Undecyl glucoside

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproduction/Developmental Toxicity Screening Test (OECD 421), rat (m/f): NOAEL (reproductive/systemic toxicity) ≥1000 mg/kg bw/day (RA from CAS 110615-47-9)

Link to relevant study records

Reference

Reference 1

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions. No data on vehicle for gavage. Limited details on test substance and examinations.

Justification for type of information:

refer to category justification provided in IUCLID section 13

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

Deviations:

yes

Remarks:

no data on vehicle for gavage; limited details on test substance and examinations

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

other: Hsd: Sprague–Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: (P) 12 weeks
- Housing: in groups of 5 per sex per cage
- Diet: laboratory rodent diet (Altromin MT pelleted diet, A. Rieper, Bolzano, Italy), ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

not specified

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
Dose volumes are calculated according to individual body weight on the first day of treatment and adjusted for body weight at weekly intervals.

Details on mating procedure:

- M/F ratio per cage: 1/1
- Length of cohabitation: approx. 3 days (mean pre-coital period) up to 20 days
- Proof of pregnancy: vaginal plug and/or vaginal smear

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

(P) Males and females: 2 weeks before pairing and continuously thereafter, up to the day before sacrifice (study day 53, day 4 post partum)

Frequency of treatment:

daily, 7 days/week

Dose / conc.:

100 mg/kg bw/day (nominal)

Dose / conc.:

300 mg/kg bw/day (nominal)

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

10

Control animals:

yes

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: clinical signs were recorded daily throughout the study.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: all animals were examined on arrival. Examinations of dams and litters took place on Day 4 post-partum.

BODY WEIGHT: Yes
- Time schedule for examinations: body weight was determined on the first day of treatment with the test material and in weekly intervals thereafter.

FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
- Food consumption: Yes, not further specified

OTHER:
- Prostate weight, testes, weight, epididymides weight, seminal vesicle weight and gestation period were determined

Oestrous cyclicity (parental animals):

Vaginal smears are taken daily for 14 days prior to pairing and each morning during the pairing period to detect marked anomalies of the estrous cycle and to determine the median pre-coital interval.

Sperm parameters (parental animals):

Parameters examined in P male parental generations: testis weight, epididymis weight, seminal vesicle weight

Litter observations:

STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no

PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, presence of gross anomalies, weight gain, food consumption, physical or behavioural abnormalities, other: implantation per litter, mean litter weights, mean pup weights, pre-birth loss

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 on Day 53 (on Day 4 post partum)
- Maternal animals: All surviving animals on Day 53 (on Day 4 post partum)

Postmortem examinations (offspring):

SACRIFICE
- The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at 4 days of age.
- These animals were subjected to postmortem examinations (macroscopic examination).

Statistics:

Mean values and standard deviations of the following parameters were calculated:
- litter weights at birth and sacrifice
- absolute and relative organ weights of testes, epididymis, seminal vesicles and prostate
- pre-coital intervals
- total litter size, sex ratio (%)
- implantation/litter
- gestation period
- pre-birth loss/litter (number and %)

Reproductive indices:

female: copulation or fertility index, pregnancy rates, copulatory intervals
males: fertility index

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not examined

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):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

no effects observed

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

no effects observed

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
No clinical signs were observed during the whole study period.

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
No effects on body weights were noted during the study.

TEST SUBSTANCE INTAKE (PARENTAL ANIMALS)
No effects on food consumption were observed during the experimental period.

REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS)
No effects on estrous cycle were reported.

REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS)
No treatment-related effects on absolute and relative weights of testis and epididymis were observed at any dose level.

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
In males and females, no substance-related effects on fertility index were observed. A slight, but not significant decrease in copulatory index was observed in females receiving the high dose (1000 mg/kg bw/d). One female in the mid-dose group and two females in the high-dose group did not mate until day 10 and were mated with another male afterwards. One female in the high dose group did not mate after a period of 20 days.

ORGAN WEIGHTS (PARENTAL ANIMALS)
No effects on relative and absolute weights of testis, epididymis, and seminal vesicles were observed between test substance-treated and control animals. A marginal reduction in absolute and relative prostate weights in all treated males compared to the control group was noted. In the low dose group (100 mg/kg bw/d) a significant reduction in the weights of prostate were observed. Due to the absence of dose-dependency, this effect was not considered to be biologically significant.

GROSS PATHOLOGY (PARENTAL ANIMALS)
No substance-related effects were seen at macroscopic examination.

Key result

Dose descriptor:

NOAEL

Remarks:

systemic toxicity

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no treatment-related effects

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Dose descriptor:

NOAEL

Remarks:

reproductive toxicity

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects on male and female reproductive organs and performance

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Critical effects observed:

no

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not examined

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings:

not examined

Other effects:

not examined

Behaviour (functional findings):

not examined

Developmental immunotoxicity:

not examined

VIABILITY (OFFSPRING)
No effects on mean litter weights and sex ratios were observed between the F1 generations of treated and control animals. Some slight, but not significant variations in pre-birth loss were seen in the high-dose group compared to controls.

CLINICAL SIGNS (OFFSPRING)
No treatment-related clinical signs were observed in pre-weaning pups.

BODY WEIGHT (OFFSPRING)
No differences in the mean litter weight on Day 0 (birth) and Day 4 (sacrifice) were noted in treated and control groups.

GROSS PATHOLOGY (OFFSPRING)
Necropsy did not reveal any substance-related effects in decedent or F1 pups.

Key result

Dose descriptor:

NOAEL

Remarks:

embryo/fetotoxicity

Generation:

F1

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects on embryo/fetotoxicity

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Critical effects observed:

no

Reproductive effects observed:

not specified

Conclusions:

A reproduction/developmental toxicity screening test performed according to OECD 421 with the test material did not result in any adverse effect on maternal/reproductive/embryo-/fetotoxicity. Thus, a NOAEL (maternal/reproduction/embryo-/fetotoxicity) of ≥1000 mg/kg bw/day was derived.

Reference 2

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

refer to category justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Species:

rat

Strain:

other: Hsd: Sprague–Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: (P) 12 weeks
- Housing: in groups of 5 per sex per cage
- Diet: laboratory rodent diet (Altromin MT pelleted diet, A. Rieper, Bolzano, Italy), ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

not specified

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
Dose volumes are calculated according to individual body weight on the first day of treatment and adjusted for body weight at weekly intervals.

Details on mating procedure:

- M/F ratio per cage: 1/1
- Length of cohabitation: approx. 3 days (mean pre-coital period) up to 20 days
- Proof of pregnancy: vaginal plug and/or vaginal smear

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

(P) Males and females: 2 weeks before pairing and continuously thereafter, up to the day before sacrifice (study day 53, day 4 post partum)

Frequency of treatment:

daily, 7 days/week

Dose / conc.:

100 mg/kg bw/day (nominal)

Dose / conc.:

300 mg/kg bw/day (nominal)

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

10

Control animals:

yes

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: clinical signs were recorded daily throughout the study.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: all animals were examined on arrival. Examinations of dams and litters took place on Day 4 post-partum.

BODY WEIGHT: Yes
- Time schedule for examinations: body weight was determined on the first day of treatment with the test material and in weekly intervals thereafter.

FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
- Food consumption: Yes, not further specified

OTHER:
- Prostate weight, testes, weight, epididymides weight, seminal vesicle weight and gestation period were determined

Oestrous cyclicity (parental animals):

Vaginal smears are taken daily for 14 days prior to pairing and each morning during the pairing period to detect marked anomalies of the estrous cycle and to determine the median pre-coital interval.

Sperm parameters (parental animals):

Parameters examined in P male parental generations: testis weight, epididymis weight, seminal vesicle weight

Litter observations:

STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no

PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, presence of gross anomalies, weight gain, food consumption, physical or behavioural abnormalities, other: implantation per litter, mean litter weights, mean pup weights, pre-birth loss

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 on Day 53 (on Day 4 post partum)
- Maternal animals: All surviving animals on Day 53 (on Day 4 post partum)

Postmortem examinations (offspring):

SACRIFICE
- The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at 4 days of age.
- These animals were subjected to postmortem examinations (macroscopic examination).

Statistics:

Mean values and standard deviations of the following parameters were calculated:
- litter weights at birth and sacrifice
- absolute and relative organ weights of testes, epididymis, seminal vesicles and prostate
- pre-coital intervals
- total litter size, sex ratio (%)
- implantation/litter
- gestation period
- pre-birth loss/litter (number and %)

Reproductive indices:

female: copulation or fertility index, pregnancy rates, copulatory intervals
males: fertility index

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not examined

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):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

no effects observed

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

no effects observed

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
No clinical signs were observed during the whole study period.

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
No effects on body weights were noted during the study.

TEST SUBSTANCE INTAKE (PARENTAL ANIMALS)
No effects on food consumption were observed during the experimental period.

REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS)
No effects on estrous cycle were reported.

REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS)
No treatment-related effects on absolute and relative weights of testis and epididymis were observed at any dose level.

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
In males and females, no substance-related effects on fertility index were observed. A slight, but not significant decrease in copulatory index was observed in females receiving the high dose (1000 mg/kg bw/d). One female in the mid-dose group and two females in the high-dose group did not mate until day 10 and were mated with another male afterwards. One female in the high dose group did not mate after a period of 20 days.

ORGAN WEIGHTS (PARENTAL ANIMALS)
No effects on relative and absolute weights of testis, epididymis, and seminal vesicles were observed between test substance-treated and control animals. A marginal reduction in absolute and relative prostate weights in all treated males compared to the control group was noted. In the low dose group (100 mg/kg bw/d) a significant reduction in the weights of prostate were observed. Due to the absence of dose-dependency, this effect was not considered to be biologically significant.

GROSS PATHOLOGY (PARENTAL ANIMALS)
No substance-related effects were seen at macroscopic examination.

Key result

Dose descriptor:

NOAEL

Remarks:

systemic toxicity

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no treatment-related effects

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Dose descriptor:

NOAEL

Remarks:

reproductive toxicity

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects on male and female reproductive organs and performance

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Critical effects observed:

no

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not examined

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings:

not examined

Other effects:

not examined

Behaviour (functional findings):

not examined

Developmental immunotoxicity:

not examined

VIABILITY (OFFSPRING)
No effects on mean litter weights and sex ratios were observed between the F1 generations of treated and control animals. Some slight, but not significant variations in pre-birth loss were seen in the high-dose group compared to controls.

CLINICAL SIGNS (OFFSPRING)
No treatment-related clinical signs were observed in pre-weaning pups.

BODY WEIGHT (OFFSPRING)
No differences in the mean litter weight on Day 0 (birth) and Day 4 (sacrifice) were noted in treated and control groups.

GROSS PATHOLOGY (OFFSPRING)
Necropsy did not reveal any substance-related effects in decedent or F1 pups.

Key result

Dose descriptor:

NOAEL

Remarks:

embryo/fetotoxicity

Generation:

F1

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects on embryo/fetotoxicity

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Critical effects observed:

no

Reproductive effects observed:

not specified

Conclusions:

A reproduction/developmental toxicity screening test performed according to OECD 421 with the test material did not result in any adverse effect on maternal/reproductive/embryo-/fetotoxicity. Thus, a NOAEL (maternal/reproduction/embryo-/fetotoxicity) of ≥1000 mg/kg bw/day was derived.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s), common precursors/breakdown products, similarities in PC/ECO/TOX properties (refer to category justification for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

There are no data available on toxicity to reproduction (fertility) of D-Glucopyranose, oligomeric, undecyl glycoside. In order to fulfil the standard information requirements set out in Annex IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from a structurally related substance is conducted following a category approach.

 

Reproduction/Developmental Toxicity Screening Test

A key reproduction/developmental toxicity screening test performed according to OECD TG 421 with the category member D-Glucopyranose, oligomeric, C10-16-alkyl glycosides (CAS 110615-47-9) is available (Messinger et al., 2007). Groups of 10 Sprague-Dawley rats of each sex per dose were administered doses of 100, 300 and 1000 mg/kg bw/day via oral gavage. Males were treated for at least 4 weeks on 7 consecutive days per week, starting from 2 weeks prior to mating; females were treated for 2 weeks prior to mating, during mating and gestation on 7 consecutive days per week until day 4 post-partum. The animals were monitored for clinical signs, body weight, food consumption, mating and litter performance, estrous cyclicity and sperm parameters. All animals were submitted to necropsy, which included weighing of testes and epididymides. No information on histopathological examination is available. Gross pathology was performed with all parental animals and the offspring. No clinical signs and no effects on body weight, food consumption, estrous cycle and sperm parameters were recorded for parental animals during the entire study period. In males and females, no substance-related effects on fertility index were observed. A slight, but not significant decrease in copulatory index was observed in females receiving the high dose (1000 mg/kg bw/day. One female in the mid-dose group and two females in the high-dose group did not mate until day 10 and were mated with another male afterwards. One female in the high dose group did not mate after a period of 20 days. No effects on relative and absolute weights of testis, epididymis, and seminal vesicles were observed between test substance-treated and control animals. A marginal reduction in absolute and relative prostate weights in all treated males compared to the control group was noted. In the low dose group (100 mg/kg bw/day) a significant reduction in the weights of prostate were observed. Due to the absence of dose-dependency, this effect was not considered to be biologically significant. Gross pathology revealed no substance-related effects for parental animals. No effects on mean litter weights and sex ratios were observed between the F1 generations of treated and control animals. Some slight, but not significant variations in pre-birth loss were seen in the high-dose group compared to controls. No treatment-related clinical signs were observed in pre-weaning pups and no differences in the mean litter weight on Day 0 (birth) and Day 4 (sacrifice) were noted in treated and control groups. Gross pathology did not reveal any substance-related effects in decedent or F1 pups. Based on the results of the study and due to the absence of any toxicologically relevant adverse effect a NOAEL of 1000 mg/kg bw/day was derived for systemic and reproductive toxicity.

Reproductive toxicity (EOGRTS) - Waiving

According to Regulation (EC) No 1907/2006, Annex IX, 8.7.3. column 1, an extended one-generation reproductive toxicity study for assessment of reproductive toxicity is not required if no adverse effects on reproductive organs or tissues were reported in a Reproduction/Developmental Toxicity Screening Test. A reproduction/developmental toxicity screening test for a period of up to eight weeks is available for the structurally similar substance D-Glucopyranose, oligomeric, C10-16-alkyl glycosides (CAS 110615-47-9) demonstrating no treatment related effects on reproductive parameters such as mating performance or fertility. No evidence of any developmental effects was observed in offspring from treated litters, and no effect on the reproductive organs was evident following post mortem assessments. Therefore, a NOAEL (systemic/fertility) of ≥1000 mg/kg bw/day was derived. Moreover, a prenatal developmental toxicity study was conducted with D-Glucopyranose, oligomeric, C10-16-alkyl glycosides (CAS 110615-47-9) according to OECD 414 in rats indicating no embryotoxic or teratogenic potential and therefore, resulting In a NOAEL (maternal/developmental) of ≥1000 mg/kg bw/day. Thus, an extended one-generation reproductive toxicity study is not indicated based on the available date for the read across substance.

Based on the above study result with the category member D-Glucopyranose, oligomeric, C10-16-alkyl glycosides (CAS 110615-47-9) the registered substance D-Glucopyranose, oligomeric, undecyl glycoside is not expected to exert adverse effects on fertility, either.

Effects on developmental toxicity

Description of key information

Developmental Toxicity (OECD 414), rat (m/f): NOAEL (maternal/developmental toxicity) ≥1000 mg/kg bw/day (RA from CAS 110615-47-9) 

Link to relevant study records

Reference

Reference 1

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 Feb - 28 Mar 1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Comparable to guideline study with acceptable restrictions. The test substance was only administered during organogenesis and not through the entire period of gestation to the day before caesarean section. Body weights were not determined in 3-day intervals during treatment period.

Justification for type of information:

refer to category justification provided in IUCLID section 13

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

test substance was only administered during organogenesis and not through the entire period of gestation to the day before caesarean section; body weights were not determined in 3-day intervals during treatment period

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: Sprague Dawley, CD

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: 8 weeks
- Weight at study initiation: 203 g (mean)
- Housing: individually in Makrolon Type M3 cages (EBECO, Castrop-Rauxel, Germany) with standard softwood bedding (ARWI-Center, Essen, Germany)
- Diet: pelleted Atromin Maintenance Diet 1324 (ALTROMIN GmbH, Lage, Germany), ad libitum
- Water: community tap water (Düsseldorf, Germany), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 40-66
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: the test substance was prepared daily before administration by dissolving appropriate amounts in distilled water.

VEHICLE
- Concentration in vehicle: 1, 3 and 10% (v/v), i.e. 10, 30 and 100 mg/mL
- Amount of vehicle: 10 mL/kg bw

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The formulations of test substance were analysed once by High Performance liquid chromatography (HPLC). The determined analytical concentrations of 0.94, 2.88 and 9.23% verified the nominal concentrations of 1, 3 and 10% of the test substance in solution.

Details on mating procedure:

- Impregnation procedure: purchased timed pregnant

Duration of treatment / exposure:

(P) Females: Day 6-15 of gestation (organogenesis period)

Frequency of treatment:

once daily in the morning

Duration of test:

20 days

Dose / conc.:

100 mg/kg bw/day (nominal)

Dose / conc.:

300 mg/kg bw/day (nominal)

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

24 P females

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: based on the results of previous toxicological examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: animals were checked at least twice daily (working days) for clinical signs and mortality.

BODY WEIGHT: Yes
- Time schedule for examinations: body weights were determined on Day 0, 6, 16 and 20

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: all maternal organs with emphasis on uterus and its content

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
- Other: position of fetuses in the uterus, distribution of implantations, live or dead fetuses

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: No
- Other: sex, weight incl. placenta

Statistics:

Mean values and standard deviations were calculated. Statistical analyses at significance levels of 5% and 1% were performed on the following parameters and using the following statistical tests:
- Steel test: implantation sites, embryonic and fetal resorptions, live and dead fetuses
- Fishers exact test (Bonferroni-Holm-corrected): pre- and post-implantation loss, total embryonic deaths, total and malformed fetuses, skeletal parameters, sex of fetuses
- Dunnett-test based on pooled variance: weights of live fetuses, placenta and uteri, body weight of dams

Indices:

Percentage of implantation sites: (no. of implantations / no. of corpora lutea) * 100
Percentage of pre-implantation loss: [(no. of corpora lutea - no. of implantations) / no. of corpora lutea] * 100
Percentage of post-implantation loss: [(no. of implantations - no. of live foetuses) / no. of implantations] * 100
Percentage of embryonic resorptions: (no. of embryonic resorptions / no. of implantations) * 100
Percentage of fetal resorptions: (no. of fetal resorptions / no. of implantations) * 100
Percentage of total fetuses: (no. of total fetuses / no. of implantations) * 100
Percentage of malformed fetuses: (no. of malformed fetuses / no. of total fetuses) * 100
Percentage of male fetuses: (no. of male fetuses / total no. of live fetuses) * 100
Percentage of female fetuses: (no. of female fetuses / total no. of live fetuses) * 100

Clinical signs:

effects observed, non-treatment-related

Description (incidence and severity):

The animal of the 100 mg/kg bw/d test group found dead on Day 11 showed impeded respiration, lethargy, and a decrease in body weight on Day 10. One animals of the high dose group (1000 mg/kg bw/d) showed impeded respiration on Day 15 and 16 and lethargy on Day 16. However, these findings were not related to treatment.

Dermal irritation (if dermal study):

not examined

Mortality:

mortality observed, non-treatment-related

Description (incidence):

No deaths occurred in dams receiving the vehicle or the test substance at doses of 300 mg/kg bw/d. Due to an application error, test substance-unrelated mortalities were found on Day 11 and 13 each in one animal of the 100 and 1000 mg/kg bw/d test group.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Maternal body weights were not affected by treatment. The mean body weights of the high dose group showed a slight increase on Day 6 compared to the controls. Mean corrected body weight gain (corrected for uterus weight) of the treated groups was comparable to the control group.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, non-treatment-related

Description (incidence and severity):

At scheduled necropsy, no macroscopic changes were observed between treated and control animals. Incidental findings in two animals either comprised white nodules in the left inguinal region or haematoma in the region of larynx.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

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:

not examined

Other effects:

not examined

Details on maternal toxic effects:

Maternal toxic effects: no effects

MORTALITY:
No deaths occurred in dams receiving the vehicle or the test substance at doses of 300 mg/kg bw/d. Due to an application error, test substance-unrelated mortalities were found on Day 11 and 13 each in one animal of the 100 and 1000 mg/kg bw/d test group.

CLINICAL SIGNS:
No substance-related symptoms were observed at any dose level during the study. The animal of the 100 mg/kg bw/d test group found dead on Day 11 showed impeded respiration, lethargy, and a decrease in body weight on Day 10. One animals of the high dose group (1000 mg/kg bw/d) showed impeded respiration on Day 15 and 16 and lethargy on Day 16. However, these findings were not related to treatment.

BODY WEIGHTS:
Maternal body weights were not affected by treatment. The mean body weights of the high dose group showed a slight increase on Day 6 compared to the controls. Mean corrected body weight gain (corrected for uterus weight) of the treated groups was comparable to the control group.

REPRODUCTION DATA:
No substance-related effects on reproduction data were noted compared to controls.

NECROPSY:
At scheduled necropsy, no macroscopic changes were observed between treated and control animals. Incidental findings in two animals of the 300 mg/kg bw/day and 1000 mg/kg bw/day, respectively, either comprised white nodules in the left inguinal region or haematoma in the region of larynx.

Key result

Dose descriptor:

NOAEL

Remarks:

maternal toxicity

Effect level:

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

Based on:

test mat.

Basis for effect level:

other: no treatment-related effects observed

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Abnormalities:

no effects observed

Fetal body weight changes:

no effects observed

Description (incidence and severity):

Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed

Reduction in number of live offspring:

no effects observed

Changes in sex ratio:

no effects observed

Changes in litter size and weights:

no effects observed

Changes in postnatal survival:

no effects observed

External malformations:

no effects observed

Skeletal malformations:

no effects observed

Visceral malformations:

no effects observed

Other effects:

no effects observed

Description (incidence and severity):

The weight of placenta and uteri including content showed no significant differences between treated and control animals.

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects: no effects

EMBRYOTOXICITY/FETOTOXICITY:
No substance-related differences in pre-and post-implantation loss, mean figures of resorptions, embryonic deaths and total fetuses were observed in treated animals compared to controls.

BODY WEIGHTS:
The weight of live fetuses exhibited not significant differences on a litter or individual basis.

PLACENTA AND UTERUS WEIGHT:
The weight of placenta and uteri including content showed no significant differences between treated and control animals.

SEX RATIOS:
The fetal sex ratio was comparable in all test groups.

EXTERNAL OBSERVATIONS:
No abnormal findings were observed that were considered to be related to treatment. Incidental findings comprised the occurrence of only one placenta for two fetuses in the control group and one fetus with hydrops in the high dose group (1000 mg/kg bw/d).

VISCERAL OBSERVATIONS:
The main figures of visceral variations (hydronephrosis, dilated and waved ureters) were similar compared to controls and variations were not considered to be related to treatment. All other findings except for one situs inversus total in the high dose group and enlarged parenchymous organs in one fetus in the controls were considered to be incidental.

SKELETAL EXAMINATION:
No substance-related abnormal findings were noted at skeletal examination of the fetuses. Spontaneous findings comprised absent or malformed cervical vertebrae arches in one mid dose fetus and luxation and malposition of the mandible in one high dose fetus when compared to the control group. Retarded ossification was found in all treatment groups and was similar to the level of skeletal ossification in the control group. The isolated statistically significant difference in the figure “14 ribs short/rudimentary bilateral” in the high dose group (100 mg/kg bw/d) was considered to be incidental and not related to treatment, since no dose-response relationship was apparent.

Key result

Dose descriptor:

NOAEL

Remarks:

developmental toxicity

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no treatment-related effects observed

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Abnormalities:

no effects observed

Key result

Developmental effects observed:

no

Conclusions:

A prenatal developmental toxicity study performed according to OECD 414 and in compliance with GLP with the test material and did not reveal any treatment-related effect. Thus, a NOAEL (maternal/developmental) of ≥1000 mg/kg bw/day was derived.

Reference 2

Endpoint:

developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

refer to category justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Species:

rat

Strain:

other: Sprague Dawley, CD

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: 8 weeks
- Weight at study initiation: 203 g (mean)
- Housing: individually in Makrolon Type M3 cages (EBECO, Castrop-Rauxel, Germany) with standard softwood bedding (ARWI-Center, Essen, Germany)
- Diet: pelleted Atromin Maintenance Diet 1324 (ALTROMIN GmbH, Lage, Germany), ad libitum
- Water: community tap water (Düsseldorf, Germany), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 40-66
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: the test substance was prepared daily before administration by dissolving appropriate amounts in distilled water.

VEHICLE
- Concentration in vehicle: 1, 3 and 10% (v/v), i.e. 10, 30 and 100 mg/mL
- Amount of vehicle: 10 mL/kg bw

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The formulations of test substance were analysed once by High Performance liquid chromatography (HPLC). The determined analytical concentrations of 0.94, 2.88 and 9.23% verified the nominal concentrations of 1, 3 and 10% of the test substance in solution.

Details on mating procedure:

- Impregnation procedure: purchased timed pregnant

Duration of treatment / exposure:

(P) Females: Day 6-15 of gestation (organogenesis period)

Frequency of treatment:

once daily in the morning

Duration of test:

20 days

Dose / conc.:

100 mg/kg bw/day (nominal)

Dose / conc.:

300 mg/kg bw/day (nominal)

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

24 P females

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: based on the results of previous toxicological examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: animals were checked at least twice daily (working days) for clinical signs and mortality.

BODY WEIGHT: Yes
- Time schedule for examinations: body weights were determined on Day 0, 6, 16 and 20

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: all maternal organs with emphasis on uterus and its content

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
- Other: position of fetuses in the uterus, distribution of implantations, live or dead fetuses

Fetal examinations:

- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: No
- Other: sex, weight incl. placenta

Statistics:

Mean values and standard deviations were calculated. Statistical analyses at significance levels of 5% and 1% were performed on the following parameters and using the following statistical tests:
- Steel test: implantation sites, embryonic and fetal resorptions, live and dead fetuses
- Fishers exact test (Bonferroni-Holm-corrected): pre- and post-implantation loss, total embryonic deaths, total and malformed fetuses, skeletal parameters, sex of fetuses
- Dunnett-test based on pooled variance: weights of live fetuses, placenta and uteri, body weight of dams

Indices:

Percentage of implantation sites: (no. of implantations / no. of corpora lutea) * 100
Percentage of pre-implantation loss: [(no. of corpora lutea - no. of implantations) / no. of corpora lutea] * 100
Percentage of post-implantation loss: [(no. of implantations - no. of live foetuses) / no. of implantations] * 100
Percentage of embryonic resorptions: (no. of embryonic resorptions / no. of implantations) * 100
Percentage of fetal resorptions: (no. of fetal resorptions / no. of implantations) * 100
Percentage of total fetuses: (no. of total fetuses / no. of implantations) * 100
Percentage of malformed fetuses: (no. of malformed fetuses / no. of total fetuses) * 100
Percentage of male fetuses: (no. of male fetuses / total no. of live fetuses) * 100
Percentage of female fetuses: (no. of female fetuses / total no. of live fetuses) * 100

Clinical signs:

effects observed, non-treatment-related

Description (incidence and severity):

The animal of the 100 mg/kg bw/d test group found dead on Day 11 showed impeded respiration, lethargy, and a decrease in body weight on Day 10. One animals of the high dose group (1000 mg/kg bw/d) showed impeded respiration on Day 15 and 16 and lethargy on Day 16. However, these findings were not related to treatment.

Dermal irritation (if dermal study):

not examined

Mortality:

mortality observed, non-treatment-related

Description (incidence):

No deaths occurred in dams receiving the vehicle or the test substance at doses of 300 mg/kg bw/d. Due to an application error, test substance-unrelated mortalities were found on Day 11 and 13 each in one animal of the 100 and 1000 mg/kg bw/d test group.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Maternal body weights were not affected by treatment. The mean body weights of the high dose group showed a slight increase on Day 6 compared to the controls. Mean corrected body weight gain (corrected for uterus weight) of the treated groups was comparable to the control group.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, non-treatment-related

Description (incidence and severity):

At scheduled necropsy, no macroscopic changes were observed between treated and control animals. Incidental findings in two animals either comprised white nodules in the left inguinal region or haematoma in the region of larynx.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

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:

not examined

Other effects:

not examined

Details on maternal toxic effects:

Maternal toxic effects: no effects

MORTALITY:
No deaths occurred in dams receiving the vehicle or the test substance at doses of 300 mg/kg bw/d. Due to an application error, test substance-unrelated mortalities were found on Day 11 and 13 each in one animal of the 100 and 1000 mg/kg bw/d test group.

CLINICAL SIGNS:
No substance-related symptoms were observed at any dose level during the study. The animal of the 100 mg/kg bw/d test group found dead on Day 11 showed impeded respiration, lethargy, and a decrease in body weight on Day 10. One animals of the high dose group (1000 mg/kg bw/d) showed impeded respiration on Day 15 and 16 and lethargy on Day 16. However, these findings were not related to treatment.

BODY WEIGHTS:
Maternal body weights were not affected by treatment. The mean body weights of the high dose group showed a slight increase on Day 6 compared to the controls. Mean corrected body weight gain (corrected for uterus weight) of the treated groups was comparable to the control group.

REPRODUCTION DATA:
No substance-related effects on reproduction data were noted compared to controls.

NECROPSY:
At scheduled necropsy, no macroscopic changes were observed between treated and control animals. Incidental findings in two animals of the 300 mg/kg bw/day and 1000 mg/kg bw/day, respectively, either comprised white nodules in the left inguinal region or haematoma in the region of larynx.

Key result

Dose descriptor:

NOAEL

Remarks:

maternal toxicity

Effect level:

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

Based on:

test mat.

Basis for effect level:

other: no treatment-related effects observed

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Abnormalities:

no effects observed

Fetal body weight changes:

no effects observed

Description (incidence and severity):

Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed

Reduction in number of live offspring:

no effects observed

Changes in sex ratio:

no effects observed

Changes in litter size and weights:

no effects observed

Changes in postnatal survival:

no effects observed

External malformations:

no effects observed

Skeletal malformations:

no effects observed

Visceral malformations:

no effects observed

Other effects:

no effects observed

Description (incidence and severity):

The weight of placenta and uteri including content showed no significant differences between treated and control animals.

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects: no effects

EMBRYOTOXICITY/FETOTOXICITY:
No substance-related differences in pre-and post-implantation loss, mean figures of resorptions, embryonic deaths and total fetuses were observed in treated animals compared to controls.

BODY WEIGHTS:
The weight of live fetuses exhibited not significant differences on a litter or individual basis.

PLACENTA AND UTERUS WEIGHT:
The weight of placenta and uteri including content showed no significant differences between treated and control animals.

SEX RATIOS:
The fetal sex ratio was comparable in all test groups.

EXTERNAL OBSERVATIONS:
No abnormal findings were observed that were considered to be related to treatment. Incidental findings comprised the occurrence of only one placenta for two fetuses in the control group and one fetus with hydrops in the high dose group (1000 mg/kg bw/d).

VISCERAL OBSERVATIONS:
The main figures of visceral variations (hydronephrosis, dilated and waved ureters) were similar compared to controls and variations were not considered to be related to treatment. All other findings except for one situs inversus total in the high dose group and enlarged parenchymous organs in one fetus in the controls were considered to be incidental.

SKELETAL EXAMINATION:
No substance-related abnormal findings were noted at skeletal examination of the fetuses. Spontaneous findings comprised absent or malformed cervical vertebrae arches in one mid dose fetus and luxation and malposition of the mandible in one high dose fetus when compared to the control group. Retarded ossification was found in all treatment groups and was similar to the level of skeletal ossification in the control group. The isolated statistically significant difference in the figure “14 ribs short/rudimentary bilateral” in the high dose group (100 mg/kg bw/d) was considered to be incidental and not related to treatment, since no dose-response relationship was apparent.

Key result

Dose descriptor:

NOAEL

Remarks:

developmental toxicity

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no treatment-related effects observed

Remarks on result:

not determinable due to absence of adverse toxic effects

Key result

Abnormalities:

no effects observed

Key result

Developmental effects observed:

no

Conclusions:

A prenatal developmental toxicity study performed according to OECD 414 and in compliance with GLP with the test material and did not reveal any treatment-related effect. Thus, a NOAEL (maternal/developmental) of ≥1000 mg/kg bw/day was derived.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Study duration:

subacute

Species:

rat

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common functional group(s), common precursors/breakdown products, similarities in PC/ECO/TOX properties (refer to category justification for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII-IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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

There are no data available on developmental toxicity of D-Glucopyranose, oligomeric, undecyl glycoside. In order to fulfil the standard information requirements set out in Annex IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from a structurally related substance is conducted following a category approach.

Developmental Toxicity

A key prenatal developmental toxicity study performed according to OECD TG 414 and in compliance with GLP with the category member D-Glucopyranose, oligomeric, C10-16-alkyl glycosides (CAS 110615-47-9) is available (Henkel, 1997). Groups of 24 pregnant female Sprague-Dawley rats per dose were administered doses of 100, 300 and 1000 mg/kg bw/day via oral gavage. Animals treated with the vehicle (water) served as controls. Treatment was only carried out once daily during the Day 6-15 of gestation (organogenesis period). Animals were observed for mortalities and clinical signs at least twice daily (except weekends). Body weights were determined on Gestation Day (GD) 0, 6, 16 and 20. Upon sacrifice on GD 20 macroscopic examinations for structural abnormalities or pathological changes were performed with emphasis on female uteri including uterus weight, number of corpora lutea, implantations and early and late resorptions. Fetuses were subjected to external examination and either soft tissue or skeletal examination (half per liter) was performed. No deaths occurred in dams receiving the vehicle or the test substance at doses of 300 mg/kg bw/day. Due to an application error, test substance-unrelated mortalities were found on GD 11 and 13 in one animal of the 100 and 1000 mg/kg bw/d test group, respectively. No substance-related symptoms were observed at any dose level during the study. Moreover, maternal body weights were generally not affected by treatment (with exception on GD 6) and no substance-related effects on reproduction data were noted when compared to controls. Necropsy revealed no macroscopic changes between treated and control animals with exception of incidental findings in two animals either comprising white nodules in the left inguinal region or hematoma in the region of larynx. No substance-related differences in pre-and post-implantation loss, mean figures of resorptions, embryonic deaths and total fetuses were observed in treated animals compared to controls. The body weight of live fetuses exhibited no significant differences on a litter or individual basis. The weight of placenta and uteri including content showed no significant differences between treated and control animals. The fetal sex ratio was comparable in all test groups. No abnormal findings were observed that were considered to be related to treatment. Incidental findings comprised the occurrence of only one placenta for two fetuses in the control group and one fetus with hydrops in the high dose group (1000 mg/kg bw/day). The main figures of visceral variations (hydronephrosis, dilated and waved ureters) were similar compared to controls and not considered to be related to treatment. Retarded ossification was found in all treatment groups and was similar to the level of skeletal ossification in the control group. In summary, administration of D-Glucopyranose, oligomeric, C10-16-alkyl glycosides (CAS 110615-47-9) at doses of 100, 300 or 1000 mg/kg bw/day by oral gavage to pregnant female Wistar rats from GD 6 to 15 resulted in no toxicologically relevant treatment-related effects. Therefore the maternal and developmental No-Observed-Adverse-Effect-Levels (NOAEL) were both considered to be 1000 mg/kg bw/day.

 

Based on the above study result with the category member D-Glucopyranose, oligomeric, C10-16-alkyl glycosides (CAS 110615-47-9) the registered substance D-Glucopyranose, oligomeric, undecyl glycoside is not considered to exert developmental toxicity, either.

Justification for classification or non-classification

The available data on toxicity to reproduction of the structurally related substance D-Glucopyranose, oligomeric, C10-16-alkyl glycosides (CAS 110615-47-9) according to Regulation (EC) No 1907/2006, Annex XI, 1.5 do not meet the criteria for classification according to Regulation (EC) No 1272/2008; therefore, D-Glucopyranose, oligomeric, undecyl glycoside is not considered to meet the criteria for classification, either, and the data are thus conclusive but not sufficient for classification.