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EC number: 800-526-8 | CAS number: 1273322-45-4
- 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:
- one-generation reproductive toxicity
- Remarks:
- based on generations indicated in Effect levels (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2012 - 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study according to GLP
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River
- Age at study initiation: males 11-12 weeks, females 11-12 weeks
- Weight at study initiation: males 302-348g, females 184-217g
- Fasting period before study: overnight
- Housing: individually in IVC cages, type III H
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 - Route of administration:
- oral: gavage
- Vehicle:
- other: sesame oil
- Details on exposure:
- VEHICLE
- Justification for use and choice of vehicle (if other than water): sesame oil is a recommended vehicle and was chosen on the basis of solubility tests. - Details on mating procedure:
- Mating was performed using a ratio of 1:1 (male to female). The vaginal smear of the females was checked every morning after the start of the mating period to confirm the pregnancy. The day of the vaginal plug and/or sperm was considered as day 0 of gestation. Females with unsuccessful mating will be allowed to mate with other male of the same group.
- Analytical verification of doses or concentrations:
- yes
- Duration of treatment / exposure:
- The animals were treated with the test item formulation or vehicle on 7 days per week for a period of 54 days, i.e. during 14 days of pre-mating and 14 days of mating in both males and females, during the gestation period and up to post-natal day 3 in females. Males were dosed after the mating period until the minimum total dosing period of 28 days were completed.
- Frequency of treatment:
- once daily
- Remarks:
- Doses / Concentrations:
0, 12, 30, 75 mg/kg body weight per day
Basis:
nominal conc. - No. of animals per sex per dose:
- 10 males and 10 female per group (in total 80 animals)
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Based on dose-range-finder
- Rationale for animal assignment (if not random): random - Positive control:
- no
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: before start of study and weekly thereafter - Sperm parameters (parental animals):
- For the testes, a detailed qualitative examination was made; taking into account the tubular stages of the spermatogenic cycle at evaluation of additional hematoxylin-PAS (Periodic Acid Schiff) stained slides.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- only high dose animals
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- mid and high dose animals
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- mid and high dose animals
- 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:
- no effects observed
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- 12 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: overall effects
- Dose descriptor:
- NOAEL
- Effect level:
- 12 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: overall effects
- Clinical signs:
- no effects observed
- Mortality / viability:
- mortality observed, treatment-related
- Description (incidence and severity):
- Total number of pubs born at PND 0 was significantly decreased in high dose animals. Additionally, number of living pubs was significantly decreased at PND 4 in high dose group.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Decreased total litter weight in high dose group at PND 0
- Sexual maturation:
- no effects observed
- 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:
- 12 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: overall effects
- Reproductive effects observed:
- not specified
- Conclusions:
- Based on the results of this study the NOAEL for male and female parental animals was 12 mg/kg body weight per day. Likewise, the NOAEL for the pubs was 12 mg/kg body weight per day.
- Executive summary:
Possible effects of C16-18-(even numbered)-alkylamines acetates on male and female fertility and embryofetal development after repeated dose administration in Wistar rats were investigated in an OECD 421 screening assay according to GLP. The test item was administered daily in graduated doses of 12, 30 and 75 mg/kg body weight per day to 3 groups of 10 test animals (5 male, 5 female), one dose level per group for a treatment period of 54 days, i.e. during 14 days of pre-mating and 14 days of mating in both males and females, during the gestation period and up to post-natal day 3 in females. Males were dosed after the mating period until the minimum total dosing period of 28 days were completed. Animals of an additional control group were treated identically but received only the vehicle sesame oil. During the period of administration, the animals were observed each day for signs of toxicity. Body weight and food consumption were measured weekly. Animals that died were examined macroscopically and at the conclusion of the test, surviving animals were sacrificed and observed macroscopically. After 14 days of treatment to both male and female, animals were mated (1:1) for a maximum of 14 days. The males were sacrificed after completion of the mating period on treatment days 29 and 30 and the females along with their pups were sacrificed on post natal day 4.
For male animals, moderate clinical symptoms and a significantly decreased body weight development was found at 75 mg/kg body weight. At 30 mg/kg body weight a significantly attenuated body weight gain was found during specific intervals, too. Hence, the observed adverse effect level (NOAEL) for male animals is assumed to be 12 mg/kg body weight.
In female animals, moderate clinical symptoms and a significantly reduced body weight development during specific intervals were observed at 75 mg/kg body weight. An attenuated body weight gain (not statistical significant) was also mentioned at 30 mg/kg body weight. Hence, the observed adverse effect level (NOAEL) for female animals is assumed to be 12 mg/kg body weight.
At a dose level of 75 mg/kg body weight, the total number of pubs born was significantly reduced at PND 0 and the number of living pubs as well as total litter weight was significantly reduced at PND 0 and PND 4, too. In addition, number of implantation sites was significantly decreased in the high dose group. 2 female dams exhibited mortalities of pubs. At 30 mg/kg a tendency towards a decreased number of born pubs was observed. Furthermore, a decrease in the number of implantation sites could be recorded. Both findings at 30 mg/kg body weight are not statistical significant. However, they confirm the findings in the high dose group and hence are assumed to be the starting point of toxicological relevance which may be attributable to the maternal toxic effects seen at these higher doses. Therefore the no observed adverse effect level (NOAEL) for toxicity of the pubs is conservatively assumed to be 12 mg/kg body weight.
Reference
BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS): Decrease in body weight in male and female animals of mid- and high dose group.
REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS): No significant effects noted
REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS): No significant effects noted
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS): No significant effects noted
ORGAN WEIGHTS (PARENTAL ANIMALS): No substance related effects noted
GROSS PATHOLOGY (PARENTAL ANIMALS): No substance related effects noted
HISTOPATHOLOGY (PARENTAL ANIMALS): No significant changes noted.
CLINICAL SIGNS (OFFSPRING): No clinical signs observed.
BODY WEIGHT (OFFSPRING): Decrease in total litter weight at PND 0 in high dose group.
SEXUAL MATURATION (OFFSPRING): No effects.
ORGAN WEIGHTS (OFFSPRING): Not examined.
GROSS PATHOLOGY (OFFSPRING): No effects.
HISTOPATHOLOGY (OFFSPRING): Not examined.
Effect on fertility: via oral route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 12 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Based on findings in a guideline conform reproductive screening study according to OECD TG 421 relevant effects were only observed in the maternal toxic range. This is in good agreement with findings, effects and NOAEL considerations of another OECD 421 study carried out on the structural and functional closely related tallow alkylamines. The available data base is considered sufficient and the information is valid and meets the data requirements.
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
- Quality of whole database:
- The available data base is considered sufficient for hazard / risk characterization.
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
- Quality of whole database:
- The available data base is considered sufficient for hazard / risk characterization.
Additional information
The registration substance was tested for potential reproductive toxicity in a screening assay according to OECD TG 421 following oral administration to rats. Based on toxicity data from a 14 -day dose-range finder, 12, 30 and 75 mg/kg body weight were selected as dose levels. Both, the parental (maternal) NOAEL and the reproductive NOAEL in this study was established at 12 mg/kg body weight. Significant reproductive toxic effects were not observed in the adult animals. Most prominent effects beside general unspecific toxicity had been gastric lesions indicative of strong irritation properties of the test item. Effects in the offspring were only observed in the range of maternal toxicity.
These findings are in line with results from a comparable OECD 421 reproductive screening assay with the analogous primary alkylamine C16 -18 -(even numbered, C18 -unsaturated)-alkylamines. Beside unspecific clinical symptoms also reductions in body weight gain were most prominent. The NOAEL for parental toxicity as well as for reproductive toxicity in the offspring was considered to be 12.5 mg/kg body weight and thus in good agreement with the above NOAELs for the registration substance.
Likewise, for both studies extended histopathological investigations of the reproductive organs including sperm staging after repeated administration of the registration substance have not revealed indications of reproductive / fertility toxic effects. From all available data, including information on analogous primary alkylamines, it can be concluded that the registration substance is devoid of a reproductive toxic potential below doses causing maternal toxic effects.
It has to be noted, that the observed effects and effect levels are in good agreement with NOAELs revealed in repeated dose toxicity studies. From all available data it can be concluded that the observed effects following oral exposure are generally related to the irritative properties rather than an expression of systemic toxicity.
Short description of key information:
The registration substance was tested in a guideline conform reproductive toxicity screening study according to OECD TG 421. No clear effects on fertility / reproduction or development were observed. The parental NOAEL in this study was 12 mg/kg body weight (based mainly on unspecific clinical symptoms, reduced body weights) and the NOAEL for fertility / reproduction was also 12 mg/kg body weight. The findings are in line with data from a comparable OECD 421 study with an analogous primary alkylamine which resulted in similar toxicity and a similar NOAEL of 12.5 mg/kg body weight. From the data it can be concluded that in adult animals significant reproductive toxic effects were not observed rather than general toxicity and that the effects observed in the offspring are in the maternal toxic range.
Justification for selection of Effect on fertility via oral route:
Guideline study according to GLP with a Klimisch rating of 1.
Effects on developmental toxicity
Description of key information
The registration substance was tested for developmental toxicityin a screening study designed to also investigate for pre-implantation loss. Pregnant female rats were administered the test item from gestation day 0 until gestation day 19. A second group of animals revealed the test item one week before mating, during the mating period and until gestation day 19. No adverse effects on reproductive parameters including pre- and/or post-implantation loss were observed and no visceral and/or skeletal abnormalities were revealed. These findings are in line with results from analogous primary alkylamines tested in guideline conform OECD TG 414 studies. Based on close structural, functional, metabolic and toxicological similarities, read-across to primary alkylamines is performed. Oral administration of 40 and 80 mg/kg body weight per day of C16-18-(even numbered, saturated and unsaturated)-alkylamines to pregnant CD rats induced dose dependent maternal toxicity indicated by adverse clinical signs, body weight loss and reduced food consumption. A dosage level of 10 mg/kg body weight per day was determined to be a no effect level for maternal toxicity. However, the test item was neither developmental toxic nor teratogenic at dosage levels of 10, 40 or 80 mg/kg body weight per day. Similar findings demonstrating the absence of developmental toxic effects even in maternal toxic ranges have been revealed with the same primary alkylamine when tested in rabbits. From the results it can be concluded, that developmental toxic properties of the registration substance can almost be excluded.
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:
- weight of evidence
- Study period:
- 1989
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Test procedure according to national guidelines and standards (TSCA Guidelines) including GLP
- Qualifier:
- according to guideline
- Guideline:
- other: EPA regulations, TSCA (40 CFR Part 798.4700, September 1985, revised edition May 1987)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Inc., Portage, Michigan
- Age at study initiation: 14 weeks
- Weight at study initiation: 229-316 g
- Housing: Animals were housed individually during acclimatization and while on study, except during cohabitation, in suspended stainless steel wire mesh cages.
- Diet (ad libitum): Purina Certified Rodent Meal #5002
- Water (ad libitum): deionized tap water
- Acclimation period: 19 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): ~22
- Humidity (%): 55 ± 15
- Photoperiod (hrs dark / hrs light): 12 / 12 - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Dose solutions were prepared daily. Appropriate amounts of the test article for each dose group were weighed into volumetric flasks. Corn oil was added in sufficient quantity to achieve the final concentrations. The flasks were inverted several times to ensure adequate mixture. Dosing solutions were stored under a nitrogen blanket at room temperature.
VEHICLE
- Justification for use and choice of vehicle (if other than water):Corn oil is a recommended vehicle for this type of study and was choosen because of solubility characteristics - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- On the first day of dosing and near the end of the dosing period, a subsample from each dosing solution, including the control, was taken and analyzed for verification of the test article concentration.
- Details on mating procedure:
- Female rats determined to be suitable test subjects were cohabitated with proven resident Sprague Dawley Cr1:COBS®CD®BR®VAF/PLUS® male rats. The male rats were of suitable health and were nine to eleven months old. Evidence of mating was determined by the presence of a copulatory plug in the vagina of a sperm positive vaginal smear and was considered day 0 of gestation.
- Duration of treatment / exposure:
- from gestation day 6 through 15
- Frequency of treatment:
- single daily doses
- Duration of test:
- 10 days
- No. of animals per sex per dose:
- 28
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Range-finding study: 50, 100, 150, 250 mg/kg/day
Mortality occurred in the 100, 150 and 250 mg/kg/day groups. Outward clinical signs of toxicity and body weight losses or reduced weight gain occurred at the 50, 100, 150 and 250 mg/kg/day levels. A dose level of 100 mg/kg/day was considered to be excessive for a high dose level of the definitive teratology study due to the induced mortality. Conversely, 50 mg/kg/day did not produce sufficient maternal toxicity to be considered suitable as a high dose level. Thus, 80 mg/kg/day was selected in anticipation of producing sufficient maternal toxicity. Graduated doses of 40 and 10 mg/kg/day were selected as the mid and low dose levels, respectively. A dose level of 40 mg/kg/day was expected to induce minimal maternal toxicity while the 10 mg/kg/day dose level was selected to determine a no effect level for maternal and developmental toxicity. - Maternal examinations:
- Animals were examined daily. Clinical signs of toxicity including physical or behavioral abnormalities were recorded. Mortality checks were performedtwice daily (morning and afternoon). During the dosing period, animals were observed for toxic effects between on-half hour and two hours postdosing.
Body weights were recorded on GD 0, 6, 9, 12, 16 and 20. BWC was recorded for GD 0-6. 6-9, 9-12, 12-16, 16-20, 6-16 and 0-20. Net maternal body weight gain (adjusted for gravid uterine weight) was also reported.
Food consumption was measured on GD 0, 6, 9, 12, 16, 20. Food consumption was calculated as g/kg/day and g/animal/day for the following gestation intervals: 0-6, 6-9, 9-12, 12-16, 16-20, 6-16, 0-20. - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes - Fetal examinations:
- Fetal morphological examination: external (each fetus), visceral (one-half of the fetuses from each litter), skeletal (one-half of the fetuses from each litter) abnormalities
- Statistics:
- Analyses were performed by a digital VAX 11/730 computer. Two-tailed tests were utilized unless otherwise indicated for a minimum significance level of 5% comparing the control group to each treatment group. Group comparisons were performed using Dunnett´s test. Count data were analyzed using Chi-square Test for fetal sex ratios, Mann-Whitney U-Test for resorptions, and Fisher´s Exact Test for the number of fetal variations and malformations.
- Historical control data:
- Cesarean section data, fetal malformation data, fetal variation data were provided.
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
Clinical signs of toxicity were observed at the 40 and 80 mg/kg/day levels. Salient clinical signs included salivation. Dose dependent body weight losses or reduced weight gain, along with a corresponding reduction in food consumption occurred. - Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- > 80 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
No treatment-related changes were apparent at any level tested concerning necropsy observations, cesarean section data or fetal morphological examinations. - Dose descriptor:
- NOAEL
- Effect level:
- > 80 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: teratogenicity
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
- Conclusions:
- Oral administration of 40 and 80 mg/kg body weight per day of Oleylamine to pregnant CD rats induced dose dependent maternal toxicity indicated by adverse clinical signs, body weight loss and reduced food consumption. A dosage level of 10 mg/kg body weight per day was determined to be a no effect level for maternal toxicity. Oleylamine was neither developmental toxic nor teratogenic at dosage levels of 10, 40 or 80 mg/kg body weight per day.
- Executive summary:
For octadecenylamine ("Oleylamine") a guideline conform teratology study in Sprague Dawley rats has been performed. Prior to initiation of the main study, a range-finding study had been conducted. During the range finding-study, treatment-related deaths had occurred in the 100, 150 and 250 mg/kg bw/day groups. Outward clinical signs of toxicity and body weight loss or reduced weight gain occurred at the 50, 100, 150 and 250 mg/kg bw/day dose levels. A dose level of 100 mg/kg bw/day was considered to be excessive for a high dose level of the main study due to the induced mortality. Conversely, 50 mg/kg bw/day did not produce sufficient maternal toxicity to be considered suitable as a high dose level. Thus, 80 mg/kg bw/day was selected for the main study in anticipation of producing sufficient maternal toxicity.
In the main study groups of 28 pregnant females were treated orally (gavage) with dosages of10, 40 or 80 mg/kg bw/day or with the vehicle (Mazola corn oil) during gestation days 6 to 15. During the study animals were examined daily. Any clinical signs of toxicity including physical or behavioural abnormalities were recorded. Individual body weights and food consumption were recorded on gestation days 0, 6, 9, 12, 16, and 20. Two animals in each group were selected to be sacrificed and necropsied after treatment on gestation day 15 to determine the appearance and severity of gastrointestinal tract irritation. On gestation day 20 caesarean section was performed on all surviving animals. The numbers of viable fetuses, early and late resorptions as well as the number of corpora lutea were recorded. Fetuses were examined for external, visceral and skeletal abnormalities.
All animals survived to scheduled sacrifice. Outward clinical signs of toxicity were observed at the 40 and 80 mg/kg bw/d dose levels. The observations most likely indicated a generalised irritative effect of the test substance as characterised by rales, salivation, unkempt appearance and changes in the amount, colour and consistency of the feces. However, no other signs of treatment-related gastrointestinal irritation or other internal changes were observed at the gestation day 15 and 20 necropsies. More pronounced signs of toxicity were apparent only in the 80 mg/kg bw/d dose group and included emaciation, rough coat and dark red material around the eyes, nose and/or mouth. Similar clinical signs were infrequently noted during the post-dose observations. Dose-dependent body weight loss (during gestation days 6-9) or reduced weight gain (during gestation days 12-16), along with a corresponding reduction in food consumption occurred during the treatment period in the 40 and 80 mg/kg bw/d dose groups. Net body weight gain (adjusted for gravid uterine weight) was also lower at these levels. Following cessation of treatment (days 16-20), increase in weight gain and food consumption were noted at both dose levels. No such effects were observed in the dose group treated with 10 mg/kg bw/d. Caesarean section data obtained from the treated groups did not reveal any meaningful differences (concerning number of corpora lutea, implantation sites, viable fetuses, fetal sex and fetal weight) when compared with the controls. Fetal evaluations of type and frequency of malformations and variations did not reveal any indications for a treatment related teratogenic effect. In summary, oral administration of octadecenylamine to pregnant rats produced dose-dependent maternal toxicity in the 40 and 80 mg/kg bw/d dose groups. No indications of an embryotoxic, fetotoxic or teratogenic effect was observed at any tested level. A NOAEL/maternal toxicity of 10 mg/kg bw/d and a NOAEL/developmental toxicity of>80 mg/kg bw/d can be derived from the study.
Reference
Gross necropsy evaluation of the gastrointestinal tracts from females sacrificed on gestation day 15 revealed no irritative effects.
The oral administration of 40 and 80 mg/kg/day of Oleylamine to pregnant CD rats, induced dose dependent maternal toxicity exhibited by adverse clinical signs, body weight losses and reduced food consumption. A dosage level of 10 mg/kg/day was determined to be a no effect level for maternal toxicity. Oleylamine was neither developmentally toxic nor teratogenic at dosage levels of 10, 40 and 80 mg/kg/day.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 80 mg/kg bw/day
- Study duration:
- subacute
- Species:
- other: rat, rabbit
- Quality of whole database:
- No study with the registration substance has been performed. However, data from analogues primary alkylamines are available which fulfil read-across principles based on structural, functional, metabolic and toxicological similarities. Based hereupon the available data base is considerd to be sufficient with regard to hazard / risk characterization of the registration substance.
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
- Quality of whole database:
- The available data base is considered sufficient for hazard / risk characterization.
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
- Quality of whole database:
- The available data base is considered sufficient for hazard / risk characterization.
Additional information
The registration substance was tested in a developmental dose-range-finder study designed as screening test to also account for pre-implantation data. One group of pregnant female rats were treated from gestation day 0 until gestation day 19 (main group) whereas a satellite group revealed the test item already one week before mating, during mating as well as during the gestation period until GD 19. The evaluation of relevant reproduction parameters in the main as well as in the satellite group did not indicate any test item related effect. Pregnancy rates were not affected. Mean number of corpora lutea, implantation sites and incidence of pre- and/or post-implantation losses were similar within the groups. Data on visceral and skeletal examinations did not indicate significant abnormalities. Based on the results of this study, administration of the test item at 75 mg/kg body weight during the gestation period caused maternal toxicity. However, no adverse effect on reproduction and/or development was revealed either in the satellite group or in the main group.
Data from guideline confrom OECD TG 414 developmental toxicity studies with analogues primary alkylamines are available which fulfill read-across principles to the registration substance based on structural, functional, metabolic and toxicological similarities. Groups of 28 pregnant females were treated orally (gavage) with dosages of10, 40 or 80 mg/kg bw/day or with the vehicle corn oil during gestation days 6 to 15. All animals survived to scheduled sacrifice. Clinical signs of toxicity were observed at the 40 and 80 mg/kg bw/d dose levels. The observations most likely indicated a generalized irritative effect of the test substance as characterized by rales, salivation, unkempt appearance and changes in the amount, colour and consistency of the feces. However, no other signs of treatment-related gastrointestinal irritation or other internal changes were observed at the gestation day 15 and 20 necropsies. More pronounced signs of toxicity were apparent only in the 80 mg/kg bw/d dose group and included emaciation, rough coat and dark red material around the eyes, nose and/or mouth. Dose-dependent body weight loss (during gestation days 6-9) or reduced weight gain (during gestation days 12-16), along with a corresponding reduction in food consumption occurred during the treatment period in the 40 and 80 mg/kg bw/d dose groups. Net body weight gain (adjusted for gravid uterine weight) was also lower at these levels. Following cessation of treatment (days 16-20), increase in weight gain and food consumption were noted at both dose levels. No such effects were observed in the dose group treated with 10 mg/kg bw/d. Caesarean section data concerning number of corpora lutea, implantation sites, viable fetuses, fetal sex and fetal weight were not changed when compared with the controls. Fetal evaluations of type and frequency of malformations and variations did not reveal any indications for a treatment related teratogenic effect. In summary, oral administration of the test compound to pregnant rats produced dose-dependent maternal toxicity in the 40 and 80 mg/kg bw/d dose groups. No indications of an embryotoxic, fetotoxic or teratogenic effect were observed at any tested level. A NOAEL/maternal toxicity of 10 mg/kg bw/d and a NOAEL/developmental toxicity of >80 mg/kg bw/d can be derived from the study.
Comparable findings indicative of the absence of embryotoxic, fetotoxic or teratogenic effetcs were also observed following oral administration of C16 -18 -(even numbered, saturated and unsaturated)-alkylamines to rabbits.
Justification for selection of Effect on developmental toxicity: via oral route:
There are two developmental studies available which fulfil read-across principles. Both tests were performed according to national guidelines and standards (TSCA Guidelines) including GLP.
Justification for classification or non-classification
Only limited data concerning reproductive toxicity on the registration substance is available. Comparative reproductive toxicity screening studies with the registration substance C16 -18 -(even numbered)-alkylamine acetates and analogous primary alkylamines exhibited good agreement in the toxicological profiles between the free amines and the amine salts. Additionally, data from a developmental toxicity screening study on the registration substance are also in line with data from OECD TG 414 studies on analogous primary alkylamines. Taking these correlations into account, data relevant for hazard assessment with respect to the endpoints fertility and developmental toxicity are available for closely related primary alkylamines which fulfill read-across principles in that they exhibit structural, functional, metabolic and toxicological similarities. Based on the results of all available studies, no significant reproductive and/or developmental toxicity is attributable to the registration substance below maternal toxic doses. Thus, classification and labelling of C16 -18 -(even numbered)-alkylamine acetates is not warranted.
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