Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

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:
2007-06-11 till 2009-07-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline-conform study under GLP without deviations (OECd 421)
Qualifier:
according to
Guideline:
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
Deviations:
yes
Remarks:
Some relatively minor deviations are discussed in the study report. These deviations were not considered to have compromised the validity or integrity of the study.
GLP compliance:
yes (incl. certificate)
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories France, L’Arbresle, France
- Age at study initiation: (P) 11 wks
- Weight at study initiation: (P) Males: mean body weight of 441 g (range: 386 g to 506 g); females: mean body weight 251 g (range: 223 g to 280 g)
- Fasting period before study: no data
- Housing: The animals were individually housed (except during mating) in suspended wire-mesh cages (43.0 x 21.5 x 18.0 cm). A metal tray, containing autoclaved sawdust (SICSA, Alfortville, France), was placed under each cage. Shortly before parturition, the females were moved to polycarbonate cages (43.0 x 21.5 x 20.0 cm) with wood shavings as nesting material.
- Diet (e.g. ad libitum): The animals had free access to SsniffR/M-H pelleted maintenance diet, batch Nos. 6557303 and 9557111 (SSNIFF Spezialdiäten GmbH, Soest, Germany) which was distributed weekly.
- Water (e.g. ad libitum): The animals had free access to bottles containing tap water (filtered with a 0.22 µm filter).
- Acclimation period: 14 days before the beginning of the treatment period


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): about 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12h/12h (7:00 - 19:00)


IN-LIFE DATES: From: 2007-06-12 To: 2007-08-21
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
DIET PREPARATION
- Rate of preparation of diet (frequency): Diet distributed weekly. Each batch of diet was analyzed by the supplier for composition and contaminant levels
- Storage temperature of food: no data

VEHICLE
- Justification for use and choice of vehicle (if other than water): no justification given
- Concentration in vehicle: 10, 30 and 90 mg/mL
- Amount of vehicle (if gavage): 5 mL/kg bw / day
- Lot/batch no. (if required): batch No. 065K0077, supplied by Sigma
- Purity: no data
Details on mating procedure:
- M/F ratio per cage: one female was placed with one male
- Length of cohabitation: Each female was placed with the same male until mating occurs or 14 days have elapsed.
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 post coitum
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: no
- After successful mating each pregnant female was caged (how): Shortly before parturition, the females were moved to polycarbonate cages (43.0 x 21.5 x 20.0 cm) with wood shavings as nesting material.
- Any other deviations from standard protocol: none reported
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The test item concentration of samples taken from each dosage form (including the control) prepared for use in weeks 1, 2 and 4 (all groups) or week 8 (group 2, see § Study plan adherence) was determined. On 27th June 2007, the control dosage form was re-sampled and analyzed in duplicate further to abnormal values obtained during the first analysis. Only replicated data was reported. The analytical procedure used is presented in the study report.
Acceptance criterion: actual concentration: nominal value ± 10%.
Duration of treatment / exposure:
Males: 2 weeks before mating, during the mating period (2 weeks), until sacrifice (i.e. at least 4 weeks in total)
Females: 2 weeks before mating, during the mating period (2 weeks), during pregnancy, during lactation until day 4 post-partum inclusive (until sacrifice).
Frequency of treatment:
once a day, 7 days per week
Details on study schedule:
- F1 parental animals not mated until [...] weeks after selected from the F1 litters. not applicable
- Selection of parents from F1 generation when pups were [...] days of age. not applicable
- Age at mating of the mated animals in the study: 11 weeks
Remarks:
Doses / Concentrations:
50 mg/ kg bw / d
Basis:
actual ingested
Remarks:
Doses / Concentrations:
150 mg/ kg bw / d
Basis:
actual ingested
Remarks:
Doses / Concentrations:
450 mg/ kg bw / d
Basis:
actual ingested
No. of animals per sex per dose:
10 males, 10 females
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: The dose-levels were selected in agreement with the Sponsor, following the results of a previously conducted prenatal toxicity study (CIT/Study No. 31486 RSR) in which the test item, UNDECYLENIC ACID (batch No. 0607007), was administered daily by gavage to pregnant
Sprague-Dawley rats from day 6 to day 20 p.c. at the dose-levels of 150 or 450 mg/kg/day. At 750 mg/kg/day, the death of eight animals occurred before mid gestation and the surviving females were prematurely sacrificed. Therefore, the dose-level of 450 mg/kg/day is anticipated to produce minor signs of toxicity (750 mg/kg/day exceeded the MTD), and the two other dose-levels were selected using a factor of 3 between each dose.
- Rationale for animal assignment (if not random): Allocation to groups: during the pre-treatment period, the required number of animals (40 males
and 40 females) were selected according to body weight (recorded twice for planning reasons, see § Study plan adherence) and clinical condition and allocated to groups (by sex), according to a computerized stratification procedure (these data were not presented in the report), so that the average body weight of each group was similar.
- Other:
Positive control:
not applicable
Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Each animal was checked at least twice a day for mortality and signs of morbidity. The pups were observed daily for clinical signs.
- Cage side observations checked in Appendices 4 to 7 of the original study report were included.


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Each animal was checked at least twice a day for mortality and signs of morbidity. The pups were observed daily for clinical signs.


BODY WEIGHT: Yes
- Time schedule for examinations: Males: days 1, 8, 15, 29; Females: days 1, 8, 15 premating period; days 0, 7, 14, 20 pregnancy period; days 1, 4 post partum; days 1 - 4 of lactation


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): not applicable


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): not applicable
- Time schedule for examinations:


OTHER:
Oestrous cyclicity (parental animals):
no data
Sperm parameters (parental animals):
no data
Litter observations:
STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no
- If yes, maximum of [...] pups/litter ([...]/sex/litter as nearly as possible); excess pups were killed and discarded.


PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities


GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; possible cause of death was not determined for pups born or found dead
Postmortem examinations (parental animals):
SACRIFICE
- Male animals: All surviving animals after the end of the mating period
- Maternal animals: All surviving animals from day 5 post-partum


GROSS NECROPSY
- A macroscopic post-mortem examination of the principal thoracic and abdominal organs (with special attention paid to the reproductive organs) was performed on all parent animals including any that died during the study. In all females, the number of implantation sites was recorded.


HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in the following table were prepared for microscopic examination and weighed, respectively.
The macroscopic lesions and the following tissues from all parent animals were preserved in 10% buffered formalin (except for testes and epididymides which were fixed in Davidson’s fixative):
. epididymides,
. ovaries,
. prostate,
. seminal vesicles,
. testes,
. uterus (horns and cervix),
. vagina.
Postmortem examinations (offspring):
SACRIFICE
- The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at 5 days of age.
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows:
A gross external examination was performed on all pups including those that died during lactation or were sacrificed moribund. There was no preservation of tissues.

GROSS NECROPSY: not conducted


HISTOPATHOLOGY / ORGAN WEIGTHS: not applicable
Statistics:
Data other than organ weights
Mean values were compared by one-way variance analysis and Dunnett's test, (mean values being considered as normally distributed, variances being considered as homogeneous). Percentage values were compared by Fisher's exact probability test.

Organ weights
PathData software (version 6.2b5) was used for the statistical analysis of organ weight data (level of significance: 0.05 or 0.01).
Reproductive indices:
Data are expressed as group mean values ± standard deviation (body weight, food consumption, corpora lutea, implantations, fetuses, resorptions, pups, gestation length) or as proportions (pre-implantation loss, post-implantation loss, fetal observations, gestation index, live birth index, viability index). Whenever necessary, the experimental unit of comparison was the litter.
The calculations were performed for each group as follows:
Pre-implantation loss: ((Number of corpora lutea - Number of implantation sites) / (Number of corpora lutea)) x 100
Post-implantation loss: ((Number of implantation sites - Number of live concepti) / (Number of implantations)) x 100
Mating index: (Number of mated animals - Number of paired animals) / x 100
Fertility index: (Number of pregnant female partners / Number of mated pairs) x 100
Gestation index: (Number of females with live born pups / Number of pregnant females) x 100
Live birth index: (Number of live born pups / Number of delivered pups) x 100
Offspring viability indices:
Viability index on day 4 post-partum:
(Number of surviving pups on day 4 post-partum / Number of live born pups) x 100
Clinical signs:
effects observed, treatment-related
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:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
no effects observed
Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed
CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
At 450 mg/kg/day, two males died on days 3 and 35 without ante-mortem clinical signs of toxicity and no evident cause of death were diagnosed at macroscopic examination.
At 150 mg/kg/day group, hypersalivation was observed in males and females and one male had loud breathing transiently.
At 50 mg/kg/day, hypersalivation was the single effect, but observed to a lower extent than in previous treated groups.

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS) no effects


TEST SUBSTANCE INTAKE (PARENTAL ANIMALS) no effects


REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS) not examined


REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS) not examined


REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS) no effects


ORGAN WEIGHTS (PARENTAL ANIMALS) no effects


GROSS PATHOLOGY (PARENTAL ANIMALS) no effects


HISTOPATHOLOGY (PARENTAL ANIMALS) no effects


OTHER FINDINGS (PARENTAL ANIMALS) no effects
Dose descriptor:
NOAEL
Remarks:
reproductive performance
Effect level:
450 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Dose descriptor:
NOAEL
Remarks:
parental toxicity
Effect level:
150 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: mortality: At 450 mg/kg/day, two males died on days 3 and 35 without ante-mortem clinical signs of toxicity and no evident cause of death were diagnosed at macroscopic examination.
Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
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
as indicated above

VIABILITY (OFFSPRING)


CLINICAL SIGNS (OFFSPRING)


BODY WEIGHT (OFFSPRING)


SEXUAL MATURATION (OFFSPRING)


ORGAN WEIGHTS (OFFSPRING)


GROSS PATHOLOGY (OFFSPRING)


HISTOPATHOLOGY (OFFSPRING)


OTHER FINDINGS (OFFSPRING)
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
450 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no adverse effect
Reproductive effects observed:
not specified

Tab. 2: Summary of relevant clinical signs

 Sex           Male   Female           
 Dose level (mg/kg/d)  50 150  450   0 50   150 450    
Male                            
Ptyalism   0 10   9   n.a.     n.a.   n.a.    n.a.    
 Loud breathing  0  1    n.a.    n.a.    n.a.   n.a.    
 Dyspnea  0  0  0 0    n.a.   n.a.    n.a.       n.a.  
Female                            
Ptyalism   n.a.    n.a.   n.a.   n.a.   0 10    
Loud breathing   n.a.   n.a.    n.a.    n.a.   0 9    
 Dyspnea  n.a.    n.a.    n.a.    n.a.  0  7 8    

n.a.: not applicable

Hypersalivation was observed from week 1 of dosing in general and continued throughout the study, with dose-related increase in terms of onset, incidence and duration. This clinical sign was considered not to be adverse as it likely represents a reaction to the dosing procedure and not a direct effect of UNDECYLENIC ACID. Loud breathing was observed in a single male given 150 mg/kg/day and in four males given 450 mg/kg/day. One out of these four males experienced dyspnea. These signs of respiratory discomfort were transiently observed.

In all other observations made (body weight, body weight gain, mating data, female fertility, delivery data, observations on the pups, and pathology) no significant deviations of the dose groups compared to the control group were being noted.

Conclusions:
Based on the results of this study, the dose-level of 150 mg/kg/day was considered to be the No Observed Adverse Effect Level (NOAEL) for parental toxicity, and the dose-level of 450 mg/kg/day was the NOEL for reproductive performance. There is no need for classification of test item undecylenic acid as to its reprotoxic properties.
Executive summary:

The objective of this study was to evaluate the potential toxic effects of the test item, UNDECYLENIC ACID, following daily oral administration (gavage) to male and female rats from before mating, through mating and gestation until the end of the parturition period. This study should provide initial information on possible toxicological effects likely to arise from repeated exposure over a relatively limited period of time and on male and female reproductive performance, such as gonadal function, mating behavior, conception, development of the conceptus and parturition. The rat was chosen because it is a rodent species commonly accepted by regulatory authorities for this type of study and the Sprague-Dawley strain was selected since background data from previous studies are available at CIT. The oral route was selected since it is a route of administration which is requested by the regulatory authorities for this type of test item. The dose-levels were selected in agreement with the Sponsor, following the results of a previously conducted prenatal toxicity study (CIT/Study No. 31486 RSR).

The test item, UNDECYLENIC ACID (CAS RN 112-38-9) batch No. 0607007 was administered to male and female Sprague-Dawley rats by oral route (gavage), under the above detailed experimental conditions, at the dose-levels of 50, 150 or 450 mg/kg/day. At 450 mg/kg/day, two males died on days 3 and 35 without ante-mortem clinical signs of toxicity and no evident cause of death were diagnosed at macroscopic examination. Hypersalivation was observed in males and females, and respiratory difficulties (loud breathing and dyspnea) were noted transiently in males. At 150 mg/kg/day group, hypersalivation was observed in males and females and one male had loud breathing transiently. At 50 mg/kg/day, hypersalivation was the single effect, but observed to a lower extent than in previous treated groups. There were no substance-induced effects on the male and female reproductive performance, or on the progeny at any dose-level. No treatment-related effects were noted on testes or epididymides weights, at necropsy or on microscopic examination of the testes, epididymides or ovaries in treated rats. Based on the results of this study, the dose-level of 150 mg/kg/day was considered to be the No Observed Adverse Effect Level (NOAEL) for parental toxicity, and the dose-level of 450 mg/kg/day was the NOEL for reproductive performance. There is no need for classification of test item undecylenic acid as to its reprotoxic properties.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
450 mg/kg bw/day
Additional information

In the GLP reproduction screening test performed according to OECD 421 guideline the following results were observed:

At 450 mg/kg/day, two males died on days 3 and 35 without ante-mortem clinical signs of toxicity and no evident cause of death were diagnosed at macroscopic examination. Hypersalivation was observed in males and females, and respiratory difficulties (loud breathing and dyspnea) were noted transiently in males.

There were no substance-induced effects on the male and female reproductive performance, or on the progeny at any dose-level. No treatment-related effects were noted on testes or epididymides weights, at necropsy or on microscopic examination of the testes, epididymides or ovaries in treated rats. Based on the results of this study, the dose-level of 150 mg/kg/day was considered to be the No Observed Adverse Effect Level (NOAEL) for parental toxicity, and the dose-level of 450 mg/kg/day was the NOEL for reproductive performance.


Short description of key information:
Toxicity for reproduction : 1 test in rats according to the OECD 421 guideline (CIT 2009).

Effects on developmental toxicity

Description of key information
Developmental toxicity : 1 test with rats according to the OECD 414 guideline (CIT 2007).
Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007-01-18 till 2007-02-14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study (OECD 414)
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
no
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
TEST ANIMALS (Caesarian-obtained, barrier-sustaines, virus-antibody free pregnant animals)
- Source: Charles River, L`Arbresle, France
- Age at study initiation: 11 weeks
- Weight at study initiation: 212-312 g
- Fasting period before study:
- Housing: barrier rodent unit, housed individually in suspended wire-mesh cages
- Diet (e.g. ad libitum): ad lib. access to pelleted standard diet
- Water (e.g. ad libitum): ad lib. access to 0.22 um-filtered tap water
- Acclimation period:3,4, or 5 days (delivered as mated females from supplier)
-individual identification by ear tattoo


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2
- Humidity (%): 50+/-20
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
-mixing: magnetic stirrer
-Rate of preparation of solution (frequency): for up to 4 / 9 days
- Storage temperature of solution: 4°C


VEHICLE
- Justification for use and choice of vehicle (if other than water): not soluble in water
- Concentration in vehicle: 30,90,150 mg/mL
- Amount of vehicle (if gavage): 5 ml/kg BW/day
- Lot/batch no. (if required): batch No. 015K0115 (Sigma)
- Purity:98.79 %
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
by HPLC-UV;
deviations from nominal value: 3-9%;
compound in vehicle stable over 9 days at 4°C;
Details on mating procedure:
- Impregnation procedure: purchased timed pregnant
- Proof of pregnancy: vaginal plug referred to as day 0 post coitum
Duration of treatment / exposure:
from day 6 to day 20 post coitum
Frequency of treatment:
once daily
Duration of test:
15 days
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: preliminary study
Maternal examinations:
MORBIDITY/MORTALITY/CLINICAL SIGNS: Yes
- Time schedule: once to twice a day during treatment, afterwards once a day

BODY WEIGHT: Yes
- Time schedule for examinations: days 2,4,6,9,12,15,18,21 post coitum

FOOD CONSUMPTION: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as mg food/kg body weight/day: Yes

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 21 (high-dose group between day 8 and 16 p.c.)
- macroscopic examination of the principal thoracic and abdominal organs

OTHER: fixation and collection of macroscopic lesions
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Number and ditribution of dead/life fetuses: Yes
- Number and distribution of uterine scars: Yes
- Other: gross evaluation of placentas, macroscopic lesions fixec and collected
Fetal examinations:
- External examinations/fetal weights/sex: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: Yes: half per litter
Statistics:
Mean values: one-way ANOVA with Dunnett`s test
Percentage Values: Fisher exact probability test
Indices:
body weight change, net body weight (chnage), total number of resorptions, total number of dead fetuses, % of dead fetuses/litter, total number of live fetuses, % of live fetuses/litter, % of pre-implantation loss, % of post-implantation loss, average fetal body weight, %of pre-implantation loss relative to number of corpora lutea
Historical control data:
no
Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
mortality 8/24 in the high dose group, termination before end of study;
reduced body weight gain (see table1) and food consumption as well as hypersalivation (24/24) in the intermediate dose group;
hypersalivation (15/24) in some animals of the low dose group
Dose descriptor:
NOAEL
Effect level:
150 mg/kg bw/day (actual dose received)
Basis for effect level:
other: maternal toxicity
Dose descriptor:
LOAEL
Effect level:
450 mg/kg bw/day (actual dose received)
Basis for effect level:
other: maternal toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
none of the parameters investigated was affected
(one fetus in the low dose group with several malformations was not considered relevant but of spontaneous origin)
Dose descriptor:
NOAEL
Effect level:
450 mg/kg bw/day (actual dose received)
Basis for effect level:
other: teratogenicity
Abnormalities:
not specified
Developmental effects observed:
not specified

Table 1: Maternal Body Weight Gain (±SD)

 

 

Interval

Dose in mg/kg bw/day (24 of Dams)

Control (N)

LDT (150)

MDT (450)

HDT (750)

Treatment:

Days 6 -12 

 40

37 

32**

 -

Treatment:

Days 6 -15 

63 

 57

 52**

 -

Treatment:

Days 6 -21 

 151

137 

135* 

 -

*  Significantly different (p 0.05) from the control

** Significantly different (p 0.01) from the control

 

Conclusions:
No hints for developmental toxic effects of undecylenic acid were identified, not even in animals with clear maternal toxicity.
Executive summary:

The potential of the test substance undecylenic acid to induce developmental toxicity was evaluated in the rat according to OECD guideline 414. Pregnant Sprague-Dawley rats were treated daily with the test substance by oral gavage between days 6 and 21 post coitum. The dams were observed during the treatement for signs of toxicity. The animals were sacrificed on day 21 post coitum and fetuses as well as maternal animals were investigated for signs of toxicity.

Unexpectedly high mortality in the high dose group led to the decision to terminate the treatment of this group. All animals of the intermediate dose group exhibited hypersalivation, and a significantly reduced body weight gain compared to control. In the low dose group, no relevant effects were observed. Hypersalivation in half of the animals was not considered as a relevant sign of toxicity.

No effects or uncommon findings were observed in the fetuses of the animals (malformations observed in a single fetus of the low dose group was considered incidental).

Consequently, the NOAEL for maternal toxicity was set to 150 mg/kg bw/day, while the LOAEL for this parameter was 450 mg/kg bw/day based on body weight and clinical signs. No signs of teratogenicity/developmental toxicity were observed in the study, and the NOAEL ws set to the highest dose level, 450 mg/kg bw/day (750 mg/kg bw/day was discontinued before end of study). A LOAEL for teratogenicity was not observed.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
450 mg/kg bw/day
Additional information

In the developmental reproduction study in rats performed according to OECD 414, unexpectedly high mortality in the high dose group led to the decision to terminate the treatment of this group. All animals of the intermediate dose group exhibited hypersalivation, and a significantly reduced body weight gain compared to control. In the low dose group, no relevant effects were observed. Hypersalivation in half of the animals was not considered as a relevant sign of toxicity.

No effects or uncommon findings were observed in the fetuses of the animals (malformations observed in a single fetus of the low dose group was considered incidental).

Consequently, the NOAEL for maternal toxicity was set to 150 mg/kg bw/day, while the LOAEL for this parameter was 450 mg/kg bw/day based on body weight and clinical signs. No signs of teratogenicity/developmental toxicity were observed in the study, and the NOAEL was set to the highest dose level, 450 mg/kg bw/day (750 mg/kg bw/day was discontinued before end of study).

Justification for classification or non-classification

Since no signs of teratogenicity / developmental toxicity were consistently observed in the reported studies (NOAEL 450 mg/kg bw/day), there is no classification of undecylenic acid as to its reprotoxic properties according to EU regulation (EC) No 1272/2008 (CLP) and to EU Directive 67/584/EEC.