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Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
one-generation reproductive toxicity
Remarks:
based on generations indicated in Effect levels (migrated information)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
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 females per group (in total 80 animals)
Control animals:
yes, concurrent vehicle
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
CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS): Unspecific clinical symptoms in high dose animals but no mortality

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.

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
VIABILITY (OFFSPRING): The total number of pubs born at PND 0, the number of living pubs at PND 0 and the number of living pubs at PND 4 was decreased in high dose group.
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.

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. Studies regarding potential developmental toxicity have not been performed with C16-18-(even numbered, C18-unsaturated)-alkylamines acetates. However, based on close structural and functional similarities with C16-18-(even numbered)-alkylamines acetates as well as respective C12-18-(even numbered)-alkylamines, read-across to findings with these surrogate substances can be used for assessment purposes. 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 C16 -18 -(even numbered, C18 -unsaturated)-alkylamines acetates was not tested for potential reproductive toxicity. However, screening assays according to OECD TG 421 following oral administration to rats are available for the structural and functional closely related C16 -18 -(even numbered)-alkylamines acetates and C16 -18 -(even numbered, saturated and unsaturated)-alkylamines (tallow alkylamines). Based on toxicity data from a 14 -day dose-range finder with C16 -18 -(even numbered)-alkylaminesacetates, 12, 30 and 75 mg/kg body weight were selected as dose levels for the main OECD 421 study. 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 in parental animals indicative of strong local 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, saturated and 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 is 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 oral administration have not revealed indications of reproductive toxic effects. From all available data, including information on analogous primary alkylamines, it can be concluded that C16 -18 -(even numbered, C18 unsaturated)-alkylamines acetates 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 which support the local nature (point of entry) of the observed effects. 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:
No data on the registration substance itself is available for this endpoint. However, based on close structural and functional similarities with C16-18-(even numbered)-alkylamine acetates as well as with C12-18-(even numbered)-alkylamines, read-across can be performed using these surrogate materials for assessment purposes. C16-18-(even numbered)-alkylamines acetates 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

Effects on developmental toxicity

Description of key information
No studies are available for the registration substance. However, the structural and functional closely related C16-18-(even numbered)-alkylamines acetates was tested for developmental toxicityin a screening study wich was designed to also investigate for pre-implantation loss. No adverse effects have been observed. 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
Reference
Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
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:
EPA OTS 798.4900 (Prenatal Developmental Toxicity Study)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
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

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.

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 of 10, 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.

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

No studies are available for the registration substance. However, the structural and functional analogue C16 -18 -(even numbered)-alkylamines acetates 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 conform 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 of 10, 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/or at necropsis on day 20. 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.

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

Additional information