Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
No other studies.
Link to relevant study records
Reference
Endpoint:
one-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 23, 1991 to January 6, 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study performed according to internationally accepted test guidelines but not to GLP.
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Combined Repeated Dose and Reproductive / Developmental Toxicity Screening Test (Precursor Protocol of GL 422)
Version / remarks:
draft 22 March 1990
GLP compliance:
no
Remarks:
The report states that the study was conducted according to the principles of GLP, but the work was not certified and was not subject to Quality Assurance review .
Limit test:
no
Species:
rat
Strain:
other: Crl:CD (SD) BR VAF/Plus
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd.
- Age at study initiation: (P) Males 12 wks ±1 day, Females (sexually mature, virgin) 7 weeks ±1day;
- Weight at study initiation: (P) Males: 440-446 g; Females: 224-228 g
- Fasting period before study: overnight
- Housing: pre-mating; suspended stainless steel cages equipped with solid sides and wire grid front, back, floor, and top. During mating male and female pairs were housed in plastic breeding cages (North Kent Plastics, RM2 type).
- Acclimatisation period: 1 week
- Diet : Biosure Laboratory Animal Diet No. 1 ad libitum
- Water : tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 55
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12/12

Five males and five females were supplied for health check purposed. They were killed within 24 hours of arrival and subjected to routine macroscopic examination.
Route of administration:
oral: gavage
Vehicle:
other: 1% methylcellulose
Details on exposure:
The test material was ground in a mortar with a small volume of 1% methylcellulose until a smooth paste was formed. The formulation was then gradually made up to volume and mixed using a high speed homogeniser. A series of suspensions were then made to give the required concentrations. Formulations were prepared daily and dosed on the day of preparation.
Details on mating procedure:
Rats were paired 1 male to 1 female during the mating period (14 days). Mating was confirmed (by the presence of a sperm plug and vaginal smears). After the mating period, the males and females were returned to standard single housing.
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
Analytical verification of doses was not carried out.
Duration of treatment / exposure:
Males: 7 weeks; Females: 9 weeks.
Frequency of treatment:
Daily
Details on study schedule:
Rats underwent 2 weeks of treatment prior to blood collection and commencement of the mating phase. The mating phase lasted for 2 weeks. Repeat blood collections were taken from female rats prior to parturition, at week 5. Males were sacrificed after 7 weeks of treatment. Females were sacrificed after 9 weeks of treatment of post partum day 4 (non-pregnant females were sacrificed after 9 weeks treatment).
Remarks:
Doses / Concentrations:
0, 500 and 1000 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
20 per dose, 10 males, 10 females
Control animals:
yes
Details on study design:
A range finding study was conducted prior to the main study, the limit dose of 1000 mg/kg/day was established as a suitable high dosage level. Controls were concurrent but it is not stated whether they were unexposed, or administered the vehicle alone.
Positive control:
A positive control was not examined.
Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily


BODY WEIGHT: Yes
- Time schedule for examinations: recorded at allocation to groups, commencement of treatment and thereafter weekly. Females also weighed daily from the commencement of the mating period until parturition and Days 0 and 4 post partum.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes, measured during the pre-treatment and pre-mate period for males and females, during the post mate period for males and post partum for females. Water intake was only measured by visual observation, and could therefore not be subjected to statistical analysis.


HAEMATOLOGY: Yes, assessed after two weeks of treatment, and again after 5 weeks treatment in females
- Anaesthetic used for blood collection: Light ether anaethesia
- Animals fasted: Yes, overnight
- Parameters examined: PCV, haemoglobin, RBC, MCHC, MCV, total and differential WBC, platelets, examination for abnormal cell morphology, thrombotest, reticulocyte count.


CLINICAL CHEMISTRY: Yes, assessed after two weeks of treatment, and again after 5 weeks treatment in females.
- Animals fasted: Yes, overnight
- Parameters examined: Glucose, GPT, GOT, CPK, gammaGT, total protein albumin, globulin, urea nitrogen, AP, total bilirubin, creatine, sodium, potassium, calcium, inorganic phosphorus, chloride, cholesterol.

Oestrous cyclicity (parental animals):
Vaginal smears were taken daily starting from 1 week prior to mating and throughout the mating phase.
Sperm parameters (parental animals):
Sperm parameters were not examined.
Litter observations:
For each litter the pups were counted, sexed, weighed and examined for gross abnormalities as soon as possible after birth. Litters were examined daily for dead/missing (i.e. cannibalised) pups. Pups were weighed again on Day 4 post partum.

Litter weight and mean pup weight were calculated from individual pup weight. Sex ratios were calculated at birth and at day 4.
Pup loss on completion of parturition was calculated according the formula: ((total no. young at birth - no. live young) / total no. young at birth) x100
Cumulative pup loss was calculated according to the formula: ((total no. young at birth - no. live young at Day 4) / total no. young at birth) x100.
Postmortem examinations (parental animals):
All rats were subject to gross necropsy at study termination, and examined for macroscopic abnormalities. Organ weights: adrenals, brain, epididymides, heart, kidneys, liver, lungs, ovaries, prostrate, testes, thymus, spleen. The following tissues were examined histologically (* denotes tissues examined from control and high dose groups only): adrenals*, brain*, epididymides*, heart*, kidneys*, liver*, lungs, mammary gland, macroscopically abnormal tissues, ovaries*, pituitary*, prostate*, seminal vesicles*, spleen*, testes*, thymus, thyroids, uterus* and vagina*.
Implantation loss was calculated according to the formula: ((no. implantation sites - total young born) / no. implantation sites) x 100.
Postmortem examinations (offspring):
Litters were examined for abnormalities and sex confirmed.
Statistics:
ANOVA followed by Williams' test, or Kruskal-Wallis 'H' statistic followed by Shirley's test where appropriate.
Reproductive indices:
Fertility index = (no. pregnant females / no. females showing evidence of copulation) x100.
Gestation index = (no. pregnant females with live young / no. pregnant females) x 100.
Offspring viability indices:
Viability index (day 4) = (no. live young at day 4 / no. live young at birth) x100.
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
: pale faeces, not considered to be of toxicological relevance
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
Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed
There were no deaths during the study. There were no clinical signs associated with treatment. The bodyweight gain of treated males was similar to that of controls throughout the study. Females given 1000 mg/kg/day showed reduced gain during pregnancy but recovered post partum.
No effects of treatment on food intake were apparent over the time periods of measurement.
There were no changes in the haematological and biochemical parameters measured that were clearly indicative of a reaction to treatment.
There were no differences in organ weights that indicated any treatment-related effects.
There were no differences or changes noted at histopathological examination that indicated any treatment-related effects.
The oestrus cycle was unaffected by treatment and the pregnancy rate was good in all groups. Time to mating and duration of pregnancy were within normal limits. Two females were not pregnant, and one dam exhibited total resorption of her litter.
Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effects were seen
Clinical signs:
no effects observed
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:
no effects observed
Histopathological findings:
not examined
There were no obvious effects of treatment on litter size or sex ratio at birth, or on survival at post partum day 4. Litter and mean pup weight also appeared unaffected. There were no findings at necropsy, and no clinical signs were reported. A small number of pups died at birth, or by post partum day 4, none of these deaths were attributed to treatment. Litter data are shown in Table 1.

Reproductive effects observed:
not specified

Litter data

Group No. of Animals Implant sites Implant loss % At birth At day 4
Litter size Pup loss % Litter Wt (g) Mean pup wt. (g) Litter size Cumulative loss% Litter wt (g) Mean pup wt.(g)
Mated Pregnant male female Total %males live male female Total %males
Control 10 10 17.5 4.6 9 7.7 16.7 54.9 16.3 2.3 102.9 6.3 8.7 7.3 16 55.3 4.2 161.6 10.2
500 mg/kg/day 10 8 18.4 4.1 9.4 8.3 17.6 53.4 17.5 0.7 107.8 6.2 9.3 8 17.3 53.8 2.1 165.2 9.6
1000 mg/kg/day 10 9 17.1 3.7 7.7 8.8 16.4 46.2 16.4 0 101.4 6.2 7.3 8.6 15.9 45.8 3.4 158.2 10
Conclusions:
The study author concluded that there were no findings at either of the dosage levels employed in this study to indicate an immediate requirement for more detailed studies.
Executive summary:

The study was conducted to assess the repeated dose oral toxicity and toxicity to reproduction of dipentaerythritol, in accordance with OECD guideline 422 (draft version; 22 March 1990).

Sexually mature rats were exposed to dipentaerythritol via oral gavage at dose levels 0, 500, and 1000 mg/kg bw/d. The rats were exposed throughout pregnancy and the effects on both parents and the F1 generation were assessed.

Male rats were exposed for 7 weeks prior to sacrifice and necropsy. Females were exposed for 9 weeks until post partum day 4, when they along with their pups were sacrificed and subjected to gross necropsy.

There were no findings at either of the dosage levels in this study to indicate an immediate requirement for more detailed studies. No effects of treatment were observed on food intake, bodyweight change, haematology, biochemistry, organ weights, post mortem findings and histopathology. There did not appear to be any effects on mating or on pup viability.

The NOAEL for reproductive and developmental effects can therefore be considered to be 1000 mg/kg bw/d.

 

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
An OECD screening study is available for the submission substance
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Screening study

A combined repeated dose oral toxicity and toxicity to reproduction study was conducted with di-pentaerythritol, according to OECD method 422 (draft version; 22 March 1990) (Powell et al, 1992). Sexually mature rats were exposed to di-pentaerythritol via gavage at 0, 500 and 1000 mg/kg bw/day. The rats were exposed throughout pregnancy and the effects on both parents and the F1 generation were assessed. Male rats were exposed for 7 weeks prior to sacrifice and necropsy. Females were exposed for 9 weeks until post partum day 4, when they and their pups were sacrificed and subject to gross necropsy. There were no findings at either dose level that would indicate an immediate requirement for more detailed studies. No effects of treatment were observed on food intake, bodyweight change, haematology, biochemistry, organ weights, post mortem findings and histopathology. There did not appear to be any effects on mating or on pup viability. The NOAEL for reproductive effects was considered to be 1000 mg/kg bw/d.


Short description of key information:
No evidence of any potential for reproductive toxicity was seen in a combined reproductive/developmental toxicity screening assay in rats performed with di-pentaerythritol at dose levels of up to and including 1000 mg/kg bw/d. A waiver is proposed for the extended one reproductive generation toxicity study based on the absence of effects seen in the standard repeat dose studies and the absence of effects seen in the screening study.

Justification for selection of Effect on fertility via oral route:
Only study available for this endpoint

Effects on developmental toxicity

Description of key information
A prenatal developmental toxicity study in the rat (OECD 414) is available. No effects of treatment were observed and the maternal and developmental NOAELs were considered to be 1000 mg/kg bw/d.
Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 August to 10 September 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and OECD guideline compliant with no deviations
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
- Strain: Crl:CD(SD) Sprague-Dawley rats (female)
- Source: Charles River UK Limited, Margate, Kent, UK
- Age at study initiation: 9-10 weeks old
- Weight at study initiation: 201 - 305 g
- Housing: Up to 2 per cage in suspended polycarbonate/polypropylene cages with stainless steel grid tops and solid bottoms. Sterilised white wood shavings were provided as bedding with a device for hiding in and an object for chewing as environmental enrichment.
- Diet (e.g. ad libitum): SDS RM1 diet, ad libitum
- Water (e.g. ad libitum): Water from the public supply, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-25°C
- Humidity (%): 34-64%
- Air changes (per hr): Ten or greater with 100% fresh air
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on exposure:
Doses of 0 (corn oil only), 25, 75 or 250 mg/mL were administered by oral gavage, at a constant dosing volume of 4 mL/kg bw. Dosing formulations were prepared based on a method established at the Test Facility at appropriate concentrations to meet dosage level requirements. The dosing formulations were prepared weekly, stored in a refrigerator set to maintain 4°C, and dispensed daily. The dosing formulations were removed from the refrigerator and stirred for at least 30 minutes before dosing. The dosing formulations were also stirred continuously during dosing. Any residual volumes were discarded.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Analyses were performed by Gas Chromatography with Flame Ionisation Detection (using a validated procedure). Dose formulaton samples were collected for analysis from all groups on Day 1 and Week 2 for determination of concentration, and from all test material groups for determination of homogeneity. Duplicate sets of samples (top, middle, and bottom samples (duplicate middle only for control)) for each sampling time point were sent to the analytical laboratory; the remaining samples were retained at the Test Facility as backup samples.
Stability analyses performed previously in conjunction with Charles River Study No. 434327 demonstrated that the test item was stable in the vehicle when prepared and stored under the same conditions at concentrations bracketing those used in the present study. Stability data were retained in the study records for Study No. 434327.
Details on mating procedure:
Time-mated females were delivered to the test facility.
Duration of treatment / exposure:
Days 6-19 of gestation
Frequency of treatment:
Once daily
Duration of test:
Day 6 to Day 20 of gestation
Remarks:
Doses / Concentrations:
0, 100, 300, 1000 mg/kg bw/d
Basis:
nominal conc.
No. of animals per sex per dose:
24 females per dose
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: Dose levels were selected in agreement with the Sponsor following review of all available toxicological data, where dose levels of up to 1000 mg/kg bw/d were well tolerated with only minimal effects of toxicity.
- Rationale for animal assignment (if not random): random allocation on arrival
Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes (general health, mortality and moribundity)
- Time schedule: twice daily; postdose observations for reaction to treatment were also made prior to daily and regularly throughout the day

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily from the start of dosing,

BODY WEIGHT: Yes
- Time schedule for examinations: once during pre-treatment (Day 5 of gestation) and daily (Day 6-20 of gestation) during dosing

FOOD CONSUMPTION: Yes
- Food consumption was measured quantitatively daily from Day 5 of gestation

WATER CONSUMPTION: No

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation Day 20 of gestation
- Organs examined: All adult animals were subjected to a complete necropsy examination, which included evaluation of the carcass and musculoskeletal system; all external surfaces and orifices; cranial cavity and external surfaces of the brain; and thoracic, abdominal, and pelvic cavities with their associated organs and tissues.

OTHER:
Ovaries and uterine content:
The reproductive tract was dissected from the abdominal cavity. The gravid uterus was weighed. The uterus was opened and the contents were examined. The fetuses were removed from the uterus. The ovaries and uterus were examined for number and distribution of corpora lutea, implantation sites, placentae (size, colour or shape) any abnormalities were recorded, live and dead fetuses and early and late embryonic deaths.
Fetal examinations:
EXTERNAL ABNORMALITIES
Fetuses were examined for external abnormalities. Late resorptions and dead fetuses were examined for external abnormalities to the extent possible. Each implant was classified as being live, or a dead fetus (dead full term fetus that shows no sign of maceration), or a late embryonic death (macerated tissue identifiable as an embryo) fetus, with recognisable external features such as tail, limbs, mouth and nares present; attached to distinct identifiable placentae), or an early embryonic death (discrete, formless, discoloured tissue mass attached to the internal uterine wall; may be of varying size).

BODY WEIGHT
The body weight of each fetus was recorded. Fetuses were individually identified within litters.

VISCERAL EXAMINATION AND SEX
Half of the viable fetuses from each uterus were fixed in methylated ethyl alcohol, examined internally for sex and eviscerated following initial fixation, the viscera were not examined from fetuses prior to disposal. The remaining half of the viable fetuses from each uterus were fixed in Bouin's fluid. The fetuses fixed in Bouin's fluid were examined for soft tissue abnormalities and sex using a freehand sectioning technique derived from that of Wilson.

SKELETAL EXAMINATION
The eviscerated carcasses were then macerated in potassium hydroxide, the skeletons stained with Alizarin Red S, and then the fetuses cleared with aqueous glycerol solutions. These preparations were examined for the presence of skeletal abnormalities and for the extent of ossification.
Statistics:
Means and standard deviations were calculated for body weight, food consumption and pregnancy data. To assist interpretations, tests were applied to determine the statistical significance of observed differences between the control group and groups receiving test item. Unless otherwise stated, all statistical tests were two-sided and performed at the 5% significance level using in house software. Pairwise comparisons were only performed against the control group.
Body weight and food consumption data were analysed for homogeneity of variance using the ‘F Max' test. If the group variances appeared homogeneous, a parametric ANOVA was used and pairwise comparisons were made using Fisher’s F protected LSD method via Student's t test i.e. pairwise comparisons were made only if the overall F test was significant. If the variances were heterogeneous, log or square root transformations were used in an attempt to stabilise the variances. If the variances remained heterogeneous, then a Kruskal-Wallis non-parametric ANOVA was used and pairwise comparisons were made using chi squared protection (via z tests, the non-parametric equivalent of Student's t test).
Indices:
Not applicable
Historical control data:
Records maintained at the test facility
Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
There were no mortalities, and no clinical signs of toxicity. Food consumption, group mean body weights and body weight gains were unaffected by treatment. There were no abnormalities detected at necropsy.
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
There was no effect of treatment on pregnancy frequency, gravid uterine weight, mean fetal weight, numbers of corpora lutea, number of implants or embryofetal survival including pre-implantation loss. The type and distribution of all fetal abnormalities and variations, including those indicating the extent of skeletal ossification were similar in all groups and did not indicate any association with treatment.
Abnormalities:
not specified
Developmental effects observed:
not specified

Dose formulation analyses: All study samples analyzed had mean concentrations within or equal to the acceptance criteria of

± 10% of their theoretical concentrations. Day 1 Group 1 control samples showed test item peaks and Day 1 Group 2 samples were not

reported due to an unexpectedly high injection, therefore, as part of the investigation, the group 1 backup samples were analyzed in triplicate and the group 2 samples were rerun, and the results were within the acceptance criteria. Group 1 backup samples and group 2 re-run samples are reported. For homogeneity, the RSD of concentrations for all samples in each group was within the acceptance criteria of ≤ 10%, except for Week 2, Group 3 (12.1%) and group 4 (13.8%); therefore as part of the investigation, group 3 and 4 samples were rerun and the results (2.1% and 1.4%) were within the acceptance criteria. It is thought that the reason the week 2 group 3 and 4 results were outside acceptance criteria initially were due to a clogged syringe on the gas chromatograph. Back-up samples for Week 2 (Groups 3-4) were also analysed in triplicate, and the results were within the acceptance criteria. Back up sample results will not be reported since rerun samples were within the acceptance criteria. The dose formulations were within specification. Homogeneity testing showed that the formulation technique used produced homogeneous preparations.

Mortality (Table 1)

There were no premature deaths during the course of this study.

 

Clinical Observations (Table 1)

At dose levels up to and including 1000 mg/kg/day there were no clinical observations that were considered to be related to Di-Pentaerythritol administration.

 

Body Weights and Body Weight Changes (Table 2)

At dose levels up to and including 1000 mg/kg/day the group mean body weights and body weight gains were similar to the control group for the duration of the study.

  

Food Consumption (Table 3)

The group mean food consumption was similar across all groups.

 

Gross Pathology (Table 1)

At all dose levels, the type and distribution of gross necropsy findings did not indicate any association with test item administration.

 

Pregnancy Performance, Gravid Uterine and Fetal Weights (Table 4)

At dose levels up to and including 1000 mg/kg/day there was no effect on pregnancy frequency, gravid uterine weight, mean fetal weight, numbers of corpora lutea, number of implants or embryofetal survival including pre-implantation loss.

 

Fetal Abnormalities and Variants (Table 5, Table 6 and Table 7)

The type and distribution of all fetal abnormalities and variations, including those indicating the extent of skeletal ossification were similar in all groups and did not indicate any association with test item administration.

 

Conclusions:
The NOEL for maternal and developmental toxicity was 1000 mg/kg bw/d.
Executive summary:

The potential for Di-Penta (Di-Pentaerythritol) to cause developmental toxicity in the rat was investigated in an OECD 414 compliant study. Four groups of 24 female Sprague-Dawley rats were dosed orally by gavage on Days 6-19 of gestation (where Day 0 was the day of detection of mating) at dose levels of 0 (corn oil only), 100, 300 or 1000 mg/kg bw/d. The following parameters were evaluated: clinical signs, body weights, food consumption, gross necropsy findings, gravid uterine weight, and examination of pregnancies and fetal examinations (external abnormalities, fetal weights, visceral and skeletal evaluations). Animals were killed on Day 20 of gestation. There were no effects of treatment on any of the measured parameters at any dose level; there was no maternal toxicity and no evidence for developmental toxicity. Therefore, under the conditions of the study, the maternal and embryofetal NOELs were considered to be 1000 mg/kg bw/d.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
A recent GLP and guideline-compliant study is available.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Prenatal developmental toxicity study with Di-Penta

A study in the rat was performed using dose levels of 0, 100, 300 and 1000 mg/kg bw/d. No maternal toxicity was observed up to and including the highest dose level. There were no effects of treatment on pregnancy performance parameters, embryofetal survival or fetal weights, fetal abnormalities and variants. Under the conditions of the study, the maternal and embryofetal NOAELs were considered to be 1000 mg/kg bw/d.




Justification for selection of Effect on developmental toxicity: via oral route:
Single study available for this endpoint

Toxicity to reproduction: other studies

Additional information

No other studies.

Justification for classification or non-classification

No evidence of reproductive or developmental toxicity potential was seen in a combined screening assay performed with di-pentaerythritol at dose levels of up to and including the limit dose of 1000 mg/kg bw/d. No effects were observed in a rat developmental study performed with di-pentaerythritol at dose levels of up to 1000 mg/kg bw/d.

No classification is therefore required for reproductive toxicity according to Regulation (EC) No 1272/2008.