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EC number: - | CAS number: -
- 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:
- two-generation reproductive toxicity
- Remarks:
- based on generations indicated in Effect levels (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Publications based on an NTP study. The information available is limited
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- NTP tested propylene glycol for reproductive/developmental toxicity. Using the reproductive assessment by continuous breeding (RACB) protocol, the reproductive function of male and female mice (COBS crl:CD-1 (ICR) BR outbred albino) exposed to propylene glycol in drinking water was investigated.
- GLP compliance:
- not specified
- Limit test:
- no
- Species:
- mouse
- Strain:
- Swiss
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Strain: COBS Crl:CD-l (ICR)BR
- Age/weight at study initiation: no data
- Housing: during breeding period 1 male + 1 female; other periods individually
- Diet: Purina rat chow or NIH-07 diet ad libitum
- Water: ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2*C.
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 10/14 - Route of administration:
- oral: drinking water
- Details on mating procedure:
- - M/F ratio per cage: 1/1
- Length of cohabitation: 98 days
- After last mating each pregnant female was caged (how): individually and allowed to raise the pups until day 21
- Any other deviations from standard protocol: litters were removed within 12 hours after delivery - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analyses were performed by an independent laboratory at least for accuracy of preparation and stability.
All results were within 5% of nominal - Duration of treatment / exposure:
- Continuous breeding phase begins with males and females separated for 1 week. The mating trial begins within a week of the start of treatment and cohabitation continues for 14 weeks to maximize the data collected on fertility. Maternal parent during gestation (3 weeks)
Last litter and mother for 21 days and mother was dosed through weaning and F1 mice were dosed until mated at 74 ± 10 days.
F1 during mating, F1Females during gestation and lactation of F2 (until day 21). - Frequency of treatment:
- continuously in drinking water
- Details on study schedule:
- Animals were exposed to propylene glycol for a total of 18 weeks: one week prior to cohabitation, 14 weeks during cohabitation, and 3 weeks after cohabitation. A vehicle control group (40 males/40 females) and 3 dose groups of 20 males and 20 females per dose group were used. Drinking water concentrations were set at 0, 1, 2.5, 5% (w/v) propylene glycol. Chemical consumption estimates in this study were 0, 1.82, 4.80, and 10.1 g/kg bw/day for each of the respective dose groups; body weights of F0 parents were monitored on study days 0, 7, 28, 56, 84, and 112. Live litters born during the cohabitation phase were weighed, sexed, and examined for external abnormalities and then sacrificed. Approximate delivery time and number of dead and cannibalized pups were noted. Offspring from the last litter (5th litter) of the control and high-dose groups were allowed to mature and reproductive performance was evaluated.
F1 males and females (20 each/dose group) were randomly selected from the control and high-dose groups and mated on post natal day 64–84 to animals from the same dose group. Breeding pairs were separated after 7 days of cohabitation or after detection of a copulatory plug; the male and female were then housed singly. F1 animals were weighed at weaning, first day of cohabitation, and then weekly. Water consumption was monitored weekly starting the first week after cohabitation. The high-dose group animals received exposure to propylene glycol until day 21 from their dosed dam and then continuous exposure from drinking water (author estimated daily dose of propylene glycol, 14.4 g/kg bw/day). - Remarks:
- Doses / Concentrations:
0, 1, 2.5, 5% (w/v)
Basis:
nominal in water - Remarks:
- Doses / Concentrations:
0, 1.82, 4.80, and 10.1 g/kg bw/day
Basis:
actual ingested
Parental - Remarks:
- Doses / Concentrations:
0 and 14.4 g/kg bw
Basis:
actual ingested
F1 and F2 - No. of animals per sex per dose:
- 20 males + 20 females for treatment groups
40 males + 40 females for controls - Control animals:
- yes
- Details on study design:
- A dose range-finding study was done with mice exposed to propylene glycol in drinking water for 14 days. Dose groups (8 male and 8 female mice/group; 2 mice of the same sex housed per cage) were 0, 0.5, 1.0, 2.5, 5.0, and 10.0% (w/v) propylene glycol. During the testing period, there was no mortality in any of the dose groups. However, in the high-dose group, males and females gained weight over control animals (2 and 7% heavier, respectively) and animals in the 10% dose group drank more water than the control group (60% more for males and 58% more for females). [Food consumption not reported; caloric intake among dose groups not standardized.]
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
BODY WEIGHT: P No data; F1 weekly
FOOD CONSUMPTION: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): P no details, F1 weekly - Oestrous cyclicity (parental animals):
- P no data; F1 estrous cycle
- Sperm parameters (parental animals):
- P no data; F1 motile sperm, epididymal sperm concentration and percentage abnormal sperm, vaginal cytology
- Litter observations:
- F1: number of litters, delivery time and number of dead and cannibalized pups, body weight, proportion of males, number of litters per pair, number of live and dead pups
F2:litter size, sex, and pup weight - Postmortem examinations (parental animals):
- P no data
F1: selected organ weights and histology (no details) - Postmortem examinations (offspring):
- not performed
- Statistics:
- Statistical significance was at the P = 0.05 level. Reproductive data were evaluated by the Cochran-Armitage Standard statistical analyses were done on the reproductive and fertility data. test for dose related trends in fertility and mating indices; pairwise comparisons between the control and dose groups were made using Fisher’s Exact test. Pup and litter data were evaluated by the Kruskal-Wallis test and Jonckheere’s test. Pairwise comparisons were made with Wilcoxon’s rank-sum test. All analyses were performed on males, females, and both sexes combined; to remove any potential effect of number of pups in litter on pup weight, an analysis of covariance was performed.
- Reproductive indices:
- For F1: mating index, fertility index
- Clinical signs:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- 10 100 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- Clinical signs:
- no effects observed
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 14 400 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Remarks:
- actually ingested
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
- Dose descriptor:
- NOAEL
- Generation:
- F2
- Effect level:
- 14 400 mg/kg bw/day (actual dose received)
- Based on:
- act. ingr.
- Remarks:
- actually ingested
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
- Reproductive effects observed:
- not specified
- Conclusions:
- No effect on reproduction at any of the doses tested.
- Executive summary:
In a continuous dosing study exposure of mice to 0, 1, 2.5 and 5 % in drinking water did not induce any effects on reproduction in parental animals. In the F1 generation exposed at 0 and 5% also no effects were found on any of the parameters evaluated. Therefore it is concluded that the NOAEL for reproductive toxicity is 5% in drinking water (10100 mg/kg bw).
- 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:
- 1987
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study under GLP with limited number of investigations. The information in the report is limited to what is included in the summary
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Mice were exposed to the substance for 13 weeks and thereafter selected for mating and reproduction testing. Exposure was continued during the mating period and pregnant females were allowed to deliver and nurse their pups until day 21 of lactation. The protocol resembles that of OECD 422.
- GLP compliance:
- yes
- Remarks:
- no QA statement and/or study director statement included in the report, but GLP is claimed
- Limit test:
- no
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Taconic Laboratory Animals and Services (Germantown, NY)
- Age at study initiation: 6-7 weeks
- Average weight at study initiation: males 20.6-24.8 g; females 17.9-19.8 g (no additional information on animals used for mating)
- Housing: individually
- Diet: Pelleted NIH-07 feed (Zeigler Brothers, Inc., Gardners, PA) ad libitum during non-exposure
- Water: ad libitum during non-exposure
- Acclimation period: 11-14 days
ENVIRONMENTAL CONDITIONS (non-exposure)
- Temperature (°C): ca 22 °C
- Humidity (%): 50% ± 15%
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- inhalation: aerosol
- Type of inhalation exposure (if applicable):
- whole body
- Details on exposure:
- For the inhalation studies, 1,6-hexanediamine was converted to 1,6-hexanediamine dihydrochloride (HDDC) by acidification with concentrated hydrochloric acid under a stream of nitrogen. The final pH was adjusted within the range of 4.5 to 5.5 before storage and again before use in the inhalation chambers.
The 70% aqueous HDDC solution was placed in a 9-liter glass reservoir and pressurized with N2 gas. HDDC was delivered to 5 Sonimist Ultrasonic Spray Nozzles (Model HS6002, Heat Systems-Ultrasonics, Inc., Farmingdale, NY) by a positive displacement metering pump. Up to this point, stainless steel lines carried the test substance. The nebulizer reservoir was kept in a separate exposure chamber (H-1000, Hazelton Systems, Inc., Aberdeen, MD). This chamber served as a mixing plenum where large droplets and nonnebulized liquid were impacted or sedimented out of the test atmosphere before the aerosol was delivered to the inhalation chambers. The HDDC aerosol was mixed with compressed breathing air that had been filtered through an ENMET (ENMET Air Filtration Panel, Model AFP-82, Enmet Co., Ann Arbor, MI) and supplied at 50 psi to generate an aerosol at a concentration equal to the highest exposure concentration. The resulting aerosol was transported to the inhalation chambers through a manifold constructed of 3-inch diameter PVC tubing. At each chamber, a metered amount of aerosol was removed from the manifold and mixed with the appropriate amount of HEPA/charcoal-filtered room air to obtain the desired test concentration, then delivered to the inhalation chamber. After exiting the chambers, the test atmospheres were delivered to a common duct and cleansed of the test substance by a Mystaire HS-7CM scrubber (Heat Systems Ultrasonics).
Method of holding animals in test chamber: individually in compartments of multi compartment wire mesh cages, during exposure in stainless steel andglass exposure chambers of 2 m3 volume, with 15 air changes per hour (500 L/min). During inhalation exposures, chambers were maintained at 22°C to 25°C and 70% to 80% relative humidity.
TEST ATMOSPHERE
- Brief description of analytical method used: forward light scatter with RAM-S real-time aerosol monitors (GCA Corporation,Technology Division, Bedford, MA) and gravimetric analyses of filter samples collected from each exposure chamber
- Samples taken from breathing zone: no, 6 RAM-S readings and 3 gravimetric samples were taken from each exposure chamber on each day of exposure. - Details on mating procedure:
- - M/F ratio per cage: 1 male and 2 females
- Length of cohabitation: maximum 10 days
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of gestation
- No replacement of first male by another male with proven fertility.
- After successful mating each pregnant female was caged (how): individually
- Any other deviations from standard protocol: exposure for 13 weeks including the mating period, but no exposure of females during gestation and lactation - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Twice monthly during the 13-week studies, glass fiber filter samples from each chamber were analyzed by gas chromatography with flame ionization detection for total hexanediamine, using the technique supplied by Midwest Research Institute. Measured concentrations of HDDC in the exposure chambers were within 6% of the target concentrations in all samples.
Spatial homogeneity of the aerosol within the exposure chambers was determined using the calibrated RAM-S monitors. Chamber concentrations were measured at 12 points within each chamber and then were compared to a fixed reference point. Time spans required to reach stable concentrations after start up and to reach background concentrations at the end of exposure were determined by taking measurements of aerosol concentrations every 60 seconds. The time span required after start up to reach 90% of the target concentration was identified as the T90; the time span required after the end of the exposure period to reach 10% of the target concentration was identified as the T10.
Triplicate particle size measurements were obtained for each exposure chamber once in the first week and monthly thereafter, using an APS 3300 aerodynamic particle sizer (TSI, Inc., Minneapolis, MN). In addition, a CFM Ambient Impactor (Flow Sensor, McLean, VA) cascade impactor was used to determine the particle size distribution in the highest exposure level chamber once during the 13-week studies. The mass median aerodynamic diameter values for each chamber ranged from 1.62 to 1.72 microns, with a geometric standard deviation of 1.52 to 1.53. All control chamber respirable mass concentration values were less than 0.005 mg/m3. - Duration of treatment / exposure:
- 13 weeks (including mating period)
- Frequency of treatment:
- 6 hours(+ T90 (=30 min))/day, 5 days per week
- Details on study schedule:
- Mating was between exposure day 68 and 80 of the study (only weekdays counted)
Males were terminated immediately thereafter. Females were checked upto 23 days after mating for signs of copulation and terminated thereafter if non-pregnant. - Remarks:
- Doses / Concentrations:
0, 15, 50 and 160 mg/m3
Basis:
analytical conc. - No. of animals per sex per dose:
- 20 males and 40 females
- Control animals:
- yes
- Details on study design:
- no data
- Positive control:
- none included
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes no details
DETAILED CLINICAL OBSERVATIONS: No data
BODY WEIGHT (GAIN): Yes
- Time schedule for examinations: both sexes at start; males at the end of the mating period; females at day 0 and 20 of gestation], day 0, 5, 14 and 21 of lactation
FOOD CONSUMPTION: No data - Oestrous cyclicity (parental animals):
- see under repeated dose
- Sperm parameters (parental animals):
- see under repeated dose
- Litter observations:
- PARAMETERS EXAMINED
The following parameters were examined in offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain (BW day 0, 5, 14 and 21 of lactation), physical abnormalities - Postmortem examinations (parental animals):
- males: none
females: necropsy only on non-pregnant females: uterus examination for signs of pregnancy (includes ammonium sulfide staining to verify implementation) - Postmortem examinations (offspring):
- none
- Statistics:
- Continuous, quantitative data, such as body weights, were analyzed by Dunnett's t-test for multiple comparisons to a single control group. Discrete, counting data, such as litter counts, were analyzed by the Mann-Whitney U nonparametric test. Percentage data, such as the fertility and survival indices, were analyzed by the Chi Square test.
- Reproductive indices:
- no data
- Offspring viability indices:
- no data
- Clinical signs:
- not examined
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEC
- Effect level:
- 5 mg/L air (analytical)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: see repeated dose toxicity study
- Clinical signs:
- not examined
- Clinical signs:
- not examined
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Dose descriptor:
- NOAEC
- Generation:
- F1
- Effect level:
- 160 mg/L air (analytical)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: see study
- Reproductive effects observed:
- not specified
- Conclusions:
- There was no effect on male or female fertility, body weight (gain), gestation length and litter size. The reduced pupweights during part of the lactation period are considered not biologically relevant. No effects were noted on neonatal survival, sex ratios of pups and pup morphology in mice exposed to the substance.
- Executive summary:
Male (n=20) and female (n=40) mice were exposed to the substance at 0, 16, 50 and 160 mg/m3 for 13 weeks (6 h/day, 5 d/wk). Animals were mated (1 male/2 females) and females showing signs of copulation and pregnancy were further evaluated during gestation and lactation (until day 21 of lactation). Males and non-pregnant females were terminated either immediately after mating (males) or after 23 days (non-pregnant females). The pups were checked for neonatal survival, weights, sex ratios and morphology. No treatment related mortality, effects on body weight(gain) or effects on reproductive performnce were observed in parental animals. No adverse effects were found in the offspring.
Referenceopen allclose all
BODY WEIGHT (PARENTAL ANIMALS): no treatment related effects
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS):
pregnancy rate: 35, 32, 33 and 35 at 0, 16, 50 and 160 mg/m3
gestation length: significantly increased at 50 and 160 mg/m3 (no biological relevance)
LITTER SIZE: no treatment related effects
SEX RATIO: no treatment related effects
CLINICAL SIGNS (OFFSPRING); no treatment related effects
BODY WEIGHT (OFFSPRING): no treatment related effects (significantly decreased in pups at 160 mg/m3 on day (14 and) 21 of lacatation)
Mean Body Weights and Length of Gestation for Female B6C3F1 Mice in the Mating Trial Study og 1,6 -hexanediamine Dihydrochloride
|
0 mg/m3 |
16 mg/m3 |
50 mg/m3 |
160 mg/m3 |
Dam Weight During Gestation1 |
22 25.6 ± 0.3 44.3 ± 0.8 18.7 ± 0.8 - |
23 25.6 ± 0.4 44.4 ± 0.8 18.8 ± 0.8 100 |
27 27.2 ± 0.5* 43.4 ± 0.8 16.2 ± 0.9 98 |
24 26.2 ± 0.3 44.2 ± 0.5 18.0 ± 0.5 100 |
Lenght of Gestation1 |
30 17.68 ± 0.10 |
30 18.00 ± 0.12 |
31 18.11 ± 0.09** |
31 18.11 ± 0.08** |
Dam Weight During Lactation1
Lactation day 0
Lactation day 5
Lactation day 14
Lactation day 21
|
35 31.4 ± 0.3
34 35.3 ± 0.4
34 39.7 ± 0.5
34 34.8 ± 0.5 |
32 32.0 ± 0.4
32 35.7 ± 0.5
32 39.6 ± 0.6
32 34.2 ± 0.5 |
33 32.5 ± 0.4
33 35.3 ± 0.4
33 38.9 ± 0.6
33 34.7 ± 0.6 |
35 31.8 ± 0.3
35 34.9 ± 0.4
35 38.8 ± 0.6
35 33.9 ± 0.61
|
1Data presented as mean ± standard deviation. Differences from the control group were evaluated by Williams’ or Dunnett’s test (weight) and Shirley’s test (gestation length)
* Significantly different (P<0.05) from the control group by Williams’ test.
** Significantly different (P<0.01) from the control group by Shirley’s test.
Survival, Sex Distribution and Mean Body Weights of B6C3F1 mouse Pups in the Mating trial Study of 1,6 -Hexanediamine Dihydrochloride.
|
0 mg/m3 |
16 mg/m3 |
50 mg/m3 |
160 mg/m3 |
Day 0 |
35 9.11 ± 0.38 8.86 ± 0.37 53.33 ± 3.51 1.37 ± 0.03 |
34 9.00± 0.44 8.53 ± 0.53 50.56 ± 3.562 1.39± 0.032 |
33 8.73± 0.46 8.61 ± 0.45 53.18 ± 2.11 1.41 ± 0.04 |
35 9.57± 0.25 9.37 ± 0.24 50.56 ± 3.25 1.37 ± 0.02 |
Day 5 |
35 8.54 55.94 ± 3.533 3.57 ± 0.083 |
34 8.44 ± 0.52 50.79 ± 3.582 3.56 ± 0.082 |
33 8.58 ± 0.46 53.28 ± 2.11 1.41 ± 0.04 |
35 9.37 ± 0.24 50.32 ± 3.29 3.55 ± 0.06 |
Day 14 |
35 8.51 ± 0.44 56.43 ± 3.513 8.19 ± 0.213 |
34 8.41 ± 0.52 50.80 ± 3.582 7.95 ± 0.152 |
33 8.58 ± 0.46 53.28 ± 2.51 8.25 ± 0.27 |
35 9.34 ± 0.24 50.08 ± 3.33 7.63 ± 0.16 |
Day 21 |
35 8.46 ± 0.43 56.15 ± 3.583 10.94 ± 0.243 |
34 8.41 ± 0.52 51.11 ± 3.572 10.68 ± 0.172 |
33 8.58 ± 0.46 53.28 ± 2.51 10.93 ± 0.29 |
35 9.31 ± 0.24 50.03 ± 3.26 10.21 ± 0.19* |
1 Data presented as mean ± standard deviation. Differences from the control group for percent of live male pups, litter size, and number of pups born alive are not significant by Dunn’s test. The significance of differences in pup weights between dosed and control groups was evaluated by Dunnett’s or William’s test.
2 n=32
3 n=34
* Significantly different (P<0.05) from the control group by William’s test
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 10 100 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- mouse
- Quality of whole database:
- limited report on potential metabolite propylene glycol
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEC
- 50 mg/m³
- Study duration:
- subchronic
- Species:
- mouse
- Quality of whole database:
- report on potential metabolite analogue 1,6-dihexanediamine
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Based on the results of the studies with the metabolites, it is most likely that the potential toxicity of the substance is expected to be determined by the diamine moiety, as the toxicity of propylene glycol is low. Therefore the NOAEL for reproductive toxicity will be based on the studies with 1,6 -hexanediamine.
Short description of key information:
1,6-hexanediamine: inhalation NOAEC rat and mouse 5 mg/m3 (local effects), rat 160 mg/m3 (systemic effects), mouse 50 mg/m3 (systemic effects)
1,6-hexanediamine: oral feed mouse NOAEL 150 mg/kg bw
propylene glycol: oral drinking water NOAEL 10100 mg/kg
Effects on developmental toxicity
Description of key information
1,6-hexanediamine: inhalation NOAEC rat 160 mg/m3 and mouse 50 mg/m3
1,6-hexanediamine: oral feed mouse NOAEL 150 mg/kg bw
propylene glycol: oral drinking water NOAEL 14400 mg/kg
From the results of the reproduction studies it can be concluded that both potential metabolites do not have adverse effects on development
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEC
- 50 mg/m³
- Study duration:
- subchronic
- Species:
- mouse
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Additional information
No effects on the offspring were reported at doses without apparent parental toxicity. The NOAEL as derived for reproductive toxicity is considered sufficiently protective for developmental effects.
Justification for classification or non-classification
No fertility effects were seen in studies on both metabolites and the developmental effects (reduced viability and reduced body weight gain in F1 and F2 pups in the feeding study at 500 mg/kg bw 1,6 -hexanediamine) or the only occurred secondary to maternal toxicity. Therefore, the substance is not classified for reproductive toxicity according to CLP (Regulation EC No 127272008).
Additional information
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.