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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information

Based on the read across substance study results, the rat NOAEL (systemic toxicity) for the test substance, C12 -14 ADEBAC, for both parental generation (P and F1) as well as for offsprings (F1 and F2) can be considered to be 1,000 ppm (i.e., equivalent to 51 mg/kg bw/day or 41.3 mg a.i./kg bw/day) and for reproductive toxicity at 2000 ppm (the highest dose tested) (i.e., 100 mg/kg bw/day or 81.09 mg a.i./kg bw/day). Therefore the test substance is not expected to pose a reproductive or developmental toxicity concern.

Link to relevant study records
Reference
Endpoint:
two-generation reproductive toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
KL2 due to RA
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
EPA OPP 83-4 (Reproduction and Fertility Effects)
Deviations:
no
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Test animals
- Source: Sprague-Dawley CD rats were obtained from Charles River Breeding Laboratories, Kingston, NY, USA
- Age at study initiation: Six weeks
- Weight at study initiation: 212.2-213.4 g (males); 148.3-150.2 g (females)
- Housing: Individually in stainless steel, wire mesh cages (22.5x15.5x18.0 cm; mating cages 22.5x31.0x18.0 cm)
- Diet: Certified Ground Rodent Chow # 5002 (Ralstor Purina Co., St. Louis, MO), ad libitum
- Water: Tap water, ad libitum. Water was provided by an automatic watering system with demand control valves mounted on each cage rack.
- Acclimation period: Two weeks

Environmental conditions
- Temperature: 66-73°F
- Humidity: 40-60%
Route of administration:
oral: feed
Vehicle:
other: Certified Ground Rodent Chow # 5002
Details on exposure:
Diet preparation: A concentrated premix was prepared by direct addition of the test substance to ground chow and mixing for approximately an hour. Test diets were prepared by appropriate dilutions of the concentrated premix or higher diet concentrations.
- Rate of preparation of diet (frequency): Fresh diet was prepared weekly.
- Mixing appropriate amounts with (Type of food): Certified Ground Rodent Chow # 5002
- Storage temperature of food: Diets were stored in polyethylene containers at room temperature.
Details on mating procedure:
- M/F ratio per cage: 1:1
- Mating procedure: After pre-breeding exposure the animals were mated on the basis of one male to one female selected randomly within each dose group for a period of 21d to produce F1 generation.
- Proof of pregnancy: Copulation plug and/or vaginal sperm as Day 0 of gestation.
- After the first 7d of the mating period females of unsuccessfully mated pairs were placed with males of other unmated pairs within the same dose group; after an additional 7d, unsuccessfully mated pairs were similarly exchanged again for a period of 7d or until successful mating had occurred, whichever came first, allowing for a total of 21d to mate.
- After successful mating each pregnant female was caged: Pregnant females were housed individually. On Day 20 of gestation each pregnant female was transferred to a shoe-box cage.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Experimental diets were analyzed for stability, homogeneity and concentration of test substance using high pressure liquid chromatography.
- Homogeneity study indicated that the distribution of the test substance in the test diet was uniform.
- Stability study indicated that the dosed feed was stable for at least 14d when stored in open glass feed jars at room temperature. Dosed feed was stable for at least 21d when stored in closed polyethylene containers at room temperature.
- Concentration verification analyses of the dosed feed indicated that the mean concentrations of the test substance in the diet for the 300, 1000 and 2000 ppm dosage levels were 95.3-109.0% of nominal for 300 ppm, 95.6-107.9% of nominal for 1000 ppm and 94.7-108.0% of nominal for 2000 ppm.
Duration of treatment / exposure:
P0 generation: 19 weeks (from 1st prebreed dose to last F0 sacrifice)
F1 generation: 25 weeks (from 1st F1 wean to last F1 sacrifice)
F2 generation: Until weaning
Frequency of treatment:
Daily
Details on study schedule:
- P1 parental animals not mated until 17-18 weeks after selection from the F1 litters.
- Selection of parents from F1 generation when pups were 28d old.
- Number of P1 generation animals selected: 28 males and 28 females

Remarks:
Doses / Concentrations:
0, 300, 1000 or 2000 ppm test substance (i.e., equivalent to 0, 16-31, 51-102, and 100-188 mg/kg bw/day (males) and 0, 21-32, 67-106 and 139-198 mg/kg bw/day (females)).
Basis: nominal in diet
No. of animals per sex per dose:
28
Control animals:
yes, plain diet
Details on study design:
- Rationale for animal assignment: Animals were randomly distributed based on body weight
- Animal identification: By ear tags
Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily

CLINICAL SIGNS: Yes
- Time schedule: Once daily for overt clinical signs.

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly during prebreed and mating for both sexes. For females on gestational Day 0, 6, 15, and 20 and on postnatal Day 0, 7, 14, and 21.

FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
- Time schedule: Weekly during prebreed for both sexes. For females in 3- or 4-day intervals throughout gestation and to postnatal Day 14.
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

WATER CONSUMPTION AND COMPOUND INTAKE: No

Litter observations:
STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: Yes, maximum of 8 pups/litter (4/sex/litter as nearly as possible). Excess pups were subjected to detailed external examination and then sacrificed.

PARAMETERS EXAMINED
The following parameters were examined in F1 and F2 offspring: Live/Still births on the day of birth (postnatal Day 0), survival indices at Days 0, 4, 7 and 14 after birth and weaning, weight on postnatal Day 1, 4, 7, 14, and at weaning (Day 21), and physical abnormalities for all pups at birth and throughout the pre-weaning period.

GROSS EXAMINATION OF DEAD PUPS: The thoracic and abdominal organs from pups which died after Day 4 were preserved for subsequent histopathological examination.
Postmortem examinations (parental animals):
SACRIFICE: Yes
- How many animals: All animals
- Necropsy method: Animals were anesthetized with methoxyflurane and exsanguinated by severing the brachial vessel.

GROSS NECROPSY: Yes
- How many animals: All animals sacrificed in P0 and P1 parental animals
- Gross necropsy consisted of: Vagina, uterus, ovaries, gross lesions, testes, epididymis, seminal vesicles and prostrate.

HISTOPATHOLOGY : Yes
- How many animals: All animals of control and high dose groups sacrificed in P0 and P1 parental animals
- Tissues evaluated: Vagina, uterus, ovaries, gross lesions, testes, epididymis, seminal vesicles and prostrate and any tissues or organs showing gross alterations from the low and mid dose groups
Postmortem examinations (offspring):
SACRIFICE
- The F1 offsprings not selected as parental animals and all F2 offsprings were sacrificed at 7d of age.

GROSS NECROPSY
- Examination for gross lesions was performed on any pup appearing abnormal or dying on test and for ten randomly selected F1 and F2 weanlings/sex/group.

Statistics:
- The results of the quantitative continuous variables (e.g., body weights, food consumption, etc.) were compared between the three treatment groups and one control group using Levene’s test for equal variances, analysis of variance and (pooled or separate variance) t-test.
- Non-parametric data were statistically evaluated using the Kruskall-Wallis test followed by the Mann-Whitney U test for pairwise comparisons when appropriate.
- Frequency data were compared using the Fisher’s exact test.
Reproductive indices:
Mating index, fertility index and gestational index were determined.
Offspring viability indices:
Live birth index, 4-d survival index, 7-d survival index, 14-d survival index, 21-d survival index and lactation index

Clinical signs:
no effects observed
Description (incidence and severity):
No significant signs of toxicity during the pre-breed, mating, gestation or lactation periods at any dose for either generation were observed.



Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
- During the 10-week pre-breed exposure, P0 males exhibited no reduction in body weight. During the same period, P0 females at 2000 ppm exhibited reduction in body weight during Weeks 5, 6, 9 and 10 of pre-breed treatment. Body weight gain was also reduced at 2000 ppm for one week (Week 8-9) during the pre-breed period.
- On lactation Day 21 mean body weight of P0 dams at 2000 ppm exhibited a significant increase. Increased lactation body weight gain was observed at 2000 ppm throughout lactation.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
- Food consumption in the P0 females at 2000 ppm was reduced for the first four exposure weeks. Food consumption in P0 males was significantly reduced at 2000 ppm for the first week of treatment only.
- At P0 breed to produce F1 litters, food consumption during gestation and lactation was unaltered by treatment.
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
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Other effects:
effects observed, treatment-related
Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed
Description (incidence and severity):
Mating index, fertility index and gestational index
Key result
Dose descriptor:
NOAEL
Remarks:
systemic toxicity
Effect level:
1 000 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
food consumption and compound intake
Remarks on result:
other: equivalent to 51-102 mg/kg bw/day in males and 67-106 mg/kg bw/day in females
Key result
Dose descriptor:
NOEL
Remarks:
reproductive toxicity
Effect level:
2 000 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no reproductive toxicity observed
Remarks on result:
not determinable due to absence of adverse toxic effects
Key result
Critical effects observed:
no
Clinical signs:
no effects observed
Description (incidence and severity):
No significant signs of toxicity during the pre-breed, mating, gestation or lactation periods at any dose for either generation were observed.
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
At 2000 ppm, only slight reduction were observed in males and females
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):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed
Description (incidence and severity):
Mating index, fertility index and gestational index
Key result
Dose descriptor:
NOAEL
Remarks:
systemic toxicity
Effect level:
1 000 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
Remarks on result:
other: equivalent to 51-102 mg/kg bw/day in males and 67-106 mg/kg bw/day in females
Key result
Dose descriptor:
NOEL
Remarks:
reproductive toxicity
Effect level:
2 000 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no reproductive toxicity observed
Remarks on result:
not determinable due to absence of adverse toxic effects
Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
2 000 ppm
System:
other: body weight
Treatment related:
yes
Dose response relationship:
yes
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality / viability:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
The F1 litters exhibited reduced body weight per litter on postnatal Days 21 and 28 at 2000 ppm. F1 pup body weight gain was reduced during lactation Days 14-21 and 21-28.
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:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed
Behaviour (functional findings):
not examined
Developmental immunotoxicity:
not examined
Key result
Dose descriptor:
NOAEL
Remarks:
general toxicity
Generation:
F1
Effect level:
1 000 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
Key result
Dose descriptor:
NOEL
Remarks:
developmental toxicity
Generation:
F1
Effect level:
2 000 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects observed
Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
2 000 ppm
System:
other: body weight
Treatment related:
yes
Dose response relationship:
yes
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality / viability:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
F2 pup weights per litter were reduced at 2000 ppm on postnatal Day 28. Pup weight gain was also reduced at 2000 ppm during lactation Days 14-21 and for Days 21-28.
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:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed
Behaviour (functional findings):
not examined
Developmental immunotoxicity:
not examined
Key result
Dose descriptor:
NOAEL
Remarks:
general toxicity
Generation:
F2
Effect level:
1 000 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
Key result
Dose descriptor:
NOEL
Remarks:
developmental toxicity
Generation:
F2
Effect level:
2 000 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects observed
Remarks on result:
not determinable due to absence of adverse toxic effects
Key result
Critical effects observed:
yes
Lowest effective dose / conc.:
1 000 ppm
System:
other: body weight
Treatment related:
yes
Dose response relationship:
yes
Key result
Reproductive effects observed:
no
Conclusions:
Based on the read across substance study results, the rat NOAEL (systemic toxicity) for the test substance for both parental generation (P and F1) and offsprings (F1 and F2) can be considered to be 1,000 ppm (i.e., equivalent to 51 or 41.3 mg a.i./kg bw/day). The rat NOEL for reproductive toxicity can be established at 2000 ppm (the highest dose tested) (i.e., 100 mg/kg bw/day or 81.09 mg a.i./kg bw/day).
Executive summary:

A study was conducted to determine the toxicity to reproduction of the read across substance, C12-16 ADBAC (active: 81.09%), according to US EPA OPP 83 -4, in compliance with GLP. The read across substance was orally administered to Sprague-Dawley CD rats (28/sex/group) at dose levels of 0, 300, 1,000 or 2,000 ppm read across substance (i.e., equivalent to 0, 16-31, 51-102, and 100-188 mg/kg bw/day (males) and 0, 21-32, 67-106 and 139-198 mg/kg bw/day (females)) in the diet. There was one control group of 28 animals/sex. Following a 10 week pre-breed exposure period, the P0 rats were randomly paired within dose groups for a 3 week mating period to produce the F1 generation. Exposure continued through mating, gestation, parturition and lactation. At weaning, 28 F1 weanling/sex/group were randomly selected and exposed to the same dietary concentration of the read across substance as their parents for 10 weeks. After their pre-breed exposure, F1/P1 animals were paired to produce the F2 generation. The animals were observed twice daily and clinical findings, body weights and food consumption were recorded periodically. All P0 and P1 animals were necropsied and examined for gross lesions; selected reproductive tissues from the high dose and control groups were examined histologically as were other tissues with gross lesions. Ten F1 and F2 weanlings/sex/dose were randomly selected and necropsied and examined for gross lesions. P0 female body weights and food consumption were reduced at 2,000 ppm during the pre-breeding exposure period. For the pre-breeding period of the P1 animals, only slight reductions in body weight gain were observed for males in the high dose group. No other treatment-related effects were observed on any of the reproductive parameters. Under study conditions, dietary administration of the read across substance at dose levels of 0, 300, 1,000 and 2,000 ppm for two generations to Sprague-Dawley rats can be considered to be well tolerated and no sign of reproductive toxicity is expected to be observed at any dose level. The rat NOAEL (systemic toxicity) for the read across substance for both parental generation (P and F1) and offsprings (F1 and F2) is considered to be 1,000 ppm (in diet), i.e., equivalent to 51-102 or 41.3-83 mg a.i./kg bw/day in males and 67-106 mg/kg bw/day or 54-86 mg a.i./kg bw/day for female, respectively. The rat NOEL (reproductive toxicity) is established at 2000 ppm (the highest dose tested; i.e., equivalent to 100-188 or 81.09 -152.45 mg a.i./kg bw/day in males and 139 -198 mg/kg bw/day or 112.72 -160.56 mg a.i./kg bw/day for female, respectively) (Neeper-Bradley, 1990). Based on the read across substance study results, similar parental and reproductive/development toxicity NOAELs can be expected for the test substance, C12-14 ADEBAC.​

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
81.09 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Guideline study
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

A study was conducted to determine the toxicity to reproduction of the read across substance, C12-16 ADBAC (active: 81.09%), according to US EPA OPP 83 -4, in compliance with GLP. The read across substance was orally administered to Sprague-Dawley CD rats (28/sex/group) at dose levels of 0, 300, 1,000 or 2,000 ppm read across substance (i.e., equivalent to 0, 16-31, 51-102, and 100-188 mg/kg bw/day (males) and 0, 21-32, 67-106 and 139-198 mg/kg bw/day (females)) in the diet. There was one control group of 28 animals/sex. Following a 10 week pre-breed exposure period, the P0 rats were randomly paired within dose groups for a 3 week mating period to produce the F1 generation. Exposure continued through mating, gestation, parturition and lactation. At weaning, 28 F1 weanling/sex/group were randomly selected and exposed to the same dietary concentration of the read across substance as their parents for 10 weeks. After their pre-breed exposure, F1/P1 animals were paired to produce the F2 generation. The animals were observed twice daily and clinical findings, body weights and food consumption were recorded periodically. All P0 and P1 animals were necropsied and examined for gross lesions; selected reproductive tissues from the high dose and control groups were examined histologically as were other tissues with gross lesions. Ten F1 and F2 weanlings/sex/dose were randomly selected and necropsied and examined for gross lesions. P0 female body weights and food consumption were reduced at 2,000 ppm during the pre-breeding exposure period. For the pre-breeding period of the P1 animals, only slight reductions in body weight gain were observed for males in the high dose group. No other treatment-related effects were observed on any of the reproductive parameters. Under study conditions, dietary administration of the read across substance at dose levels of 0, 300, 1,000 and 2,000 ppm for two generations to Sprague-Dawley rats can be considered to be well tolerated and no sign of reproductive toxicity is expected to be observed at any dose level. The rat NOAEL (systemic toxicity) for the read across substance for both parental generation (P and F1) and offsprings (F1 and F2) is considered to be 1,000 ppm (in diet), i.e., equivalent to 51-102 or 41.3-83 mg a.i./kg bw/day in males and 67-106 mg/kg bw/day or 54-86 mg a.i./kg bw/day for female, respectively. The rat NOEL (reproductive toxicity) is established at 2000 ppm (the highest dose tested; i.e., equivalent to 100-188 or 81.09 -152.45 mg a.i./kg bw/day in males and 139 -198 mg/kg bw/day or 112.72 -160.56 mg a.i./kg bw/day for female, respectively) (Neeper-Bradley, 1990). Based on the read across substance study results, similar parental and reproductive/development toxicity NOAELs can be expected for the test substance, C12-14 ADEBAC.​

Effects on developmental toxicity

Description of key information

Based on the results of the read across study, the NOELs for the test substance, C12 -14 ADEBAC, for maternal toxicity and developmental toxicity can be considered to be 15 mg/kg bw/day (i.e., equivalent to 7.5 mg/kg bw/day a.i.) and >50 mg/kg bw/day (i.e., equivalent to 25 mg a.i./kg bw/day) respectively. Therefore, the test substance is not expected to pose a developmental toxicity concern.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
January 28, 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
not applicable
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
other: Female Wistar derived albino
Details on test animals or test system and environmental conditions:
-Individual mesh bottom cages in temperature controlled quarters
-Free access to food and fresh tap water
Route of administration:
oral: gavage
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Dose levels: 0, 5, 15 and 50 mg/kg bw/day (0, 2.5, 7.5 and 25 mg/kg bw/day a.i.)
Details on mating procedure:
Adult female rats were mated with young adult male and detection of the vaginal sperm plus was considered to occur on day 0 of gestation
Duration of treatment / exposure:
Days 6 - 15 of gestation
Frequency of treatment:
Once daily during exposure period
Duration of test:
Dams were scacrificed on day 20 of gestation
Dose / conc.:
0 mg/kg bw/day
Remarks:
Without test substance (Only vehicle - Water)
Dose / conc.:
5 mg/kg bw/day
Remarks:
2.5 mg/kg bw/day (a.i.)
Dose / conc.:
15 mg/kg bw/day
Remarks:
7.5 mg/kg bw/day (a.i.)
Dose / conc.:
50 mg/kg bw/day
Remarks:
25 mg/kg bw/day (a.i.)
No. of animals per sex per dose:
22-37/group female rats
Control animals:
yes
yes, concurrent no treatment
Maternal examinations:
Clinical signs: Daily
Mortality: Daily
Bodyweight: Days 0, 6, 11, 15 and 20
Number of corpora lutea
Number of implantation and resorptions sites
Number of corpora lutea
Urogenital tract gross necropsy
Ovaries and uterine content:
Not examined
Fetal examinations:
Body weight
Gross necropsy
Skeletal examinations - Two thirds of the foetuses were used for this examination
Visceral examinations - One third of the foetuses were used for this examination
Statistics:
Confidence Belts for proportions with a confidence coefficient of 0.95 was used to compare the experimental and control groups. If the significance was not clearly definable, the probability of the occurrence was determined by the computation of exact probabilities.
Clinical signs:
not examined
Mortality:
mortality observed, treatment-related
Description (incidence):
3 dams died in the 50 mg/kg/day test group.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
There were no effects of treatment on gestational body weight.
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:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
not examined
Number of abortions:
not examined
Pre- and post-implantation loss:
not examined
Total litter losses by resorption:
not examined
Early or late resorptions:
not examined
Dead fetuses:
not examined
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:
no effects observed
Description (incidence and severity):
Affects on gestation were not noted in any treatment group. Twelve females in the positive control group resorbed their uterine contents.
Key result
Dose descriptor:
NOEL
Effect level:
ca. 15 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
mortality
Remarks on result:
other: NOEL 7.5 mg a.i./kg bw/day
Key result
Abnormalities:
effects observed, treatment-related
Localisation:
other: General toxicity - Mortality
Description (incidence and severity):
3 dams in the 50 mg/kg bw/day test group died
Fetal body weight changes:
no effects observed
Description (incidence and severity):
No treatment-related effects were observed in all treated group. Decreased weights were observed in the positive control group.
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not examined
Reduction in number of live offspring:
not examined
Changes in sex ratio:
not examined
Changes in litter size and weights:
not examined
Changes in postnatal survival:
not examined
External malformations:
not examined
Skeletal malformations:
no effects observed
Description (incidence and severity):
No treatment-related variations or malformations
Visceral malformations:
effects observed, non-treatment-related
Description (incidence and severity):
No treatment-related variations or malformations
Other effects:
no effects observed
Description (incidence and severity):
No malformations
Details on embryotoxic / teratogenic effects:
No developmental toxicity including teratogenicity was observed at any dosage employed, as compared to the negative control group.
Key result
Dose descriptor:
NOEL
Effect level:
> 50 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
other: No developmental toxicity, including teratogenicity was observed at any dosage employed.
Remarks on result:
other: NOEL 25 mg a.i./kg bw/day
Key result
Abnormalities:
no effects observed
Description (incidence and severity):
No developmental toxicity, including teratogenicity was observed at any dosage employed.
Key result
Developmental effects observed:
no
Lowest effective dose / conc.:
50 other: mg/kg bw day test material (NOEL 25 mg a.i./kg bw/day)
Treatment related:
no
Conclusions:
Based on the results of the read across study, the no observable effect level (NOEL) for maternal toxicity and developmental toxicity were determined to be 15 mg/kg bw/day (7.5 mg/kg bw/day a.i.) and >50 mg/kg bw/day (25 mg a.i./kg bw/day) respectively.
Executive summary:

A study was conducted to determine the developmental toxicity of read across substance, C12-18 ADEBAC (active: 50%), according to the method equivalent or similar to OECD 414 guideline. 22-37 pregnant female Wistar rats/group were treated with read across substance at concentrations of 0, 5, 15 and 50 mg/kg bw/day (0, 2.5, 7.5 and 25 mg a.i./kg bw/day) or aspirin at 250 mg/kg bw/day. The dams were sacrificed at day 20 and the foetuses were examined for visceral and skeletal variations and malformations. There were no treatment-related effects on the body weight or reproductive parameters. Increased mortality was observed at 50 mg/kg/day, however, this finding was not statistically significant. There were no treatment-related effects on foetal body weight or visceral/skeletal findings. In the positive control group, increased fetal resorption, decreased fetal weight and increase incidences of skeletal and soft tissue variations were observed. No developmental toxicity, including teratogenicity was observed at any dosage employed. Under study conditions, for read across substance, the no observable effect level (NOEL) for maternal toxicity and developmental toxicity were determined to be 15 mg/kg bw/day (7.5 mg/kg bw/day a.i.) and >50 mg/kg bw/day (25 mg a.i./kg bw/day) respectively (Knickerbocker and Stevens, 1977). Based on the results of the read across study, similar NOELs for maternal toxicity and developmental toxicity can be expected for the test substance, C12-14 ADEBAC.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
25 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
comparable to guideline study with acceptable restrictions
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

A study was conducted to determine the developmental toxicity of read across substance, C12-18 ADEBAC (active: 50%), according to the method equivalent or similar to OECD 414 guideline. 22-37 pregnant female Wistar rats/group were treated with read across substance at concentrations of 0, 5, 15 and 50 mg/kg bw/day (0, 2.5, 7.5 and 25 mg a.i./kg bw/day) or aspirin at 250 mg/kg bw/day. The dams were sacrificed at day 20 and the foetuses were examined for visceral and skeletal variations and malformations. There were no treatment-related effects on the body weight or reproductive parameters. Increased mortality was observed at 50 mg/kg/day, however, this finding was not statistically significant. There were no treatment-related effects on foetal body weight or visceral/skeletal findings. In the positive control group, increased fetal resorption, decreased fetal weight and increase incidences of skeletal and soft tissue variations were observed. No developmental toxicity, including teratogenicity was observed at any dosage employed. Under study conditions, for read across substance, the no observable effect level (NOEL) for maternal toxicity and developmental toxicity were determined to be 15 mg/kg bw/day (7.5 mg/kg bw/day a.i.) and >50 mg/kg bw/day (25 mg a.i./kg bw/day) respectively (Knickerbocker and Stevens, 1977). Based on the results of the read across study, similar NOELs for maternal toxicity and developmental toxicity can be expected for the test substance, C12-14 ADEBAC.

Overall, based on the absence of adverse effects in the 2-generation reproductive toxicity study with the read across substance, C12-16 ADBAC, as well as in the pre-natal development toxicity study with C12-18 ADEBAC, the test substance, C12-14 ADEBAC can be expected to have a similar behaviour and hence is not considered to pose a reproductive or a developmental toxicity concern.​

Justification for classification or non-classification

Based on the results of the read across studies, the test substance, C12-14 ADEBAC, does not warrant classification for reproductive or development toxicity according to the EU CLP criteria (Regulation 1272/2008/EC).​​​

Additional information