Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

NOAEC for reproductive effects is 33.6 mg/m3 (14.4 ppm), Brooker (2013)

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 March 2013 to 09 September 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted in accordance with intertnational guidelines (OECD 421) and in compliance with the UK Good Laboratory Practive Regulations. All relevant validity criteria were met.
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
Deviations:
yes
Remarks:
Dosing of females was until Day 19 of gestation only, due to inhalation dosing
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK
- Age at study initiation: Nominall 10 weeks
- Weight at study initiation: Males: 374 to 453 g; Females: 235 to 287 g
- Fasting period before study: No
- Housing:5/cage prior to pairing, then 1M:1F. After mating, males re-housed as previously and females housed singly
- Diet (e.g. ad libitum): Ad lib
- Water (e.g. ad libitum): Ad lib
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 40-70
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From: March 2013 To: May 2013
Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
air
Details on exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Directed Flow Whole Body Exposure Chamber:
0.75 m3 chamber of stainless-steel and glass construction.
Animal Restraint:
Wire mesh modular caging.
Vapour Generator:
Medium sintered glass vaporiser for Groups 2 to 4. Feed rate used to alter concentration.
Test groups 18 L/min.
Diluent Airflow:
From in-house compressed air system – breathing quality. Group 1: 150 L/min.
Groups 2-4: 130 L/min.
Extract Airflow:
Drawn by a fan extract system.
Drawn from base of exposure system.
Controlled by a gate clamp situated at the rear of the chamber.
Airflow Monitoring:
In-line flowmeters monitored continuously for generation and diluent airflows.
Chamber pressure differential monitored by Magnelhelic set at -1 to -5m/H2O to ensure a slight negative pressure within the chamber
~ 150 L/min.

TEST ATMOSPHERE
- Brief description of analytical method used: samples in trapping solvent, followed by HPLC analysis. minimum of 3 samples/group/exposure, plus one from control chamber
- Samples taken from breathing zone: yes

Details on mating procedure:
- M/F ratio per cage: 1M : 1F
- Length of cohabitation: Up to 2 weeks
- Proof of pregnancy: Ejected copulation plugs, sperm in vaginal smear: referred to as Day 0 of pregnancy

- After successful mating each pregnant female was caged (how): singly
- Any other deviations from standard protocol: No
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Vapour samples collected as follows:
Sample frequency – minimum of 1 sample/ exposure for Group 1 and minimum of 3 samples/exposure for Groups 2 to 4.
Sample location – representative animal level.
Sample position remained constant.
Sample analysis:
HPLC.
Vapour samples were analysed as μg/L and subsequently converted to ppm.
Duration of treatment / exposure:
6 hours per day
Frequency of treatment:
Daily for 2 weeks prior to mating, then for a total of 4 weeks for males, and for females until Day 19 of gestation.
Details on study schedule:
Males were treated for 2 weeks prior to pairing, and then for a total of 4 weeks.
Females were treated for 2 weeks prior to pairing, then throughout mating and until Day 19 of gestation. Females were then retained and allowed to litter and raise their pups until at least Day 4 post partum.
Dose / conc.:
3.57 ppm (analytical)
Dose / conc.:
7.53 ppm (analytical)
Dose / conc.:
14.4 ppm (analytical)
No. of animals per sex per dose:
10M / 10F per dose group
Control animals:
yes, concurrent vehicle
Positive control:
None
Parental animals: Observations and examinations:
CLINICAL OBSERVATIONS: Yes
- Time schedule: Before dosing, during dosing if visible, on return to home cage, at end of working day
- Cage side observations were included.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly for males and for females prior to pairing. Females on Days 0, 3, 7, 10, 14, 17 and 20 of gestation, and Days 1 and 4 of lactation.

FOOD CONSUMPTION : Yes. Weekly prior to pairing, then at approximately 3 day intervals for females during gestation and lactation.


WATER CONSUMPTION : No

OTHER:
Oestrous cyclicity (parental animals):
Vaginal lavages were taken daily from pairing until mating.
Sperm parameters (parental animals):
Parameters examined in all males: testis weight, epididymis weight, histopathology of male reproductive organs, including PAS stain of the testes. Sperm counts were estimated from vaginal smears at mating.
Litter observations:
Time elapsed between mating and commencement of parturition recorded, including any difficulty with parturition.
Number of live and dead offspring recorded at birth
Litter size recordecdaily from Day 1-4
Sex ratio and individual offspring body weights recorded on Day 1 and 4 of age
Postmortem examinations (parental animals):
SACRIFICE
Scheduled kill - males: During week 5 of treatment.
Females failing to produce viable litter: Day 25 after mating.
Scheduled kill - females: Day 4 of lactation

GROSS NECROPSY
All adult animals were subject to a complete macroscopic examination. For all females, the following was recorded:
Uterus: Number of implantation sites.

HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table 1 were prepared for microscopic examination and weighed, respectively.
Postmortem examinations (offspring):
SACRIFICE
Scheduled kill - Day 4 of age

GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.

Premature deaths: Missing offspring and any grossly autolysed or grossly cannibalised could not be examined. All other remaining offspring dying were examined as detailed above; the examination also included an assessment for the presence of milk in the stomach, where this was possible.
Scheduled kill (Day 4 of age): Only offspring that were externally abnormal were examined. Offspring considered to be externally normal were discarded without examination.

HISTOPATHOLOGY / ORGAN WEIGHTS
For all offspring, samples of any abnormal tissues were retained, but since no treatment- related findings were detected, these tissues were not processed for examination.
Statistics:
All statistical analyses were carried out separately for males and females. Data relating to food consumption before pairing were analysed on a cage basis. For all other parameters, the analyses were carried out using the individual animal as the basic experimental unit.
The following data types were analysed at each timepoint separately:
Bodyweight, using absolute weights and gains over appropriate study periods Food consumption, over appropriate study periods
Gestation length
Litter size and survival indices
Organ weights, either absolute or adjusted for teminal bodyweight where appropriate.
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
At 7.53 and 14.4 ppm, animals were underactive, unresponsive, with hunched posture and piloerection. At 3.57 ppm the signs were generally limited to underactivity and piloerection
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Dose related decrease in weight gain in pre-mating period (92, 70 and 59% of Control, males; 73, 71 and 55% of Control , females) at 3.42, 7.53 and 14.4 ppm. Similar effect over Day 0-3 of gestation ,but gains similar for remainder of gestation.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Dose related decrease in weight gain in pre-mating period (92, 70 and 59% of Control, males; 73, 71 and 55% of Control , females) at 3.42, 7.53 and 14.4 ppm. Similar effect over Day 0-3 of gestation ,but gains similar for remainder of gestation.
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Immunological findings:
no effects observed
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No treatment related changes were observed in the limited tissues examined.
Histopathological findings: neoplastic:
not examined
Other effects:
not examined
Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Description (incidence and severity):
Sperm parameters at mating were similar in all groups.
Reproductive performance:
no effects observed
Description (incidence and severity):
There was no effect on pre-coital interval. All animals showed evidence of mating, and all allylamine-treated females were pregnant. There was no treatment-related effect on gestation length or gestation index.
Key result
Dose descriptor:
LOAEC
Effect level:
3.57 ppm (analytical)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Reduced body weight gain
Key result
Dose descriptor:
NOAEC
Effect level:
3.57 ppm (analytical)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Slight body weight effects not considered as adverse
Key result
Critical effects observed:
no
Key result
Dose descriptor:
NOAEC
Effect level:
14.4 ppm (analytical)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reproductive performance
Remarks on result:
not determinable due to adverse toxic effects at highest dose / concentration tested
Key result
Critical effects observed:
no
Clinical signs:
no effects observed
Description (incidence and severity):
There were no treatment-related clinical observations noted for the offspring in life.
Dermal irritation (if dermal study):
not examined
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
There were no treatment-related effects on the bodyweight of male or female offspring to Day 4 post partum.
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings:
not examined
Other effects:
no effects observed
Behaviour (functional findings):
not examined
Developmental immunotoxicity:
not examined
Key result
Dose descriptor:
NOAEC
Generation:
F1
Effect level:
14.4 ppm (analytical)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Litter size, offspring survival and body weights
Key result
Critical effects observed:
no
Key result
Reproductive effects observed:
no
Conclusions:
Exposure of rats to Allylamine in this screening study to assess the general systemic toxic potential, including reproductive/developmental effects, following administration by whole body inhalation at concentrations of 3.57, 7.53 or 14.4 ppm was associated with systemic effects (clinical signs during exposure, and lower bodyweight gain and food consumption), but had no effect on reproductive or developmental endpoints.
Within this screening study, a no observed adverse effect level (NOAEL) for systemic toxicity was not established; whilst the no observed adverse effect level (NOAEL) for reproductive and developmental toxicity was considered to be 14.4 ppm.
Executive summary:

The objective of this study was the assessment of Allylamine (a raw material in polymer manufacture) on the general systemic toxic potential in rats, including reproductive/developmental effects, with administration of the test substance by inhalation administration for at least 4 weeks.

Three groups of 10 male and 10 female rats received Allylamine by whole body inhalation at target exposure levels of 4, 7.5 or 15 ppm, 7 days per week, 6 hours per day. The adults were treated daily for fifteen days before pairing until Week 5 for males and, for females, until Day 19 of gestation. Females were untreated from Day 20 post coitum to necropsy on Day 4 after birth of F1 generation. A similarly constituted Control group received air only for the same duration.

The F1 generation received no direct administration of the test substance; any exposure was in utero or via the milk.

During the study, data was recorded on clinical condition, bodyweight, food consumption, mating performance and fertility, gestation length, parturition observations and reproductive performance. Organ weight, macroscopic and limited microscopic pathology investigations were undertaken on the F0 generation adults. The clinical condition of offspring, litter size and survival, sex ratio and bodyweight was assessed on the F1 generation offspring to Day 4 post partum.

The achieved chamber concentrations of Allylamine were 3.57, 7.53 and 14.4 ppm (89, 100 and 96% of the target concentration) for Groups 2, 3 and 4 respectively.

Signs during exposure included underactivity, unresponsiveness, hunched posture and piloerection at 7.53 and 14.4 ppm, with partially closed eyelids also noted at 14.4 ppm and, to a lesser extent, 7.53 ppm. At 3.57 ppm, signs during exposure were limited to underactivity and piloerection, with hunched posture and partially closed eyelids being noted infrequently.

Bodyweight gain of treated males and females were reduced in the first 2 weeks of treatment, in a dose related manner. Thereafter bodyweight gain was similar to the controls. Food consumption at 7.53 ppm for males and 14.4 ppm for males and females was slightly lower in the first 2 weeks of treatment and the first 2 days of gestation for females at 14.4 ppm.

There was no effect of Allylamine on mating performance, maintenance of pregnancy or gestation length, or growth and survival of the offspring to Day 4 of lactation.

There were no pathological changes in the reproductive organs investigated.

Exposure of rats to Allylamine in this screening study to assess the general systemic toxic potential, including reproductive/developmental effects, following administration by whole body inhalation at concentrations of 3.57, 7.53 or 14.4 ppm was associated with systemic effects (clinical signs during exposure, and lower bodyweight gain and food consumption), but had no effect on reproductive or developmental endpoints.

Within this screening study, a no observed adverse effect level (NOAEL) for systemic toxicity was not established; whilst the no observed adverse effect level (NOAEL) for reproductive and developmental toxicity was considered to be 14.4 ppm.

Effect on fertility: via oral route
Endpoint conclusion:
no study available
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
33.6 mg/m³
Study duration:
subacute
Species:
rat
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

An inhalation study to OECD Guideline 421 has shown no effects on reproductive function or offspring development and survival, in the presence of maternal toxicity.


Short description of key information:
NOAEC for reproductive effects is 33.6 mg/m3 (14.4 ppm). (Brooker, 2013)

Justification for selection of Effect on fertility via inhalation route:
Key screening study to OECD 421.

Effects on developmental toxicity

Description of key information

NOAEC for developmental effects is 33.6 mg/m3 (14.4 ppm), Brooker (2013)

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 March 2013 to 09 September 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted in accordance with intertnational guidelines (OECD 421) and in compliance with the UK Good Laboratory Practive Regulations. All relevant validity criteria were met.
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
other: OECD Guideline 421
Deviations:
yes
Remarks:
Dosing of females was until Day 19 of gestation only, due to inhalation dosing
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK
- Age at study initiation: Nominall 10 weeks
- Weight at study initiation: Males: 374 to 453 g; Females: 235 to 287 g
- Fasting period before study: No
- Housing:5/cage prior to pairing, then 1M:1F. After mating, males re-housed as previously and females housed singly
- Diet (e.g. ad libitum): Ad lib
- Water (e.g. ad libitum): Ad lib
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 40-70
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From: March 2013 To: May 2013
Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
air
Details on exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
Directed Flow Whole Body Exposure Chamber:
0.75 m3 chamber of stainless-steel and glass construction.
Animal Restraint:
Wire mesh modular caging.
Vapour Generator:
Medium sintered glass vaporiser for Groups 2 to 4. Feed rate used to alter concentration.
Test groups 18 L/min.
Diluent Airflow:
From in-house compressed air system – breathing quality. Group 1: 150 L/min.
Groups 2-4: 130 L/min.
Extract Airflow:
Drawn by a fan extract system.
Drawn from base of exposure system.
Controlled by a gate clamp situated at the rear of the chamber.
Airflow Monitoring:
In-line flowmeters monitored continuously for generation and diluent airflows.
Chamber pressure differential monitored by Magnelhelic set at -1 to -5m/H2O to ensure a slight negative pressure within the chamber
~ 150 L/min.

TEST ATMOSPHERE
- Brief description of analytical method used: samples in trapping solvent, followed by HPLC analysis. minimum of 3 samples/group/exposure, plus one from control chamber
- Samples taken from breathing zone: yes


Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Vapour samples collected as follows:
Sample frequency – minimum of 1 sample/ exposure for Group 1 and minimum of 3 samples/exposure for Groups 2 to 4.
Sample location – representative animal level.
Sample position remained constant.
Sample analysis:
HPLC.
Vapour samples were analysed as μg/L and subsequently converted to ppm.
Details on mating procedure:
- M/F ratio per cage: 1M : 1F
- Length of cohabitation: Up to 2 weeks
- Proof of pregnancy: Ejected copulation plugs, sperm in vaginal smear: referred to as Day 0 of pregnancy

- After successful mating each pregnant female was caged (how): singly
- Any other deviations from standard protocol: No
Duration of treatment / exposure:
6 hours per day
Frequency of treatment:
Daily for 2 weeks prior to mating, then for a total of 4 weeks for males, and for females until Day 19 of gestation.
Duration of test:
Males were treated for 2 weeks prior to pairing, and then for a total of 4 weeks.
Females were treated for 2 weeks prior to pairing, then throughout mating and until Day 19 of gestation. Females were then retained and allowed to litter and raise their pups until at least Day 4 post partum.
Dose / conc.:
3.57 ppm (analytical)
Dose / conc.:
7.53 ppm (analytical)
Dose / conc.:
14.4 ppm (analytical)
No. of animals per sex per dose:
10M/ 10F
Control animals:
yes, concurrent vehicle
Maternal examinations:
Females were allowed to litter and rear their litters to Day 4 post partum
Ovaries and uterine content:
Uteri examined for number of implantation sites
Fetal examinations:
Females allowed to litter, but pups examined daily from birth until Day 4 post partum, including survival and weights on Days 1 and 4.
Indices:
Post-implantation survival index, live birth index, viability index
Clinical signs:
no effects observed
Description (incidence and severity):
There were no treatment-related clinical signs observed during the weekly detailed physical examination.
Dermal irritation (if dermal study):
not examined
Mortality:
mortality observed, non-treatment-related
Description (incidence):
One female in the control group (number 49) was sacrificed due to signs of dystocia on Day 21 after mating, red staining (presumed blood) was noted in the cage and clinical signs included underactivity, reduced body temperature, hunched posture, piloerection and general pallor. At necropsy, one partially cannibalised pup was found in the cage (presumably born between transportation between the animal unit and the necropsy suite) and the uterus contained 2 live pups in the right horn and one live pup and one late resorption in the left horn. The spleen was enlarged. The microscopic correlate for the enlarged spleen was moderate extramedullary haematopoiesis suggestive of suppurative lesions elsewhere in the body. In the absence of microscopic examination of other organs from this animal, the histopathological factor contributory to death is undetermined.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Mean bodyweight gain of treated females was also lower than the controls, in a dose dependent manner, during the 2 weeks prior to pairing (73, 71 and 55% of Control for females at 3.57, 7.53 and 14.4 ppm, respectively). The lower bodyweight gain was most apparent between Days 8 and 11, which coincided with the period of higher achieved exposure levels.There were considered to be no effects of treatment on bodyweight gain during gestation (Days 0-20) or from Day 1 to 4 post partum.
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
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
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
Mean seminal vesicles weights (adjusted for bodyweight as covariate) were slightly high for males at 14.4 ppm compared with control (114% of Control, respectively). Review of weights for individual animals did not reveal any obvious outlier and as there were no histopathological findings in animals in this group, this finding is considered to be unrelated to treatment.
There were considered to be no treatment related effects on the other organ weights assessed.
Gross pathological findings:
no effects observed
Description (incidence and severity):
The macroscopic examinations performed after the scheduled treatment of F0 animals revealed no intergroup differences of note.
The nature and incidence of all the findings were consistent with the commonly seen background of macroscopic changes in Sprague-Dawley rats at these laboratories.
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Other effects:
no effects observed
Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Total litter losses by resorption:
no effects observed
Early or late resorptions:
no effects observed
Dead fetuses:
no effects observed
Changes in pregnancy duration:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): no effects observed
Changes in number of pregnant:
no effects observed
Other effects:
no effects observed
Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Maternal weight gain was reduced, in dose-dependent manner in 2 weeks prior to pairing and also over Day 0-3 of gestation. Thereafter weight gains similar in all groups. At 7.53 and 14.4 ppm, animals were underactive, unresponsive, with hunched posture and piloerection; at 3.57 ppm, animals were underactive with piloerection.
Key result
Dose descriptor:
LOAEC
Effect level:
3.57 ppm (analytical)
Based on:
test mat.
Basis for effect level:
body weight and weight gain
Key result
Abnormalities:
no effects observed
Fetal body weight changes:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Reduction in number of live offspring:
no effects observed
Changes in sex ratio:
no effects observed
Changes in litter size and weights:
no effects observed
Changes in postnatal survival:
no effects observed
External malformations:
no effects observed
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Other effects:
no effects observed
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No effects on litter size and survival, pup development and weight
Key result
Dose descriptor:
NOAEL
Effect level:
14.4 ppm (analytical)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effects observed
Key result
Abnormalities:
no effects observed
Key result
Developmental effects observed:
no
Conclusions:
Based on the data available at the time of submission, the following NOAEC/LOAEC's are indicated:
LOAEC for parental effects: 3.57 ppm
NOAEC for mating, fertility and offspring effects: 14.4 ppm
Executive summary:

The objective of this study was the assessment of Allylamine (a raw material in polymer manufacture) on the general systemic toxic potential in rats, including reproductive/developmental effects, with administration of the test substance by inhalation administration for at least 4 weeks.

Three groups of 10 male and 10 female rats received Allylamine by whole body inhalation at target exposure levels of 4, 7.5 or 15 ppm, 7 days per week, 6 hours per day. The adults were treated daily for fifteen days before pairing until Week 5 for males and, for females, until Day 19 of gestation. Females were untreated from Day 20 post coitum to necropsy on Day 4 after birth of F1 generation. A similarly constituted Control group received air only for the same duration.

The F1 generation received no direct administration of the test substance; any exposure was in utero or via the milk.

During the study, data was recorded on clinical condition, bodyweight, food consumption, mating performance and fertility, gestation length, parturition observations and reproductive performance. Organ weight, macroscopic and limited microscopic pathology investigations were undertaken on the F0 generation adults. The clinical condition of offspring, litter size and survival, sex ratio and bodyweight was assessed on the F1 generation offspring to Day 4 post partum.

The achieved chamber concentrations of Allylamine were 3.57, 7.53 and 14.4 ppm (89, 100 and 96% of the target concentration) for Groups 2, 3 and 4 respectively.

Signs during exposure included underactivity, unresponsiveness, hunched posture and piloerection at 7.53 and 14.4 ppm, with partially closed eyelids also noted at 14.4 ppm and, to a lesser extent, 7.53 ppm. At 3.57 ppm, signs during exposure were limited to underactivity and piloerection, with hunched posture and partially closed eyelids being noted infrequently.

Bodyweight gain of treated males and females were reduced in the first 2 weeks of treatment, in a dose related manner. Thereafter bodyweight gain was similar to the controls. Food consumption at 7.53 ppm for males and 14.4 ppm for males and females was slightly lower in the first 2 weeks of treatment and the first 2 days of gestation for females at 14.4 ppm.

There was no effect of Allylamine on mating performance, maintenance of pregnancy or gestation length, or growth and survival of the offspring to Day 4 of lactation.

There were no pathological changes in the reproductive organs investigated.

Exposure of rats to Allylamine in this screening study to assess the general systemic toxic potential, including reproductive/developmental effects, following administration by whole body inhalation at concentrations of 3.57, 7.53 or 14.4 ppm was associated with systemic effects (clinical signs during exposure, and lower bodyweight gain and food consumption), but had no effect on reproductive or developmental endpoints.

Within this screening study, a no observed adverse effect level (NOAEL) for systemic toxicity was not established; whilst the no observed adverse effect level (NOAEL) for reproductive and developmental toxicity was considered to be 14.4 ppm.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
33.6 mg/m³
Study duration:
subacute
Species:
rat
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

An inhalation study to OECD Guideline 421 has shown no effects on reproductive function or offspring development and survival, in the presence of maternal toxicity.


Justification for selection of Effect on developmental toxicity: via inhalation route:
Key screening study to OECD 421.

Mode of Action Analysis / Human Relevance Framework

Not applicable, no relevant effects observed for reproductive/developmental toxicity.

Justification for classification or non-classification

In accordance with Regulation (EC) No 1272/2008 (CLP) the test material is not classified for developmental and reproductive effects.