 mg/kg bw/day. No test item-related observations were noted in pups during the first litter check or during lactation at any dose level. Pups sex ratio was not affected by the exposure to the test item at any dose level. Treatment with the test item at the dose level of 250 mg/kg bw/day caused a reduction in body weights of pups recorded on day 1 and 4 of the lactation period. During this period, body weight gain of pups at the high-dose level was similar to body weight gain of pups in the control group. Reduction in absolute body weights of pups was considered to be test item-related adverse effect. No test item-related effects on body weights or body weight gain of pups were noted at the dose levels of 25 and 80 mg/kg bw/day. No test item-related macroscopical findings were found in pups at any dose level.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.