Fatty acids, tall-oil, reaction products with triethanolamine

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Version / remarks:

of 1996

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sprague Dawley rats, strain: Crl:CD(SD) with appropriate range of bodyweight at study start.
- Source: Charles River (UK) Ltd.
- Age at treatment start: 10 to 11 weeks.
- Weight at treatment start: Males: minimum 321 g, maximum 381 g,
Females: minimum 209 g, maximum 264 g.
- Housing Inside a barriered rodent facility:
all animals pre-mating + toxicity subgroup: In groups up to 5 by sex in solid floor polycarbonate cages.
during mating (1 male+1 female/cage): In RB3 modified propylene cages with stainless steel grid-floor over absorbent paper-lined trays.
males after mating: In groups up to 5 by sex in solid floor polycarbonate cages.
females during gestation and lactation: Females housed individually in solid floor polycarbonate cages.
- Bedding material (in solid floor cages): Wood based bedding, sterilised by autoclaving before use.
- Cage enrichment: Aspen chew block + plastic shelter (except during mating or post gestation day 20).
- Diet (ad libitum): Standard rodent diet (SDS VRF1 Certified) without antibiotic, chemotherapeutic or prophylactic agent.
- Fasting (diet withheld): Toxicity subgroup animals overnight before blood sampling for hematology/clinical blood chemistry.
- Water (ad libitum): Pottable drinking water from the public supply.
- Acclimation period: 13 days before treatment start, under laboratory conditions.

Routine analysis of the batch of diet used and water, chew blocks and wood bedding did not provide evidence of contamination that might have prejudiced the study.

IN-LIFE DATES:
- Duration of test, males & toxicity subgroup females: Five weeks
Duration of test, reproductive subgroup females: From 14 days prior to mating to day 7 of lactation.
Duration of test, offspring: From birth to day 7 of lactation.

ENVIRONMENTAL CONDITIONS

Air conditioned room kept at positve pressure without re-circulation of the filtered fresh air supplied to the room.
Controlled environment, environmental conditions were set at:
- Temperature (°C): 21 ± 2°C
- Relative Humidity (%): 40 to 70%
- Photoperiod (artificial lighting): 12 hrs day / 12 hrs night
Deviations from these target ranges were not evident.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

Treatment of parental animals by oral gavage administration. Test substance was not directly administered to F1 animals.

- Concentration in vehicle: The concentration of the test material in vehicle varied between dose groups thus allowing constant dosage volume in terms of mL/kg bw/day.
- Amount (dose volume by gavage): 2 mL/kg bw/day.
Actual dose volumes were calculated at about weekly or shorter intervals accounting for the latest body weight. Litter animals were not dosed.

CONCENTRATION OF TEST MATERIAL IN VEHICLE

Group Concentration of Test Substance Treatment Volume Dose Level of Test Substance
(mg/mL) (mL/kg bw/day) (mg/kg bw/day)
Vehicle Control 0 2 0
Low Dose 50 2 100
Mid Dose 150 2 300
High Dose 500 2 1000

Details on mating procedure:

- Male/female ratio per cage: 1/1
- Length of cohabitation: At the most 14 days, until proof of pregnancy was confirmed. 
- Proof of pregnancy: Formation of copulation plug or sperm in vaginal smear referred to as day 0 of gestation.
(During cohabitation, females were checked every morning for pregnancy).

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

- Chemical analysis of test material formulations by high performance liquid chromatography (HPLC/UV) using an external standard technique.
- Concentrations (verified at first and last treatment week) of the test material formulations were confirmed at each dose level.
- Chemical analysis confirmed that the prepared formulations were 102% to 108% of the corresponding nominal concentration.

Duration of treatment / exposure:

- Treatment period, males & toxicity subgroup females: Daily, for five consecutive weeks
- Treatment period, reproductive subgroup females: Ca. 6 to 8 weeks (from 14 days before mating to day 7 of lactation)

Frequency of treatment:

Daily, 7 days/week (during parturition, dosing omitted as appropriate)

Details on study schedule:

- Age at mating of the mated animals in the study: 12 to 14 weeks

Dose / conc.:

100 mg/kg bw/day (actual dose received)

Dose / conc.:

300 mg/kg bw/day (actual dose received)

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

Toxicity subgroups: 5 males* / 5 females
Reproductive subgroups: 5 males* / 10 females
* All males were killed at the same time (Week 6) after pairing with reproductive subgroup females

Control animals:

yes, concurrent vehicle

Details on study design:

This study was conducted to examine both repeated dose toxicity and  reproductive/developmental toxicity as an OECD screening combined study
(OECD 422 test guideline).  Therefore, animals initially entering the study were divided into toxicity subgroup animals and reproductive subgroup animals, whereby 5 of the 10 F0 males (used for pairing) per dose group formed the toxicity male subgroups.

Dose selection was based on the results of a 7-day preliminary oral toxicity study in the rat in which dose levels of 100, 300 or 1000 mg/kg/day did not have any overt treatment-related effects on young adult animals (females nulliparous and non-pregnant). The high dose level of 1000 mg/kg/day was considered to be the maximum practical dose level for the present OECD 422 study and was therefore chosen as the high dose level.

Positive control:

Not included in the study.

Parental animals: Observations and examinations:

Clinical observations performed and frequency:
- Clinical signs : At least twice a day (before and after administration)
- Detailed physical examination
and arena observations: Before treatment start and at least once a treatment week.
- Functional Observation Battery: During treatment week 5 (before dosing) on all toxicity subgroup animals (5 parental males/group inclusively)*.
- Body weight, all males: Weekly throughout the study.
Body weight, Toxicity Females: Weekly throughout the study.
Body weight, Repro. Subgr. Females: Weekly for pre-mating and mating period; on gestation days 0, 7, 14, 20; on lactation days 1, 4 & 7.
- Food consumption, all animals: Weekly for pre-mating period.
Food cons., Repro. Subgr. Females: During gestation for days 0-7, 7-14, 14-20, during lactation for days 1-4 & 4-7.
- Water consumption: Daily (based on visual observation inidicative of overt water intake).
- Hematology: During treatment week 5 after functional observation battery*
- Blood (plasma) chemistry: During treatment week 5 after functional observation battery*

* Examinations confined to toxicity subgroup animals are marked above with an asterisk*
and are detailed in the separate endpoint study record "7.5.1 Repeated dose toxicity: oral - Repeat dose tox combined, oral, rat_HLS_Proj_GAH0008"

Explanatory note
This study was conducted to examine both repeated dose toxicity and  reproductive/developmental toxicity as an OECD screening combined study
(OECD 422 test guideline).  Therefore, animals initially entering the study were divided into toxicity subgroup animals and reproductive subgroup animals whereby 5 of the 10 F0 males (used for mating) per dose group formed the toxicity male subgroups.

Oestrous cyclicity (parental animals):

Frequency of vaginal estrus was determined by examination of vaginal smears taken daily and checking for copulation plugs daily from all reproductive subgroup females from the beginning of the treatment period to the day of confirmed copulation.
- Regular: All observed cycles of 4 or 5 days
- Irregular: At least one cycle of 2, 3 or 6 to 10 days
- Acyclic: At least 10 days without oestrus

Sperm parameters (parental animals):

Parameters examined in male parental animals:
- testis weight,
- epididymis weight
- detailed qualitative histopathology examination of the testes taking into account the tubular stages of the spermatogenic cycle. This was to identify treatment related effects such as missing germ cell layers or types, retained spermatids, multinucleate or apoptotic germ cells and sloughing of spermatogenic cells in the lumen. Any cell- or stage-specificity of testicular findings was noted.

Litter observations:

STANDARDISATION OF LITTERS: Not performed. The study ended on lactation day 7.

LITTER PARAMETERS EXAMINED
- From Day 20 post copulation 3 times a day checks for evidence of parturition, any difficulties and numbers of live and dead offspring.
- Total litter size on day 1 of age and mortality/live litter size on each day until 7 days after littering.
- Sex ratio expressed as percentage males  (Total No. of male pups in litter/Total No. of offspring in litter) x 100
- Gestation index (No. of live litters born on day 0/No. of living pregnant females) x 100
- Clinical signs, recorded daily
- Body weight of live pups (on days 1, 4 and 7 after littering) and weight change from days 1-4 and 1-7.

Postmortem examinations (parental animals):

GROSS PATHOLOGY: Yes, see below
WEIGHING OF ORGANS: Yes, see below
HISTOPATHOLOGY: Yes, see below

Terminal sacrifice
- all males: Killed in Week 6, after completion of the Treatment Week 5 investigations.
- reproductive subgr. females: Killed on Day 7 post partum. 1 female without viable litter was killed on Day 25 after mating.

Gross pathology
- all rats: Full macroscopic examination  with tissue collection.
- reproduction subgroup females: Recording of the number of uterine implatation sites.

Organs Weights:
- toxicity subgroup animals: Adrenals, brain, epididymides*, heart, kidneys, liver, ovaries*, pituitary, prostate*, seminal vesicles
& coagulation gland*, spleen, testes*, thymus, thyroid with parathyroids, uterus with cervix and oviducts*.
- reproductive subgroup animals: * These organs were also weighed for adult/parental reproductive subgroup animals.
Histopathology:
- reproductive subgroup animals: The following organs were microscopically examined for the control and 1000 mg/kg bw/day groups:
Epididymides, testes, ovaries, uterus (with cervix & oviducts), vagina, mammary area (caudal), seminal vesicle &
coagulation gland, prostate.
- toxicity subgroup animals: For the control and 1000 mg/kg bw/day groups (5 adult/parental males per group inclusive):
Brain, pituitary gland, thyroid with parathyroids, heart, thymus, liver, spleen, adrenals, kidneys, testes,
epididymides, ovaries, lung, trachea, esophagus, stomach, duodenum, jejunum, ileum, caecum, rectum,
colon, Peyer's patch, lymph node (left axillary, mesenteric), urinary bladder, uterus (with cervix & oviducts),
vagina, spinal cord, sciatic nerve, mammary area (caudal),  sternum with marrow, seminal vesicle &
coagulation gland, prostate.
In addition, the kidneys were also examined for the 100 and 300 mg/kg bw/day toxicity subgroups.

Postmortem examinations (offspring):

Pup survivors were killed on Day 7 post partum.
Full macroscopic examination of decedent and surviving pups including assessment of the presence of milk in the stomach, where possible.
(Missing or grossly autolysed or cannibalised pups could not be examined).

Statistics:

As detailed in Endpoint study record "7.5.1 Repeated dose toxicity: oral - Repeat dose tox combined, oral, rat_HLS_Proj_GAH0008"

Reproductive indices:

- No. of animals mating (evidence of successful copulation, i.e. spermatozoa in vaginal smears and/or copulation plugs)
- Percentage mating (No. of animals mating/No. of animals paired) x 100
- Pre-coital interval (pairing days until detection of mating)
- No. of animals achieving pregnancy
- Conception rate (No. of animals achieving pregnancy/No. of animals mated) x 100
- Fertility index (No. of animals achieving pregnancy/ No. or animals pairing) x 100
- Gestation length (time elapsing between detection of mating and commencement of parturition
- No. of living pregnant females
- For further reproductive parameters, see also the above section "Litter observations" and section "Offspring viability indices" below.

Offspring viability indices:

- Post-implantation survival index  (Total no. of pups born/Total no. of uterine implantation sites) x 100
- Live birth index (No. of live pups on day 1 after littering/Total no. of pups born) x 100
- Viability index (No. of live pups on day 4 after littering /No. of live pups on day 1 after littering) x 100
- Lactation index (No. of live pups on day 7 after littering /No. of live pups on day 1 after littering) x 100
- For further parameters indicative of the viability of the offspring, see also the above section "Litter observations"

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

no effects observed

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

no effects observed

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

in kidneys at 1000 mg/kg/day: Slight increase in incidence and/or severity of tubular casts in both sexes and in cortical tubular basophilia in females. Examination only in 5 toxicity subgroup females/group and 5 F0 males/group, not examined in F0 females

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

Description (incidence and severity):

At 1000 mg/kg/day, 1 pair failed to produce a litter. Macroscopically no evidence of any implantation sites in the affected female, microscopically no changes in the reproductive tract in both F0 animals. This was not attributed to the test substance.

Mortality:
- No deaths occurred in all F0 males or females during the study.

Water consumption:
- No overt effects, based on daily visual observation.

Histopathology:
Further details on renal histopathology findings in F0 animals of the present study are given in separate endpoint study record "7.5.1 Repeated dose toxicity: oral - Repeat dose tox combined, oral, rat_HLS_Proj_GAH0008", e.g. in Table 1 and the commenting text underneath this table.

Key result

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

reproductive performance

other: see 'Remark'

Key result

Critical effects observed:

no

Clinical signs:

no effects observed

Mortality / viability:

mortality observed, non-treatment-related

Description (incidence and severity):

mortality of pups was observed in all dose groups and the control group within the normal range of rats of this strain.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

until postnatal day 7, the day of scheduled sacrifice of the pups.

No treatment-related abnormality was observed.

No abnormality in sex ratio.

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

>= 1 000 mg/kg bw/day (nominal)

Based on:

other: F1 generation was not dosed directly but may have been exposed via milk from dosed dams.

Sex:

male/female

Basis for effect level:

viability

body weight and weight gain

other: NOAEL = highest dose tested.

Key result

Critical effects observed:

no

Key result

Reproductive effects observed:

no

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Study duration:

subacute

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Short description of key information:
WS400128 was tested in a Combined Repeated Dose Oral (Gavage) Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (OECD 422) at dose levels of 0 (vehicle control), 100, 300, 1000 mg/kg bw/day. The NOAEL regarding fertility was derived at 1000 mg/kg/day.
In a 90 day repeated dose study the NOAEL was derived at 1000 mg/kg/day; no effects were observed in reproduction organs and tissues.

Effects on developmental toxicity

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS Sprague Dawley rats, strain Crl:CD(SD)
- Source: Charles River (UK) Ltd.
- Age at study initiation: approx. 70 days (Day 0 of gestation)
- Weight at study initiation: 227-278 g
- Fasting period before study: none
- Housing: one cage per animal during gestation
- Diet (e.g. ad libitum): ad libitum (pelleted diet)
- Water (e.g. ad libitum): ad libitum (tap water)
- Acclimation period: five days before commencement of pairing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23°C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12 h light, 12 h dark

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:

VEHICLE
- Justification for use and choice of vehicle (if other than water): corn oil allows good dispersion of test substance, experience from other gavage studies
- Concentration in vehicle: 50, 150, 500 mg/ml
- Amount of vehicle (if gavage): 2 ml/kg body weight

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

- Chemical analysis of test material formulations by high performance liquid chromatography (HPLC/UV) using an external standard technique.
- Concentrations (verified for first and last preparation) of the test material formulations were confirmed at each dose level.
- Chemical analysis confirmed that the prepared formulations were within 4% of the corresponding nominal concentration.

Details on mating procedure:

- M/F ratio per cage: 1 : 1 with identified stock males
- Length of cohabitation: until positive evidence of mating was detected
- Proof of pregnancy: ejected copulation plugs and vaginal smears were checked for presence of sperm; when positive then referred to as day 0 of pregnancy

Duration of treatment / exposure:

females were treated from Day 6 to Day 19 (inclusive)

Frequency of treatment:

once daily

Duration of test:

animals were killed on Day 20 after mating

Dose / conc.:

100 mg/kg bw/day (actual dose received)

Dose / conc.:

300 mg/kg bw/day (actual dose received)

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

20 animals per group

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: based on result of reproduction toxicity screening study

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: at least twice daily

BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 3 and 6-20 after mating

FOOD CONSUMPTION AND COMPOUND INTAKE : Yes
- Food consumption for each animal determined for days: 0-2, 3-5, 6-9, 10-13, 14-17 and 18-19

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- Organs examined: detailed necropsy and macroscopic examination of tissues

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
- Number of fetuses: Yes

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: No

Statistics:

The analyses were carried out using the individual animal as the basic experimental unit. For litter/fetal findings the litter was taken as the treated unit and the basis for statistical analysis and biological significance was assessed with relevance to the severity of the anomaly and the incidence of the finding within the background control population.
The following data types were analysed at each timepoint separately:
Body weight, using absolute values and gains over appropriate study periods
Gravid uterine weight and adjusted body weight
Food consumption, over appropriate study periods
Litter size and survival indices
Fetal, placental and litter weight

A sequence of statistical tests was used for body weight, gravid uterine weight, food consumption, corpora lutea, implantations, live young, fetal, placental and litter weight data.

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

no effects observed

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:

not examined

Gross pathological findings:

not examined

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

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:

not examined

Description (incidence and severity):

Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not examined

Changes in number of pregnant:

no effects observed

Key result

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day (actual dose received)

Basis for effect level:

other: no effects observed in maternal animals

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:

not examined

External malformations:

no effects observed

Skeletal malformations:

no effects observed

Visceral malformations:

no effects observed

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The incidence of major and minor visceral and skeletal abnormalities and skeletal variants showed no relationship to treatment.

Across all treated groups there was a slightly higher incidence of incompletely ossified hyoid and 13/14 14/14 short supernumerary ribs compared to concurrent control but was within Historical Control Data (HCD) (see attachment "historical control data").

At 1000 mg/kg/day there was also a slightly higher incidence of incompletely ossified sacrocaudal vertebrae compared to concurrent control but again this was within HCD.

These findings are therefore considered to be unrelated and incidental, showing no clear treatment relationship.

Key result

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day (actual dose received)

Basis for effect level:

other: teratogenicity, embryotoxicity, fetotoxicity

Key result

Abnormalities:

no effects observed

Key result

Developmental effects observed:

no

There was no effect of WS400128 on body weight and body weight change as well as food consumption during gestation (Tables 2, 3, 4 in the attachment "result tables from OECD 414 study with WS400128).

There was no effect of WS400128 on implantations, early or late resorptions, live young or sex ratio (Table 5 in the attachment "result tables from OECD 414 study with WS400128).

There was no effect of treatment on placental weight or litter weight (Table 6 in the attachment "result tables from OECD 414 study with WS400128).

The incidence of major and minor visceral and skeletal abnomalities and skeletal variants showed no relationship to treatment (Tables 7, 8, 9 in the attachment "result tables from OECD 414 study with WS400128).

Conclusions:

Based on the results of this study the No Observed Adverse Effect Level for maternal toxicity, embryo-fetal survival, growth and development was considered to be at least 1000 mg/kg body weight/day.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available results classification of WS400128 regarding reprotoxic or developmental toxicity according to European classification rules [REGULATION (EC) 1272/2008] is not necessary.